Efficacy of carbapenems against a metallo- -lactamase-producing Escherichia coli clinical isolate in a rabbit intra-abdominal abscess model

Souli, María; Konstantinidou, Eleftheria; Tzepi, Ira-Maria; Τσαγανός, Θωμάς; Pefanis, Angelos; Chryssouli, Zoi; Galani, Irene; Giamarellos‐Bourboulis, Evangelos J.; Giamarellou, Helen

doi:10.1093/jac/dkq470

Cited by 21 publications

(20 citation statements)

References 16 publications

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“…Carbapenems and aztreonam were shown to be effective in the treatment of this infection with regard to reductions in bacterial densities and mortality of the animals compared with those of untreated controls. Aztreonam, however, resulted in a more favorable outcome overall than that seen with carbapenems (239).…”

Section: Experimental Infection Modelsmentioning

confidence: 81%

Carbapenemases in Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions

et al. 2012

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SUMMARY The spread of Enterobacteriaceae , primarily Klebsiella pneumoniae , producing KPC, VIM, IMP, and NDM carbapenemases, is causing an unprecedented public health crisis. Carbapenemase-producing enterobacteria (CPE) infect mainly hospitalized patients but also have been spreading in long-term care facilities. Given their multidrug resistance, therapeutic options are limited and, as discussed here, should be reevaluated and optimized. Based on susceptibility data, colistin and tigecycline are commonly used to treat CPE infections. Nevertheless, a review of the literature revealed high failure rates in cases of monotherapy with these drugs, whilst monotherapy with either a carbapenem or an aminoglycoside appeared to be more effective. Combination therapies not including carbapenems were comparable to aminoglycoside and carbapenem monotherapies. Higher success rates have been achieved with carbapenem-containing combinations. Pharmacodynamic simulations and experimental infections indicate that modification of the current patterns of carbapenem use against CPE warrants further attention. Epidemiological data, though fragmentary in many countries, indicate CPE foci and transmission routes, to some extent, whilst also underlining the lack of international collaborative systems that could react promptly and effectively. Fortunately, there are sound studies showing successful containment of CPE by bundles of measures, among which the most important are active surveillance cultures, separation of carriers, and assignment of dedicated nursing staff.

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Section: Experimental Infection Modelsmentioning

confidence: 81%

Carbapenemases in Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions

et al. 2012

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“…Indeed, in studies of carbapenems and aztreonam in animal models of infection due to an MBL-producing (ESBL-negative) Enterobacteriaceae clinical isolate (6), treatment with aztreonam significantly reduced mortality (28).…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Screening of Carbapenemases and Associated β-Lactamases in Carbapenem-Resistant Enterobacteriaceae

et al. 2012

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e Dissemination of carbapenem resistance among Enterobacteriaceae poses a considerable threat to public health. Carbapenemase gene detection by molecular methods is the gold standard but is available in only a few laboratories. The aim of this study was to test phenotypic methods for the detection of metallo-␤-lactamase (MBL)-or Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and associated mechanisms of ␤-lactam resistance against a panel of 30 genotypically characterized carbapenem-resistant Enterobacteriaceae : 9 MBL, 7 KPC, 6 OXA-48, and 8 extended-spectrum ␤-lactamase (ESBL) or AmpC ␤-lactamases associated with decreased permeability. We used carbapenemase inhibitor-impregnated agar to test for carbapenem-resistant strains. Differences in the inhibition zone sizes of the meropenem, imipenem, ertapenem, and doripenem disks were measured between control and inhibitor (EDTA or phenylboronic acid [PBA] with or without cloxacillin)-impregnated Mueller-Hinton agar with a cutoff of 10 mm. All 9 MBL-and 7 KPC-producing Enterobacteriaceae were identified from the differences in zone size in the presence and absence of specific inhibitors, regardless of the carbapenem MICs and including isolates with low-level resistance to carbapenems. We also detected their associated ␤-lactam resistance mechanisms (11 ESBL-type and 5 class A ␤-lactamase 2b). No differences in zone size were observed for OXA-48-producing strains or other carbapenem resistance mechanisms such as ESBL and decreased permeability. We propose a new strategy to detect carbapenemases (MBL-and KPC-type) and associated mechanisms of ␤-lactam resistance (ESBL or class A ␤-lactamase 2b) by the use of inhibitor-impregnated agar. A rapid phenotypic detection of resistance mechanisms is important for epidemiological purposes and for limiting the spread of resistant strains by implementing specific infection control measures.

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“…Several studies provided evidence that carbapenems might have an effect on carbapenemase-producing Enterobacteriaceae (7,13,43). Additionally, it has been recently shown by in vitro time-kill assay that meropenem at concentrations 4ϫ the MIC was bactericidal (Ͼ3 log 10 reduction CFU/ml) even when tested alone against various strains of Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae with an MIC of 2 to 4 mg/liter (38).…”

Section: Discussionmentioning

confidence: 99%

“…Of note, it has also been suggested that trough levels severalfold above the MIC could be useful for carbapenems in some settings (23,44,45) and that this approach could be worthwhile even against low-MIC carbapenemase producers (6,7,13,38,43).…”

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confidence: 99%

Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach

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Viale

Cojutti

et al. 2012

Antimicrob Agents Chemother

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The worrisome increase in Gram-negative bacteria with borderline susceptibility to carbapenems and of carbapenemase-producing Enterobacteriaceae has significantly undermined their efficacy. Continuous infusion may be the best way to maximize the time-dependent activity of meropenem. The aim of this study was to create dosing nomograms in relation to different creatinine clearance (CL Cr ) estimates for use in daily clinical practice to target the steady-state concentrations (C ss s) of meropenem during continuous infusion at 8 to 16 mg/liter (after the administration of an initial loading dose of 1 to 2 g over 30 min). The correlation between meropenem clearance (CL m ) and CL Cr was retrospectively assessed in a cohort of critically ill patients (group 1, n ‫؍‬ 67) to create a formula for dosage calculation to target C ss . The performance of this formula was validated in a similar cohort (group 2, n ‫؍‬ 56) by comparison of the observed and the predicted C ss s. A significant relationship between CL m and CL Cr was observed in group 1 (r ‫؍‬ 0.72, P < 0.001). The application of the formula to meropenem dosing in group 2, infusion rate (g/24 h) ‫؍‬ [0.078 ؋ CL Cr (ml/min) ؉ 2.85] ؋ target C ss ؋ (24/1,000), led to a significant correlation between the observed and the predicted C ss s (r ‫؍‬ 0.92, P < 0.001). Dosing nomograms based on CL Cr were created to target the meropenem C ss at 8, 12, and 16 mg/liter in critically ill patients. These nomograms could be helpful in improving the treatment of severe Gram-negative infections with meropenem, especially in the presence of borderline susceptible pathogens or even of carbapenemase producers and/or of pathophysiological conditions which may enhance meropenem clearance.

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Efficacy of carbapenems against a metallo- -lactamase-producing Escherichia coli clinical isolate in a rabbit intra-abdominal abscess model

Cited by 21 publications

References 16 publications

Carbapenemases in Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions

Carbapenemases in Klebsiella pneumoniae and Other Enterobacteriaceae: an Evolving Crisis of Global Dimensions

Phenotypic Screening of Carbapenemases and Associated β-Lactamases in Carbapenem-Resistant Enterobacteriaceae

Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach

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