CROSS INFECTION

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 five patients did not. After returning from camp, all 22 patients harboured P. aeruginosa in the sputum. The typing results showed that the five cystic fibrosis 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 cystic fibrosis 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 with CF who were already chronically infected.

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 Liverpool adult CF Centre, of a transmissible Liverpool strain of P. aeruginosa, shown to be identical by genotyping, infecting patients in the same clinic. Eventually the “Liverpool strain” (LES strain), first recognised in the Liverpool paediatric clinic,(Cheng et al, 1996 above) was identified in a number of other UK CF centres.

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 advised other centres to undertake microbiological surveillance of their patients.
A very important paper by Dr Andy Jones (figure 18), Consultant Physician at the Manchester Adult CF Unit, which was influential in the eventual introduction of widespread microbiological surveillance of CF centres in the UK that revealed cross infection was a common occurrence in many of the large CF centres (Scott & Pitt, 2004 below). A similar clinical situation had been reported from the Liverpool paediatric CF clinic in 1996 (Cheng K et al, 1996 above). Both these papers were influential in the introduction of a more rigorous policy of segregation according to microbiological status in most CF centres – but in some not without a degree of reluctance on the part of some very experienced CF clinicians – for example “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 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”; one of his paediatric colleagues, at the same major CF Centre, described those in favour of segregation at the CF Trust as “an unruly bunch of zealots”. Fortunately only a minority of CF clinicians held these Luddite views!

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 woman 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) was isolated from specimens of the patient's sputum and was 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 get into the water supply and there are now almost 70 cases of the infection causing serious illness reported in people with cystic fibrosis. So going on holiday to Thailand is a risk for a person with CF particularly in the rainy season and B. pseudomallei seems to be the main danger (also Barth AL et al, 2007 below).

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 observe that cross-infection by Pseudomonas aeruginosa between unrelated patients with CF is believed to be uncommon. After detecting a genotypically identical strain of P. aeruginosa in five unrelated children with CF dying from severe lung disease, the authors determined its prevalence within a large CF clinic using pulsed-field gel electrophoresis and random amplified polymorphic DNA assays. The clinical status of P. aeruginosa-infected patients was also determined. Between September and December 1999, 152 patients, aged 3.9 to 20.7 years, provided sputum for culture. P. aeruginosa was detected in 118 (78%) children of mean age 13.5 years. The genotyping techniques were concordant, showing that 65 (55%) of infected patients carried an indistinguishable or closely related strain. No distinctive antibiogram or environmental reservoir was found. Patients with the clonal strain were more likely than those with unrelated isolates 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 paediatric CF clinic. Whether this strain is also more virulent than sporadic isolates remains to be determined. As transmissible strains could emerge elsewhere, 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 dangers of spread of highly transmissible strains of P. aeruginosa. The fact the five children died attests to its virulence and this infection also leads to a requirement for more treatments. 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 in 1996 from Liverpool (Cheng et al, 1996 above).

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 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 been described previously, and this finding raises significant issues relevant to the treatment of patients with non-CF suppurative lung disease
The spread of infection from patients with CF is a definite risk in children’s wards, particularly if there are immunocompromised patients – a situation I have observed. Dr Phil Robinson (figure 26) is Head of CF Services and Respiratory Physician at the Royal Melbourne Children’s Hospital.

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 past studies of cross-infection with Pseudomonas aeruginosa among patients with CF in the UK suggest that it is a rare occurrence. However, two recent UK reports of highly transmissible strains 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. This prompted the UK CF Trust to fund a nationwide survey to establish the distribution of P. aeruginosa strain genotypes among these patients. Isolates of P. aeruginosa 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 of the survey were as follows:-
- At least 72% of all people with CF harboured strains with unique genotypes.
- Small clusters of related strains were evident in some 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 P. aeruginosa 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 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.

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 cystic fibrosis. 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 may 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.
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 P. aeruginosa (Moore JE et al. Incidence of Pseudomonas aeruginosa in recreational and hydrotherapy pools. Commun Dis Pub Health 2002; 5:23-26). A ”Which” (a consumer magazine) report in 2002 also showed 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 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, P. aeruginosa cross-infection has continued. In contrast, individuals segregated from the cohort of patients with chronic P. aeruginosa infection but who attend the same centre have not acquired infection with transmissible P. aeruginosa strains. Simple infection control measures alone do not prevent the spread of some transmissible P. aeruginosa strains between individuals with cystic fibrosis. However, patient segregation effectively controlled spread of such strains.
These were the same transmissible P. aeruginosa strains previously described from Manchester (Jones et al, 2001 above; Jones et al, 2002 above).

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 what evidence is 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, 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 to support patient segregation according to microbiological status and a controlled trial would be quite unethical. Surely the delay in introducing patient segregation and the occurrence of cross infection in some CF centres has provided adequate information!

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]
A study to determine the spectrum of hygienic measures employed by German families and to evaluate the restrictions and impact caused by these measures. 130 parents from 10 CF centres responded to a questionnaire (63% response rate). 76% of the respective children had always been P. aeruginosa (PA) negative. Most parents displayed erroneous beliefs regarding PA infection (mean: 3.5 correct replies to 9 questions). 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. Striking a balance between a normal life style and over caution is very difficult for the parents as many of the avoidance recommendation have not been put to any form of trial.

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 above). 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. The authors suggested that future studies should address barriers to implementation of these evidence-based guidelines and continue to monitor their 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.