Burkholderia cepacia complex in cystic fibrosis and non-cystic fibrosis patients: identification of a cluster of epidemic lineages

doi:10.1053/jhin.2001.1160

Journal of Hospital Infection

Volume 50, Issue 3, March 2002, Pages 188-195

https://doi.org/10.1053/jhin.2001.1160 Get rights and content

Abstract

This study was performed in order to compare Burkholderia cepacia complex strains from cystic fibrosis (CF) and non-CF patients at the genomovar, genetic and epidemiological levels. A total of 92 B. cepacia respiratory tract isolates were obtained from patients attending the following CF centres: Catania and Palermo, Sicily; Gualdo Tadino, Central Italy, and Milan, Northern Italy. A total of 23 B. cepacia isolates were obtained from blood, surgical wound, and intravenous catheter sources of patients without CF, hospitalized in Catania and Varese, Northern Italy. Genomovar status identification, clonality and genetic relatedness determination, antibiotic susceptibility pattern determination and electron microscopy were performed. Transmission of infection was shown in both CF and non-CF patients by identifying clonality of responsible strains. In total 13 clones were involved in cross-transmission episodes. No outbreak was described involving both CF and non-CF patients. The present study indicates the existence of a distinct cluster of strains responsible for epidemics in CF and non-CF patients, based on their genetic relatedness, distinct from strains associated with no or negligible transmissibility. This result suggests that transmissibility is not only associated with a specific genomovar in CF patients, but also with a group of genetically related lineages in CF and non-CF patients. A key role is shown for both segregation measures and careful surveillance of infection, based on selective culture, molecular identification and epidemiological characterization of individual isolates.

