RESUMEN
Rib osteomyelitis is a rare disease, comprising 1% or less of all osteomyelitis. Treatment of rib osteomyelitis includes prolonged antibiotic therapy and surgical intervention. Indications for surgical treatment of rib osteomyelitis remain unclear, however, because of few reported cases. We report the first known case of extended-spectrum ß-lactamase-producing Escherichia coli rib osteomyelitis caused by urosepsis. The 69-year-old male patient remains free of recurrence and symptoms after rib resection and vacuum-assisted closure treatment with antibiotic therapy. Rib osteomyelitis should be considered as differential diagnosis when patients report chest pain after bacteraemic infection. We recommend surgical treatment for patients with drug-resistant bacterial rib osteomyelitis.
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Absceso/terapia , Antibacterianos/uso terapéutico , Cefmetazol/uso terapéutico , Desbridamiento/métodos , Infecciones por Escherichia coli/terapia , Osteomielitis/terapia , Costillas/cirugía , Absceso/etiología , Absceso/patología , Anciano , Infecciones por Escherichia coli/microbiología , Humanos , Masculino , Terapia de Presión Negativa para Heridas/métodos , Osteomielitis/etiología , Osteomielitis/patología , Costillas/patología , Sepsis/complicaciones , Pared Torácica , Tomografía Computarizada por Rayos X , Infecciones Urinarias/complicaciones , Resistencia betalactámica/fisiologíaRESUMEN
The dramatic increase in prevalence and clinical impact of infections caused by carbapenemase-producing Enterobacterales (CPE) are major and ongoing public health problems globally. The carbapenemase groups most commonly encountered include Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-ß-lactamase (NDM), and OXA-48, with OXA-48 thought to be endemic to North Africa. These enzymes are frequently found on mobile genetic elements and have the potential to be widespread over the world, while the situation in Algeria is not well documented. In this article, we provide an in-depth review of CPE in Algeria, providing up-to-date information on the subject.
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Proteínas Bacterianas/biosíntesis , Enterobacteriaceae/enzimología , Resistencia betalactámica/fisiología , beta-Lactamasas/biosíntesis , Argelia , Animales , Electroforesis en Gel de Campo Pulsado , Infecciones por Enterobacteriaceae/epidemiología , HumanosRESUMEN
Even with the emergence of antibiotic resistance, penicillin and the wider family of ß-lactams have remained the single most important family of antibiotics. The periplasmic/extra-cytoplasmic targets of penicillin are a family of enzymes with a highly conserved catalytic activity involved in the final stage of bacterial cell wall (peptidoglycan) biosynthesis. Named after their ability to bind penicillin, rather than their catalytic activity, these key targets are called penicillin-binding proteins (PBPs). Resistance is predominantly mediated by reducing the target drug concentration via ß-lactamases; however, naturally transformable bacteria have also acquired target-mediated resistance by inter-species recombination. Here we focus on structural based interpretations of amino acid alterations associated with the emergence of resistance within clinical isolates and include new PBP3 structures along with new, and improved, PBP-ß-lactam co-structures.
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Proteínas de Unión a las Penicilinas/química , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/química , Resistencia betalactámica/fisiología , beta-Lactamas/química , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Cristalografía por Rayos X , Escherichia coli/enzimología , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Haemophilus influenzae/enzimología , Modelos Moleculares , Mutación , Neisseria gonorrhoeae/enzimología , Proteínas de Unión a las Penicilinas/genética , Proteínas de Unión a las Penicilinas/metabolismo , Peptidoglicano Glicosiltransferasa/química , Peptidoglicano Glicosiltransferasa/genética , Peptidoglicano Glicosiltransferasa/metabolismo , Conformación Proteica , Dominios Proteicos , Pseudomonas aeruginosa/enzimología , Alineación de Secuencia , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/genética , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina/metabolismo , beta-Lactamasas/química , beta-Lactamasas/metabolismo , beta-Lactamas/farmacologíaRESUMEN
The bacterial cell wall plays a crucial role in viability and is an important drug target. In Escherichia coli, the peptidoglycan crosslinking reaction to form the cell wall is primarily carried out by penicillin-binding proteins that catalyse D,D-transpeptidase activity. However, an alternate crosslinking mechanism involving the L,D-transpeptidase YcbB can lead to bypass of D,D-transpeptidation and beta-lactam resistance. Here, we show that the crystallographic structure of YcbB consists of a conserved L,D-transpeptidase catalytic domain decorated with a subdomain on the dynamic substrate capping loop, peptidoglycan-binding and large scaffolding domains. Meropenem acylation of YcbB gives insight into the mode of inhibition by carbapenems, the singular antibiotic class with significant activity against L,D-transpeptidases. We also report the structure of PBP5-meropenem to compare interactions mediating inhibition. Additionally, we probe the interaction network of this pathway and assay beta-lactam resistance in vivo. Our results provide structural insights into the mechanism of action and the inhibition of L,D-transpeptidation, and into YcbB-mediated antibiotic resistance.
