RESUMEN
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.
Asunto(s)
Infecciones por Burkholderia , Complejo Burkholderia cepacia , Fibrosis Quística , Recién Nacido , Humanos , Complejo Burkholderia cepacia/genética , Infecciones por Burkholderia/prevención & control , Infecciones por Burkholderia/complicaciones , Infecciones por Burkholderia/epidemiología , Fibrosis Quística/microbiología , Agua , Preparaciones FarmacéuticasRESUMEN
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.
Asunto(s)
Bacteriemia , Infecciones por Burkholderia , Complejo Burkholderia cepacia , Burkholderia cepacia , Infección Hospitalaria , Sepsis , Humanos , Masculino , Adulto , Femenino , Bacteriemia/epidemiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Infecciones por Burkholderia/epidemiología , Infecciones por Burkholderia/prevención & control , Brotes de Enfermedades , Sepsis/epidemiología , India/epidemiología , Hospitales Públicos , Hospitales de Enseñanza , Atención a la SaludRESUMEN
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.
Asunto(s)
Bacteriemia , Infecciones por Burkholderia , Burkholderia gladioli , Infección Hospitalaria , Bacteriemia/epidemiología , Bacteriemia/prevención & control , Infecciones por Burkholderia/epidemiología , Infecciones por Burkholderia/etiología , Infecciones por Burkholderia/prevención & control , Croacia/epidemiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Atención a la Salud , Brotes de Enfermedades , Hospitales , Humanos , Solución SalinaRESUMEN
A cluster of Burkholderia cepacia complex cases from January to October 2020 among outpatients undergoing urologic procedures within a Kentucky hospital's operating rooms was investigated. This investigation included a laboratory look-back, chart reviews, exposure tracing, staff interviews, and direct observation of infection prevention and control practices. A significant protocol breach in a laboratory procedure led to contamination of surgical specimens submitted for culture with nonsterile saline. Pseudo-outbreaks often highlight gaps in infection control processes. Healthcare facilities can make substantial improvements in patient care quality and safety as they respond to identified gaps and improve systems and protocols.
Asunto(s)
Infecciones por Burkholderia , Complejo Burkholderia cepacia , Infección Hospitalaria , Infecciones por Burkholderia/epidemiología , Infecciones por Burkholderia/prevención & control , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Brotes de Enfermedades , Hospitales , Humanos , Kentucky/epidemiologíaRESUMEN
Burkholderia cenocepacia (B. cenocepacia) is an opportunistic bacterium; causing severe life threatening systemic infections in immunocompromised individuals including cystic fibrosis patients. The lack of gasdermin D (GSDMD) protects mice against endotoxin lipopolysaccharide (LPS) shock. On the other hand, GSDMD promotes mice survival in response to certain bacterial infections. However, the role of GSDMD during B. cenocepacia infection is not yet determined. Our in vitro study shows that GSDMD restricts B. cenocepacia replication within macrophages independent of its role in cell death through promoting mitochondrial reactive oxygen species (mROS) production. mROS is known to stimulate autophagy, hence, the inhibition of mROS or the absence of GSDMD during B. cenocepacia infections reduces autophagy which plays a critical role in the restriction of the pathogen. GSDMD promotes inflammation in response to B. cenocepacia through mediating the release of inflammasome dependent cytokine (IL-1ß) and an independent one (CXCL1) (KC). Additionally, different B. cenocepacia secretory systems (T3SS, T4SS, and T6SS) contribute to inflammasome activation together with bacterial survival within macrophages. In vivo study confirmed the in vitro findings and showed that GSDMD restricts B. cenocepacia infection and dissemination and stimulates autophagy in response to B. cenocepacia. Nevertheless, GSDMD promotes lung inflammation and necrosis in response to B. cenocepacia without altering mice survival. This study describes the double-edged functions of GSDMD in response to B. cenocepacia infection and shows the importance of GSDMD-mediated mROS in restriction of B. cenocepacia.
