RESUMO
OBJECTIVES: Cefiderocol maintains activity against most MDR Gram-negative pathogens including Pseudomonas aeruginosa. In laboratory-derived isolates, down-regulation of TonB-dependent siderophore receptors have been implicated in resistance to cefiderocol. METHODS: In this report, the expression of seven TonB-dependent siderophore receptors was examined in 10 clinical isolates with cefiderocol MICs ranging from ≤0.03-8â mg/L. In addition, genetic sequences of the siderophore receptors were analysed to identify potentially disruptive mutations. RESULTS: There was no clear association between expression of the receptors with cefiderocol susceptibility, including the receptors piuA/piuD and pirA previously implicated in cefiderocol uptake. In addition, there were no disabling mutations identified in the receptors. Acquired ß-lactamase activity also could not explain the range in cefiderocol susceptibility. CONCLUSIONS: The aetiology of reduced susceptibility to cefiderocol in clinical isolates of P. aeruginosa remains an enigma and worthy of further investigation.
Assuntos
Farmacorresistência Bacteriana Múltipla , Pseudomonas aeruginosa , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/genética , CefiderocolRESUMO
Delafloxacin is an option for infections due to methicillin-resistant Staphylococcus aureus. In 2017, 22% of isolates from 7 hospitals in Brooklyn, New York, were nonsusceptible to delafloxacin. Isolates belonging to ST105, a strain associated with healthcare-related infections, predominated. Resistance was also found in ST8, a strain (USA300) associated with community-associated infections.
Assuntos
Infecções Comunitárias Adquiridas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Fluoroquinolonas , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , New York/epidemiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureusRESUMO
Cefiderocol is a siderophore cephalosporin active against many multidrug-resistant (MDR) Gram-negative pathogens. We examined the resistance mechanisms in 12 Acinetobacter baumannii strains with cefiderocol MICs ranging from ≤0.03 to >32 µg/ml. Cefiderocol resistance could not be explained by ß-lactamase activity. Cefiderocol resistance was associated with reduced expression of the siderophore receptor gene pirA Mutations involving PBP3 may have contributed to resistance in one strain. Additional studies are needed to assess the role of other siderophore receptors.
Assuntos
Acinetobacter baumannii , Acinetobacter baumannii/genética , Antibacterianos/farmacologia , Proteínas da Membrana Bacteriana Externa , Cefalosporinas/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Bactérias Gram-Negativas , Proteínas de Ligação às Penicilinas/genética , Receptores de Superfície Celular , beta-Lactamases/genética , beta-Lactamases/farmacologia , CefiderocolRESUMO
WCK 4234 is a novel diazabicyclooctane with potent inhibitory activity against class A and D carbapenemases and class C enzymes. We examined the in vitro activity of meropenem plus WCK 4234 (4 or 8 µg/ml) against Gram-negative pathogens from New York City. Three groups of isolates were analyzed: a contemporary collection of isolates, a collection of known carbapenem-resistant isolates, and a collection of isolates with defined resistance mechanisms. From the contemporary collection, we found (i) that all Enterobacteriaceae were susceptible to meropenem plus WCK 4234, (ii) that susceptibility rates for Acinetobacter baumannii were 56.5% for meropenem alone, 82.6% with 4 µg/ml WCK 4234, and 95.7% with 8 µg/ml WCK 4234, and (iii) that WCK 4234 had a modest effect on susceptibility of Pseudomonas aeruginosa Against a collection of carbapenem-resistant isolates, the addition of WCK 4234 to meropenem (i) restored meropenem susceptibility against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates, (ii) improved susceptibility against A. baumannii, and (iii) had a negligible effect against P. aeruginosa When tested against isolates with defined mechanisms of resistance, MICs of meropenem plus WCK 4234 were higher for K. pneumoniae with blaKPC albeit well below the susceptibility breakpoint; efflux systems or porins did not correlate with susceptibility. For A. baumannii, MICs of meropenem plus WCK 4234 did not correlate with efflux systems, outer membrane protein, blaampC, or blaoxa-51; however, MICs were higher in isolates with extended-spectrum ß-lactamases (ESBLs). For P. aeruginosa, isolates with relatively higher MICs of meropenem plus WCK 4234 had increased expression of ampC WCK 4234 is a potent ß-lactamase inhibitor that, when combined with meropenem, displays promising activity against multidrug-resistant pathogens.
