RESUMO
Bordetella pertussis is a Gram-negative bacterium that causes respiratory infections in humans. Ongoing molecular surveillance of B. pertussis acellular vaccine (aP) antigens is critical for understanding the interaction between evolutionary pressures, disease pathogenesis, and vaccine effectiveness. Methods currently used to characterize aP components are relatively labor-intensive and low throughput. To address this challenge, we sought to derive aP antigen genotypes from minimally processed short-read whole-genome sequencing data generated from 40 clinical B. pertussis isolates and analyzed using the SRST2 bioinformatic package. SRST2 was able to identify aP antigen genotypes for all antigens with the exception of pertactin, possibly due to low read coverage in GC-rich low-complexity regions of variation. Two main genotypes were observed in addition to a singular third genotype that contained an 84-bp deletion that was identified by SRST2 despite the issues in allele calling. This method has the potential to generate large pools of B. pertussis molecular data that can be linked to clinical and epidemiological information to facilitate research of vaccine effectiveness and disease severity in the context of emerging vaccine antigen-deficient strains.
Assuntos
Bordetella pertussis/genética , Bordetella pertussis/imunologia , Monitoramento Epidemiológico , Genoma Bacteriano/genética , Vacina contra Coqueluche/imunologia , Coqueluche/epidemiologia , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Sequência de Bases , Bordetella pertussis/isolamento & purificação , Criança , Pré-Escolar , DNA Bacteriano/genética , Humanos , Lactente , Ontário , Análise de Sequência de DNA , Coqueluche/microbiologia , Coqueluche/patologiaRESUMO
Delafloxacin, an investigational anionic fluoroquinolone, is active against a broad range of Gram-positive and Gram-negative bacteria. In this study, 200 Streptococcus pneumoniae (plus 30 levofloxacin-resistant isolates), 200 Haemophilus influenzae, and 100 Moraxella catarrhalis isolates selected primarily from the United States (2014) were tested against delafloxacin and comparator agents. Delafloxacin was the most potent agent tested. MIC50 and MIC90 values against all S. pneumoniae isolates were 0.008 and 0.015 µg/ml. Delafloxacin susceptibility was not affected by ß-lactamase status against H. influenzae and M. catarrhalis.
Assuntos
Antibacterianos/farmacologia , Fluoroquinolonas/farmacologia , Haemophilus influenzae/efeitos dos fármacos , Moraxella catarrhalis/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Haemophilus influenzae/isolamento & purificação , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Moraxella catarrhalis/isolamento & purificação , Streptococcus pneumoniae/isolamento & purificação , Estados UnidosRESUMO
The in vitro activities of ceftolozane-tazobactam, meropenem, and metronidazole were determined against anaerobic organisms isolated from patients with complicated intraabdominal infections (cIAI) in global phase III studies. Ceftolozane-tazobactam activity was highly variable among different species of the Bacteroides fragilis group, with MIC90 values ranging from 2 to 64 µg/ml. More-potent in vitro activity was observed against selected Gram-positive anaerobic organisms; however, small numbers of isolates were available, and, therefore, the clinical significance of these results is unknown. Variable activity of ceftolozane-tazobactam against anaerobic organisms necessitates use in combination with metronidazole for the treatment of cIAI.
