Challenges and mitigation strategies associated with Burkholderia cepacia complex contamination in pharmaceutical manufacturing.

Burkholderia cepacia complex (BCC) is a Gram-negative, non-spore-forming bacterium with more than 20 opportunistic pathogenic species, most commonly found in soil and water. Due to their rapid mutation rates, these organisms are adaptable and possess high genomic plasticity. BCC can cause life-threatening infections in immunocompromised individuals, such as those with cystic fibrosis, chronic granulomatous disease, and neonates. BCC contamination is a significant concern in pharmaceutical manufacturing, frequently causing non-sterile product recalls. BCC has been found in purified water, cosmetics, household items, and even ultrasound gel used in veterinary practices. Pharmaceuticals, personal care products, and cleaning solutions have been implicated in numerous outbreaks worldwide, highlighting the risks associated with intrinsic manufacturing site contamination. Regulatory compliance, product safety, and human health protection depend on testing for BCC in pharmaceutical manufacturing. Identification challenges exist, with BCC often misidentified as other bacteria like non-lactose fermenting Escherichia coli or Pseudomonas spp., particularly in developing countries where reporting BCC in pharmaceuticals remains limited. This review comprehensively aims to address the organisms causing BCC contamination, genetic diversity, identification challenges, regulatory requirements, and mitigation strategies. Recommendations are proposed to aid pharmaceutical chemists in managing BCC-associated risks and implementing prevention strategies within manufacturing processes.

Diving deep for the needle in the haystack: An outbreak investigation of Burkholderia cenocepacia bacteremia.

In an Indian oncology setting, between August and December 2021, 56 patients, developed Burkholderia cenocepacia bacteremia. An investigation revealed a contaminated batch of the antiemetic drug palonosetron. The outbreak was terminated by withdrawing the culprit batch and the findings were reported promptly to regulatory authorities.

Outbreak investigation of NDM-producing Burkholderia cepacia causing neonatal sepsis in Pakistan.

Aim: To investigate the outbreak of Burkholderia cepacia complex (BCC), mortality, antimicrobial resistance and associated risk factors in the neonatal intensive care unit. Method: Eighteen blood culture samples from neonates and twenty swab samples from different neonatal intensive care unit surfaces were collected. The VITEK 2 was used to confirm the isolates and generate the antibiogram. PCR was used to identify blaNDM. Results: Eighteen samples tested positive for BCC, and 10/18 (55.5%) of the neonates died. 13/18 (72%) of the neonates had late-onset neonatal sepsis, and 10/18 (55%) had low birth weight. Resistance to minocycline and chloramphenicol was 100%, 72.2% to meropenem; 72.2% NDM gene was found in neonates and was 20% from the environment. Conclusion: Outbreak of NDM-producing BCC resulting in high neonatal mortality in NICU.

Neonatal septicemia, or blood poisoning, is a dangerous illness in newborns. It is caused by bacteria or other infections entering the blood and spreading. Pregnancy, labor, delivery and exposure after birth can result in infection of the newborn. Neonatal septicemia kills 700,000 babies worldwide, mostly in low- and middle-income countries. Burkholderia cepacia complex bacteria can cause infections in people with weaker immune systems or other disorders. They are particularly dangerous in hospitals, as they can cause chronic lung problems. This study collected blood samples from newborns with blood poisoning. Most samples that contained Burkholderia cepacia complex were not susceptible to drugs. Four of the newborns carried the same bacteria, indicating that hospital staff should practice hand washing and equipment and environmental cleaning to prevent the spread of the bacteria.

Two consecutive outbreaks caused by chlorhexidine mouthwash contaminated with Burkholderia contaminans in a two-hospital tertiary care system.

