The History of Cystic Fibrosis by Dr James Littlewood OBE

Edited and produced by Daniel Peckham

 

 

Including some unusual organisms and Burkholderia cepacia complex (see also the B. cepacia compex TOPIC)

An article - "The environment as a source of Pseudomonas aeruginosa and some other potential pathogens" by Jim Littlewood, with expert advice from Dr Miles Denton, is reproduced at the end of this TOPIC

 

 

General comment on cross infection from introduction to Nineties section in main text 

 

Infection between people with CF - a new major problem.  In 1979 Pseudomonas (now Burkholderia) cepacia in people with CF was first reported in North America and thereafter reports of this new pathogen, with the potential to spread between patients and cause serious illness, occurred with increasing frequency both from North America (Isles et al, 1984 above; Thomassen et al, 1985 above) and later from the UK (Simmonds et al, 1990 below). At first some clinicians were slow to accept that cross infection with B. cepacia between patients occurred until the early Nineties when this was established beyond any doubt (LiPuma et al, 1990 below; Govan et al, 1993 below). The severity and fatal nature of the associated illness (“cepacia syndrome”) in a proportion of infected patients with CF and its propensity to spread between patients led to a radical change in both clinic practice and the social habits of people with cystic fibrosis. Holiday camps for people with CF – so popular in N. America and so appreciated by some patients from the UK - were a source of cross infection and eventually abandoned (Pegues et al, 1994 below). Eventually, in 1993, the Infection Control Group of the UK CF Trust recommended strict the segregation of patients infected with Burkholderia cepacia. This was the start of the era of cross-infection control, which was to radically alter the whole attitude to infection, cross-infection and social contact in CF Centres and in the community.

 

Also there was increasing evidence of cross-infection with Pseudomonas aeruginosa. The concept of cross-infection between people with CF with organisms other than B. cepacia had not been regarded as a major consideration by the staff in most CF centres; the exception was the Danish CF Centre in Copenhagen where Niels Hoiby and his colleagues realised segregation of patients according to their microbiological status was important. Cross-infection with so-called ‘highly transmissible’ strains of Pseudomonas aeruginosa has been increasingly reported (Cheng et al, 1996 below; Jones et al, 2001 below) and there followed many reports of cross-infection with P. aeruginosa in cystic fibrosis.

 

As a result of these developments it is was recommended that people with CF should be segregated according to their microbiological status and those with B. cepacia should also be segregated even from each other as those with less virulent genomovars (strains) may be infected by those with the more severe ones.

 

 

 

1982 Kelly NM, Fitzgerald MX, Tempany E, O'Boyle C, Falkiner FR, Keane CT. Does Pseudomonas cross infection occur between cystic fibrosis patients? Lancet 1982; 2:688-690. [PubMed]
This study from Prof. Eddie Tempany’s unit in Dublin was published long before Pseudomonas was considered to spread between patients in CF clinics and at a time when Pseudomonas positive patients mixed freely with Pseudomonas negative patients in all CF centres, clinics and socially.
Over a 12-month period respiratory Pseudomonas aeruginosa isolated from CF patients were typed by serology and pyocin production to determine whether cross-infection was occurring. Although one strain appeared in four unrelated patients, none of these patients had been in contact with each other and the strains were considered to have been acquired from the environment. However, it is relevant that each of six pairs of siblings with CF shared the same strain, but the pairs of strains were distinct from each other.

These results suggested to the authors that the general environment was the most important source of Pseudomonas strains for CF patients and that for cross-infection to occur prolonged intimate contact was required – such as living in the same household.

 

This was an early study on the possibility of cross infection which at the time was considered to be reassuring. However subsequently, with the advent of more sensitive genetic testing, cross infection was shown to be relatively common in CF centres and clinics, although in 1982 there were relatively few such large groups of patients with CF in the UK.

 

 

1984 Isles A, McLuskey I, Corey M. Pseudomonas cepacia infection in cystic fibrosis: an emerging problem. J Pediatr 1984; 104:206-210. [PubMed]
The prevalence of Pseudomonas cepacia infection in a population of approximately 500 patients with CF in the Toronto CF centre, increased from 10% in 1971 to 18% by 1981. The carriage of P. aeruginosa had remained unchanged at 70% to 80% over the same period. Patients infected with P. cepacia had greater impairment of pulmonary function than those with P. aeruginosa alone. A syndrome characterized by high fever, severe progressive respiratory failure, leukocytosis, and elevated erythrocyte sedimentation rate (“cepacia syndrome”) had occurred in eight patients over the previous three years, with a 62% fatality rate. Because P. cepacia strains are uniformly resistant to ticarcillin, piperacillin, and aminoglycosides, and because ceftazidime is ineffective despite in vitro activity, treatment of these infections was very difficult. Prevention of acquisition and effective treatment of P. cepacia in patients with cystic fibrosis had become a major problem in the Toronto clinic.


This paper from Toronto describes the devastating effect of the introduction of B. cepacia into a CF clinic population very clearly and heralded a new era in CF care. This organism was to have a profound permanent effect on the treatment and social life of people with CF and their families.
The potential for spread between people with CF and the serious, often fatal, consequences (the so-called “cepacia syndrome”) were not fully appreciated in the UK until the early Nineties when John Govan’s publication documented definite person to person spread between people with CF (Govan et al, 1993 below). From 1993 there was a general introduction of infection control measures in CF Centres in the UK; also there was an end to the North American CF holiday camps which were shown to be an important source of acquisition of the B. cepacia infection.


In Leeds we had three patients who developed serious B. cepacia infections some months after visiting Canadian CF camps. In 1990 we published the first UK paper on B. cepacia in CF, having identified 11 patients with the infection over 6 years since 1984 but we found no evidence of obvious cross infection between our patients when we first identified the infection (Simmonds EJ, et al. Pseudomonas cepacia: a new pathogen in patients with cystic fibrosis referred to a large centre in the United Kingdom Arch Dis Child 1990; 65:874-877.[PubMed]).

 

 

1986 Pedersen SS, Koch C, Hoiby N, Rosendal K. An epidemic spread of multiresistant Pseudomonas aeruginosa in a cystic fibrosis centre. J Antimicrob Chemother 1986; 17:505-516.
[PubMed]

Early in 1983 an epidemic of a Pseudomonas aeruginosa resistant to aminoglycosides, carbenicillin, ureidopenicillins, ceftazidime, cefsulodin and imipenem occurred in the Danish CF centre. Most of the epidemic could be attributed to a specific nosocomial strain by means of O-grouping and phage- typing. This strain was present in the centre at a low frequency in 1973 and developed resistance during repeated courses of chemotherapy.

The epidemic was stopped by isolating the patients with the resistant strains. Restrictive and selective use of antibiotics was not sufficient to eradicate the resistant strains, which persisted in 42% of the patients. The extensive use of the third generation cephalosporins in the clinic was probably responsible for inducing and selecting for the resistant strains. Clustering of patients in the centre facilitated the spread. First-line use of older beta-lactam antibiotics, close bacteriological monitoring and prompt isolation of patients with resistant strains was implemented.

 

The Danish CF centre was unusual in giving regular 3-monthly courses of IV antibiotics to all their patients who were chronically infected with Pseudomonas aeruginosa (Pedersen et al, 1987 below). It is interesting that in the Liverpool paediatric CF clinic the routine use of ceftazidime monotherapy was associated with the development of a resistant Pseudomonas aeruginosa with epidemic spread amongst the patients there (Cheng et al, 1996 below).

 

 

1987 Pedersen SS, Jensen T, Hoiby N, Koch C, Flensborg EW. Management of Pseudomonas aeruginosa lung infection in Danish cystic fibrosis patients. Acta Paediatr Scand 1987; 76:955-961. [PubMed]
This is one of the main publications justifying the Danish policy of 3-monthly courses of intravenous antibiotics for patients chronically infected with Pseudomonas – a policy which has never been subjected to an acceptable clinical trial and was initiated before the advent of inhaled antibiotics. The annual mortality rate of cystic fibrosis patients with chronic P. aeruginosa lung infection at the Danish CF-centre ranged from 10 to 20% in the years 1970-1975 - in this period the patients received anti-Pseudomonal chemotherapy only during acute exacerbations of infection. From 1976-1979 patients who acquired chronic P. aeruginosa infection were given regular and intensive anti-Pseudomonal treatment three to four times per year. The patients were followed for 6-12 patient-years; seven died and the 10-year survival rate after onset of P. aeruginosa infection was 90% (+/- 4%). The annual mortality rate is now only 1-2%. Although precipitating antibodies against P. aeruginosa increased significantly, pulmonary function did not deteriorate with duration of infection.


An unwelcome consequence was an increase in cross-infection between patients associated with more frequent hospitalisation and an increased incidence of new P. aeruginosa infection in 1976 which was steadily reduced, starting in the late Seventies, by improved hygienic measures and a new ward in the CF centre.

 

 

1990 Simmonds EJ, Conway SP, Ghoneim ATM, Ross H, Littlewood JM. Pseudomonas cepacia: a new pathogen in patients with cystic fibrosis referred to a large centre in the United Kingdom. Arch Dis Child 1990; 65:874-877. [PubMed]
Although the first reports from N. America of this organism appeared in the late Seventies (Lararya-Cuassay et al, 1977 above), this report from Leeds was the first to report Burkholderia cepacia in the UK – previously known as Pseudomonas cepacia. We were impressed by the very serious consequences of this infection in some patients. Some clinicians in the UK still doubted the serious nature of this infection although three of our 11 patients died – two after an alarming and rapid deterioration now described as the “cepacia syndrome”. We could not identify any source of cross infection in the Leeds CF centre at that stage nor was there an inappropriate use of antibiotics. However, in retrospect, we suspected that at least two of our patients had acquired the infection at CF holiday camps in N. America some months before the organism appeared in their respiratory cultures.

 

A further report of 13 infected patients (three of whom died) from the paediatric CF centre in Manchester in the UK also failed to show evidence of cross infection and the authors suggested that further studies were required before segregation of patients should be recommended (Gladman G et al, Arch Dis Child 1992; 67:192-195.[PubMed]). It was not until 1993, following Professor Govan’s publication from Edinburgh (Govan et al, 1993 below), that the UK CF Trust’s advisory group recommended strict segregation of all B. cepacia infected patients.

 

 

1993 Govan JR, Brown PH, Maddison J, Doherty CJ, Nelson JW, Dodd M, et al. Evidence for transmission of Pseudomonas cepacia by social contact in cystic fibrosis Lancet 1993; 342:15-19.[PubMed]
Prof. John Govan of Edinburgh  has for many years been a leading UK and international authority on CF microbiology. In this very important paper he reported the definite transfer of B. cepacia infection between people with CF which finally convinced most CF clinicians. An analysis of isolates from 210 patients attending regional CF clinics in Edinburgh and Manchester between 1986 and 1992 showed that the main cause of increased isolations of P. cepacia from 1989 was the emergence of an epidemic strain that had spread between patients in both clinics. Epidemiological evidence indicated that social contact was important in spread of the epidemic strain within and between clinics. Guidelines to limit the acquisition of B. cepacia should not be restricted to patients in hospital, and that intimate or frequent social contact is associated with a high risk of cross-infection.

 

Following this important paper the UK CF Trust advisory group of clinicians and microbiologists advised that strict segregation of B. cepacia-infected patients was essential as some clinics, even in 1993, were not yet segregating B. cepacia infected patients from other CF patients. The widespread introduction of segregation from this time led to a steady reduction in the incidence of new B. cepacia infections and a reduction in the prevalence of chronic B. cepacia infections.

 

Rosenstein & Hall reported pneumonia and septicemia due to Pseudomonas cepacia in a patient with CF (Rosenstein BJ, Hall DE. Johns Hopkins Med J 1980; 147:188-189.[PubMed]) before the first report from Toronto describing major problems in treating the infection (Gold R et al. J Antimicrob Chemother 1983; 12 Suppl A: 331-336.[PubMed]) and before the other major publication from Toronto (Isles A, et al. Pseudomonas cepacia infection in cystic fibrosis: an emerging problem. J Pediatr 1984; 104:206-210. [PubMed]above). This Toronto paper describes how the prevalence of Pseudomonas cepacia infection in a population of approximately 500 patients with CF in the Toronto CF centre, increased from 10% in 1971 to 18% by 1981. The carriage of P. aeruginosa had remained unchanged at 70% to 80% over the same period. Patients infected with P. cepacia had greater impairment of pulmonary function than those with P. aeruginosa alone. A syndrome characterized by high fever, severe progressive respiratory failure, leukocytosis, and elevated erythrocyte sedimentation rate (“cepacia syndrome”) had occurred in eight patients over the previous three years, with a 62% fatality rate. Because P. cepacia strains are uniformly resistant to ticarcillin, piperacillin, and aminoglycosides, and because ceftazidime is ineffective despite in vitro activity, treatment of these infections was very difficult. Prevention of acquisition and effective treatment of B. cepacia in patients with cystic fibrosis had become a major problem in the Toronto clinic and this paper describes the devastating effect of the introduction of B. cepacia into a CF clinic population very clearly.

 

In 1990 we published from Leeds the first UK paper on B. cepacia in CF, having identified 11 patients with the infection over 6 years since 1984 but we found no evidence of obvious cross infection between our patients when we first identified the infection (Simmonds EJ, et al. Pseudomonas cepacia: a new pathogen in patients with cystic fibrosis referred to a large centre in the United Kingdom Arch Dis Child 1990; 65:874-877.[PubMed]).

 

 

1993 Smith DL, Gumery LB, Smith EG, Stableforth DE, Kaufmann ME, Pitt TL. Epidemic of Pseudomonas cepacia in an adult cystic fibrosis Unit: Evidence of person-to-person transmission. J Clin Microbiol 1993; 31:3017-3022.[PubMed]
Report of transmission between patients in the Birmingham Adult CF Centre investigated in collaboration with Dr Ty Pitt of the Central Public Health Laboratory, London. Prevalence rose from 1.4% in 1988 to 8.3% in 1992. At the time of writing five of the 17 (30%) of the affected patients had died. In only two of the six patients referred to the Birmingham CF centre had P. cepacia been identified before referral.

