International journal of antimicrobial agents
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Int. J. Antimicrob. Agents · Oct 2012
Case ReportsDecreased meropenem levels in Intensive Care Unit patients with augmented renal clearance: benefit of therapeutic drug monitoring.
One of the first-line drugs for empirical antibiotic therapy in patients with hospital-acquired infections is meropenem. An often neglected problem in sepsis is that patients with a normal serum creatinine concentration (SCr) might display augmented renal clearance (ARC). Here we describe two cases of sepsis with subtherapeutic exposures with standard meropenem dosing in whom therapy could be optimised by therapeutic drug monitoring (TDM). ⋯ TDM may represent an invaluable approach to optimising drug exposure of β-lactam antibiotics in patients with ARC in the ICU. Further trials are clearly needed to become better informed about empirical dosing regimens usable in the ICU setting with regard to the relevance of ARC. In the meantime, daily measurement of creatinine clearance as well as TDM can be used to identify patients who manifest ARC, thereby allowing drug therapy to achieve the therapeutic range.
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Int. J. Antimicrob. Agents · Oct 2012
ReviewProbiotics for infectious diseases: more drugs, less dietary supplementation.
According to current definitions, probiotics are live microorganisms that, when ingested in adequate quantities, exert a health benefit to the host. The action of probiotics in the host is exerted by three mechanisms: modulation of the content of gut microbiota; maintenance of the integrity of the gut barrier and prevention of bacterial translocation; and modulation of the local immune response by the gut-associated immune system. Regarding their role for the prevention and treatment of infectious diseases, adequate evidence coming from randomised clinical trials (RCTs) is available for antibiotic-associated diarrhoea (AAD), Clostridium difficile infection (CDI), acute gastroenteritis and infectious complications following admission to the Intensive Care Unit (ICU). ⋯ Available evidence is not sufficient to support administration for the management of CDI. Regarding populations of critically ill patients, data from many RCTs suggest a decrease of infectious complications by starting feeding with probiotics following ICU admission, with the exception of patients suffering from severe pancreatitis. However, it should be underscored that all analysed RCTs are characterised by marked heterogeneity regarding the type of administered probiotic species, precluding robust recommendations.
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Int. J. Antimicrob. Agents · Oct 2012
Comparative StudyEfficacy of tigecycline/colistin combination in a pneumonia model caused by extensively drug-resistant Acinetobacter baumannii.
Due to increasing drug resistance, available antimicrobial options are limited in the treatment of Acinetobacter baumannii infections. Particularly in cases caused by extensively drug-resistant (XDR) A. baumannii, combination regimens must also be taken into consideration. In this study, the efficacies of tigecycline, colistin and tigecycline/colistin combination on bacterial counts in lung tissue were investigated in a rat pneumonia model. ⋯ A greater reduction in bacterial counts was observed at 48 h compared with 24 h in the tigecycline group than in the colistin group (P=0.038 and P=0.139, respectively); the most significant decrease between 24 h and 48 h was observed in the combination group (P=0.014). Despite detection of in vitro synergistic activity in this study, no statistically significant differences were found between colistin, tigecycline and combination treatments in terms of efficacy on bacterial counts in lung tissue. In the treatment of infections with a high mortality rate such as pneumonia caused by XDR A. baumannii, combining tigecycline with colistin during the first 48 h and continuing treatment with one of these agents seems a rational approach.
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Int. J. Antimicrob. Agents · Oct 2012
Impacts of a long-term programme of active surveillance and chlorhexidine baths on the clinical and molecular epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) in an Intensive Care Unit in Scotland.
Evidence is accumulating that active surveillance, when combined with appropriate infection control, is a successful measure for controlling hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA). In this study, the impacts of a long-term control strategy of this type, including the use of chlorhexidine baths, on the clinical and molecular epidemiology of MRSA in the Intensive Care Unit of Aberdeen Royal Infirmary were investigated. Characterisation of 85 sequential index MRSA isolates was performed using phenotypic methods (biotyping), antibiotic susceptibility testing and three genotypic methods (pulsed-field gel electrophoresis, spa typing and multilocus sequence typing) over a 4-year period. ⋯ There was no increase in antibiotic or chlorhexidine resistance. Long-term chlorhexidine bathing was not associated with any detectable loss of efficacy or increase in resistance in MRSA or with any increase in infection with other organisms. Changing clonal epidemiology occurred with no overall change in the prevalence of MRSA.
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Int. J. Antimicrob. Agents · Oct 2012
Simplified dosing regimens of teicoplanin for patient groups stratified by renal function and weight using Monte Carlo simulation.
The purpose of this study was (i) to determine the optimal dosage of teicoplanin for each patient group stratified by renal function and weight based on a population pharmacokinetic model and observed distribution of patient characteristics and (ii) to develop new simplified dosing regimens designed to achieve 15-30 μg/mL. Patient data were collected retrospectively from routine therapeutic drug monitoring files of adult patients who were given the standard loading dose regimen of teicoplanin (400 mg twice on Day 1, followed by 400 mg once daily for 2 days) and whose trough concentration was measured just before administration on Day 4. Monte Carlo simulation was conducted to estimate the trough concentration at 72 h after the initial loading dose (C(min)(72 h)) and at steady state (C(ss)(min)). ⋯ Simplified loading dose and maintenance dose regimens for each group stratified by renal function and weight were created to achieve C(min)(72 h) and C(ss)(min) of 15 μg/mL and 20-25 μg/mL, respectively. The percentage of C(min)(72 h) and C(ss)(min) in the range 15-30 μg/mL was 43-65% and 61-82% across each renal function and weight strata, respectively. These new simplified dosing regimens of teicoplanin could be helpful in individual adjustment of the loading and maintenance doses to achieve 15-30 μg/mL.