BACKGROUND: Hospital outbreaks caused by Burkholderia spp. have been linked to contamination of several medical solutions and products and are frequently associated with delayed detection and high mortality. AIM: To describe the management of two consecutive Burkholderia contaminans outbreaks caused by contaminated mouthwash of different brands during the COVID-19 pandemic. METHODS: This was a retrospective cohort study of all patients involved in two outbreaks caused by B. contaminans detected in 2021 and 2022. The investigation was initiated after a cluster of positive respiratory specimens, followed by retrospective and prospective case-finding. FINDINGS: A total of 69 patients were affected, 47 in 2021 and 22 in 2022. The majority of affected patients had positive respiratory specimens (85.5%); 55.1% of cases had COVID-19, and 72.5% had multidrug-resistant organisms. Almost all (97.1%) patients required ventilation and 42.0% died. Seventeen percent of cases in the first outbreak were deemed to have been acquired by patient-to-patient transmission, whereas all of the cases in the second outbreak were infected directly from using mouthwash. The experience gained from the first outbreak and the formation of a multidisciplinary Infection Control Rapid Response Team resulted in more rapid recognition and control of the second outbreak. Multivariate analysis showed that older age, intensive care unit admission, and COVID-19 infection were independent predictors of mortality. CONCLUSION: Burkholderia outbreaks at the time of COVID-19 were associated with high mortality. Rapid detection and response by a dedicated experienced team (as in the second outbreak) can reduce mortality and prevent superimposed cross-transmission between patients.

Burkholderia cepacia infections at sites other than the respiratory tract: A large case series from a tertiary hospital in Madurai.

Sparsely reported extrapulmonary Burkholderia cepacia complex (Bcc) infections highlights the importance of this study. This was a retrospective chart review of 37 patients with extrapulmonary Bcc infections admitted between December 2019 and July 2022 in a tertiary hospital. Males accounted for 70% of cases. 78% had atleast one underlying comorbid illness. Among 37 isolates, 22 were from blood, others include exudates, urine and peritoneal fluid. Susceptibility rates of ceftazidime, meropenem, minocycline, cotrimoxazole and levofloxacin were 88, 88, 70, 65.7 and 56.7% respectively. Eleven died of septic shock and 24 patients (64.8%) had good outcomes, while two were lost to followup.

Genomic features, antimicrobial susceptibility, and epidemiological insights into Burkholderia cenocepacia clonal complex 31 isolates from bloodstream infections in India.

Introduction: Burkholderia cepacia complex (Bcc) clonal complex (CC) 31, the predominant lineage causing devastating outbreaks globally, has been a growing concern of infections in non-cystic fibrosis (NCF) patients in India. B. cenocepacia is very challenging to treat owing to its virulence determinants and antibiotic resistance. Improving the management of these infections requires a better knowledge of their resistance patterns and mechanisms. Methods: Whole-genome sequences of 35 CC31 isolates obtained from patient samples, were analyzed against available 210 CC31 genomes in the NCBI database to glean details of resistance, virulence, mobile elements, and phylogenetic markers to study genomic diversity and evolution of CC31 lineage in India. Results: Genomic analysis revealed that 35 isolates belonging to CC31 were categorized into 11 sequence types (ST), of which five STs were reported exclusively from India. Phylogenetic analysis classified 245 CC31 isolates into eight distinct clades (I-VIII) and unveiled that NCF isolates are evolving independently from the global cystic fibrosis (CF) isolates forming a distinct clade. The detection rate of seven classes of antibiotic-related genes in 35 isolates was 35 (100%) for tetracyclines, aminoglycosides, and fluoroquinolones; 26 (74.2%) for sulphonamides and phenicols; 7 (20%) for beta-lactamases; and 1 (2.8%) for trimethoprim resistance genes. Additionally, 3 (8.5%) NCF isolates were resistant to disinfecting agents and antiseptics. Antimicrobial susceptibility testing revealed that majority of NCF isolates were resistant to chloramphenicol (77%) and levofloxacin (34%). NCF isolates have a comparable number of virulence genes to CF isolates. A well-studied pathogenicity island of B. cenocepacia, GI11 is present in ST628 and ST709 isolates from the Indian Bcc population. In contrast, genomic island GI15 (highly similar to the island found in B. pseudomallei strain EY1) is exclusively reported in ST839 and ST824 isolates from two different locations in India. Horizontal acquisition of lytic phage ST79 of pathogenic B. pseudomallei is demonstrated in ST628 isolates Bcc1463, Bcc29163, and BccR4654 amongst CC31 lineage. Discussion: The study reveals a high diversity of CC31 lineages among B. cenocepacia isolates from India. The extensive information from this study will facilitate the development of rapid diagnostic and novel therapeutic approaches to manage B. cenocepacia infections.