Assuntos
Compostos Azabicíclicos/farmacologia , Carbapenêmicos/farmacologia , Ciclo-Octanos/farmacologia , Meropeném/farmacologia , Proteínas de Bactérias/metabolismo , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/metabolismo , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , beta-Lactamases/metabolismoRESUMO
BACKGROUND: The combination of cefepime and zidebactam (WCK5222), a novel ß-lactam enhancer, has demonstrated activity against a wide variety of Gram-negative pathogens and is currently under clinical evaluation. OBJECTIVES: To examine the activity of cefepime/zidebactam against: (i) a contemporary collection of Gram-negative isolates from New York City; (ii) a collection of carbapenem-resistant clinical isolates; and (iii) a collection of isolates with characterized resistance mechanisms. METHODS: Susceptibility tests were performed using broth microdilution for cefepime, zidebactam and cefepime/zidebactam (1:1). RESULTS: More than 99% of a contemporary collection of Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. had cefepime/zidebactam MICs ≤2 mg/L, the susceptibility breakpoint for cefepime. For K. pneumoniae, the acquisition of blaKPC resulted in increased MICs, although MICs remained ≤2 mg/L for 90% of KPC-possessing isolates. Overall for Pseudomonas aeruginosa, 98% of isolates had MICs ≤8 mg/L and MICs were affected by increased expression of ampC. For carbapenem-resistant P. aeruginosa, 78% of isolates had cefepime/zidebactam MICs ≤8 mg/L. The activity of cefepime/zidebactam against Acinetobacter baumannii was lower, with 85% of all isolates and 34% of carbapenem-resistant isolates with MICs ≤8 mg/L (cefepime interpretative criteria). CONCLUSIONS: Cefepime/zidebactam demonstrated excellent activity against Enterobacteriaceae and P. aeruginosa, although activity was reduced in carbapenem-non-susceptible isolates. The activity against A. baumannii was reduced and studies examining the therapeutic efficacy in strains with high cefepime/zidebactam MICs are warranted.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Cefepima/farmacologia , Ciclo-Octanos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Piperidinas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/isolamento & purificação , Interações Medicamentosas , Doenças Endêmicas , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Instalações de Saúde , Humanos , Testes de Sensibilidade Microbiana , Cidade de Nova Iorque/epidemiologia , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificaçãoRESUMO
Objectives: Carbapenemase-producing Enterobacteriaceae are important nosocomial pathogens in many medical centres. Surveillance is needed to track trends and detect emergence of new carbapenemases. Methods: Single-patient isolates of Enterobacteriaceae were gathered from seven medical centres in New York City over a 3 month period in 2017. Susceptibility testing was performed and isolates were screened for selected carbapenemases. Additional isolates referred to our laboratory in 2018 were also tested. Results: KPC was found in 3/1911 (0.16%) isolates of Escherichia coli, 22/533 (4.1%) isolates of Klebsiella pneumoniae and 3/175 (1.7%) isolates of Enterobacter spp. Compared with prior surveillance studies performed over the past decade, there has been a persistent decline in the number of KPC-possessing K. pneumoniae. However, in 2018 two patients from the same skilled nursing facility admitted to two separate hospitals were found to harbour Enterobacteriaceae with NDM-5 and CTX-M-15. Conclusions: Since the height of the outbreak in 2006, there has been a decline in the number of KPC-possessing Enterobacteriaceae in New York City acute care medical centres. However continued vigilance is needed to detect the emergence of other carbapenemases.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , beta-Lactamases/genética , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/epidemiologia , Escherichia coli/enzimologia , Escherichia coli/genética , Hospitais/estatística & dados numéricos , Humanos , Testes de Sensibilidade Microbiana , Cidade de Nova Iorque/epidemiologiaRESUMO
