Activity of Eravacycline against Enterobacteriaceae and Acinetobacter baumannii, Including Multidrug-Resistant Isolates, from New York City

Abdallah, Marie; Olafisoye, Olawole; Cortes, Christopher; Urban, Carl; Landman, David; Quale, John

doi:10.1128/aac.04809-14

Cited by 126 publications

(99 citation statements)

References 12 publications

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“…This is in contrast to the OXA-48 enzyme found in K. pneumoniae which is inhibited by avibactam, (MIC for ceftazidime = 128 µg/ml, MIC for CA = 0.75 µg/ml). Among Acinetobacter isolates, OXA-23 and OXA-24 were the predominant carbapenemases, a finding consistent with our earlier studies [16] [17]. While all P. aeruginosa in this study were reported as carbapenem resistant by the Vitek 2® system, the Check-MDR CT103 XL Microarray reported no carbapenem resistant genotypes likely due to lack of specific ampC primers for Pseudomonas aeruginosa.…”

Section: Discussionsupporting

confidence: 80%

Detection and Characterization of <i>β</i>-Lactamase Encoding Genes in Carbapenem Non-Susceptible Gram-Negative Bacteria and Susceptibility of Isolates to Ceftazidime-Avibactam at a New York City Community Hospital

Urban¹,

Colon-Urban²,

LaBombardi³

et al. 2016

OJMM

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A surveillance study was undertaken to identify prominent β-lactamase encoding genes in 131 carbapenem non-susceptible gram-negative clinical isolates at a New York City community hospital. KPC carbapenemases were detected in 89% of Enterobacteriaceae as well as additional TEM, SHV, and CTX-M class A enzymes. OXA-23 and OXA-24 were the prevalent class D carbapenemases identified in Acinetobacter species. One OXA-23 in M. morganii and one OXA-48 in K. pneumoniae were also identified. Among class C β-lactamases CMY, ACT/MIR, DHA, and FOX were detected. The in vitro activity of ceftazidime-avibactam by E-test methodology was tested with minimal inhibitory concentrations (MIC) of ≤3 µg/ml for 97.8% of all Enterobacteriaceae, MIC 50/90 of 16/>256 µg/ml for carbapenem non-susceptible Acinetobacter, and 3/6 µg/ml for carbapenem non-susceptible Pseudomonas aeruginosa. Periodic surveillance of isolates to characterize current and emerging β-lactamase genotypes present in local isolates may help identify outbreak situations, provide assistance to infection control and antibiotic stewardship programs, and potentially improve patient outcomes.

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Section: Discussionsupporting

confidence: 80%

Detection and Characterization of <i>β</i>-Lactamase Encoding Genes in Carbapenem Non-Susceptible Gram-Negative Bacteria and Susceptibility of Isolates to Ceftazidime-Avibactam at a New York City Community Hospital

Urban¹,

Colon-Urban²,

LaBombardi³

et al. 2016

OJMM

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“…With regard to in vitro MIC studies, eravacycline has demonstrated MIC 90 values against Enterobacteriaceae that are 1-fold to 4-fold lower than those seen with tigecycline; however, tigecycline's MIC against E. coli C3-14 was 1 dilution lower than that of eravacycline, potentially resulting in the discordance in bacterial kill results (3,21). Similarly to eravacycline, tigecycline was not bactericidal in two of the three Enterobacteriaceae isolates, but both antimicrobials achieved Ն3-log killing against the MRSA isolates.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Efficacy of Eravacycline In Vivo against Gram-Positive and Gram-Negative Organisms

