RESUMO
PURPOSE: The aim of this study was to assess the risk factors for colistin-resistant carbapenemase-producing Enterobacterales (CR-CPE), and describe the mortality associated with this organism, in a low-income country. METHODS: A descriptive, observational, and prospective multicenter study was carried out in Guayaquil, Ecuador. All patients with carbapenem-resistant Enterobacterales admitted between December 2021 and May 2022 were enrolled. Infection definitions were established according to the Centers for Disease Control and Prevention (CDC) protocols. The presence of carbapenemase-producing Enterobacterales was confirmed with a multiplex PCR for blaKPC, blaNDM, blaOXA-48, blaVIM, and blaIMP genes. MCR-1 production was studied molecularly, and MLST assays were carried out. RESULTS: Out of 114 patients enrolled in the study, 32 (28.07%) had at least one positive sample for CR-CPE. Klebsiella pneumoniae ST512-KPC-3 was the most frequent microorganism isolated. Parenteral feeding, ß-lactamase inhibitor use, recent hemodialysis, and renal failure were all considered independent risk factors for carrying CR-CPE. A mortality of 41.22% was detected, but we could not find any difference between colistin-resistant and colistin-susceptible CPE. MCR-1 production was not detected in any of the isolates studied. CONCLUSION: A significant burden for CR-CPE was found in a South American country that was mainly caused by the high-risk clone K. pneumoniae ST512-KPC-3 and not mediated by mcr-1 production. Its acquisition involved parenteral feeding, ß-lactamase inhibitor use, recent hemodialysis, and renal failure as independent risk factors, demonstrating the critical need for infection prevention and stewardship programs to avoid dissemination to other countries in the region.
Assuntos
Colistina , Inibidores de beta-Lactamases , Humanos , Colistina/farmacologia , Tipagem de Sequências Multilocus , Estudos Prospectivos , Proteínas de Bactérias/genética , beta-Lactamases/genética , Klebsiella pneumoniae , Monobactamas , Fatores de Risco , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologiaRESUMO
Multidrug-resistant bacteria present resistance mechanisms against ß-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-ß-lactamases enzymes (MBLs) which are operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of ß-lactam antibiotic resistance genes and the microbiome circulating in Quito's Public Transport (QTP). A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify and to amplify 16S rDNA for barcoding, followed by clone analysis, Sanger sequencing, and BLAST search. ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations, blaTEM being the most widely spread. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species, including those classified by the WHO as pathogens of critical and high-priority surveillance. ß-lactam antibiotic resistance genes are prevalent throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs.
Assuntos
Antibacterianos , beta-Lactamases , Humanos , Equador , beta-Lactamases/genética , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias/metabolismo , Monobactamas , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade MicrobianaRESUMO
The aim of this review is to present an update on the susceptibility of viridans group streptococci (VGS) to ß-lactam antimicrobials, with emphasis on the Argentinean scenario. VGS are a heterogeneous group including five groups of species, each one exhibiting peculiar susceptibility patterns to penicillin (PEN). Species of the Streptococcus mitis group are frequently nonsusceptible to PEN. PEN resistance is associated with changes in PEN-binding proteins. In Argentina, one to two thirds of VGS are nonsusceptible to PEN. Third generation cephalosporins and carbapenems are currently more effective in vitro than PEN against VGS. Mortality was associated to nonsusceptibility to PEN in at least two studies involving patients with bacteremia caused by VGS. Treatment of endocarditis due to VGS should be adjusted/to the PEN susceptibility of the isolates. Vancomycin may be an alternative choice for treating endocarditis caused by PEN-resistant isolates (MIC≥4µg/ml).
Assuntos
Endocardite , Infecções Estreptocócicas , Humanos , Testes de Sensibilidade Microbiana , Infecções Estreptocócicas/tratamento farmacológico , Estreptococos Viridans , Penicilinas , Monobactamas , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Endocardite/tratamento farmacológicoRESUMO
Os betalactâmicos são a classe de drogas que mais causam reações de hipersensibilidade envolvendo um mecanismo imunológico específico, e são os principais desencadeantes entre os antimicrobianos. São representados pelas penicilinas, cefalosporinas, carbapenêmicos, monobactâmicos e inibidores da betalactamase. A estrutura química básica destes fármacos consiste na presença dos seguintes componentes: anel betalactâmico, anel adjacente e cadeias laterais, sendo todos potenciais epítopos. Os anticorpos da classe IgE e linfócitos T estão frequentemente envolvidos no reconhecimento desses epítopos. A reatividade cruzada depende da estabilidade dos produtos intermediários (determinantes antigênicos) derivados da degradação dos anéis betalactâmicos, anéis adicionais e da semelhança estrutural das cadeias laterais entre as drogas. Classicamente acreditava-se num grande potencial de reatividade cruzada dentro de cada classe e até entre as classes, mas estudos da última década mostraram que indivíduos alérgicos à penicilina (com testes cutâneos positivos) reagiam às cefalosporinas em aproximadamente 3% dos casos, aos carbapenêmicos em cerca de 1%, e praticamente não reagiam aos monobactâmicos. Essa reatividade ou tolerância parece estar vinculada ao grau de similaridade entre as cadeias laterais desses antibióticos. Nesta revisão, ressaltamos a importância da investigação sistematizada na confirmação ou exclusão de alergia aos betalactâmicos, descrevemos a prevalência da reatividade cruzada entre estes fármacos e sugerimos um algoritmo de abordagem desses pacientes baseados em sua estrutura química e nos dados publicados na literatura.