Assuntos
Antibacterianos/uso terapêutico , Infecções por Bacteroides/tratamento farmacológico , Cefalosporinas/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções Intra-Abdominais/tratamento farmacológico , Metronidazol/uso terapêutico , Ácido Penicilânico/análogos & derivados , Anaerobiose , Bacteroides/efeitos dos fármacos , Bacteroides/isolamento & purificação , Infecções por Bacteroides/microbiologia , Bacteroides fragilis/efeitos dos fármacos , Bacteroides fragilis/isolamento & purificação , Quimioterapia Combinada/métodos , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Infecções Intra-Abdominais/microbiologia , Testes de Sensibilidade Microbiana , Ácido Penicilânico/uso terapêutico , TazobactamRESUMO
Fusidic acid (FA) activity was evaluated against 2,002 clinical staphylococcal isolates collected in U.S. hospitals during 2014. FA (MIC50/90, 0.12/0.12 µg/ml) inhibited 99.8% of Staphylococcus aureus isolates at ≤1 µg/ml. Only four S. aureus isolates displayed FA values of >2 µg/ml (three strains with fusC and one with an L461K substitution in fusA), and they were isolated from patients in four states. In conclusion, FA demonstrated sustained, potent activity against this recent collection of U.S. staphylococci.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana/genética , Ácido Fusídico/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Monitoramento Epidemiológico , Expressão Gênica , Hospitais , Humanos , Testes de Sensibilidade Microbiana , Mutação , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/isolamento & purificação , Estados Unidos/epidemiologiaRESUMO
Solithromycin, a fourth-generation macrolide (a fluoroketolide with enhanced activity against macrolide-resistant bacteria due to interaction with three ribosomal sites) and the first fluoroketolide, was tested against a 2014 collection of 6,115 isolates, including Streptococcus pneumoniae (1,713 isolates), Haemophilus influenzae (1,308), Moraxella catarrhalis (577), Staphylococcus aureus (1,024), and beta-hemolytic streptococci (1,493), by reference broth microdilution methods. The geographic samples included 2,748 isolates from the United States, 2,536 from Europe, 386 from Latin America, and 445 from the Asia-Pacific region. Solithromycin was observed to be very active against S. pneumoniae (MIC50/90, 0.008/0.12 µg/ml), demonstrating 2-fold greater activity than telithromycin (MIC50/90, 0.015/0.25 µg/ml) and 16- to >256-fold greater activity than azithromycin (MIC50/90, 0.12/>32 µg/ml), with all strains being inhibited at a solithromycin MIC of ≤1 µg/ml. Against H. influenzae, solithromycin showed potency identical to that of telithromycin (MIC50/90, 1/2 µg/ml), and both of these compounds were 2-fold less active than azithromycin (MIC50/90, 0.5/1 µg/ml). All but one of the M. catarrhalis isolates were inhibited by solithromycin at ≤0.25 µg/ml. Solithromycin inhibited 85.3% of S. aureus isolates at ≤1 µg/ml, and its activity was lower against methicillin-resistant (MIC50/90, 0.06/>32 µg/ml) than against methicillin-susceptible (MIC50/90, 0.06/0.06 µg/ml) isolates. Little variation in solithromycin activity was observed by geographic region for the species tested. Solithromycin was very active against beta-hemolytic streptococci (MIC50/90, 0.015/0.03 µg/ml), and all isolates were inhibited at MIC values of ≤0.5 µg/ml. In conclusion, solithromycin demonstrated potent activity against global and contemporary (2014) pathogens that represent the major causes of community-acquired bacterial pneumonia. These data support the continued clinical development of solithromycin for the treatment of this important indication.
Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Monitoramento Epidemiológico , Macrolídeos/farmacologia , Triazóis/farmacologia , Ásia/epidemiologia , Azitromicina/farmacologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Europa (Continente)/epidemiologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/crescimento & desenvolvimento , Haemophilus influenzae/isolamento & purificação , Humanos , Cooperação Internacional , Cetolídeos/farmacologia , América Latina/epidemiologia , Testes de Sensibilidade Microbiana , Moraxella catarrhalis/efeitos dos fármacos , Moraxella catarrhalis/crescimento & desenvolvimento , Moraxella catarrhalis/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/isolamento & purificação , Streptococcus/efeitos dos fármacos , Streptococcus/crescimento & desenvolvimento , Streptococcus/isolamento & purificação , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/crescimento & desenvolvimento , Streptococcus pneumoniae/isolamento & purificação , Estados Unidos/epidemiologiaRESUMO
Tedizolid and linezolid in vitro activities against 3,032 Gram-positive pathogens collected in Asia-Pacific, Eastern European, and Latin American medical centers during 2014 were assessed. The isolates were tested for susceptibility by the current reference broth microdilution methods. Due to concern over the effect of MIC endpoint criteria on the results of testing the oxazolidinones tedizolid and linezolid, MIC endpoint values were read by two methods: (i) reading the MIC at the first well where the trailing began without regard for pinpoint trailing, according to CLSI M07-A10 and M100-S26 document instructions for reading linezolid (i.e., 80% inhibition of growth; these reads were designated tedizolid 80 and linezolid 80), and (ii) at 100% inhibition of growth (designated tedizolid 100 and linezolid 100). All Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus faecalis isolates were inhibited at tedizolid 80 and 100 MIC values of 0.25 and 0.5, 0.25 and 0.25, 0.25 and 0.5, 0.12 and 0.25, and 0.5 and 1 µg/ml, respectively. Generally, MIC50 and MIC90 results for tedizolid 80 and linezolid 80 were one doubling dilution lower than those read at 100% inhibition. Tedizolid was 4- to 8-fold more potent than linezolid against all the isolates tested regardless of the MIC endpoint criterion used. Despite the differences in potency, >99.9% of isolates tested in this survey were susceptible to both linezolid and tedizolid using CLSI and EUCAST interpretive criteria. In conclusion, tedizolid demonstrated greater in vitro potency than linezolid against Gram-positive pathogens isolated from patients in medical centers across the Asia-Pacific region, Eastern Europe, and Latin America.
Assuntos
Antibacterianos/farmacologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Linezolida/farmacologia , Organofosfatos/farmacologia , Oxazóis/farmacologia , Ásia/epidemiologia , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/crescimento & desenvolvimento , Europa Oriental/epidemiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , América Latina/epidemiologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/crescimento & desenvolvimento , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/crescimento & desenvolvimentoRESUMO
We evaluated the antimicrobial susceptibility of 1,454 organisms consecutively collected from patients with bacteremia associated with skin and skin structure infections. The most common organisms obtained wereStaphylococcus aureus(670 organisms [46.1%]),Escherichia coli(200 organisms [13.8%]), ß-hemolytic streptococci (ßHS) (138 organisms [9.5%]), andKlebsiella pneumoniae(109 organisms [7.5%]). The susceptibility rates for ceftaroline were 97.9% forS. aureus(95.9% among methicillin-resistantS. aureus[MRSA]), 100.0% for ßHS, 86.5% forE. coli, and 89.0% forK. pneumoniae Ceftaroline and tigecycline provided the best overall coverage.
Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Streptococcus/efeitos dos fármacos , Centros Médicos Acadêmicos , Infecções Comunitárias Adquiridas , Escherichia coli/crescimento & desenvolvimento , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Minociclina/análogos & derivados , Minociclina/farmacologia , Pele/efeitos dos fármacos , Pele/microbiologia , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus/crescimento & desenvolvimento , Tigeciclina , Estados Unidos/epidemiologia , CeftarolinaRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Resistência beta-Lactâmica/fisiologia , Centros Médicos Acadêmicos , Censos , Combinação de Medicamentos , Humanos , Meropeném , Testes de Sensibilidade Microbiana , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Piperacilina/farmacologia , Combinação Piperacilina e Tazobactam , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Pseudomonas aeruginosa/isolamento & purificação , Vigilância em Saúde Pública , Tienamicinas/farmacologia , Estados UnidosRESUMO
Oritavancin (MIC50/90, 0.03/0.06 to 0.12 µg/ml) had potent activity against linezolid-resistant staphylococci, as well as Enterococcus faecalis and Enterococcus faecium (oritavancin MIC50/90, 0.015/0.12 µg/ml against both species). All linezolid-resistant isolates were inhibited by oritavancin at ≤0.12 µg/ml. These results confirmed the absence of cross-resistance between linezolid and oritavancin in staphylococci and enterococci.
