Therapeutic activity of meropenem in experimental infections

Abstract

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.

Intramuscularly administered peptide A3‐APO is effective against carbapenem‐resistant Acinetobacter baumannii in mouse models of systemic infections

“…Encouraged by this finding we relyophilized the peptide from 1% acetic acid and tested the ability of A3‐APO to eradicate MDR gram‐negative nonfermenting strains by im route of administration. We selected A. baumannii , for which resistance to carbapenems, the “silver bullets” against gram‐negative pathogens11 is rapidly increasing 12. Current treatment of carbapenem‐resistant A. baumannii infections employs im administered colistin 13, 14.…”

The designer proline-rich antibacterial peptide A3-APO is effective against systemic Escherichia coli infections in different mouse models

“…The designer proline-rich peptide A3-APO exhibits attractive biochemical, microbiological and pharmacological properties and belongs to the very limited number of synthetic antibacterial peptides that show efficacy in research scale and pharmaceutically approved mouse bacteraemia models comparable with the current silver bullet carbapenems [26]. Currently known resistance mechanisms do not hamper designer proline-rich peptide activity either in vitro or in vivo [21,27].…”

Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients

“…The toxicity profile of meropenem is comparable to that of imipenem except that data from animal studies suggest that meropenem may be less epileptogenic and less nephrotoxic. Meropenem has been shown to be effective in several animal models [13]. In clinical trials, it has been used successfully to treat pneumonia [26,29], meningitis [11,21,37], intra-abdominal infections [16,17,20], soft tissue infections [22,30], bacteremia [29], and urinary tract infections [8,29].…”