Sensitive and specific phenotypic assay for metallo-beta-lactamase detection in Enterobacteria by use of a moxalactam disk supplemented with EDTA.

Moxalactam is highly hydrolyzed by plasmid-mediated metallo-ß-lactamases (MBLs), whereas it is poorly inactivated by serine-active carbapenemases. This study demonstrated that moxalactam resistance constituted an effective screen for MBL expression in enterobacteria, which could be confirmed, even in low-MBL-producing isolates, by a disk potentiation test using moxalactam and EDTA.

Quantitative relationship between sensitivity to beta-lactam antibiotics and beta-lactamase production in gram-negative bacteria--II. Non-steady-state treatment and progress curves.

A non-steady-state model is discussed for the study of the interplay between beta-lactamase activity and outer membrane permeability with slowly hydrolysed beta-lactams. The analysis shows: (1) that the simple, steady-state model presented in the accompanying paper remains valid as long as kcat (i.e. k3 with chromosome-encoded class C beta-lactamases) is larger than 10(-3)/sec (generation time = 20 min or more); (2) that among the beta-lactam antibiotics studied here, the complete, non-steady-state model needs only be used in the case of aztreonam; (3) that the term "trapping" should be replaced by "formation of a covalent acyl-enzyme" and that such a phenomenon only contributes significantly to the resistance when penetration and hydrolysis are very slow and the periplasmic beta-lactamase concentration is very high. Aztreonam seems to be the only compound which fulfils the first two conditions.

A multiclinic randomized study of the comparative efficacy, safety and tolerance of imipenem/cilastatin and moxalactam.

The efficacy, safety and tolerance of imipenem/cilastatin and moxalactam were compared in a randomized trial in the United States involving 19 centers and 441 patients. Significantly more organisms were susceptible to imipenem than moxalactam. Although the bacteriological outcomes were similar, the clinical outcome was significantly better in the imipenem/cilastatin treatment group. The incidence of colonization and superinfection was similar in both groups. Moxalactam was less irritating at the site of injection than imipenem/cilastatin. The safety profiles were similar except for bleeding episodes in the moxalactam group.

Moxalactam therapy of serious pediatric infections.

Forty children with documented or suspected bacterial infections arising outside the central nervous system (CNS) were studied. Fifteen different pathogens for a total of 30 isolates were obtained from multiple sources. Staphylococcus aureus (minimum inhibitory concentrations 4-8 micrograms/ml) was the most common pathogen isolated, involving seven patients. Each patient received moxalactam 50 mg/kg iv over 15 minutes q8h and responded favorably to therapy, exhibiting bacteriologic and/or clinical cures. Toxicity associated with moxalactam occurred in only two patients and necessitated discontinuation of drug therapy. Moxalactam 50 mg/kg iv q8h is effective therapy for non-CNS infections occurring in infants and children.

Curved anaerobic bacteria in bacterial (nonspecific) vaginosis and their response to antimicrobial therapy.

Vaginal fluid samples from normal college students, college students with bacterial (nonspecific) vaginosis, and sexually transmitted disease clinic patients with bacterial vaginosis, before and after therapy with metronidazole, ampicillin, or amoxicillin, were evaluated by direct Gram stain and culture for the predominant anaerobic and facultative flora. Curved rods were detected by direct Gram stain of vaginal fluid from 31 (51%) of 61 women with bacterial vaginosis and none of 42 normal student controls (P less than 0.001). Curved, gram-variable to gram-negative organisms were recovered from six of these 31 women, seven other women with bacterial vaginosis, and no controls. All 13 isolates were anaerobic, motile, and oxidase-negative, produced succinic acid as their major metabolic product, and hydrolyzed starch. After treatment with ampicillin or amoxicillin (n = 10) or greater than or equal to 2 g of metronidazole (n = 9), no curved motile rods were detected by Gram stain or culture, although the minimal inhibitory concentration of metronidazole was greater than or equal 8 micrograms/ml for 11 of the 13 isolates tested.