RESUMO
Traditional studies on the evolution of antibiotic resistance development use approaches that can range from laboratory-based experimental studies, to epidemiological surveillance, to sequencing of clinical isolates. However, evolutionary trajectories also depend on the environment in which selection takes place, compelling the need to more deeply investigate the impact of environmental complexities and their dynamics over time. Herein, we explored the within-patient adaptive long-term evolution of a Pseudomonas aeruginosa hypermutator lineage in the airways of a cystic fibrosis (CF) patient by performing a chronological tracking of mutations that occurred in different subpopulations; our results demonstrated parallel evolution events in the chromosomally encoded class C ß-lactamase (blaPDC). These multiple mutations within blaPDC shaped diverse coexisting alleles, whose frequency dynamics responded to the changing antibiotic selective pressures for more than 26 years of chronic infection. Importantly, the combination of the cumulative mutations in blaPDC provided structural and functional protein changes that resulted in a continuous enhancement of its catalytic efficiency and high level of cephalosporin resistance. This evolution was linked to the persistent treatment with ceftazidime, which we demonstrated selected for variants with robust catalytic activity against this expanded-spectrum cephalosporin. A "gain of function" of collateral resistance toward ceftolozane, a more recently introduced cephalosporin that was not prescribed to this patient, was also observed, and the biochemical basis of this cross-resistance phenomenon was elucidated. This work unveils the evolutionary trajectories paved by bacteria toward a multidrug-resistant phenotype, driven by decades of antibiotic treatment in the natural CF environmental setting. IMPORTANCE Antibiotics are becoming increasingly ineffective to treat bacterial infections. It has been consequently predicted that infectious diseases will become the biggest challenge to human health in the near future. Pseudomonas aeruginosa is considered a paradigm in antimicrobial resistance as it exploits intrinsic and acquired resistance mechanisms to resist virtually all antibiotics known. AmpC ß-lactamase is the main mechanism driving resistance in this notorious pathogen to ß-lactams, one of the most widely used classes of antibiotics for cystic fibrosis infections. Here, we focus on the ß-lactamase gene as a model resistance determinant and unveil the trajectory P. aeruginosa undertakes on the path toward a multidrug-resistant phenotype during the course of two and a half decades of chronic infection in the airways of a cystic fibrosis patient. Integrating genetic and biochemical studies in the natural environment where evolution occurs, we provide a unique perspective on this challenging landscape, addressing fundamental molecular mechanisms of resistance.
Assuntos
Fibrose Cística , Infecções por Pseudomonas , Humanos , Cefalosporinase/genética , Fibrose Cística/microbiologia , Ceftazidima/farmacologia , Infecções por Pseudomonas/microbiologia , Pseudomonas/metabolismo , Testes de Sensibilidade Microbiana , beta-Lactamases/metabolismo , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Metallo-ß-lactamases (MBLs) are the major group of carbapenemases produced by bacterial pathogens. The design of MBL inhibitors has been limited by, among other issues, incomplete knowledge about how these enzymes modulate substrate recognition. While most MBLs are broad-spectrum enzymes, B2 MBLs are exclusive carbapenemases. This narrower substrate profile has been attributed to a sequence insertion present in B2 enzymes that limits accessibility to the active site. In this work, we evaluate the role of sequence insertions naturally occurring in the B2 enzyme Sfh-I and in the broad-spectrum B1 enzyme SPM-1. We engineered a chimeric protein in which the sequence insertion of SPM-1 was replaced by the one present in Sfh-I. The chimeric variant is a selective cephalosporinase, revealing that the substrate profile of MBLs can be further tuned depending on the protein context. These results also show that the stable scaffold of MBLs allows a modular engineering much richer than the one observed in nature.
