RESUMO
Resistance to Ceftazidime-Avibactam in Enterobacter cloacae is poorly understood. Whole genome sequencing identified 6 variants in isolates collected from a patient before and after acquiring Ceftazidime-Avibactam resistance. This included a Phe396Leu mutation in acrB, a component of the AcrAB-TolC efflux pump, possibly mediating enhanced efflux of Ceftazidime and/ or Avibactam.
Assuntos
Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Enterobacter cloacae/genética , Infecções por Enterobacteriaceae/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/farmacologia , Proteínas de Bactérias/genética , Ceftazidima/farmacologia , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Genoma Bacteriano/genética , Genômica , Humanos , Masculino , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , MutaçãoRESUMO
Clinical justification for rapid antimicrobial susceptibility testing (AST) in Gram-negative rod (GNR) bacteremia is compelling; however, evidence supporting its value is sparse. We investigated the impact of rapid AST on clinical and antimicrobial stewardship outcomes in real-world practice. We performed a before-and-after quasi-experimental study from February 2018 to July 2019 at a tertiary hospital of the 24-h/day, 7-day/week implementation of the direct Vitek 2 AST method from positive blood culture broth for GNR bacteremia with electronic isolate-specific de-escalation comments and daytime antibiotic stewardship program (ASP) intervention. The primary outcome was time to appropriate antibiotic escalation or de-escalation, and secondary outcomes included time to oral antibiotic stepdown, hospital length of stay (LOS), all-cause 30-day mortality, 7-day incidence of acute kidney injury (AKI), and 30-day incidence of Clostridioides difficile infection (CDI). A total of 671 GNR isolates were included from 643 adult patients. Among patients for whom antibiotic change occurred after rapid AST result, rapid AST was associated with a trend in decreased time to escalation or de-escalation (hazard ratio, 1.22; 95% confidence interval [CI], 0.99 to 1.51; P = 0.06), with median times of 52.3 versus 42.2 h. Secondary outcomes were similar in both groups and include median time to oral antibiotic stepdown, LOS, all-cause mortality, and incidence of AKI and CDI. Rapid AST led to improved stewardship measures but did not impact clinical patient outcomes. These results highlight that multiple variables in addition to the timing of the AST result contribute to clinical outcome and that further intervention may be required to clinically justify rapid AST implementation.
Assuntos
Gestão de Antimicrobianos , Bacteriemia , Infecções por Bactérias Gram-Negativas , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bactérias Gram-Negativas , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Tempo de InternaçãoRESUMO
The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) blaOXA-48 like, 20.8% (5/24) blaKPC, 20.8% (5/24) blaNDM, 20.8% (5/24) blaSME, 8.3% (2/24) blaIMP, and 4.2% (1/24) blaVIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing blaKPC were 100% susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam; blaOXA-48 like-positive isolates were 100% susceptible to ceftazidime-avibactam; and metallo ß-lactamase-positive isolates were nearly all nonsusceptible to above antibiotics. Carbapenemase gene-negative CRE were 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) susceptible to ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and ceftolozane-tazobactam, respectively. None of the CRE strains were identical by whole genome sequencing. At this health system, CRE were mediated by diverse mechanisms with predictable susceptibility to newer ß-lactamase inhibitors.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Infecções por Enterobacteriaceae/microbiologia , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Bactérias/metabolismo , California/epidemiologia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Enterobacteriáceas Resistentes a Carbapenêmicos/metabolismo , Criança , Pré-Escolar , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Expressão Gênica , Variação Genética , Genoma Bacteriano/genética , Genótipo , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular , Fenótipo , Porinas/deficiência , Porinas/genética , Adulto Jovem , beta-Lactamases/deficiência , beta-Lactamases/metabolismoRESUMO
We report the second pediatric case of New Delhi metallo-ß-lactamase-1-producing Enterobacteriaceae in the United States. Laboratory methods included various phenotypic antimicrobial susceptibility testing assays, as well as polymerase chain reaction assays for carbapenemase-encoding genes. Laboratory challenges and the limited number of effective antimicrobial agents and the lack of pediatric-specific safety and efficacy data for these drugs are discussed.
Assuntos
Antibacterianos/uso terapêutico , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/enzimologia , beta-Lactamases/biossíntese , Antibacterianos/farmacologia , Criança , Enterobacteriaceae/classificação , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Minociclina/análogos & derivados , Minociclina/farmacologia , Minociclina/uso terapêutico , Tigeciclina , Estados Unidos , Resistência beta-LactâmicaRESUMO
The emergence and spread of carbapenem-resistant Enterobacteriaceae (CRE) producing acquired carbapenemases have created a global public health crisis. In the United States, CRE producing the Klebsiella pneumoniae carbapenemase (KPC) are increasingly common and are endemic in some regions. Metallo-ß-lactamase (MBL)-producing CRE have recently been reported in the United States among patients who received medical care in countries where such organisms are common. Here, we describe three carbapenem-resistant K. pneumoniae isolates recovered from pediatric patients at a single U.S. health care facility, none of whom had a history of international travel. The isolates were resistant to carbapenems but susceptible to aztreonam, trimethoprim-sulfamethoxazole, and fluoroquinolones. The three isolates were closely related to each other by pulsed-field gel electrophoresis and contained a common plasmid. PCR and sequence analysis confirmed that these isolates produce IMP-4, an MBL carbapenemase not previously published as present among Enterobacteriaceae in the United States.