meropenem and Lung-Diseases--Obstructive

Meropenem and imipenem/cilastatin were compared in an open, randomised prospective multicentre study in the treatment of acute exacerbations of severe chronic obstructive pulmonary disease in hospitalised patients. One-hundred-and-seventy-three patients were enrolled; 164 were evaluable for clinical efficacy and 98 for bacteriological efficacy, with 144 pathogens isolated. The predominant pathogens were Haemophilus influenzae (n = 30), Streptococcus pneumoniae (18), Staphylococcus aureus (12), Pseudomonas aeruginosa (11), Moraxella catarrhalis (8), other Gram-negative bacteria (Neisseria, Klebsiella, Proteus, and Enterobacter spp.) (53) and other Gram-positive bacteria (12). A single bacterial pathogen was identified in 61 patients, whereas two bacterial pathogens were isolated in 31 patients and three in six patients. The clinical response at the end of treatment was very high in both groups with a satisfactory outcome (cured or improved) in 97.6% of the meropenem patients and in 96.3% of the imipenem/cilastatin patients; at follow-up the rates were 89.1% and 89.8%, respectively. The bacterial success (eradication or presumed eradication) was 88.2% in the meropenem group and 89.4% in the comparator group. Nausea or vomiting were reported more frequently in patients treated with imipenem/cilastatin, whereas in the meropenem group an increase in aminotransferases was reported. One patient treated with imipenem/cilastatin was withdrawn from the study due to seizures. Meropenem and imipenem/cilastatin were highly effective for the treatment of severe bacterial exacerbations of chronic bronchitis but meropenem was better tolerated.

Topics: Bacterial Infections; Bronchitis; Carbapenems; Cilastatin; Drug Therapy, Combination; Drug Tolerance; Hospitalization; Humans; Imipenem; Lung Diseases, Obstructive; Meropenem; Prospective Studies; Thienamycins; Treatment Outcome

We investigated the pharmacokinetics of meropenem after the first and tenth i.m. administration in patients with respiratory tract infections. Ten patients (mean age 63.8 +/- 5.2 years) received meropenem 500 mg tds for at least ten doses, and plasma and urine antibiotic concentrations were determined by microbiological assay. After the first injection a mean peak plasma concentration of 7.93 +/- 1.29 mg/L was observed at 1 h. Trough levels at 8 h (0.29 +/- 0.16 mg/L) were detectable in five of ten treated patients. The mean terminal half-life was 1.08 +/- 0.2 h with an area under the curve (AUC) value of 23.8 +/- 4.59 mg/L.h, and a cumulative urinary recovery at 8 h of 48.43 +/- 3.12%. There was no evidence of change in the pharmacokinetics of meropenem after repeated i.m. administration, though the mean peak plasma concentration and AUC value were slightly increased. The accumulation ratio (assessed using AUC values) was 1.18 +/- 0.19 after multiple doses and was considered to be of little kinetic and clinical importance. Moreover, many of the trough concentrations of meropenem were below the limit of detection of the assay. After i.m. administration meropenem concentrations exceeded 0.5 mg/L for longer than previously described following i.v. infusion. No adverse events were reported.

Topics: Aged; Bronchitis; Female; Humans; Injections, Intramuscular; Lung Diseases, Obstructive; Male; Meropenem; Middle Aged; Thienamycins