 

 

1996 Cheng K, Smyth RL, Govan JRW, Doherty C, Winstanley C, Denning N, Heaf DP, Saene H van, Hart CA. Spread of ß-lactam resistant Pseudomonas aeruginosa in a cystic fibrosis clinic. Lancet 1996; 348:639-642.[PubMed]
A high proportion of children attending the Liverpool Paediatric CF centre were found to be chronically infected with a P. aeruginosa that was resistant to ceftazidime and other beta-lactam antibiotics. Two genomic fingerprinting techniques were used to see if this had arisen from epidemic spread of a single strain. This had indeed occurred and 92 (76.7%) of the 120 children attending the clinic were infected with P aeruginosa, and 65 (71%) of these 92 infected infants harboured isolates that were resistant to ceftazidime; 55 of the 65 children harboured the same epidemic strain - resistant to ceftazidime, azlocillin, and imipenem, and sensitive to tobramycin and ciprofloxacin.

 

This study provides the first molecular evidence of a long-term “outbreak” of P. aeruginosa in a CF centre. The authors suggested that careful surveillance of the prevalence of antibiotic resistance in CF centres should be instituted with measures to prevent cross-infection. They suggested that anti-Pseudomonal monotherapy “should be considered with caution”. This lesson had already been learned in Copenhagen in the early Eighties (Pedersen et al, 1986 above) and in the past a number of writers had already cautioned against the use of monotherapy. Most CF centres at the time already followed the recommendation to use two antibiotics when treating exacerbations of Pseudomonas infection. However, prior to this outbreak, intravenous ceftazidime monotherapy had been routine in the Liverpool CF clinic.

This was a very important paper which highlighted the risk of cross infection with Pseudomonas aeruginosa in CF clinics now clearly identified by genomic finger printing techniques. Later this highly transmissible “Liverpool epidemic strain” of Pseudomonas aeruginosa was reported elsewhere and subsequently spread to many other CF centres in the UK.

It is cause for concern that, even after experience such as reported here, there is still discussion as to the use of one or two antibiotics for the treatment of exacerbations – even to the extent of a Cochrane review which failed to give firm advice to use two antibiotics!! (Ephick HE, Tan A. Single versus combination intravenous antibiotic therapy for people with cystic fibrosis. Cochrane Database of Systematic Reviews. 2005).

 

Comment - Avoidance of cross infection became an increasingly important part of management as it became apparent that, not only could B. cepacia spread between patients, but also cross infection with "highly transmissible" strains of Pseudomonas aeruginosa was by no means rare (Jones et al, 2001 below). A survey of UK CF centres showed that cross infection with P. aeruginosa was relatively common both within and between CF centres (Scott & Pitt, 2004 below). The need to segregate patients according to their microbiological status had a major effect on the social lives of people with CF and their families and also on clinic routines in the CF centres.

 

 

2000 Saiman L, Macdonald N, Burns JL, Hoiby N, Speert DP, Weber D. Infection control in cystic fibrosis: practical recommendations for the hospital, clinic, and social settings. Am J Infect Contr 2000; 28:381-385. [PubMed]
Very detailed report of the findings of a CFF consensus meeting on infection control which included Europeans Niels Hoiby, Gerd Doering and Jim Littlewood. The great detail in this report is a reflection of the increasing realization that cross infection was a common and potentially harmful occurrence in CF centres.

 

 

2000 Ojeniyi B, Frederiksen B, Hoiby N. Pseudomonas aeruginosa cross-infection among patients with cystic fibrosis during a winter camp. Pediatr Pulmonol 2000; 29:177-181.[PubMed]
In 1990 twenty-seven patients with CF from the Danish Cystic Fibrosis Centre went to a winter camp for a week. The study is based on 22 of these patients. Prior to attending camp, 17 out of the 22 patients harboured Pseudomonas aeruginosa in their sputum, but 5 patients did not. After returning from camp, all 22 patients harboured P. aeruginosa in the sputum. The typing results showed that the 5 CF patients who were free of P. aeruginosa in their sputum prior to the winter camp had acquired P. aeruginosa isolates identical to the P. aeruginosa strains isolated from the other 17 CF patients. The authors concluded that separate holiday camps based on the infection status of the patients with cystic fibrosis are necessary to avoid cross-infection of patients not infected with P. aeruginosa.

 

This is one of the more conclusive reports of people with CF contracting new P. aeruginosa infection during a holiday with others who also have CF and who were already chronically infected. The report was important for at this time there were still experienced and respected CF physicians who questioned the importance of segregation according to microbiological status (Geddes DM. Of isolates and isolation: Pseudomonas aeruginosa in adults with cystic fibrosis. Lancet 2001; 358:522-523.).

 

 

2001 McCallum SJ, Corkill J, Gallagher M, Ledson MJ, Hart CA, Walshaw MJ. Superinfection with a transmissible strain of Pseudomonas aeruginosa in adults with cystic fibrosis chronically colonised by P. aeruginosa. Lancet 2001; 358:558-560.[PubMed]
Two further examples, from the Liverpool Adult CF Centre, of a transmissible Liverpool strain of P. aeruginosa shown to be identical by genotyping, infecting patients in the same clinic. Here it was shown to have infected patients already chronically infected with another strain of Pseudomonas. The Liverpool strain (LES strain), was first recognised in the Liverpool paediatric clinic (Cheng et al.1996. above [PubMed]), and was identified in a number of other UK CF centres in a subsequent survey carried out by Scott and Pitt (J Med Microbiol 2004; 53:609-615. below.[PubMed]).

 

 

2001 Visca P, Cazzola G, Petrucca A, Braggion C. Travel-associated Burkholderia pseudomallei infection (Melioidosis) in a patient with cystic fibrosis: a case report. Clin Infect Dis 2001; 32:E15-6.[PubMed]
In September 1997, a 25-year-old Italian lady with CF spent 3 weeks in Thailand. In August 1998, her pulmonary function rapidly declined, with productive cough and intermittent fever. The chest x-ray films revealed diffuse, small, patchy opacities in the upper lobes. Burkholderia pseudomallei (BP) were isolated from specimens of the patient's sputum and were identified by means of 16S rDNA sequencing. The diagnosis of melioidosis was serologically confirmed. Continuous therapy with ceftazidime and co-trimoxazole and maintenance with co-trimoxazole, doxycycline, and chloramphenicol resulted in eradication of Burkholderia pseudomallei.

 

 

This infection appears to be a particular risk for the increasing number of adults with CF travelling aboard to places such as Thailand as they seem to be prone to melioidosis. Subsequently further cases were reported. Burkholderia pseudomallei is an important cause of pneumonia and septicaemia in Thailand particularly in the rainy season when it may contaminate the water supply. There are now almost 70 cases of the infection causing serious illness reported in people with cystic fibrosis. So going on holiday to Thailand represents a definite risk for a person with CF particularly in the rainy season. B. pseudomallei infection has also been reported affecting a person with CF in Brazil (Barth AL et al, 2007. [PubMed] below).

 

 

2001 Jones AM, Govan JR, Doherty CJ, Dodd ME, Isalska BJ, Stanbridge TN, Webb AK. Spread of a multiresistant strain of Pseudomonas aeruginosa in an adult cystic fibrosis clinic. Lancet 2001; 358:557-558. [PubMed]
A prospective surveillance study in the Manchester Adult CF centre showed 22 (14%) of 154 patients with chronic P. aeruginosa had isolates with similar and new pyocin and pulsed-field gel electrophoresis types. Cross-infection by a new multiresistant P. aeruginosa strain had therefore occurred. The authors recommended CF centres should undertake microbiological surveillance of their patients.


A subsequent report from Manchester showed that patients infected with this strain of Pseudomonas required more intensive treatment (Jones AM et al. Thorax 2002; 57:924-925. below [PubMed]).

This was a landmark paper by Dr Andy Jones, consultant physician at the Manchester Adult CF Centre working with Prof. John Govan of Edinburgh, that was influential in the eventual introduction of widespread microbiological surveillance of CF centres in the UK. This led to the discovery that cross infection was a common occurrence in many of the large CF centres (Scott & Pitt 2004. below). A similar clinical situation with a transmissible P. aeruginosa had been reported from the Liverpool Paediatric CF clinic in 1996 (Cheng K et al, 1996 above) but did not have the same influence of national policy.

 

The papers from Manchester were influential in the introduction of a more rigorous policy of segregation according to microbiological status in most UK CF centres. In May 2001 the CF Trust published the report of its Control of Infection Group "Pseudomonas aeruginosa infection in people with cystic fibrosis. Suggestions for prevention and infection control". However, some clinicians accepted the report with some degree of reluctance for example one senior respected physician wrote in the Lancet- "There is a real risk of stigmatisation by sputum bacteriology, enhanced anxiety about what may be a relatively benign organism (many adults with CF remain well despite positive cultures of Pseudomonas aeruginosa for decades) and fear of attending a CF centre or any school or social event where another person with CF may be met. There are risks in doing too little but it may be worse to do too much". (Geddes DM. Lancet 2001; 358:522-523).

 

Also one London paediatrician wrote - "This (segregation) means there will be loss of continuity of care as well as flexibility for the families choosing which days they come to see us". Another of his paediatric colleagues described those of us at the UK CF Trust responsible for recommending patient segregation as "an unruly bunch of zealots" Fortunately only a minority of clinicians held these views!!

 

 

2001 Mahenthiralingam E, Vandamme P, Campbell ME, Henry DA, Gravelle AM, Wong LT, Davidson AG, Wilcox PG, Nakielna B, Speert DP. Infection with Burkholderia cepacia complex genomovars in patients with cystic fibrosis: virulent transmissible strains of genomovar III can replace Burkholderia multivorans. Clin Infect Dis 2001; 33:1469-1475.[PubMed]
Infection with Burkholderia cepacia complex in patients with cystic fibrosis (CF) results in highly variable clinical outcomes. The purpose of this study was to determine if there are genomovar-specific disparities in transmission and disease severity. B. cepacia complex was recovered from 62 patients with CF on one or more occasions (genomovar III, 46 patients; genomovar II [B. multivorans], 19 patients; genomovar IV [B. stabilis], 1 patient; genomovar V [B. vietnamiensis], 1 patient; and an unclassified B. cepacia complex strain, 1 patient).

Patient-to-patient spread was observed with B. cepacia genomovar III, but not with B. multivorans. Genomovar III strains replaced B. multivorans in 6 patients. Genomovar III strains were also associated with a poor clinical course and high mortality. Infection control practices should be designed with knowledge about B. cepacia complex genomovar status; patients infected with transmissible genomovar III strains should not be cohorted with patients infected with B. multivorans and other B. cepacia genomovars.

 

An important paper regarding the management of people with CF who are infected with organisms in the B. cepacia complex from experts in this area. Dr Mahenthiralingam is a leading CF microbiologist and now at Cardiff University in the UK.

 

 

2001 Moore JE, McIlhatton B, Shaw A, Murphy PG, Elborn JS. Occurrence of Burkholderia cepacia in foods and waters: clinical implications for patients with cystic fibrosis. J Food Protect 2001; 64:1076-1078.[PubMed].
Two hundred forty-eight retail "ready-to-eat" foodstuffs in eight food categories and 134 waters categorized into nine types were analyzed for the presence of the Burkholderia cepacia complex of organisms. Of these, 14 of 26 (53.8%) samples of raw unpasteurized bovine milk were positive for this organism. Consumption of raw unpasteurized milk may therefore act as a potential source of infection with this organism, which is of particular concern for patients with cystic fibrosis, where colonization and infection with this B. cepacia can lead to a fatal necrotizing pneumonia and premature death. In addition to the associated risk of infection from fecal pathogens, patients with cystic fibrosis should therefore avoid the consumption of raw unpasteurized milk to minimize the risk of becoming infected with this organism.

 

Of considerable practical importance as unpasteurised milk is still available in some countries. Distribution of raw milk is illegal in Scotland while it is legal in England, Wales, and Northern Ireland, the only registered producers are in England. About 200 producers sell raw, or "green top" milk direct to consumers, either at the farm, at a farmers' market, or through a delivery service. The bottle must display the warning "this product has not been heat-treated and may contain organisms harmful to health", and the dairy must conform to higher hygiene standards than dairies producing only pasteurised milk. As it is only legal to supply unpasteurised milk direct to consumers, it is illegal to be sold on the High Street, via shops or supermarkets. Raw milk is available in the USA but illegal in Canada.

 

 

2002 Moore JE, McIlhatton B, Buchanan J, Gilpin D, Shaw A, Hall V, Murphy PG, Elborn JS. Occurrence of Burkholderia cepacia in the hospital environment. Irish J Med Sci 2002; 171:131-133. [PubMed].
To determine the prevalence of Burkholderia cepacia from the environment in a regional adult cystic fibrosis (CF) care centre. B. cepacia was not detected from commonly shared items of equipment, staff hands, staff uniforms or toilets. In addition, the organism was not detected in toilet bowls, even in the B. cepacia unit.

With regard to positive environments for B. cepacia, 4/10 (40%) of the outside surfaces and inner rims of patients' plastic disposable sputum collection containers and 4/17 (23.5%) of air from patients' rooms, following physiotherapy, were positive. All positive samples originated in the B. cepacia segregation area of the inpatient wards and B. cepacia was not detected in the non-cepacia area of the CF centre. Consequently, these two positive sites should therefore be treated as high risk, where organisms may be potentially transmitted from environment to patient.

 

Dr John Moore is Clinical Microbiologist at the Belfast City Hospital and very active in research and clinical work including many practically useful papers on cystic fibrosis relating to the environment and infection prevention and control. This present study confirming that B.cepacia only appeared to be a potential problem in areas inhabited by CF patients already infected by the organism.

 

 

2002 Armstrong DS, Nixon GM, Carzino R, Bigham A, Carlin JB, Robins-Browne RM, Grimwood K. Detection of a widespread clone of Pseudomonas aeruginosa in a pediatric cystic fibrosis clinic. Am J Resp Crit Care 2002; 166:983-987 [PubMed]
The authors comment that cross-infection by Pseudomonas aeruginosa between unrelated patients with CF is believed to be uncommon. However, after detecting a genotypically identical strain of P. aeruginosa in five unrelated children with CF dying from severe lung disease at their centre, the authors determined its prevalence within a large CF clinic using pulsed-field gel electrophoresis and random amplified polymorphic DNA assays. P. aeruginosa was detected in 118 (78%) children of mean age 13.5 years - 65 (55%) of infected patients carried an indistinguishable or closely related strain and were more likely to have been hospitalized in the preceding 12 months for respiratory exacerbations.

