Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy.

AIM: To compare the pharmacokinetics/pharmacodynamics, antibiotic resistance and clinical efficacy of continuous (CA) vs. intermittent administration (IA) of cefotaxime in patients with obstructive pulmonary disease and respiratory infections. METHODS: A randomized controlled prospective nonblinded study was performed in 93 consecutive hospitalized patients requiring antibiotics for acute exacerbations of chronic obstructive pulmonary disease. Forty-seven patients received 2 g of cefotaxime intravenously over 24 h plus a loading dose of 1 g, and 46 patients were given the drug intermittently (1 g three times daily). RESULTS: Similar pathogens were identified in both groups, being mostly Haemophilus influenzae (51%), Streptococcus pneumoniae (21%) and Moraxella catharralis (18%). Mean minimal inhibitory concentration (MIC) values were also similar before and after treatment in both groups. Clinical cure was achieved in 37/40 (93%) (CA) vs. 40/43 (93%) (IA) of patients (P = 0.93). In microbiologically evaluable patients, criteria such as 70% of treatment time with antibiotic concentrations > or = MIC (CA 100%vs. IA 60% of patients) and/or > or = 5 x MIC (CA 100%vs. IA 55% of patients) were significantly better following continuous administration (P < 0.01). Samples with suboptimal antibiotic concentrations were found in 0% of CA vs. 65% of IA patients (P < 0.01). CONCLUSIONS: Although clinical cure rates were comparable, continuous cefotaxime administration led to significantly greater proportions of concentrations > MIC and > 5 x MIC compared with intermittent dosing. Continuous administration of cefotaxime at a lower dose [2 g (CA) vs. 3 g (CI)] is equally effective pharmacodynamically and microbiologically, may be more cost-effective and offers at least the same clinical efficacy. Based on these observations, we recommend continuous administration of cefotaxime as the preferred mode of administration.

Urinary concentrations of fosfomycin after a single 3 g dose of fosfomycin to elderly nursing-home patients.

The urinary concentrations of fosfomycin in 7 elderly patients with impaired renal function (mean creatinine clearance 40 ml/min) were studied after a single oral dose of 3 g fosfomycin as the trometamol salt. Urine samples were collected as 12 h portions for 84 h. Urinary concentrations of fosfomycin were 1,383 mg/l (range 314 to 4,200 mg/l) in the first 12 h and gradually declined to 165 mg/l (range 65 to 365 mg/l) between 36 and 48 h. 37% of the oral dose was recovered in the urine unchanged after 84 h, but a wide range (15-60%) in urinary recovery was observed. The elimination half-lives in the patients (estimated from the renal excretion profile of fosfomycin) ranged between 7 and 24 h. These data suggest that the urinary levels obtained in this patient population exceed the minimum inhibiting concentration of the usual pathogens involved in uncomplicated cystitis for at least 48 h. After 24 h the urinary concentrations of fosfomycin are higher than those reported for healthy young subjects.

Diagnostic problems with imported cases of mycetoma in The Netherlands.

Eight cases of imported mycetomata in The Netherlands are reviewed. Seven of these were cultured; only one isolate, Actinomadura madurae, belonged to a species commonly known as an agent of mycetoma. The remaining strains either belonged to very rare species, such as Phialophora cyanescens, or could not be identified at all. The list of possible agents of mycetoma apparently needs to be expanded. In addition, the concept of endemic occurrence of aetiological agents of eumycetoma needs revision. Divergent saprophytes may be involved which are able to survive in human tissue.