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Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: a report from the OPTAMA Program.
Crit Care Med. 2005 Oct; 33(10):2222-7.CC

Abstract

OBJECTIVE

To compare the probability of achieving specific pharmacodynamic exposures of commonly used intravenous antibiotics for the empirical treatment of nosocomial pneumonia against those pathogens most commonly implicated in the disease.

DESIGN

Ten thousand-subject Monte Carlo simulation.

SETTING

Research center.

SUBJECT

None.

INTERVENTIONS

Pharmacodynamic analysis was conducted for the following antimicrobials at standard doses: meropenem, imipenem-cilastatin, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin. Prevalence of causative pathogens was based on the 2000 SENTRY Antimicrobial Surveillance Study, and minimum inhibitory concentration (MIC) values were obtained using the 2003 US MYSTIC database. The probabilities of each drug and dosing regimen in achieving pharmacodynamic targets were calculated. Bactericidal targets were defined as 40% T>MIC for the carbapenems, 50% T>MIC for other beta-lactams, and an area under the curve (AUC)/MIC ratio of 125 for ciprofloxacin. A sensitivity analysis was performed using two alternate models to determine the impact of varying pathogen prevalence on target attainment.

MEASUREMENTS AND MAIN RESULTS

Meropenem and imipenem provided high probabilities of achieving their bactericidal target of 40% T>MIC, with target attainments of 98% for all regimens. At the bactericidal end point of 50% T>MIC, cefepime 2 g every 8 hrs displayed the highest target attainment at 99.9%, followed by cefepime 2 g every 12 hrs, ceftazidime 2 g every 8 hrs, piperacillin/tazobactam 4.5 g every 6 hrs and 3.375 g every 6 hrs, cefepime 1 g every 12 hrs, and ceftazidime 1 g every 8 hrs with target attainments of 95.0%, 92.5%, 92.3%, 91.3%, 90.3%, and 67.9%, respectively. Ciprofloxacin presented the lowest probability of achieving its bactericidal target of an AUC/MIC ratio of 125, with target attainments of 54.7% and 12.0% when given as 400 mg every 8 hrs and 400 mg every 12 hrs, respectively.

CONCLUSIONS

Meropenem, imipenem, cefepime, ceftazidime (2 g every 8 hrs), and piperacillin/tazobactam have high probabilities of achieving adequate pharmacodynamic exposures when given for the empirical treatment of nosocomial pneumonia in the absence of methicillin-resistant S. aureus. Ceftazidime 1g every 8 hrs and ciprofloxacin produce low target attainment rates and will not likely result in high clinical success rates when given as monotherapy.

Authors+Show Affiliations

Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16215374

Citation

Sun, Heather K., et al. "Pharmacodynamics of Antimicrobials for the Empirical Treatment of Nosocomial Pneumonia: a Report From the OPTAMA Program." Critical Care Medicine, vol. 33, no. 10, 2005, pp. 2222-7.
Sun HK, Kuti JL, Nicolau DP. Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: a report from the OPTAMA Program. Crit Care Med. 2005;33(10):2222-7.
Sun, H. K., Kuti, J. L., & Nicolau, D. P. (2005). Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: a report from the OPTAMA Program. Critical Care Medicine, 33(10), 2222-7.
Sun HK, Kuti JL, Nicolau DP. Pharmacodynamics of Antimicrobials for the Empirical Treatment of Nosocomial Pneumonia: a Report From the OPTAMA Program. Crit Care Med. 2005;33(10):2222-7. PubMed PMID: 16215374.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacodynamics of antimicrobials for the empirical treatment of nosocomial pneumonia: a report from the OPTAMA Program. AU - Sun,Heather K, AU - Kuti,Joseph L, AU - Nicolau,David P, PY - 2005/10/11/pubmed PY - 2005/12/24/medline PY - 2005/10/11/entrez SP - 2222 EP - 7 JF - Critical care medicine JO - Crit Care Med VL - 33 IS - 10 N2 - OBJECTIVE: To compare the probability of achieving specific pharmacodynamic exposures of commonly used intravenous antibiotics for the empirical treatment of nosocomial pneumonia against those pathogens most commonly implicated in the disease. DESIGN: Ten thousand-subject Monte Carlo simulation. SETTING: Research center. SUBJECT: None. INTERVENTIONS: Pharmacodynamic analysis was conducted for the following antimicrobials at standard doses: meropenem, imipenem-cilastatin, ceftazidime, cefepime, piperacillin/tazobactam, and ciprofloxacin. Prevalence of causative pathogens was based on the 2000 SENTRY Antimicrobial Surveillance Study, and minimum inhibitory concentration (MIC) values were obtained using the 2003 US MYSTIC database. The probabilities of each drug and dosing regimen in achieving pharmacodynamic targets were calculated. Bactericidal targets were defined as 40% T>MIC for the carbapenems, 50% T>MIC for other beta-lactams, and an area under the curve (AUC)/MIC ratio of 125 for ciprofloxacin. A sensitivity analysis was performed using two alternate models to determine the impact of varying pathogen prevalence on target attainment. MEASUREMENTS AND MAIN RESULTS: Meropenem and imipenem provided high probabilities of achieving their bactericidal target of 40% T>MIC, with target attainments of 98% for all regimens. At the bactericidal end point of 50% T>MIC, cefepime 2 g every 8 hrs displayed the highest target attainment at 99.9%, followed by cefepime 2 g every 12 hrs, ceftazidime 2 g every 8 hrs, piperacillin/tazobactam 4.5 g every 6 hrs and 3.375 g every 6 hrs, cefepime 1 g every 12 hrs, and ceftazidime 1 g every 8 hrs with target attainments of 95.0%, 92.5%, 92.3%, 91.3%, 90.3%, and 67.9%, respectively. Ciprofloxacin presented the lowest probability of achieving its bactericidal target of an AUC/MIC ratio of 125, with target attainments of 54.7% and 12.0% when given as 400 mg every 8 hrs and 400 mg every 12 hrs, respectively. CONCLUSIONS: Meropenem, imipenem, cefepime, ceftazidime (2 g every 8 hrs), and piperacillin/tazobactam have high probabilities of achieving adequate pharmacodynamic exposures when given for the empirical treatment of nosocomial pneumonia in the absence of methicillin-resistant S. aureus. Ceftazidime 1g every 8 hrs and ciprofloxacin produce low target attainment rates and will not likely result in high clinical success rates when given as monotherapy. SN - 0090-3493 UR - https://www.unboundmedicine.com/medline/citation/16215374/Pharmacodynamics_of_antimicrobials_for_the_empirical_treatment_of_nosocomial_pneumonia:_a_report_from_the_OPTAMA_Program_ L2 - https://dx.doi.org/10.1097/01.ccm.0000181528.88571.9b DB - PRIME DP - Unbound Medicine ER -