This study demonstrates extensive spread of a single, clonal strain of P. aeruginosa in a large pediatric CF clinic. Whether such a strain is also more virulent than sporadic isolates remains to be determined however the fatal outcome for 5 of these children suggests this was almost certainly the case. As transmissible strains could emerge elsewhere, the authors suggested that other CF clinics may also need to consider molecular methods of surveillance for cross-infection.

This is a really tragic story and further evidence of the potential and at times very real dangers of spread of highly transmissible strains of P. aeruginosa. The fact the 5 children died attests to this strain's virulence and this type of highly transmissible infection also leads to a requirement for more treatment (Jones AM et al. 2002 below). This is another study recommending to others that molecular methods should be used when studying cross infection in CF centres. It is interesting and of some concern that around this time in some major CF centres, there were still clinicians who doubted the need for segregation even though the first major epidemic had been described as long ago as 1996 from Liverpool (Cheng et al, 1996 above).

 

 

2002 McCallum SJ, Gallagher MJ, Corkill JE, Hart CA, Ledson MJ, Walshaw MJ. Spread of an epidemic Pseudomonas aeruginosa strain from a patient with cystic fibrosis (CF) to non-CF relatives. Thorax 2002; 57:559-560.[PubMed]
Chronic infection with Pseudomonas aeruginosa is common in adults with CF and there is increasing evidence that transmissible strains may cross colonise patients. However, transmission of these strains by social contact to healthy non-CF individuals has not been described.
A case is presented where an adult CF patient colonised by an epidemic P. aeruginosa strain infected her non-CF parents with subsequent morbidity. This the first report of this occurring.

 

 

2002 Jones AM, Dodd ME, Doherty CJ, Govan JR, Webb AK. Increased treatment requirements of patients with cystic fibrosis who harbour a highly transmissible strain of Pseudomonas aeruginosa. Thorax 2002; 57:924-925.[PubMed]
A study was undertaken to see if there was a difference in treatment requirements between CF patients with chronic infection with their own unique P. aeruginosa strains (group 1) and those who harbour a highly transmissible strain (group 2). It was apparent that the patients who harbour the highly transmissible P. aeruginosa strain have a greater treatment burden than patients with CF who harbour their own unique strains.
The authors suggest that these findings support the need for microbiological surveillance for highly transmissible P. aeruginosa and the implementation of infection control measures to prevent cross infection.

 

 

2003 Robinson P, Carzino R, Armstrong D, Olinsky A. Pseudomonas cross-infection from cystic fibrosis patients to non-cystic fibrosis patients: implications for inpatient care of respiratory patients. J Clin Microbiol 2003; 41: 5741.[PubMed]
A 14-year-old boy with non-CF bronchiectasis secondary to chronic aspiration developed multiresistant Pseudomonas aeruginosa lower respiratory disease following several inpatient periods where accommodation and physiotherapy services were shared with CF patients known to be infected with the genetically identical strain of P. aeruginosa. Cross-infection with P. aeruginosa between CF patients and non-CF patients had not previously been described, and this finding raises significant issues relevant to the treatment of patients with non-CF suppurative lung disease.


Spread of a highly transmissible P. aeruginosa to a CF patient already chronically infected with P. aeruginosa had already been described from Liverpool (McCallum SJ et al. Lancet 2001; 358:558-560. above [PubMed]). The spread of infection to non-CF patients from CF patients is a definite risk in hospital wards, particularly if there are immunocompromised patients mixing with CF patients who have chronic P. aeruginosa infection a situation. I have observed this on a paediatric ward on one occasion in the years before cross infection with P. aeruginosa was not considered to be a significant risk and CF children mixed with non-CF children on the paediatric ward.

 

 

2003 Jørgensen IM, Johansen HK, Frederiksen B, Pressler T, Hansen A, Vandamme P, Høiby N, Koch C. Epidemic spread of Pandoraea apista, a new pathogen causing severe lung disease in cystic fibrosis patients. Pediatr Pulmonol 2003; 36:439-446. [PubMed]
Pandoraea apista must be added to the increasing list of pathogens capable of causing chronic lung infection in cystic fibrosis patients. It is most likely that this strain of P. apista was transmissible among patients with CF, leading to spread of infection from the index patient to 5 other patients exposed during participation in winter camps and/or hospitalization. All patients developed chronic infection with high levels of antibodies, and 4 patients had a downhill course of lung disease.


P. apista must therefore be considered a new and sometimes important pathogen for CF patients and one of the increasing number of unusual organism which are significant pathogens for people with CF. In this instance cohort isolation prevented further spread of P. apista in the CF centre. Such reports from large CF centres such as Copenhagen are useful for clinicians who subsequently encounter such organisms.

 

 

2003 Saiman L, Siegel J. Cystic Fibrosis Foundation. Infection control recommendations for patients with cystic fibrosis: microbiology, important pathogens, and infection control practices to prevent patient-to-patientransmission. [Review] [395 refs] Infect Cont Hosp Ep 2003; 24(5 Suppl):S6-52.[PubMed]
Report of a Consensus Development Conference organised by the CF Foundation to which representatives from both USA and Europe were invited. The result is a very detailed paper full of information and nearly 400 references!

 

 

2004 Al-Aloul M, Crawley J, Winstanley C, Hart CA, Ledson MJ, Walshaw MJ. Increased morbidity associated with chronic infection by an epidemic Pseudomonas aeruginosa strain in CF patients. Thorax 2004; 59:334-336. [PubMed]
Chronic infection with the Liverpool epidemic P. aeruginosa strain in CF patients confers a worse prognosis than infection with unique strains alone, confirming the need for patient segregation. Since this strain is common in many CF units, strain identification in all CF centres is essential. This can only be carried out using genomic typing methods.

The long term effects of the epidemic strain originally described by Cheng et al in 1996 in the Liverpool paediatric CF unit (Cheng K, et al. Spread of ß-lactam resistant Pseudomonas aeruginosa in a cystic fibrosis clinic. Lancet 1996; 348:639-642. [PubMed]).

 

 

 

2004 Regnath T, Kreutzberger M, Illing S, Oehme R, Liesenfeld O. Prevalence of Pseudomonas aeruginosa in households of patients with cystic fibrosis. Internat J Hyg Envir Health 2004; 207:585-588. [PubMed]
Using a standardized sampling protocol, the authors prospectively examined the presence of Pseudomonas aeruginosa (PA) in 102 households of people with CF in Germany. PA was detected in 73 (71.6%) of 102 households. PA was detected most frequently in drains of showers (39.6%), drainpipes of hand-basins in kitchens (35.0%) and bathrooms (34.7%), and drainpipes of toilets (26.5%). Toilet seats and dish-clothes did not show PA in any household. The frequency and intensity of cleaning measures did not impact the detection rate of PA.

 

Results of the present study for the first time determine the rate of contamination with PA in households of patients with CF. Future studies would determine the risk of transmission of PA from households locations to people with CF.

As staff in CF centres became aware of and took measures to prevent patient to patient spread of infection in hospitals, it became apparent that many new Pseudomonas infections were acquired from the environment outside the hospitals. Here the home is shown to be a rich source of these organisms.

 

 

2004 The Burkholderia cepacia complex. Suggestions for Prevention and Infection Control. Cystic Fibrosis Trust Infection Control Group. Second edition. London. Cystic Fibrosis Trust, September 2004.
Full text available on (www.cftrust.org.uk).


2004 Pseudomonas aeruginosa infection in people with cystic fibrosis. 2nd edition. Cystic Fibrosis infection Control Group. London. Cystic Fibrosis Trust, November 2004. Full text available on (www.cftrust.org.uk)

 

 

2004 Scott FW, Pitt TL. Identification and characterization of transmissible Pseudomonas aeruginosa strains in cystic fibrosis patients in England and Wales. J Med Microbiol 2004; 53:609-615. [PubMed]
Most previous studies of cross-infection with P. aeruginosa (PA) among patients with CF in the UK suggested that it is a rare occurrence. However, two recent UK reports of highly transmissible strains of PA in patients in regional centres in Liverpool (Cheng et al, 1996 above) and Manchester (Jones et al, 2001 above) raised questions as to the extent of the problem. These reports prompted the UK CF Trust to fund this nationwide survey to establish the distribution of PA genotypes among these patients. Isolates of PA were requested from over 120 hospitals in England and Wales and a sample size of approximately 20% of the CF patient population in each centre was recommended. In total, 1225 isolates were received from 31 centres (range 1 to 330). Single patient isolates were typed by SpeI macrorestriction and PFGE. A panel of strains of the common genotypes including representatives of reported transmissible strains was assembled and further characterized by fluorescent amplified fragment length polymorphism (FAFLP) genotyping.

 

The important findings were as follows:-

- At least 72% of all patients harboured strains with unique genotypes.
- Small clusters of related strains were evident in some CF centres, presumably indicating limited transmission of local strains.
- The most prevalent strain was indistinguishable from that previously described as the 'Liverpool' genotype, and accounted for approximately 11% of patient isolates from 15 centres in England and Wales.
- The second most common genotype (termed Midlands 1) was recovered from 86 patients in nine centres
- The third genotype, which matched closely the PFGE profile of Clone C, a genotype originally described in Germany, was found in eight centres and was isolated from 15 patients.
- A fourth genotype, identical to the published Manchester strain, was found in three centres.

 

FAFLP analysis revealed some microheterogeneity among strains of the Liverpool genotype but all isolates of this genotype were positive by PCR for a strain-specific marker.

 

These data are mentioned in detail in view of their great importance for clinic routines and suggest that cross-infection with PA has occurred both within and widely between CF centres in England and Wales.

The two most common genotypes accounted for more than one-fifth of patients' isolates examined and transmissible genotypes were found in all but three of the 31 CF centres studied. These results emphasize the need for continued surveillance of P. aeruginosa genotypes in CF patients to provide informed infection control policy in treatment centres.

 

 

2004 Jones AM, Dodd ME, Govan JR, Barcus V, Doherty CJ, Morris J, Webb AK. Burkholderia cenocepacia and Burkholderia multivorans: influence on survival in cystic fibrosis. Thorax 2004; 59:948-951. [PubMed]
Forty nine patients had an initial infection with either B. multivorans (n = 16) or B. cenocepacia (n = 33); 8/16 and 31/33, respectively, developed chronic infection (p<0.001). Deaths from "cepacia syndrome" occurred in both BCC groups. Patients with B. cenocepacia infection had a shorter survival than patients with P. aeruginosa infection (p = 0.01). There was no difference in survival between CF patients infected with B multivorans and P aeruginosa. There were no observed differences in changes in spirometry and BMI or treatment requirements between the BCC groups and respective controls. In CF, the genomovar status of BCC may influence both the likelihood of progression from initial to chronic infection and the overall survival of the patients.

 

This study from a large CF centre in Manchester confirms the more serious prognosis for patients infected with B. cenocepacia than for those infected with B. multivorans.

 

 

2004 Blackburn L, Brownlee K, Conway S, Denton M. 'Cepacia syndrome' with Burkholderia multivorans, 9 years after initial colonization. J Cyst Fibros 2004; 3:133-134. [PubMed]
A 16-year-old boy with cystic fibrosis developed 'cepacia syndrome' 9 years after the first isolation of Burkholderia multivorans. It is important to recognise that 'cepacia syndrome' is not restricted to those infected with genomovar type III strains and that rapid, irreversible clinical decline can occur many years after the first isolation of Burkholderia cepacia complex (Bcc).

 

So a word of warning after the reassuring report from the Manchester CF centre (Blackburn L et al, 2004 above) reproting that B. multivorans may occaisionally cause the cepacia syndrome.

 

 

2004 Courtney JM, Dunbar KE, McDowell A, Moore JE, Warke TJ, Stevenson M, Elborn JS. Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults. J Cyst Fibros 2004; 3:93-98. [PubMed]
Nineteen CF adults infected with BCC and 19 controls infected with Pseudomonas aeruginosa were studied over a 4-year period at the Adult CF Centre in Belfast. The BCC infected group displayed a significantly greater reduction of FEV(1) and BMI compared to the P. aeruginosa infected group. Sixteen patients infected with a single Burkholderia cenocepacia strain had a significantly greater rate of FEV(1) decline compared to those infected with Burkholderia multivorans (n=3) or P. aeruginosa (p=0.01 and p<0.0001, respectively). The rate of BMI decline was significantly greater in patients infected with B. cenocepacia compared to those with P. aeruginosa (p=0.007), but not significantly different in those with B. multivorans (p=0.29). BCC infection is associated with an accelerated decline in pulmonary function and BMI. Infection with a single B. cenocepacia strain was associated with a more rapid decline in lung function than those infected with either B. multivorans or P. aeruginosa.

 

Confirmation the B. cepacia should be avoided at all costs by people with CF, the infection with B. cenocepacia being more serious than with B. multivorans.

 

 

2004 O'Carroll MR, Syrmis MW, Wainwright CE, Greer RM, Mitchell P, Coulter C, Sloots TP, Nissen MD, Bell SC. Clonal strains of Pseudomonas aeruginosa in paediatric and adult cystic fibrosis units. Eur Respir J 2004; 24:101-106. [PubMed]
Despite recent reports of clonal strains of Pseudomonas aeruginosa in cystic fibrosis units, the need for routine microbiological surveillance remains contentious. Sputum was collected prospectively from productive patients attending the regional paediatric and adult CF units in Brisbane, Australia. All P. aeruginosa isolates were typed using pulsed-field gel electrophoresis. Spirometry, anthropometrics, hospitalisations and antibiotic sensitivity data were recorded.

The first 100 sputum samples (first 50 patients at each clinic) harboured 163 isolates of P. aeruginosa. A total of 39 patients shared a common strain (pulsotype 2), 20 patients shared a strain with at least one other patient and 41 patients harboured unique strains. Eight patients shared a strain identical to a previously reported Australian transmissible strain (pulsotype 1).

Compared with the unique strain group, patients harbouring pulsotype 2 were younger and had poorer lung function. Treatment requirements were similar in these two groups, as were the rates of multi resistance.

In conclusion, 59% of patients harboured a clonal strain, supporting the need for routine microbiological surveillance. In contrast to previously described clonal strains, the dominant pulsotype was indistinguishable from non clonal strains with respect to both colonial morphology and multi resistance. The clinical significance of clonal strains remains uncertain and requires longitudinal study.

 

Yet another major clinic where a significant number of patients shared a particular strain with others. In the case of those harbouring pulsotype2 strain, they were in worse condition. Most centres now regard the need for microbiological surveillance as mandatory.

