Once-daily dosing regimen for aminoglycoside plus β-Lactam combination therapy of serious bacterial infections: Comparative trial with netilmicin plus ceftriaxone

Braak, Edith Wmt ter; Vries, Peter J. de; Bouter, K.P.; Vegt, Sytze G. van der; Dorrestein, Gijsbert C.; Nortier, J.W.R.; Dijk, Arie P.J. van; Verkooyen, R. P.; Verbrugh, Henri A.

doi:10.1016/0002-9343(90)90099-y

Cited by 141 publications

(63 citation statements)

References 27 publications

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“…Nevertheless, previous observations with these and other strains suggest that derepression of ␤-lactamases of the two types, penicillinase and cephalosporinase, may occur after a short exposure to these antibiotic classes (10). In our previous studies, resistance to other commonly used agents (fluoroquinolones, tetracyclines, clindamycin, etc.)…”

Section: Discussionmentioning

confidence: 66%

Is In Vitro Antibiotic Combination More Effective than Single-Drug Therapy against Anthrax?

Athamna

Nura

et al. 2005

Antimicrob Agents Chemother

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Anthrax has recently been the focus of attention as a potential biological warfare agent. The therapy and prophylaxis of anthrax require vaccination combined with prolonged antibacterial therapy. It is important to examine if antibiotic combinations might shorten the 60-day period recommended for postexposure prophylaxis by providing a more radical and rapid killing of the vegetative anthrax forms and thus reducing the infective load (5). Of equal interest is the question whether combinations might reduce the risk for the development of resistance by Bacillus anthracis. During the last bioterror attack in the United States, in 2001, many individuals received antibiotic combinations as therapy and as postexposure prophylaxis (6). Clindamycin was often used based on the assumption that it might decrease the production of bacterial toxins and thus diminish the severity of disease manifestations (3).The aim of the present study was to investigate possible interactions among several antibiotics potentially effective against B. anthracis. MATERIALS AND METHODSAntibacterial agents. The antibiotics tested in this study were as follows: ciprofloxacin and moxifloxacin (Bayer, Leverkusen, Germany), tetracycline (Sigma, Rehovot, Israel), penicillin G (Rafa Laboratories, Jerusalem, Israel), amoxicillin (GSK, Petach Tiqva, Israel), vancomycin (Eli Lilly, Sesto Fiorentino, Italy), clarithromycin (Abbott, Promedico, Petch-Tiqva, Israel), telithromycin and quinupristin-dalfopristin (Q-D) (Aventis, Paris, France), clindamycin and linezolid [Pharmacia (Agis), Bnei Braq, Israel, and Pharmacia, Kalamazoo, Mich.], and rifampin (Sigma).Penicillin G, vancomycin, rifampin, clindamycin, linezolid, and Q-D were received as dry laboratory powders and were dissolved in phosphate-buffered saline (pH 7.2). Amoxicillin was dissolved in distilled water. Clarithromycin was dissolved in analytical-grade acetone, while telithromycin and tetracycline were dissolved initially in 2 drops of acetic acid and ethanol (100%), respectively, and all three of these antibiotics were subsequently diluted in distilled water to the required concentration; at the final concentrations used, these solvents had no demonstrable antibacterial activity. Prepared solutions were frozen in small aliquots and thawed before use. Antibiotic solutions were sterilized through 0.45-m-pore-size filters (Millipore S.A., Paris, France). Moxifloxacin and ciprofloxacin were obtained as injectable solutions. Bacterial strains and growth conditions. The bacteria used in this study were two strains of B. anthracis: strain Sterne (a gift from the Colorado Serum Institute, Denver, Colo.) and the Russian strain STi, purchased in Moscow, Russia. Neither strain is a human pathogen, because both lack the plasmid necessary to produce the capsule of the vegetative form, which is necessary for human pathogenicity. Bacterial spores were stored in sterile 30% glycerol in phosphate-buffered saline and were spread on brain heart infusion (BHI) agar (Difco Laboratories, Detroit, Mich.) and incubate...

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Section: Discussionmentioning

confidence: 66%

Is In Vitro Antibiotic Combination More Effective than Single-Drug Therapy against Anthrax?

Athamna

Nura

et al. 2005

Antimicrob Agents Chemother

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“…Using pharmacokinetic individualisation, Konrad et al [7] found that the average total daily dose of netilmicin in patients with normal renal function was 7.8 mg kg-" day-l and recommended a starting dose of once-daily therapy of 7.0 mg kg-' day-'. Retrospective A variety of authors have recommended or implied that trough concentrations of less than 2 mg 1-are acceptable when using once-daily dosing [3,7,10,11]. Others have said that 2 mg 1-1 is too high and have suggested an upper limit of 1 mg 1-1 for a 24 h trough concentration [9,12].…”

Section: Introductionmentioning

confidence: 99%

A suggested approach to once‐daily aminoglycoside dosing.

