PMID- 20110018
OWN - NLM
STAT- MEDLINE
DCOM- 20100409
LR  - 20100129
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 31
IP  - 11
DP  - 2009 Nov
TI  - Probability of pharmacodynamic target attainment with standard and 
      prolonged-infusion antibiotic regimens for empiric therapy in adults with 
      hospital-acquired pneumonia.
PG  - 2765-78
LID - 10.1016/j.clinthera.2009.11.026 [doi]
AB  - BACKGROUND: The pharmacodynamic characteristics of antibiotics should be 
      considered when choosing empiric dosage regimens for the treatment of pneumonia. 
      OBJECTIVE: This study compared the probabilities of achieving requisite 
      pharmacodynamic exposure (ie, f T > MIC, AUC/MIC) for antibiotics given for the 
      empiric treatment of hospital-acquired pneumonia (HAP) as recommended by the 2005 
      guidelines of the American Thoracic Society and the Infectious Diseases Society 
      of America. METHODS: In a 5000-patient Monte Carlo simulation, pharmacodynamic 
      analyses were performed for standard doses of cefepime, ceftazidime, ceftriaxone, 
      ciprofloxacin, ertapenem, imipenem, levofloxacin, meropenem, and 
      piperacillin/tazobactam. Prolonged 3-hour infusion regimens were also evaluated 
      for anti-pseudomonal beta-lactams. MIC data were incorporated from the 2007 
      Meropenem Yearly Susceptibility Test Information Collection, a national 
      surveillance study. The weighted cumulative fraction of response (wCFR) against 
      common pneumonia pathogens was determined for each regimen. A second scenario was 
      conducted by altering the pathogen prevalence to assess wCFR for late-onset 
      pneumonia (ie, HAP in patients with prolonged mechanical ventilation). Optimal 
      wCFR was defined a priori as >or=90%. RESULTS: Among the 0.5-hour infusions, 
      cefepime, ceftazidime, and meropenem had the highest wCFRs (>or=90%) against 
      pathogens that cause HAP (cefepime, 1 g q8h, 92.8%; 2 g q8h, 97.2%; 2 g q12h, 
      94.3%; ceftazidime, 2 g q8h, 93.2%; meropenem, 1 g q8h, 90.9%; 2 g q8h, 93.9%). 
      Imipenem (500 mg q6h, 85.5%; 1 g q8h, 88.1%) and piperacillin/tazobactam (4.5 g 
      q6h, 80.5%) as 0.5-hour infusions were nearly optimal, whereas ceftriaxone, 
      ertapenem, and the fluoroquinolones had the lowest wCFR values. All regimens 
      showed lower wCFRs for late-onset pneumonia than for HAP. Optimal wCFRs were 
      found only with prolonged (3-hour) infusions of 2 g q8h for ceftazidime (94.5%) 
      and meropenem (90.1%), whereas cefepime 2 g q8h achieved optimal wCFR with both a 
      0.5-hour infusion (93.1%) and a 3-hour infusion (95.3%). CONCLUSIONS: Results of 
      this model suggest that standard doses of most antipseudomonal beta-lactams 
      (cefepime, ceftazidime, and meropenem) had high probabilities of achieving 
      optimal pharmacodynamic exposure as empiric therapy for HAP, whereas the low 
      probabilities predicted from ceftriaxone, ertapenem, and the fluoroquinolones 
      suggest that these agents would be inappropriate as monotherapy. For late-onset 
      HAP, prolonged infusions of cefepime, ceftazidime, and meropenem offered the 
      highest probabilities of achieving bactericidal exposure.
CI  - Copyright 2009 Excerpta Medica Inc. All rights reserved.
FAU - Kim, Aryun
AU  - Kim A
AD  - Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, 
      Connecticut 06102, USA.
FAU - Kuti, Joseph L
AU  - Kuti JL
FAU - Nicolau, David P
AU  - Nicolau DP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anti-Bacterial Agents)
SB  - IM
MH  - Algorithms
MH  - Anti-Bacterial Agents/*administration & dosage/pharmacokinetics/*therapeutic use
MH  - Area Under Curve
MH  - Computer Simulation
MH  - Cross Infection/*drug therapy/microbiology
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Infusions, Intravenous
MH  - Metabolic Clearance Rate
MH  - Microbial Sensitivity Tests
MH  - Monte Carlo Method
MH  - Pneumonia, Bacterial/*drug therapy/microbiology
MH  - Population
EDAT- 2010/01/30 06:00
MHDA- 2010/04/10 06:00
CRDT- 2010/01/30 06:00
PHST- 2009/09/28 00:00 [accepted]
PHST- 2010/01/30 06:00 [entrez]
PHST- 2010/01/30 06:00 [pubmed]
PHST- 2010/04/10 06:00 [medline]
AID - S0149-2918(09)00416-0 [pii]
AID - 10.1016/j.clinthera.2009.11.026 [doi]
PST - ppublish
SO  - Clin Ther. 2009 Nov;31(11):2765-78. doi: 10.1016/j.clinthera.2009.11.026.