2.50
Hdl Handle:
http://hdl.handle.net/2336/33012
Title:
Penicillin pharmacodynamics in four experimental pneumococcal infection models
Authors:
Erlendsdottir, H; Knudsen, JD; Odenholt, I; Cars, O; Espersen, F; Frimodt-Møller, N; Fuursted, K; Kristinsson, KG; Gudmundsson, S
Citation:
Antimicrob. Agents Chemother. 2001, 45(4):1078-85
Issue Date:
1-Apr-2001
Abstract:
Clinical and animal studies indicate that with optimal dosing, penicillin may still be effective against penicillin-nonsusceptible pneumococci (PNSP). The present study examined whether the same strains of penicillin-susceptible pneumococci (PSP) and PNSP differed in their pharmacodynamic responses to penicillin by using comparable penicillin dosing regimens in four animal models: peritonitis, pneumonia, and thigh infection in mice and tissue cage infection in rabbits. Two multidrug-resistant isolates of Streptococcus pneumoniae type 6B were used, one for which the penicillin MIC was 0.016 microg/ml and the other for which the penicillin MIC was 1.0 microg/ml. Two additional strains of PNSP were studied in the rabbit. The animals were treated with five different penicillin regimens resulting in different maximum concentrations of drugs in serum (C(max)s) and times that the concentrations were greater than the MIC (T(>MIC)s). The endpoints were bacterial viability counts after 6 h of treatment in the mice and 24 h of treatment in the rabbits. Similar pharmacodynamic effects were observed in all models. In the mouse models bactericidal activity depended on the T(>MIC) and to a lesser extent on the Cmax/MIC and the generation time but not on the area under the concentration-time curve (AUC)/MIC. Maximal bactericidal activities were similar for both PSP and PNSP, being the highest in the peritoneum and blood (approximately 6 log10 CFU/ml), followed by the thigh (approximately 3 log10 CFU/thigh), and being the lowest in the lung (approximately 1 log10 CFU/lung). In the rabbit model the maximal effect was approximately 6 log10 CFU/ml after 24 h. In the mouse models bactericidal activity became marked when T(>MIC) was > or =65% of the experimental time and C(max) was > or =15 times the MIC, and in the rabbit model bactericidal activity became marked when T(>MIC) was > or =35%, Cmax was > or =5 times the MIC, and the AUC at 24 h/MIC exceeded 25. By optimization of the Cmax/MIC ratio and T(>MIC), the MIC of penicillin for pneumococci can be used to guide therapy and maximize therapeutic efficacy in nonmeningeal infections caused by PNSP.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://aac.asm.org/cgi/content/abstract/45/4/1078

Full metadata record

DC FieldValue Language
dc.contributor.authorErlendsdottir, H-
dc.contributor.authorKnudsen, JD-
dc.contributor.authorOdenholt, I-
dc.contributor.authorCars, O-
dc.contributor.authorEspersen, F-
dc.contributor.authorFrimodt-Møller, N-
dc.contributor.authorFuursted, K-
dc.contributor.authorKristinsson, KG-
dc.contributor.authorGudmundsson, S-
dc.date.accessioned2008-07-24T11:25:07Z-
dc.date.available2008-07-24T11:25:07Z-
dc.date.issued2001-04-01-
dc.date.submitted2008-07-24-
dc.identifier.citationAntimicrob. Agents Chemother. 2001, 45(4):1078-85en
dc.identifier.issn0066-4804-
dc.identifier.pmid11257018-
dc.identifier.doi10.1128/AAC.45.4.1078-1085.2001-
dc.identifier.urihttp://hdl.handle.net/2336/33012-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractClinical and animal studies indicate that with optimal dosing, penicillin may still be effective against penicillin-nonsusceptible pneumococci (PNSP). The present study examined whether the same strains of penicillin-susceptible pneumococci (PSP) and PNSP differed in their pharmacodynamic responses to penicillin by using comparable penicillin dosing regimens in four animal models: peritonitis, pneumonia, and thigh infection in mice and tissue cage infection in rabbits. Two multidrug-resistant isolates of Streptococcus pneumoniae type 6B were used, one for which the penicillin MIC was 0.016 microg/ml and the other for which the penicillin MIC was 1.0 microg/ml. Two additional strains of PNSP were studied in the rabbit. The animals were treated with five different penicillin regimens resulting in different maximum concentrations of drugs in serum (C(max)s) and times that the concentrations were greater than the MIC (T(>MIC)s). The endpoints were bacterial viability counts after 6 h of treatment in the mice and 24 h of treatment in the rabbits. Similar pharmacodynamic effects were observed in all models. In the mouse models bactericidal activity depended on the T(>MIC) and to a lesser extent on the Cmax/MIC and the generation time but not on the area under the concentration-time curve (AUC)/MIC. Maximal bactericidal activities were similar for both PSP and PNSP, being the highest in the peritoneum and blood (approximately 6 log10 CFU/ml), followed by the thigh (approximately 3 log10 CFU/thigh), and being the lowest in the lung (approximately 1 log10 CFU/lung). In the rabbit model the maximal effect was approximately 6 log10 CFU/ml after 24 h. In the mouse models bactericidal activity became marked when T(>MIC) was > or =65% of the experimental time and C(max) was > or =15 times the MIC, and in the rabbit model bactericidal activity became marked when T(>MIC) was > or =35%, Cmax was > or =5 times the MIC, and the AUC at 24 h/MIC exceeded 25. By optimization of the Cmax/MIC ratio and T(>MIC), the MIC of penicillin for pneumococci can be used to guide therapy and maximize therapeutic efficacy in nonmeningeal infections caused by PNSP.en
dc.language.isoenen
dc.relation.urlhttp://aac.asm.org/cgi/content/abstract/45/4/1078en
dc.subject.meshAnimalsen
dc.subject.meshDiffusion Chambers, Cultureen
dc.subject.meshDrug Administration Scheduleen
dc.subject.meshHalf-Lifeen
dc.subject.meshLungen
dc.subject.meshMiceen
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshPenicillin Resistanceen
dc.subject.meshPenicillinsen
dc.subject.meshPeritoneumen
dc.subject.meshPeritonitisen
dc.subject.meshPneumococcal Infectionsen
dc.subject.meshPneumonia, Pneumococcalen
dc.subject.meshRabbitsen
dc.subject.meshSerum Bactericidal Testen
dc.subject.meshThighen
dc.titlePenicillin pharmacodynamics in four experimental pneumococcal infection modelsen
dc.typeArticleen
dc.contributor.departmentDepartments of Microbiology, Landspitalinn (University Hospital), Reykjavík, Iceland.en
dc.identifier.journalAntimicrobial agents and chemotherapyen

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