[68Ga]Ga-Ornibactin for Burkholderia cepacia complex Infection Imaging Using Positron Emission Tomography.

Bacteria from the Burkholderia cepacia complex are generally considered to be non-pathogenic to the healthy population. However, some of these species may cause serious nosocomial infections in immunocompromised patients; as such, it is essential to diagnose these infections rapidly so that adequate treatment can be initiated. We report here the use of a radiolabeled siderophore, ornibactin (ORNB), for positron emission tomography imaging. We successfully radiolabeled ORNB with gallium-68 with high radiochemical purity and proved that the resulting complex has optimal in vitro characteristics. In mice, the complex did not show excessive accumulation in organs and was excreted in the urine. We demonstrated that the [68Ga]Ga-ORNB complex accumulates at the site of Burkholderia multivorans infection, including pneumonia, in two animal infection models. These results suggest that [68Ga]Ga-ORNB is a promising tool for the diagnosis, monitoring, and evaluation of the therapeutic response to B. cepacia complex infection.

Identification of Burkholderia cenocepacia non-coding RNAs expressed during Caenorhabditis elegans infection.

Small non-coding RNAs (sRNAs) are key regulators of post-transcriptional gene expression in bacteria. Despite the identification of hundreds of bacterial sRNAs, their roles on bacterial physiology and virulence remain largely unknown, as is the case of bacteria of the Burkholderia cepacia complex (Bcc). Bcc is a group of opportunistic pathogens with relatively large genomes that can cause lethal lung infections amongst cystic fibrosis (CF) patients. To characterise sRNAs expressed by Bcc bacteria when infecting a host, the nematode Caenorhabditis elegans was used as an infection model by the epidemic CF strain B. cenocepacia J2315. A total of 108 new and 31 previously described sRNAs with a predicted Rho independent terminator were identified, most of them located on chromosome 1. RIT11b, a sRNA downregulated under C. elegans infection conditions, was shown to directly affect B. cenocepacia virulence, biofilm formation, and swimming motility. RIT11b overexpression reduced the expression of the direct targets dusA and pyrC, involved in biofilm formation, epithelial cell adherence, and chronic infections in other organisms. The in vitro direct interaction of RIT11b with the dusA and pyrC messengers was demonstrated by electrophoretic mobility shift assays. To the best of our knowledge this is the first report on the functional characterization of a sRNA directly involved in B. cenocepacia virulence. KEY POINTS: • 139 sRNAs expressed by B. cenocepacia during C. elegans infection were identified • The sRNA RIT11b affects B. cenocepacia virulence, biofilm formation, and motility • RIT11b directly binds to and regulates dusA and pyrC mRNAs.

A study on the occurrence of Burkholderia cepacia complex in ultrasound gels used in different veterinary clinical settings in India.

