13-Lactamase production (nitrocefin disk method) and agar dilution susceptibility of amoxicillin, amoxicillin- Among the fusobacteria, Fusobacterium mortferum showed the highest rate of 3-lactamase positivity (76.9%).MICs of amoxicillin (128 ,g/ml) and ticarcillin (64 ,g/ml) for 90% of all ,B-lactamase-positive strains were reduced to 4 and 2 ,ug/ml, respectively, with the addition of clavulanate. MICs of amoxicillin and ticarcillin for 90% of all 1-lactamase-negative strains were 1 and 4 ,ug/ml, respectively, and .98.4% of the strains were susceptible to the P-lactams tested. Of the j-lactamase-producing strains, 45.9% were susceptible to amoxicilHin at c4 pg/ml and 93.4% were susceptible to ticarcillin at c64 ,ug/ml; the addition of clavulanate raised the rates to 90.4 and 100%, respectively. All strains were susceptible to cefoxitin, imipenem, and metronidazole. The activity of amoxicillin against 29 ,B-lactamase-producing strains (10 Bacteroides species and 19 fusobacteria) was not enhanced by the addition of clavulanate; however, 82.7% of these strains were susceptible to amoxicillin, and all were susceptible to ticarcillin. Although P-lactamase positivity is on the increase in non-B. fragilis group Bacteroides species and fusobacteria, amoxicillin-clavulanate, ticarcilHin, cefoxitin, imipenem, and metronidazole should be suitable for the treatment of infections with these strains. The addition of clavulanate does not appreciably improve the efficacy of ticarcillin against these organisms.

The MICs of four new quinolones, sparfloxacin (AT4140, CI-978), PD 131628 (the active form of the prodrug Susceptibility to RP 59500, a new streptogramin, was also tested and compared with those to the quinolones, erythromycin, and vancomycin. All MICs were determined by a standardized agar dilution method by using Mueller-Hinton agar supplemented with sheep blood. Quinolone, vancomycin, and RP 59500 susceptibilities were not affected by susceptibility or resistance to penicillin. For Win 57273, the MICs for 50%o (MIC50) and 90%YO (MIC90) of strains tested were 0.015 and 0.03 JLg/ml, respectively. MIC,Os of both sparfloxacin and PD 131628 were 0.25 pg/ml, and MIC,0s were 0.5 jag/ml. The MIC. of temafloxacin was 0.5 ,ug/ml, and the MIC,, was 1.0 pg/ml. By comparison, ofloxacin and ciprofloxacin both yielded MIC-.s of 1.0 jag/ml and MIC90s of 2.0 pLg/ml. RP 59500 yielded an MIC. of 0.5 zg/ml and an MIC90 of 1.0 pg/ml and was only 1 doubling dilution less active against 17 erythromycin-resistant strains. Vancomycin was active against all strains (MIC50, 0.25 iag/ml; MIC90, 0.5 jag/mI). All four experimental quinolones as well as RP 59500 show promise for therapy of infections with penicillin-resistant and -susceptible pneumococci.

MICs of six oral cephalosporins (cefdinir, cefpodoxime, cefaclor, cefuroxime, cefixime and Ro 40-6890), four quinolones (ciprofloxacin, ofloxacin, OPC-17116 and fleroxacin), desacetylcefotaxime, Ro 23-9424 (a fused combination of fleroxacin + desacetylcefotaxime) and RP 67829 (a benzonaphthyridine) were determined for 49 penicillin-susceptible (S), 38 penicillin-intermediate (I), and 83 penicillin-resistant (R) strains of Streptococcus pneumoniae. All MICs were determined by a standardized agar dilution method utilizing Mueller-Hinton agar supplemented with sheep blood. MIC90s of OPC-17116 and RP 67829 were < or = mg/L, and were unaffected by penicillin-susceptibility. MICs of all beta-lactams increased with increasing penicillin-MICs, with cefdinir, cefpodoxime, cefuroxime and Ro 40-6890 being the most active compounds, followed by cefaclor and cefixime. MIC90s of ciprofloxacin and ofloxacin were 2 mg/L. MIC90s of Ro 23-9424 were lower than those of either parent compound (fleroxacin 8 mg/mL for all three groups; desacetylcefotaxime 0.5 mg/mL [S], 0.5 mg/mL [I], 4 mg/mL [R]; Ro 23-9424 0.125 mg/L [S], 0.25 mg/L [I], 0.5 mg/L [R]). The results indicated that several newly introduced and experimental antimicrobials have potential for the treatment of infections caused by resistant strains of S. pneumoniae.