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Antibacterianos/farmacología , Proteínas de Escherichia coli/metabolismo , Escherichia coli/fisiología , Meropenem/farmacología , Peptidil Transferasas/metabolismo , Resistencia betalactámica/fisiología , Acilación/efectos de los fármacos , Sustitución de Aminoácidos/genética , Antibacterianos/química , Dominio Catalítico/fisiología , Pared Celular/efectos de los fármacos , Pared Celular/metabolismo , Cristalografía por Rayos X , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/aislamiento & purificación , Meropenem/química , Simulación de Dinámica Molecular , Proteínas de Unión a las Penicilinas/metabolismo , Peptidoglicano/metabolismo , Peptidil Transferasas/química , Peptidil Transferasas/genética , Peptidil Transferasas/aislamiento & purificación , Mapas de Interacción de Proteínas/fisiología , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismoRESUMEN
As human population density and antibiotic exposure increase, specialised bacterial subtypes have begun to emerge. Arising among species that are common commensals and infrequent pathogens, antibiotic-resistant 'high-risk clones' have evolved to better survive in the modern human. Here, we show that the major matrix porin (OmpK35) of Klebsiella pneumoniae is not required in the mammalian host for colonisation, pathogenesis, nor for antibiotic resistance, and that it is commonly absent in pathogenic isolates. This is found in association with, but apparently independent of, a highly specific change in the co-regulated partner porin, the osmoporin (OmpK36), which provides enhanced antibiotic resistance without significant loss of fitness in the mammalian host. These features are common in well-described 'high-risk clones' of K. pneumoniae, as well as in unrelated members of this species and similar adaptations are found in other members of the Enterobacteriaceae that share this lifestyle. Available sequence data indicate evolutionary convergence, with implications for the spread of lethal antibiotic-resistant pathogens in humans.
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Proteínas Bacterianas/fisiología , Farmacorresistencia Bacteriana/genética , Porinas/fisiología , Resistencia betalactámica/genética , Antibacterianos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Farmacorresistencia Bacteriana/fisiología , Farmacorresistencia Microbiana , Humanos , Infecciones por Klebsiella/genética , Infecciones por Klebsiella/metabolismo , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Pruebas de Sensibilidad Microbiana , Porinas/genética , Porinas/metabolismo , Virulencia , Resistencia betalactámica/fisiología , beta-Lactamasas/farmacologíaRESUMEN
The objective of this study was to assess the antimicrobial resistance of enteroaggregative Escherichia coli (EAEC) and enterotoxigenic E. coli (ETEC) strains causing traveler's diarrhea (TD) and to investigate the molecular characterization of antimicrobial resistance genes to third-generation cephalosporins, cephamycins, and quinolones. Overall, 39 EAEC and 43 ETEC clinical isolates were studied. The susceptibilities of EAEC and ETEC against ampicillin, amoxicillin-clavulanic acid, cefotaxime, imipenem, chloramphenicol, tetracycline, co-trimoxazole, nalidixic acid, ciprofloxacin, azithromycin, and rifaximin were determined. All genes encoding resistance determinants were detected by PCR or PCR plus DNA sequencing. The epidemiology of selected EAEC and ETEC strains was studied using multilocus sequence typing (MLST). The resistance to quinolones of EAEC and ETEC strains causing TD has significantly increased over the last decades, and high percentages have been found especially in patients traveling to India and sub-Saharan Africa. Sequence type 38 (ST38) and ST131, carrying the blaCTX-M-15 and blaCTX-M-27 genes, respectively, are highly prevalent among extended-spectrum ß-lactamase (ESBL)-producing EAEC and ETEC strains. The cephamycinase ACT-20 is described in the present study for the first time in EAEC and ETEC strains causing TD in patients who had traveled to Central America. The percentages of resistance to azithromycin in EAEC and ETEC isolates from patients to Southeast Asia/India and Africa are above 25%. Meanwhile, rifaximin is still active against EAEC and ETEC, with the prevalence of resistant strains not being high. In conclusion, fluoroquinolones should no longer be considered the drugs of choice for the prevention or treatment in TD for travelers traveling to India and Africa. Azithromycin and rifaximin are still a good alternative to treat TD caused by EAEC or ETEC.
