Comparative time–kill study of doxycycline, tigecycline, sulbactam, and imipenem against several clones of Acinetobacter baumannii

Bantar, Carlos; Schell, Celia María; Posse, Graciela; Limansky, Adriana S.; Ballerini, Viviana; Mobilia, Liliana

doi:10.1016/j.diagmicrobio.2008.02.014

Cited by 20 publications

(13 citation statements)

References 31 publications

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“…To overcome these limitations, other susceptibility breakpoints, such as the EC 50 , have been suggested to be the PD input for PK-PD indices (25). The EC 50 can be obtained, together with parameters characterizing bacterial growth and maximum antibiotic-induced kill, from continuous measure- ment of the antibiotic concentration-effect relationship over time (time-kill curves) (1,22,31). In general, there are two different types of time-kill curves, based on the concentration profile used in these in vitro models: static and dynamic timekill curves (26).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic-Pharmacodynamic Modeling of the In Vitro Activities of Oxazolidinone Antimicrobial Agents against Methicillin-ResistantStaphylococcus aureus

Schmidt

Sabarinath

Barbour

et al. 2009

Antimicrob Agents Chemother

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Linezolid is the first FDA-approved oxazolidinone with activity against clinically important gram-positive pathogens, including methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). RWJ-416457 is a new oxazolidinone with an antimicrobial spectrum similar to that of linezolid. The goal of the present study was to develop a general pharmacokinetic (PK)-pharmacodynamic (PD) model that allows the characterization and comparison of the in vitro activities of oxazolidinones, determined in time-kill curve experiments, against MRSA. The in vitro activities of RWJ-416457 and the first-in-class representative, linezolid, against MRSA OC2878 were determined in static and dynamic time-kill curve experiments over a wide range of concentrations: 0.125 to 8 g/ml (MIC, 0.5 g/ml) and 0.25 to 16 g/ml (MIC, 1 g/ml), respectively. After correction for drug degradation during the time-kill curve experiments, a two-subpopulation model was simultaneously fitted to all data in the NONMEM VI program. The robustness of the model and the precision of the parameter estimates were evaluated by internal model validation by nonparametric bootstrap analysis. A two-subpopulation model, consisting of a self-replicating, oxazolidinone-susceptible and a persistent, oxazolidinone-insusceptible pool of bacteria was appropriate for the characterization of the time-kill curve data. The PK-PD model identified was capable of accounting for saturation in growth, delays in the onsets of growth and drug-induced killing, as well as naturally occurring bacterial death. The simultaneous fit of the proposed indirect-response, maximum-effect model to the data resulted in concentrations that produced a half-maximum killing effect that were significantly (P < 0.05) lower for RWJ-416457 (0.41 g/ml) than for linezolid (1.39 g/ml). In combination with the appropriate PK data, the susceptibility-based two-subpopulation model identified may provide valuable guidance for the selection of oxazolidinone doses or dose regimens for use in clinical studies.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic-Pharmacodynamic Modeling of the In Vitro Activities of Oxazolidinone Antimicrobial Agents against Methicillin-ResistantStaphylococcus aureus

Schmidt

Sabarinath

Barbour

et al. 2009

Antimicrob Agents Chemother

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“…As was mentioned earlier, MIN (and tetracyclines in general) typically have a bacteriostatic activity; however, some authors have reported a bactericidal effect in A. baumannii isolates (Bantar et al, 2008). In our study, MIN showed bactericidal activity only at concentrations i32 mg ml 21 or when the related concentration/MIC in killing curves was i64 mg ml…”

Section: Discussionmentioning

confidence: 35%

In vitro activity of minocycline alone or in combination in multidrug-resistant Acinetobacter baumannii isolates

Rodríguez

Nastro

Vay

et al. 2015

Journal of Medical Microbiology

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Minocycline (MIN) usually shows good activity against Acinetobacter baumannii strains. The reintroduction to the market of intravenous MIN provides an additional agent to the limited options for the treatment of A. baumannii infections. The activity of MIN as a single agent and in combination with rifampicin (RIF), colistin (COL) or imipenem (IMI) was evaluated by means of killing curves and 24 h-time-kill curves in five A. baumannii isolates which were selected on the basis of different antimicrobial resistance profiles. MIN showed bacteriostatic activity in three isolates (26 or 166 MIC) and bactericidal activity in the other isolates (646 MIC). In isolates harbouring the tetB gene, the associations studied were always indifferent. However, in isolates not harbouring tetB, the use of MIN in combination showed a rapid synergistic effect (at 4 h) in four out of nine combinations (two with RIF and one each with IMI and COL). At 24 h, this effect was observed in six out of nine combinations (two in each association). MIN in combination with RIF, IMI and COL showed bactericidal synergy in most of the isolates which did not harbour the tetB gene, but the combinations were not synergistic in tetB-positive isolates.

