Therapeutic activity of meropenem in experimental infections.
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.
Edwards
J R
JR
Antibiotic Development Group, Bioscience I, ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
Williams
S
S
Nairn
K
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D015780:Carbapenems / Q000627:therapeutic use*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D006168:Guinea Pigs; D007165:Immunosuppression Therapy; D008171:Lung Diseases / Q000188:drug therapy / Q000382:microbiology; D008297:Male; D000077731:Meropenem; D051379:Mice; D008815:Mice, Inbred Strains; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology; D013845:Thienamycins / Q000627:therapeutic use*; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins; D000077731:Meropenem