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Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/fisiología , Escherichia coli Enterotoxigénica/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Quinolonas/uso terapéutico , beta-Lactamas/uso terapéutico , Infecciones por Escherichia coli/microbiología , Enfermedades Gastrointestinales/tratamiento farmacológico , Enfermedades Gastrointestinales/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Resistencia betalactámica/fisiologíaRESUMEN
ß-Lactam resistance levels vary among methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, mediated by chromosomal mutations and exogenous resistance gene mecA However, MRSA resistance mechanisms are incompletely understood. A P440L mutation in the RNA polymerase ß' subunit (RpoC) in slow-vancomycin-intermediate S. aureus (sVISA) strain V6-5 is associated with conversion of heterogeneous VISA (hVISA) to sVISA. In this study, we found a V6-5-derivative strain (L4) with significantly decreased MICs to oxacillin (OX) and vancomycin. Whole-genome sequencing revealed that L4 has nonsense mutations in two genes, relQ, encoding (p)ppGpp synthetase, an alarmone of the stringent response, and a gene of unknown function. relQ deletion in the hVISA strain Mu3 did not affect OX MIC. However, introducing nonsense mutation of the unknown gene into Mu3 decreased OX MIC, whereas wild-type gene recovered high-level resistance. Thus, mutation of this unknown gene (ehoM) decreased ß-lactam resistance in Mu3 and L4. Presence of relQ in a multicopy plasmid restored high-level resistance in strain L4 but not in the ehoM mutant Mu3 strain, indicating a genetic interaction between ehoM and relQ depending on the L4 genetic background. While mupirocin (a stringent response inducer) can increase the ß-lactam resistance of MRSA, mupirocin supplementation in an ehoM deletion mutant of N315 did not elevate resistance. ehoM expression in N315 was induced by mupirocin, and the relative amount of ehoM transcript in Mu3 was higher than in N315 induced by the stringent response. Our findings indicate that ehoM plays an essential role in high-level ß-lactam resistance in MRSA via the stringent response.
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Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/genética , Vancomicina/farmacología , Resistencia betalactámica/fisiología , Codón sin Sentido/genética , Meticilina/farmacología , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Resistencia betalactámica/genéticaRESUMEN
INTRODUCTION: Acinetobacter species are short, stout, gram-negative coccobacilli, generally considered to be a relatively low-grade pathogen. However, its resistance towards multiple classes of antibiotics through an array of resistance mechanisms including its ability to form biofilm has led to its emergence as an important pathogen in hospital settings. This study was done to determine the prevalence of biofilm former and Extended-spectrum Beta-Lactamase producer among Acinetobacter species. METHODS: A descriptive cross-sectional study was done in the clinical microbiology laboratory, Kathmandu Medical College from January to June 2019. Convenient sampling method was used. Ethical approval was taken from the Institutional Review Committee, Ref no. 2812201805. Preliminary identification followed by characterization of Acinetobacter species was done. Antibiotic susceptibility test was done using the Kirby-Bauer method following Clinical and Laboratory Standards Institute guidelines. Extended-spectrum Beta-Lactamase was detected by combined disc method and Biofilm detection was done using congo red agar method. Statistical Package for Social Sciences 16.0 version statistical software package was used for statistical analysis. Point estimate at 95% Confidence Interval was calculated along with frequencyand proportion for binarydata. RESULTS: Among 108 Acinetobacter species, 86 (79.7%) Acinetobacter calcoaceticus-A. baumannii complex was seen. Seventy-eight (72%) of the isolates were multidrug-resistant, 34 (31%) of the isolates were Extended-spectrum Beta-Lactamase producer and only 10 (9.3%) of the isolates, were biofilm producers. CONCLUSIONS: Multidrug-resistant Acinetobacter spp. with the ability to produce Extended-spectrum Beta-Lactamase is prevalent in our hospital settings. Strict compliance with infection control practices is necessary to curb its spread.
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Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/fisiología , Acinetobacter calcoaceticus/fisiología , Biopelículas/crecimiento & desarrollo , Resistencia betalactámica/fisiología , Acinetobacter/aislamiento & purificación , Acinetobacter/fisiología , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter calcoaceticus/aislamiento & purificación , Bacteriemia/microbiología , Estudios Transversales , Resistencia a Múltiples Medicamentos/fisiología , Humanos , Pruebas de Sensibilidad Microbiana , Nepal , Infecciones del Sistema Respiratorio/microbiología , Centros de Atención Terciaria , Infecciones Urinarias/microbiología , beta-Lactamasas/metabolismoRESUMEN
The irrational use of antibiotics in agriculture and in the medical field has led to a variety of pathogenic microorganisms that produce drug resistance and even multidrug resistance. B-lactam is one of the most widely used antibiotics to treat infectious diseases. Resistance to ß-lactam resistance can be primarily due to the presence ß-lactamase, mutation of ß-lactam targets and overexpression of efflux pumps. Two-component regulatory systems are composed of histidine kinase and response regulator that regulate gene expression under different environmental conditions. In this review, we summarized the mechanisms by which ß-lactam resistance is developed and the role of the two-component regulatory system in ß-lactam resistance.
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Antibacterianos/farmacología , Resistencia betalactámica/efectos de los fármacos , Resistencia betalactámica/fisiología , beta-Lactamas/farmacología , Agricultura , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Regulación Bacteriana de la Expresión Génica/genética , Histidina Quinasa/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Resistencia betalactámica/genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , beta-Lactamas/químicaRESUMEN
Antibiotic resistance, and the emergence of pan-resistant clinical isolates, seriously threatens our capability to treat bacterial diseases, including potentially deadly hospital-acquired infections. This growing issue certainly requires multiple adequate responses, including the improvement of both diagnosis methods and use of antibacterial agents, and obviously the development of novel antibacterial drugs, especially active against Gram-negative pathogens, which represent an urgent medical need. Considering the clinical relevance of both ß-lactam antibiotics and ß-lactamase-mediated resistance, the discovery and development of combinations including a ß-lactamase inhibitor seems to be particularly attractive, despite being extremely challenging due to the enormous diversity, both structurally and mechanistically, of the potential ß-lactamase targets. This review will cover the evolution of currently available ß-lactamase inhibitors along with the most recent research leading to new ß-lactamase inhibitors of potential clinical interest or already in the stage of clinical development.
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Proteínas Bacterianas/antagonistas & inhibidores , Descubrimiento de Drogas , Bacterias Gramnegativas/fisiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Inhibidores de beta-Lactamasas/farmacología , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Combinación de Medicamentos , Diseño de Fármacos , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/microbiología , Estructura Molecular , Relación Estructura-Actividad , Resistencia betalactámica/efectos de los fármacos , Resistencia betalactámica/fisiología , Inhibidores de beta-Lactamasas/química , Inhibidores de beta-Lactamasas/uso terapéutico , beta-Lactamasas/química , beta-Lactamasas/metabolismoRESUMEN
Surface carbohydrate moieties are essential for bacterial communication, phage-bacteria and host-pathogen interaction. Most Staphylococcus aureus produce polyribitolphosphate type Wall teichoic acids (WTAs) substituted with α- and/or ß-O-linked N-acetyl-glucosamine (α-/ß-O-GlcNAc) residues. GlcNAc modifications have attracted particular interest, as they were shown to govern staphylococcal adhesion to host cells, to promote phage susceptibility conferring beta-lactam resistance and are an important target for antimicrobial agents and vaccines. However, there is a lack of rapid, reliable, and convenient methods to detect and quantify these sugar residues. Whole cell Fourier transform infrared (FTIR) spectroscopy could meet these demands and was employed to analyse WTAs and WTA glycosylation in S. aureus. Using S. aureus mutants, we found that a complete loss of WTA expression resulted in strong FTIR spectral perturbations mainly related to carbohydrates and phosphorus-containing molecules. We could demonstrate that α- or ß-O-GlcNAc WTA substituents can be clearly differentiated by chemometrically assisted FTIR spectroscopy. Our results suggest that whole cell FTIR spectroscopy represents a powerful and reliable method for large scale analysis of WTA glycosylation, thus opening up a complete new range of options for deciphering the staphylococcal pathogenesis related glycocode.
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Proteínas Bacterianas/metabolismo , Staphylococcus aureus/metabolismo , Ácidos Teicoicos/metabolismo , Glicosilación , Glicosiltransferasas/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Resistencia betalactámica/fisiologíaRESUMEN
All domains of life utilize protein phosphorylation as a mechanism of signal transduction. In bacteria, protein phosphorylation was classically thought to be mediated exclusively by histidine kinases as part of two-component signaling systems. However, it is now well appreciated that eukaryotic-like serine/threonine kinases (eSTKs) control essential processes in bacteria. A subset of eSTKs are single-pass transmembrane proteins that have extracellular penicillin-binding-protein and serine/threonine kinase-associated (PASTA) domains which bind muropeptides. In a variety of important pathogens, PASTA kinases have been implicated in regulating biofilms, antibiotic resistance, and ultimately virulence. Although there are limited examples of direct regulation of virulence factors, PASTA kinases are critical for virulence due to their roles in regulating bacterial physiology in the context of stress. This review focuses on the role of PASTA kinases in virulence for a variety of important Gram-positive pathogens and concludes with a discussion of current efforts to develop kinase inhibitors as novel antimicrobials.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana/fisiología , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Factores de Virulencia/metabolismo , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Proteínas Bacterianas/metabolismo , Biopelículas/crecimiento & desarrollo , División Celular/fisiología , Pared Celular , Regulación Bacteriana de la Expresión Génica , Histidina Quinasa , Homeostasis , Proteínas de la Membrana/metabolismo , Proteínas de Unión a las Penicilinas , Fosforilación , Dominios Proteicos , Proteínas Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Transducción de Señal , Virulencia , Resistencia betalactámica/fisiologíaRESUMEN
OBJECTIVES: In Klebsiella pneumoniae, overproduction of RamA results in reduced envelope permeability and reduced antimicrobial susceptibility but clinically relevant resistance is rarely observed. Here we have tested whether RamA overproduction can enhance acquired ß-lactam resistance mechanisms in K. pneumoniae and have defined the envelope protein abundance changes upon RamA overproduction during growth in low and high osmolarity media. METHODS: Envelope permeability was estimated using a fluorescent dye accumulation assay. ß-Lactam susceptibility was measured using disc testing. Total envelope protein production was quantified using LC-MS/MS proteomics and transcript levels were quantified using real-time RT-PCR. RESULTS: RamA overproduction enhanced ß-lactamase-mediated ß-lactam resistance, in some cases dramatically, without altering ß-lactamase production. It increased production of efflux pumps and decreased OmpK35 porin production, though micF overexpression showed that OmpK35 reduction has little impact on envelope permeability. A survey of K. pneumoniae bloodstream isolates revealed ramA hyperexpression in 3 of 4 carbapenemase producers, 1 of 21 CTX-M producers and 2 of 19 strains not carrying CTX-M or carbapenemases. CONCLUSIONS: Whilst RamA is not a key mediator of antibiotic resistance in K. pneumoniae on its own, it is potentially important for enhancing the spectrum of acquired ß-lactamase-mediated ß-lactam resistance. LC-MS/MS proteomics analysis has revealed that this enhancement is achieved predominantly through activation of efflux pump production.
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Proteínas Bacterianas/biosíntesis , Permeabilidad de la Membrana Celular/fisiología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/metabolismo , Porinas/biosíntesis , Resistencia betalactámica/fisiología , Farmacorresistencia Bacteriana Múltiple/fisiología , Humanos , Klebsiella pneumoniae/genética , beta-Lactamasas/genéticaRESUMEN
OBJECTIVES: This study aims to assess the in vitro activity of cefoperazone alone and different cefoperazone-sulbactam ratios against different inoculum sizes of multidrug resistant organisms. METHODS: Minimum inhibitory concentrations (MICs) of cefoperazone, cefoperazone-sulbactam at fixed ratio of 1:1 and 2:1 against a normal inoculum size of 5 × 105 CFU/ml and a high inoculum size of 5 × 107 CFU/ml were measured. RESULTS: Each 33 isolates of extended-spectrum ß-lactamases (ESBL)-producing Escherichia coli, ESBL-producing Klebsiella pneumoniae, carbapenem-resistant E. coli, and carbapenem-resistant Pseudomonas aeruginosa and a total of 122 isolates of carbapenem-resistant Acinetobacter baumannii were collected. After the addition of sulbactam at a 1:1 ratio, most MIC50 and MIC90 values decreased. Cefoperazone-sulbactam at a 1:1 ratio had a higher susceptibility rate against ESBL-producing E. coli, carbapenem-resistant E. coli, and carbapenem-resistant A. baumannii than cefoperazone-sulbactam at a 2:1 ratio (all P < 0.05). For ESBL-producing E. coli, the susceptibility rate of cefoperazone-sulbactam at ratios of (1:1) and (2:1) decreased from 97.0 to 87.9% and 90.9 to 60.6%, for normal to high inoculum, respectively. For ESBL-producing K. pneumoniae, both susceptibility rate of cefoperazone-sulbactam at ratios of (1:1) and (2:1) decreased from 75.8%, and 63.6% at normal inoculum to 51.5% and 42.4% at high inoculum. CONCLUSIONS: Cefoperazone-sulbactam at a 1:1 ratio has greater in vitro activity against most multidrug resistant organisms than cefoperazone-sulbactam at a 2:1 ratio. Such combinations were not influenced by the inoculum size of ESBL-producing E. coli and K. pneumoniae and could be a therapeutic option for treating severe infections.
Asunto(s)
Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Cefoperazona/farmacología , Escherichia coli/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Sulbactam/farmacología , Acinetobacter baumannii/aislamiento & purificación , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana Múltiple/fisiología , Escherichia coli/aislamiento & purificación , Humanos , Klebsiella pneumoniae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/aislamiento & purificación , Resistencia betalactámica/fisiología , beta-Lactamasas/metabolismoRESUMEN
Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species. We found eight species exhibiting resistance, with the majority of our sample being the sequence type 258 (ST258) lineage of Klebsiella pneumoniae There was very little evidence of extensive hospital outbreaks, but a great deal of variation in resistance mechanisms and the genomic backgrounds carrying these mechanisms. Local transmission was evident in clear phylogeographic structure between the samples from the two coasts. The most common resistance mechanisms were KPC (K. pneumoniae carbapenemases) beta-lactamases encoded by blaKPC2, blaKPC3, and blaKPC4, which were transferred between strains and species by seven distinct subgroups of the Tn4401 element. We also found evidence for previously unrecognized resistance mechanisms that produced resistance when transformed into a susceptible genomic background. The extensive variation, together with evidence of transmission beyond limited clonal outbreaks, points to multiple unsampled transmission chains throughout the continuum of care, including asymptomatic carriage and transmission of CRE. This finding suggests that to control this threat, we need an aggressive approach to surveillance and isolation.
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Carbapenémicos/farmacología , Elementos Transponibles de ADN/genética , Brotes de Enfermedades , Infecciones por Enterobacteriaceae/microbiología , Enterobacteriaceae/efectos de los fármacos , Factores R/genética , Resistencia betalactámica/genética , Proteínas Bacterianas/genética , Boston/epidemiología , Células Clonales , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Infección Hospitalaria/transmisión , Enterobacteriaceae/enzimología , Enterobacteriaceae/genética , Infecciones por Enterobacteriaceae/epidemiología , Infecciones por Enterobacteriaceae/transmisión , Variación Genética , Genoma Bacteriano , Humanos , Estudios Prospectivos , Alineación de Secuencia , Transformación Bacteriana , Resistencia betalactámica/fisiología , beta-Lactamasas/genéticaRESUMEN
Performance of the CHROMagar mSuperCARBA media was assessed in both well-characterized carbapenem-resistant Enterobacteriaceae (n=52) and routine surveillance rectal swab specimens (n=211). Limit of detection ranged between 101 and 102CFU/mL except for OXA-48 producers with low-carbapenem MICs (106CFU/mL). High sensitivity (100%) and specificity (100%) were obtained with rectal swabs.
