A case series of macrolide treatment failures in community acquired pneumonia.

This was a retrospective, multi-center study of patients admitted to hospital with community-acquired pneumonia, caused by Streptococcus pneumoniae, after failing to respond to >2 days of outpatient macrolide therapy. 122 cases, treated between 2000-2004, were enrolled from 31 North American sites between January 2004 - March 2005. Non-susceptible isolates (predominately low-level resistance: erythromycin MICs of 1-16 mcg/ml) were recovered from 87 patients (71%). Bacteremia was present in 63 patients (52%). The in-hospital mortality rate was 5.7 %; all 7 patients who died were bacteremic, 6 had a non-susceptible isolate. We report here the largest series of macrolide failures published to date. The patients were notable for their high rates of macrolide resistance, bacteremia, and mortality. High-level macrolide resistance remains rare among US patients failing outpatient macrolides. The majority of cases and virtually all of the mortality occurred in patients with low-level resistant strains.

Analysis of trends in antimicrobial resistance patterns among clinical isolates of Bacteroides fragilis group species from 1990 to 1994.

Antimicrobial resistance, including plasmid-mediated resistance, among Bacteroides fragilis group species is well documented. A 5-year (1990-1994) prospective, eight-center survey of 3,177 clinical isolates of Bacteroides species was undertaken to review trends in resistance, using the breakpoints for full and intermediate susceptibility established by the National Committee for Clinical Laboratory Standards. No documented resistance to either metronidazole or chloramphenicol was found in this survey. Among B. fragilis isolates virtually no resistance was seen to imipenem, meropenem, ampicillin/sulbactam, piperacillin/tazobactam, or ticarcillin/clavulanate. Significant increases in resistance among B. fragilis isolates to cefotetan, ceftizoxime, and clindamycin (p < .01) were noted. Resistance to cefoxitin remained unchanged. Among the non-fragilis species of the B. fragilis group, there was virtually no resistance to imipenem, meropenem, chloramphenicol, or metronidazole. The three beta-lactamase inhibitors had increasing levels of resistance, although 95%-98% of strains were susceptible (p < .05). There was a significant decline in cefoxitin, cefmetazole, and clindamycin activity over time against these strains (p <.01). There was a significant (P < .001) increase in geometric mean minimum inhibitory concentration for most drugs and species tested from 1990 to 1994. Clusters in the eight institutions could not account for this rise in resistance. This survey demonstrates that rates of resistance of B. fragilis and non-fragilis species of B. fragilis group are increasing.

Antimicrobial susceptibility patterns of the Bacteroides fragilis group in the United States, 1989.

A national survey of Bacteroides fragilis group was continued in 1989 for the ninth consecutive year. Seven hundred thirty-nine isolates of B fragilis group from eight centers were tested for susceptibility to 14 antimicrobials. Sulbactam and clavulanic acid, beta-lactamase inhibitors, were tested at a constant concentration of 8 micrograms/ml and 2 micrograms/ml, respectively. Sulbactam was also tested in a fixed ratio of 1:2. Imipenem, ampicillin+sulbactam, and ticarcillin+clavulanic acid had resistance of less than 1% at breakpoints of 8 micrograms/ml, 16 micrograms/ml, and 64 micrograms/ml, respectively. At 32 micrograms/ml, resistance to cefoxitin, cefotetan, ceftizoxime, and ceftriaxone were 4%, 25%, 26%, and 46%, respectively. Clindamycin resistance was 10% at a breakpoint of 4 micrograms/ml. No isolates were resistant to chloramphenicol or metronidazole. Resistance for five B fragilis species to cefoxitin, ceftizoxime, and cefotetan varied greatly among both species and participating institutions. The addition of a beta-lactamase inhibitor increased the potency of the beta-lactam drugs tested as combinations. This finding suggests that beta-lactamase production is the major resistance factor in members of the B fragilis group.

Norfloxacin use in urinary tract infection by urologists and infectious disease specialists.