Assuntos
Antibacterianos/farmacologia , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Glicopeptídeos/farmacologia , Linezolida/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Farmacorresistência Bacteriana , Enterococcus faecalis/crescimento & desenvolvimento , Enterococcus faecalis/isolamento & purificação , Enterococcus faecium/crescimento & desenvolvimento , Enterococcus faecium/isolamento & purificação , Humanos , Lipoglicopeptídeos , Testes de Sensibilidade Microbiana , Peptídeos Cíclicos/farmacologia , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/isolamento & purificação , beta-Lactamas/farmacologiaRESUMO
Lefamulin was evaluated against various Streptococcus pneumoniae serotypes that were collected from adults with lower respiratory tract infections. Lefamulin exhibited MIC50 and MIC90 values of 0.12 and 0.25 µg/ml, respectively, against the entire collection (n = 822). Similar results were obtained for lefamulin against each of the most common serotypes as well as against multidrug-resistant isolates and strains that are nonsusceptible to ceftriaxone or erythromycin. These data support the clinical development of lefamulin for the treatment of community-acquired respiratory tract infections.
Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Eritromicina/farmacologia , Infecções Respiratórias/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade Microbiana , Sorogrupo , Estados UnidosRESUMO
This study determined the performance of BD Max StaphSR and the rate of methicillin-resistant Staphylococcus aureus (MRSA) with an unrecognized staphylococcal cassette chromosome mec (SCCmec) right-extremity junction (MREJ) region among 907 methicillin-resistant S. aureus (MRSA) and 900 methicillin-susceptible S. aureus (MSSA) isolates. The rate of mecA/mecC dropout mutants was also evaluated. Only three MRSA isolates (99.7% sensitivity; 904/907) were classified as MSSA by the BD Max StaphSR assay, due to negative results for MREJ. Eight MSSA isolates (99.1% sensitivity; 892/900) were assigned as MRSA. However, six of these MSSA isolates had the mecA gene confirmed by PCR and sequencing (99.8% sensitivity; 898/900). Overall, 7.1% (64/900) of MSSA isolates showed results compatible with a mecA dropout genotype.
Assuntos
Técnicas Bacteriológicas/métodos , Programas de Rastreamento/métodos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Proteínas de Ligação às Penicilinas/deficiência , Infecções Estafilocócicas/diagnóstico , Proteínas de Bactérias , DNA Bacteriano/genética , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Sensibilidade e Especificidade , Infecções Estafilocócicas/microbiologia , Estados UnidosRESUMO
OBJECTIVES: The objective of this study was to evaluate the prevalence and in vitro susceptibility of enterococci and VRE among bloodstream infections in European and US hospitals over time. METHODS: Isolates recovered from the blood of infected patients in Europe (72â996) and the USA (67â725) between 2001 and 2014 were included in the prevalence analysis. A subset (2349) collected during 2011-13 was used for the in vitro activity analysis. RESULTS: Enterococcus faecium rates increased in Europe (from 1.4% in 2001 to 4.3% in 2014). These rates also increased in the USA (from 3.0% in 2001 to 5.4% in 2010), with decreasing prevalence (4.6% in 2011 to 3.6% in 2014) in later years. Enterococcus faecalis rates remained stable in Europe, but rose in the USA from 6.9% in 2001 to 8.8% in 2009, declining later (from 7.4% to 5.0%). VRE rates among E. faecalis did not vary in either region, while VRE rates among E. faecium increased in Europe (from 4.7% to 20.3%). US VRE rates among E. faecium increased until 2010 (60.0% in 2001 to 80.7% in 2010), decreasing from 75.1% in 2011 to 68.4% in 2013. Oritavancin demonstrated activity against vancomycin-susceptible E. faecalis (MIC50/90, 0.015/0.06 mg/L; 99.5% susceptible) and vancomycin-resistant E. faecalis (MIC50/90, 0.25/0.5 mg/L). Oritavancin showed MIC50, MIC90 and MIC100 values of 0.03, 0.12 and 0.25 mg/L, respectively, for VanA E. faecium. CONCLUSIONS: Rates of E. faecium and VRE increased in Europe. Although still elevated, VRE rates appeared to show a decreasing trend in the USA since 2010. Oritavancin demonstrated activity against enterococci, including VRE.
