Imipenem versus moxalactam in the treatment of serious infections

Abstract

Imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK0787) was compared to moxalactam in a randomized therapeutic trial involving 39 evaluable patients with serious bacterial infections. Of those treated with imipenem, 89% were cured or improved versus 60% for moxalactam (P = 0.06). Although mucocutaneous fungal infections occurred in both groups (25 and 10%, respectively), Streptococcus faecalis superinfection was seen in two patients in the moxalactam group only. Adverse drug reactions occurred with both drugs, although bleeding occurred in three patients treated with moxalactam.Imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK0787) is a novel betalactam antibiotic having desthiocarbapenem as its nucleus. In vitro studies (5) MATERIALS AND METHODSPatients with septicemia, soft tissue, respiratory tract, and urinary tract infections were admitted to a randomized study at The Fairfax Hospital (Falls Church, Va.) comparing moxalactam (2 g intravenously every 8 h) to imipenem (0.5 g intravenously every 6 h) combined with MK0791, a structural analog of imipenem designed to block catabolism of the drug by the brush border of the kidney (6). The method of culturing, laboratory tests for safety, and informed consent have all been described previously (2), with the exception that Mueller-Hinton broth was used for the determination of MICs rather than Trypticase soy broth (BBL Microbiology Systems). Susceptibility to imipenem and moxalactam was initially determined for all isolates by using 10-,ug disks for imipenem and 30-,ug disks for moxalactam. Zones equal to or greater than 16 and 18 mm, respectively, were used to indicate sensitivity. Although we hoped that all isolates would be sensitive to both antibiotics, in several instances in the imipenem group, bacteria were resistant to moxalactam. One patient who had been started on moxalactam was dropped from the study when her P. aeruginosa isolate was shown to be moxalactam resistant. A second patient who developed a rash after a small dose of imipenem was also dropped from the study. Gramstained specimens were examined for the presence of polymorphonuclear leukocytes and homogeneous populations of organisms (except in polymicrobial infections) in an attempt to distinguish pathogens from colonizers identified on cultures.Wound infections showed signs of local inflammation with purulent drainage. Intraabdominal infections consisted of abscesses or cholangitis or both. Respiratory tract infections were diagnosed by the presence of purulent sputum or sinus drainage and radiological evidence of infection of the lung or sinus. Urinary tract infections had colony counts greater than 105 per ml of urine with pyuria noted on urinalysis. Septicemia was defined as the occurrence of two or more positive blood cultures.Cure was defined as the complete resolution of signs of infection accompanied by sterilization of the infected site at the conclusion of therapy. When culture specimens were no longer available, assessment of response was made on clinical g...

Imipenem-cilastatin in the treatment of methicillin-sensitive and methicillin-resistant Staphylococcus aureus infections

“…Bacteriologic eradication was achieved with 93% of 30 Staphylococcus aureus isolates treated with I/C, compared with 96% of 29 Staphylococcus aureus isolates in the cefazolin group. Favorable results were obtained in other clinical trials by Eron et al and Schreiner et al, although one drug addict with Staphylococcus aureus endocarditis was considered a failure when blood cultures persisted after 5 days of therapy (5,15). While these clinical studies reported Staphylococcus aureus infections that were treated successfully with I/C, methicillin susceptibility was not evaluated.…”

Imipenem pharmacokinetics and body fluid concentrations in patients receiving high-dose treatment for serious infections

“…(ii) The drug administration was carried out by staff nurses on the regular medical and surigcal in-patient units, rather than in the carefully moni- (10) suggested that diarrhea would not be a side effect of this drug (1). However, occasional diarrhea has occurred in some clinical trials, including several cases associated with the isolation of Clostridium difficile toxin (3,5). The gastrointestinal fluid imipenem concentrations reported here (0.4 to 2.5 ,ug/ml), although much lower than plasma drug levels, are above the MIC for 90% of the strains for most of the common aerobic and anaerobic stool bacteria (6,9,15).…”

Biliary excretion of imipenem-cilastatin in hospitalized patients

“…It was thought that it might not cause diarrhea because Norrby et al (10) found that less than 2% bf the radiolabeled, intravenously administered drug,could be recovered in the stool and because Nord and his colleagues (8) detected only minor changes in bowel flora after 6 to 11 days of its use. However, the review by Calandra et al (2) of adverse experiences among the first 2,516 patients treated with imipenem-cilastatin reported a 3.3% incidence of diarrhea, including several cases in which Clostridium difficile toxin was isolated (3,7,16). In an earlier report, we demonstrated concentrations of imipenem in various gastrointestinal fluids that were high enough to inhibit' most intestinal flora (7).…”