<i>In Vitro</i>
            Pharmacodynamics of Simulated Pulmonary Exposures of Tigecycline Alone and in Combination against
            <i>Klebsiella pneumoniae</i>
            Isolates Producing a KPC Carbapenemase

Wiskirchen, Dora E.; Koomanachai, Pornpan; Nicasio, Anthony M.; Nicolau, David P.; Kuti, Joseph L.

doi:10.1128/aac.01253-10

Cited by 28 publications

(14 citation statements)

References 46 publications

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“…In comparison, significantly greater CFU reductions were observed and maintained against the 6 P. aeruginosa isolates matched by MIC (126). A similar result was observed in another in vitro pharmacodynamic study, in which monotherapy with prolongedinfusion meropenem failed to preserve bactericidal reductions in CFU over 48 h when tested against 5 KPC-producing isolates, including 4 with meropenem MICs of 8 to 16 g/ml (127). The combination regimen of meropenem plus tigecycline achieved significantly delayed regrowth comparatively.…”

Section: Beyond the Mic: Genotypic Profilingsupporting

confidence: 63%

Continuous and Prolonged Intravenous β-Lactam Dosing: Implications for the Clinical Laboratory

2016

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SUMMARYBeta-lactam antibiotics serve as a cornerstone in the management of bacterial infections because of their wide spectrum of activity and low toxicity. Since resistance rates among bacteria are continuously on the rise and the pipeline for new antibiotics does not meet this trend, an optimization of current beta-lactam treatment is needed. This review provides an overview of optimization through use of prolonged- and continuous-infusion dosing strategies compared with more traditional intermittent infusions. Included is an overview of the scientific basis for using these nontraditional prolonged- and continuous-infusion-based regimens, with a focus on major areas in which the clinical laboratory can support the clinical use of these regimens.

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Section: Beyond the Mic: Genotypic Profilingsupporting

confidence: 63%

Continuous and Prolonged Intravenous β-Lactam Dosing: Implications for the Clinical Laboratory

2016

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“…Unlike monotherapy with tigecycline or meropenem, their combination caused a significant reduction in CFU/ml at 24 and 48 h for isolates with tigecycline and meropenem MICs of Յ2 and Յ16 g/ ml, respectively, compared to the case with either agent alone. None of the studied regimens, however, was able to maintain a significant bactericidal effect for periods over 48 h (262).…”

Section: In Vitro Pharmacodynamic Modelsmentioning

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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“…A one-compartment chemostat in vitro model was used for all experiments (28). Briefly, each experiment consisted of three independent models (two experimental treatment models and one growth control model), which ran simultaneously for each isolate.…”

Section: Methodsmentioning

confidence: 99%

In Vitro Pharmacodynamics of Polymyxin B and Tigecycline Alone and in Combination against Carbapenem-Resistant Acinetobacter baumannii

Hagihara

Housman

Nicolau

et al. 2014

Antimicrob Agents Chemother

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b Carbapenem-resistant Acinetobacter baumannii is increasing in prevalence. Polymyxin B and tigecycline are among the most active antibiotics used against this pathogen in vitro. Past in vitro studies, however, neglected the importance of simulating exposures observed in humans to determine their antibacterial effects. In this study, four carbapenem-resistant A. baumannii isolates were evaluated using an in vitro pharmacodynamic model. Free-drug exposures using 1 mg/kg of body weight of polymyxin B every 12 h (q12h), 100 and 200 mg tigecycline q12h, and the combination of these regimens were simulated. The microbiological responses to these treatments were measured by the change in log 10 CFU/ml over 24 h and the area under the bacterial killing and regrowth curve (AUBC). Resistance was assessed by a population analysis profile (PAP) conducted after 24 h of treatment. Polymyxin B achieved a reduction on the order of ؊2.05 ؎ 0.68 log 10 CFU/ml against these A. baumannii isolates, while all isolates grew to control levels with tigecycline monotherapy. Combination therapy with polymyxin B plus 200 mg tigecycline q12h achieved a greater reduction in bacterial density than did therapy with polymyxin B alone (؊3.31 ؎ 0.71 versus ؊2.05 ؎ 0.68 log 10 CFU/ml, P < 0.001) but not significantly different than combination therapy with 100 mg tigecycline q12h (؊2.45 ؎ 1.00 log 10 CFU/ml, P ‫؍‬ 0.370). Likewise, combination therapy with polymyxin B plus 200 mg tigecycline q12h significantly reduced the AUBC compared to that with polymyxin B alone (62.8 ؎ 8.9 versus 79.4 ؎ 10.5 log 10 CFU/ml, P < 0.05). No changes in the PAP from baseline were observed for either antibiotic alone. In this study, combination therapy with simulated exposures of polymyxin B and tigecycline at an aggressive dose of 200 mg q12h produced synergistic or additive effects on humans against these multidrug-resistant A. baumannii strains.

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In Vitro Pharmacodynamics of Simulated Pulmonary Exposures of Tigecycline Alone and in Combination against Klebsiella pneumoniae Isolates Producing a KPC Carbapenemase

Cited by 28 publications

References 46 publications

Continuous and Prolonged Intravenous β-Lactam Dosing: Implications for the Clinical Laboratory

Continuous and Prolonged Intravenous β-Lactam Dosing: Implications for the Clinical Laboratory

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

In Vitro Pharmacodynamics of Polymyxin B and Tigecycline Alone and in Combination against Carbapenem-Resistant Acinetobacter baumannii

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