Assuntos
Antibacterianos/farmacologia , Bacteriemia/epidemiologia , Infecção Hospitalar/epidemiologia , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Glicopeptídeos/farmacologia , Bacteriemia/microbiologia , Infecção Hospitalar/microbiologia , Europa (Continente) , Hospitais , Humanos , Lipoglicopeptídeos , Estudos Longitudinais , Testes de Sensibilidade Microbiana , Prevalência , Estados Unidos , Resistência a VancomicinaRESUMO
RX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shown in vitro activity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis. Enterobacteriaceae (657), Pseudomonas aeruginosa (200), and Acinetobacter baumannii (202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were tested in vitro by broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC90, 0.5 µg/ml) was >32-fold more active than ceftazidime and inhibited 97.1% and 99.5% of Enterobacteriaceae isolates at MIC values of ≤1 and ≤4 µg/ml, respectively. There were only three isolates with an MIC value of >4 µg/ml (all were indole-positive Protea). RX-P873 (MIC50/90, 2/4 µg/ml) was highly active against Pseudomonas aeruginosa isolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active against P. aeruginosa than tobramycin (MIC90, 2 µg/ml; 91.0% susceptible) and colistin (MIC90, 2 µg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC90, 8 µg/ml; 93.5% susceptible) and meropenem (MIC90, 8 µg/ml; 76.0% susceptible). RX-P873, the most active agent against Acinetobacter baumannii (MIC90, 1 µg/ml), was 2-fold more active than colistin (MIC90, 2 µg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC90, 4 µg/ml). This novel agent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Guanidinas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pirimidinonas/farmacologia , Antibacterianos/química , Guanidinas/química , Testes de Sensibilidade Microbiana , Pirimidinonas/químicaRESUMO
Arbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States. We evaluated the occurrence of organisms isolated from pneumonias in U.S. hospitalized patients (PHP), including ventilator-associated pneumonia (VAP), and the in vitro activity of arbekacin. Organism frequency was evaluated from a collection of 2,203 bacterial isolates (339 from VAP) consecutively collected from 25 medical centers in 2012 through the SENTRY Antimicrobial Surveillance Program. Arbekacin activity was tested against 904 isolates from PHP collected in 2012 from 62 U.S. medical centers and 303 multidrug-resistant (MDR) organisms collected worldwide in 2009 and 2010 from various infection types. Susceptibility to arbekacin and comparator agents was evaluated by the reference broth microdilution method. The four most common organisms from PHP were Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella spp., and Enterobacter spp. The highest arbekacin MIC among S. aureus isolates from PHP (43% methicillin-resistant S. aureus [MRSA]) was 4 µg/ml. Among P. aeruginosa isolates from PHP, only one had an arbekacin MIC of >16 µg/ml (MIC50 and MIC90, 1 and 4 µg/ml), and susceptibility rates for gentamicin, tobramycin, and amikacin were 88.0, 90.0, and 98.0%, respectively. Arbekacin (MIC50, 2 µg/ml) and tobramycin (MIC50, 4 µg/ml) were the most potent aminoglycosides tested against Acinetobacter baumannii. Against Enterobacteriaceae from PHP, arbekacin and gentamicin (MIC50 and MIC90, 0.25 to 1 and 1 to 8 µg/ml for both compounds) were generally more potent than tobramycin (MIC50 and MIC90, 0.25 to 2 and 1 to 32 µg/ml) and amikacin (MIC50 and MIC90, 1 to 2 and 2 to 32 µg/ml). Arbekacin also demonstrated potent in vitro activity against a worldwide collection of well-characterized MDR Gram-negative and MRSA strains.