Beta-lactams are the drugs most commonly involved in hypersensitivity reactions mediated by a specific immune mechanism and are the main triggers among antibiotics. They include penicillins, cephalosporins, carbapenems, monobactams and beta-lactam inhibitors. The basic chemical structure of these drugs consist on the presence of the following components: betalactam ring, an adjacent ring and side chains, all of which are potential epitopes. IgE antibodies and T lymphocytes are often involved in recognizing those epitopes. Cross-reactivity depends on the stability of intermediate products (antigenic determinants) derived from the degradation of the beta-lactam ring, on the adjacent rings, and on the structural similarity of the side chains between drugs. Classically, it was believed that there was a great potential for cross-reactivity within each class and even between classes, but studies from the last decade showed that individuals allergic to penicillin (with positive skin tests) reacted to cephalosporins in approximately 3% of cases, to carbapenems in about 1%, and rarely reacted to monobactams. This reactivity or tolerance seems to be linked to the degree of similarity between the side chains of these antibiotics. In this review, we emphasize the importance of systematic investigation to confirm or exclude allergy to beta-lactams, we describe the prevalence of crossreactivity between these drugs and we suggest an algorithm for approaching these patients based on their chemical structure and on data published in the literature.
Assuntos
Humanos , Penicilinas , Monobactamas , Imunoglobulina E , Linfócitos T , Carbapenêmicos , Cefalosporinas , beta-Lactamas , Hipersensibilidade , Pacientes , Preparações Farmacêuticas , PrevalênciaRESUMO
A monocyclic ring in their structure characterizes monobactams, a subclass of ß-lactam antibiotics. Many of these compounds have a bactericidal mechanism of action and acts as penicillin and cephalosporins, interfering with bacterial cell wall biosynthesis. The synthesis of novel ß-lactams is an emerging area of organic synthesis research due to the problem of increasing bacterial resistance to existing ß -lactam antibiotics, and, in this way, new compounds have been presented with several structural modifications, aiming to improve biological activities. Among the biological activities studied, the most outstanding are antibacterial, antitubercular, anticholesterolemic, anticancer, antiinflammatory, antiviral, and anti-enzymatic, among others. This review explores the vast number of works related to monocyclic ß-lactams, compounds of great importance in scientific research.
Assuntos
Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antituberculosos/farmacologia , Monobactamas/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antituberculosos/síntese química , Antituberculosos/química , Estrutura Molecular , Monobactamas/síntese química , Monobactamas/químicaRESUMO
Three Klebsiella pneumoniae clinical isolates demonstrating carbapenem resistance were recovered from different patients hospitalized at two medical centers in São Paulo, Brazil. Resistance to all ß-lactams, quinolones, and some aminoglycosides was observed for these isolates that were susceptible to polymyxin B. Carbapenem hydrolysis, which was inhibited by clavulanic acid, was observed for all K. pneumoniae isolates that belonged to the same pulsed-field gel electrophoresis (PFGE) type and a novel sequence type (ST), ST1781 (clonal complex 442 [CC442]). A 10-kb nonconjugative incompatibility group Q (IncQ) plasmid, denominated p60136, was transferred to Escherichia coli strain TOP10 cells by electroporation. The full sequencing of p60136 showed that it was composed of a mobilization system, ISKpn23, the phosphotransferase aph3A-VI, and a 941-bp open reading frame (ORF) that codified a 313-amino acid protein. This ORF was named bla BKC-1. Brazilian Klebsiella carbapenemase-1 (BKC-1) showed a pI of 6.0 and possessed the highest identity (63%) with a ß-lactamase of Sinorhizobium meliloti, an environmental bacterium. Hydrolysis studies demonstrated that purified BKC-1 not only hydrolyzed carbapenems but also penicillins, cephalosporins, and monobactams. However, the carbapenems were less efficiently hydrolyzed due to their very low kcat values (0.0016 to 0.031 s(-1)). In fact, oxacillin was the best substrate for BKC-1 (kcat /Km , 53,522.6 mM(-1) s(-1)). Here, we report a new class A carbapenemase, confirming the diversity and rapid evolution of ß-lactamases in K. pneumoniae clinical isolates.