Assuntos
Antibacterianos/farmacologia , Cefalosporinase/metabolismo , beta-Lactamases/metabolismo , Cefalosporinase/genética , Farmacorresistência Bacteriana/genética , Especificidade por Substrato , beta-Lactamases/genéticaRESUMO
Extended-spectrum-cephalosporin-resistant Enterobacteriaceae are a public health concern due to limited treatment options. Here, we report on the occurrence and the molecular characteristics of extended-spectrum-cephalosporin-resistant Enterobacteriaceae recovered from wild birds (kelp gulls). Our results revealed kelp gulls as a reservoir of various extended-spectrum cephalosporinase genes associated with different genetic platforms. In addition, we report for the first time the presence of a known epidemic clone of Salmonella enterica serotype Heidelberg (JF6X01.0326/XbaI.1966) among wild birds.
Assuntos
Resistência às Cefalosporinas/genética , Charadriiformes/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Animais , Antibacterianos/farmacologia , Resistência às Cefalosporinas/efeitos dos fármacos , Cefalosporinase/genética , Cefalosporinas/farmacologia , Enterobacteriaceae/isolamento & purificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Plasmídeos/genética , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/genética , América do SulRESUMO
An investigation was carried out into the genetic mechanisms responsible for multidrug resistance in nine carbapenem-resistant Pseudomonas aeruginosa isolates from different hospitals in Recife, Brazil. Susceptibility to antimicrobial agents was determined by broth microdilution. Polymerase chain reaction (PCR) was employed to detect the presence of genes encoding ß-lactamases, aminoglycoside-modifying enzymes (AMEs), 16S rRNA methylases, integron-related genes and OprD. Expression of genes coding for efflux pumps and AmpC cephalosporinase were assessed by quantitative PCR. The outer membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The blaSPM-1, blaKPC-2 and blaGES-1 genes were detected in P. aeruginosa isolates in addition to different AME genes. The loss of OprD in nine isolates was mainly due to frameshift mutations, premature stop codons and point mutations. An association of loss of OprD with the overexpression of MexAB-OprM and MexXY-OprM was observed in most isolates. Hyper-production of AmpC was also observed in three isolates. Clonal relationship of the isolates was determined by repetitive element palindromic-PCR and multilocus sequence typing. Our results show that the loss of OprD along with overexpression of efflux pumps and ß-lactamase production were responsible for the multidrug resistance in the isolates analysed.
Assuntos
Carbapenêmicos/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Mutação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Resistência beta-Lactâmica/genética , beta-Lactamases/metabolismo , Aminoglicosídeos/metabolismo , Anfotericina B/análogos & derivados , Anfotericina B/metabolismo , Antifúngicos/metabolismo , Brasil , Cefalosporinase/classificação , Cefalosporinase/metabolismo , Códon sem Sentido/metabolismo , Ativação Enzimática/genética , Mutação da Fase de Leitura/genética , Regulação Bacteriana da Expressão Gênica/genética , Humanos , Proteínas de Membrana Transportadoras/metabolismo , Metiltransferases/metabolismo , Nucleotidiltransferases/metabolismo , Mutação Puntual/genética , Porinas/metabolismo , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/isolamento & purificação , Sequências Repetitivas de Ácido Nucleico , beta-Lactamases/genéticaRESUMO
An investigation was carried out into the genetic mechanisms responsible for multidrug resistance in nine carbapenem-resistant Pseudomonas aeruginosaisolates from different hospitals in Recife, Brazil. Susceptibility to antimicrobial agents was determined by broth microdilution. Polymerase chain reaction (PCR) was employed to detect the presence of genes encoding β-lactamases, aminoglycoside-modifying enzymes (AMEs), 16S rRNA methylases, integron-related genes and OprD. Expression of genes coding for efflux pumps and AmpC cephalosporinase were assessed by quantitative PCR. The outer membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The blaSPM-1, blaKPC-2 and blaGES-1 genes were detected in P. aeruginosaisolates in addition to different AME genes. The loss of OprD in nine isolates was mainly due to frameshift mutations, premature stop codons and point mutations. An association of loss of OprD with the overexpression of MexAB-OprM and MexXY-OprM was observed in most isolates. Hyper-production of AmpC was also observed in three isolates. Clonal relationship of the isolates was determined by repetitive element palindromic-PCR and multilocus sequence typing. Our results show that the loss of OprD along with overexpression of efflux pumps and β-lactamase production were responsible for the multidrug resistance in the isolates analysed.