Asunto(s)
Infecciones por Burkholderia/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Animales , Autofagia/fisiología , Infecciones por Burkholderia/prevención & control , Burkholderia cenocepacia/patogenicidad , Caspasas Iniciadoras/genética , Caspasas Iniciadoras/metabolismo , Muerte Celular , Femenino , Inflamasomas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/fisiología , Lipopolisacáridos/metabolismo , Macrófagos/citología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/metabolismo , Proteínas de Unión a Fosfato/genética , Proteínas de Unión a Fosfato/fisiología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The genus Burkholderia includes a wide range of Gram-negative bacterial species some of which are pathogenic to humans and other vertebrates. The most pathogenic species are Burkholderia mallei, Burkholderia pseudomallei, and the members of the Burkholderia cepacia complex (Bcc). B. mallei and B. pseudomallei, the cause of glanders and melioidosis, respectively, are considered potential bioweapons. The Bcc comprises a subset of Burkholderia species associated with respiratory infections in people with chronic granulomatous disease and cystic fibrosis. Antimicrobial treatment of Burkholderia infections is difficult due to the intrinsic multidrug antibiotic resistance of these bacteria; prophylactic vaccines provide an attractive alternative to counteract these infections. Although commercial vaccines against Burkholderia infections are still unavailable, substantial progress has been made over recent years in the development of vaccines against B. pseudomallei and B. mallei. This review critically discusses the current advances in vaccine development against B. mallei, B. pseudomallei, and the Bcc.
Asunto(s)
Vacunas Bacterianas/administración & dosificación , Infecciones por Burkholderia/prevención & control , Burkholderia/inmunología , Animales , Vacunas Bacterianas/inmunología , Burkholderia/genética , Burkholderia/patogenicidad , Infecciones por Burkholderia/inmunología , Infecciones por Burkholderia/microbiología , Humanos , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunología , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/inmunologíaRESUMEN
Patients undergoing hemodialysis are at an increased risk for bloodstream infections (BSIs). Infection usually occurs because of contamination of water supply, water treatment, distribution systems, or reprocessing dialyzers. Here, we report an outbreak of BSIs caused by Stenotrophomonas maltophilia (n = 21) and Burkholderia cepacia (n = 22) among dialyzed patients at a large hemodialysis center in Brazil. Overall, three patients died (7%), two of which had bacteremia caused by S. maltophilia and the other had a B. cepacia infection. We collected water samples from different points of the hemodialysis system for culture and typing. Genetic patterns were identified through polymerase chain reaction-random amplified polymorphic DNA (PCR-RAPD) and pulsed-field gel electrophoresis. The same genotypes of S. maltophilia and B. cepacia recovered from blood cultures were found in dialysis water. Also, multiple genetic profiles were identified among water isolates, suggesting heavy contamination. Bacteremia cases persisted even after implementing standard control measures, which led us to believe that the piping system was contaminated with microbial biofilms. Soon after we changed the entire plumbing system, reported cases dropped back to the number typically expected, and the outbreak came to an end.
