Postantibiotic Suppression of Bacterial Growth

Bundtzen, Robert W.; Gerber, Andreas; Cohn, David L.; Craig, William A.

doi:10.1093/clinids/3.1.28

Cited by 307 publications

(213 citation statements)

References 19 publications

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“…This finding reflected the dose-response curve observed with gentamicin in vitro which showed that increasing concentrations of gentamicin increased both absolute bacterial killing and the speed of killing. In addition, Bundtzen et al (1981) have demonstrated a PAE of gentamicin on Ps. aeruginosa which lasted 1-6-2-6 h. This effect may thus cover, at least in part, the period of sub-MIC plasma levels between doses and prevent early bacterial regrowth during that phase of treatment In conclusion, a gentamicin-type response, i.e.…”

Section: Discussionmentioning

confidence: 94%

“…However, it should be remembered that ticarcillin clearly lacks a PAE on Ps. aeruginosa in vitro (Bundtzen et al, 1981). Therefore, it is logical to conclude that any antibiotic showing a response like that of ticarcillin does require super-MIC drug levels at all times in order to exert its maximal antimicrobial activity in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…In similar experiments, the regrowth pattern of bacteria can be studied in vitro after short exposure of the organisms to the study drug. Using such technique, Bundtzen et al, (1981) and have shown that exposure of various Gram-negative bacteria to inhibitors of protein-or nucleic acid-synthesis is followed by a persistent post-antibiotic effect (PAE); i.e. a persistent suppression of bacterial growth upon removal of the drug.…”

Section: Introductionmentioning

confidence: 99%

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In-vivo assessment of in-vitro killing patterns of Pseudomonas aeruginosa

Gerber

Feller-Segessenmann

1985

Journal of Antimicrobial Chemotherapy

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In-vivo assessment of in-vitro killing patterns of Pseudomonas aeruginosa

Gerber

Feller-Segessenmann

1985

Journal of Antimicrobial Chemotherapy

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“…On the basis of sound experimental work it has been postulated that the activity of j3-lactam drugs on organisms other than Pseudomonas depends also on the aggregate time the drug level stays above the MIC [15,16]. In addition, no substantial postantibiotic effect (PAE; i.e., suppression of bacterial growth after removal of the drug) could be demonstrated for /3-lactam drugs against gram-negative organisms [17]. This lack of a PAE may be an additional factor that explains the poor efficacy of bolus injections of P-lactam antibiotics in the present study.…”

Section: Discussionmentioning

confidence: 99%

Antibiotic Therapy of Infections Due to Pseudomonas aeruginosa in Normal and Granulocytopenic Mice: Comparison of Murine and Human Pharmacokinetics

Gerber¹,

Brugger²,

Feller³

et al. 1986

Journal of Infectious Diseases

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112

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An effort was made to elucidate the limits of drug-activity tests in small animals. Human plasma kinetics of gentamicin, netilmicin, ticarcillin, ceftazidime, and ceftriaxone were approximated in normal and in granulocytopenic mice infected with various strains of Pseudomonas aeruginosa in the thigh muscle or intraperitoneally. The effect of such dosing on bacterial time-kill curves and on survival was compared with the effect of identical amounts of drug given as a single-bolus injection. With fl-lactams, a highly significant superiority of fractionated dosing (simulated human kinetics) over bolus injections (murine plasma kinetics) was demonstrated, whereas with aminoglycosides it was a singlebolus injection that tended to be more active. Thus, when tested in conventional smallanimal models, aminoglycoside activity may be overestimated, whereas fl-lactam activity may be underestimated in respect to humans. These differences found in vivo most probably reflect the different pharmacodynamics between aminoglycosides and f3-lactam drugs (time-kill curves, dose-response curves, and postantibiotic effect) similar to those previously observed in vitro.In a first approach, the in vivo activity and toxicity of any new drug is routinely studied in experimental models by using small animals such as mice, rats, guinea pigs, or rabbits. Moreover, some measure of the activity and toxicity of a single dose has become a mandatory requirement for any new drug to be licensed. Although conclusions from such studies are not directly transferable to man, they are at least looked on as a basis for investigations to be performed in more expensive animal models or humans. However, major biologic differences have to be considered between small experimental animals and man, one of which is metabolic activity in general. This difference becomes most evident in a compari- The present study was based on the hypothesis that the difference between small animals and man regarding drug kinetics cannot be overcome by just injecting larger amounts (per kilogram of body weight) of that substance into small animals. Rather, some kind of "human-adapted" pharmacokinetics of the study drug should be approximated in small animals.In a tentative pioneering effort we used an experimental thigh infection -as well as the standard mouse peritonitis model -to elucidate the impact of murine vs. human half-life of J3-lactam drugs and aminoglycosides on activity against Pseudomonas aeruginosa. In one group of mice the study drug was given as a single-bolus injection that was followed 90

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“…There is the possibility that the drug binds to sites of the bacterial cell surface in quantities sufficient to produce a bacteriostatic effect as the result of reversible damages 27 . Regarding β-lactam antibiotics, the PAE could represent the time required for the bacteria to produce new enzymes necessary to the cell wall synthesis or for liberation of the enzymes bound to the drug 7,26,40 .…”

Section: Discussionmentioning

confidence: 99%

Cell surface hydrophobicity and adherence of a strain of group B streptococci during the post-antibiotic effect of penicillin

Araújo¹,

Oliveira²,

Mattos³

et al. 2008

Rev. Inst. Med. trop. S. Paulo

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SUMMARYThe minimum inhibitory concentration and post-antibiotic effects of an antimicrobial agent are parameters to be taken into consideration when determining its dosage schedules. The in vitro post-antibiotic effects on cell surface hydrophobicity and bacterial adherence were examined in one strain of group B streptococci. Exposure of the microorganism for 2 h at 37 °C to 1 x MIC of penicillin induced a PAE of 1.1 h. The cell surface charge of the Streptococcus was altered significantly during the postantibiotic phase as shown by its ability to bind to xylene: hydrophobicity was decreased. Bacterial adherence to human buccal epithelial cells was also reduced. The results of the present investigation indicate that studies designed to determine therapeutic regimens should evaluate the clinical significance of aspects of bacterial physiology during the post-antibiotic period.

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Postantibiotic Suppression of Bacterial Growth

Cited by 307 publications

References 19 publications

In-vivo assessment of in-vitro killing patterns of Pseudomonas aeruginosa

In-vivo assessment of in-vitro killing patterns of Pseudomonas aeruginosa

Antibiotic Therapy of Infections Due to Pseudomonas aeruginosa in Normal and Granulocytopenic Mice: Comparison of Murine and Human Pharmacokinetics

Cell surface hydrophobicity and adherence of a strain of group B streptococci during the post-antibiotic effect of penicillin

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