Assuntos
Humanos , Carbapenêmicos/metabolismo , Farmacorresistência Bacteriana Múltipla/genética , Mutação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Resistência beta-Lactâmica/genética , beta-Lactamases/metabolismo , Aminoglicosídeos/metabolismo , Anfotericina B/análogos & derivados , Anfotericina B/metabolismo , Antifúngicos/metabolismo , Brasil , Cefalosporinase/classificação , Cefalosporinase/metabolismo , Códon sem Sentido/metabolismo , Ativação Enzimática/genética , Mutação da Fase de Leitura/genética , Regulação Bacteriana da Expressão Gênica/genética , Proteínas de Membrana Transportadoras/metabolismo , Metiltransferases/metabolismo , Nucleotidiltransferases/metabolismo , Mutação Puntual/genética , Porinas/metabolismo , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/isolamento & purificação , Sequências Repetitivas de Ácido Nucleico , beta-Lactamases/genéticaRESUMO
BACKGROUND: Pseudomonas aeruginosa commonly causes nosocomial bloodstream infections and the emergence of a variety of ß-lactamases (BLs) is worrying. In 5 hospitals in Belo Horizonte, Brazil, the presence of phenotypes encoding BL genes was established and the genetic diversity of the P. aeruginosa strains recovered from bloodstream infections was analyzed. MATERIALS AND METHODS: The isolates were investigated using a disk diffusion (DD) method and the Etest, for encoding metallo-ß-lactamases (MBLs), oxacillinases and cephalosporinases. Genes and genetic diversity were evaluated by random amplified polymorphic DNA (RAPD) genotyping and enterobacterial repetitive intergenic consensus (ERIC)-PCR. RESULTS: Twelve strains (30%) were positive for MBLs by Etest and DD, 15 were cephalosporinase-positive and 87.5% were positive for blaSPM-1 and blaVIM-1. Twenty-three strains (57.5%) were grouped into profile A, 32.5% into profile B and 10% into profile C by RAPD genotyping. ERIC-PCR revealed a varying degree of similarity between strains, ranging from 45 to 100%. CONCLUSIONS: The results suggest distinct clonal populations in the 5 hospitals studied, indicating a potentially problematic epidemiological situation in Belo Horizonte, Brazil.
Assuntos
Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Anti-Infecciosos/farmacologia , Brasil , Cefalosporinase/genética , Cefalosporinase/metabolismo , DNA Bacteriano/análise , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Genótipo , Hospitais , Humanos , Fenótipo , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/isolamento & purificação , Técnica de Amplificação ao Acaso de DNA Polimórfico , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
In this study, phenotypic and genotypic methods were used to detect metallo-ß-lactamases, cephalosporinases and oxacillinases and to assess genetic diversity among 64 multiresistant Acinetobacter baumannii strains recovered from blood cultures in five different hospitals in Brazil from December 2008 to June 2009. High rates of resistance to imipenem (93.75%) and polymyxin B (39.06%) were observed using the disk diffusion (DD) method and by determining the minimum inhibitory concentration (MIC). Using the disk approximation method, thirty-nine strains (60.9%) were phenotypically positive for class D enzymes, and 51 strains (79.6%) were positive for cephalosporinase (AmpC). Using the E-test, 60 strains (93.75%) were positive for metallo-ß-lactamases (MßLs). All strains were positive for at least one of the 10 studied genes; 59 (92.1%) contained blaVIM-1, 79.6% contained blaAmpC, 93.7% contained blaOXA23 and 84.3% contained blaOXA51. Enterobacteria Repetitive Intergenic Consensus (ERIC)-PCR analysis revealed a predominance of certain clones that differed from each other. However, the same band pattern was observed in samples from the different hospitals studied, demonstrating correlation between the genotypic and phenotypic results. Thus, ERIC-PCR is an appropriate method for rapidly clustering genetically related isolates. These results suggest that defined clonal clusters are circulating within the studied hospitals. These results also show that the prevalence of MDR A. baumannii may vary among clones disseminated in specific hospitals, and they emphasize the importance of adhering to appropriate infection control measures.