Asunto(s)
Infecciones por Burkholderia/epidemiología , Burkholderia cepacia/aislamiento & purificación , Brotes de Enfermedades , Infecciones por Bacterias Gramnegativas/epidemiología , Diálisis Renal/efectos adversos , Stenotrophomonas maltophilia/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Infecciones por Burkholderia/etiología , Infecciones por Burkholderia/prevención & control , Burkholderia cepacia/clasificación , Burkholderia cepacia/genética , Desinfección/métodos , Femenino , Infecciones por Bacterias Gramnegativas/etiología , Infecciones por Bacterias Gramnegativas/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal/normas , Sepsis/epidemiología , Sepsis/etiología , Sepsis/prevención & control , Stenotrophomonas maltophilia/clasificación , Stenotrophomonas maltophilia/genéticaRESUMEN
OBJECTIVE: To examine the global burden, associated point sources, and successful prevention and control measures for documented outbreaks of Burkholderia cepacia healthcare-associated infections (HAIs). DESIGN: Integrative review. METHODS: A review of all outbreaks of Burkholderia cepacia HAIs published in the peer-reviewed literature between January 1970 and October 2019 was conducted to identify the global burden, associated point sources, and successful prevention and control measures using the Guidelines for Outbreak Reports and Intervention Studies of Nosocomial Infections (ORION). RESULTS: In total, we reviewed 125 documented outbreaks of Burkholderia cepacia-related HAIs worldwide. The reported B. cepacia HAIs for this period involved 3,287 patients. The point sources were identified in most outbreaks of B. cepacia HAIs (n = 93; 74.4%); they included medication vials, disinfectants, and antiseptics. Moreover, 95 of the outbreak reports (76%) described effective prevention and control measures, but only 33 reports indicated the use of a combination of environment-, patient- and staff-related measures. None of the outbreak reports used the ORION guidelines. CONCLUSIONS: Outbreaks of Burkholderia cepacia HAIs are an ongoing challenge. They are often associated with immunocompromised patients who acquire the infection from exposure to contaminated medications, products, and equipment. These outbreaks are not infrequent, and a range of infection prevention and control measures have been effective in arresting spread. The use of ORION guidelines for outbreak reporting would improve the quality of information and data to generate evidence for translation into practice.
Asunto(s)
Infecciones por Burkholderia , Burkholderia cepacia , Infección Hospitalaria , Brotes de Enfermedades , Infecciones por Burkholderia/epidemiología , Infecciones por Burkholderia/prevención & control , Costo de Enfermedad , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Atención a la Salud , Notificación de Enfermedades , Salud Global , HumanosRESUMEN
BACKGROUND: Burkholderia cepacia complex (Bcc) is a group of serious pathogens in cystic fibrosis patients and causes life threatening infections in immunocompromised patients. Species within the Bcc are widely distributed within the environment, can survive in the presence of disinfectants and antiseptics, and are inherently multidrug resistant (MDR). METHODS: Dhaka Medical College Hospital (DMCH) patients with a B. cepacia positive blood culture between 20 October 2016 to 23rd September 2017 were considered as outbreak cases. Blood stream infections (BSIs) were detected using BacT/ALERT 3D at DMCH. B. cepacia was isolated on chromogenic UTI media followed by MALDI-TOF. Minimum inhibitory concentration (MIC) of clinically relevant antibiotics was determined by agar dilution. Whole genome sequencing was performed on an Illumina MiSeq platform. Patients' demographic and clinical data were collected. Patients' clinical history and genomic data of the outbreak strains were merged to investigate possible outbreaks. Ninety-one B. cepacia genomes were downloaded from 'Burkholderia Genome Database' and the genomic background of the global strains were compared with our outbreak strains. RESULTS: Among 236 BSIs, 6.35% (15/236) were B. cepacia. Outbreak cases were confined to the burn critical care unit and, to a lesser extent, the paediatrics department. There was a continuum of overlapping cases at DMCH between 23 October 2016 to 30 August 2017. Core genome SNPs showed that the outbreak strains were confined to a single clade, corresponded to a common clone (ST1578). The strains were shown to be MDR and associated with a mortality of 31% excluding discharge against medical advice. MIC profiles of the strains suggested that antibiotics deployed as empirical therapy were invariably inappropriate. The genetic background of the outbreak strains was very similar; however, a few variations were found regarding the presence of virulence genes. Compared to global strains from the Burkholderia Genome Database, the Bangladeshi strains were genetically distinct. CONCLUSIONS: Environmental surveillance is required to investigate the aetiology and mode of transmission of the B. cepacia outbreak. Systematic management of nosocomial outbreaks, particularly in resource limited regions, will mitigate transmission and will improve patients' outcomes.
