Archive for June 13, 2012

In vitro and in vivo activities of linezolid alone and combined with vancomycin and imipenem against Staphylococcus aureus with reduced susceptibility to glycopeptides.

Eur J Clin Microbiol Infect Dis. 2010 Nov  V.29 N.11 P.1361-7.

Ribes S, Pachón-Ibáñez ME, Domínguez MA, Fernández R, Tubau F, Ariza J, Gudiol F, Cabellos C.

Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L’Hospitalet de Llobregat, Barcelona, Spain.


The objective of this study was to evaluate the in vitro and in vivo efficacies of linezolid (35 mg/kg/5 h), vancomycin (60 mg/kg/5 h), imipenem (30 mg/kg/5 h), linezolid+imipenem, linezolid+vancomycin and vancomycin+imipenem against two clinical Staphylococcus aureus isolates with reduced susceptibility to glycopeptides using time-kill curves and the murine peritonitis model. Time-kill curves were performed over 24 h. For the murine peritonitis model, peritonitis was induced by the intraperitoneal inoculation of 10(8) CFU/ml of each bacterial strain. Four hours later (0 h), the mice were randomly assigned to a control group or to therapeutic groups receiving subcutaneous treatment for 25 h. Bacterial counts in peritoneal fluid, bacteraemia and mortality rates were determined. The time-kill curves showed that the addition of linezolid to imipenem yielded synergistic results after 24 h. The addition of linezolid decreased vancomycin activity. In the animal model, vancomycin and linezolid monotherapies produced comparable bacterial decreases in mice infected with each strain but linezolid achieved higher rates of blood sterilisation. Linezolid tested either in monotherapy or in combination showed similar efficacy against both strains in terms of bacterial killing, number of negative blood cultures and survival. Linezolid and vancomycin were moderately bactericidal and similar in efficacy against glycopeptide-intermediate or -resistant S. aureus. Linezolid combinations, as effective as linezolid tested alone, could be considered as alternative options for the treatment of glycopeptide-intermediate S. aureus (GISA) infections.



June 13, 2012 at 3:04 pm

Pharmacokinetics/pharmacodynamics of colistin and imipenem on mucoid and nonmucoid Pseudomonas aeruginosa biofilms.

Antimicrob Agents Chemother. 2011 Sep  V.55 N.9  P.4469-74.

Hengzhuang W, Wu H, Ciofu O, Song Z, Høiby N.

Department of Clinical Microbiology, Rigshospitalet, University Hospital of Copenhagen, Juliane Maries Vej 22, DK-2100 Copenhagen, Denmark.


The time course of activity of colistin and imipenem against mucoid and nonmucoid Pseudomonas aeruginosa growing in a biofilm showed that compared with those for planktonic bacteria, the kinetics of colistin and imipenem retained the concentration- and time-dependent killing, respectively, but higher doses of antibiotics and longer dosing periods were required for biofilm eradication. Biofilms of mucoid P. aeruginosa were more difficult to eradicate than nonmucoid biofilms.


June 13, 2012 at 3:03 pm

Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of β-lactams.

Crit Care. 2011  V.15 N.5 R206..

Gonçalves-Pereira J, Póvoa P.

Polyvalent Intensive Care Unit, São Francisco Xavier Hospital, Estrada do Forte do Alto do Duque, 1449-005 Lisboa, Portugal.



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.


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.


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.


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.


June 13, 2012 at 3:02 pm


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