Activity of cephalosporins against coagulase-negative staphylococci.

Staphylococcus epidermidis has become an increasingly important pathogen as the cause of serious postoperative infection after heart and orthopedic surgery. We studied the susceptibilities of 80 blood, sternotomy, and hip isolates to vancomycin, cefazolin, cefuroxime, oxacillin, erythromycin, ciprofloxacin, and ofloxacin. The MIC90 of methicillin-susceptible isolates was 4 micrograms/ml for cefazolin and cefamandole, 8 micrograms/ml for cefuroxime, and 4 micrograms/ml for vancomycin. At 48 hr the MIC90 rose to 32 micrograms/ml for cefazolin and greater than 128 micrograms/ml for cefuroxime, and remained at 4 micrograms/ml for cefamandole and vancomycin. The MIC90 of methicillin-resistant isolates at 48 hr was 16 micrograms/ml cefamandole, 64 micrograms/ml cefazolin, greater than 128 micrograms/ml cefuroxime, and 4 micrograms/ml vancomycin. Ciprofloxacin and ofloxacin inhibited the majority of isolates at 1 microgram/ml, and vancomycin at 4 micrograms/ml. The new peptolide, daptomycin, also inhibited S. epidermidis at less than or equal to 1 microgram/ml.

Synergy of sulbactam and ampicillin against methicillin-resistant staphylococci.

Methicillin resistance in staphylococci is an increasing problem both for Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), which cause infections of the heart and after central nervous system surgery. Resistance seems to be due primarily to production of altered penicillin-binding proteins. The present study determined whether a combination of beta-lactamase inhibitor sulbactam and ampicillin or sulbactam and cefazolin would inhibit MRSA and MRSE. Sulbactam, ampicillin and cefazolin at 32 micrograms/ml did not inhibit MRSA or MRSE. At 8 micrograms/ml of each agent all isolates were inhibited. Synergy of sulbactam and ampicillin could be demonstrated against MRSA by the agar fixed ratio method, checkerboard dilution and by killing curves. This suggests that in certain situations MRSA and MRSE may be effectively eliminated by this method.

Synergy of fosfomycin with beta-lactam antibiotics against staphylococci and aerobic gram-negative bacilli.

Fosfomycin inhibits bacterial cell wall synthesis at the initial stage. It can act synergistically with beta-lactams. The effect of the combination of fosfomycin and selected penicillins and cephalosporins against staphylococci, Pseudomonas aeruginosa, Pseudomonas cepacia and selected Gram-negative bacteria was determined. Synergy was determined by agar dilution and checkerboard titration methods; synergy was defined as an FIC index less than or equal to 0.5 and partial synergy greater than 0.5 to 0.75. Concentrations of drugs used were those that would be reached in man by intravenous and oral routes. Fosfomycin combined with nafcillin and with cefotaxime against staphylococci showed synergy for most isolates. For methicillin-resistant Staphylococcus aureus, synergy or partial synergy was found for 90% of isolates. Synergy was less frequently found with Staphylococcus epidermidis. The MICs for S. aureus were reduced from greater than or equal to 32 micrograms/ml to less than or equal to 1 microgram/ml. Fosfomycin was synergistic with ticarcillin, piperacillin, azlocillin, ceftazidime, aztreonam and imipenem against 31 to 61% of P. aeruginosa. MICs were reduced from greater than or equal to 128 micrograms/ml to 8-32 micrograms/ml, depending upon the agent. Although fosfomycin acted synergistically with azlocillin, piperacillin and ceftazidime against some P. cepacia, most often there was an indifferent interaction and MICs were in the resistant range, greater than or equal to 128 micrograms/ml. The interaction of fosfomycin and ampicillin was synergistic against a number of strains of Enterobacteriaceae, Proteus vulgaris and Providencia rettgeri, yielding MICs in an achievable range. The combination of fosfomycin with beta-lactams may be clinically useful in selected situations, particularly for methicillin-resistant staphylococci and beta-lactam-resistant P. aeruginosa.

In vitro activity of A-16686, a new glycopeptide.

A-16686 is a novel glycopeptide antibiotic derived from Actinoplanes. A-16686 inhibited hemolytic streptococci groups A, B, C, F, and G at concentrations of less than or equal to 0.06 to 0.5 microgram/ml, with 90% inhibited by 0.5 microgram/ml, including erythromycin-resistant isolates. S. bovis, various viridans groups streptococci, S. mitis, S. mutans, and S. sanguis were inhibited by less than or equal to 1 microgram/ml, and MICs of S. faecalis and S. faecium were 0.5-2 micrograms/ml. Most staphylococci, including methicillin-resistant strains, were inhibited by 1 or 2 micrograms/ml. A-16686 was bactericidal with minimal difference between MIC and MBC for gram-positive species. A-16686 did not inhibit Enterobacteriaceae or Pseudomonas.

In vitro activity and beta-lactamase stability of a new penem, CGP 31608.

