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Our study shows satisfactory results, with linezolid concentrations exceeding the susceptibility breakpoint for Gram-positive bacteria in both plasma and epithelial lining fluid. This suggests that a dosage of 600 mg administered intravenously twice daily to critically ill patients with Gram-positive ventilator-associated pneumonia would achieve success against organisms with minimum inhibitory concentrations as high as 2-4 mg/L in both plasma and epithelial lining fluid.

The administration of 4 g of cefepime in continuous infusion in critically ill patients with severe nosocomial pneumonia appears to optimize the pharmacodynamic profile of this beta-lactam by constantly providing concentrations in excess of minimal inhibitory concentration of most of susceptible organisms over the course of therapy in both serum and epithelial lining fluid.

The response to regimens including lopinavir-ritonavir (LPV/r) in patients who have received multiple protease (PR) inhibitors (PI) can be analyzed in terms of human immunodeficiency virus type 1 (HIV-1) genotypic and pharmacokinetic (pK) determinants. We studied these factors and the evolution of HIV-1 resistance in response to LPV/r in a prospective study of patients receiving LPV/r under a temporary authorization in Bordeaux, France. HIV-1 PR and reverse transcriptase sequences were determined at baseline LPV/r for all the patients and at month 3 (M3) and M6 in the absence of response to treatment. pK measurements were determined at M1 and M3. Virological failure (VF) was defined as a plasma viral load >400 copies/ml at M3. , and the individual exposure to LPV were also included covariates. Sixty-eight patients were enrolled. Thirty-four percent had a virological response at M3. An LPV mutation score of >5 mutations, the presence of the PR I54V mutation at baseline, a high number of previous PIs, prior therapy with ritonavir or indinavir, absence of coprescription of efavirenz, and a lower exposure to LPV or lower LPV trough concentrations were independently associated with VF on LPV/r. Additional PI resistance mutations, including primary mutation I50V, could be selected in patients failing on LPV/r. Genotypic and pK parameters should be used to optimize the virological response to LPV/r in PI-experienced patients and to avoid further viral evolution. Treatment of human immunodeficiency virus (HIV)-in-fected individuals with combination therapy including protease inhibitors (PI) results in a significant suppression of HIV replication (1, 2, 3, 11) and in improvement in clinical outcomes, with marked reductions in HIV-associated morbidity and mortality (5, 9). However, the efficacy of antiretroviral (ARV) treatment can be impaired by several factors, including poor compliance with treatment regimens, suboptimal antiviral potency and drug concentrations, and selection of ARV-resistant HIV quasispecies (6). Resistance to PI is driven by the selection of primary mutations located close to the active site of the HIV type 1 (HIV-1) protease, producing significant changes in the affinity of the binding of the inhibitor to the mutant active site (4) and often occurs early during virological rebound. Secondary resistance mutations may be selected later and may compensate for the initial decrease of viral fitness related to the appearance of primary mutations. These secondary mutations tend to be common to all PI, facilitating the emergence of resistance to the whole PI class.Lopinavir (LPV)-ritonavir (LPV/r) is a coformulation of lopinavir, an HIV PI, and low-dose ritonavir, which inhibits LPV metabolism and which enhances plasma LPV levels (12). LPV/r has shown significant potency in treatment-naive and in PI-experienced patients. Few data concerning the determinants and the emergence of drug resistance in LPV/r-treated patients are available. In the LPV/r arm of a first-line ARV therapy protocol, all virological fa...

Maximizing clinical outcomes and minimizing antibiotic resistance using individualized doses may be best achieved with therapeutic drug monitoring of carbapenems.

The monitoring of lopinavir/rironavir-based HAART efficacy should include the number of baseline lopinavir/ritonavir mutations, intracellular and plasma lopinavir Cmin and GIQ calculation.

A target piperacillin serum concentration of at least 35-40 mg/L is probably required to provide alveolar concentrations exceeding the susceptibility breakpoint for gram-negative bacteria (16 mg/L) during ventilator-associated pneumonia. In patients with no/mild renal failure, a continuous daily dose of piperacillin/tazobactam 16/2 g allows reaching this target concentration, which might be not observed with 12/1.5 g/day. In patients with moderate/advanced renal failure, both dosages achieve serum concentrations far above the 35-40 mg/L threshold, suggesting that in that case, therapeutic drug monitoring should be performed in order to adjust the daily dose.

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