Biomedical subjects
Publications and source records attributed to C V Sanders.
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Through the use of time-kill kinetic studies, the bactericidal activity of cefotaxime (CTX) and desacetylcefotaxime (dCTX) alone and in combination against 18 strains of Bacteroides fragilis group was studied. Each isolate was tested at subinhibitory, inhibitory, and suprainhibitory concentrations of each drug as determined from the MIC values. Overall CTX was more bactericidal than dCTX at each of the three concentration levels tested. The combination of CTX and dCTX showed comparable bactericidal activity to CTX at the subinhibitory and inhibitory concentrations, even though each component was present at only one-half the concentration of CTX alone. At suprainhibitory concentrations, the combination of CTX/dCTX appeared synergistic since the combination with each component at a concentration of 1 x MIC was as bactericidal as CTX at a concentration of 4 x MIC. CTX and dCTX alone and in combination exhibited comparable bactericidal activity against test isolates with high (greater than or equal to 32 micrograms/ml) or low (less than or equal to 16 micrograms/ml) MICs. Thus, in vitro the combination of CTX and its naturally occurring metabolite dCTX interacts to produce an additive or synergistic effect against strains of B. fragilis group. Whether the in vitro testing of the combinations is more relevant to clinical outcome than testing CTX alone needs further study.
Lomefloxacin (NY-198; SC-47111), a potent new difluoroquinolone, was studied to compare its in vitro activity with that of other antimicrobials against 2194 clinical isolates. Lomefloxacin showed excellent inhibitory and bactericidal activity against strains of Enterobacteriaceae and inhibited greater than 99% of the isolates at a concentration of 4 micrograms/ml or less. Lomefloxacin exhibited good-to-moderate activity against strains of Acinetobacter (MIC90 4 micrograms/ml) and Pseudomonas aeruginosa (MIC90 8 micrograms/ml), but poor activity for Pseudomonas cepacia (MIC90 greater than 16 micrograms/ml). Staphylococcus aureus, and Staphylococcus epidermidis isolates, both oxacillin-susceptible and -resistant strains, were susceptible (MIC90 1 micrograms/ml) to lomefloxacin and the other fluoroquinolones. Strains of Haemophilus influenzae, (MIC90 less than or equal to 0.13 micrograms/ml) Neisseria gonorrhoeae (MIC90 less than or equal to 0.03 micrograms/ml), and Branhamella catarrhalis (MIC90 less than or equal to 0.03 micrograms/ml) were highly susceptible to lomefloxacin. Streptococcal isolates, especially viridans streptococci, were considerably less susceptible to the fluoroquinolones. Overall, lomefloxacin had comparable activity to norfloxacin, fleroxacin, and ofloxacin, and against many facultative anaerobes lomefloxacin was more active than imipenem, cefotaxime, ceftazidime, ticarcillin/clavulanic acid, aztreonam, trimethoprim/sulfamethoxazole and gentamicin. Development of resistance to lomefloxacin by spontaneous mutation was low and comparable to that of other fluoroquinolones. Growth in subinhibitory concentrations resulted in increased resistance to fluoroquinolones for selected test strains.
Using a broth microdilution method, we compared the in vitro activity of lomefloxacin to other broad spectrum antimicrobials against clinical strains of Enterobacteriaceae, Acinetobacter spp, Aeromonas spp, and P. aeruginosa. Against the Enterobacteriaceae and A. hydrophila, lomefloxacin showed excellent activity with MIC50 values ranging from 0.12-0.5 micrograms/ml and MIC90 values ranging from 0.12-1.0 micrograms/ml. By comparison, lomefloxacin had superior activity to nalidixic acid and difloxacin, comparable activity to norfloxacin and fleroxacin, and slightly less activity than ciprofloxacin. Lomefloxacin was also more active than imipenem, ceftazidime, aztreonam, ticarcillin/clavulanic acid (T-CA), and gentamicin. Lomefloxacin was less active (MIC90, 4 micrograms/ml) against Acinetobacter strains than Enterobacteriaceae strains. Against these same Acinetobacter strains, lomefloxacin was 8- to 64-fold more active than ceftazidime, aztreonam, T-CA, and gentamicin but slightly less active than imipenem. Lomefloxacin was 2- to 8-fold more active than fleroxacin, difloxacin, and nalidixic acid against strains of P. aeruginosa. However, lomefloxacin was less active than ciprofloxacin and norfloxacin. Lomefloxacin had comparable activity to imipenem but was 2- to 16-fold more active than ceftazidime, aztreonam, T-CA, and gentamicin. Thus, lomefloxacin demonstrated comparable activity to other fluorinated quinolones in that it possesses high active against clinical strains of Enterobacteriaceae and had good-to-moderate activity against most strains of Acinetobacter and P. aeruginosa.
Nineteen strains of the Bacteroides fragilis group were used to determine the bactericidal activity of ceftizoxime, cefoxitin, cefotetan, and penicillin G with time-kill kinetics studies. Each antimicrobial agent was tested at subinhibitory (1/2 X MIC), inhibitory (1 X MIC), and suprainhibitory (4 X MIC) concentrations. Penicillin G exhibited virtually no sustained bactericidal activity at any of the antimicrobial concentrations tested. At subinhibitory concentrations, ceftizoxime was considerably more bactericidal than cefoxitin or cefotetan: At 12 hr, ceftizoxime killed 89% of the inoculum, whereas cefoxitin and cefotetan killed 35% and 33% of the inoculum, respectively. At inhibitory concentrations, ceftizoxime was again more bactericidal than cefoxitin and cefotetan: At 12 hr, ceftizoxime killed 90% of the inoculum, whereas cefoxitin and cefotetan killed 78% and 73%, respectively. At suprainhibitory concentrations, all three antimicrobial agents showed comparable bactericidal activity at 12 and 24 hr. Ceftizoxime and cefoxitin had somewhat lower killing rates overall against test strains with high MICs (greater than or equal to 32) versus low MICs (less than or equal to 16). However, at subinhibitory concentrations, ceftizoxime killed the B. fragilis group strains with high or low MIC values more effectively than cefotetan killed strains with low MICs. At the highest antibiotic concentrations tested (4 X MIC), only slight differences were seen in the bactericidal activity of the three compounds, regardless of MICs.
Puerperal uterine infection, or endomyometritis, occurs more commonly after cesarean section than after vaginal birth. With the rate of cesarean delivery almost 25% of all births in this country, such infection is relatively common. The classic therapy for postcesarean endomyometritis is the combination of clindamycin and an aminoglycoside, usually gentamicin or tobramycin. This regimen has requisite antimicrobial activity against the aerobes and anaerobes of the cervicovaginal flora that usually cause this illness. In the last decade, however, the availability of broad-spectrum beta-lactam antibiotics has enabled the clinician to combat postcesarean infection with single-agent antimicrobial chemotherapy, or monotherapy. "Higher-generation" cephalosporins such as cefoxitin, cefotetan, and moxalactam, as well as the semisynthetic penicillins ticarcillin, piperacillin, and mezlocillin, have all been used alone in the therapy for postpartum infection. The addition of a beta-lactamase inhibitor to this class of drugs now offers a further resource to the practitioner if beta-lactamase-mediated antibiotic resistance arises in the patient population being treated.