Indian Journal of Medical Microbiology, (2011) 29(1): 4-12 1

Review Article

Burkholderia cepacia complex: Beyond pseudomonas and acinetobacter

*V Gautam, L Singhal, P Ray

Abstract
Burkholderia cepacia complex (BCC) is an important nosocomial pathogen in hospitalised patients, particularly those
with prior broad-spectrum antibacterial therapy. BCC causes infections that include bacteraemia, urinary tract infection,
septic arthritis, peritonitis and respiratory tract infection. Due to high intrinsic resistance and being one of the most
antimicrobial-resistant organisms encountered in the clinical laboratory, these infections can prove very difficult to treat
and, in some cases, result in death. Patients with cystic fibrosis (CF) and those with chronic granulomatous disease are
predisposed to infection by BCC bacteria. BCC survives and multiplies in aqueous hospital environments, including
disinfectant agents and intravenous fluids, where it may persist for long periods. Outbreaks and pseudo-outbreaks of
BCC septicaemia have been documented in intensive care units, oncology units and renal failure patients. BCC
is phenotypically unremarkable, and the complex exhibits an extensive diversity of genotypes. BCC is of increasing
importance for agriculture and bioremediation because of their antinematodal and antifungal properties as well as their
capability to degrade a wide range of toxic compounds. It has always been a tedious task for a routine microbiological
laboratory to identify the nonfermenting gram-negative bacilli, and poor laboratory proficiency in identification of
this nonfermenter worldwide still prevails. In India, there are no precise reports of the prevalence of BCC infection,
and in most cases, these bacteria have been ambiguously reported as nonfermenting gram-negative bacilli or simply
Pseudomonas spp. The International Burkholderia cepacia Working Group is open to clinicians and scientists
interested in advancing knowledge of BCC infection/colonisation in persons with CF through the collegial exchange of
information and promotion of coordinated approaches to research.

Key words: Burkholderia cepacia complex, cystic fibrosis, nonfermenter, septicaemia

Introduction complex, Stenotrophomonas maltophilia and Burkholderia

cepacia complex (BCC).[2] Pseudomonas cepacia was
What better microbial challenge to unite agricultural originally described by William Burkholder in 1950 as
and medical microbiologists than an organism that reduces the causative agent of bacterial rot of onion bulbs and
an onion to a macerated pulp, protects other crops from was later transferred to the new genus Burkholderia in
bacterial and fungal disease, devastates the health and 1992.[3,4] BCC, a devastating pulmonary pathogen in CF
social life of cystic fibrosis (CF) patients and not only is and chronic granulomatous disease (CGD) patients, has
resistant to the most famous of antibiotics, penicillin, but also been reported as a cause of bacteraemia, particularly
can use it as a nutrient.[1] in patients with indwelling catheters, urinary tract infection,
Even after a decade, four nonfermenting gram-negative septic arthritis, peritonitis and respiratory tract infection.
bacilli (NFGNB) continue to be recognised as notorious The ability for Burkholderia species to thrive in the diverse
multidrug-resistant organisms. These are Pseudomonas range of environments is testament to the fact that they can
aeruginosa, Acinetobacter calcoaceticus-baumannii be considered as one of the most versatile groups of gram-
negative bacteria. BCC survives and multiplies in aqueous
hospital environments, including detergent solutions
*Corresponding author (email:<r_vg@yahoo.co.uk>) and intravenous fluids, where it may persist for long
Department of Medical Microbiology, Postgraduate Institute of periods.[4,5] Outbreaks of BCC septicaemia have been
Medical Education and Research (PGIMER), Chandigarh, India. documented in intensive care units (ICUs), oncology
Received: 30-11-2010 units and renal failure patients.[6] The ability of BCC to
Accepted: 06-12-2010 cause disease is not limited to the human host, as these
bacteria are also important plant pathogens. In addition,
Access this article online BCC bacteria may have useful commercial properties and
Quick Response Code: Website:
facilitate highly beneficial processes such as the breakdown
www.ijmm.org of pollutants or enhancement of crop yield.[7]
DOI:
10.4103/0255-0857.76516
BCC has emerged as an important cause of morbidity
and mortality in hospitalised patients largely because of
PMID:
high intrinsic antibiotic resistance.[4] It has always been
*****************************
a tedious task for a routine microbiological laboratory to
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January-March 2011 Gautam, et al.: Burkholderia cepacia complex 5

identify the NFGNBs, and poor laboratory proficiency
in identification of BCC prevails worldwide, including
our own country. For this reason, reports of disease due
to this organism are rare from India.[8-12] It needs to be
differentiated from P. aeruginosa as BCC has inherently
contrasting susceptibility pattern to that of P. aeruginosa.