Begg

Barclay

Duffull

1995

Brit J Clinical Pharma

310

201

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1. Once‐daily aminoglycoside dosing has many advantages and has been widely advocated. However, existing guidelines for methods of administration and monitoring are non‐specific and may lead to excessive dosing. 2. The traditional approach of aiming for target peak and trough concentrations is not appropriate for once‐daily dosing. 3. A method is proposed which uses a target area under the concentration‐ time curve (AUC) for the aminoglycoside based on the 24 h AUC that would result with conventional dosing. This method requires measurement of two drug concentrations, one approximately 0.5 h after the end of the infusion and another at a later time (6‐22 h) depending on renal function. 4. A simpler, graphical method is also proposed for patients with normal renal function, which requires the measurement of a single concentration at a time between 6 and 14 h. 5. Both methods are likely to be safer than existing guidelines.

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“…The exploration of dosing strategies to enhance the utility of an antibiotic agent is not a new approach (23,25). This approach was utilized previously with daptomycin and was pivotal in the discovery that skeletal muscle toxicity issues were associated with more frequent dosing rather than a maximum concentration (15).…”

Section: Discussionmentioning

confidence: 99%

“…The vancomycin concentrations used in the timekill study (0, 0.75, 2. 25,8,16,25, and 50 g/ml) reflected the freevancomycin peak and trough concentrations for the dosing regimens evaluated in the HFIM. A starting inoculum of the same density as that for the HFIM (10 5.8 CFU/ml) was used, and various concentrations of vancomycin were added to conical tubes.…”

Section: Time-kill Assaymentioning

confidence: 99%

Evaluation of Once-Daily Vancomycin against Methicillin-Resistant Staphylococcus aureus in a Hollow-Fiber Infection Model

Nicasio

Bulitta

Lodise

et al. 2012

Antimicrob Agents Chemother

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For methicillin-resistant Staphylococcus aureus (MRSA) infections, data suggest that the clinical response is significantly better if the total vancomycin area under the concentration-time curve (AUC)/MIC ratio is >400. While the AUC/MIC ratio is the accepted pharmacokinetic/pharmacodynamic (PK/PD) index for vancomycin, this target has been achieved using multiple daily doses. We are unaware of a systematically designed dose fractionation study to compare the bactericidal activity of once-daily administration to that of traditional twice-daily administration. A dose fractionation study was performed with vancomycin in an in vitro hollow-fiber infection model against an MRSA USA300 strain (MIC of 0.75 g/ml) using an inoculum of ϳ10 6 CFU/ ml. The three vancomycin regimens evaluated for 168 h were 2 g every 24 h (q24h) as a 1-h infusion, 1 g q12h as a 1-h infusion, and 2 g q24h as a continuous infusion. Free steady-state concentrations (assuming 45% binding) for a total daily AUC/MIC ratio of >400 were simulated for all regimens. A validated liquid chromatography-tandem mass spectrometry method was used to determine vancomycin concentrations. Although once-daily and twice-daily dosage regimens exhibited total trough concentrations of <15 g/ml, all regimens achieved similar bactericidal activities between 24 and 168 h and suppressed the amplification of nonsusceptible subpopulations. No colonies were found on agar plates with 3؋ MIC for any of the treatment arms. Overall, the results suggest that once-daily vancomycin administration is feasible from a PK/PD perspective and merits further inquiry in the clinical arena. Given the dual threat of diminishing vancomycin efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and recent reports of rising nephrotoxicity (10, 22) (albeit potentially due to concomitant dosing increases), new vancomycin dosing strategies are urgently needed. From a pharmacodynamic viewpoint, there is an opportunity to alter standard dosage regimens of vancomycin in clinical practice to optimize outcomes and minimize toxicity. Data suggest that killing by vancomycin is concentration dependent, and a near-maximal bactericidal effect is achieved against MRSA when the ratio of the area under the total vancomycin concentration-time curve (AUC) to the MIC exceeds 400 (22). While an AUC/MIC ratio of 400 is a well-recognized pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin, this target has been determined using multiple daily doses, which has resulted in the default stance of using multiple-daily-dosing regimens in clinical practice (4,5,7,9,12,13,20,21). The possibility of once-daily administration is appealing from a PK/PD perspective, as it affords the ability to achieve more robust AUCs in a defined interval (i.e., during the first 6 to 12 h) while minimizing trough concentrations, which predicts nephrotoxicity (10). However, we are unaware of a systematically designed dose fractionation study that compared the bactericidal activity of a once-daily administration of vanc...

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Once-daily dosing regimen for aminoglycoside plus β-Lactam combination therapy of serious bacterial infections: Comparative trial with netilmicin plus ceftriaxone

Cited by 141 publications

References 27 publications

Is In Vitro Antibiotic Combination More Effective than Single-Drug Therapy against Anthrax?

Is In Vitro Antibiotic Combination More Effective than Single-Drug Therapy against Anthrax?

A suggested approach to once‐daily aminoglycoside dosing.

Evaluation of Once-Daily Vancomycin against Methicillin-Resistant Staphylococcus aureus in a Hollow-Fiber Infection Model

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