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Streptococcus pneumoniae bacteraemia: pharmacodynamic correlations with outcome and macrolide resistance--a controlled study.
Int J Antimicrob Agents. 2007 Sep; 30(3):264-9.IJ

Abstract

There are few data on macrolide pharmacodynamics in pneumococcal infections. We evaluated pneumococcal area under the inhibitory concentration-time curve (AUIC) values at the point of hospital admission in 59 bacteraemic patients failing in the community and in 98 bacteraemic controls without macrolide exposure. The area under the 24-h concentration-time curve (AUC24) was calculated for each patient using age, weight and daily dose; using minimum inhibitory concentrations (MICs), the values of AUIC (i.e. AUC24/MIC) were then computed. Clinical and outcome information was also collected in hospital. Five of six patients who died of pneumococcal bacteraemia in hospital received azithromycin, with a mean AUIC of 8.1 prior to hospital admission. Resistant isolates were recovered in 35 (59%) macrolide failures and in only 28 (29%) controls (P=0.001). Azithromycin AUICs averaged 10 in failure patients and 17 in controls. For clarithromycin and erythromycin, the mean AUIC values in failures were 31 and 53, respectively, and the AUIC in controls was >100. Low AUIC values against Streptococcus pneumoniae precede macrolide failures in the community. Patient factors do not predict these outcomes and thus the most likely explanation for macrolide failure in the community is inadequate macrolide activity in patients who receive these antibiotics for treatment of organisms that are not sufficiently susceptible.

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Authors+Show Affiliations

Schentag JJ
CPL Associates, LLC, 3980 Sheridan Drive, Suite 501, Amherst, NY 14226-1727, USA. Schentag@buffalo.edu
Klugman KP
No affiliation info available
Yu VL
No affiliation info available
Adelman MH
No affiliation info available
Wilton GJ
No affiliation info available
Chiou CC
No affiliation info available
Patel M
No affiliation info available
Lavin B
No affiliation info available
Paladino JA
No affiliation info available

MeSH

Anti-Bacterial AgentsArea Under CurveAzithromycinBacteremiaClarithromycinDrug Resistance, BacterialErythromycinHumansMacrolidesMicrobial Sensitivity TestsPneumococcal InfectionsRetrospective StudiesStreptococcus pneumoniaeTreatment Failure

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17587549

Citation

Schentag, Jerome J., et al. "Streptococcus Pneumoniae Bacteraemia: Pharmacodynamic Correlations With Outcome and Macrolide Resistance--a Controlled Study." International Journal of Antimicrobial Agents, vol. 30, no. 3, 2007, pp. 264-9.
Schentag JJ, Klugman KP, Yu VL, et al. Streptococcus pneumoniae bacteraemia: pharmacodynamic correlations with outcome and macrolide resistance--a controlled study. Int J Antimicrob Agents. 2007;30(3):264-9.
Schentag, J. J., Klugman, K. P., Yu, V. L., Adelman, M. H., Wilton, G. J., Chiou, C. C., Patel, M., Lavin, B., & Paladino, J. A. (2007). Streptococcus pneumoniae bacteraemia: pharmacodynamic correlations with outcome and macrolide resistance--a controlled study. International Journal of Antimicrobial Agents, 30(3), 264-9.
Schentag JJ, et al. Streptococcus Pneumoniae Bacteraemia: Pharmacodynamic Correlations With Outcome and Macrolide Resistance--a Controlled Study. Int J Antimicrob Agents. 2007;30(3):264-9. PubMed PMID: 17587549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Streptococcus pneumoniae bacteraemia: pharmacodynamic correlations with outcome and macrolide resistance--a controlled study. AU - Schentag,Jerome J, AU - Klugman,Keith P, AU - Yu,Victor L, AU - Adelman,Martin H, AU - Wilton,Gregory J, AU - Chiou,Christine C, AU - Patel,Manish, AU - Lavin,Bruce, AU - Paladino,Joseph A, Y1 - 2007/06/22/ PY - 2007/02/20/received PY - 2007/03/23/revised PY - 2007/04/23/accepted PY - 2007/6/26/pubmed PY - 2007/10/30/medline PY - 2007/6/26/entrez SP - 264 EP - 9 JF - International journal of antimicrobial agents JO - Int J Antimicrob Agents VL - 30 IS - 3 N2 - There are few data on macrolide pharmacodynamics in pneumococcal infections. We evaluated pneumococcal area under the inhibitory concentration-time curve (AUIC) values at the point of hospital admission in 59 bacteraemic patients failing in the community and in 98 bacteraemic controls without macrolide exposure. The area under the 24-h concentration-time curve (AUC24) was calculated for each patient using age, weight and daily dose; using minimum inhibitory concentrations (MICs), the values of AUIC (i.e. AUC24/MIC) were then computed. Clinical and outcome information was also collected in hospital. Five of six patients who died of pneumococcal bacteraemia in hospital received azithromycin, with a mean AUIC of 8.1 prior to hospital admission. Resistant isolates were recovered in 35 (59%) macrolide failures and in only 28 (29%) controls (P=0.001). Azithromycin AUICs averaged 10 in failure patients and 17 in controls. For clarithromycin and erythromycin, the mean AUIC values in failures were 31 and 53, respectively, and the AUIC in controls was >100. Low AUIC values against Streptococcus pneumoniae precede macrolide failures in the community. Patient factors do not predict these outcomes and thus the most likely explanation for macrolide failure in the community is inadequate macrolide activity in patients who receive these antibiotics for treatment of organisms that are not sufficiently susceptible. SN - 0924-8579 UR - https://www.unboundmedicine.com/medline/citation/17587549/Streptococcus_pneumoniae_bacteraemia:_pharmacodynamic_correlations_with_outcome_and_macrolide_resistance__a_controlled_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(07)00220-8 DB - PRIME DP - Unbound Medicine ER -