Burkholderia cepacia complex (Bcc) organisms are emerging multidrug-resistant pathogens. They are opportunistic and cause severe diseases in humans that may result in fatal outcomes. They are mainly reported as nosocomial pathogens, and transmission often occurs through contaminated pharmaceutical products. From 1993 to 2019, 14 Bcc outbreaks caused by contaminated ultrasound gels (USGs) have been reported in several countries, including India. We screened a total of 63 samples of USGs from various veterinary and human clinical care centers across 17 states of India and isolated 32 Bcc strains of Burkholderia cenocepacia (46.8%), B. cepacia (31.3%), B. pseudomultivorans (18.8%) and B. contaminans (3.1%) species. Some isolates were co-existent in a single ultrasound gel sample. The isolation from unopened gel bottles revealed the intrinsic contamination from manufacturing sites. The MALDI-TOF analysis to identify the Bcc at the species level was supported by the partial sequencing of the recA gene for accurate species identification. The phylogenetic analysis revealed that isolates shared clades with human clinical isolates, which is an important situation because of the possible infections of Bcc by USGs both in humans and animals. The pulsed field gel electrophoresis (PFGE) typing identified the genetic variation among the Bcc isolates present in the USGs. The findings indicated USGs as the potential source of Bcc species.

Cepacia syndrome in cystic fibrosis: A systematic review of the literature and possible new perspectives in treatment.

BACKGROUND: Cepacia syndrome (CS) is an acute, necrotizing pneumonia with a high mortality rate, occurring in patients with cystic fibrosis (CF) infected with Burkholderia cepacia complex (BCC). Due to its low incidence, data on this condition are limited. METHODS: We conducted a systematic review of the reported cases of CS by searching MEDLINE, Embase and the Cochrane Library to improve knowledge of this rare but potentially lethal condition. RESULTS: We included 15 eligible articles, describing 18 cases (9 females) of CS. Median age at onset was 22 years (range: 10-60 years); median time to CS after first infection by BCC was 5 years (range: 1-26 years). Burkholderia cenocepacia was the most frequently reported causative agent. All patients received intravenous antibiotic treatment (most frequently including cotrimoxazole), while inhaled antibiotics were used in five patients (27.8%). Immunosuppressant agents were the most commonly prescribed supportive treatment (n = 7, 38.9%). Half of the patients died (9/18, 50%). CONCLUSIONS: This study describes epidemiological, clinical characteristics, and prognosis of CS cases reported over the last 24 years. CS is a rare yet severe complication of BCC infection in patients with CF, which occurs several years after BCC colonization and has a negative outcome in 50% of the patients. Data are too scanty to identify the most effective therapeutic approach.

Design, Development, and Validation of a Culture-Independent Nucleic Acid Diagnostics Method for the Rapid Detection and Quantification of the Burkholderia cepacia Complex in Water with an Equivalence to ISO/TS 12869:2019.

In the wake of a series of outbreaks of finished pharmaceutical product-related Burkholderia cepacia complex (Bcc) human infections worldwide, the United States Food and Drug Administration (FDA) in 2017, and subsequently in 2021, issued advisory notifications to the pharmaceutical industry for stringent Bcc testing requirements for pharmaceutical manufacturing processes and for finished pharmaceutical products prior to release to the marketplace. The advisory notifications highlight non-sterile aqueous finished pharmaceutical products as being a major culprit associated with many of these human infection events. As such, there has been a significant number of Bcc-contaminated finished product recalls resulting in company revenue losses, delayed finished product release, finished product shortages for patients, and manufacturing plant shutdowns coupled with company reputational damage. With many of the finished product recall events, pharmaceutical grade water and/or manufacturing facility water distribution systems were identified as the primary origin source of Bcc contamination. Testing and monitoring regimes currently employed to identify Bcc contamination of water associated with pharmaceutical manufacturing are often limited by costly, laborious, lengthy, and nonspecific traditional microbial culture-based methodologies. Presently FDA approved, European Conformity (CE) marked, and International Organization for Standardization (ISO) standard microbial culture-independent rapid, quantitative, specific, and sensitive nucleic acid diagnostics (NAD) methodologies are now gaining greater widespread acceptance in their routine usage in testing laboratories. Here we present the development of a rapid (<4 hours from sample in to result out) single test culture-independent Bcc NAD method, incorporating a quantitative real-time polymerase chain reaction (qPCR) assay. This method can be used for the detection and simultaneous identification of all 24 Bcc species currently assigned, directly from water samples. This culture-independent Bcc NAD method is validated to the testing method equivalent of the ISO/TS 12869:2019 standard, which is a widely used rapid culture-independent NAD method for detecting Gram-negative Legionella species in water.