BCC is the fourth most common pathogenic NFGNB
worldwide after P. aeruginosa, A. calcoaceticus-baumannii
complex and S. maltophilia.[4] However, in Postgraduate
Institute of Medical Education and Research (PGIMER),
BCC has been recognised as the third most common
nonfermenter over the last 6 years.[8-11]
Taxonomy
In 1950, William Burkholder, an American
microbiologist first described this microorganism as the
causative agent of bacterial rot of onion bulbs at Cornell
University. Until 1992, it was classified as P. cepacia. In
1992, P. cepacia and six other species belonging to rRNA
group II of the genus Pseudomonas were transferred to
the new genus Burkholderia, a name given in honour of
its discoverer.[3,4] In contrast to the genus Pseudomonas,
the genus Burkholderia belongs to the subdivision of the
phylum Proteobacteria. All Burkholderia species possess
very large genomes ranging between 6 and 9 Mb in size,
and it is this huge genetic capacity which underpins their
versatility in disease and natural biology. All species also
separate this DNA into two or more chromosomal replicons
which may add greater flexibility in the acquisition, loss
and expression of genes. Their classification has undergone
considerable taxonomic changes over the last two decades.
Based on phenotypic and genotypic analyses, BCC is
currently divided into 10 genomic species [Table 1].[13] The
term genomovar was introduced to denote phenotypically
similar genomic species and presently, genomovars are
recognised as new species. Recently, seven novel species,
B. latens, B. diffusa, B. arboris, B. seminalis, B. metallica,
B. contaminans and B. sabiae, have been proposed as
members of the BCC, using a polyphasic approach based
on comparative 16S ribosomal RNA and recA sequencing,
multilocus sequence typing (MLST) and intermediate
DNA-DNA binding values.[14,15]
Epidemiology
BCC organisms are distributed ubiquitously and found
most commonly on plant roots, the rhizosphere, soil and
moist environments. The ability of BCC to cause disease
is not limited to the human host, as these bacteria are
also important plant pathogens.[16] In addition, BCC may
have useful commercial properties and have been used in
agriculture as biocontrol agents and in the bioremediation
of toxic agents.[7,16] Plants of the Gramineae group appear
to be particularly important rhizospheric hosts for BCC
bacteria. Unlike P. aeruginosa which may be carried
by around 10% of humans (e.g., as a gut coloniser),
BCC bacteria have not yet been recovered from human
sources other than the sites of infection. Therefore, in the
absence of patient-to-patient transmission in CF infection,
the natural environment must be the reservoir of BCC
infection.[13] A highly comprehensive evidence has recently
been shown by MLST, whereby greater than 20% of the
clinical isolates were indistinguishable from environmental
isolates recovered from diverse environments such as river
water, onion, radish, maize rhizosphere, pharmaceutical
solutions, hospital equipment, shampoo and industrial
settings.[17]
The availability of rapid and accurate tests for
genomovar identification allowed for a comprehensive
analysis of the prevalence of different BCC species. By
the age of 18 years, about 3.5% of CF patients harbour
BCC. B. cenocepacia and B. multivorans are more
predominant amongst CF patients than non-CF patients
in four CF populations (United States, Canada, Italy and
Australia).[18-20] Other than B. cenocepacia and B.

Table 1: Species (formerly Genomovars) within the Burkholderia cepacia complex

Genomovar Species name Salient features
I Burkholderia cepacia
II Burkholderia multivorans Since 2000, this spp. has been more prevalent than B. cenocepacia infection
amongst the UK CF patients.
III Burkholderia cenocepacia Most common spp. in United States, Canada, Italy, Australia and India in CF and
non-CF patients.
IV Burkholderia stabilis
V Burkholderia vietnamiensis
VI Burkholderia dolosa
VII Burkholderia ambifaria Despite having over 100 isolates, all isolates have been recovered from CF
patients.