Objectives: Options for treatment of infections due to KPC-producing Klebsiella pneumoniae are limited and combination therapy is often recommended. In this report, the in vitro and in vivo activity of potential therapeutic agents and combinations was assessed against four KPC-producing K. pneumoniae isolates. Methods: Using clinically relevant concentrations, time-kill experiments and the Galleria mellonella model of infection were used to examine the activity of polymyxin B, ceftazidime/avibactam, meropenem, rifampicin and amikacin alone and in combination. Results: Two K. pneumoniae isolates were resistant to polymyxin B and had ceftazidime/avibactam MICs of 8/4 mg/L. When ceftazidime/avibactam was combined with either amikacin or meropenem, synergy was observed in vitro, and these combinations were associated with improved survival in the in vivo model. Improved survival was also observed using higher doses of ceftazidime/avibactam. The other two K. pneumoniae isolates were susceptible to polymyxin B and had lower (1/4 mg/L) MICs of ceftazidime/avibactam. For these two isolates, bactericidal activity was observed in vitro at ceftazidime/avibactam concentrations four times the MIC. At one-quarter of the MIC, synergy was observed when ceftazidime/avibactam was combined with meropenem. In the in vivo model with the two susceptible isolates, improved survival rates were observed following therapy with ceftazidime/avibactam monotherapy. For all four isolates, polymyxin B with or without rifampicin or meropenem performed poorly in the in vivo model. Conclusions: Pending clinical studies, combining ceftazidime/avibactam with another agent (e.g. a carbapenem) should be considered when treating serious infections due to these pathogens, particularly for isolates with ceftazidime/avibactam MICs near the susceptibility breakpoint.
Assuntos
Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , beta-Lactamases/metabolismo , Animais , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Lepidópteros , Testes de Sensibilidade Microbiana , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: The study objective was to examine the epidemiological trends of KPC-producing Klebsiella pneumoniae in New York City medical centres. PATIENTS AND METHODS: Single patient isolates of K. pneumoniae were collected from nine medical centres in New York City during a 3 month period from 2013 to 2014. Isolates were tested for the presence of blaKPC. Results were compared with similar surveillance studies conducted in 2006 and 2009. Infection control data, including utilization of medical devices, were analysed at a subset of hospitals. RESULTS: There was a progressive decline in the percentage of K. pneumoniae harbouring blaKPC from 2006 to 2013-14. For the nine hospitals that participated in all three surveillance studies, the percentages of isolates with blaKPC fell from 36% in 2006 to 25% in 2009 to 13% in 2013-14. Seven of the nine hospitals had marked declines in isolates with blaKPC, while two hospitals continued to struggle with this pathogen. These two hospitals were smaller and had longer lengths of patient stay. Device utilization rates were obtained from two hospitals that successfully controlled the spread of KPC-producing K. pneumoniae; both had â¼20%-25% reduction in the usage of urinary catheters. Changes in antibiotic usage at one hospital could not explain the decline in these pathogens. CONCLUSIONS: Over the past decade there has been a steady decline in KPC-producing K. pneumoniae in most New York City hospitals. The reason for the decline is probably multifactorial, involving a reduction in device (catheter) utilization and possibly an improvement in infection control practices.
Assuntos
Infecção Hospitalar/epidemiologia , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Catéteres , Infecção Hospitalar/microbiologia , DNA Bacteriano/genética , Surtos de Doenças/estatística & dados numéricos , Hospitais , Humanos , Controle de Infecções/métodos , Klebsiella pneumoniae/isolamento & purificação , Testes de Sensibilidade Microbiana , Cidade de Nova Iorque/epidemiologia , Inquéritos e Questionários , beta-Lactamases/biossínteseRESUMO
Eravacycline demonstrated in vitro activity against a contemporary collection of more than 4,000 Gram-negative pathogens from New York City hospitals, with MIC50/MIC90 values, respectively, for Escherichia coli of 0.12/0.5 µg/ml, Klebsiella pneumoniae of 0.25/1 µg/ml, Enterobacter aerogenes of 0.25/1 µg/ml, Enterobacter cloacae 0.5/1 µg/ml, and Acinetobacter baumannii of 0.5/1 µg/ml. Activity was retained against multidrug-resistant isolates, including those expressing KPC and OXA carbapenemases. For A. baumannii, eravacycline MICs correlated with increased expression of the adeB gene.
Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Tetraciclinas/uso terapêutico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/isolamento & purificação , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Hospitais , Humanos , Testes de Sensibilidade Microbiana/métodos , Cidade de Nova IorqueRESUMO
Imipenem with relebactam was active against Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp., including K. pneumoniae carbapenemase (KPC)-producing isolates. Loss of OmpK36 in KPC-producing K. pneumoniae isolates affected the susceptibility of this combination. Enhanced activity was evident against Pseudomonas aeruginosa, including isolates with depressed oprD and increased ampC expression. However, the addition of relebactam to imipenem did not provide added benefit against Acinetobacter baumannii. The combination of imipenem with relebactam demonstrated activity against KPC-producing Enterobacteriaceae and multidrug-resistant P. aeruginosa.
Assuntos
Acinetobacter baumannii/genética , Compostos Azabicíclicos/farmacologia , Enterobacteriaceae/genética , Imipenem/farmacologia , Pseudomonas aeruginosa/genética , Inibidores de beta-Lactamases/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Farmacorresistência Bacteriana Múltipla/genética , Quimioterapia Combinada , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Cidade de Nova Iorque , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , beta-LactamasesRESUMO
Multidrug-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are endemic to hospitals in New York City and other regions. RPX7009 is a novel ß-lactamase inhibitor with activity against serine carbapenemases. We tested the activity of meropenem plus RPX7009 against 4,500 recent Gram-negative clinical isolates from 11 New York City hospitals. The meropenem-RPX7009 combination was found to have excellent in vitro activity against Escherichia coli, K. pneumoniae, and Enterobacter spp., including multidrug-resistant (MDR) KPC-producing strains. Overall, 131/133 (98.5%) KPC-producing Enterobacteriaceae strains were inhibited by meropenem (≤1 µg/ml) plus RPX7009 (8 µg/ml). In a limited number of strains, the combination appeared to have reduced activity against KPC-producing K. pneumoniae isolates with diminished ompK35 and ompK36 expression. The addition of RPX7009 did not affect the activity of meropenem against Acinetobacter baumannii and Pseudomonas aeruginosa. The meropenem-RPX7009 combination shows promise as a novel agent against KPC-producing Enterobacteriaceae and deserves further study. Other approaches will be needed to address multidrug-resistant A. baumannii and P. aeruginosa, which typically possess different mechanisms of carbapenem resistance.
Assuntos
Antibacterianos/farmacologia , Ácidos Borônicos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Compostos Heterocíclicos com 1 Anel/farmacologia , Tienamicinas/farmacologia , Inibidores de beta-Lactamases/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Quimioterapia Combinada/métodos , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Hospitais , Humanos , Meropeném , Testes de Sensibilidade Microbiana/métodos , Cidade de Nova IorqueRESUMO
Carbapenem-resistant Enterobacter species are emerging nosocomial pathogens. As with most multidrug-resistant Gram-negative pathogens, the polymyxins are often the only therapeutic option. In this study involving clinical isolates of E. cloacae and E. aerogenes, susceptibility testing methods with polymyxin B were analyzed. All isolates underwent testing by the broth microdilution (in duplicate) and agar dilution (in duplicate) methods, and select isolates were examined by the Etest method. Selected isolates were also examined for heteroresistance by population analysis profiling. Using a susceptibility breakpoint of ≤2 µg/ml, categorical agreement by all four dilution tests (two broth microdilution and two agar dilution) was achieved in only 76/114 (67%) of E. cloacae isolates (65 susceptible, 11 resistant). Thirty-eight (33%) had either conflicting or uninterpretable results (multiple skip wells, i.e., wells that exhibit no growth although growth does occur at higher concentrations). Of the 11 consistently resistant isolates, five had susceptible MICs as determined by Etest. Heteroresistant subpopulations were detected in eight of eight isolates tested, with greater percentages in isolates with uninterpretable MICs. For E. aerogenes, categorical agreement between the four dilution tests was obtained in 48/56 (86%), with conflicting and/or uninterpretable results in 8/56 (14%). For polymyxin susceptibility testing of Enterobacter species, close attention must be paid to the presence of multiple skip wells, leading to uninterpretable results. Susceptibility also should not be assumed based on the results of a single test. Until the clinical relevance of skip wells is defined, interpretation of polymyxin susceptibility tests for Enterobacter species should be undertaken with extreme caution.