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Biochemical and structural characterization of two cif-like epoxide hydrolases from Burkholderia cenocepacia
2021, Current Research in Structural Biology
Citation Excerpt :
It is commonly found in the soil where it can cause plant infections, serve as a biocontrol agent to prevent plant infections, and degrade aromatic hydrocarbon compounds (Juhasz et al., 1997; Huang and Wong, 1998; Jacobs et al., 2008; Krumme et al., 1993; Chen et al., 2020; Khodai-Kalaki et al., 2015). B. cenocepacia can also colonize the lung extracellular milieu of immunocompromised and non-immunocompromised patients, where it causes high morbidity and mortality, in part due to its broad antibiotic resistance (Agodi et al., 2002; Belchis et al., 2000; Scoffone et al., 2017). The bacteria are also able to cause a systemic infection by entering the patient's bloodstream, a condition known “Cepacia Syndrome” (Kalferstova et al., 2015).
Epoxide hydrolases catalyze the conversion of epoxides to vicinal diols in a range of cellular processes such as signaling, detoxification, and virulence. These enzymes typically utilize a pair of tyrosine residues to orient the substrate epoxide ring in the active site and stabilize the hydrolysis intermediate. A new subclass of epoxide hydrolases that utilize a histidine in place of one of the tyrosines was established with the discovery of the CFTR Inhibitory Factor (Cif) from Pseudomonas aeruginosa. Although the presence of such Cif-like epoxide hydrolases was predicted in other opportunistic pathogens based on sequence analyses, only Cif and its homolog aCif from Acinetobacter nosocomialis have been characterized. Here we report the biochemical and structural characteristics of Cfl1 and Cfl2, two Cif-like epoxide hydrolases from Burkholderia cenocepacia. Cfl1 is able to hydrolyze xenobiotic as well as biological epoxides that might be encountered in the environment or during infection. In contrast, Cfl2 shows very low activity against a diverse set of epoxides. The crystal structures of the two proteins reveal quaternary structures that build on the well-known dimeric assembly of the α/β hydrolase domain, but broaden our understanding of the structural diversity encoded in novel oligomer interfaces. Analysis of the interfaces reveals both similarities and key differences in sequence conservation between the two assemblies, and between the canonical dimer and the novel oligomer interfaces of each assembly. Finally, we discuss the effects of these higher-order assemblies on the intra-monomer flexibility of Cfl1 and Cfl2 and their possible roles in regulating enzymatic activity.
ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients
2014, Clinical Microbiology and Infection
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However, a few outbreaks of indistinguishable strains related to a common environmental source or cross-transmission have been reported [82–85]. Burkholderia cepacia may also cause nosocomial outbreaks, typically associated with medical products or environmental moist sources [51,82] Cross-transmission has been documented between cystic fibrosis patients [86,87] and may occur among non-cystic fibrosis patients [88]. The role of HCWs’ hand contamination has been under investigation since the 1960s [89].
Healthcare-associated infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB) are a leading cause of morbidity and mortality worldwide. These evidence-based guidelines have been produced after a systematic review of published studies on infection prevention and control interventions aimed at reducing the transmission of MDR-GNB. The recommendations are stratified by type of infection prevention and control intervention and species of MDR-GNB and are presented in the form of ‘basic’ practices, recommended for all acute care facilities, and ‘additional special approaches’ to be considered when there is still clinical and/or epidemiological and/or molecular evidence of ongoing transmission, despite the application of the basic measures. The level of evidence for and strength of each recommendation, were defined according to the GRADE approach.
Burkholderia cepacia complex: Beyond pseudomonas and acinetobacter
2011, Indian Journal of Medical Microbiology
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.
Identification of lysine positive non-fermenting gram negative bacilli (Stenotrophomonas maltophilia and Burkholderia cepacia complex)
2009, Indian Journal of Medical Microbiology
Background: The Burkholderia cepacia complex (BCC) and Stenotrophomonas maltophilia are closely related groups of non-fermenting gram-negative bacilli (NFGNBs) having a similar spectrum of infections ranging from superficial to deep-seated and disseminated infections. Identification of these lysine decarboxylase-positive NFGNBs lags behind in most Indian laboratories. A simplified identification scheme was devised for these two pathogens that allowed us to isolate them with an increasing frequency at our tertiary care institute. Materials and Methods: A simple five-tube conventional biochemical identification of these bacteria has been standardized. In the beginning, some of the isolates were confirmed from the International B. cepacia Working group, Belgium. Molecular identification and typing using recA polymerase chain reaction-restriction fragment length polymorphism was also standardized for BCC. For short-term preservation of BCC, an innovative method of preserving the bacteria in Robertson’s cooked medium tubes kept in a domestic refrigerator was developed. Results: Thirty-nine isolates of BCC isolates were obtained from various specimens (30 from blood cultures) and 22 S. maltophilia (13 blood cultures and 9 respiratory isolates) were isolated during the year 2007 alone. Conclusions: BCC and S. maltophilia can be identified with relative ease using a small battery of biochemical reactions. Use of simplified methods will allow greater recognition of their pathogenic potential and correct antimicrobials should be advised in other clinical laboratories and hospitals.
An outbreak of Burkholderia cepacia associated with contamination of albuterol and nasal spray
2006, Chest
Citation Excerpt :
The new strain recovered from the nasal spray did not appear to be associated with any adverse outcomes, even in the presence of CF. However, the outbreak strain was associated with patient-to-patient transmission and severe pneumonia and death in two patients. These results support other studies1,32,33 suggesting higher transmissibility and virulence for certain strains within the complex, although the molecular mechanisms are still unclear. Our investigation had several limitations.
Species within the Burkholderia cepacia complex (Bcc) can contaminate medications and disinfectants and cause severe pneumonia in critically ill patients or persons with cystic fibrosis. In March 2004, we investigated a hospital outbreak of Bcc possibly associated with a contaminated nasal spray.
We conducted a matched case-control study, environmental sampling, and observations of infection control practices. Case patients had infection or colonization with Bcc, and control patients had sputum culture not yielding Bcc. Isolates from patients and environmental samples were compared by pulsed-field gel electrophoresis (PFGE).
Bcc was recovered from sputum in 18 patients. Compared with matched control patients (n = 18), case patients were more likely to be receiving mechanical ventilation (p = 0.01), to have been hospitalized > 6 days (p = 0.01), and to have received antimicrobial treatment within 7 days before sputum collection (p = 0.03). Bcc was cultured from opened, but not unopened, multidose albuterol bottles, a nebulizer attached to a ventilator, and opened and unopened nasal spray bottles from contaminated lots. PFGE showed that isolates from albuterol samples and from patients were indistinguishable but unrelated to the nasal spray strain. Observations revealed improper aseptic techniques during respiratory therapy procedures and inadequate nebulizer cleaning.
Despite a temporal association with use of a contaminated nasal spray, this outbreak was caused by extrinsic contamination of multidose albuterol used for nebulization treatments and lack of adherence to infection control precautions. Implementation and re-enforcement of infection control measures successfully terminated the outbreak.
A National Guard outbreak of Burkholderia Cepacia infection and colonization secondary to intrinsic contamination of Albuterol nebulization solution
2005, American Journal of Infection Control
Citation Excerpt :
The Saudi Ministry of Health was also notified, and a nationwide recall took place. B cepacia is a pathogen known for its association with lower respiratory tract disease in cystic fibrosis patients.11,12 It is also known to cause outbreaks of noscomial infections of the bloodstream and respiratory tract, mainly via a common contaminated source, such as contaminated disinfectants, aqueous solutions, liquid reservoirs, and pharmaceutics.7,8,13-17
Burkholderia cepacia, a gram-negative pathogen, has been a known cause of hospital outbreaks because of a contaminated common source such as multidose medications. We describe an outbreak with Burkholderia cepacia infection in 2 major hospitals affiliated to the National Guard, related to an intrinsic contamination of a locally manufactured, multidose Albuterol nebulization solution (Tabouk Pharmaceutical Company, Tabouk, Saudi Arabia) and we report the interventions taken to interrupt this outbreak.
During the outbreak period between May 2003 and March 2004, a combined prospective surveillance and a retrospective chart and microbiologic data review were conducted in 4 major hospitals affiliated to the National Guard. Microbiologic cultures were also performed on environmental objects of concern, as well as certain medications. In addition, a questionnaire was distributed to the respiratory therapy staff to evaluate the process of administering respiratory medications and their adherence to sound infection control practices.
An intrinsic contamination of a locally manufactured brand of multidose Albuterol nebulization with B cepacia was identified. Two of the 4 hospitals were found to be involved: hospital A a 700-bed tertiary care center and Hospital B a 150-bed hospital. A total of 2121 patients were exposed to Albuterol nebulization as inpatients at hospital A and 318 as outpatients. For hospital B, a total of 283 inpatients and 34 outpatients were exposed to the Albuterol nebulization. Forty and 12 patients, from hospital A and hospital B, respectively, were found to have at least 1 positive culture for B cepacia. From hospital A, most samples were respiratory, and, from hospital B, most were from blood. Molecular typing of 34 available isolates showed that 23 cases were of a single strain of B cepacia that matched the strain isolated from the 3 different batches of multidose Albuterol nebulization. Three culture-positive patients never received Albuterol nebulization of that brand but were in the same room of a patient who had been receiving the medication.
We identified a large outbreak of B cepacia in 2 major hospitals affiliated with the National Guard, linked to an intrinsic contamination of a multidose Albuterol nebulization solution. During the period of prospective surveillance, only a few cases were identified as a result of nosocomial transmission. Immediate notification of the Ministry of Health and withdrawal of the medication and revisiting the respiratory therapy practices were necessary to halt this outbreak.

