title: Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams.
abstract: BACKGROUND
  Several reports have shown marked heterogeneity of antibiotic pharmacokinetics (PK) in patients admitted to ICUs, which might potentially affect outcomes. Therefore, the pharmacodynamic (PD) parameter of the efficacy of β-lactam antibiotics, that is, the time that its concentration is above the bacteria minimal inhibitory concentration (T > MIC), cannot be safely extrapolated from data derived from the PK of healthy volunteers.
  
  
  METHODS
  We performed a full review of published studies addressing the PK of intravenous β-lactam antibiotics given to infected ICU patients. Study selection comprised a comprehensive bibliographic search of the PubMed database and bibliographic references in relevant reviews from January 1966 to December 2010. We selected only English-language articles reporting studies addressing β-lactam antibiotics that had been described in at least five previously published studies. Studies of the PK of patients undergoing renal replacement therapy were excluded.
  
  
  RESULTS
  A total of 57 studies addressing six different β-lactam antibiotics (meropenem, imipenem, piperacillin, cefpirome, cefepime and ceftazidime) were selected. Significant PK heterogeneity was noted, with a broad, more than twofold variation both of volume of distribution and of drug clearance (Cl). The correlation of antibiotic Cl with creatinine clearance was usually reported. Consequently, in ICU patients, β-lactam antibiotic half-life and T > MIC were virtually unpredictable, especially in those patients with normal renal function. A better PD profile was usually obtained by prolonged or even continuous infusion. Tissue penetration was also found to be compromised in critically ill patients with septic shock.
  
  
  CONCLUSIONS
  The PK of β-lactam antibiotics are heterogeneous and largely unpredictable in ICU patients. Consequently, the dosing of antibiotics should be supported by PK concepts, including data derived from studies of the PK of ICU patients and therapeutic drug monitoring.
authors.affiliation: Polyvalent Intensive Care Unit, São Francisco Xavier Hospital, Estrada do Forte do Alto do Duque, 1449-005 Lisboa, Portugal. joaogpster@gmail.com
authors.forename: Joao
authors.initials: J
authors.lastname: Gonçalves-Pereira
authors.forename: Pedro
authors.initials: P
authors.lastname: Póvoa
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D000077723:Cefepime; D002442:Ceftazidime / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000493:pharmacokinetics; D016638:Critical Illness; D006801:Humans; D015378:Imipenem / Q000493:pharmacokinetics; D007239:Infections / Q000378:metabolism; D000077731:Meropenem; D010878:Piperacillin / Q000493:pharmacokinetics; D013845:Thienamycins / Q000493:pharmacokinetics; D047090:beta-Lactams / Q000493:pharmacokinetics*; D000097572:Cefpirome
chemical_list: D000900:Anti-Bacterial Agents; D000077723:Cefepime; D002442:Ceftazidime; D002511:Cephalosporins; D015378:Imipenem; D000077731:Meropenem; D010878:Piperacillin; D013845:Thienamycins; D047090:beta-Lactams; D000097572:Cefpirome