meropenem and Lung-Diseases

Concentrations of unbound meropenem in the cerebral extracellular fluid (ECF) of two patients with acute brain injury were assessed by microdialysis. Brain ECF unbound-meropenem concentrations were lower than serum unbound-meropenem concentrations, with brain-to-serum area under the concentration-time curve ratios of 0.73 and 0.14. A pharmacokinetic model was developed to fit the experimental data adequately.

Topics: Adult; Brain; Brain Injuries; Extracellular Fluid; Humans; Infusions, Intravenous; Lung Diseases; Male; Meropenem; Microdialysis; Thienamycins; Young Adult

Topics: Adult; Humans; Lung Diseases; Male; Meropenem; Pseudomonas Infections; Thienamycins

Meropenem and comparative antibiotics were evaluated in five models of infection. All antibiotics were administered parenterally; imipenem was used in combination with cilastatin but meropenem and other agents were given alone. Generalized infections in mice caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Serratia marcescens, Proteus mirabilis or Pseudomonas aeruginosa all responded to low doses of meropenem or imipenem. Immunocompromised mice infected with Ps. aeruginosa responded to slightly higher doses of meropenem or gentamicin but required four to seven times the dose of other agents. Those given a greater challenge of Ps. aeruginosa were treated most successfully by meropenem. Treatment with meropenem, imipenem or ceftazidime caused significant reductions of E. coli in the urinary bladder and kidneys of mice challenged per urethram. Infection with Ps. (Xanthomonas) maltophilia localized to the subcutaneous neck tissue of guinea pigs was also treated successfully. Lung infections caused by Ps. aeruginosa in guinea pigs were treated effectively by meropenem, imipenem, and ceftazidime at the dose of 10 mg/kg but only meropenem eradicated bacteria from all the tissues examined. These results demonstrate that meropenem has excellent antibacterial activity in vivo in both normal and immunocompromised animals and in some models of infection is superior to imipenem.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Escherichia coli Infections; Guinea Pigs; Immunosuppression Therapy; Lung Diseases; Male; Meropenem; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Pseudomonas Infections; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections