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Among 6,068 strains of Staphylococcus epidermidis, 75.5% were oxacillin-resistant. Oxacillin-susceptible strains were more frequently susceptible to erythromycin, clindamycin, ciprofloxacin, trimethoprim/sulfamethoxazole, gentamicin, and tetracycline than oxacillin-resistant strains. With the exception of erythromycin, non-beta-lactam MICs were less discriminatory for identifying oxacillin-resistant strains with oxacillin MICs < or = 2 micrograms/ml than for those with oxacillin MICs > or = 4 micrograms/ml.

Over 2800 clinical strains of the Bacteroides fragilis group were collected during a 5-year period from ten geographically separate sites and tested for their susceptibility to various antimicrobial agents using a broth microdilution method. Among the cephalosporins, ceftizoxime was the most active (13% resistance) and importantly exhibited relatively equal activity against both B. fragilis species and non-B. fragilis species. Cefotaxime exhibited similar activity with an overall resistance rate of 18%. Both ceftriaxone and cefoperazone were appreciably less active cephalosporins especially against non-B. fragilis species. With regard to cephamycins, cefoxitin (MIC90, 32 micrograms/ml) was more active than cefotetan (MIC90, > or = 256 micrograms/ml) and cefmetazole (MIC90, 64 micrograms/ml). Non-B. fragilis species were highly resistant to cefotetan and cefmetazole. Imipenem was highly active against all strains with the exception of four strains of B. fragilis. Ampicillin-sulbactam, amoxicillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam were all highly active with resistance rates < 2%. No resistance was detected to metronidazole, whereas 14% of isolates were resistant to clindamycin. When compared with other studies, these findings underscore the wide variability in susceptibility patterns reported nationwide and the need to continue monitoring these patterns to aid in choosing the most active compounds for therapy.

Cefixime, a new orally absorbed cephalosporin, was compared by in vitro testing with other oral beta-lactams, including cephalexin, cefaclor, cefuroxime, amoxicillin, and amoxicillin + clavulanate. Enterobacteriaceae were inhibited by lower concentrations of cefixime than any of the reference drugs; 90% and 95% were inhibited by less than or equal to 1.0 and less than or equal to 8.0 micrograms/ml, respectively. Cefixime was the least active among these drugs against staphylococci, with only 31% of 1106 strains inhibited by less than or equal to 8.0 micrograms/ml and less than 1% by less than or equal to 1.0 microgram/ml. Enterococci and pseudomonads were not susceptible to any of the drugs tested. Penicillin-resistant pneumococci were relatively resistant to cefixime, but penicillin-susceptible pneumococci were very susceptible to cefixime. Other streptococci were generally susceptible to all compounds tested, with relative activities of amoxicillin greater than cefaclor and cefuroxime greater than cefixime greater than cephalexin. Cefixime was inactive against Bacteroides species. A slight inoculum effect occurred with cefixime with inocolum concentrations varying from 10(5) to 10(6) colony forming units per milliliter, but this was more marked at 10(7) colony forming units per milliliter. Cefixime was resistant to hydrolysis by seven common beta-lactamases. It inhibited the hydrolysis of nitrocefin only by type 1 cephalosporinases. The disk diffusion zone diameter breakpoints for the 30-micrograms cefixime disk were determined by regression analysis to be greater than or equal to 27 mm (susceptible) and less than or equal to 23 mm (resistant), respectively corresponding to minimal inhibitory concentration breakpoints of less than or equal to 1.0 and greater than or equal to 4.0 micrograms/ml. Because of the high interpretive error rate (13.8%) and the occurrence of these breakpoints on the parabolic portion of the regression curve, we recommend further evaluation of cefixime disks with lower potencies.

For 45-60 days four geographically separate clinical laboratories tested routine clinical bacterial isolates for susceptibility to carumonam, aztreonam, BMY-28142, and ceftazidime by the broth microdilution method. All four drugs were highly active against Enterobacteriaceae, inhibiting greater than 96% of the 4887 strains tested at less than or equal to 8.0 microgram/ml. The minimal inhibitory concentration at which 50% of the isolates were inhibited for each drug was less than or equal to 0.125 micrograms/ml. Ceftazidime was the most active against nonenteric gram-negative bacilli (86% inhibited at less than or equal to 8.0 micrograms/ml), followed by BMY 28142 (82%), carumonam (75%), and aztreonam (68%). The two monobactams exhibited no activity against gram-positive cocci at the concentrations tested, whereas BMY-28142 had excellent activity against nonenterococcal streptococci and good activity against staphylococci.

The susceptibility of over 7000 recent clinical bacterial isolates to RO 23-6240, a new trifluorinated quinolone, was determined at four medical centers. Over 99% of Enterobacteriaceae and 97% of staphylococci were inhibited by less than or equal to 2.0 micrograms/ml of RO 23-6240. Only 71% of Pseudomonas spp. were inhibited by this concentration. Streptococci and enterococci were resistant to RO 23-6240. Clinical isolates of Haemophilus spp., pathogenic Neisseria spp., and Branhamella catarrhalis were inhibited by less than or equal to 0.25 micrograms/ml of RO 23-6240. This drug's antibacterial activity was comparable with that of enoxacin and norfloxacin, but was less than that of ciprofloxacin against most species. Using less than or equal to 2.0 micrograms/ml and greater than or equal to 8.0 micrograms/ml as the susceptible and resistant MIC breakpoints for RO 23-6240, the regression analysis-derived disk diffusion zone diameter breakpoints for the 5 micrograms disk are: Susceptible greater than or equal to 19 mm intermediate 16-18 mm, and resistant less than or equal to 15 mm.