Assuntos
Antibacterianos/farmacologia , Dibecacina/análogos & derivados , Pneumonia/microbiologia , Amicacina/farmacologia , Dibecacina/farmacologia , Enterobacter/efeitos dos fármacos , Humanos , Klebsiella/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Tobramicina/farmacologiaRESUMO
Staphylococcus aureus and coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human infections. The investigational antibacterial Debio1450 (previously AFN-1720), a prodrug of Debio1452 (previously AFN-1252), specifically targets staphylococci without significant activity against other Gram-positive or Gram-negative species. Debio1452 inhibits FabI, an enzyme critical to fatty acid biosynthesis in staphylococci. The activity of Debio1452 against CoNS, methicillin-susceptible S. aureus (MSSA), and methicillin-resistant S. aureus (MRSA), including significant clones, was determined. A globally diverse collection of 574 patient isolates from 35 countries was tested that included CoNS (6 species, 103 strains), MSSA (154 strains), MRSA (163 strains), and molecularly characterized strains (including spa-typed MRSA clones; 154 strains). The isolates were tested for susceptibility by CLSI broth microdilution methods against Debio1452 and 10 comparators. The susceptibility rates for the comparators were determined using CLSI and EUCAST breakpoint criteria. All S. aureus and CoNS strains were inhibited by Debio1452 concentrations of ≤ 0.12 and ≤ 0.5 µg/ml, respectively. The MIC50s for MSSA, MRSA, and molecularly characterized MRSA strains were 0.004 µg/ml, and the MIC90s ranged from 0.008 to 0.03 µg/ml. The MICs were higher for the CoNS isolates (MIC50/90, 0.015/0.12 µg/ml). Among S. aureus strains, resistance was common for erythromycin (61.6%), levofloxacin (49.0%), clindamycin (27.6%), tetracycline (15.7%), and trimethoprim-sulfamethoxazole (7.0%). Debio1452 demonstrated potent activity against MSSA, MRSA, and CoNS. Debio1452 showed significantly greater activity overall (MIC50, 0.004 µg/ml) than the other agents tested against these staphylococcal species, which included dominant MRSA clones and strains resistant to currently utilized antimicrobial agents.
Assuntos
Antibacterianos/farmacologia , Coagulase/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/enzimologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus/enzimologiaRESUMO
A total of 84,704 isolates were collected from 191 medical centers in 2009 to 2013 and tested for susceptibility to ceftaroline and comparator agents by broth microdilution methods. Ceftaroline inhibited all Staphylococcus aureus isolates at ≤2 µg/ml and was very active against methicillin-resistant strains (MIC at which 90% of the isolates tested are inhibited [MIC90], 1 µg/ml; 97.6% susceptible). Among Streptococcus pneumoniae isolates, the highest ceftaroline MIC was 0.5 µg/ml, and ceftaroline activity against the most common Enterobacteriaceae species (MIC50, 0.12 µg/ml; 78.9% susceptible) was similar to that of ceftriaxone (MIC50, ≤0.25 µg/ml; 86.8% susceptible).
Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Cefalosporinas/farmacologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Ceftriaxona/farmacologia , Enterobacteriaceae/efeitos dos fármacos , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Estados Unidos/epidemiologia , CeftarolinaRESUMO
Pseudomonas aeruginosa isolates (n = 3,902) from 75 U.S. medical centers were tested against ceftazidime-avibactam and comparator agents by the reference broth microdilution method. Overall, 96.9% of the strains were susceptible (MIC, ≤8 µg/ml) to ceftazidime-avibactam, while the rates of susceptibility for ceftazidime, meropenem, and piperacillin-tazobactam were 83.8, 81.9, and 78.5%, respectively. Multidrug-resistant and extensively drug-resistant phenotypes were observed in 14.9 and 8.7% of the strains, respectively, and 81.0 and 73.7% of the strains were susceptible to ceftazidime-avibactam, respectively.