Agar dilution was used to compare the in vitro activity of CP 99,219 with those of ciprofloxacin, grepafloxacin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam against 489 anaerobes. CP 99,219 yielded a MIC for 50%6 of the strains tested (MIC..) of 0.25 ,ug/ml and a MIC90 of 1.0 pg/ml, with 99.6% of the strains susceptible at a breakpoint of 2.0 ,ug/ml. Ciprofloxacin and grepafloxacin were less active (MIC50, 4.0 ,ug/ml; MIC90, 32.0 ,ug/ml and 2.0 and 16.0 ,ug/ml, respectively). Metronidazole was active against all gram-negative rods (MIC%0, 4.0 ,ug/ml), but 31% of the gram-positive anaerobes were resistant at >8.0 ,ug/ml. Cefoxitin was active against 84% of all strains at <16.0 ,g/mli, with a MIC50 of 4.0 ,ug/ml and a MIC90 of 32.0 ,ug/ml. Tazobactam enhanced the activity of piperacillin against >95% of the j-lactamase-producing gram-negative anaerobic rods (MIC90, 16.0 ,ug/ml).Anaerobes are becoming increasingly resistant to 13-lactams because of P-lactamase production and other mechanisms.Metronidazole resistance in organisms other than non-sporeforming gram-positive rods has been described previously, as has clindamycin resistance in anaerobic gram-negative rodsCommercially available quinolones, such as ciprofloxacin, ofloxacin, fleroxacin, pefloxacin, enoxacin, and lomefloxacin, are inactive or marginally active against anaerobes, with MICs either higher than or clustering around breakpoints. Experimental quinolones with increased anti-anaerobic activity include (i) those with slightly increased activity (sparfloxacin, OPC 17116 [grepafloxacin], tosufloxacin, temafloxacin [now discontinued], CI-990, AM-1155, and levofloxacin) and (ii) those with significantly improved anti-anaerobic activity (Win 57273, Bay y3118, clinafloxacin, and DU-6859a) (6-8, 12, 19, 24, 25). Development of both Win 57273 and Bay y3118 has been discontinued because of toxicity.CP 99,219 is a novel investigational trifluoronaphthyridone with a structure differing from those of norfloxacin, ciprofloxacin, and enoxacin. It contains the C-7 moiety 7-(3-azabicyclo [3.1.0.]hexyl) on a basic naphthyridone configuration (9). The bicyclo C-7 substitution has been previously evaluated and described for 667 (17). The 1-N substitution of CP 99,219 is a difluorinated structure identical to that of tosufloxacin that produces enhanced activity against some ciprofloxacinresistant strains. CP 99,219 possesses a broad spectrum of activity against gram-positive and -negative organisms, including those resistant to ciprofloxacin (9,10,13,14,18,21

The in vitro activities of the P-lactamase inhibitors YTR 830, clavulanate, and sulbactam combined with six P-lactams against 88 ,-lactamase-producing anaerobes were determined. When combined with the ,-lactams, the three ,-lactamase inhibitors showed no synergy against the 10 Bacteroides fragilis homology group II strains. When the B-lactams were combined with the inhibitors, their geometric mean MICs against the remaining 78 strains were reduced from 4.2 to 150.2 ,ug/ml to 0.2 to 12.9 ,ug/ml. The activity of the P-lactams combined with the P-lactamase inhibitors was significantly greater than that of the ,-lactams alone against all groups except B. fragilis homology group II, with 76 to 100% of the strains susceptible to ampicillin plus inhibitor and .90% susceptible to the other combinations.Although the antimicrobial susceptibility spectrum of anaerobes has remained relatively stable, P-lactamasemediated resistance to penicillin and other P-lactams has been described for species in the Bacteroides fragilis group and for other Bacteroides spp., Fusobacterium nucleatum, and Clostridium butyricum (3,7,15,18,19). Several studies have demonstrated that the ,-lactamase inhibitors clavulanate and sulbactam act synergistically in vitro with ,-lactams against P-lactamase-positive, but not P-lactamase-negative, anaerobic organisms (2,4,5,16,20,21). YTR 830 is a new ,-lactamase inhibitor (1) with activity comparable to that of clavulanate and superior to that of sulbactam against ,1-lactamase-producing members of the family Enterobacteriaceae (6, 10). The purpose of this study was to compare the in vitro activities of six P-lactams (ampicillin, ticarcillin, mezlocillin, piperacillin, apalcillin, and cefoperazone) The presence of 3-lactamase was detected by a chromogenic cephalosporin method on growth from enriched blood agar plates by using nitrocefin disks (BBL Microbiology Systems, Cockeysville, Md.), in accordance with standard practice (4, 10). Organisms were stored at -70°C in thioglycolateglycerol (85:15, vol/vol) and were subcultured on enriched blood agar plates before testing.Laboratory reference powders of the following agents were used: ticarcillin and clavulanate (Beecham Laboratories, Bristol, Tenn.); mezlocillin (Miles Laboratories, Inc., West Haven, Conn.); piperacillin (Lederle Laboratories, Pearl River, N.Y.); apalcillin (Wyeth Laboratories, Philadelphia, Pa.); cefoperazone and sulbactam (Pfizer Inc., New York, N.Y.); ampicillin (Bristol-Myers Laboratories, Wallingford, Conn.); cefoxitin (Merck Sharpe & Dohme, West Point, Pa.); and YTR 830 (Taiho Pharmaceuticals, Tokyo, Japan). The powders were dissolved and diluted in accordance with the instructions of the manufacturers, and the potency of the agents was checked by determination of the MICs for quality control strains.Susceptibility testing of the isolates was performed by agar dilution on Wilkins-Chalgren agar (Difco Laboratories, Detroit, Mich.) (14,17). Plates contained serial doubling dilutions of the 3-lactams (ampicillin, 0.125 to 256 ,ug/...