Monogue

Thabit

Hamada

et al. 2016

Antimicrob Agents Chemother

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Members of the tetracycline class are frequently classified as bacteriostatic. However, recent findings have demonstrated an improved antibacterial killing profile, often achieving >3 log 10 bacterial count reduction, when such antibiotics have been given for periods longer than 24 h. We aimed to study this effect with eravacycline, a novel fluorocycline, given in an immunocompetent murine thigh infection model over 72 h against two methicillin-resistant Staphylococcus aureus (MRSA) isolates (eravacycline MICs ‫؍‬ 0.03 and 0.25 g/ml) and three Enterobacteriaceae isolates (eravacycline MICs ‫؍‬ 0.125 to 0.25 g/ml). A humanized eravacycline regimen, 2.5 mg/kg of body weight given intravenously (i.v.) every 12 h (q12h), demonstrated progressively enhanced activity over the 72-h study period. A cumulative dose response in which bacterial density was reduced by more than 3 log 10 CFU at 72 h was noted over the study period in the two Gram-positive isolates, and eravacycline performed similarly to comparator antibiotics (tigecycline, linezolid, and vancomycin). A cumulative dose response with eravacycline and comparators (tigecycline and meropenem) over the study period was also observed in the Gram-negative isolates, although more variability in bacterial killing was observed for all antibacterial agents. Overall, a bacterial count reduction of >3 log was achieved in one of the three isolates with both eravacycline and tigecycline, while meropenem achieved a similar endpoint against two of the three isolates. Bactericidal activity is typically defined in vitro over 24 h; however, extended regimen studies in vivo may demonstrate an improved correlation with clinical outcomes by better identification of antimicrobial effects.

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“…In vitro, it has activity against most KPC producers. 89 It remains to be tested clinically against substantial numbers of patients with infections with CPE.…”

Section: Antimicrobial Agents Used For Treatment Of Cpe Infectionsmentioning

confidence: 99%

Carbapenemase-Producing Enterobacteriaceae

Doi

Paterson

2015

Semin Respir Crit Care Med

185

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Carbapenemase-producing Enterobacteriaceae (CPE) were almost nonexistent up to the 1990s, but are today encountered routinely in hospitals and other healthcare facilities in many countries including the United States. KPC-producing Klebsiella pneumoniae was the first to emerge and spread globally and is endemic in the United States, Israel, Greece, and Italy. Recently, NDM-producing Enterobacteriaceae and OXA-48-producing K. pneumoniae appear to be disseminating from South Asia and Northern Africa, respectively. They are almost always resistant to all β-lactams including carbapenems and many other classes. Mortality from invasive CPE infections reaches up to 40%. To obtain the maximal benefit from the limited options available, dosing of antimicrobial agents should be optimized based on pharmacokinetic data, especially for colistin and carbapenems. In addition, multiple observational studies have associated combination antimicrobial therapy with lower mortality compared with monotherapy for these infections. The outcomes appear to be especially favorable when patients are treated with a carbapenem and a second agent such as colistin, tigecycline, and gentamicin, but the best approach is yet to be defined.

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Activity of Eravacycline against Enterobacteriaceae and Acinetobacter baumannii, Including Multidrug-Resistant Isolates, from New York City

Cited by 126 publications

References 12 publications

Detection and Characterization of <i>β</i>-Lactamase Encoding Genes in Carbapenem Non-Susceptible Gram-Negative Bacteria and Susceptibility of Isolates to Ceftazidime-Avibactam at a New York City Community Hospital

Detection and Characterization of <i>β</i>-Lactamase Encoding Genes in Carbapenem Non-Susceptible Gram-Negative Bacteria and Susceptibility of Isolates to Ceftazidime-Avibactam at a New York City Community Hospital

Antibacterial Efficacy of Eravacycline In Vivo against Gram-Positive and Gram-Negative Organisms

Carbapenemase-Producing Enterobacteriaceae

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Activity of Eravacycline against Enterobacteriaceae and Acinetobacter baumannii, Including Multidrug-Resistant Isolates, from New York City

Cited by 126 publications

References 12 publications

Detection and Characterization of &lt;i&gt;β&lt;/i&gt;-Lactamase Encoding Genes in Carbapenem Non-Susceptible Gram-Negative Bacteria and Susceptibility of Isolates to Ceftazidime-Avibactam at a New York City Community Hospital

Detection and Characterization of &lt;i&gt;β&lt;/i&gt;-Lactamase Encoding Genes in Carbapenem Non-Susceptible Gram-Negative Bacteria and Susceptibility of Isolates to Ceftazidime-Avibactam at a New York City Community Hospital

Antibacterial Efficacy of Eravacycline In Vivo against Gram-Positive and Gram-Negative Organisms

Carbapenemase-Producing Enterobacteriaceae

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Detection and Characterization of <i>β</i>-Lactamase Encoding Genes in Carbapenem Non-Susceptible Gram-Negative Bacteria and Susceptibility of Isolates to Ceftazidime-Avibactam at a New York City Community Hospital

Detection and Characterization of <i>β</i>-Lactamase Encoding Genes in Carbapenem Non-Susceptible Gram-Negative Bacteria and Susceptibility of Isolates to Ceftazidime-Avibactam at a New York City Community Hospital