Assuntos
Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Ceftazidima/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Combinação de Medicamentos , Meropeném , Testes de Sensibilidade Microbiana , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Piperacilina/farmacologia , Tazobactam , Tienamicinas/farmacologia , Estados UnidosRESUMO
Pexiganan, a 22-amino-acid synthetic cationic peptide, is currently in phase 3 clinical trials as a topical antimicrobial agent for the treatment of mild infections associated with diabetic foot ulcers. Bacterial isolates from the 2013 SENTRY Antimicrobial Surveillance Program designated as pathogens from diabetic foot infections (DFI) and Gram-negative and -positive pathogens from various infection types that harbored selected resistance mechanisms/phenotypes were tested against pexiganan in reference cation-adjusted Mueller-Hinton broth. The MIC50 and MIC90 against all organisms tested from DFI were 16 and 32 µg/ml, respectively. Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter cloacae, Acinetobacter species, and Pseudomonas aeruginosa MIC values ranged from 8 to 16 µg/ml. Pexiganan MIC values among Staphylococcus aureus (methicillin-resistant S. aureus [MRSA] and methicillin-susceptible S. aureus [MSSA]), beta-hemolytic streptococci, and Enterococcus faecium ranged from 8 to 32 µg/ml. Pexiganan activity was not adversely affected for members of the family Enterobacteriaceae or P. aeruginosa that produced ß-lactamases or resistance mechanisms to other commonly used antimicrobial agents. Decreased susceptibility to vancomycin did not affect pexiganan activity against S. aureus or E. faecium. Enterococcus faecalis appears to be intrinsically less susceptible to pexiganan (MIC, 32 to 256 µg/ml). The "all organism" MIC90 of 32 µg/ml for pexiganan in this study was >250-fold below the pexiganan concentration in the cream/delivery vehicle being developed for topical use.
Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Pé Diabético/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana/métodosRESUMO
Telavancin had MIC50, MIC90, and MIC100 values of 0.03, 0.06, and 0.12 µg/ml, respectively, against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and non-multidrug-resistant (non-MDR) and MDR subsets. MRSA with elevated MIC values for vancomycin (2 to 4 µg/ml) or daptomycin (1 to 2 µg/ml) had telavancin MIC50 (0.06 µg/ml) values 2-fold higher than those of isolates with lower MIC results (MIC50, 0.03 µg/ml). However, telavancin had MIC90 and MIC100 results of 0.06 and 0.12 µg/ml (100% susceptible), respectively, regardless of the MRSA subset.
Assuntos
Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Daptomicina/farmacologia , Humanos , Lipoglicopeptídeos , Testes de Sensibilidade Microbiana/métodos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Estados Unidos , Vancomicina/farmacologiaRESUMO
Telavancin had MIC50 and MIC90 values of 0.03 and 0.06 µg/ml (100.0% susceptible), respectively, against methicillin-resistant and -susceptible Staphylococcus aureus. Telavancin was active against vancomycin-susceptible Enterococcus faecalis (MIC50/90, 0.12/0.12 µg/ml; 100% susceptible) and Enterococcus faecium (MIC50/90, 0.03/0.06 µg/ml), while higher MIC values were obtained against vancomycin-resistant E. faecium (MIC50/90, 1/2 µg/ml) and E. faecalis (MIC50/90, >2/>2 µg/ml). Streptococci showed telavancin modal MIC results of ≤ 0.015 µg/ml, except against Streptococcus agalactiae (i.e., 0.03 µg/ml). This study reestablishes the telavancin spectrum of activity against isolates recovered from the United States (2011-2012) using the revised broth microdilution method.