Ertapenem or ticarcillin/clavulanate for the treatment of intra-abdominal infections or acute pelvic infections in pediatric patients
Albert E. YellinJeffrey P. JohnsonIliana HigaredaBlaise L. CongeniAntonio ArrietaDoreen FernslerJoseph A. WestRichard Gesser
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Ertapenem
Ticarcillin
Tolerability
Carbapenem
Ertapenem
Carbapenem
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Objective. To study the sensitivity level of extended spectrum beta-lactamase-producing Enterobacteriaceae to Carbapenems (Imipenem, Ertapenem) marketed in Morocco and discusses the place of Ertapenem in the treatment of extended spectrum-beta-lactamase-producing. Materials and Methods. A retrospective study of 110 extended spectrum beta-lactamase-producing Enterobacteriaceae. Isolates obtained from blood cultures, superficial and deep pus, and catheters were conducted. The minimum inhibitory concentrations of Imipenem and Ertapenem were done by the E-test. The modified Hodge test was conducted for resistant or intermediate strains. Results. 99.1% of isolates were susceptible to Imipenem. For Ertapenem, 4 were resistant and 4 intermediate. The modified Hodge test was positive for all 08 isolates. A minimum inhibitory concentration comparison of K. pneumoniae, E. cloacae, and E. coli for Imipenem has noted a significant difference between E. cloacae on one hand and E. coli, K. pneumoniae on the other hand (). No significant difference was noted for minimum inhibitory concentration of Ertapenem. Conclusion. Our results confirm in vitro effectiveness of Ertapenem against extended spectrum beta-lactamase-producing Enterobacteriaceae as reported elsewhere. However, the emergence of resistance to Carbapenems revealed by production of carbapenemases in this study confirmed a necessary bacteriological documented infection before using Ertapenem.
Ertapenem
Carbapenem
Beta-lactamase
Enterobacter cloacae
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Carbapenemase-resistant bacteria are increasingly spreading worldwide causing public concern due to their ability to elude antimicrobial treatment. Early identification of these bacteria is therefore of high importance. Here, we describe the development of a simple and robust protocol for the detection of carbapenemase activity in clinical isolates of Enterobacteriaceae, suitable for routine and clinical applications. The final protocol involves cellular lysis and enzyme extraction from a defined amount of bacterial cells followed by the addition of a benchmark drug (e.g. the carbapenem antibiotic imipenem or ertapenem). Carbapenem inactivation is mediated by enzymatic hydrolysis (cleavage) of the β-lactam common structural motif, which can be detected using MALDI-TOF MS. A total of 260 strains were studied (208 carbapenemase producers and 52 non-carbapenemase producers) resulting in 100% sensitivity and 100% specificity for the KPC, NDM and OXA-48-like PCR-confirmed positive isolates using imipenem as benchmark. Differences between the benchmark (indicator) antibiotics imipenem and ertapenem, buffer constituents and sample preparation methods have been investigated. Carbapenemase activity was further characterized by performing specific inhibitor experiments. Intraday and interday reproducibility (coefficient of variation) of the observed hydrolysis results were 15% and 30%, respectively. A comparative study of our extraction method and a recently published method using whole bacterial cells is presented and differences are discussed. Using this method, an existing carbapenemase activity can be directly read from the mass spectrum as a ratio of hydrolysed product and substrate, setting an important step towards routine application in clinical laboratories.
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Carbapenem-resistant enterobacteriaceae
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Objective: To determine mutant prevention concentrations of carbapenems and resistance development during carbapenem treatment of infections due to extended spectrum beta lactamase (ESBL) and/or pAmpC beta-lactamase producing bacteria. Method: Escherichia coli and Klebsiella pneumoniae isolates having imipenem and meropenem MIC= 256 µg/ml). In ESBL(+) strains, imipenem and meropenem even in very low MICs (0,015-0,06 µg/ml) have selected carbapenem resistant mutants in a rate of 50%. Conclusion: According to the results, i) ESBL and pAmpC production bring about selection of carbapenem resistant mutants even though strains are carbapenem susceptible in routine tests, ii) Infections caused by strains with carbapenem MICs in susceptible range but producing carbapenemase may have high probability of treatment failure, iii) Among carbapenems, doripenem and ertapenem have the lowest imipenem and meropenem have the highest potential for mutant selection
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Enterobacter spp. are an important cause of infections and antibiotic resistance, including carbapenem resistance. Recent studies suggest that infections due to carbapenem-resistant Enterobacteriaceae (CRE) carrying carbapenemase-encoding genes carry a worse prognosis than CRE that do not carry a carbapenemase-encoding gene, but it is unknown whether there are differences by different bacterial genera/species. CRE that are resistant only to one carbapenem –almost always ertapenem –have been reported, but the frequency of discordance between ertapenem and imipenem/meropenem is not known for Enterobacter spp. We examined all cases of Enterobacter bacteremia from January 2012 to December 2016 at the Michael E. DeBakey VA Medical Center in Houston, Texas, USA. Clinical and microbiological data were independently extracted by two investigators. Antibiotic suscepitibilty testing results were interpreted according to current CLSI breakpoints. Discordance between ertapenem and imipenem susceptibilities was found in 14/67 (20.9%) isolates; eight isolates were ertapenem susceptible/imipenem non-susceptible, and six isolates were ertapenem non-susceptible/imipenem susceptible. Bacteremia cleared in 94.5% (3/55) of all patients who had follow-up cultures, including infection by all (13/13) isolates with discordant carbapenem susceptibilities. Fourteen-day mortality was not different between the patients with concordant and discordant carbapenem susceptibilities (7.5% vs. 21.4%; P = 0.3408, Fisher's exact test); four patients died within 48 hours of bacteremia and the remaining three deaths had documented clearance of bacteremia. To our knowledge, these are the first systematic data showing bacteremia by Enterobacter spp. with discordant ertapenem and imipenem/meropenem susceptibilities is not infrequent; interestingly, ertapenem susceptible/imipenem non-susceptible was more common than ertapenem non-susceptible/imipenem susceptible isolates. Bacteremia by Enterobacter isolates with discordant carbapenem results were rapidly cleared and no difference in mortality was detected. All authors: No reported disclosures.