Asunto(s)
Infecciones por Burkholderia/epidemiología , Burkholderia/aislamiento & purificación , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Adolescente , Adulto , Bacteriemia/epidemiología , Bangladesh , Burkholderia/genética , Infecciones por Burkholderia/prevención & control , Niño , Preescolar , Infección Hospitalaria/prevención & control , Infección Hospitalaria/transmisión , Electroforesis en Gel de Campo Pulsado , Femenino , Genotipo , Humanos , Lactante , Control de Infecciones/métodos , Unidades de Cuidados Intensivos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Aislamiento de Pacientes , Centros de Atención Terciaria , Adulto JovenRESUMEN
Cystic fibrosis (CF) patients are at particular risk of infection by microorganisms that are resistant to several antibiotics. About 3% of CF patients are colonized by Burkholderia cenocepacia, and this represents a major threat because of its intrinsic high level of drug resistance and the lack of a safe and effective treatment protocol. The development of anti-Burkholderia vaccines is a valuable and complementary approach, but only a few studies have been reported to date. In this review we discuss recent advances in the vaccine field and how new technologies, including structural reverse vaccinology, could drive the design of an effective vaccine against B. cenocepacia for use in preventive and therapeutic applications.
Asunto(s)
Antibacterianos/farmacología , Infecciones por Burkholderia/tratamiento farmacológico , Infecciones por Burkholderia/prevención & control , Burkholderia cenocepacia/efectos de los fármacos , Vacunas/farmacología , Animales , Burkholderia cenocepacia/genética , Fibrosis Quística/microbiología , Farmacorresistencia Bacteriana/efectos de los fármacos , Humanos , Pulmón/microbiología , Microbiota , Factores de VirulenciaRESUMEN
Adhesion is the initial step in the infection process of gram-negative bacteria. It is usually followed by the formation of biofilms that serve as a hub for further spread of the infection. Type V secretion systems engage in this process by binding to components of the extracellular matrix, which is the first step in the infection process. At the same time they provide protection from the immune system by either binding components of the innate immune system or by establishing a physical layer against aggressors. Trimeric autotransporter adhesins (TAAs) are of particular interest in this family of proteins as they possess a unique structural composition which arises from constraints during translocation. The sequence of individual domains can vary dramatically while the overall structure can be very similar to one another. This patchwork approach allows researchers to draw conclusions of the underlying function of a specific domain in a structure-based approach which underscores the importance of solving structures of yet uncharacterized TAAs and their individual domains to estimate the full extent of functions of the protein a priori. Here, we describe recent advances in understanding the translocation process of TAAs and give an overview of structural motifs that are unique to this class of proteins. The role of BpaC in the infection process of Burkholderia pseudomallei is highlighted as an exceptional example of a TAA being at the centre of infection initiation.
Asunto(s)
Adhesinas Bacterianas/química , Adhesinas Bacterianas/metabolismo , Burkholderia pseudomallei/patogenicidad , Bacterias Gramnegativas/fisiología , Bacterias Gramnegativas/patogenicidad , Sistemas de Secreción Tipo V/química , Sistemas de Secreción Tipo V/metabolismo , Animales , Infecciones por Burkholderia/microbiología , Infecciones por Burkholderia/prevención & control , Humanos , Estructura Terciaria de Proteína , Factores de VirulenciaRESUMEN
As awareness of the risks of cross infection has increased, infection prevention and control measures have become more draconian. Infection control measures can have a profound effect of the organisation and delivery of CF services and on the lives of people with CF outside the hospital. However, the consequences of inadequate infection control measures may be the permanent acquisition of a chronic infection which is virtually untreatable. Recommendations for infection prevention and control therefore must protect patients but should also be evidence-based and proportionate. This article will review the literature, juxtaposing evidence and popular practise.