 

 

2004 Al-Aloul M, Crawley J, Winstanley C, Hart CA, Ledson MJ, Walshaw MJ. Increased morbidity associated with chronic infection by an epidemic Pseudomonas aeruginosa strain in CF patients. Thorax 2004; 59:334-336. [PubMed]
Chronic infection with the Liverpool epidemic P. aeruginosa strain in CF patients confers a worse prognosis than infection with unique strains alone, confirming the need for patient segregation. Since this strain is common in many CF units, strain identification in all CF centres is essential. This can only be carried out using genomic typing methods.

 

The long term effects of the epidemic strain originally described by Cheng et al in 1996 in the Liverpool paediatric CF unit (Cheng K, et al. Spread of ß-lactam resistant Pseudomonas aeruginosa in a cystic fibrosis clinic. Lancet 1996; 348:639-642. [PubMed]).

 

 

2005 Barben J, Hafen G, Schmid J. Swiss Paediatric Respiratory Research Group. Pseudomonas aeruginosa in public swimming pools and bathroom water of patients with cystic fibrosis. J Cyst Fibros 2005; 4:227-231. [PubMed]
This study aimed to identify the prevalence of Pseudomonas aeruginosa (PA) in public swimming pools and water taps. Water was collected from public indoor and outdoor pools in the area of St. Gallen, Switzerland. In addition, standing and running water was sampled from bathroom water taps of 50 patients with CF. Outdoor pools: In 2002, none of the 72 specimens from 28 pools revealed PA. In 2003, three specimens from 46 pools (7%) revealed PA, each were from a different paddling pool. Indoor pools: two of 128 specimens from 56 pools (4%) identified PA, both were from non-public hydrotherapy pools. Water taps: in winter, none of the 102 specimens was colonized with PA. In summer, only two out of 50 specimens of the standing water were positive for PA but none of the running water revealed PA.

 

So the prevalence of PA in public swimming pools and bathroom water taps in the eastern part of Switzerland is very low. On hot summer days, outdoor paddling pools and standing tap water can contain PA. This study does not support recommendations to avoid public swimming pools or running tap water if the water is maintained according to hygiene guidelines. However, although the swimming pools in Switzerland are essentially free of bacteria unfortunately this is not general European experience. For example, a report from Northern Ireland found public swimming pools were frequently infected with PA (Moore JE et al. Incidence of Pseudomonas aeruginosa in recreational and hydrotherapy pools. Commun Dis Pub Health 2002; 5:23-26.[PubMed]). Also the consumer magazine "Which" in 2002 reported 35 of 61 samples from UK pools and spas fell outside acceptable bacteriological standards.

 

 

2005 Jones AM, Dodd ME, Govan JR, Doherty CJ, Smith CM, Isalska BJ, Webb AK. Prospective surveillance for Pseudomonas aeruginosa cross-infection at a cystic fibrosis center. Am J Resp Crit Care Med 2005; 171:257-260.[PubMed]
A 4-year prospective surveillance for Pseudomonas aeruginosa (PA) cross-infection at a large regional adult cystic fibrosis centre (Manchester, UK) showed that, despite purpose-built facilities in a new building and the practice of strict hygiene, PA cross-infection has continued. In contrast, individuals segregated from the cohort of patients with chronic PA infection but who attend the same centre have not acquired infection with transmissible PA strains. Simple infection control measures alone do not prevent the spread of some transmissible PA strains between individuals with cystic fibrosis. However, patient segregation effectively controlled spread of such strains.


These were the same transmissible PA strains previously described from Manchester (Jones et al, 2001 above; Jones et al, 2002 above).  So the term "highly transmissable" is very approriate when applied to these strains of P. aeruginosa.

 

 

2005 Al-Aloul M, Miller H, Stockton P, Ledson MJ. Walshaw MJ. Acute renal failure in CF patients chronically infected by the Liverpool epidemic Pseudomonas aeruginosa strain (LES). J Cyst Fibros 2005; 4:197-201. [PubMed]
Eight episodes of acute renal failure in adult CF patients, all occurring during the use of intravenous aminoglycosides for the treatment of pulmonary exacerbations with an epidemic multi-resistant Pseudomonas aeruginosa strain. Potential contributory factors are discussed.

 

These cases demonstrate another complication of infection by epidemic Pseudomonas strains in CF, and confirm the need for effective segregation policies to prevent this.

 

 

2005 Panagea S, Winstanley C, Walshaw MJ, Ledson MJ, Hart CA. Environmental contamination with an epidemic strain of Pseudomonas aeruginosa in a Liverpool cystic fibrosis centre, and study of its survival on dry surfaces. J Hosp Infect 205; 59:102-107. [PubMed]
The authors conducted an environmental survey in the Liverpool adult cystic fibrosis centre in order to determine the extent of environmental contamination with an epidemic strain of Pseudomonas aeruginosa that colonizes most CF patients in Liverpool, and to identify possible reservoirs and routes of cross-infection. In addition, they studied the survival of this Liverpool strain on dry surfaces, compared with that of other CF P. aeruginosa strains, to explore factors that might contribute to its high transmissibility.

Environmental contamination with Liverpool strain (LES) was only detected in close proximity to colonized patients (external surfaces of their respiratory equipment, and spirometry machine tubing and chair) and was short-lived. No persistent environmental reservoirs were found. LES was detected in the majority of air samples from inside patients' rooms, the ward corridor and the outpatient clinic. Survival of LES on dry surfaces was significantly longer than that for some other strains tested, but not compared with other strains shown not to be transmissible.
Improved environmental survival on its own, therefore, cannot explain the high transmissibility of this epidemic strain. The findings suggests that airborne dissemination plays a significant role in patient-to-patient spread of LES, and confirms the need to segregate those patients colonized by epidemic P. aeruginosa strains from all other CF patients.

 

A very helpful study when considering the management of patients infected with highly transmissible strains of P. aeruginosa.

 

 

2006 Festini F, Buzzetti R, Bassi C, Braggion C, Salvatore D, Taccetti G Mastella G. Isolation measures for prevention of infection with respiratory pathogens in cystic fibrosis: a systematic review. J Hosp Infect 2006; 64:1-6. [PubMed]
The aim of this review was to determine the evidence available to support the efficacy of isolation (or segregation) practices in preventing, delaying or reducing the risk for CF patients of acquiring P. aeruginosa and B. cepacia. In the absence of studies with an experimental, controlled design, the efficacy of isolation practices in preventing the transmission of respiratory pathogens in CF remains unproven. However, it is no surprise that the observational studies reviewed seem to support the implementation of isolation (or segregation) measures to reduce the risk of transmission of B. cepacia and P. aeruginosa in CF patients.

 

There is now certainly enough published evidence to support patient segregation according to microbiological status and a controlled trial would be unethical. The delay in introducing patient segregation and the reported occurrence of cross infection in some CF centres has provided adequate information that the practice is fully justified!!!

 

 

2006 Rønne Hansen C, Pressler T, Høiby N, Gormsen M. Chronic infection with Achromobacter xylosoxidans in cystic fibrosis patients; a retrospective case control study. J Cyst Fibros 2006; 5:245-251. [PubMed]
In cystic fibrosis, chronic infection of the airways with Achromobacter xylosoxidans has become more frequent. The pathogenic role of this is yet unclear. A retrospective case-control study of all patients chronically infected with A. xylosoxidans for at least 3 years. 15 patients (6 males) with chronic A. xylosoxidans infection were matched by age, FEV(1) and body mass index z-score to 15 controls (7 males) at the time of establishment of chronic infection. Eight patients harboured a common A. xylosoxidans strain, indicating either cross-infection or a common source.

The authors conclude that A. xylosoxidans may lead to a decline in lung function in a subgroup of chronically infected CF patients characterised by a rapid increase in specific precipitating antibodies. Cross-infection may possibly occur.

 

A review from the Copenhagen CF Centre of a relatively new problem in people with CF.

 

 

2007 Barth AL, de Abreu E Silva FA, Hoffmann A, Vieira MI, Zavascki AP, Ferreira AG, da Cunha LG Jr, Albano RM, de Andrade Marques E. Cystic fibrosis patient with Burkholderia pseudomallei infection acquired in Brazil. Microbiology 2007; 45:4077-80. [PubMed]
Burkholderia pseudomallei is rarely isolated from patients with CF outside known areas of endemicity such as Thailand. These authors report the recovery of B. pseudomallei from the sputum of a cystic fibrosis patient who lives in Brazil and highlight the importance of careful attention to unusual non-fermentative gram-negative rods in cystic fibrosis patients (also Visca et al. 2001 above for Thailand experience).

 

 

2007 Kennedy MP, Coakley RD, Donaldson SH, Aris RM, Hohneker K, Wedd JP, Knowles MR, Gilligan PH, Yankaskas JR. Burkholderia gladioli: five year experience in a cystic fibrosis and lung transplantation center. J Cyst Fibros 2007; 6:267-273. [PubMed]
The impact of infection with Burkholderia gladioli in CF is unknown. Thirty-five patients were culture positive for B. gladioli, including 33 CF patients. Two-thirds of these isolates were susceptible to usual anti-Pseudomonal antibiotics. After acquisition, only 40% of the CF patients became chronically infected; chronic infection was associated with resistance to antibiotics on initial culture and failure of eradication after antibiotic therapy. The impact of acquisition of B. gladioli infection in chronic infection was variable. Three CF patients with chronic infection underwent lung transplantation. One post-transplant patient developed a B. gladioli mediastinal abscess, which was treated successfully. The authors concluded that the majority of patients who culture positive for B. gladioli have CF. B. gladioli infection is often transient and is compatible with satisfactory post-lung transplantation outcomes.

 

Unfamiliar organisms are periodically isolated from people with CF and reports of experience such as this are very helpful in defining their importance for the clinician encountering the infection for the first time.

 

 

2008 Ullrich G, Wiedau S, Schulz W, Steinkamp G. Parental knowledge and behaviour to prevent environmental P. aeruginosa acquisition in their children with CF. J Cyst Fibros 2008; 7:231-237. [PubMed]
Most parents displayed erroneous beliefs regarding P. aeruginosa (PA) infection. Families performed a mean of 11 different hygienic measures, e.g. they prevented their child from being the first person to use the bathroom in the morning (72%) or from bathing in gravel pits and standing water (52%). The majority of parents felt markedly (44%) or somewhat (44%) stressed that their child might acquire PA, and many parents felt markedly (16%) or somewhat (43%) restricted and stressed by the hygienic measures. Less stressed parents tended to have more knowledge and undertook fewer measures.
The authors suggest that when informing and teaching parents on the nature of PA infection, caregivers should provide clear recommendations on reasonable actions to be taken. Also, physicians should anticipate and adequately respond to parental fears and misconceptions.

 

It is understandable that parents seek to prevent their children being exposed unnecessarily to P. aeruginosa which is unfortunately ubiquitous in the environment. Striking a balance between a normal life style and over caution is very difficult for the parents as most of the avoidance recommendation have not been put to any form of trial. However, it seems sensible to reduce exposure to environments which are known to harbour P. aeruginosa. They can be reassured that, provided regular cultures are performed, an early infection with P. aeruginosa can be eradicated by appropriate antibiotic treatment so, although better avoided, the early infection is not the potentially disastrous occurrence it was in years gone by.

 

An article at the end of this Cross Infection section reviews the likely sources of P. aeruginosa in the environment - "The environment as a source of Pseudomonas aeruginosa and some other potential pathogens".” Sept. 2007 Revised 2014 by Jim Littlewood with expert advice from Dr Miles Denton.

 

 

2008 Jacobs JL, Fasi AC, Ramette A, Smith JJ, Hammerschmidt R, Sundin GW. Identification and onion pathogenicity of Burkholderia cepacia complex isolates from the onion rhizosphere and onion field soil. Appl & Environ Microbiol 2008; 74:3121-3129. [PubMed]
Genotypic identification and pathogenicity characterization were performed on B. cepacia complex isolates from the rhizosphere of onion and organic soils in Michigan. A total of 1,290 isolates, 980 rhizosphere and 310 soil isolates, were assigned to the species B. cepacia (160), B. cenocepacia (480), B. ambifaria (623), and B. pyrrocinia (27). The majority of isolates identified as B. cepacia (85%), B. cenocepacia (90%), and B. ambifaria (76%) were pathogenic in a detached onion bulb scale assay and caused symptoms of water soaking, maceration, and/or necrosis.

 

This study confirmed that multiple B. cepacia complex species colonize the onion rhizosphere and have the potential to cause sour skin rot disease of the onion. In addition, the onion rhizosphere is a natural habitat and a potential environmental source of B. cenocepacia. Following the introduction of segregation of patients growing B. cepacia most new infections were with such environmentally acquired organisms.

 

 

2008 Zhou J, Garber E, Saiman L. Survey of infection control policies for patients with cystic fibrosis in the United States. Am J Infect Contr 2008; 36:220-222. [PubMed]
Written infection control policies used at CF care sites in the United States were compared with recently published guidelines (Saiman et al, 2003). Most policies recommended contact precautions for hospitalized patients infected with Burkholderia cepacia complex (73%), multidrug-resistant organisms (63%), and methicillin-resistant Staphylococcus aureus (64%). Socializing among CF patients was discouraged in 80% of inpatient policies and 55% of outpatient policies. Although routine mask use by patients remains an unresolved issue, many policies advocated this practice. Future studies should address barriers to implementation of these evidence-based guidelines and continue to monitor implementation.

 

That contact precautions were only recommended in 73% of centres even with B. cepacia is rather surprising one would have expected 100%. Permitting contact between people with B. cepacia in a CF centre would raise serious issues in the UK.

 

 

2008 Brimicombe RW, Dijkshoorn L, van der Reijden TJ, Kardoes I, Pitt TL, van den Broek PJ, Heijerman HG. Transmission of Pseudomonas aeruginosa in children with cystic fibrosis attending summer camps in The Netherlands. J Cyst Fibros 2008; 7:30-36.[PubMed]
This study aimed to establish the degree of transmission resulting in subsequent infection of P. aeruginosa among 80 children with CF attending holiday camps in The Netherlands. The study was performed in the summer of 2001 in four camps organised simultaneously at different locations. Sputum was collected on day 1 of the holiday, and three and six months later. Different morphotypes of P. aeruginosa from sputum were genotyped by AFLP analysis. Criteria were defined for the degree of evidence of transmission. There were 18 cases of possible, 2 cases of “probable” transmission and 1 case of “highly probable” transmission. Two predominant types of P. aeruginosa were found (types 18 and 23). Type 18 was already prevalent on day 1 mostly in younger children and was involved in eleven cases of transmission; type 23 was involved in six cases of transmission among older children.

