International journal of antimicrobial agents
-
Int. J. Antimicrob. Agents · May 2015
Randomized Controlled TrialPharmacokinetic/pharmacodynamic analysis of an intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis.
Recent data suggest that intensified antimicrobial treatment may improve the outcome of tuberculous meningitis (TBM). Considering that drug exposure is the intermediate link between dose and effect, we examined the concentration-response relationship for rifampicin and moxifloxacin in TBM patients. In an open-label, phase 2 clinical trial performed in Indonesia (ClinicalTrials.gov NCT01158755), 60 TBM patients were randomised to receive standard-dose (450mg oral) or high-dose rifampicin (600mg intravenous) plus either oral moxifloxacin (400mg or 800mg) or ethambutol (750mg). ⋯ From exposure-response curves, a rifampicin plasma AUC0-6h of ∼70mg·h/L (AUC0-24h of ∼116mgh/L) and a Cmax of ∼22mg/L were deduced as minimum target values for treatment. A strong concentration-effect relationship was found, with higher rifampicin exposure leading to better TBM survival. The current treatment dose of rifampicin is suboptimal; higher doses of rifampicin should be evaluated.
-
Int. J. Antimicrob. Agents · May 2015
Differences in risk factors and drug susceptibility between Mycobacterium avium and Mycobacterium intracellulare lung diseases in China.
The aim of this study was to investigate the differences in risk factors and drug susceptibility between Mycobacterium avium and Mycobacterium intracellulare lung diseases in China. In total, 452 nontuberculous mycobacteria (NTM) strains isolated from patients with NTM lung diseases in four specialised TB hospitals were enrolled in this study. The minimum inhibitory concentration (MIC) was used to evaluate the drug susceptibility of M. avium and M. intracellulare isolates. ⋯ In conclusion, these data demonstrated that M. intracellulare was the most common NTM species in China. This study also revealed that M. intracellulare and M. avium differed in their drug susceptibility profiles. In addition, clinical cases of M. intracellulare lung diseases were more likely to be found in the aged population and among patients with COPD co-morbidity.
-
Int. J. Antimicrob. Agents · May 2015
Subtleties in practical application of prolonged infusion of β-lactam antibiotics.
Prolonged infusion (PI) of β-lactam antibiotics is increasingly used in order to optimise antibiotic exposure in critically ill patients. Physicians are often not aware of a number of subtleties that may jeopardise the treatment. In this clinically based paper, we stress pragmatic issues, such as the importance of a loading dose before PI, and discuss a number of important practicalities that are mandatory to benefit from the pharmacokinetic advantages of prolonged β-lactam antibiotic administration.
-
Int. J. Antimicrob. Agents · May 2015
Cefepime free minimum concentration to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneumonia.
Cefepime is an antibiotic commonly used in nosocomial infections. The objective of this study was to elucidate the relationship between cefepime exposure and clinical outcome in patients with Gram-negative bacterial pneumonia. A previously published population pharmacokinetic model of cefepime was validated in 12 adult patients with normal renal function by measuring plasma concentrations at steady-state. ⋯ CART analysis determined patients with an fCmin/MIC≥2.1 had a significantly lower risk of clinical failure (OR=0.11, 95% CI 0.02-0.67; P=0.017). The fCmin/MIC ratio is a useful predictor of clinical failure in Gram-negative bacterial pneumonia. The clinical utility of fCmin/MIC in therapeutic drug monitoring should be further explored.
-
Int. J. Antimicrob. Agents · Apr 2015
Observational StudyAugmented renal clearance, low β-lactam concentrations and clinical outcomes in the critically ill: an observational prospective cohort study.
Whilst augmented renal clearance (ARC) is associated with reduced β-lactam plasma concentrations, its impact on clinical outcomes is unclear. This single-centre prospective, observational, cohort study included non-pregnant, critically ill patients aged 18-60 years with presumed severe infection treated with imipenem, meropenem, piperacillin/tazobactam or cefepime and with creatinine clearance (CL(Cr)) ≥60 mL/min. Peak, intermediate and trough levels of β-lactams were drawn on Days 1-3 and 5. ⋯ A link between ARC and clinical failure (18/98; 18%) was not observed. ARC and subthreshold β-lactam antibiotic concentrations were widespread but were not associated with clinical failure. Larger studies are necessary to determine whether standard dosing regimens in the presence of ARC impact negatively on clinical outcome and antibiotic resistance.