Burkholderia vietnamiensis causing infections in noncystic fibrosis patients in a tertiary care hospital in Mexico.

Burkholderia cepacia complex (Bcc) species are opportunistic pathogens widely distributed in the environment and often infect people with cystic fibrosis (CF). This study aims to determine which genomovars of the Bcc can cause infections in non-CF patients from a tertiary care hospital in Mexico and if they carry virulence factors that could increase their pathogenicity. We identified 23 clinical isolates that carry the recA gene. Twenty-two of them belongs to the genomovar V (B. vietnamiensis) and one to the genomovar II (B. multivorans). Thirteen pulsotypes were identified among 22 B. vietnamiensis isolates. All clinical isolates produced biofilm were motile and cytotoxic on murine macrophage-like RAW264.7 and in A549 human lung epithelial cells. In conclusion, B. vietnamiensis causes infections in non-CF patients in a tertiary care hospital in Mexico, rapid identification of this pathogen can help physicians to establish a better antimicrobial treatment.

An outbreak of Burkholderia cepacia bloodstream infections in a tertiary-care facility in northern India detected by a healthcare-associated infection surveillance network.

OBJECTIVE: The burden of healthcare-associated infections (HAIs) is higher in low- and middle-income countries, but HAIs are often missed because surveillance is not conducted. Here, we describe the identification of and response to a cluster of Burkholderia cepacia complex (BCC) bloodstream infections (BSIs) associated with high mortality in a surgical ICU (SICU) that joined an HAI surveillance network. SETTING: A 780-bed, tertiary-level, public teaching hospital in northern India. METHODS: After detecting a cluster of BCC in the SICU, cases were identified by reviewing laboratory registers and automated identification and susceptibility testing outputs. Sociodemographic details, clinical records, and potential exposure histories were collected, and a self-appraisal of infection prevention and control (IPC) practices using assessment tools from the World Health Organization and the US Centers for Disease Control and Prevention was conducted. Training and feedback were provided to hospital staff. Environmental samples were collected from high-touch surfaces, intravenous medications, saline, and mouthwash. RESULTS: Between October 2017 and October 2018, 183 BCC BSI cases were identified. Case records were available for 121 case patients. Of these 121 cases, 91 (75%) were male, the median age was 35 years, and 57 (47%) died. IPC scores were low in the areas of technical guidelines, human resources, and monitoring and evaluation. Of the 30 environmental samples, 4 grew BCC. A single source of the outbreak was not identified. CONCLUSIONS: Implementing standardized HAI surveillance in a low-resource setting detected an ongoing Burkholderia cepacia outbreak. The outbreak investigation and use of a multimodal approach reduced incident cases and informed changes in IPC practices.

An outbreak of Burkholderia contaminans at a quaternary children's hospital linked to equipment reprocessing.

Burkholderia cepacia complex (BCC) has been increasingly implicated in local and multistate outbreaks in both adult and pediatric healthcare settings. However, a lack of source identification may be common for BCC outbreak investigations. We describe, in detail, the investigation of an outbreak of BCC (B. contaminans) among pediatric patients at a large quaternary-care children's hospital and our system-level changes and outcomes.

Outbreak of Burkholderia stabilis Infections Associated with Contaminated Nonsterile, Multiuse Ultrasound Gel - 10 States, May-September 2021.