VIII Burkholderia anthina
IX Burkholderia pyrrocinia
X Burkholderia ubonensis

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6 Indian Journal of Medical Microbiology
multivorans, the remaining formally named species
account for less than 10% of all CF infections caused by
the complex.[13] Since 2000, B. multivorans infection has
been more prevalent than B. cenocepacia infection amongst
the UK CF population, indicating that regional differences
may be present in the epidemiological distribution of
BCC.[21] For the isolates recovered from non-CF
opportunistic infections, B. cenocepacia IIIA is again the
most dominant in terms of total numbers.[13] However, some
authors have detected B. cepacia more frequently amongst
non-CF patients.[20]
Further analysis of the different recA lineages revealed
significant geographical differences. Although type
IIIB strains represented 75% of all US B. cenocepacia
isolates, type IIIA strains are more prevalent in Canada
and Europe, accounting for about 70% of all genomovar
III isolates.[13,22] The unique distribution of selected BCC
genomovars indicates the presence of epidemic strains
exhibiting particular virulence and transmissibility. So far,
the following two genetic elements have been identified
that are associated with epidemic spread: cblA, a gene
encoding a protein for cable pilus production, and esmR
(or the B. cepacia epidemic strain marker), detected only
in B. cenocepacia strains. cblA and esmR sequences may
be encoded on a chromosomal region which is unstable
in some B. cenocepacia epidemic strains.[23,24] As B.
cenocepacia ET12 (‘Edinburgh⁄Toronto⁄ET12 epidemic B.
cepacia’ lineage) is mainly isolated from clinical settings
and not from the natural environment, we assume not only
that these species occupy the same niche, but also that
genetic exchange is occurring within human beings and not
in the natural environment.[25]
In contrast to B. cenocepacia, where direct patient-to-
patient contact and socialisation have been reported as the
most probable mechanisms by which infections spread,
the mode of transmission for B. multivorans infection
has not been determined.[26] It is interesting that despite
having more than 100 isolates of B. ambifaria, not one
has been recovered from a source of infection outside
of CF, suggesting that this species may have very limited
virulence as an invasive human opportunistic pathogen.[13]
It has been observed that B. cenocepacia can replace
other Burkholderia spp. In a study by Mahenthiralingam
et al., B. cenocepacia strains replaced B. multivorans in 6
patients, and were associated with a poor clinical outcome
and high mortality.[27] Out of the five isolates from a
50-year-old female patient admitted in PGIMER, three
isolates (out of four isolates processed) were B. cepacia
(restriction fragment length polymorphism [RFLP] type E)
and the last isolate identified was B. cenocepacia (RFLP
type G).[10]
A population structure analysis of B. cenocepacia
revealed that 86.7% of all restriction types clustered
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vol. 29, No. 1
into three major clonal complexes, comprising epidemic
clones ET12 (RT-6 complex), PHDC (the Philadelphia-
District Columbia) (RT-46 complex) and Midwest (RT-
88 complex).[28] These clones have a wide geographic
distribution and exhibit varying degrees of genetic
recombination. Infection with clone ET12 has been
associated with increased mortality and the so-called
“cepacia syndrome.”[29] In the United States, other epidemic
strains such as the PHDC and Mid-West strains were also
identified and classified as the B. cenocepacia recA III-B
subgroup.[30] A strain belonging to PHDC clonal lineage has
been isolated from organic soils in four agricultural fields
that had been planted with onions for several years. This
indicates that environmental strains may play a pivotal role
in the epidemiology of BCC infections and could explain
the ongoing human acquisition despite infection control
measures.[31] In contrast to some reports advocating the
identification of the cblA gene as a means of influencing
patient segregation and infection control strategies, the
absence of such markers from some epidemic strains
indicates that the cblA or esmR markers may not be reliable
indicators of transmissibility.[28,32]
It is interesting that man-made industrial settings also
appear to be prone to contamination with BCC bacteria.
Contamination with BCC bacteria may also occur in the oil
and fuel industry, which is not surprising given that these
bacteria are able to grow on a diverse range of hydrocarbon
substrates.[33] Using MLST, several BCC sequence types
have been found that overlap clinical, industrial and
natural sources [Figure 1], which clearly demonstrates the
Figure 1: Overlap of Burkholderia cepacia complex sequence types
from different sources. The 798 isolates in the Cardiff collection are
discriminated into 376 sequence types (ST). The total number of ST
and the occurrence of identical clones (overlapping ST) recovered
from clinical, industrial and natural sources are shown. (reproduced
with permission from Mahenthiralingam et al) [13]
January-March 2011 Gautam, et al.: Burkholderia cepacia complex
remarkably versatility of this group of bacteria to survive
and grow in highly diverse environments.[13]
International Burkholderia cepacia Working Group
The International Burkholderia cepacia Working Group
(IBCWG) was established in Spring, 1996 with support
from the Cystic Fibrosis Foundation (US). It gathers
emerging clinical and research data on BCC. It serves to
keep the CF medical community informed of developments
regarding these bacteria, and encourages and coordinates
continuing clinical and basic research on these bacteria.