 

There was a considerable risk of transmission of P. aeruginosa during these holiday camps for children with CF in The Netherlands. Two genotypes of P. aeruginosa appeared to be easily transmissible, one of which seemed common in the Dutch CF population.

Previous work from the Netherlands had shown little evidence of cross infection at camps and at the time the professionals involved considered the benefits of the holidays outweighed the risks of infection. For example in 1995 Hoogkamp-Korstanje et al (J Clin Microbiol 1995; 33:572-575.[PubMed]) considered the risk was comparable with that observed in the community. "We conclude that the risk of cross infection is trivial compared with the obvious joy and social benefit derived from a holiday camp". It is interesting how many years elapsed before these findings were published - holiday in 2001 and publication in 2008. A similar long interval occurred in the paper from Copenhagen (Ojeniyi et al, 2000. [PubMed] when the study in 1990 was reported in 2000.[PubMed].

 

 

2008 Mohan K, Fothergill JL, Storrar J, Ledson MJ, Winstanley C, Walshaw MJ. Transmission of Pseudomonas aeruginosa epidemic strain from a patient with cystic fibrosis to a pet cat. Thorax 2008; 63:839-840. [PubMed]
Chronic infection with Pseudomonas aeruginosa is common in cystic fibrosis (CF) and certain strains are more transmissible and virulent than others. Of these, the Liverpool Epidemic Strain (LES) is highly transmissible and cross infection has been reported between patients with CF and healthy non-CF relatives. However, the risk of transmission from humans to animals is unknown. The first report of interspecies transmission of the LES strain of P. aeruginosa from an adult patient with CF to a pet cat is described. This development further complicates the issue of infection control policies required to prevent the spread of this organism.

 

 

2008 Mahenthiralingam E, Baldwin A, Dowson CG. Burkholderia cepacia complex bacteria: opportunistic pathogens with important natural biology. J App Microbiol 2008; 104:1539-1551. [PubMed]
Interaction with plants around their roots and foliage forms the natural habitat for a wide range of gram-negative bacteria such as Burkholderia, Pseudomonas and Ralstonia. During these interactions many of these bacteria facilitate highly beneficial processes such as the breakdown of pollutants or enhancement of crop growth. All these bacterial species are also capable of causing opportunistic infections in vulnerable individuals, especially people with cystic fibrosis (CF).

Here the authors review the current understanding of the Burkholderia cepacia complex (Bcc) as a group of model opportunistic pathogens, contrasting their clinical epidemiology with their ecological importance. Currently, the B. cepacia complex is composed of nine formally named species groups which are all difficult to identify using phenotypic methods. Genetic methods such as 16S rRNA and recA gene sequence analysis have proven useful for Bcc species identification. Multilocus sequence typing (MLST) is also emerging as a very useful tool for both Bcc strain and species identification.

Historically, Burkholderia cenocepacia was the most dominant Bcc pathogen in CF, however, probably as a result of strict infection control practices introduced to control the spread of this species, its prevalence has been reduced. Burkholderia multivorans is the now the most dominant Bcc infection encountered in the UK CF population, a changing epidemiology that also appears to be occurring in the US CF population. The distribution of Bcc species residing in the natural environment may vary considerably with the type of environment examined. Clonally identical Bcc strains have been found to occur in the natural environment and cause infection. The contamination of medical devices, disinfectants and pharmaceutical formulations has also been directly linked to several outbreaks of infection. In the last 10 years considerable progress has been made in understanding the natural biology and clinical infections caused by this fascinating group of bacteria.

An up-to-date review of the B. cepacia complex by Esch. Malhenthiralingam, an expert on the subject of BC complex.The summary is reproduced in full.

 

 

2008 Johansen HK, Moskowitz SM, Ciofu O, Pressler T, Høiby N. Spread of colistin resistant non-mucoid Pseudomonas aeruginosa among chronically infected Danish cystic fibrosis patients. J Cyst Fibros 2008; 7:391-397. [PubMed]

Colistin resistant Pseudomonas aeruginosa have rarely been reported in cystic fibrosis (CF) patients. We performed a 17-year prospective study on colistin susceptibility and compared our findings with clinical variables. The first outbreak started in 1995 and lasted 5 years. It involved 27 CF patients who had inhaled colistin twice daily for a median of 10 years. Colistin resistant isolates persisted in individual patients for a median of 75 days after colistin was withdrawn. A second outbreak started in 2004. It involved 40 patients, 17 of whom were the same as in the first outbreak. Most resistant isolates belonged to two major clones that had similar genotypes in the two outbreaks. The P. aeruginosa isolates were all non-mucoid and they appeared in a group of chronically infected patients that had been admitted to the same ward for antibiotic treatment and had been followed at the same week-days in the outpatient clinic. Patients were individually isolated to avoid cross-infection and colistin inhalation was avoided in the CF outpatient clinic and in the ward after both outbreaks.

 

Since 2004, no further spread has been observed. It is important that the colistin resistant clones do not spread to non-infected patients since colistin is an important antibiotic for eradication of initial and intermittent P. aeruginosa colonisation. There is infrequent resistance even with widespread use of colistin in the Danish CF centre.

 

 

2009 Wainwright CE, France MW, O'Rourke P, Anuj S, Kidd TJ, Nissen MD, Sloots TP, Coulter C, Ristovski Z, Hargreaves M, Rose BR, Harbour C, Bell SC, Fennelly KP. Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis. Thorax 2009; 64:926-931. [PubMed]
Pseudomonas aeruginosa was isolated in cough aerosols of 25 subjects (89%), 22 of whom produced sputum samples. P aeruginosa from sputum and paired cough aerosols were indistinguishable by molecular typing. In four cases the same genotype was isolated from ambient room air. Approximately 70% of viable aerosols collected during voluntary coughing were of particles <or=3.3 micron aerodynamic diameter. P aeruginosa, Burkholderia cenocepacia, Stenotrophomonas maltophilia and Achromobacter xylosoxidans were cultivated from respiratory particles in this size range. Positive room air samples were associated with high total counts in cough aerosols (p = 0.003). The magnitude of cough aerosols was associated with higher forced expiratory volume in 1 s (r = 0.45, p = 0.02) and higher quantitative sputum culture results (r = 0.58, p = 0.008).

The authors concluded that during coughing, patients with CF produce viable aerosols of P aeruginosa and other Gram-negative bacteria of respirable size range, suggesting the potential for airborne transmission.

 

This study provides further evidence of the potential for airbourne transmission of pathogens between people with CF indications that segregation rather than mere hygienic measures are required to prevent spread of infection.

 

 

2009 Albini S, Abril C, Franchini M, Hüssy D, Filioussis G. Stenotrophomonas maltophilia isolated from the airways of animals with chronic respiratory disease. Schweizer Archiv fur Tierheilkunde 2009; 151:323-328. [PubMed]
Stenotrophomonas maltophilia (S. maltophilia) is frequently isolated from humans with cystic fibrosis. Seven strains of S. maltophilia isolated from animals are described, of which 5 strains were harvested from 3 horses, a dog and a cat with chronic respiratory disease. Analysis with pulsed field gel electrophoresis revealed that 2 horses, which were boarded in the same clinic but two years apart, harboured the same strain of S. maltophilia.

 

In recent years S. maltophilia is more frequently isolated from people with CF and although the organism appears to be ubiquitous it is useful to know that animals are one potential source.

 

 

2010 Aaron SD, Vandemheen KL, Ramotar K, Giesbrecht-Lewis T, Tullis E, Freitag A, Paterson N, Jackson M, Lougheed MD, Dowson C, Kumar V, Ferris W, Chan F, Doucette S, Fergusson D. Infection with transmissible strains of Pseudomonas aeruginosa and clinical outcomes in adults with cystic fibrosis. JAMA 2010; 304:2145-2153. [PubMed]
Of 446 patients with CF, 102 were infected with 1 of 2 common transmissible strains of P. aeruginosa. Sixty-seven patients were infected with strain A (15%), 32 were infected with strain B (7%), and 3 were simultaneously infected with both strains (0. 6%). Strain A was found to be genetically identical to the Liverpool epidemic strain but strain B has not been previously described as an epidemic strain. Compared with patients infected with unique strains of P. aeruginosa, these patients had similar declines in lung function but the 3-year rate of death or lung transplantation was significantly greater in those infected with the Liverpool epidemic strain (18. 6%) compared with those infected with unique strains (8. 7%). The authors concluded that a common strain of P. aeruginosa (Liverpool epidemic strain/strain A) infects patients with cystic fibrosis in Canada and the United Kingdom. Infection with this strain in adult Canadian patients with cystic fibrosis was associated with a greater risk of death or lung transplantation.

 

This study from Canada confirms the increased morbidity of those patients who are infected by a transmissible strain of P. aeruginosa (Liverpool epidemic strain/strain A). This was the experience from the UK reported initially by Andy Jones and colleagues from Manchester (Jones AM et al. Lancet 2001; 358:557-558. [PubMed]).  The Liverpool strain was initially reported in children attending the Alder Hey Children's Hospital CF clinic in Liverpool (Cheng K et al. Lancet 1996; 348:639-642. [PubMed]) where it is still a significant problem in the Liverpool adult CF unit.

 

 

2010 Maeda Y, Stanley T, Stirling J, Griffiths M, Calvert A, Stuart Elborn J, Cherie Millar B, Goldsmith CE, Rendall J, Loughrey A, Rooney PJ, Moore JE. No evidence of transmission of bacteria between reptiles and a CF patient--a case report of a young adult CF patient and reptiles. Zoonoses & Public Hlth 2010; 57:e47-53. [PubMed]
A microbiological study was undertaken to assess the risk of infection to a CF patient from a collection of pet reptiles, particularly atypical mycobacteria. This study helped to verify that the reptiles under the care of the CF patient did not harbour bacterial organisms that would normally be pathogenic to CF patients. However, the chronic carriage of Pseudomonas aeruginosa and other pathogens in the CF patient may constitute a greater risk of infection to the animals being handled! Therefore, stringent infection control precautions by CF patients and their pets are indicated, particularly adherence to hand washing and disinfection, when handling the animals, their litter or when working with their immediate environment, to potentially minimize the spread of bacterial and other pathogens from animal to human and vice versa. Detailed risk assessments therefore need to be undertaken by clinicians and veterinarians to detail working models that protect both animals and patients from pathogens originating from the other.

 

This single case report draws attention to the potential risks from reptiles and similar pets which have been reported a potential source of infection for people with CF. (www. PetEducation. com Common bacterial infections in Turtles and Tortoises).

 

 

2010 Clifton IJ, Peckham DG. Defining routes of airborne transmission of Pseudomonas aeruginosa in people with cystic fibrosis. [Review]. Exp Rev Respir Med 2010; 4:519-529. [PubMed]
The route of cross-infection between people with CF is not clear, but there is increasing evidence that an airborne route may be important. Laboratory studies have shown that P. aeruginosa can survive within droplet nuclei and can potentially remain suspended within aerosols for prolonged periods. Depending upon the air flows, this may result in the bacteria travelling significant distances. A number of clinical studies have demonstrated that people with CF can produce aerosols containing P. aeruginosa and Burkholderia cepacia complex. Infection control guidelines need to consider the possibility of droplet, including small-droplet nuclei, transmission of P. aeruginosa and other pathogens between people with CF. Further studies are needed to more accurately quantify the risk of cross-infection between people with CF and to evaluate interventions to minimize the risk.

 

A number of recent studies raise the possibility of droplet airbourne spread is a factor to be considered when organising cross infection measures in a CF unit.

 

 

2010 Jones AM, Dodd ME, Morris J, Doherty C, Govan JR, Webb AK. Clinical outcome for cystic fibrosis patients infected with transmissible Pseudomonas aeruginosa: an 8-year prospective study. Chest 2010; 137:1405-9. [PubMed]
Although there is now compelling evidence for cross-infection by strains of Pseudomonas aeruginosa at some specialist cystic fibrosis centres, the clinical impact of infection by transmissible strains is unclear. In an 8-year prospective study, the authors compared the clinical outcome of two groups of patients with CF infected by transmissible (n = 28) and sporadic strains (n = 52) of P. aeruginosa. There were no differences between the two groups in survival, annual changes in spirometry, or BMI. ; but there were differences in requirements for IV antibiotic treatment (mean [SD]: 29. 3 [21. 9] days vs 53. 1 [32. 5] days) and hospitalization (median [range]: 11. 6 [1. 1, 49. 3] days vs 23. 3 [5. 5, 103. 6] days) between patients infected with sporadic and transmissible strains of P aeruginosa, respectively. The authors concluded that infection by transmissible P. aeruginosa does not increase mortality but is associated with increased health-care and antibiotic use for patients with CF.

 

Highly transmissible strains of P. aeruginosa were described from the Liverpool paediatric CF clinic in 1996 (Cheng et al. 1996.[PubMed]) and from the Manchester unit by Andy Jones and colleagues and this paper is a follow-up prospective study from Manchester comparing the outlook for patients infected with transmissible strains and sporadic strains. The results confirm that the patients with the transmissible strains have more problems, need more care and IV antibiotics but do not have an increased mortality during the 8 years of the study.

 

 

2010 Mohan K, Lakshman V, Fothergill JL, Ledson MJ, Winstanley C, Walshaw MJ. Empyema due to a highly transmissible Pseudomonas aeruginosa strain in an adult cystic fibrosis patient. J Med Microbiol 2010; 59:614-616. [PubMed]
Despite the predilection of P. aeruginosa for the lungs of CF people, infection of the pleura is much less common and is not well described in the CF population. These authors describe what is believed to be the first case of pleural empyema due to a particularly pathogenic transmissible strain of P. aeruginosa (the Liverpool epidemic strain) in an adult CF patient.