Assuntos
Acinetobacter baumannii/genética , Bacteriemia/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana/genética , Acinetobacter baumannii/enzimologia , Bacteriemia/genética , Cefalosporinase/metabolismo , Infecção Hospitalar/genética , Variação Genética , Genótipo , Técnicas de Genotipagem , Humanos , Testes de Sensibilidade Microbiana , Fenótipo , beta-Lactamases/genética , beta-Lactamases/metabolismoRESUMO
Introducción. Los sistemas de vigilancia son una pieza clave para la detección y control de la resistencia bacteriana. Es indispensable recolectar constantemente la información de cada institución por la variabilidad existente entre países, ciudades y hospitales frente a los mecanismos de resistencia bacteriana y así plantear intervenciones apropiadas para cada institución. De enero 2003 a diciembre de 2005, el Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) desarrolló un proyecto de vigilancia en un grupo de 10 hospitales de tercer nivel, en seis ciudades de Colombia. Objetivos. Presentar el comportamiento de Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii y Enterobacter cloacae, considerados los Gram negativos patógenos más relevantes en infección nosocomial, frente a antimicrobianos seleccionados. Materiales y métodos. Las pruebas de susceptibilidad se realizaron por métodos automatizados en 9 hospitales y por Kirby Bauer en un hospital. Se eligieron antibióticos con actividad reconocida contra Gram negativos, de acuerdo con las guías del Comité Nacional para el Control de Estándares en el Laboratorio Clínico (NCCLS). Los laboratorios realizaron control de calidad interno y externo. Mensualmente se recibió la información procedente del laboratorio de microbiología de cada institución y se centralizó en una base de datos en WHONET 5.3 en CIDEIM . Se realizó un análisis conglomerado de frecuencias y porcentajes de resistencia a antibióticos. Resultados. Los altos porcentajes de resistencia reportados en especial para A. baumannii, corroboraron la presencia de bacterias multirresistentes en las UCI en las instituciones participantes durante el periodo de estudio. Conclusiones. Es urgente crear una red nacional de vigilancia de la resistencia a antimicrobianos de los patógenos hospitalarios y de esta manera mejorar nuestra habilidad para detectar, supervisar y manejar la resistencia a antimicrob...
Introduction. Surveillance systems play a key role in the detection and control of bacterial resistance. It is necessary to constantly collect information from all institutions because the mechanisms of bacterial resistance can operate in different ways between countries, cities and even in hospitals in the same area. Therefore local information is important in order to learn about bacterial behaviour and design appropriate interventions for each institution. Between January 2003 and December 2004, the Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM) developed a surveillance project in 10 tertiary hospitals in 6 cities of Colombia. Objectives. Describe the trends of antibiotic resistance among the isolates of Escherichia coli, Klebsiella pneumoniae, Pseudomona aeruginosa, Acinetobacter baumannii and Enterobacter cloacae, five of the most prevalent nosocomial Gram negative pathogens. Materials and Methods: The susceptibility tests were performed by automated methods in 9 hospitals and by Kirby Bauer in 1 hospital. Antibiotics with known activity against Gram negatives, according to the Clinical Laboratory Standards Institute guidelines, were selected. The laboratories performed internal and external quality controls. During the study period, the information was downloaded monthly from the databases of each microbiology laboratory and sent to CIDEIM where it was centralized in a database using the system WHONET 5.3. Results. The high resistance rates reported especially for A. baumannii, evidenced the presence of multidrug resistant bacteria in both ICUs and wards at every studied institution. Conclusions. The creation of a national surveillance network to improve our capabilities to detect, follow up, and control the antibiotic resistance in Colombia is urgently needed.