In July 2021, the Virginia Department of Health notified CDC of a cluster of eight invasive infections with Burkholderia stabilis, a bacterium in the Burkholderia cepacia complex (BCC), among hospitalized patients at hospital A. Most patients had undergone ultrasound-guided procedures during their admission. Culture of MediChoice M500812 nonsterile ultrasound gel used in hospital A revealed contamination of unopened product with B. stabilis that matched the whole genome sequencing (WGS) of B. stabilis strains found among patients. CDC and hospital A, in collaboration with partner health care facilities, state and local health departments, and the Food and Drug Administration (FDA), identified 119 B. stabilis infections in 10 U.S. states, leading to the national recall of all ultrasound gel products produced by Eco-Med Pharmaceutical (Eco-Med), the manufacturer of MediChoice M500812. Additional investigation of health care facility practices revealed frequent use of nonsterile ultrasound gel to assist with visualization in preparation for or during invasive, percutaneous procedures (e.g., intravenous catheter insertion). This practice could have allowed introduction of contaminated ultrasound gel into sterile body sites when gel and associated viable bacteria were not completely removed from skin, leading to invasive infections. This outbreak highlights the importance of appropriate use of ultrasound gel within health care settings to help prevent patient infections, including the use of only sterile, single-use ultrasound gel for ultrasonography when subsequent percutaneous procedures might be performed.

Molecular Research Comparing the Probabilities of Burkholderia Cepacia Bacterium Diagnosis Procedures.

Burkholderia cepacia is found as part of the B. cepacia complex (Bcc), a collection of highly pathogenic organisms. The Bcc is present almost everywhere in nature; however, it is most prevalent in damp settings, plant roots, and soils. Moreover, Bcc is a major source of morbidity and death in patients due to its high intrinsic antibiotic resistance. The present study aims to isolate and identify gram-negative aerobic bacteria from clinical samples derived from a variety of pathological diseases and investigate the bacterium's virulence factors and genes. The current study included 250 specimens collected from patients suffering from diabetic foot ulcers, urine, burn, wound, sputum, and discharge from the eyes. The samples were collected from both sexes with the age range of 1-75 years. The recorded data showed that males had a higher frequency of infection (79.2%) than females (52%). The results revealed that 7.6% of infected females were between 1-15 years old, while 22% of infected males were aged between 31-45 years. In addition, 26.8% of infected patients (both males and females) were aged between 31-45 years.

Burkholderia cepacia complex outbreak linked to a no-rinse cleansing foam product, United States - 2017-2018.

In March 2018, the US Food and Drug Administration (FDA), US Centers for Disease Control and Prevention, California Department of Public Health, Los Angeles County Department of Public Health and Pennsylvania Department of Health initiated an investigation of an outbreak of Burkholderia cepacia complex (Bcc) infections. Sixty infections were identified in California, New Jersey, Pennsylvania, Maine, Nevada and Ohio. The infections were linked to a no-rinse cleansing foam product (NRCFP), produced by Manufacturer A, used for skin care of patients in healthcare settings. FDA inspected Manufacturer A's production facility (manufacturing site of over-the-counter drugs and cosmetics), reviewed production records and collected product and environmental samples for analysis. FDA's inspection found poor manufacturing practices. Analysis by pulsed-field gel electrophoresis confirmed a match between NRCFP samples and clinical isolates. Manufacturer A conducted extensive recalls, FDA issued a warning letter citing the manufacturer's inadequate manufacturing practices, and federal, state and local partners issued public communications to advise patients, pharmacies, other healthcare providers and healthcare facilities to stop using the recalled NRCFP. This investigation highlighted the importance of following appropriate manufacturing practices to minimize microbial contamination of cosmetic products, especially if intended for use in healthcare settings.

The Genetic relatedness of Burkholderia contaminans clinical isolates from cystic fibrosis and non-cystic fibrosis patients in Argentina.