Asunto(s)
Infección Hospitalaria/prevención & control , Fibrosis Quística/terapia , Control de Infecciones/métodos , Infecciones del Sistema Respiratorio/prevención & control , Administración por Inhalación , Administración Intravenosa , Filtros de Aire , Antibacterianos/uso terapéutico , Infecciones por Burkholderia/tratamiento farmacológico , Infecciones por Burkholderia/prevención & control , Fibrosis Quística/microbiología , Manejo de la Enfermedad , Farmacorresistencia Bacteriana , Farmacorresistencia Bacteriana Múltiple , Práctica Clínica Basada en la Evidencia , Higiene de las Manos , Humanos , Máscaras , Staphylococcus aureus Resistente a Meticilina , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/prevención & control , Aislamiento de Pacientes , Equipo de Protección Personal , Distanciamiento Físico , Guías de Práctica Clínica como Asunto , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/prevención & control , Pseudomonas aeruginosa , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Espirometría , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/prevención & control , VentilaciónRESUMEN
Quorum sensing (QS) signals are widely used by bacterial pathogens to control biological functions and virulence in response to changes in cell population densities. Burkholderia cenocepacia employs a molecular mechanism in which the cis-2-dodecenoic acid (named Burkholderiadiffusible signal factor [BDSF]) QS system regulates N-acyl homoserine lactone (AHL) signal production and virulence by modulating intracellular levels of cyclic diguanosine monophosphate (c-di-GMP). Thus, inhibition of BDSF signaling may offer a non-antibiotic-based therapeutic strategy against BDSF-regulated bacterial infections. In this study, we report the synthesis of small-molecule mimics of the BDSF signal and evaluate their ability to inhibit BDSF QS signaling in B. cenocepacia A novel structural analogue of BDSF, 14-Me-C16:Δ2 (cis-14-methylpentadec-2-enoic acid), was observed to inhibit BDSF production and impair BDSF-regulated phenotypes in B. cenocepacia, including motility, biofilm formation, and virulence, while it did not inhibit the growth rate of this pathogen. 14-Me-C16:Δ2 also reduced AHL signal production. Genetic and biochemical analyses showed that 14-Me-C16:Δ2 inhibited the production of the BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Notably, 14-Me-C16:Δ2 attenuated BDSF-regulated phenotypes in various Burkholderia species. These findings suggest that 14-Me-C16:Δ2 could potentially be developed as a new therapeutic agent against pathogenic Burkholderia species by interfering with their QS signaling.IMPORTANCEBurkholderia cenocepacia is an important opportunistic pathogen which can cause life-threatening infections in susceptible individuals, particularly in cystic fibrosis and immunocompromised patients. It usually employs two types of quorum sensing (QS) systems, including the cis-2-dodecenoic acid (BDSF) system and N-acyl homoserine lactone (AHL) system, to regulate virulence. In this study, we have designed and identified an unsaturated fatty acid compound (cis-14-methylpentadec-2-enoic acid [14-Me-C16:Δ2]) that is capable of interfering with B. cenocepacia QS signaling and virulence. We demonstrate that 14-Me-C16:Δ2 reduced BDSF and AHL signal production in B. cenocepacia It also impaired QS-regulated phenotypes in various Burkholderia species. These results suggest that 14-Me-C16:Δ2 could interfere with QS signaling in many Burkholderia species and might be developed as a new antibacterial agent.