Assuntos
Resistência Microbiana a Medicamentos , Infecções por Bactérias Gram-Negativas , Carbapenêmicos , Cefalosporinase , PiperacilinaRESUMO
The minimum inhibitory concentrations of six broad-spectrum beta-lactam antimicrobial agents were determined in 1998 by use of the Etest versus a total of 502 bacteria in seven Venezuelan hospital laboratories. These data were compared with results of a similar study performed in 1997. The organisms tested included 309 recent clinical isolates of Enterobacteriaceae, 70 Pseudomonas aeruginosa, 54 Acinetobacter species, and 69 oxacillin-susceptible Staphylococcus aureus. Extended spectrum beta-lactamase production was noted among 30% of Klebsiella pneumoniae isolates. Hyperproduction of Amp C cephalosporinase producing resistance to ceftazidime and cefotaxime was observed with 10 to 37% of isolates of Enterobacter spp., Serratia spp., and Citrobacter freundii. The overall rank order of activity of the six beta-lactams tested in this study against all clinical isolates was imipenem (96.6% susceptible) > cefepime (90.4%) > piperacillin/tazobactam (85.7%) > ceftazidime (73.5%) > cefotaxime (70.5%) > piperacillin (55.0%). These findings were very similar to those reported for 1997.
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cefalosporinase/biossíntese , Resistência Microbiana a Medicamentos , Enterobacteriaceae/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , Fatores de Tempo , Venezuela , beta-LactamasRESUMO
The zinc metalloenzyme beta-lactamase II (betaLII) from Bacillus cereus has been overexpressed in Escherichia coli as a fusion protein with glutathione-S-transferase, and the metal binding properties of recombinant betaLII toward Zn(II) and Co(II) have been studied by fluorescence and activity measurements. The apoenzyme is able to bind two metal ion equivalents, which confer on betaLII its maximum enzymatic efficiency. The enzyme is partially active with one metal ion equivalent. The diCo(II) and a mixed Zn(II)Co(II) derivative of betaLII were obtained and probed by electronic and paramagnetic NMR spectroscopy. In the high-affinity site, the metal is bound to three His residues and a solvent molecule, adopting a tetrahedral geometry. A Cys, a His, and an Asp residue are coordinated to the low-affinity metal site, together with two or three solvent molecules. This coordination polyhedron resembles the binuclear metal site of the Bacteroides fragilis beta-lactamase [Concha, N., Rasmussen, B. A., Bush, K., and Herzberg, O. (1996) Structure 4, 823-836; Carfi, A., Duée, E., Paul-Soto, R., Galleni, M., Frère, J. M., and Dideberg, O. (1998) Acta Crystallogr. D54, 47-57] but differs from that resulting from the X-ray study of betaLII [Carfi, A., Pares, S., Duée, E., Galleni, M., Duez, C., Frère, J. M., and Dideberg, O. (1995) EMBO J. 14, 4914-4921]. These results suggest that this binuclear metal site may be a general feature of metallo-beta-lactamases.
Assuntos
Bacillus cereus/enzimologia , Cefalosporinase/química , Zinco/química , Sequência de Aminoácidos , Sítios de Ligação , Cefalosporinase/biossíntese , Cefalosporinase/genética , Cobalto/química , Sequência Conservada , Escherichia coli/genética , Espectroscopia de Ressonância Magnética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Espectrometria de Fluorescência , EspectrofotometriaRESUMO
The need for comprehensive and quantitative accurate antimicrobial resistance surveillance systems has become acute as a guide to problem recognition and to focus local interventions. A multilaboratory (10 medical centers) Colombia surveillance project was initiated in early 1997 to monitor the potency and spectrum of six (cefepime, cefotaxime, ceftazidime, cefoperazone/sulbactam, aztreonam, and imipenem) broad-spectrum antimicrobial agents tested against 100 organisms per participant center (802 strains). Ten groups of organisms were tested by a reference-quality method (Etest; AB BIODISK, Solna, Sweden) with results validated by concurrent quality control and additional challenge strain analysis. Results from nine qualifying medical centers were tabulated, and 95.7 to 96.8% of quality assurance tests were within expected ranges. Only cefepime (90.1-100.0% susceptible) and imipenem (96.3-100.0%) were active against all Enterobacteriaceae at > 90% of susceptible isolates using the breakpoint concentrations recommended by the National Committee for Clinical Laboratory Standards. Among ceftazidime- (or cefotaxime- or aztreonam-) resistant Enterobacter spp. and Citrobacter freundii, cefepime remained active, but not cefoperazone with sulbactam. Escherichia coli and Klebsiella spp. strains having resistance phenotypes consistent with extended spectrum beta-lactamase production were discovered in approximately 5 to 10% of isolates. All tested drugs except ceftazidime (31.8-57.7% susceptible) were active against > 94% of oxacillin-susceptible staphylococci. Similar rates of resistance (9.1-14.8%) were observed in Pseudomonas aeruginosa for five of six drugs (not cefotaxime; 15.9% of strains were susceptible). Acinetobacter spp. isolates were most susceptible to imipenem (95.8%), cefepime (86.1%), and cefoperazone/sulbactam (83.3%). Overall for the 1997 order of antimicrobial spectrums for these tested compounds was: imipenem (96.6%) > cefepime (93.6%) > cefoperazone/sulbactam (90.5%) > cefotaxime (74.9%) > aztreonam (74.3% for Gram-negative bacilli only) > ceftazidime (73.2%). These data should be used to guide empiric regimens in Colombia, and additionally will provide a resistance statistical baseline to which future studies in this nation can be compared.