Assuntos
Proteínas de Bactérias/metabolismo , Klebsiella pneumoniae/enzimologia , beta-Lactamases/metabolismo , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Brasil , Carbapenêmicos/metabolismo , Carbapenêmicos/farmacologia , Cefalosporinas/metabolismo , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana , Eletroforese em Gel de Campo Pulsado , Testes de Sensibilidade Microbiana , Monobactamas/metabolismo , Monobactamas/farmacologia , Penicilinas/metabolismo , Penicilinas/farmacologia , Sinorhizobium meliloti/efeitos dos fármacos , Sinorhizobium meliloti/metabolismoRESUMO
A resistência bacteriana aos agentes antimicrobianos se tornou uma séria ameaça à saúde pública em todo o mundo, transformando-se em um problema crescente tanto nos ambientes hospitalares quanto na vida diária das comunidades. A busca de novas substâncias capazes de reduzir a atuação e a disseminação dessas bactérias resistentes se tornou um objetivo importante a ser alcançado, notadamente no que diz respeito aos bacilos Gram negativos produtores de enzima β-lactamase de espectro expandido (ESBL), principalmente no caso de Klebsiella e Escherichia coli, que apresentam uma crescente resistência aos agentes β-lactâmicos de amplo espectro. O ertapenem se apresenta hoje como uma das novas alternativas para o tratamento de infecções causadas por estas bactérias. Este trabalho tem como objetivo verificar a eficácia do tratamento antimicrobiano com o Ertapenem, nas infecções causadas por ESBL. Os resultados obtidos apontam para a comprovação de sua eficácia, visto que de 50 amostras testadas, de bacilos Gram negativos, comprovadamente ESBL, 48 se mostraram realmente eficientes, eliminando ou impedindo a proliferação de bactérias. Podemos concluir que o Ertapenem sódico realmente atua de forma eficaz no tratamento das infecções causadas por Bactérias comprovadamente produtoras de ESBL
Assuntos
Humanos , beta-Lactamases , Farmacorresistência Bacteriana , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas , MonobactamasRESUMO
Solid-phase organic synthesis (SPOS) has become an effective synthetic tool for the preparation of combinatorial libraries of non-oligomeric small molecules. Owing to their high efficacy and extremely safe toxicological profile, beta-lactam antibiotics are the first choice for bacterial infectious diseases. Moreover, beta-lactam compounds have also showed other biological activities that include inhibition of prostate specific antigen, thrombin, human cytomegalovirus protein, human leukocyte elastase and cholesterol absorption. Thus, the application of combinatorial and related methodologies to the chemistry of the beta-lactam ring has been recognized as a very attractive challenge by different research groups around the world. This review covers the solid-phase and combinatorial chemistry related to mono-and multicyclic beta-lactam compounds that has been reported in the literature from 1999 to 2004.
Assuntos
Técnicas de Química Combinatória/métodos , beta-Lactamas/síntese química , Azetidinas/síntese química , Azetidinas/química , Compostos Bicíclicos com Pontes/síntese química , Catálise , Ciclização , Iminas/química , Estrutura Molecular , Monobactamas/síntese química , Resinas Sintéticas/químicaRESUMO
INTRODUCTION: Expanded-spectrum betalactamases (ESBLs) are the main source of resistance to oxyimino cephalosporins and monobactams in Enterobacteriaceae. Most of them derive from TEM or SHV, however the incidence of other families like CTX-M, OXA and PER has increased. In Argentina, the most frequent ESBL in Enterobacteriaceae is CTX-M-2. This specific circumstance, which differs from the situation in the Northern Hemisphere, motivated us to study new diagnostic strategies for the detection of ESBLs in our region. METHOD: Microbiological ESBL detection was performed by double-disk synergy tests, cefotaxime and ceftazidime disks with and without clavulanic acid (NCCLS), and cefotaxime and ceftazidime disks in Müeller-Hinton agar supplemented with lithium clavulanate (MH-cla). Betalactamases were characterized by isoelectric focusing, hydrolysis profile and PCR amplification. RESULTS: Among 575 clinical isolates of Enterobacteriaceae, 14% were oxyimino cephalosporin-resistant. Two different ESBLs were detected in 31 resistant strains: CTX-M-2 (28) and PER-2 groups (3). The double-disk synergy test was the least sensitive method for ESBL detection. ESBLs were detected by the other two methods in all isolates with the use of cefotaxime disks, but not with ceftazidime disks. CONCLUSION: The microbiological method employing MH-cla with cefotaxime disks had a sensitivity and specificity comparable to the referral test using the same antibiotic proposed by the NCCLS for the detection of ESBLs.