Asunto(s)
Burkholderia cenocepacia/efectos de los fármacos , Ácidos Grasos Monoinsaturados/antagonistas & inhibidores , Ácidos Grasos Monoinsaturados/farmacología , Percepción de Quorum/efectos de los fármacos , Acil-Butirolactonas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biopelículas/efectos de los fármacos , Infecciones por Burkholderia/microbiología , Infecciones por Burkholderia/prevención & control , Burkholderia cenocepacia/genética , Burkholderia cenocepacia/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Regulación Bacteriana de la Expresión Génica , Pruebas de Sensibilidad Microbiana , Fenotipo , Transducción de Señal , Virulencia/efectos de los fármacos , Virulencia/genéticaRESUMEN
Burkholderia cepacia complex (BCC) bacteria are a group of opportunistic pathogens that cause severe lung infections in cystic fibrosis (CF). Treatment of BCC infections is difficult, due to the inherent and acquired multidrug resistance of BCC. There is a pressing need to find new bacterial targets for antimicrobials. Here, we demonstrate that the novel compound Q22, which is related to the bacterial cytoskeleton destabilising compound A22, can reduce the growth rate and inhibit growth of BCC bacteria. We further analysed the phenotypic effects of Q22 treatment on BCC virulence traits, to assess its feasibility as an antimicrobial. BCC bacteria were grown in the presence of Q22 with a broad phenotypic analysis, including resistance to H2O2-induced oxidative stress, changes in the inflammatory potential of cell surface components, and in-vivo drug toxicity studies. The influence of the Q22 treatment on inflammatory potential was measured by monitoring the cytokine responses of BCC whole cell lysates, purified lipopolysaccharide, and purified peptidoglycan extracted from bacterial cultures grown in the presence or absence of Q22 in differentiated THP-1 cells. BCC bacteria grown in the presence of Q22 displayed varying levels of resistance to H2O2-induced oxidative stress, with some strains showing increased resistance after treatment. There was strain-to-strain variation in the pro-inflammatory ability of bacterial lysates to elicit TNFα and IL-1ß from human myeloid cells. Despite minimal toxicity previously shown in vitro with primary CF cell lines, in-vivo studies demonstrated Q22 toxicity in both zebrafish and mouse infection models. In summary, destabilisation of the bacterial cytoskeleton in BCC, using compounds such as Q22, led to increased virulence-related traits in vitro. These changes appear to vary depending on strain and BCC species. Future development of antimicrobials targeting the BCC bacterial cytoskeleton may be hampered if such effects translate into the in-vivo environment of the CF infection.
Asunto(s)
Antiinfecciosos/uso terapéutico , Complejo Burkholderia cepacia/metabolismo , Complejo Burkholderia cepacia/patogenicidad , Citoesqueleto/metabolismo , Animales , Infecciones por Burkholderia/tratamiento farmacológico , Infecciones por Burkholderia/prevención & control , Modelos Animales de Enfermedad , Humanos , Ratones , Células THP-1 , Pez CebraRESUMEN
BACKGROUND: We report an outbreak of Burkholderia cenocepacia bacteremia and infection in 11 patients predominately in intensive care units caused by contaminated ultrasound gel used in central line insertion and sterile procedures within 4 hospitals across Australia. METHODS: Burkholderia cenocepacia was first identified in the blood culture of a patient from the intensive care unit at the Gold Coast University Hospital on March 26, 2017, with 3 subsequent cases identified by April 7, 2017. The outbreak response team commenced investigative measures. RESULTS: The outbreak investigation identified the point source as contaminated gel packaged in sachets for use within the sterile ultrasound probe cover. In total, 11 patient isolates of B cenocepacia with the same multilocus sequence type were identified within 4 hospitals across Australia. This typing was the same as identified in the contaminated gel isolate with single nucleotide polymorphism-based typing, demonstrating that all linked isolates clustered together. CONCLUSION: Arresting the national point-source outbreak within multiple jurisdictions was critically reliant on a rapid, integrated, and coordinated response and the use of informal professional networks to first identify it. All institutions where the product is used should look back at Burkholderia sp blood culture isolates for speciation to ensure this outbreak is no larger than currently recognized given likely global distribution.