Assuntos
Antibacterianos/farmacologia , Enterobacter aerogenes/efeitos dos fármacos , Enterobacter cloacae/efeitos dos fármacos , Polimixina B/farmacologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are endemic in many medical centres. Because therapeutic options are limited, understanding the epidemiology and controlling the spread of these pathogens are of paramount importance. METHODS: Isolates of K. pneumoniae, A. baumannii and P. aeruginosa were collected from 14 hospitals in New York City over a 3 month period in 2009, and analysed for the presence of genes encoding important carbapenemases. Comparisons were made with a similar study conducted in 2006. Demographic and infection control-related information from hospitals was collected. RESULTS: Overall, 29% of K. pneumoniae possessed the carbapenemase KPC, significantly improved from the 38% observed in 2006 (P < 0.001). However, carbapenem resistance worsened in A. baumannii (mostly due to the emergence of strains with OXA-type carbapenemases) and P. aeruginosa. The decline in KPC-possessing K. pneumoniae was not uniformly observed in all of the hospitals. In a subset analysis of nine hospitals, those with a decreasing prevalence of bla(KPC) had shorter average lengths of stay. CONCLUSIONS: Measurable improvement has occurred in reducing the spread of KPC-possessing K. pneumoniae, and reducing the average length of stay may augment infection control efforts. However, the problem of carbapenem-resistant A. baumannii and P. aeruginosa lingers. New approaches, including respiratory isolation and environmental cleaning, need to be examined to control the spread of A. baumannii and P. aeruginosa.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Infecções por Bactérias Gram-Negativas/transmissão , Klebsiella pneumoniae/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Resistência beta-Lactâmica , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/isolamento & purificação , Proteínas de Bactérias/metabolismo , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/transmissão , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Hospitais , Humanos , Controle de Infecções/métodos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Tempo de Internação/estatística & dados numéricos , Cidade de Nova Iorque/epidemiologia , Prevalência , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/isolamento & purificação , beta-Lactamases/metabolismoRESUMO
Infections due to extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales are an increasingly common problem. For many of these infections, no oral treatment options are available. The activity of amoxicillin-clavulanate combined with ceftibuten or cefpodoxime was evaluated against a group of Escherichia coli and Klebsiella pneumoniae clinical isolates possessing a variety of CTX-M- and SHV-type ESBLs; some possessed blaTEM1 as well. In time-kill studies, the combination of subinhibitory concentrations of amoxicillin-clavulanate with ceftibuten was bactericidal and synergistic for all strains with an amoxicillin-clavulanate MIC ≤32 µg/mL, regardless of the type of ESBL and the cephalosporin minimal inhibitory concentration (MIC). The combination with cefpodoxime was also bactericidal and synergistic against all but one of these strains. These combinations were further tested against two strains of K. pneumoniae and one E. coli in a sepsis model using Galleria mellonella larvae. The combination of amoxicillin-clavulanate with ceftibuten demonstrated a synergistic survival benefit against all three strains. The combination with cefpodoxime also improved survival against the two K. pneumoniae strains, but not the E. coli strain. These findings support combining amoxicillin-clavulanate with ceftibuten, and possibly cefpodoxime, for the treatment of infections due to ESBL producers and suggest that having an amoxicillin-clavulanate MIC of 32 µg/mL or less may predict activity at clinically achievable concentrations. Clinical studies are warranted to further evaluate this therapeutic approach.
