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Members of the Burkholderia cepacia complex (BCC), of which there are 18 different species, which are grouped into nine genomovars. These are aerobic organisms, widely distributed, and found in soil and water[i]. Importantly they can additionally survive for long periods in low-nutrient moist environments[ii], which make these organisms probable survivors within pharmaceutical grade water systems.
By Tim Sandle
B. cepacia is a human opportunistic pathogen and can cause pneumonia in immunocompromised individuals (when introduced into the air passages of a susceptible population); other risks to patients include endocarditis, wound infections, intravenous bacteremia, foot infection, respiratory infections. Some patient groups are at a greater risk than others, including elderly people, young children, cancer patients, pregnant women, and people with chronic illness[iii].
Bcc is of concern in relation to many pharmaceutical and healthcare facilities because many of the organisms within the group are resistant to organic solvents and antiseptics, and, to a degree, certain disinfectants[iv], with the resistance arising from several factors, including efflux pump mechanisms and resistance conferred through the organisms having a tendency to form biofilms under optimal conditions. Bcc organisms are also persistent, and they can readily survive in low nutrient conditions (such purified or distilled water).
It is important to understand the potential points or origin in pharmaceutical facilities (which is primarily low-nutrient environs like water, with the organisms adept at surviving under low nutrient conditions[v] [vi]; and which are reflective of the organisms often being able to adapt to different environmental conditions[vii]).
Organism characteristics
Burkholderia is a genus composed of over 60 organisms, many of which were formerly classed as Pseudomonas species. Within this are the Burkholderia cepacia complex, a group of some 17 organisms which are so closely related that they can, for the most part, only be differentiated by using a combination of multiple molecular diagnostic procedures.
Members of the Burkholderia cepacia complex are Gram-negative bacteria of the β-proteobacteria subdivision. This group is composed of plant, animal, and human pathogens. The organisms are widespread in both natural and ‘as built’ habitats[viii]. The organism after which the group is named was known as Pseudomonas cepacia prior to 1992. The bacterium was discovered by Walter H. Burkholder at Cornell Universityin1947. Burkholder identified the bacterium as the source of onion skin rot (cepacia is Latin for “like onion”).
Burkholderia cepacia, along with other members, is an aerobic bacterium, elliptically shaped with a length of 5–15 μm. In term of biohazard, the organism has a biosafety level of 2.
Origins in pharmaceutical and healthcare
Bcc organisms are common to the environment and to water[ix]. With the manufacturing of drug products, the most common point of origin is with pharmaceutical water systems; a review by Sandle (2015) indicated that organisms fall into the top five category of recovered water-borne contaminants, as assessed over a fifteen year period[x]. This related to recoveries of water microbiota from purified water and Water-for-Injections systems. Issues arise foremost due to deficiencies in the design, operation and monitoring of water systems. A key risk relates to maintenance work like valve changes or where the system requires ‘cutting into’, such as to alter pipework[xi].
[i] Lipuma J.J.. Update on the Burkholderia cepacia complex, Curr Opin Pulm Med. 2005; 11(6): 528-33
[ii] Lipuma, J.J, Currie B.J, Lum G.D, and Vandamme P. Burkholderia, Stenotrophomonas, Ralstonia, Cupriavidus, Pandoraea, Brevundimonas, Comamonas, Delftia, and Acidovorax In: Murray P.R, Baron E J, Jorgensen J.H, Landry ML, and Pfaller MA, editors. Manual of Clinical Microbiology. 9th Ed. Washington DC: ASM Press; 2007. p. 749-769.
[iii] Torbeck L, D. Raccasi, D.E. Guilfoyle, R.L. Friedman, D. Hussong. 2011. Burkholderia cepacia: This Decision is Overdue. PDA J. Pharm. Sci. Tech., 65(5): 535-43.
[iv] Hugo, WB et al. 1986. Factors Contributing to the Survival of a Strain of Pseudomonas cepacia In Chlorhexidine Solutions. Lett Appl Microbiol. 2:37-42
[v] W. Beckman and T.G. Lessie. Response of Pseudomonas cepacia to p-lactam antibiotics: utilization of penicillin G as the carbon source. J. Bacteriol. 1979; 140: 1126-1128
[vi] Martin, M et al 2011. Hospital-wide outbreak of Burkholderia contaminans caused by prefabricated moist washcloths. J Hosp Infect 77:267-270
[vii] Vial, L., et al 2011. The various lifestyles of the Burkholderia cepacia complex species: a tribute to adaptation. Envir Microb 13(1):1-12
[viii] E. Mahenthiralingam, T.A. Urban, and J.B. Goldberg. The multifarious, multireplicon Burkholderia cepacia complex. Nature Reviews Microbiol. 2005; 3(2): 144–156
[ix] Springman, A.; Jacobs, J. L.; Somvanshi, V. S.; Sundin, G. W.; Mulks, M. H.; Whittam, T. S.; Viswanathan, P.; Gray, R. L.; Lipuma, J. J.; Ciche, T. A. Genetic diversity and multihost pathogenicity of clinical and environmental strains of Burkholderia cenocepacia. Appl. Environ. Microbiol. 2009, 75 (16), 5250–5260
[x] Sandle T (2015) Characterizing the Microbiota of a Pharmaceutical Water System-A Metadata Study. SOJ Microbiol Infect Page 5 of 8 Dis 3(2): 1-8
[xi] Ali, M. (2016) Burkholderia Cepacia in Pharmaceutical Industries, Int J Vaccines Vaccin 3(2): 00064. DOI: 10.15406/ijvv.2016.03.00064
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