Asunto(s)
Bacteriemia/transmisión , Infecciones por Burkholderia/transmisión , Burkholderia cenocepacia/aislamiento & purificación , ADN Bacteriano/genética , Brotes de Enfermedades , Contaminación de Medicamentos , Adulto , Australia/epidemiología , Bacteriemia/epidemiología , Bacteriemia/microbiología , Bacteriemia/prevención & control , Infecciones por Burkholderia/epidemiología , Infecciones por Burkholderia/microbiología , Infecciones por Burkholderia/prevención & control , Burkholderia cenocepacia/clasificación , Burkholderia cenocepacia/genética , Cateterismo Periférico , Notificación de Enfermedades , Femenino , Geles , Hospitales Universitarios , Humanos , Unidades de Cuidados Intensivos , Masculino , Tipificación de Secuencias Multilocus , Ultrasonografía/instrumentaciónRESUMEN
BACKGROUND: We reviewed Burkholderia cepacia infections in a hospital from 2013-2016 to report a suspicious outbreak that occurred in a surgical intensive care unit in 2015, and to outline the infection control measures adopted thereafter. METHODS: Review of the health care-associated infection data regarding B cepacia via the surveillance system, hospital information system, electronic medical records, and laboratory information system together with the outbreak investigation was managed by the health care-associated infection control team. RESULTS: During June 1-14, 2015, 4 cases of ventilator-associated pneumonia (VAP) were identified; B cepacia was isolated from endotracheal aspirate samples. On June 16, 120 environmental samples were collected and analyzed for microbiologic differentiation. Thirteen strains of B cepacia were prominently found in the expiratory blocks of ventilators, revealing the biocontamination source. After chemical disinfection without damaging ventilator components, repeat microbiologic testing of random ventilator samples yielded negative results until July 30, 2015. Retrospective data showed that isolation rates of B cepacia strains had increased since 2014. Although the resistance phenotype of these strains varied slightly, they exhibited similar patterns of antibiotic susceptibility. CONCLUSIONS: Routine cleaning and disinfection of ventilators, in addition to an intervention bundle, should form part of an integrated VAP prevention and management approach.
Asunto(s)
Infecciones por Burkholderia/epidemiología , Burkholderia cepacia , Brotes de Enfermedades/estadística & datos numéricos , Control de Infecciones/métodos , Neumonía Asociada al Ventilador/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Infecciones por Burkholderia/microbiología , Infecciones por Burkholderia/prevención & control , Cuidados Críticos/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Asociada al Ventilador/microbiología , Neumonía Asociada al Ventilador/prevención & control , Estudios Retrospectivos , Ventiladores Mecánicos/microbiologíaRESUMEN
PURPOSE: To determine the antimicrobial activity of the melimine derived peptide Mel4 against Delftia, Stenotrophomonas, Elizabethkingia, Burkholderia and to investigate biocompatibility of Mel4 as an antimicrobial coating on contact lenses in animals and humans. METHODS: In vitro antimicrobial activity of Mel4 was determined against the four Gram negative bacteria by investigating growth curves for 24h followed by viable counts to determine the minimum inhibitory concentration (MIC). Contact lenses were coated by covalently binding Mel4, characterized by amino acid analysis, and were investigated for changes in lens parameters. Safety of Mel-4 coated lenses were determined in a rabbit model of daily contralateral wear. A prospective, randomised, double-masked, contralateral, 1week daily wear human clinical trial was used to evaluate subjective responses and ocular physiology. RESULTS: Mel4 was active against all the bacteria tested (MIC50 ranged from 31-1000µgml-1) and produced an antimicrobial surface on contact lenses. Mel4-coating resulted hydrophilic surface without any significant change in contact lens parameters, and showed no signs of cytotoxicity or ocular irritation during rabbit wear. During human clinical trial, there were no differences between Mel4 coated and uncoated contact lenses in lens performance indicators and ocular signs such as corneal fluorescein staining. Mel4 and control uncoated lenses had no differences in ocular symptoms during lens wear. CONCLUSION: Mel4 has achieved antimicrobial activity against variety of Gram negative bacteria that are often resistant to the action of cationic peptides and have been implicated in contact lens related adverse events. Mel4-coated contact lenses were safe to wear.
Asunto(s)
Péptidos Catiónicos Antimicrobianos/farmacología , Infecciones por Burkholderia/prevención & control , Burkholderia/efectos de los fármacos , Materiales Biocompatibles Revestidos/química , Lentes de Contacto/microbiología , Infecciones Bacterianas del Ojo/prevención & control , Stenotrophomonas/efectos de los fármacos , Animales , Adhesión Bacteriana/efectos de los fármacos , Burkholderia/aislamiento & purificación , Infecciones por Burkholderia/microbiología , Modelos Animales de Enfermedad , Contaminación de Equipos/prevención & control , Infecciones Bacterianas del Ojo/microbiología , Femenino , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/prevención & control , Ensayo de Materiales/métodos , Pruebas de Sensibilidad Microbiana/métodos , Estudios Prospectivos , Conejos , Stenotrophomonas/aislamiento & purificaciónRESUMEN
We report the result of retrospective record review of the clinical profile of 59 neonates who presented to a tertiary-care extramural neonatal unit with Burkholderia cepacia complex infection. Among the 3265 admissions over 45 months, incidence of Burkholderia sepsis was 18 per 1000 admissions. Case fatality rate was 17%. Most (95%) isolates were sensitive to cotrimoxazole.