DJ-6783 is a new keto carboxylic acid having an expanded antimicrobial activity when compared with nalidixic acid or cinoxacin. Its usable activity includes the following: Enterobacteriaceae (MIC90, less than or equal to 0.06-4.0 micrograms/ml), Acinetobacter species (MIC90, 0.25-1.0 microgram/ml), Pseudomonas species (MIC90, 1.0-2.0 micrograms/ml), P. aeruginosa (MIC90, 16 micrograms/ml), Staphylococcus species (MIC90, 1.0-32 micrograms/ml), Haemophilus influenzae (MIC900, less than or equal to 0.06 microgram/ml), and Neisseria species (MIC90 less than or equal to 0.06 microgram/ml). The Streptococcus species were resistant to DL-6783 with MIC50 ranging from 16 to greater than 32 micrograms/ml. The drug appears to be bactericidal, minimally influenced by increasing inocula, but resistant mutants can be selected by serial subinhibitory concentration passages of strains in DJ-6783. The resulting resistant organisms also have higher MICs to related drugs such as norfloxacin, cinoxacin, and nalidixic acid. DJ-6783 was the most active organic acid not having structural characteristics of the fluorinated 4-quinolones.

The susceptibility of 7,763 clinical isolates at four medical centers to CI-934 and three comparative quinolones was tested. CI-934 was the most active compound against Gram-positive isolates, such as staphylococci (MIC 90 = 0.25 microgram/ml), and enterococci (MIC 90 = 0.5 microgram/ml). CI-934 was the least active of these drugs against Pseudomonas spp. (MIC 90 = greater than 8.0 micrograms/ml). Against all other organisms CI-934 was very effective, being most comparable with enoxacin. With a selected group of isolates, CI-934 demonstrated high activity against Haemophilus influenzae (MIC 90 = 0.06 microgram/ml), Neisseria meningitidis and N. gonorrhoeae (MIC 90 = 0.13 microgram/ml), Listeria monocytogenes (MIC 90 = 1.0 microgram/ml), methicillin-resistant staphylococci (MIC 90 = 0.13 microgram/ml), and modest activity against anaerobes. Disk diffusion susceptibility testing of CI-934 was evaluated using 3-, 5-, and 10-micrograms disks. Because of its lower interpretive error rate, the 3-micrograms disk is tentatively recommended. With less than or equal to 2 micrograms/ml and greater than 4 micrograms/ml as the susceptible and resistant MIC breakpoints, the corresponding 3-micrograms disk zone diameters breakpoints are greater than or equal to 15 mm and less than or equal to 11 mm. Because most isolates of Pseudomonas spp. are not susceptible to CI-934 and the zone size interpretive error rate is particularly high (33%) with Pseudomonas spp., we suggest that isolates of this genus not be tested for clinical purposes.

A six-laboratory collaborative study was performed in order to define quality control limits for microdilution tests with seven new beta-lactams (aztreonam, imipenem, ceftriaxone, ceftazidime, ceftizoxime, cefuroxime, and cefonicid). Four standard control strains were tested and the expected MIC limits for each of the appropriate drug-microorganism combinations were defined.

In vitro studies with imipenem (N-formimidoyl thienamycin or MK0787) were performed with 8481 clinical isolates in three separate medical centers. More extensive comparative studies were also performed with 605 representative isolates, comparing imipenem to six other beta-lactams. Although the newer beta-lactams were often more active against susceptible species, imipenem demonstrated the broadest spectrum of antibacterial activity, with MIC 90s less than or equal to 4.0 micrograms/ml for all species tested except Pseudomonas maltophilia and P. cepacia. Imipenem was very active against all streptococci and staphylococci, in contrast to the third-generation cephalosporins. There was no evidence of cross-resistance between imipenem and the cephalosporins or penicillins. Resistance to hydrolysis by seven beta-lactamase preparations was documented for imipenem, cefotaxime, and moxalactam. Like many other beta-lactams, imipenem inhibited the Type I beta-lactamase produced by Enterobacter cloacae. Other beta-lactamases from gram-negative bacilli were also inhibited by high concentrations of imipenem.

U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807), was tested against 4,742 fresh clinical isolates from four large medical centers. U-76,253A was very active against nearly all species of Enterobacteriaceae (87.7% inhibited at less than or equal to 4.0 micrograms/ml). Staphylococcus spp., and the streptococci. The U-76,253A spectrum was superior to the comparison orally administered cephalosporins (cephalexin, cephradine, cefaclor). Pseudomonas spp., Acinetobacter spp., and the enterococci were resistant to U-76,253A and the other tested drugs. Broth microdilution MIC quality control (QC) limits were established for U-76,253A in a multilaboratory investigation using a minimum of 125 MIC determinations per organism. The following MIC QC ranges were recommended; Escherichia coli (ATCC 25922) = 0.25-1.0 micrograms/ml, Staphylococcus aureus (ATCC 29213) = 2.0-4.0 micrograms/ml and Pseudomonas aeruginosa (ATCC 27853) = greater than 32 micrograms/ml.

The susceptibility testing of 7,745 recent clinical isolates from four medical centers showed Ro 19-5247 to be eight- to greater than 64-fold more active than cephalexin against the Enterobacteriaceae. Ro 19-5247 was comparable with cephalexin in anti-staphylococcal activity (MIC50, 4.0 micrograms/ml) and fourfold more active than cefixime. None of the oral cephalosporins were effective (MIC50, greater than 32 micrograms/ml) against enterococci, Pseudomonas aeruginosa and P. maltophilia. beta-lactamase hydrolysis experiments failed to demonstrate significant Ro 19-5247 inactivation by ten commonly encountered chromosomal- or plasmid-mediated enzymes (P99, K1, K14, TEM, CARB, OXA).