Assuntos
Escherichia coli , Klebsiella pneumoniae , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/farmacologia , Ceftibuteno , Ceftizoxima/análogos & derivados , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , CefpodoximaRESUMO
Using the updated 2010 CLSI carbapenem breakpoints for the Enterobacteriaceae, nonsusceptibility to ertapenem and imipenem predicted the presence of bla(KPC) poorly, especially among Escherichia coli and Enterobacter species. In regions where KPC-producing bacteria are endemic, testing for nonsusceptibility to meropenem may provide improved accuracy in identifying these isolates.
Assuntos
Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , beta-Lactamases/metabolismo , Humanos , Testes de Sensibilidade Microbiana/métodos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa have become a global problem, often leaving the polymyxins as therapeutic agents of last resort. ACHN-490, a next-generation aminoglycoside with activity against a broad range of Gram-positive and Gram-negative pathogens, was examined against clinical isolates of A. baumannii and P. aeruginosa. METHODS: The activity of aminoglycosides and ACHN-490 was determined against a contemporary collection of A. baumannii and P. aeruginosa. Selected aminoglycoside-resistant isolates were screened for the presence of genes encoding common aminoglycoside-modifying enzymes and methylases. RESULTS: Resistance to the traditional aminoglycosides was common in the collection of A. baumannii. ACHN-490 possessed superior activity against these isolates, with an MIC(50) value of 8 mg/L. In P. aeruginosa, the activity of ACHN-490 was similar to that of amikacin (MIC(50) value of 8 mg/L for both agents). For both A. baumannii and P. aeruginosa, the MICs of ACHN-490 did not correlate with the presence of commonly encountered aminoglycoside-modifying enzymes. CONCLUSIONS: For A. baumannii, the MICs of ACHN-490 were lower than those of traditional aminoglycosides. For P. aeruginosa, the activity of ACHN-490 was similar to that of amikacin.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Sisomicina/análogos & derivados , Acinetobacter baumannii/enzimologia , Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana , Cidade de Nova Iorque , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Sisomicina/farmacologiaRESUMO
Antibiotic-resistant Enterobacteriaceae and Acinetobacter baumannii are problematic pathogens, with few treatment options for multidrug-resistant (MDR)-A. baumannii and few oral options for extended spectrum ß-lactamase (ESBL)-producing and MDR-Enterobacteriaceae. Omadacycline, a newer tetracycline derivative, has activity against some of these pathogens. We tested the in vitro activity of omadacycline against a contemporary collection of over 2,600 consecutive unique clinical isolates of Enterobacteriaceae and A. baumannii, a previous collection of carbapenem-resistant Klebsiella pneumoniae and A. baumannii from a surveillance study in 2013-2014, and a group of K. pneumoniae and A. baumannii isolates with previously defined resistance mechanisms. For the contemporary collection, over 96% of Escherichia coli and 70% of K. pneumoniae isolates were inhibited by omadacycline at ≤4 µg/mL including 95% of E. coli and 49% of K. pneumoniae with presumptive ESBLs. Nearly 90% of A. baumannii were inhibited by omadacycline at ≤4 µg/mL. The omadacycline MIC50/90 was 1/4 µg/mL, 4/>8 µg/mL, and 0.5/8 for E. coli, K. pneumoniae, and A. baumannii, respectively. For the carbapenem-resistant collection of isolates, 56% of A. baumannii were inhibited by omadacycline at ≤4 µg/mL, but only 30% of Klebsiella pneumoniae carbapenemase (KPC)-possessing K. pneumoniae were susceptible. Expression of the efflux gene adeB appeared to affect the activity of omadacycline against A. baumannii, but could not fully explain resistance to this agent. Omadacycline may prove to be a parenteral or oral option for some infections due to ESBL-producing Enterobacteriaceae and carbapenem-resistant A. baumannii, and clinical studies are warranted.
