Comparative in vitro killing of carbapenems and aztreonam against Klebsiella pneumoniae producing VIM-1 metallo-β-lactamase

Παναγιωτακοπούλου, Αγγελική; Daikos, George L.; Miriagou, Vivì; Loli, A.; Tzelepi, E.; Tzouvelekis, L. S.

doi:10.1016/j.ijantimicag.2006.11.004

Cited by 12 publications

(10 citation statements)

References 6 publications

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“…As mentioned previously, aztreonam is not hydrolyzed by M␤Ls and therefore is a potentially useful agent against M␤L producers. A time-kill study assessed the in vitro activity of aztreonam in comparison to carbapenems against VIM-1-producing ESBL-negative K. pneumoniae isolates (197). Aztreonam exhibited slow bactericidal activity that was sustained for 24 h, whereas carbapenems resulted in more rapid bacterial killing for the first 6 h but regrowth to the level of antibiotic-free controls at 24 h.…”

Section: In Vitro Synergymentioning

confidence: 99%

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: In Vitro Synergymentioning

confidence: 99%

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

et al. 2012

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“…Despite initial killing (at 2 h), regrowth was observed with all tested isolates after 24 h of incubation with 8–16 mg/L imipenem, meropenem or ertapenem, irrespective of the MIC levels. In the same study, aztreonam exhibited bactericidal activity against all susceptible isolates [9]. In contrast, in the second study, imipenem exhibited bactericidal activity against some of the tested VIM‐1‐producing K. pneumoniae clinical isolates with MICs ≤4 mg/L [10].…”

Section: Clinical and Therapeutic Issuesmentioning

confidence: 99%

Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control

Carmeli

Akova

Cornaglia

et al. 2010

Clinical Microbiology and Infection

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235

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Although the rapid spread of carbapenemase-producing Gram-negatives (CPGNs) is providing the scientific community with a great deal of information about the molecular epidemiology of these enzymes and their genetic background, data on how to treat multidrug-resistant or extended drug-resistant carbapenemase-producing Enterobacteriaceae and how to contain their spread are still surprisingly limited, in spite of the rapidly increasing prevalence of these organisms and of their isolation from patients suffering from life-threatening infections. Limited clinical experience and several in vitro synergy studies seem to support the view that antibiotic combinations should be preferred to monotherapies. But, in light of the data available to date, it is currently impossible to quantify the real advantage of drug combinations in the treatment of these infections. Comprehensive clinical studies of the main therapeutic options, broken down by pathogen, enzyme and clinical syndrome, are definitely lacking and, as carbapenemases keep spreading, are urgently needed. This spread is unveiling the substantial unpreparedness of European public health structures to face this worrisome emergency, although experiences from different countries-chiefly Greece and Israel-have shown that CPGN transmission and cross-infection can cause a substantial threat to the healthcare system. This unpreparedness also affects the treatment of individual patients and infection control policies, with dramatic scarcities of both therapeutic options and infection control measures. Although correct implementation of such measures is presumably cumbersome and expensive, the huge clinical and public health problems related to CPGN transmission, alongside the current scarcity of therapeutic options, seem to fully justify this choice.

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“…Carbapenem resistance levels of MBL-positive Enterobacteriaceae are variable and often below the proposed resistance breakpoint (20) as a result of differences in outer membrane permeability or in the levels of VIM-1 production (13), but most experts recommend against the use of carbapenem monotherapy for treatment (4,17), based on evidence of a strong inoculum effect in vitro (14). Other experimental data suggested that an increased imipenem dosage could be efficacious against susceptible isolates (5).…”

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confidence: 99%

Does the Activity of the Combination of Imipenem and Colistin In Vitro Exceed the Problem of Resistance in Metallo-β-Lactamase-Producing Klebsiella pneumoniae Isolates?

Souli

Rekatsina

Chryssouli

et al. 2009

Antimicrob Agents Chemother

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Using time-kill methodology, we investigated the interactions of an imipenem-colistin combination against 42 genetically distinct Klebsiella pneumoniae clinical isolates carrying a bla VIM-1 -type gene. Irrespective of the imipenem MIC, the combination was synergistic (50%) or indifferent (50%) against colistin-susceptible strains, while it was antagonistic (55.6%) and rarely synergistic (11%) against non-colistin-susceptible strains (with synergy being observed only against strains with colistin MICs of 3 to 4 g/ml). The combination showed improved bactericidal activity against isolates susceptible either to both agents or to colistin.

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Comparative in vitro killing of carbapenems and aztreonam against Klebsiella pneumoniae producing VIM-1 metallo-β-lactamase

Cited by 12 publications

References 6 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

Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control

Does the Activity of the Combination of Imipenem and Colistin In Vitro Exceed the Problem of Resistance in Metallo-β-Lactamase-Producing Klebsiella pneumoniae Isolates?

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