Asunto(s)
Infecciones por Burkholderia , Burkholderia , Sepsis Neonatal , Infecciones por Burkholderia/epidemiología , Infecciones por Burkholderia/microbiología , Infecciones por Burkholderia/prevención & control , Femenino , Humanos , India/epidemiología , Recién Nacido , Masculino , Sepsis Neonatal/epidemiología , Sepsis Neonatal/microbiología , Sepsis Neonatal/prevención & control , Estudios RetrospectivosRESUMEN
Members of the Burkholderia cepacia complex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells. Fourteen proteins were reproducibly identified by two-dimensional gel electrophoresis from four Bcc strains representative of two Bcc species: Burkholderia cenocepacia, the most virulent, and B. multivorans, the most frequently acquired. Seven proteins were identified in both species, but only two were common to all four strains, linocin and OmpW. Both proteins were selected based on previously reported data on these proteins in other species. Escherichia coli strains expressing recombinant linocin and OmpW showed enhanced attachment (4.2- and 3.9-fold) to lung cells compared to the control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc-colonized CF patients confirmed that both proteins elicit potent humoral responses in vivo Mice immunized with either recombinant linocin or OmpW were protected from B. cenocepacia and B. multivorans challenge. Both antigens induced potent antigen-specific antibody responses and stimulated strong cytokine responses. In conclusion, our approach identified adhesins that induced excellent protection against two Bcc species and are promising vaccine candidates for a multisubunit vaccine. Furthermore, this study highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens.
Asunto(s)
Adhesinas Bacterianas/metabolismo , Adhesión Bacteriana , Proteínas de la Membrana Bacteriana Externa/metabolismo , Bacteriocinas/metabolismo , Infecciones por Burkholderia/prevención & control , Complejo Burkholderia cepacia/fisiología , Células Epiteliales/microbiología , Adhesinas Bacterianas/inmunología , Animales , Proteínas de la Membrana Bacteriana Externa/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Bacteriocinas/inmunología , Infecciones por Burkholderia/inmunología , Fibrosis Quística/inmunología , Fibrosis Quística/microbiología , Modelos Animales de Enfermedad , Escherichia coli/genética , Escherichia coli/fisiología , Femenino , Expresión Génica , Humanos , Ratones Endogámicos BALB C , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Resultado del TratamientoRESUMEN
INTRODUCTION: In January 2014 a possible outbreak of Burkholderia cepacia bacteremia occurred in a hemodialysis center situated in La Linea de la Concepción (Cadiz). An investigation was begun to confirm the outbreak, identify the source, and implement control measures. METHODS: A descriptive analysis was performed to describe the characteristics of the patients affected with Burkholderia cepacia bacteremia from November 2013 to February 2014. Environmental samples were taken. A molecular typing study was performed using pulsed field gel electrophoresis (SpeI PFGE) and MLST analysis in order to determine the genetic similarity between the isolates. RESULTS: The bacterium was isolated from blood cultures of 7 patients during the study period. Three of the samples (2 of which were also cases) were endoluminal fluid from catheter locks, and 4 chlorhexidine bottle samples. The patients were coincident in 2 of the 6 work shifts. The mean age of the cases was 67 years of whom 57% were women. Human samples and an environmental sample was analyzed and found to be genetically identical (ST653 clone). CONCLUSIONS: The analysis confirmed the outbreak of Burkholderia cepacia, with 7 cases among the patients of the hemodialysis center. The outbreak was due to the same strain, probably a common source and secondary transmission from person to person.