The in vitro activity of CGP 31608, a new penem, against aerobic and anaerobic organisms was evaluated and compared with those of other beta-lactams. CGP 31608 inhibited Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Citrobacter diversus, and Salmonella, Shigella, Aeromonas, and Yersinia spp. with MICs for 50% of the strains (MIC50s) of 2 to 4 micrograms/ml and MIC90s of 4 micrograms/ml, compared with cefotaxime, ceftazidime, aztreonam, and imipenem MICs of less than 0.25 microgram/ml. MIC90s were 8 micrograms/ml for Enterobacter species and C. freundii, for which other agents had MICs of 32 micrograms/ml, except imipenem, which had equal activity. The MIC90 for Proteus vulgaris, Morganella morganii, Providencia stuartii, and Providencia rettgeri was 8 micrograms/ml, compared with less than 2 micrograms/ml shown by the other agents. Acinetobacter species resistant to other agents except imipenem were inhibited by 4 micrograms/ml, as were Pseudomonas aeruginosa, including piperacillin-, ceftazidime-, and gentamicin-resistant isolates. The MIC for P. cepacia, P. fluorescens, and P. acidovorans was less than or equal to 8 micrograms/ml, but that for P. maltophilia was greater than or equal to 128 micrograms/ml. Hemolytic streptococci A, B, C, G, and F were inhibited by less than 1 micrograms/ml, but the MIC for Streptococcus faecalis was greater than or equal to 32 micrograms/ml. MICs for Staphylococcus aureus methicillin-susceptible and -resistant strains were less than or equal to 1 microgram/ml, as were those for methicillin-susceptible and -resistant S. epidermidis. Bacteroides fragilis and Clostridium species and Fusobacterium spp. were inhibited by less than or equal to 4 micrograms/ml. CGP 31608 was not hydrolyzed by plasmid beta-lactamases TEM-1, TEM-2, SHV-1, PSE-1, OXA-2, PSE-4, or by S. aureus. Chromosomal beta-lactamases of type Ia in Enterobacter cloacae P99 and Morganella morganii, Ic in P. vulgaris, K-1 in K. oxytoca, and Id in P. aeruginosa also did not hydrolyze CGP 31608. It inhibited TEM-1, but the 50% inhibitory concentration was 14.2 micrograms/ml compared with 0.15 micrograms/ml for the P99 enzyme. CGP 31608 induced beta-lactamases in P. aeruginosa, E. cloacae, C. freundii and Providencia rettgeri, but there was no increase in MICs for the isolates and it did not select strains derepressed for beta-lactamase production. Synergy of CGP 31608 and gentamicin was found against 90% P. aeruginosa, 60% Enterobacter cloacae, and 50% Serratia marcescens strains. No synergy was found with rifampin. A postantibiotic effect was found against E. coli.

Genital chlamydial disease in an urban, primarily Hispanic, family planning clinic.

BACKGROUND AND OBJECTIVES: Although chlamydia is a well-studied disease, little is known about the rates of genital chlamydial disease among female Hispanics in urban family planning clinics. GOALS: To determine the prevalence of women with chlamydia in two clinic populations during 1994. We also sought to describe previously identified and novel risk factors for chlamydial disease in this unique population. STUDY DESIGN: We conducted a retrospective case-control analysis in two community clinics in the Washington Heights section of New York City. RESULTS: In 1994, 4,190 screening tests were done for Chlamydia trachomatis in these clinics, and the prevalence of positive tests was 5.4% (227/4,190). The mean age of the women screened was 19.2 years and most were of Hispanic origin (76%), students (51%), and received Medicaid (61%). Risk factors found to be associated with C. trachomatis infection included young age; earlier age at first coitus; pregnancy at the time of chlamydia screening; concurrent gonorrheal infection; and the clinical findings of cervical abnormalities, vaginal discharge, and adnexal tenderness. Hormonal contraception appeared to be protective against chlamydial infection (odds ratio, 0.36%; confidence interval, 0.17-0.77). CONCLUSION: Sexually transmitted diseases were common in our population because 5.4% of the women screened had chlamydial infection and 1.5% had concurrent gonorrheal infection. Our study confirmed risk factors established in other populations. These data support the need for enhanced screening efforts for chlamydia to decrease the prevalence of disease in our population.

PIP: The prevalence of and risk factors associated with chlamydia infection were investigated retrospectively among 4190 US women under 30 years (mean age, 19.2 years) who were patients at two young adult family planning clinics in New York City, New York. Immigrants from the Dominican Republic comprise the largest segment of the population served by these clinics. 76% of study participants were Hispanic, 61% were Medicaid recipients, and 51% were students. 227 women (5.4%) were positive for Chlamydia trachomatis. 7 women (3.5%) with chlamydia had concurrent gonorrhea. Compared with their counterparts with a negative chlamydia test, women with chlamydia were younger (mean age, 19.4 vs. 18.8 years) and had a lower mean age at first coitus (16 vs. 15 years). Use of barrier methods of contraception alone conferred no more protection against chlamydia than contraceptive nonuse, presumably because of inconsistent or improper use. However, women who used both a barrier and hormonal method were less than half as likely to be infected with chlamydia than those using no protection. 39% of women diagnosed with chlamydia had no cervical or vaginal abnormalities, while 20% of women with a negative chlamydia test had physical examination findings suggestive of genital infection. Regression analysis identified three factors significantly associated with chlamydia infection: positive pregnancy test at the time of the first clinic visit, vaginal discharge on pelvic examination, and self-reported drug use. The positive predictive value of diagnosing an infection increased from 50% using the clinical impressions of the providers to 61% with this model.

Activity of A-56268 compared with that of erythromycin and other oral agents against aerobic and anaerobic bacteria.

A-56268 was compared with erythromycin, roxithromycin (RU 28965), and perorally administered antimicrobial agents. Its in vitro activity was similar to that of erythromycin and slightly greater than that of roxithromycin, with beta-hemolytic streptococci and Streptococcus pneumoniae inhibited by less than 2 micrograms of A-56268 per ml (50% inhibited by 0.06 microgram/ml). Streptococcus pyogenes, S. agalactiae, S. Pneumoniae, and S. faecalis resistant to erythromycin were resistant to A-56268, and 4 micrograms/ml inhibited 90% of Haemophilus influenzae isolates.