Yet another complication related to the Liverpool epidemic strain of P. aeruginosa

 

 

2010 Doe SJ, McSherry A, Iceless B, Earns AM, Bright-Thomas R, Brennan AL, Webb AK, Jones AM. Patient segregation and aggressive antibiotic eradication therapy can control methicillin-resistant Staphylococcus aureus at large cystic fibrosis centres. J Cyst Fibros 2010; 9:104-109.
The prevalence of MRSA in patients with CF has risen in recent years. The authors adhere to a policy of segregation and barrier nursing to manage patients with MRSA, and actively pursue eradication of MRSA. They have evaluated their experiences of MRSA infection in their large adult CF centre. A retrospective review of all MRSA-positive patients from 1998 to 2008 was undertaken. Isolates were subjected to molecular identification to elucidate possible patient-to-patient transmission events. Eradication attempts were scrutinised. They have maintained a low incidence and prevalence (below 3%) of MRSA within this large cohort. A total of 15 pulsotypes of MRSA were identified among the 24 isolates examined, epidemiological data suggested no patient-patient transmission. Based on 6 month follow-up data, successful eradication was achieved in 81% patients. This includes those who had harboured infection for some time. Twenty-one (80. 8%) required only one course of treatment, 3 (11. 6%) patients required two different regimes and 2 (7. 5%) required three courses to fully eradicate the organism. They concluded that strict infection control procedures can control MRSA infection and keep the prevalence low in CF clinics. Eradication is achievable in the majority of patients even when significant time has lapsed from initial isolation. In some instances, up to 3 courses of antibiotics were required to achieve eradication.

 

Encouraging experience from the Manchester Adult CF Centre showing the prevalence of MRSA can be maintained at a low level with careful monitoring, infection control procedures and aggressive treatment

 

 

2010 Clifton IJ, Fletcher LA, Eggs CB, Denton M, Conway SP, Peckham DG. An aerobiological model of aerosol survival of different strains of Pseudomonas aeruginosa isolated from people with cystic fibrosis. J Cyst Fibros 2010; 9:64-68.[PubMed] .

Pseudomonas aeruginosa is a common and important pathogen in people with cystic fibrosis (CF). Recently epidemic strains of P. aeruginosa associated with increased morbidity, have been identified. The method of transmission is not clear, but there is evidence of a potential airborne route. The aim of this study was to determine whether different strains of P. aeruginosa isolated from people with CF were able to survive within artificially generated aerosols in an aerobiological chamber. Viable P. aeruginosa could still be detected up to 45min after halting generation of the aerosols. All of the strains of P. aeruginosa expressing a non-mucoid phenotype isolated from people with CF had a reduced ability to survive within aerosols compared to an environmental strain. Expression of a mucoid phenotype by the strains of P. aeruginosa isolated from people with CF promoted survival in the aerosol model compared to strains expressing a non-mucoid phenotype.

 

Increasing evidence of airbourne transmission of P. aeruginosa between people with CF.

 

Clifton IJ, Fletcher LA, Eggs CB, Denton M, Conway SP, Peckham DG. An aerobiological model of aerosol survival of different strains of Pseudomonas aeruginosa is a common and important pathogen in people with cystic fibrosis (CF). J Cyst Fibros 2010;9:64-68. 19944655 [PubMed]

Recently epidemic strains of P. aeruginosa associated with increased morbidity, have been identified. The method of transmission is not clear, but there is evidence of a potential airborne route. The aim of this study was to determine whether different strains of P. aeruginosa isolated from people with CF were able to survive within artificially generated aerosols in an aerobiological chamber. Viable P. aeruginosa could still be detect of Pseudomonas aeruginosa isolated from people with cystic fibrosis. J Cyst Fibros 2010; 9:64-68. [PubMed] led up to 45min after halting generation of the aerosols. All of the strains of P. aeruginosa expressing a non-mucoid phenotype isolated from people with CF had a reduced ability to survive within aerosols compared to an environmental strain. Expression of a mucoid phenotype by the strains of P. aeruginosa isolated from people with CF promoted survival in the aerosol model compared to strains expressing a non-mucoid phenotype.

 

 

 

2010 Feasting F, Tetany G, Glassy V, Nary S, Bisotun S, Sci-fi D, Bragging C. A 1-m distance is not safe for children with cystic fibrosis at risk for cross-infection with Pseudomonas aeruginosa. Am J Infect Control 2010; 38:244-245. [PubMed]

Although maintaining a distance of 1 meter between persons with cystic fibrosis is a universal recommendation to prevent respiratory cross-infections such as Pseudomonas aeruginosa, evidence supporting this preventive measure is scarce. Examining 336 samples from 42 patients with CF collected experimentally from sterile surfaces after speaking and coughing, we found that transmission of P. aeruginosa beyond 1 meter is possible during both talking and coughing, although the probability is low (1.7%).

 

This is valuable information and similar to that from Leeds indicating that P. aeruginosa may travel greater distances than 1 meter with obvious implications for cross infection measures (Clifton IJ. Peckham DG. Exp Rev Respir Med 2010; 4:519-529. [PubMed]).

 

 

2011 Lutz JK, Lee J. Prevalence and antimicrobial-resistance of Pseudomonas aeruginosa in swimming pools and hot tubs. Int J Environ Res [Electronic Resource] 2011; 8:554-564. [PubMed]
The aim of this surveillance study was to determine the background prevalence and antimicrobial resistance profile of P. aeruginosa in 8 swimming pools and 3 hot tubs. Twenty-three samples (21%) were positive for P. aeruginosa. Resistance was noted to several antibiotic agents. The results of this surveillance study indicate that 96% of P. aeruginosa isolates tested from swimming pools and hot tubs were multidrug resistant. These results may have important implications for cystic fibrosis patients and other immune-suppressed individuals, for whom infection with multidrug-resistant P. aeruginosa would have greater impact. The results underlie the importance of rigorous facility maintenance, and provide prevalence data on the occurrence of antimicrobial resistant strains of this important recreational water-associated and nosocomial pathogen.

 

This study from Ohio USA shows 21% of a small sample of indoor swimming pool samples were infected with multidrug resistant P. aeruginosa. Findings from different studies of different environments do vary however but this present finding does seem particularly high. Swimming pools are generally safe provided the recommended programme of maintenance is carried out. - but standards do vary. In a "Which" magazine survey in the UK in 2002 no less than 35 of 61 samples from pools and spas fell outside acceptable microbiological standards. 9 posed a definite and 3 a serious risk to bathers; spa pools were worse than swimming pools.

 

 

2011 Zalar P, Novak M, de Hoog GS, Gunde-Cimerman N. Dishwashers - a man-made ecological niche accommodating human opportunistic fungal pathogens. Fungal Biology 2011; 115:997-1007. [PubMed]
Enrichment of fungi that may require specific environmental conditions was observed in dishwashers, 189 of which were sampled in private homes of 101 towns or communities. One-hundred-two were sampled from various localities in Slovenia; 42 from other European countries; 13 and 3 from North and South America, respectively; 5 from Israel; 10 from South Africa; 7 from Far East Asia; and 7 from Australia. Isolation was performed on samples incubated at 37C. Species belonging to genera Aspergillus, Candida, Magnusiomyces, Fusarium, Penicillium and Rhodotorula were found occasionally, while the black yeasts Exophiala dermatitidis and Exophiala phaeomuriformis (Chaetothyriales) were persistently and most frequently isolated. Sixty-two percent of the dishwashers were positive for fungi, and 56% of these accommodated Exophiala. Both Exophiala species are known to be able to cause systemic disease in humans and frequently colonize the lungs of patients with cystic fibrosis.

The authors conclude that high temperature, high moisture and alkaline pH values typically occurring in dishwashers can provide an alternative habitat for species also known to be pathogenic to humans.

 

This is a very detailed paper the full version of which is available without cost on the internet. In view of the increasing importance of fungal infections such as Aspergillus in people with CF, this is useful information although the presence of these organisms seem to represent a potential more than definite threat at this stage.

 

 

2012 Register KB, Sukumar N, Palavecino EL, Rubin BK, Deora R. Bordetella bronchiseptica in a Paediatric Cystic Fibrosis Patient: Possible Transmission from a Household Cat. Zoonoses & Public Health 2012: 59:246-250. [PubMed]
Bordetella bronchiseptica is a zoonotic respiratory pathogen commonly found in domesticated farm and companion animals, including dogs and cats. Here, we report isolation of B. bronchiseptica from a sputum sample of a cystic fibrosis patient recently exposed to a kitten with an acute respiratory illness. Genetic characterization of the isolate and comparison with other isolates of human or feline origin strongly suggest that the kitten was the source of infection.

 

Domestic pets seem to to be increasingly identified as a source of respiratory infection for people with CF. This is a new one!

 

2012 Wiehlmann L, Cramer N, Ulrich J, Hedtfeld S, Weissbrodt H, Tummler B. Effective prevention of Pseudomonas aeruginosa cross-infection at a cystic fibrosis centre - results of a 10-year prospective study. Int J Med Microbiol 2012; 302:69-77.[PubMed]
The authors tested the efficacy of measures to prevent nosocomial acquisition of P. aeruginosa at their Paediatric CF centre in a prospective 10-year study. P. aeruginosa-positive and P. aeruginosa-negative patients were seen in alternating weeks at the outpatient clinic. Faucets were equipped with filters to prevent bacterial contamination of tap water. Serial isolates were collected since the first documentation of a P. aeruginosa-positive culture and genotyped with a multimarker microarray.

During the 10-year study, the annual prevalence of patients with at least one P. aeruginosa-positive culture was 39+/-6% in a population of 149+/-12 patients. P. aeruginosa was detected for the first time in 54 patients of whom 11 patients became chronically colonised with P. aeruginosa. Transient colonisations were recorded 97 times. A nosocomial acquisition of P. aeruginosa at the CF centre probably happened in one case. The worldwide dominant clones in the global P. aeruginosa population were also the most abundant clones in the panel of 324 early CF isolates. No rare clone had expanded by nosocomial transmission.

The authors concluded that cross-infection with P. aeruginosa was prevented with simple hygienic measures at a CF centre that had experienced local outbreaks of nosocomial spread among unrelated patients in the past.

 

It was disappointing that 11 of the 54 (20%) patients who had P. aeruginosa for the first time became chronically infected. However, the study is reassuring in showing that all the various precautions which are now customary are effective in preventing cross infection in the CF clinic.

 

 

2012 Griffiths AL, Wurzel DF, Robinson PJ, Carzino R, Massie J. Australian epidemic strain pseudomonas (AES-1) declines further in a cohort segregated cystic fibrosis clinic. J Cyst Fibros 2012; 11:49-52. [PubMed]
To evaluate changes in prevalence of an epidemic strain of Pseudomonas aeruginosa (AES-1, Australian epidemic strain, type 1) in a paediatric cystic fibrosis (CF) centre practising cohort segregation, to describe the patients' clinical characteristics at acquisition and observe mortality rates.

Cohort segregation was introduced in our paediatric CF clinic January 2000. The prevalence of AES-1 was analysed in 1999, 2002 and 2007. Age at acquisition, lung function, presence of bronchiectasis, hospitalisations, prior P. aeruginosa infection and mortality rates were collected. AES-1 infection was determined by pulse-field-gel-electrophoresis (PFGE) on airway specimen cultures taken three monthly.

The prevalence of AES-1 declined from 21% in 1999 to 14% in 2002 (risk difference 7% (95% CI 1,13) p=0.0256) and to 6% in 2007 (risk difference 8% (95% CI 3,13) p=0.0018). New acquisitions after the introduction of cohort segregation were uncommon (10 by 2002 and another 7 by 2007) with a declining incidence of 3.3 cases/year (1999 to 2002) compared to 1.4 cases/year (2002 to 2007). Twenty-two of 32 (69%) deaths between 1999 and 2007 occurred in patients infected with AES-1.

The authors concluded that cohort segregation has been associated with reductions in the prevalence of AES-1 in their CF clinic. Mortality was higher in patients infected with AES-1 than other organisms.

 

The effects of this Australian epidemic strain of P. aeruginosa have been reported previously and although segregation has significantly reduced the numbers infected the effects have been serious during the decade (Griffiths AL et al. Am J Resp Crit Care 2005; 171:1020-1025.[PubMed].

 

 

2012 Miroballi Y, Garber E, Jia H, Zhou JJ, Alba L, Quittell LM, Angst D, Cabana M, Saiman L. CF Infection control knowledge, attitudes, and practices among cystic fibrosis patients and their families. Infection Control Study Consortium. Pediatr Pulmonol 2012; 47:144-152. [PubMed].
In 2003, the Cystic Fibrosis (CF) Foundation in the United States published evidence-based infection control guidelines and distributed these to CF care centers. However, it is unclear how well the guidelines have been disseminated to patients and families, how well patients and families understand the principles of infection control, and what barriers they experience implementing the guidelines.

The authors assessed infection control knowledge, attitudes, and practices among CF patients and their families at 17 randomly selected CF centers. Anonymous surveys were completed by CF patients (>=16 years old) or their family members (patients <16 years old). To adjust for similarities of patients within each center, generalized estimating equations regression was used. From January 2007 to May 2009, 1,399 respondents completed surveys of whom 38% were patients and 62% were family members (overall mean age of patients 14 years). Overall, 65% of respondents were aware of the CF infection control guidelines, but only 30% had discussed them more than once with their CF care team. More than one discussion was associated with increased knowledge of infection control, including routes of pathogen transmission; the importance of avoiding close contact with other CF patients; increased confidence in practicing infection control; and increased belief in the health benefits of infection control.

 

The study revealed that although 65% of CF patients and families are aware of the infection control guidelines, but that only 30% had discussed them more than once with their CF teams. The authors stress that their findings underscore the importance of engaging patients and their families in regular discussions about infection control that address questions and concerns including the potential impact of infection control on health and well-being. Further strategies are needed to overcome barriers to implementing these guidelines.

 

 

2012 Cargill J. Etherington C. Peckham D. Conway S. Denton M. Blood stream infections in cystic fibrosis: nine years experience in both adults and children. J Cyst Fibros 2012; 11:337-339. [PubMed]

A report the aetiology and outcome of bloodstream infections (BSI) occurring at two regional cystic fibrosis (CF) centres (one adult, one paediatric) between 1998 and 2006. A retrospective analysis of all positive blood cultures during the study period was performed.

During the study period 1691 blood culture sets were taken. Fifty-seven clinically significant episodes of BSI in 48 people with CF (36 adult, 12 paediatric) were identified, along with 28 other episodes considered to be contamination or not clinically significant. The most common BSIs were caused by coagulase-negative staphylococci (13) Candida spp (10), and Stenotrophomonas maltophilia (8). The majority (82%) of significant BSIs were considered to originate from totally-implantable vascular access devices (TIVADs); only 9% were attributed to the lower respiratory tract. The TIVAD was removed in two-thirds of cases of TIVAD-associated BSI. There were three deaths (60% of cases) attributable to BSI originating from the lower respiratory tract but no deaths attributable to TIVAD-associated BSI.