One hundred thirty-one patients of urologists and infectious disease specialists were entered into an open trial of norfloxacin in the therapy of urinary tract infections (UTIs). All patients were evaluable for tolerability and 98 were evaluable for efficacy. The patient population in this study was older (mean age 53 years) and had more underlying urogenital disorders (30%) or recent invasive urologic procedures (20%) than the typical patient population with UTIs. Over 50% of the patients had infections due to organisms other than Escherichia coli, including Pseudomonas aeruginosa (14), Klebsiella pneumoniae (5), Enterobacter spp (3) and Group D streptococcus (6). Clinical and bacteriologic cure rates were 90 and 91%, respectively. Side effects occurred in 5 patients and were generally mild.

Imipenem/cilastatin: general experience in a community hospital.

Imipenem/cilastatin is a new carbapenem antibiotic with broad spectrum antimicrobial activity. Forty two patients with infections of various types, including skin and soft tissue, respiratory tract, bone and joint, and urinary tract, were treated with this antibiotic in an open noncomparative study. Clinical responses to therapy were excellent and failures were only encountered with infections caused by Pseudomonas aeruginosa strains that developed resistance during therapy. Superinfection rates were minimal as were toxicities. Imipenem/cilastatin appears to be a relatively safe and highly effective broad spectrum antibiotic.

An overview of cefotaxime therapy in infections caused by gram-positive pathogens.

The in vitro activity of cefotaxime and other third-generation cephalosporins against gram-positive pathogens is generally considered to be less than that of earlier cephalosporins, such as cefazolin. A review of pooled pre-release data collected by numerous investigators and supplied by Hoechst-Roussel made it possible to evaluate the clinical and bacteriologic efficacy of cefotaxime in more than 900 infections caused by gram-positive organisms. The most commonly isolated pre-treatment organisms were Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and other streptococcal species. The overall clinical efficacy rate was 95% and the bacteriologic eradication rate was 94.5%. Side-effects were limited to rash in two, diarrhea in one and fever in one. Pain at the administration site was reported by four patients. Comparative studies with cefazolin against S. aureus showed no statistically significant differences in efficacy. The highest failure rates were seen in enterococcal urinary tract infections, as predicted by in vitro sensitivity tests. Cefotaxime appears to be a safe, effective antibiotic for the therapy of infections caused by gram-positive pathogens.

Cefonicid in a once-daily regimen for treatment of osteomyelitis in an ambulatory setting.

Fifteen patients with bone joint infections were treated with 1.0 g of cefonicid administered intravenously or intramuscularly once daily. Single organisms isolated included Staphylococcus aureus (from six patients), Staphylococcus epidermidis (three), and Peptococcus species (one). For four patients infection was polymicrobial, and for one patient no organism was isolated. The mean duration of therapy was 40.4 days, only 10.9 days of which were spent in the hospital. The remainder of therapy was administered intramuscularly in an ambulatory setting. Therapy was successful in all 12 assessable patients. No clinical or bacteriologic relapse occurred in the follow-up period of three to 13 months. The occurrence of adverse effects prompted discontinuation of cefonicid therapy in three patients. Minimum savings in hospital-bed costs alone were $64,350, with 390 hospital days avoided. The minimum savings in work income were $10,010, with 182 days of absenteeism avoided. These data are preliminary but suggest efficacy of cefonicid in a mode of therapy that could have profound cost benefits.

Susceptibility of the Bacteroides fragilis group in the United States in 1981.

The minimal inhibitory concentrations of nine antimicrobial agents was determined for over 750 clinical isolates of the Bacteroides fragilis group of anaerobic bacteria collected from nine centers in the United States during 1981. High resistance rates were documented for cefoperazone, cefotaxime, and tetracycline. Cefoxitin had the best activity of the beta-lactam antibiotics, whereas moxalactam and piperacillin had good activities. The resistance rate for clindamycin was 6%. There were no metronidazole- or chloramphenicol-resistant isolates encountered. There were significant differences in susceptibility among the various species of the B. fragilis group, particularly with moxalactam, cefoxitin, and clindamycin. Clustering of clindamycin-, piperacillin-, and cefoxitin-resistant isolates was observed at different hospitals. The variability of resistance rates with the beta-lactam antibiotics and clindamycin indicates that susceptibility testing of significant clinical isolates should be performed to define local resistance patterns.