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“…These findings suggest that, if 1g of sulbactam is going to be used to treat an infection associated with A. baumannii, a dosing interval no longer than 4-h should be preferred, whereas using a 2-g dosage would allow a 6-h dosing schedule. Although we have used only one A. baumannii strain in the present study, one of us has recently demonstrated the bactericidal property of sulbactam against several clones of this organism at concentrations equal or higher than the MIC values [25]. …”

Section: Discussionmentioning

confidence: 99%

“…Levels of antibiotics were determined in all serum samples by a bioassay method as previously described [13]. The Bacillus subtilis ATCC 6633 strain and a clinical isolated of A. baumannii (strain 5355-81, sulbactam MIC, 2µg/mL) were used for testing amoxicillin and sulbactam, respectively.…”

Section: Antibiotic Concentration In Serummentioning

confidence: 99%

“…Both early [12] and present [13] evidences suggest that sulbactam is active in vitro against Acinetobacter spp, whereas some reports showed that this drug, given as a combination of ampicillin-sulbactam, may yield acceptable clinical success when treating infections associated with this pathogen [11,14]. However, neither large controlled clinical trials, nor pharmacodynamic studies have been undertaken to assess the efficacy of sulbactam against Acinetobacter spp [11,14].…”

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confidence: 99%

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Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model

Bantar¹,

Canigia²,

Berger³

et al. 2009

Braz J Infect Dis

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Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/ß-lactamase inhibitor combination currently available in 29 countries and may be a suitable option for treating infections caused by Acinetobacter spp. Thus, we sought to search the optimal dosing strategy for this formulation through an ex vivo pharmacodynamic human model against Acinetobacter baumanniii. Four volunteers were randomized to receive alternatively a single dose AMX-SUL infused both either over 30 min or 3h at the following ratios (g/g): 1/0.5; 1/1, and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6-and 8-h sera after dose against a clinical isolate of A. baumannii (sulbactam MIC, 4µg/mL). Bactericidal activity (i.e. a mean decrease ≥3 log 10 CFU/mL in the viable cell counts from the initial inoculum) was displayed by the 0.5-and the 2-h sera after dose for all formulations. The 4-h sera proved inhibitory with the AMX-SUL 1g/1g formulation, albeit a trend to regrowth was observed after 24-h incubation. With the AMX-SUL 0g/2g dose, the 4-h sera proved almost bactericidal activity (i.e. a mean decrease of 2.4 log 10 CFU/mL in the viable cell counts from the initial inoculum), whereas the 6-h sera was inhibitory, with a trend to regrowth after 24-h incubation. When infused over 3h, AMX-SUL 1g/0.5g and 1g/1g, bactericidal activity was displayed by the 0.5-, 2-and the 4-h sera after dose and the 6-h sera proved inhibitory with the AMX-SUL 1g/1g formulation. The present study, albeit preliminary, might give a rationale for the dosing strategy to treat infections caused by A. baumannii with sulbactam, either alone or combined with amoxicillin. A 2-g sulbactam dose seems to be optimal to be infused over 30 min with a 6-h dosing interval. When infused over 3h, AMX-SUL 1g/1g given every 6h or 8h seems a suitable dosing schedule.

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Comparative time–kill study of doxycycline, tigecycline, sulbactam, and imipenem against several clones of Acinetobacter baumannii

Cited by 20 publications

References 31 publications

Pharmacokinetic-Pharmacodynamic Modeling of the In Vitro Activities of Oxazolidinone Antimicrobial Agents against Methicillin-ResistantStaphylococcus aureus

Pharmacokinetic-Pharmacodynamic Modeling of the In Vitro Activities of Oxazolidinone Antimicrobial Agents against Methicillin-ResistantStaphylococcus aureus

In vitro activity of minocycline alone or in combination in multidrug-resistant Acinetobacter baumannii isolates

Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model

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