BURKHOLDERIA CEPACIA COMPLEX

The importance of B. cepacia complex in CF cannot be over emphasised. It was the organism that showed patient to patient transmission was a real and serious problem. By 2010 there were no less than 934 references to CF and B. cepacia complex on Medline.

1977 Lararya-Cuasay LR, Lipstein M, Huang NN. Pseudomonas cepacia in the respiratory flora of patients with cystic fibrosis. Pediatr Res 1977; 11:502.
One of the earliest reports of Pseudomonas cepacia (later called first Burkholderia cepacia, then Burkholderia cepacia complex) isolated between 1973 and 1976 from 54 patients with cystic fibrosis; many were severely affected and 14 died. The presence of the organism made treatment more difficult.
This was a very early report of P. cepacia which did not appear cause concern at the time - in fact in John Lloyd-Still's 1983 Textbook of Cystic Fibrosis there is very brief mention of P.cepacia as one of the "other gram-negative rods that may infect people with cystic fibrosis". Later Rosenstein & Hall reported pneumonia and septicemia due to Pseudomonas cepacia in a patient with CF (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) 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] below).
The first report from the UK was from the Leeds centre and did not appear until 1990 when we had identified 11 cases since 1984 (Simmonds EJ et al. Arch Dis Child 1990; 65:874-877. [PubMed] below). The tendency for B. cepacia to spread between patients was not generally accepted in the UK until 1993 when John Govan from Edinburgh published definite evidence of patient to patient spread (Govan et al, 1993 [PubMed] below).

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 3 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 was now a major problem in the Toronto clinic.

This paper, which describes the devastating effect of the introduction of B. cepacia into a CF clinic population very clearly, heralded a new era in CF care and 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 until John Govan’s publication documented definite person to person spread (Govan et al, 1993 below). From 1993 there was a general introduction of infection control measures in CF Centres; 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 below).

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 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 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). 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 (Figure 27) has for many years been a leading UK and international authority on CF microbiology. In this 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 others in the clinic. 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.

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 (30%) of the 17 affected patients had died. In only two of the six patients referred to the CF centre had P. cepacia been identified before referral.

Dr Ty Pitt (fig 27.1) has been a central figure in understanding the microbiological aspects of cystic fibrosis collaborating closely with clinicians both at the Brompton Hospital in London and also with national studies. Of particular importance was the national survey of CF centres revealing widespread evidence of cross infection both within and between CF Centres in the UK (Scott and Pitt, 2003).

2000 Cooper RA, Wigley P, Burton NF. Susceptibility of multiresistant strains of Burkholderia cepacia to honey. Lett Appl Microbiol 2000; 31:20-24. [PubMed]
Twenty strains of Burkholderia cepacia, isolated principally from the sputum of people with CF, were tested in the laboratory for their susceptibility to eight antibiotics. All strains exhibited multiple, but not identical, patterns of antibiotic resistance. However, all strains exhibited susceptibility to concentrations of honey below 6% (v/v). The authors suggested that honey may have a potential role in the clinical management of B. cepacia infections.

As yet (2011) honey has not proved to be of value in the treatment of people with CF although it has been used with success in other infections particularly involving the skin. Professor John Govan of Edinburgh had a PhD student and a chemist working on the anti-bacterial effect of honey but they were unable to identify the active component. One experienced CF physician tried treating an adult patient with CF with nebulised solution of honey but again without obvious clinical benefit.

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.