Assuntos
Infecção Hospitalar/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Tetraciclinas/farmacologia , Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Hospitais Urbanos , Humanos , Testes de Sensibilidade Microbiana/métodos , Cidade de Nova IorqueRESUMO
BACKGROUND: Central-line bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) negatively impact clinical outcomes and hospital reimbursement. In this report, 4 year trends involving 11 hospitals in New York City were examined. METHODS: Data from the National Healthcare Safety Network (NHSN) were extracted for 11 acute-care hospitals belonging to the NYC Health + Hospital system from 2016 through 2019. Trends in device infections per 1,000 patient days, device utilization ratios, and standardized infection ratios (SIRs) were examined for the 11 hospitals and for the entire system. RESULTS: Over the 4-year period, there were progressive declines in central-line days, infections per 1,000 central-line days, and device utilization ratios for the system. The average annual SIRs for the system also declined: 1.40 in 2016, 1.09 in 2017, 1.04 in 2018, and 0.82 in 2019. Case-mix indices correlated with SIRs for CLABSIs. Level 1 trauma centers had higher SIRs and a disproportionately greater number of CLABSIs in patients located in NHSN-defined surgical intensive care units. Similar trends with CAUTIs were noted, with progressive declines in catheter days, infections per 1,000 patient days, device utilization ratios, and SIRs (1.42 in 2016, 0.93 in 2017, 1.18 in 2018, and 0.78 in 2019) over the 4-year period. CONCLUSIONS: Across an 11-hospital system, continuing efforts to reduce device utilization and infection rates resulted in declining SIRs for CLABSIs and CAUTIs. Hospitals with higher case-mix indices, and particularly level 1 trauma centers, had significantly higher central-line infection rates and SIRs.
Assuntos
Infecções Relacionadas a Cateter , Cateteres Venosos Centrais , Infecção Hospitalar , Pneumonia Associada à Ventilação Mecânica , Sepse , Infecções Urinárias , Infecções Relacionadas a Cateter/epidemiologia , Infecção Hospitalar/epidemiologia , Hospitais , Humanos , Unidades de Terapia Intensiva , Cidade de Nova Iorque/epidemiologia , Sepse/epidemiologia , Sepse/etiologia , Infecções Urinárias/epidemiologiaRESUMO
BACKGROUND: Healthcare facility-onset Clostridioides difficile infection is associated with adverse clinical outcomes and hospital reimbursement. A four-year review involving eleven hospitals of the NYC Healthâ¯+â¯Hospital system was undertaken. METHODS: From 2016-2019, infection rates and standardized infection ratios (SIRs) were gathered from National Healthcare Safety Network. The C. difficile testing scheme at each facility was recorded. RESULTS: For the eleven hospitals, declines in rates of C. difficile infection and SIRs were documented. However, this decline was driven by two hospitals that had high rates of infection in 2016; for the remaining nine hospitals, rates of infection and SIRs were at a plateau. Most hospitals used a testing scheme that fell into the nucleic acid amplification test (NAAT) category for SIR risk adjustment. Hospitals that used the algorithm glutamate dehydrogenase (GDH) and toxin A/B immunoassay (EIA) followed by NAAT for discrepant results had significantly lower rates of C. difficile infection but similar SIRs. CONCLUSIONS: For most hospitals in this system, rates of C. difficile remained level. Within the NAAT test categories, SIRs may not correlate with infection rates. Given the controversies regarding testing and calculation of SIRs, alternatives to C. difficile infection should be sought as a hospital quality measurement.
Assuntos
Toxinas Bacterianas , Clostridioides difficile , Infecções por Clostridium , Clostridioides , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Atenção à Saúde , Hospitais , Humanos , Cidade de Nova Iorque/epidemiologiaRESUMO
The detection of Enterobacteriaceae carrying the carbapenemase KPC has been problematic. Thirty isolates of KPC-possessing Escherichia coli were gathered from hospitals in New York City and Connecticut. The imipenem, meropenem, doripenem, and ertapenem MIC50 values were 4, 2, 1, and 4 µg/ml, respectively. Over half of the isolates belonged to a single ribotype. Using an ertapenem breakpoint of 0.25 µg/ml would efficiently detect these isolates.