The IBCWG includes microbiologists involved in basic
science research and CF physicians from the United States,
Canada, Australia and Europe (www.cff.org).
Clinical Spectrum
Patients with CF and those with CGD are predisposed
to infection by BCC bacteria. BCC is being increasingly
recognised as an important pathogen of human beings
in both immunocompromised and hospitalised patients
who are infected by contact with contaminated equipment
during hospitalisation. BCC bacteraemia should be
considered in febrile patients with nosocomial infections,
especially those who have an indwelling catheter, are on
ventilators, have CF or have immune dysfunction.[4,21,34]
Cystic Fibrosis
Chronic microbial colonisation of the major airways,
leading to exacerbations of pulmonary infection, is the
major cause of morbidity and mortality in patients with
CF (the most common lethal genetic disorder in Caucasian
populations). Staphylococcus aureus and P. aeruginosa
are the primary etiologic agents of pulmonary infection
in patients with CF. In childhood or early adolescence,
patients with CF become chronically infected with P.
aeruginosa.[34] As life expectancy has increased in patients
with CF, BCC has emerged as an important pathogen, and
it is being recovered from approximately 10% of adults
with CF. Pulmonary colonisation/infection by these bacteria
may persist for months or even years, but a minority of
adolescent and young adult patients with CF may exhibit
“cepacia syndrome” characterised by high fever, severe
progressive respiratory failure, leukocytosis and elevated
erythrocyte sedimentation rate. The patient may develop
bacteraemia and die within 6 months. Other patients with
CF may be infected with BCC without a corresponding
decline in clinical status.[13,34] Overall, in common with
many other opportunistic pathogens, it appears that severe
disease and death may result after infection with all BCC
species dependent on the clinical state and predisposition of
CF individuals at the time of infection. Clinical outcomes
may vary greatly amongst CF patients infected with the
same strain.[26,29]
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7
Non-CF Patients
BCC infections in immunocompetent patients occur
only sporadically, but several cases of pseudoepidemics
and nosocomial infections, often caused by contaminated
disinfectants and anaesthetic solutions, have been
reported. BCC bacteraemia, most often catheter-related
and polymicrobial, has been reported in cancer patients
and in patients undergoing haemodialysis, and nosocomial
pneumonia was observed in intensive care patients
who were mechanically ventilated and pretreated with
broad-spectrum antibiotics such as fluoroquinolones and
ceftazidime.[4,6,34,35] BCC skin and soft tissue infection
may occur in patients with burns or surgical wounds
and in soldiers with prolonged foot immersion in water.
Genitourinary tract infections caused by BCC have been
reported after urethral instrumentation, after transrectal
prostate biopsy or through exposure to contaminated
solutions.[34]
Outbreaks
Outbreaks have been reported originating from diverse
sources such as contaminated nebulisers, chlorhexidine
solution, alcohol-free mouthwash, multidose albuterol
vials used amongst multiple patients, indigo-carmine
dye used in enteral feeding, tap water, bottled water,
cosmetics, napkins, nasal sprays and ultrasound gel.[4,20,34]
An epidemic of BCC bacteraemia and pseudobacteraemia
occurred in the medical ICU at the Clinical Centre of
the National Institutes of Health. Sixteen patients in
ICU became colonised or infected with this organism
in a 21-month period, whereas BCC had been isolated
only 16 times in the preceding 90 months from the entire
hospital. Intensive investigation of the involved ICU and
its surrounding environment eventually demonstrated that
a blood gas analyser in an adjacent satellite laboratory was
the reservoir for the outbreak. Replacement of the machine
resulted in termination of the outbreak.[36] Its ability to
grow in distilled water and ability to fix CO2 from air
makes BCC probably the most nutritionally adaptable of all
pseudomonads.[37]
Indian Scenario
Indian CF patients
CF was thought to be extremely rare in India. However,
published reports, reviews and comments indicate that CF
is probably far more common in people of Indian origin
than previously thought but is underdiagnosed or missed
in the majority of cases. A total of 1200 children were
subjected to sweat chloride test and 120 (3.5%) children
were diagnosed of having CF in a study conducted at All
India Institute of Medical Sciences (AIIMS). Henceforth,
cystic fibrosis services at AIIMS were established with
the help of International Cystic Fibrosis (Mucoviscidosis)
8 Indian Journal of Medical Microbiology
Association.[38] The first patient of CF was diagnosed at PGI
in 1968 (six cases).[39] At present, there are approximately
60 CF patients on regular follow-up in Advanced Paediatric
Centre. Since this organism is difficult to eradicate after
colonisation, initial screening plays a pivotal role, and the
patient may be accordingly segregated. There is no report
of isolation of BCC from Indian CF patients. However,
recently, it has been isolated from six patients of CF
at PGIMER from the respiratory specimens and blood
(unpublished data).
