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Hypotheses for this failure include possible hidden side-effects (for example, neurological) or inappropriate pharmacokinetic\/pharmacodynamic (PK\/PD) parameters for bacteria with cefepime minimal inhibitory concentrations (MIC) at the highest limits of susceptibility (8 mg\/l) or intermediate-resistance (16 mg\/l) for pathogens such as<jats:italic>Enterobacteriaceae<\/jats:italic>,<jats:italic>Pseudomonas aeruginosa<\/jats:italic>and<jats:italic>Staphylococcus aureus<\/jats:italic>. We examined these issues in a prospective non-interventional study of 21 consecutive intensive care unit (ICU) adult patients treated with cefepime for nosocomial pneumonia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients (median age 55.1 years, range 21.8 to 81.2) received intravenous cefepime at 2 g every 12 hours for creatinine clearance (CL<jats:sub>Cr<\/jats:sub>) \u2265 50 ml\/min, and 2 g every 24 hours or 36 hours for CL<jats:sub>Cr<\/jats:sub>&lt; 50 ml\/minute. Cefepime plasma concentrations were determined at several time-points before and after drug administration by high-pressure liquid chromatography. PK\/PD parameters were computed by standard non-compartmental analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventeen first-doses and 11 steady states (that is, four to six days after the first dose) were measured. Plasma levels varied greatly between individuals, from two- to three-fold at peak-concentrations to up to 40-fold at trough-concentrations. Nineteen out of 21 (90%) patients had PK\/PD parameters comparable to literature values. Twenty-one of 21 (100%) patients had appropriate duration of cefepime concentrations above the MIC (T<jats:sub>&gt;MIC<\/jats:sub>\u2265 50%) for the pathogens recovered in this study (MIC \u2264 4 mg\/l), but only 45 to 65% of them had appropriate coverage for potential pathogens with cefepime MIC \u2265 8 mg\/l. Moreover, 2\/21 (10%) patients with renal impairment (CL<jats:sub>Cr<\/jats:sub>&lt; 30 ml\/minute) demonstrated accumulation of cefepime in the plasma (trough concentrations of 20 to 30 mg\/l) in spite of dosage adjustment. Both had symptoms compatible with non-convulsive epilepsy (confusion and muscle jerks) that were not attributed to cefepime-toxicity until plasma levels were disclosed to the caretakers and symptoms resolved promptly after drug arrest.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These empirical results confirm the suspected risks of hidden side-effects and inappropriate PK\/PD parameters (for pathogens with upper-limit MICs) in a population of ICU adult patients. Moreover, it identifies a safety and efficacy window for cefepime doses of 2 g every 12 hours in patients with a CL<jats:sub>Cr<\/jats:sub>\u2265 50 ml\/minute infected by pathogens with cefepime MICs \u2264 4 mg\/l. On the other hand, prompt monitoring of cefepime plasma levels should be considered in case of lower CL<jats:sub>Cr<\/jats:sub>or greater MICs.<\/jats:p><\/jats:sec>","DOI":"10.1186\/cc8941","type":"journal-article","created":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T18:14:55Z","timestamp":1270145695000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Prospective monitoring of cefepime in intensive care unit adult patients"],"prefix":"10.1186","volume":"14","author":[{"given":"Thomas M","family":"Chapuis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Giannoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A","family":"Majcherczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Chiol\u00e9ro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Denise","family":"Schaller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette M","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Bolay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent A","family":"D\u00e9costerd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Bugnon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Moreillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,4,1]]},"reference":[{"key":"8371_CR1","doi-asserted-by":"publisher","first-page":"2563","DOI":"10.1128\/AAC.01149-05","volume":"50","author":"E Giannoni","year":"2006","unstructured":"Giannoni E, Moreillon P, Cotting J, Moessinger A, Bille J, Decosterd L, Zanetti G, Majcherczyk P, Bugnon D: Prospective determination of plasma imipenem concentrations in critically ill children. 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