Assuntos
Antibacterianos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , Resistência beta-Lactâmica/fisiologia , Aztreonam/farmacologia , Cefepima , Cefoperazona/farmacologia , Cefotaxima/farmacologia , Ceftazidima/farmacologia , Cefalosporinase/biossíntese , Cefalosporinas/farmacologia , Estudos de Coortes , Colômbia , Enterobacteriaceae/enzimologia , Humanos , Imipenem/farmacologia , Testes de Sensibilidade Microbiana , Reprodutibilidade dos Testes , Sulbactam/farmacologiaRESUMO
En este trabajo se évalua el problema de la resistencia bacteriana a los antibióticos betalactamicos en venezuela. Se presentan los datos de resistencia bacteriana de varios hospitales venezolanos desde 1988 hasta 1992. Se analizan los resultados de las siguientes bacterias: Staphylococcus aureus, Staphylococus epidermidis, Enterococus faecalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Salmonella sp., Shigella sp., Pseudomonas aeruginosa, Streptococus pneumoniae, Neisseria gonorrhoeae y Neisseria meningitidis
Assuntos
Humanos , Masculino , Feminino , Cefalosporinase , Resistência Microbiana a Medicamentos , Penicilinase , Antibacterianos , Bactérias/análiseRESUMO
Se estudiaron 100 muestras de exudados nasales obtenidos de estudiantes de segundo año de Medicina del Instituto Superior de Ciencias Médicas de Villa Clara, de enero a julio de 1987. El objectivo es conocer el índice de portadores de estafilococos por la implicación que tiene en su futura actividad hospitalaria a partir del tercer año, y para investigar la sensibilidad y resistencia de las cepas a los diferentes antimicrobianos. Se aislaron 86 cepas de estafilococos y se les realizó la prueba coagulasa, de las que 48 resultaron positivas. Se comprobó que la novobiocina era el agente antimicrobiano más efectivo. Se verificó la alta resistencia de los estafilococos a la penicilina y se pudo comprobar que un gran por ciento de las cepas son productoras de Beta-lactamasas
Assuntos
Antibacterianos , Cefalosporinase , Tolerância a Medicamentos , Penicilinase , Streptococcus/isolamento & purificaçãoRESUMO
The in vitro activity of cefpirome was evaluated against strains that showed conflicting results for third generation cephalosporins. Against isolates with derepressed inducible chromosomal cephalosporinase (n = 40) cefpirome was the sole cephalosporin with an MIC90 in the susceptible range; Klebsiella spp. with plasmid-mediated beta-lactamases (broad spectrum SHV-2 or SHV-2 type) (n = 40) remained most susceptible to ceftizoxime and cefpirome; against aminoglycoside-resistant Pseudomonas aeruginosa (n = 50), cefpirome was as active as ceftazidime and cefoperazone; against oxacillin-susceptible and oxacillin-resistant Staphylococcus spp., (n = 40), cefpirome was more active than other third generation cephalosporins but killing was inadequate against both oxacillin-resistant staphylococci and enterococci.