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Selection of resistance to cefamandole has been observed, and the drug has failed to protect animals lethally infected with certain Enterobacteriaceae that appeared to be highly susceptible in vitro. Using spectrophotometric assays, some of these organisms were found to produce beta-lactamases highly active against cefamandole. Cefoxitin, a poor enzyme substrate, was found to be superior to both cephalothin and cefamandole in induction of these enzymes. A simple disk induction test was developed and used to examine 147 Enterobacteriaceae for production of these beta-lactamases. The enzymes were found in 69% of cephalothin-resistant, cefamandole-susceptible strains and in only 3% of strains susceptible to both cephalothin and cefamandole. They were most prevalent among isolates of Enterobacter, indole-positive Proteus, and Serratia. Since selection of resistance and therapeutic failures have occurred most often among these genera, the relationship between presence of inducible enzymes and outcome of therapy should be examined further in humans.Cefamandole (CM;6,11,26) and cefoxitin (CX; 3, 24) possess a greater spectrum of antibacterial activity than previously marketed cephalosporins. Possible bases for the expanded spectrum of these new compounds include their resistance to a variety of beta-lactamases and/ or greater intrinsic activity, i.e., better penetration into the cell and attachment to target proteins (3,5,11,20,22,26). However, results of a recent study with these new drugs showed significant discrepancies between in vitro and in vivo tests, especially with CM (9). Animals infected with organisms appearing to be susceptible to CM in vitro failed to respond to therapy with the drug. Furthermore, in vivo selection of resistant mutants was observed in several instances. The purpose of this investigation was to analyze strains used in the previous study to determine if beta-lactamase production might be responsible for the discrepancies observed. MATERIALS AND METHODSAntibiotics. All drug solutions (weight compensated for purity) were prepared the day of use. Working standards were prepared from the following anti- Beta-lactamase assays. Beta-lactamase activity was evaluated by direct spectrophotometric methods (19) on whole cells. Cells from a 24-h Mueller-Hinton agar culture (Difco) were suspended in phosphate buffer (pH 7) so as to give 109 colony-forming units per ml. Fresh drug solution was added to the cell suspension to give a final concentration of 100 ,M, and, after incubation for 4 h at 37°C in air, the cells were removed by filtration (Millipore membrane filter). Plate counts of the drug-cell suspensions indicated no loss in viability during the 4-h incubation. The concentration of active drug remaining in the filtrate was determined by reading the optical density of the solution at the wavelength of maximal absorption associated with the beta-lactam ring (Beckman DB-GT). This wavelength varied between 255 and 270 nm for the different drugs tested. Drug solutions incubated similarly without cell...

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Periprosthetic infections due to Mycobacterium fortuitum and Mycobacterium chelonei occurred in 17 women over a 3.5-year period after implantation of prostheses for breast augmentation. The median incubation period for 16 of the women was 28 days (range, one week to over two years) after surgery; etiologic diagnosis was usually delayed for weeks to months. Odorless and serosanguineous or purulent material was found when the implants were removed, and acid-fast bacilli were often present when smears were examined. Wound infections were chronic and refractory to therapy with various antimicrobial agents. Persistent or recurrent mycobacterial infections complicated attempts to implant new prostheses. Whereas M. fortuitum isolates were susceptible to amikacin, multiple strains of M. fortuitum were distinguished by conventional antituberculous and broth microdilution susceptibility tests. Several clusters of infections were temporally and geographically related; however, sporadic cases were also reported, and no evidence of a contaminated common product or other single source of infection was found.

Cefepime is a new cephalosporin with an enhanced antibacterial potency and spectrum. More rapid penetration into many gram-negative bacilli, targeting of multiple penicillin-binding proteins, and resistance to inactivation by many beta-lactamases account for its activity against organisms that have developed resistance to agents such as ceftazidime, cefotaxime, or ceftriaxone. This study identified 16 patients with 17 infections due to Enterobacter species organisms with reduced susceptibility or resistance to ceftazidime. Most isolates were multiply resistant to other beta-lactam drugs as well, but all were susceptible to cefepime. All 17 infections, which included pneumonia, urinary tract infection, intraabdominal infection, and bacteremia, responded clinically to intravenous cefepime. In particular, cefepime was successfully used in the management of cases of chronic infection that had responded poorly to repeated therapy with imipenem, aminoglycosides, or ciprofloxacin. Eradication of Enterobacter species organisms occurred at 15 (88.2%) of the 17 sites of infection. No emergence of resistance to cefepime was noted.