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^f1: Author for correspondence: Prof. S. Stefani, Section of Microbiology of the Department of Microbiological and Gynecological Sciences, University of Catania, Via Androne 81, 95124 Catania Italy. Fax: 39 (095) 325032; E-mail:[email protected]

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Regular ArticleBurkholderia cepacia complex in cystic fibrosis and non-cystic fibrosis patients: identification of a cluster of epidemic lineages

Abstract

Am J Kidney Dis

Clin Chest Med

Clin Microbiol Inf

Am J Infect Control

An outbreak of Burkholderia cepacia with septicemia on a cardiology ward

Infect Control Hosp Epidemiol

Endemic Burkholderia cepacia bacteraemia: clinical features and antimicrobial susceptibilities of isolates

Scand J Infect Dis

Nosocomial outbreak of Pseudomonas cepacia associated with contamination of reusable electronic ventilator temperature probes

Infect Control Hosp Epidemiol

Burkholderia cepacia respiratory tract acquisition: epidemiology and molecular characterization of a large nosocomial outbreak

Epidemiology Infect

An outbreak of Burkholderia cepacia lower respiratory tract infection associated with contaminated albuterol nebulization solution

Infect Control Hosp Epidemiol

Nosocomial Burkholderia cepacia infection and colonization associated with intrinsically contaminated mouthwash—Arizona 1998

MMWR Morb Mortal Wkly Rep

Polyphasic taxonomy in the genus Burkholderia leading to an emended description of the genus and proposition ofBurkholderia vietnamiensis sp. nov. for N2-fixing isolates from rice in Vietnam

Int J Syst Bacteriol

Identification and population structure of Burkholderia stabilis sp. nov. (formerly Burkholderia cepacia genomovar IV)

J Clin Microbiol

Burkholderia ambifaria sp.nov., a novel member of the Burkholderia cepacia complex comprising biocontrol and cystic-fibrosis related isolates

Int J Syst Evol Microbiol

Structurally variant classes of pilus appendage fibers coexpressed from

Burkholderia (Pseudomonas) cepacia. J Bacteriol

Polyphasic taxonomy, a consensus approach to bacterial systematics

Microbiol Rev

Occurrence of multiple genomovars of Burkholderia cepacia in cystic fibrosis patients and proposal ofBurkholderia multivorans sp. nov

Int J Syst Bacteriol

Discrimination of Burkholderia multivorans and Burkholderia vietnamiensis from Burkholderia cepacia genomovars I, III, and V by PCR

J Clin Microbiol

Regular Article
Burkholderia cepacia complex in cystic fibrosis and non-cystic fibrosis patients: identification of a cluster of epidemic lineages