The authors concluded most significant BSIs in patients with CF originate from TIVADs. Targeted antimicrobial therapy and appropriate early device removal is associated with good clinical outcome. BSI originating from the lower respiratory tract is associated with poor clinical outcome.

A valuable report of experience in a large CF centres for children and adults.

 

2013 Kidd TJ, Ramsay KA, Hu H, Marks GB, Wainwright CE, Bye PT, Elkins MR, Robinson PJ, Rose BR, Wilson JW, Grimwood K, Bell SC. ACPinCF Investigator Group. Shared pseudomonas aeruginosa genotypes are common in Australian cystic fibrosis centres. Eur Resp J 2013; 41:1091-100. [PubMed]

Recent molecular-typing studies suggest cross-infection as one of the potential acquisition pathways for Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In Australia, there is only limited evidence of unrelated patients sharing indistinguishable P. aeruginosa strains. The authors therefore examined the point-prevalence, distribution, diversity and clinical impact of P. aeruginosa strains in Australian CF patients nationally.

983 patients attending 18 Australian CF centres provided 2887 sputum P. aeruginosa isolates for genotyping by enterobacterial repetitive intergenic consensus-PCR assays with confirmation by multilocus sequence typing. Demographic and clinical details were recorded for each participant.

Overall, 610 (62%) patients harboured at least one of 38 shared genotypes. Most shared strains were in small patient clusters from a limited number of centres. However, the two predominant genotypes, AUST-01 and AUST-02, were widely dispersed, being detected in 220 (22%) and 173 (18%) patients attending 17 and 16 centres, respectively. AUST-01 was associated with significantly greater treatment requirements than unique P. aeruginosa strains.

 

Thus multiple clusters of shared P. aeruginosa strains are common in Australian CF centres. At least one of the predominant and widespread genotypes is associated with increased healthcare utilisation.

Although the authors conclude that longitudinal studies are now needed to determine the infection control implications of these findings, experience from elsewhere, such as the UK, indicates that strict patient segregation is required. A similar survey was carried out in the UK in 2003/4 (Scott FW et al. 2004. J Med Microbiol 2004; 53:609-615.) the results of which had a major influence on the national introduction of infection control measures

 

2013 Ashish A. Shaw M. Winstanley C. Humphreys L. Walshaw MJ. Halting the spread of epidemic Pseudomonas aeruginosa in an adult cystic fibrosis centre: a prospective cohort study. JRSM Short Reports. 4(1):1, 2013 Jan. [PubMed]
To assess if cohort segregation policies are effective in preventing cross-infection in cystic fibrosis (CF) clinics. A prospective cohort study in a large adult CF centre in Northwest England including all CF patients cared for at the Liverpool adult CF centre 2003-2009. Regular sputum sampling with genotyping of pseudomonas aeruginosa (Psa) isolates led to a policy of inpatient and outpatient segregation by microbiological group. MAIN OUTCOME MEASURES: Prevalence and cross-infection/super-infection rates of a transmissible Psa strain, i.e. the Liverpool epidemic strain (LES) in adult CF patients at the Liverpool adult CF centre from 2003 to 2009.
RESULTS: There was a decline in the proportion of patients with LES (71-53%) and an increase in those with unique strains (23-31%) and without Psa infection (6-17%) from 2003 to 2009. There were two cases of LES super-infection and one case of new chronic Psa infection (with a unique strain). There were no cases of transmissible strain infection in patients previously uninfected by Psa.

The authors concluded that their segregation policy has halted the spread of the commonest highly transmissible strain in the UK (LES) in their clinic, without endangering patients who were not previously infected with Psa. They consider that the findings confirm that if genotypic surveillance is used, it is unnecessary to segregate patients infected with unique strains from those without Psa infection.
Not all would agree that uninfected patients be allowed to mix with those infected even by unique strains of P. aeruginosa.

 


2015 Driessche KV, Hens N, Tilley P, Quon BS, Chilvers MA, de Groot R, Cotton MF, Marais BJ, Speert DP, Zlosnik JE. Surgical Masks Reduce Airborne Spread of Pseudomonas  aeruginosa in Colonized Patients with Cystic Fibrosis. J Respir Crit Care Med. 2015 Oct 1;192(7):897-9. doi: 10.1164/rccm.201503-0481LE. [PubMed]

Extract from the letter. – “The controlled human aerosol model used in our study produced relatively precise and repeatable results despite a small sample size. Among patients with CF colonised with P. aeruginosa and producing infectious aerosol particles (55%), we demonstrated a greater than 80% reduction in infectious aerosol particle production when wearing a surgical mask while coughing.  Our data provide evidence for the new Cystic Fibrosis Foundation guideline to wear surgical masks in healthcare settings”.


Zuckerman JB, Clock SA, Prato BS, McDevitt JJ, Zhou JJ, Leclair LW, Lucas FL, Saiman L.  Air contamination with bacteria in cystic fibrosis clinics: implications for prevention strategies.  Am J Respir Crit Care Med. 2015 Mar 1;191(5):598-601. doi: 10.1164/rccm.201410-1877LE.
25723827 [PubMed]

The authors concluded air contamination with CF respiratory pathogens during clinic visits was infrequent, and use of surgical masks did not reduce contamination in examination  rooms. They found that the air of spirometry rooms was more likely to be contaminated than that of exam rooms, presumably as a result of the generation of contaminated aerosols during forced expiratory manoeuvres and cough. Contamination in spirometry rooms cleared by 30 minutes and was not associated with age, signs and symptoms, air exchange rates, or specific CF pathogens.
The findings provide the basis for the recommendation in the updated Infection Prevention and Control Guideline for CF to allow 30 minutes to elapse between patients with CF during performance of spirometry (unless high-efficiency particulate absolute filtration or negative pressure ventilation is used). Mask use by patients with CF is not advised in examination rooms but is recommended in common areas such as waiting rooms and clinic corridors.

 

 


2015 Ridderberg W, Andersen C, Væth M, Bregnballe V, Nørskov-Lauritsen N, Schiøtz PO. . Lack of evidence of increased risk of bacterial transmission during cystic fibrosis educational programmes.  J Cyst Fibros. 2015 May 20. pii: S1569-1993(15)00115-0. doi: 10.1016/j.jcf.2015.04.007. [Epub ahead of print]     [PubMed]
Educational and rehabilitation programmes increase the quality-of-life of patients with cystic fibrosis, but patients are discouraged to participate because of the risk of cross-infections.
Isolates of Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae cultured one year before to one year after attendance were investigated by pulsed field gel electrophoresis, multilocus sequence typing and/or spa-typing.
We typed 984 bacterial isolates cultured from 46 patients aged 5-18years attending educational programmes at Aarhus University Hospital during 2009-2011. There were no cross-infections with P. aeruginosa. Six cases of S. aureus or H. influenzae strain replacement with a new strain-type shared with a fellow attendee were found. However, the probability of acquiring a shared strain of S. aureus or H. influenzae was not increased for patients attending educational programmes.
Transmission of P. aeruginosa, S. aureus and H. influenzae related to attendance to the investigated educational programmes could not be documented.
 

- The recognition of cross infection between people with CF and the taking of precautions to avoid it, has been one of the most important advances n CF care. Although sporadic publications have appeared failing to demonstrate such cross infection and questioning the need for cross infection avoidance policies (Hoogkamp-Korstanje JA et al, J Clin Microbiol1995; 33(3):572-575. 7751359 ;Tubbs et al, Respir Med 2001; 95(2):147-52 11217911) most clinic staff now accept the need to conform to the infection control recommendations of the expert committees. The Aarhus CF centre is one of the two major centres in Denmark and it may be relevant that other publications indicate the percentage of patients infected by S. aureus is significantly higher there than in the Copenhagen centre.

 

 

 

 

 

 

The following article, written initially for CF families by Dr Jim Littlewood, contains some additional information and advice. 

 

 

THE ENVIRONMENT AS A SOURCE OF PSEUDOMONAS AERUGINOSA

AND SOME OTHER PATHOGENS

 

The risk for people with cystic fibrosis (PWCF) of encountering Pseudomonas

aeruginosa (PA) and other potentially harmful organisms in various

environments has been a frequent question for the CF Trust’s “Ask the Expert”

service. Here we review some of the evidence that is available on the subject,

with emphasis on Pseudomonas aeruginosa as questions most frequently

concern this organism.

This document does not deal in detail with the occurrence and prevention of

cross infection in CF Centres and Clinics, nor at CF camps and holidays, for

when recommended precautions of hygiene and segregation are in operation

it is apparent that most new infections are acquired outside hospital. (See

“Publications” on CF Trust website www.cftrust.org.uk where there are the

following Standards Documents - Pseudomonas aeruginosa infection in

people with cystic fibrosis. Suggestions for prevention and infection

control. 2004; also Burkholderia cepacia complex. Suggestions for

prevention and control. 2004).

 

So where are PWCF likely to encounter Pseudomonas? Advice from CF

centres varies widely concerning precautions for families to take. The

impression of widespread parental anxieties regarding PA infection was

confirmed in a study from Germany; if precautions were exaggerated

inappropriate advice could lead to non-intended side effects to the detriment

of the child’s quality of life (1). For example, in Germany some CF physicians

are recommending that people with CF should avoid public showers and

swimming pools and should drink only tap water that has been boiled (2).

Although eradication of early PA infection is now usually feasible and well

established practice in most centres, it is certainly preferable to avoid

infection rather than eradicate it as second and subsequent episodes of

infection are increasingly difficult to eradicate. Also, although the proportion

of people with CF who have chronic PA infection (prevalence) has steadily

fallen at centres where early eradication has been practiced, the number of

new infections (incidence) has remained much the same (3, 4). So it is timely to

review the possible environmental sources of these new infections and the

reasonable precautions which could be taken to avoid infection.

 

General environment

 

People with “colds”.

The increase in first isolations of PA and the onset of

chronic infections between October and March has been attributed to the

increased likelihood of viral infections (5). A recent, interesting and rather

surprising study of individuals, who do not have CF, shows more than a third

may carry PA transitorily in their airways at times of acute viral respiratory

infections during the winter months, but they clear the organism

spontaneously when they recover; in contrast, the 30% of PWCF who

become PA positive during “colds” often fail to clear the infection

spontaneously when the viral infection settles. So otherwise healthy children

with “colds” may be not only a source of viral infections but also of PA

infection for people with cystic fibrosis (6). A number of studies have shown that P. aeruginosa may travel more that 1 meter from infected individuals with both talking and coughing (6a, 6b)).

 

Households of people with CF.

Pseudomonas was detected in 73 of 102 (71.6%) households of PWCF –

most frequently in drains of showers (39.6%),drainpipes of kitchen hand basins (35%)

and bathrooms (34.7%) and drainpipes of toilets (26.5%)7. However, it was not stated how many patients werechronically infected with PA and therefore the possible source of re-infection

of the household environment.

Dishwashers have been described as "a man-made ecological niche accomodating

human opportunistic fungal pathogens (7a) This is a very detailed paper the full

version of which is available without cost on the internet. In view of the increasing

importance of fungal infections such as Aspergillus in people with CF, this is useful

information although the presence of these organisms seem to represent a potential

more than definite threat at this stage.

 

Domestic showers.

Showers have not been reported as a source of PA

cross-infection in people with CF nor have domestic cold-water tanks in the

roof, although the organism can be recovered from the drains.

 

Tropical fish tanks.

Tanks with heated water are a potential source of

infection if the patient is in direct contact with the water e.g. cleaning out,

hands in the water etc. There are various reports of infection with various

organisms from fish tanks including Salmonella, Mycobacterium marinum but

not of Pseudomonas or in people with CF.

 

Greenhouses and garden centres.

These are considered to be a potential

risk as they have warm humid conditions. After discussion with an expert CF

microbiologist we recently advised that a boy with CF did not become

involved with regular holiday work in the family garden centre.

 

Domestic pets.

Relatively little attention has been paid to household pets in

the context of infection in PWCF but “companion animals” do appear to

constitute a definite, but as yet unproven, risk.

A study from Canada reported detailed microbiological findings on 102

apparently healthy dogs taken to visit people in hospital. No less than 80%

of the animals carried a potentially harmful infectious agent. Clostridium

difficile was isolated from 58%, E. coli from 3%, Salmonella from 3%,

Pasteurella canis from 29%, and a variety of other organisms although PA

was not detected (8) .

Dogs and cats in Japan carried a variety of organisms on their paw and hair

samples. Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, Proteus

and others were detected on each sampling area on dogs and cats kept

outdoors (9). Staphylococci and PA are frequently isolated from the ears of

dogs (10) and those with bacterial keratitis eye infection (11). In a 6 year study from

canine skin and ear samples PA was isolated from 7.5% and 27.8% of skin

and ear samples respectively (12). Dogs can carry strains of MRSA and the

organism caused an outbreak in dogs in Leeds (Dr Miles Denton, 2005,

personal communication).

In one instance infection with Bordetella bronchoseptica, previously described in two

lung transplant CF patients and acquired from pet dogs, was also possibly acquired from

a domestic cat (12a). Infection can be two ways and transfer of a epidemic

strain of Pseudomonas aeruginosa from an adult with CF to a pet cat has been

documented (12b).

In recent years S. maltophilia is more frequently isolated from people with CF and

although the organism appears to be ubiquitous it is useful to know that animals

(horses, dogs and cats) may harbour this organism and are potential sources of

infection (12c).

With regard to reptiles, one recent report failed to demonstrate any risk to a

CF patient (12d) although reptiles and similar pets have been reported as a

potential source of infection for people with CF (www.PetEducation.com Common

bacterial Infectionsin Turtles and Tortoises).

 

 

Pseudomonas aeruginosa is found in many natural and domestic

environments

These include plants, soils and surface water, especially warm

moist environments containing organic material or contaminated by

human or animal waste. Although PA thrives in moist environments, it is not

considered to be a marine organism because the high salt concentrations in

seawater are considered to inhibit its growth – so sea bathing and playing on

the beach have been considered no problem. However, there is some

evidence to suggest this is not always the case as some beaches have

significant contamination by sewage and there is some evidence that PA can

survive in seawater (13).

 

Soil samples

Soil may contain Pseudomonas aeruginosa. 24% of soil samples

from various areas of California contained Pseudomonas which were of

similar types to those causing illness. The soil is a reservoir for P. aeruginosa

which will colonize plants in suitable conditions. Sprinkler watering was

suggested as a contributory factor (14).