Asunto(s)
Antibacterianos/farmacología , Carbapenémicos/farmacología , Infecciones por Enterobacteriaceae/diagnóstico , Enterobacteriaceae/efectos de los fármacos , Resistencia betalactámica/fisiología , Técnicas Bacteriológicas , Compuestos Cromogénicos , Medios de Cultivo , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Humanos , Límite de Detección , Pruebas de Sensibilidad Microbiana , Recto/microbiología , Sensibilidad y EspecificidadRESUMEN
UNLABELLED: The epidemiology of antimicrobial resistance is extremely complex and involves humans, domestic animals (companion and agricultural) and wildlife. In North America there have been very few investigations targeting antimicrobial-resistant organisms in wildlife. In this study, we characterized the susceptibility of Escherichia coli isolated from 75 birds including great horned owls, crows and American robins from the region of Saskatoon, Canada. The recovery rate of E. coli varied significantly between species from 44·8% of robins to 92% of crows. The majority (88·2%) of colonized birds carried only pan-susceptible organisms. Among isolates resistant to at least one antimicrobial, ampicillin resistance was most commonly identified. Three birds carried multidrug-resistant isolates (resistant to ≥3 drug classes), and extended-spectrum ß-lactamase (ESBL)-producing organisms (CTX-M-15 and SHV2a) were grown from two. We identified a significant relationship between the presence of drug-resistant E. coli and an urban (vs rural) origin of the bird. Our findings suggest that crows, due to their ubiquity and high rate of colonization with E. coli, may be efficient targets for future resistance surveillance studies targeting urban wildlife. SIGNIFICANCE AND IMPACT OF THE STUDY: Antimicrobial resistance is a global problem affecting people and animals. Few investigations describing the presence drug-resistant organisms in wildlife in North America have been published. In this study, resistant Escherichia coli, including extended-spectrum ß-lactamase-producing strains, were isolated from wild birds in the Saskatoon region of Canada. We found that the recovery rate of E. coli varied significantly by species and was highest among crows. There was also a significant association between drug resistance and urban vs rural birds. Our results suggest that crows may be a good target for future studies investigating antimicrobial resistance in urban wildlife.
Asunto(s)
Antibacterianos/farmacología , Aves/microbiología , Infecciones por Escherichia coli/veterinaria , Escherichia coli/efectos de los fármacos , Resistencia betalactámica/fisiología , beta-Lactamasas/farmacología , Animales , Animales Salvajes , Canadá , Escherichia coli/aislamiento & purificación , Escherichia coli/metabolismo , Infecciones por Escherichia coli/microbiología , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Acinetobacter baumannii is grouped in the ESKAPE pathogens by Infectious Disease Society of America, which is linked to high degree of morbidity, mortality, and increased costs. The high level of acquired and intrinsic resistance mechanisms of these bacteria makes it an urgent requirement to find a suitable alternative to carbapenem, a commonly prescribed drug for Acinetobacter infection. In this study, methanolic extracts of six medicinal plants were subjected to phytochemical screening and their antimicrobial activity was tested against two strains of A. baumannii (ATCC 19606, carbapenem-sensitive strain, and RS 307, carbapenem-resistant strain). Synergistic effect of the plant extracts and antibiotics was also tested. Bael or Aegle marmelos contains tannin, phenol, terpenoids, glycoside, alkaloids, coumarine, steroid, and quinones. Flowers of madar or Calotropis procera possess tannin, phenol, terpenoids, glycoside, quinone, anthraquinone, anthocyanin, coumarin, and steroid. An inhibitory growth curve was seen for both the bacterial strains when treated with A. marmelos, Curcuma longa, and leaves and flowers of C. procera. Antibiotics alone showed a small zone of inhibition, but when used with herbal extracts they exhibited larger zone of inhibition. Synergistic effect of A. marmelos and imipenem was the best against both the strains of A. baumannii. From this study, it can be concluded that extracts from A. marmelos and leaves and flowers of C. procera exhibited the most effective antibacterial activity. These herbal extracts may be used to screen the bioactive compound against the carbapenem-resistant strain of A. baumannii.