INTRODUCTION: The Burkholderia cepacia complex (BCC) bacteria are opportunistic pathogens that cause nosocomial infections and are especially dangerous for cystic fibrosis (CF) patients. Burkholderia contaminans is an emerging BCC species isolated from CF patients that also occurs as a contaminant in pharmaceutical and personal care products, sometimes linking it with outbreaks. METHODOLOGY: A total of 55 B. contaminans isolates from CF and non-CF patients in Argentina were identified by recA sequencing and MALDI TOF MS. A standardized Pulsed Field Gel Electrophoresis (PFGE) protocol was set up in order to assess genetic diversity, outbreak investigations, and possible clone persistence. RESULTS: All isolates were identified as B. contaminans by both MALDI-TOF MS and recA sequence analysis. PFGE has enabled us to compare and determine the genetic relationship between B. contaminans isolates. Isolates were distributed in different PFGE clusters with evidence of the presence and persistence of a clone, over a period of 3 years, in the same hospital. This large hospital outbreak involved CF and non-CF patients. Moreover, PFGE results showed a good correlation between sporadic or outbreak-related isolates and the available epidemiological information. CONCLUSIONS: These findings highlight the importance of B. contaminans in Argentina and provide evidence for encouraging the surveillance of highly transmissible clones. The study also contributes to global knowledge about B. contaminans infections.

Burkholderia cepacia Infections at Sites Other than the Respiratory Tract: A Large Case Series from a Tertiary Referral Hospital in Lebanon.

OBJECTIVES: The Burkholderia cepacia complex (Bcc), which was originally thought to be a single species, represents a group of 24 distinct species that are often resistant to multiple antibiotics, and usually known to cause life-threatening pulmonary infections in cystic fibrosis patients. Herein we describe a series of non-respiratory Bcc infections, the risk factors and epidemiologic factors, in addition to the clinical course. PATIENTS AND METHODS: This is a retrospective chart review of 44 patients with documented B. cepacia infections isolated from sites other than the respiratory tract admitted between June 2005 and February 2020 to the American University of Beirut Medical Center (AUBMC), a tertiary referral hospital for Lebanon and the Middle East region. The epidemiological background of these patients, their underlying risk factors, the used antibiotic regimens, and the sensitivities of the B. cepacia specimens were collected. RESULTS: The majority of the Bcc infections (26/44, 59.1%) were hospital-acquired infections. The most common nationality of the patients was Iraqi (18/44, 40.9%), and the most common site of infection was bacteremia (17/44, 38.6%), followed by skin and soft tissues infections (16/44, 36.4%) and vertebral osteomyelitis (8/44, 18.2%). Most of the isolated B. cepacia were susceptible to ceftazidime, carbapenems, followed by TMP-SMX. Patients responded well to therapy with good overall outcome. CONCLUSIONS: Bcc can cause infections outside the respiratory tract, mostly as hospital-acquired infections and in immunocompromised patients. Most patients were referred from countries inflicted by wars raising the possibility of a potential role of conflicts which need to be investigated in future studies. Directed therapy according to susceptibility results proved effective in most patients.

Outbreak of healthcare-associated bacteremia caused by Burkholderia gladioli due to contaminated multidose vials with saline solutions in three Croatian hospitals.

OBJECTIVES: Burkholderia gladioli has been associated with infections in patients with cystic fibrosis, chronic granulomatous disease, and other immunocompromising conditions. The aim of this study was to better depict the outbreak of healthcare-associated bacteremia caused by B. gladioli due to exposure to contaminated multidose vials with saline solutions. METHODS: An environmental and epidemiologic investigation was conducted by the Infection Prevention and Control Team (IPCT) to identify the source of the outbreak in three Croatian hospitals. RESULTS: During a 3-month period, 13 B. gladioli bacteremia episodes were identified in 10 patients in three Croatian hospitals. At the time of the outbreak, all three hospitals used saline products from the same manufacturer. Two 100-ml multidose vials with saline solutions and needleless dispensing pins were positive for B. gladioli. All 13 bacteremia isolates and two isolates from the saline showed the same antimicrobial susceptibility patterns and pulsed-field gel electrophoresis profile, demonstrating clonal relatedness. CONCLUSION: When an environmental pathogen causes an outbreak, contamination of intravenous products must be considered. Close communication between the local IPCT and the National Hospital Infection Control Advisory Committee is essential to conduct a prompt and thorough investigation and find the source of the outbreak.