Postantibiotic effect in vitro

Fuursted, Kurt

doi:10.1111/j.1600-0463.1999.tb05752.x

APMIS

1999

DOI: 10.1111/j.1600-0463.1999.tb05752.x

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Postantibiotic effect in vitro

Kurt Fuursted

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2001

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“…Amikacin and ofloxacin used in combination with rifampin gave PAEs of over 95 h (PAE for isoniazid-rifampin-amikacin, 97.2 h; PAE for ofloxacin-rifampin-amikacin, 95.0 h). The mechanisms by which PAEs occur have not been fully understood but are probably related to the time for recovery from the sublethal damage (structural or metabolic alterations) induced by the antimicrobial agent (10). It appears that the PAEs of rifampin and isoniazid contribute predominantly to the PAEs of combinations.…”

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confidence: 99%

Postantibiotic Effects of Antituberculosis Agents Alone and in Combination

Chan

Au-Yeang

Yew

et al. 2001

Antimicrob Agents Chemother

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The postantibiotic effects (PAEs) of seven antimycobacterial agents, tested at their respective peak concentrations in serum alone and in different combinations, against Mycobacterium tuberculosis ATCC 27294 were studied with a radiometric culture system in parallel with the viable count method. Rifampin gave the longest PAE (67.8 h) among the drugs used alone, and combinations of first-line drugs generally gave PAEs longer than 120 h. The data obtained might help provide a better understanding of the scientific basis of intermittently administered antituberculosis chemotherapy.Postantibiotic effect (PAE) refers to the continued suppression of bacterial growth following limited exposure of organisms to an antimicrobial agent (1,15,21). A prolonged PAE may allow wider dosing intervals without the loss of therapeutic efficacy (3). For the treatment of tuberculosis, administration of drugs at wider intervals would reduce the costs and toxicities of drugs and facilitate directly observed antituberculosis chemotherapy, thus enhancing patient adherence (8) and leading to a favorable outcome. Earlier work on pulsed exposure to isoniazid, rifampin, and pyrazinamide for 6 to 96 h has provided hints about the suitability of intermittent administration of these drugs for the treatment of tuberculosis (4-7, 16). In an attempt to better understand the scientific basis of the efficacies of certain established intermittently administered antituberculosis regimens, as well as to gain pertinent knowledge about newer antimycobacterial agents, we embarked on a study that addresses the PAEs of various antituberculosis drugs in vitro.The standard strain of Mycobacterium tuberculosis chosen for the study, strain H37Rv (ATCC 27294), was susceptible to all drugs tested. The MICs of all single drugs except pyrazinamide were determined by the broth macrodilution method (25), while susceptibility testing with pyrazinamide was done by the absolute concentration method (12). Altogether, seven antituberculosis drugs were assessed by using concentrations equivalent to their respective peak concentrations in serum (C max ) in humans (17): amikacin (32 mg/liter), ethambutol (5 mg/ liter), isoniazid (4 mg/liter), ofloxacin (8 mg/liter), rifampin (16 mg/liter), streptomycin (40 mg/liter), and pyrazinamide (60 mg/liter). Stock solutions of the drugs (all drugs except ofloxacin were purchased from Sigma, St. Louis, Mo.; ofloxacin was a gift from Daiichi, Tokyo, Japan) were prepared in appropriate solvents, stored at Ϫ70°C in 1.0-ml aliquots, and used within 6 months. For each experiment, aliquots of the stock solutions were thawed and subsequently diluted in Middlebrook 7H9 broth supplemented with 2% glycerol and 10% oleic acid-dextrose-catalase (Difco Laboratories).To determine the PAE, a homogeneous suspension of cells whose turbidity matched that of a no. 1 McFarland standard was obtained from a 3-week-old culture and stored at Ϫ40°C in 1.0-ml aliquots. For each experiment, a single vial of cells was quickly thawed at 37°C and inoculated into 10...

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Postantibiotic Effects of Antituberculosis Agents Alone and in Combination

Chan

Au-Yeang

Yew

et al. 2001

Antimicrob Agents Chemother

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Postantibiotic effect in vitro

Cited by 1 publication

References 187 publications

Postantibiotic Effects of Antituberculosis Agents Alone and in Combination

Postantibiotic Effects of Antituberculosis Agents Alone and in Combination

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