The Journal of antimicrobial chemotherapy
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J. Antimicrob. Chemother. · Jul 1996
ReviewIs continuous infusion of beta-lactam antibiotics worthwhile?--efficacy and pharmacokinetic considerations.
The most important pharmacodynamic parameter for beta-lactam antibiotics has been shown to be the time above the MIC, which is used as an argument to administer beta-lactam antibiotics by continuous infusion. Studies in vitro and in laboratory animals comparing efficacy of continuous and intermittent infusion of beta-lactam antibiotics generally show continuous infusion to be more efficacious. While comparative trials in humans are scarce and a significant difference was only found in subgroup analysis in one study, several case-reports support the use of continuous infusion. ⋯ Pharmacokinetic studies which have been performed in humans during continuous infusion show that serum concentrations can be predicted from total clearance or, using population pharmacokinetic modelling, the elimination rate constant as obtained during intermittent infusion. A nomogram is presented which allows calculation of the daily dose to obtain the target steady state blood concentrations suggested by the susceptibility of the infecting bacterium, usually 4 x MIC. For bacteria with a low MIC, the daily dose may be substantially lower than that used in conventional dosing regimens, while in infections which are difficult to treat as a result of more resistant bacteria, continuous infusion may be more effective than an equivalent bolus dose.
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J. Antimicrob. Chemother. · Jun 1996
ReviewThe use of corticosteroids in the management of bacterial meningitis in adults.
Despite the introduction of newer antimicrobial agents, bacterial meningitis continues to be associated with significant morbidity and mortality. Evidence from in-vitro studies, experimental animal models, and clinical studies indicate that the host inflammatory response is responsible for much of the deleterious consequences of this disease. ⋯ Although there is considerable evidence from animal models and from clinical trials in children that adjunctive antiinflammatory therapy with corticosteroids is effective in reducing inflammation and in improving long-term outcomes, similar data involving adults are largely lacking. The rationale for the use of corticosteroids in the management of bacterial meningitis, and the applicability to disease in adults, are discussed, and some recommendations for their use in this setting are made.
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J. Antimicrob. Chemother. · Mar 1996
Activity of rifabutin, clarithromycin, ethambutol, sparfloxacin and amikacin, alone and in combination, against Mycobacterium avium complex in human macrophages.
Disseminated infection with Microbacterium avium complex (MAC) in patients with AIDS is currently treated with a combination of antimycobacterial agents in order to prevent the selection of resistant mutant strains. Although clinical and microbiological responses can generally be achieved within a few weeks, relapses are common and require modification of the combination regimen or identification of effective alternate therapies. In this study we investigated the activities of rifabutin 0.5 mg/L, sparfloxacin 1 mg/L, clarithromycin 4 mg/L, amikacin 16 mg/L and ethambutol 2 mg/L, alone and in combination, against nine strains of M. avium isolated from the blood of patients with AIDS in order to identify regimens with the greatest therapeutic potential. ⋯ At day 4 and at day 7, the combination of rifabutin, clarithromycin, amikacin and sparfloxacin displayed the highest degree of activity. However, the activity did not differ significantly from that of the combination of rifabutin, clarithromycin and ethambutol. The results of this study confirm the activity of combinations including rifabutin and clarithromycin (+/- ethambutol) in human monocyte-derived macrophages and suggest potentially useful associations in incorporating sparfloxacin and amikacin.
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J. Antimicrob. Chemother. · Jul 1995
Acquired resistance in Mycobacterium avium complex strains isolated from AIDS patients and beige mice during treatment with clarithromycin.
Clarithromycin has been reported to select clarithromycin resistant mutants of Mycobacterium avium complex (MAC) during treatment with clarithromycin in AIDS patients and beige mice. We selected resistant mutants in vitro at a frequency of 5 x 10(-9). ⋯ In contrast, the pattern of resistance to non-macrolide antibiotics remained unchanged in clarithromycin resistant strains. A dramatic decrease in ribosome affinity for clarithromycin and erythromycin was found in clarithromycin resistant strains, but no mutation was found in the peptidyl domain of the 23S rRNA, indicating that another ribosomal modification is involved.
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J. Antimicrob. Chemother. · Feb 1995
Randomized Controlled Trial Comparative Study Clinical TrialGentamicin once-daily versus thrice-daily in children.
Fifty children aged 3 months--16 y with Gram-negative bacterial infections, were evaluated in this open randomized study; 26 received gentamicin 4.5 mg/kg/day, once daily, and 24 received the same daily dosage, in three divided doses. The groups had similar demographic and clinical characteristics. Serum trough gentamicin concentrations were significantly lower in the od group than in the tds group, while peak concentration were significantly higher in the od group. ⋯ Microbiological cure was obtained in 10/10 (100%) and 12/13 (92%) of the evaluated cases. Nephrotoxicity was not observed but ototoxicity occurred in two children in each group. These results, although obtained from a small number of patients, showed a similar outcome in children receiving gentamicin 4.5 mg/kg/day whether administered once or thrice daily.