Indian non-CF cases
In India, there are no precise reports of the prevalence
of BCC infection due to the lack of specific laboratory tests
and, in most cases, these bacteria have been ambiguously
reported as NFGNB or simply Pseudomonas spp. For this
reason, reports of diseases due to these organisms are rare
and it has been reported from few tertiary care centres
in north India.[8-11] A sudden upsurge of BCC has been
observed in non–CF-septicaemic patients of PGIMER,
Chandigarh, and in Escorts Heart Institute and Research
Centre (EHIRC), Delhi. Within four years (2006-2009),
approximately 150 isolates of BCC were obtained in
PGIMER. This is in comparison to a study by Reik et al.
who reported 90 isolates over the span of eight years from
various clinical specimens of non-CF patients.[8,20] BCC
from PGIMER has been isolated from blood cultures,
pus, respiratory specimens, body fluids and CSF. All
BCC isolates of EHIRC, Delhi, were from blood culture.
At PGIMER, BCC has been isolated from the patients
admitted in the different wards of PGIMER, with increased
isolation from children admitted in the Advanced Pediatric
Centre.[8,10] BCC has been recognised as the third most
common nonfermenter over the last six years in PGIMER
after P. aeruginosa and A. calcoaceticus-baumannii
complex.[8-11] It has been observed that B. cenocepacia
(RFLP type G, [Figure 2]) continues to be the most
prevalent species of BCC amongst Indian non-CF patients
(PGIMER and Escorts, 2006). This is a cause of concern
as patients with B. cenocepacia infections face the highest
mortality and have higher rate of transmission.[8-11]
Laboratory Diagnosis
It has always been a tedious task for a routine
microbiological laboratory to identify this NFGNB,
and poor laboratory proficiency prevails worldwide. In
routine clinical laboratories, the identification of putative
BCC isolates is generally performed using a combination
of selective media, conventional biochemical analysis
and/or commercial systems. Three media commonly
used are as follows: the P. cepacia agar (PCA), the
oxidation-fermentation polymyxin bacitracin lactose
agar (OFPBL),and more recently the B. cepacia selective
agar (BCSA) (containing 1% lactose and 1% sucrose in
an enriched base of casein and yeast extract with 600  U
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vol. 29, No. 1
Figure 2: RFLP analysis (HaeIII) of the B. cepacia complex recA
amplified by PCR. The most common pattern G is shown in all the
lanes. Molecular size standard (50-bp ladder) is in the first lane.
of polymyxin B per ml, 10  µg of gentamicin per ml and
2.5  µg of vancomycin per ml).[4,37] A comparison of all
three media revealed a superior performance of the BCSA,
achieving 43, 93, and 100% growth of BCC organisms at
24, 48, and 72 hours, respectively. BCSA is more selective,
acts by suppressing growth of non-BCC bacteria, whereas
BCC members form visible, smooth, pinpoint colonies
within 24 hours. Non-BCC organisms that are capable
of growing on BCSA are B. gladioli, Ralstonia spp. and
Pandoraea spp.[40,41] To aid routine diagnostic laboratories,
the authors have described the methods to identify BCC
by conventional biochemical reactions with the available
infrastructure and resources, which may be substantiated
by molecular methods for species identification.[11] Out of
58,717 blood cultures performed at PGIMER from April,
2007 to March, 2009, 21% (12 331/58 717) tested positive
for bacterial culture and 1,256 (1  256/12  331, 10.2%)
of these positive cultures grew NFGNB. Of these 1,256
NFGNB, 825 (825/1,256, 65.7%) were Acinetobacter
spp., 324 (324/1,256, 25.8%) were Pseudomonas spp.
and 60 (60/1,256, 4.8%) were BCC. Thirty five (35/1,256,
2.8%) isolates were identified as S. maltophilia. Twelve
(12/1,256, 0.9%) isolates could not be identified with
the limited available conventional biochemical tests
(unpublished data). Hence, by the conventional methods
for the identification of the NFGNB, 99% of the NFGNB
in a routine microbiology laboratory can be identified, and
accordingly the appropriate antimicrobial therapy can be
given to the patient.