Asunto(s)
Acinetobacter baumannii/efectos de los fármacos , Aegle/química , Antibacterianos/farmacología , Calotropis/química , Imipenem/farmacología , Extractos Vegetales/farmacología , Resistencia betalactámica/efectos de los fármacos , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/crecimiento & desarrollo , Acinetobacter baumannii/aislamiento & purificación , Alcaloides/aislamiento & purificación , Antibacterianos/química , Curcuma/química , Combinación de Medicamentos , Sinergismo Farmacológico , Glicósidos/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Fenoles/aislamiento & purificación , Extractos Vegetales/química , Hojas de la Planta/química , Taninos/aislamiento & purificación , Resistencia betalactámica/fisiologíaRESUMEN
Thein vitroantibacterial activities of ceftazidime-avibactam and comparator agents were evaluated using reference broth microdilution methods against 1,743Pseudomonas aeruginosaisolates collected in 2014 from 69 U.S. medical centers, representing each of the nine census regions. Ceftazidime-avibactam demonstrated potent activity againstP. aeruginosa, including many isolates not susceptible to ceftazidime, meropenem, and piperacillin-tazobactam. In each of the nine census regions, ceftazidime-avibactam demonstrated the highest percentage of susceptible isolates.
Asunto(s)
Antibacterianos/farmacología , Compuestos de Azabiciclo/farmacología , Ceftazidima/farmacología , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Resistencia betalactámica/fisiología , Centros Médicos Académicos , Censos , Combinación de Medicamentos , Humanos , Meropenem , Pruebas de Sensibilidad Microbiana , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/farmacología , Piperacilina/farmacología , Combinación Piperacilina y Tazobactam , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/aislamiento & purificación , Vigilancia en Salud Pública , Tienamicinas/farmacología , Estados UnidosRESUMEN
Metallo-ß-lactamases (MBLs) hydrolyze all classes of ß-lactams except monobactams and are not inhibited by classic serine ß-lactamase inhibitors. Gram-negative pathogens isolated from patient infections were collected from 202 medical centers in 40 countries as part of a global surveillance study from 2012 to 2014. Carbapenem-nonsusceptible Enterobacteriaceae and Pseudomonas aeruginosa were characterized for bla genes encoding VIM, IMP, NDM, SPM, and GIM variants using PCR and sequencing. A total of 471 MBL-positive isolates included the following species (numbers of isolates are in parentheses): P. aeruginosa (308), Klebsiella spp. (85), Enterobacter spp. (39), Proteeae (16), Citrobacter freundii (12), Escherichia coli (6), and Serratia marcescens (5) and were submitted by sites from 34 countries. Of these, 69.6% were collected in 9 countries (numbers of isolates are in parentheses): Russia (72), Greece (61), Philippines (54), Venezuela (29), and Kuwait, Nigeria, Romania, South Africa, and Thailand (20 to 25 isolates each). Thirty-two different MBL variants were detected (14 VIM, 14 IMP, and 4 NDM enzymes). Seven novel MBL variants were encountered in the study, each differing from a previously reported variant by one amino acid substitution: VIM-42 (VIM-1 [V223I]), VIM-43 (VIM-4 [A24V]), VIM-44 (VIM-2 [K257N]), VIM-45 (VIM-2 [T35I]), IMP-48 (IMP-14 [I69T]), IMP-49 (IMP-18 [V49F]), and NDM-16 (NDM-1 [R264H]). The in vitro activities of all tested antibiotics against MBL-positive Enterobacteriaceae were significantly reduced with the exception of that of aztreonam-avibactam (MIC90, 0.5 to 1 µg/ml), whereas colistin was the most effective agent against MBL-positive P. aeruginosa isolates (>97% susceptible). Although the global percentage of isolates encoding MBLs remains relatively low, their detection in 12 species, 34 countries, and all regions participating in this surveillance study is concerning.