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This study aimed to analyse the in vitro activity of dual combinations of carbapenems against Klebsiella pneumoniae producing the main carbapenemase types. MIC values of the carbapenems, imipenem, meropenem, ertapenem and doripenem were determined alone and in dual combinations for 20 clinical K. pneumoniae isolates producing representative carbapenemases, i.e. OXA-48 (n = 6), NDM-1 (n = 4), NDM-1 + OXA-48 (n = 2) and KPC-2 (n = 8). MICs were also determined for Escherichia coli recombinant strains with or without permeability defects producing NDM-1, OXA-48 or KPC-2. In vitro synergy combination testing was performed using the microdilution and chequerboard techniques. Fractional inhibitory concentration indexes were calculated to determine whether the combinations were synergistic, indifferent or antagonistic. All carbapenemase producers were resistant to the tested carbapenems, with most isolates showing MICs of carbapenems >32 mg/L. None of the combinations was antagonistic. For KPC producers, synergistic combinations were observed with imipenem/ertapenem (5/8 isolates), imipenem/doripenem (4/8), imipenem/doripenem (4/8), meropenem/doripenem (3/8) and ertapenem/doripenem (3/8), while no synergy was observed with meropenem/ertapenem. For OXA-48 producers, synergies were observed with imipenem/ertapenem and with imipenem/meropenem for both isolates tested. Notably, combining imipenem with a non-carbapenem β-lactam (cefalotin) did not give any synergistic result. No synergy was observed for all NDM-1 and NDM-1+OXA-48 producers. Time–kill assays confirmed most of the data obtained by chequerboard testing. The data strongly support the hypothesis that dual carbapenem combinations might be effective against serine-β-lactamase producers (KPC, OXA-48). The imipenem-containing combinations appeared to be the most efficient.
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Doripenem
Carbapenem
Cilastatin
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Ertapenem
Carbapenem
Doripenem
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Purpose. The aim of this study was to evaluate the in vitro activity of double-carbapenem combinations against OXA-48-producing Klebsiella pneumoniae clinical isolates.Methodology. Double combinations of ertapenem, meropenem and imipenem were evaluated for synergy and bactericidal activity using the time-kill methodology. All antibiotics were tested at 10 mg l-1 and at a sub-inhibitory concentration of 0.5× minimum inhibitory concentration (MIC) for isolates with a carbapenem MIC≤8 mg l-1. Synergy was defined as a ≥2log10 colony-forming units (c.f.u.) ml-1 decrease of viable colonies at 24 h compared to the most active carbapenem alone.Results. Ten distinct K. pneumoniae clinical isolates were tested. All carried blaOXA-48 and blaCTX-M-15, and exhibited an MIC range of 64-128, 4-32 and 1-32 mg l-1 for ertapenem, meropenem and imipenem, respectively. Out of 48 isolate-combinations, synergy was observed in 9 (18.8 %) and cidal activity was observed in 13 (27.1 %). In vitro synergistic activity was noted for 5 out of 29 (17.2 %) ertapenem-, 6 out of 29 (20.7 %) meropenem- and 7 out of 38 (18.4 %) imipenem-containing combinations. No combination exhibited antagonism. Bactericidal activity was observed in 7 (24.1 %) ertapenem-, 8 (27.6 %) meropenem- and 11 (28.9 %) imipenem-containing combinations. Among the sub-inhibitory concentration combinations, three (15 %) ertapenem-, four (20 %) meropenem- and three (15 %) imipenem-containing ones showed synergistic interaction.Conclusion. Dual combinations of carbapenems, including those containing sub-inhibitory concentrations of antibiotics, were synergistic against multidrug-resistant (MDR) and extensively drug-resistant (XDR) K. pneumoniae isolates harbouring blaOXA-48.
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Carbapenem-resistant Acinetobacter baumannii group organisms (CRAB) are challenging because the choice between targeted, new antibiotic drug options and hygiene measures should be guided by a timely identification of resistance mechanisms. In CRAB, acquired class-D carbapenemases (CHDLs) are active against meropenem and imipenem. If PCR methods are not the first choice, phenotypic methods have to be implemented. While promising, the carbapenemase inactivation method (CIM) using meropenem-hydrolysis is, however, hampered by poor performance or overly long time-to-result. We developed a rapid CIM (rCIM-A) with good performance using ertapenem, imipenem, and meropenem disks, 2-h permeabilization and incubation with the test strain in trypticase soy broth, and a read-out of residual carbapenem activity after 6 h, and optionally after 16-18 h. Using clinical isolates and type-strains of Acinetobacter (n = 67) not harboring carbapenemases (n = 28) or harboring acquired carbapenemases (n = 39), the sensitivity of detection was 97.4% with the imipenem disk after 6 h at a specificity of 92.9%. If the inhibition zone around the ertapenem disk at 6 h was 6 or ≤26 mm at 16-18 h, or ≤25.5 mm for meropenem, the specificity was 100%. Because of the high negative predictive value, the rCIM-A seems particularly appropriate in areas of lower CRAB-frequency.
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