Automated Identification Systems
Members of the BCC can be identified by available
commercial tests, such as API 20NE, Phoenix, MicroScan
or Vitek. Identification through commercial kits and
automated systems is not fool-proof as many non-
Burkholderia betaproteobacteria (Ralstonia picketti
and Pandoraea species) are misidentified as BCC and
some BCC strains as P. aeruginosa. A large polyphasic
analysis of 1,051 isolates from 115 CF treatment centres
in 91 US cities conducted in 2000 revealed an overall
January-March 2011 Gautam, et al.: Burkholderia cepacia complex
misidentification rate of 11% for isolates identified as
BCC by referring laboratories. This rate was even higher
(36%) for isolates not specifically identified or identified
as a species other than BCC.[4,42] In authors’ experience,
S. maltophilia has been labeled as BCC (95% probability
indicated by the system, Vitek) and another system
(Microscan Walkaway) labeled BCC as Burkholderia
pseudomallei (99% probability).[11] The laboratories which
are tentatively identifying Burkholderia species using
an automated system should confirm isolate identity by
growth on BCSA, conventional biochemical testing and, if
necessary, molecular techniques.[4,11,37]
Molecular identification
Identification is usually performed by DNA-based
polymerase chain reaction (PCR) methods, exploiting
sequence differences in the single locus of the 16S rRNA
gene or recA gene (recA is a protein essential for repair and
recombination of DNA) to assign isolates to the appropriate
species. This is achieved by PCR using primers specific
for the BCC, RFLP analysis of the product and further
PCR with a series of species-specific primers. However,
misidentification of BCC species has occurred using
these approaches as a RFLP-based strategy. Furthermore,
the medically important BCC member B. cenocepacia
is divided into four different recA phylotypes (IIIA-D),
complicating the identification of this species. The BCC
fur gene-based PCR (encoding the ferric uptake regulator
protein) has also been found to be useful for differentiating
between members of the BCC.[15,24]
Based on PCR-based techniques, unidentified
isolates have been reported in previous epidemiological
studies.[8,10,24,43-45] In a Brazilian study, 41 CF isolates
of BCC were identified by culture, and confirmation of
identity and genomovar determination was obtained in
32 isolates by recA-based PCR.[46] Fifty two BCC clinical
isolates from two centres in northern region of India were
subjected to recA-based PCR. Nine (9/40) isolates from
PGIMER and five (5/12) isolates from EHIRC, Delhi
remained unidentified by recA-based PCR.[8]
Other techniques used to discriminate beyond the
species-level include multilocus restriction typing, pulsed-
field gel electrophoresis, random amplified polymorphic
DNA and BOX-PCR. A relatively new technique that is fast
becoming the “gold standard” of bacterial typing methods
is MLST. MLST utilises the amplification by PCR and
DNA sequencing of seven putative housekeeping genes.
The method provides highly discriminatory information
from gene sequencing which can be shared and compared
easily between laboratories.[47] Recently, expanded MLST
typing has been described that addresses the shortcomings
in the original MLST methodology. It could type 25 BCC
strains that failed to be recognized with the original BCC
MLST.[48]
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9
Therapy
A significant problem in managing BCC-infected
patients is the organism’s resistance to various
antimicrobials and lack of newer effective antibiotics.
BCC is intrinsically resistant to antimicrobial agents
such as aminoglycosides, first-and second-generation
cephalosporins, antipseudomonal penicillins and
polymyxins. These various groups are commonly used
in Pseudomonas infections, and the value of proper
identification of BCC comes to the forefront.[4,37] BCC
often develops resistance to β-lactams due to presence
of inducible chromosomal β-lactamases and altered
penicillin-binding proteins. Antibiotic efflux pumps in
BCC mediate resistance to chloramphenicol, trimethoprim
and fluoroquinolones. On initial isolation, the organism
may be susceptible to trimethoprim-sulfamethoxazole and
antipseudomonal β-lactams. However, under antimicrobial
pressure, resistance quickly develops and the clinicians
frequently face the challenge of managing a patient infected
with an organism resistant to all available antimicrobials.
