Re: Re: noninherited resistance

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Tony's been saying streptomycin is the drug of choice for almost as long as I've known him. Unfortunately, I think it's i.v. only. penny <usenethod@...> wrote: Also:http://jac.oxfordjournals.org/cgi/content/abstract/59/2/254The results here with E coli and rifampin are markedly different thanwhat you'd see with MTB. Rifampin at clinical concentrations is apotent killer of

nongrowing MTB.=======================================================Antibiotic treatment in vitro of phenotypically tolerant bacterialpopulationsCamilla Wiuff* and Dan I. AnderssonDepartment of Medical Biochemistry and Microbiology, UppsalaUniversity Box 582, S-751 23 Uppsala, SwedenReceived 2 August 2006; returned 4 October 2006; revised 19 October2006; accepted 21 October 2006*Correspondence address. Health Protection Scotland, Section for HAI & IC, 1 Cadogan Square, Cadogan Street, Glasgow G2 7HF, UK. Tel:+44-141-2822927; Fax: +44-141-8470399; E-mail:camilla.wiuffhps (DOT) scot.nhs.ukObjectives: Most pharmacodynamic models used for design of treatmentregimens are based on time–kill data obtained with normal cells in thesusceptible state without taking into account the killing kinetics ofthe

antibiotic-tolerant cells in the population. We compared themicrobiological efficacy of six antibiotics against tolerant cells andby mathematical modelling explored the potential clinical implicationsof tolerance.Methods: Tolerant cells were obtained by filtration of bacterialcultures of Escherichia coli MG1655 after antibiotic exposure. Killingkinetics of the tolerant cells was compared with that of exponentiallygrowing naive cells. To examine the nutrient dependency of thereversion from the tolerant state to the susceptible state, tolerantcells were re-suspended in Luria–Bertani and PBS and re-exposed toantibiotics. A mathematical model was used to explore the clinicalimplications of antibiotic tolerance.Results: Streptomycin was the most efficient drug against tolerantcells. Ciprofloxacin and ampicillin had intermediate activity againsttolerant cells while rifampicin, tetracycline and erythromycin

hadpoor activity against tolerant cells. No correlation could beestablished between the microbiological efficacies against susceptibleand tolerant cells. Reversion from tolerance to susceptibility wasdependent on the presence of nutrients and growth. Computersimulations demonstrated that the efficacy of antibiotics againsttolerant cell populations has a large influence on treatment outcome.Conclusions: The in vitro killing kinetics of tolerant cells isantibiotic-dependent and different from that of cells in thesusceptible state. This difference in efficacy could have an influenceon treatment outcome and tolerance should therefore be studied furtherin vivo.