 

Hydrotherapy pools, Jacuzzis and hot tubs

These represent a definite risk for people with CF because the combination

of water, warmth, aeration and human contamination impair adequate

disinfection whilst providing ideal growthconditions for bacteria such as

P. aeruginosa (15, 16) A variety of infections

acquired from these sources have been reported including hot tub folliculitis,

green nail syndrome, infective endocarditis, invasive external ear infections

and puncture wound osteomyelitis (17).

 

Swimming pools

These are generally safe provided the recommended programme

of maintenance is carried out - but standards do vary. In a “Which” survey in

2002 no less than 35 of 61 samples from pools and spas fell outside

acceptable microbiological standards – 9 posed a definite risk and 3 a serious

health risk to bathers; spa pools were worse than swimming pools.

Pseudomonas poses a particular risk in spa pools and outbreaks of infection

in non-CF people have been reported. A list of pools and their standards were

included in the report (Which, June 2002). If water is faecally contaminated by

bathers the water will not be immediately sterilized and thus would be a risk to

other bathers.

Pseudomonas skin infection has been associated with a swimming pool

inflatable. A child with a positive skin swab for PA attended the local

swimming pool and played on an inflatable and later developed folliculitis. A

total of 35 further cases were identified during the outbreak. Nine of 10 (90%)

of the inflatables sampled were colonized by P. aeruginosa. The authors

suggest that attention should be given to the problem of routine

decontamination of swimming pool inflatables (18).

In a study from Northern Ireland 4/13 (30.8%) of hydrotherapy pools,

37/51(72.5%) of Jacuzzis/spas and 26/68 (38.2%) of swimming pools were

positive for P. aeruginosa – it is important to note that private facilities were

worse than public facilities. The authors concluded that the “water may be a

potential source of P. aeruginosa infection for susceptible patient groups

including patients with cystic fibrosis” (19).

In contrast, in Switzerland in 2002 none of 72 specimens from 28 outdoor

swimming pools revealed P. aeruginosa. In 2003 only 3/46 (7%) grew P.

aeruginosa – in each instance from paddling pools. Two of 128 (4%)

specimens from 56 indoor pools grew P. aeruginosa – both positives were

from private pools (20). Acquisition of a PA infection by a person with CF from a

swimming pool has never been documented there; they do not consider tap water

or swimming pools to be a significant risk. Obviously the risks vary according

to the location and it is impossible to generalize.

A recent study from Ohio showed 23% of samples from 8 swimming pools and

3 hot tubs were positive for P. aeruginosa which were usually multi-drug resistant (21a)

 

 

Fresh water lakes

Fresh water lakes may contain P. aeruginosa. In Holland external ear

infections were closely associated with swimming in recreational fresh water

lakes in the previous 2 weeks. The lakes met Dutch standards but PA was

isolated from all of them as well as from 83% of ear swabs of affected

patients. “Even when current bathing water standards are met, swimming can

be associated with a substantial risk of otitis external because of exposure to

P. aeruginosa” (21).

 

The Eden project, Cornwall UK.

Recently we discussed visiting the Eden Project in Cornwall with a CFmicrobiologist

and also with the very helpful technical staff at the Eden project

itself. The humidity in the Biomes (the large domes) is high (50% to 90%) but

the moist humid air is filtered and will not contain bacteria. The humidity is

higher on cool days but less on hot days when the ventilation panels will be

open. There is no rotting vegetation but there are ferns - however, we are not

aware these are a risk. The microbiologist noted that B. cepacia has been

found in the soil of one botanical garden and Gram negative organisms are

more likely to grow in moist conditions. However, our overall conclusion, taking

everything into consideration, was that the risks of a person with CF visiting

the Eden Project are very low and perhaps it would be better to go on a warm

day when the ventilators would be open wider! It reassuring that the staff

confirmed that the moisture in the air is filtered.

 

Foods and drinking water

 

There are numerous publications reporting the variable bacterial quality of

assorted bottled waters; usually the carbonated specimens are less likely to

be contaminated than the still specimens. Also ice cubes are a potential risk

depending on the quality of the water used.

The bacteriological content of water in large dispensers (coolers) and from

the 20 litre supply bottles had P. aeruginosa in 25% of samples from the large

supply bottles and also in 24% of water specimens from the actual coolers. A

further 21.6% of 162 specimens from the coolers yielded P. aeruginosa (22).

 

Bottled water and tap water

Samples were tested using standard microbiology

techniques. The bacterial count of bottled water increased dramatically from

1colonies/ml to 38,000 colonies /ml over 48 hours at 37ºC after drinking once

from the bottle but markedly reduced at cooler temperatures (23). Half the

samples of drinking water from mobile food vendors in Cheshire were

examined microbiologically and found to be unsatisfactory. There was a

relation between the frequencies with which the containers were cleaned and

the viable counts (24). The bacterial content of carbonated and non-carbonated

commercial bottled water samples were examined and showed no growth

from carbonated water but of 22 samples from non-carbonated water, 3 grew

S. maltophilia and 8 grew P. aeruginosa (25).

None of 102 running water specimens from water taps were infected in

winter and only 2/50 of the standing water (first specimen after turning on)

were positive in summer; but none of the running water specimens were

positive (23). In another study tap water resulted in only minimal growth

particularly at low temperatures (20).

Water softeners should not be a problem. P. aeruginosa is not usually

present in drinking water but can be present where there are repairs or

alterations to the plumbing system. The water softener should remove any

bacteria that enter the system; compliance with regulation DIN 19636 will

apparently ensure this occurs (26).

 

Vegetables and salads.

A considerable time ago a study of food in a

hospital kitchen (27, 28) recovered PA from 82% of tomatoes, and 27% of

tomato salads. The organism was also present in 7 of 9 radishes, 4/6 celery,

3/10 carrots, 2/8 endives, 2/7 cabbages, 2/6 cucumbers, 1/5 onions, 1/9

lettuces and 30/111 tomato salads. Subsequently 44% of 116 vegetable

salads prepared for patients yielded PA in addition to a variety of other

Gram negativeorganisms (29).

Pseudomonas aeruginosa multiplied in lettuce and beans when temperature

and humidity were high (270C and 80-95% humidity). Three hundred and

eight vegetable samples from 3 German supermarkets were screened for

organisms including PA which was detected in 15 (4.9%) of samples. Other

Pseudomonas species were detected in 73.1% of the vegetable specimens –

in green salad (7.4%), tomatoes (10%), and cucumber (13.8%); however,

neither Staphylococcus aureus nor B. cepacia were found (30).

Button and open cap mushrooms purchased from several leading

supermarkets from five different countries all contained P. aeruginosa; also

the organism has been consistently isolated from spent mushroom

compost purchased from garden centres as a soil improver. Also PA was

isolated from packets of bean sprouts but not detected in a selection of other

common supermarket fruit and vegetables. Thorough cooking should be

sufficient to kill the organism but handling uncooked mushrooms or bean

sprouts may constitute a risk to a person with cystic fibrosis (31).

 

Equipment

 

Toys used by children with CF who are chronically infected with PA

are a

potential source of infection; the organism can exist on hands contaminated

with infected sputum for up to 180 minutes.

Sponges and tooth brushes at home should not be a risk for personal use

provided they are dried thoroughly after use – drying of all equipment is

particularly important.

 

Respiratory function equipment has not proved to be a major source of

infection provided there are appropriate standards of hygiene in operation. 33

of 155 samples cultured from the proximal (patients’ end of the equipment)

and only 2 of 155 from the distal (equipment) side of single use bacterial viral

filters grew pathogenic organisms (32).

Home nebulisers of 34 PWCF who had chronic PA infection did not

harbour the organism, although other pathogens were identified. Drying was

emphasized as an important part of the cleaning procedure (33).

 

Dental equipment may be a source of PA but is a relatively low risk and

patients should not be deterred from visiting the dental surgeon! Three of 103

(2.9%) water samples from 25 dental sessions in an oral health care service

in Denmark were positive for P. aeruginosa. Eighteen of 327 samples (5.5%)

from 9/82 (11%) sessions from various clinics were positive for P. aeruginosa.

One was the same strain as isolated from a CF patient (34). In a recent survey

in a Dental Hospital 43% of suction hoses were infected with P. aeruginosa

and corroded at their attachment to the main dental chair unit. The problem

was eliminated by replacement hose connectors (35). Very detailed

recommendations for infection control procedures for dentistry have been

published by the US Centers for Disease Control and Prevention in 2003 –

including references to and details for preventing water borne infection (36).

 

Washing machines in three Italian commercial launderettes were examined.

Bacterial contamination was highest in the most frequently used launderette.

Low temperature washing (25-30ºC) did not guarantee elimination of bacteria

from the inside of the machine or from the fabric. Only washing at 550C+ with

the addition of an oxygen-based bleach ensured almost total elimination of

bacteria such as P. aeruginosa 37. Domestic washing machines were shown

to reduce the viable count of Staphylococcus aureus below detectable levels

from the uniforms of hospital staff even using a low temperature programme.

Gram negative flora were introduced from the machine but were destroyed by

tumble drying or ironing (38).

 

Gymnasiums and health clubs. A number of studies have shown apparatus in

health clubs may harbor significant numbers of harmful bacteria in the residue left

on gym equipment,bench-press headrests, dumbbells, dirty towels, in hot tubs, spas,

whirlpools,saunas and changing rooms and even in drinking water from plastic bottles

(Peta Bee, Daily Mail. July 4th 2006).

 

Hospital environments

 

Pseudomonas aeruginosa is frequently found in some hospital environments,

particularly intensive care units. In one study, washbasins and sinks were

found to be contaminated and identical strains were identified on the hands of

staff. The contamination level of P. aeruginosa in aerosols from the sinks was

greater in the mornings, presumably because of the opportunity for overnight

bacterial growth (39, 40).

In a 4-week study 88% of all hospital ward washbasin drains contained P.

aeruginosa, which correlated with the strains isolated from patients; four of 16

patients grew the organism from hand cultures. The organisms were detected

for up to 180 minutes from hands experimentally contaminated with sputum.

Genomic fingerprinting of the bacteria did not distinguish between

contamination of the environment from secretions or cross-infection i.e.

patient-to-patient transmission (41).

.

Rates of fecal carriage of PA differ widely. In healthy individuals PA carriage

rates are generally low (less than 10%) but may rise to 40% in hospitalized

patients (42).

In a study from the Danish CF Centre, where precautions are taken to avoid

PA cross-infection, including segregation of patients according to their

microbiological status and good hygienic practice, there was no evidence that

the hospital environment was an important source of infection (43). This is the

impression gained from experience at many large CF centres where policies

to reduce the risk of cross infection are in operation. This supports the view

that most new Pseudomonas infections in people with CF are acquired from

the environment away from hospital.

 

So what are we to recommend for people with CF?

 

The CF Trust document “Pseudomonas aeruginosa infection in people

with cystic fibrosis. Suggestions for prevention and control. 2004”

lists simple precautions to take when away from hospital as follows and

these are still relevant in 2014:-

 

• Casual meetings between people with CF, including brief encounters

indoors and outdoors, carry a low risk of infection and this risk is

increased the longer and closer the contact.

• Avoid contact with all people who have acute viral respiratory

infections including those without CF.

• Patients should discuss cross-infection issues with their physician and

CF Team and be aware of what usually grows from their sputum/throat

swab samples (their own “microbiological status”).

8

• All communal camps and holidays for groups of people with CF should

be avoided.

• Spa and other forms of aerated baths should be avoided. Check the

swimming pool used is serviced regularly and reliably.

• Schooling: although there is no evidence that P. aeruginosa infection

can be transmitted between children in the school environment, it is

preferable for children with CF attending the same school to be in

different classes.

• Higher education: students should be aware of their microbiological

status and may wish to discuss this with their CF physician, the

Student Health Service (who then has legal responsibility) and their

personal tutor.

• Workplace: People with CF should be aware of their microbiological

status and may wish to discuss this with their CF physician and

Occupational Health Services who can then take appropriate action to

minimize the risk of cross-infection.

• Siblings with CF should have separate bedrooms and should do their

airway clearance and other treatments separately.

 

To these we suggest considering the following precautions –

 

• Avoid swimming in rivers and fresh water lakes particularly if there is a

well-maintained swimming pool as an alternative.

• Notice the hygienic precautions taken in gymnasiums and health clubs

that you may visit. Take your own towel.

• Remember that some domestic pets can be a source of Pseudomonas

aeruginosa and Staphylococcus aureus, particularly if they have ear or

eye infections. So avoid pets who are unwell particularly with ear or

eye infections and always wash your hands after handling pets

• Avoid close contact with, and becoming involved in the cleaning of,

tropical fish tanks.

• Greenhouses and indoor garden centres where there are damp warm

conditions may be a risk both for Pseudomonas and also for spores of

Aspergillus.

• Damp straw in stables is a proven risk for Aspergillus fumigatus spores

and if people with CF go horse riding they should avoid “mucking out”

stables or being in the stables when this is in progress for he air

becomes laden with fungal spores.

• Wash all fruit, vegetables and salads thoroughly including those

described as ready washed in packets in and cook all mushrooms.

• Ensure all equipment and toys are cleaned regularly and dried. Allow

tooth brushes to dry after use.

• Use washing machine at 55ºC+ and use an oxygen based bleach.

• Ensure plastic bottles and containers used for drinking water are

sterilized with boiling water before refilling. Tap water and carbonated

bottled water are preferable to still bottled water. Allow tap water to run

for a minute if used for the first time that day

 

 

Comment

The risk of acquiring Pseudomonas and other harmful organisms obviously

differs according to local conditions. However, it is likely that people with CF

do acquire the organism from the general environment outside the hospital

and it is likely to be via water or in damp situations.

It seems reasonable, when possible, to avoid the situations described above

which have proved a problem particularly warm pools, Jacuzzis and hot tubs

and also to enquire as to the bacteriological supervision of any swimming

pool a person with CF intends to visit on a regular basis. Even though the

Swiss pools appear satisfactory, the standards in some UK and US pools obviously

do vary considerably and some are a definite health hazard and are best

avoided.

 

It is hoped that the information in this document will not engender

excessive anxiety in parents and people with CF for in many of the

situations discussed the risk of an individual acquiring Pseudomonas

aeruginosa, after a relatively short exposure, would be very low.

                                                             

Jim Littlewood 2014

                                                              

Many thanks to Dr Miles Denton, Consultant Microbiologist, Regional

Cystic Fibrosis Centres, Leeds Teaching Hospitals for his expert advice.

 

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