Some antibiotics such as ceftazidime, carbapenem and
ciprofloxacin display some in vitro activities against BCC.
As per the CLSI 2010 guidelines, the drugs recommended
against BCC are ceftazidime, minocycline, meropenem
and cotrimoxazole.[4,37] With the exception of the epidemic
B. cenocepacia ET12 lineage, previous studies of the
BCC have shown greatest susceptibility to meropenem,
irrespective of species status.[49] The antimicrobial
susceptibility profile of PGIMER isolates revealed near-
complete resistance to fluoroquinolones and more than 50%
resistance to carbapenems, the first-line therapeutics of
choice against serious pseudomonal infections.[8,10,11] These
isolates behaved similar to non-CF nosocomial Italian
isolates by showing susceptibility to ceftazidime.[50]
Successful treatment using combinations of meropenem
with ciprofloxacin and tobramycin has been reported,
as has been for ceftazidime and tobramycin. Additional
nebulisation of antimicrobial agents such as meropenem
or tobramycin has been reported to be effective as well.[4]
Amongst more recently developed antimicrobial agents,
doripenem appears to have therapeutical potential against
BCC.[51] All 50 clinical isolates of BCC obtained from
various specimens over the last four years in PGIMER were
found susceptible to doripenem by E-test as per CLSI 2010
guidelines (unpublished data).[52]
Prevention and Control
Patients may acquire BCC either from the environment
or through patient-to-patient transmission.[13,17] BCC has
generated considerable anxiety amongst patients with
CF and has led to the development of stringent infection
control procedures for managing CF patients with BCC
infection.[53] These include discontinuing sponsorship
and support of CF summer camps and segregation of
10 Indian Journal of Medical Microbiology
colonised patients. In 2002, no new patients were infected
with BCC for the next 1 year with the introduction of such
measures in Palermo, Italy.[54] However, segregation will
not prevent sporadic acquisition of BCC organisms from
natural environments.[18] Accepted prophylactic measures
include (a) an appropriate antibiotic policy, particularly a
critical use of ciprofloxacin, cefepime and imipenem; (b)
strict hand hygiene and institution of barrier techniques for
colonised or infected patients and (c) surveillance amongst
CF patients and identification of potential nosocomial
reservoirs such as the public water system, commercially
available drinking water, sink drains and medical
equipment. Education of patients and health care workers is
a cornerstone of such preventive measures. Implementation
of these draconian infection control measures has a
tremendous impact on the lives of CF patients, and not
all patients or caregivers accept such measures. The
widespread use of BCC in agriculture and bioremediation
of contaminated environmental sites causes a conflict about
its commercial use in light of its potentially life-threatening
impact on CF patients.[7,16] After a risk assessment of
BCC bacteria as model opportunistic pathogens with
biopesticidal uses in 1999, the United States Environmental
Protection Agency placed a moratorium on the new
registrations of products containing these bacteria (Federal
Register; http://www.epa.gov /fedrgstr/EPA-PEST/2004/
September/Day-29/p21695.htm).[13]
Conclusions
BCC, a devastating pulmonary pathogen in CF patients,
has also been reported as a cause of bacteraemia in few
centres from our country. Due to its ability to thrive in
the diverse range of environments, BCC contributes
to increased morbidity and mortality in hospitalised
patients. Various outbreaks and pseudo-outbreaks of
BCC septicaemia have also been documented in these
patients.[4,20,34] Due to high intrinsic resistance and
being one of the most antimicrobial-resistant organisms
encountered in the clinical laboratory, these infections can
prove very difficult to treat and, in some cases, result in
death.[4] Therefore, it needs to be correctly identified and
differentiated from P. aeruginosa as BCC has inherently
contrasting susceptibility pattern to that of P. aeruginosa. In
addition, BCC has diverse properties and has been used in
agriculture as biocontrol agent and in the bioremediation of
toxic agents.[7,16] BCC is phenotypically unremarkable, and
the complex exhibits an extensive diversity of genotypes.[13]
Hence, Burkholderia cepacia complex can be termed as
a diverse complex, truly complex.
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Source of Support: Nil, Conflict of Interest: None declared.

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