In vitro activity of biapenem (L-627), a new carbapenem, against anaerobes.

We tested 441 clinical strains of anaerobes by using a broth microdilution method to determine the in vitro activity of biapenem for comparison with those of other agents. Biapenem had activity comparable to those of imipenem and meropenem against all groups of anaerobes with MICs for 90% of the strains tested of 0.06 to 2 micrograms/ml. Against the Bacteroides fragilis group, biapenem was more active than ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin, cefoxitin, cefotaxime, and ceftriaxone. Biapenem was also active against all of the B. capillosus, Prevotella, Clostridium, and Eubacterium strains and anaerobic cocci tested. Against all of the anaerobes tested, biapenem was 32- and 4-fold more active than clindamycin and metronidazole, respectively. These data indicate broad-spectrum activity by biapenem against anaerobes.     

Increased activity of a new chlorofluoroquinolone, BAY y 3118, compared with activities of ciprofloxacin, sparfloxacin, and other antimicrobial agents against anaerobic bacteria.

A total of 435 clinical isolates of anaerobes were tested with a broth microdilution method to determine the activity of BAY y 3118 compared with those of other agents against anaerobic bacteria. All strains of Bacteroides capillosus, Prevotella spp., Porphyromonas spp., Fusobacterium spp., Clostridium spp., Eubacterium spp., Peptostreptococcus spp., and Veillonella parvula were susceptible (MICs of < or = 2 micrograms/ml) to BAY y 3118. Against the 315 strains of the Bacteroides fragilis group, five strains required elevated MICs (> or = 4 micrograms/ml) of BAY y 3118. Only imipenem and metronidazole were active against all anaerobes. Overall, BAY y 3118 was more active than ciprofloxacin, sparfloxacin, piperacillin, cefotaxime, and clindamycin against the test isolates.     

Activity of Telithromycin (HMR 3647) against Anaerobic Bacteria Compared to Those of Eight Other Agents by Time-Kill Methodology

Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition of Oxyrase in order to prevent the introduction of CO(2). Macrolide-azalide-ketolide MICs were 0.004 to 32.0 microg/ml. Of the latter group, telithromycin had the lowest MICs, especially against non-Bacteroides fragilis group strains, followed by azithromycin, clarithromycin, erythromycin A, and roxithromycin. Clindamycin was active (MIC /=99.9% killing) against 6 strains, with 99% killing of 9 strains and 90% killing of 10 strains. After 24 h at twice the MIC, 90, 99, and 99.9% killing of nine, six, and three strains, respectively, occurred. Lower rates of killing were seen at earlier times. Similar kill kinetics relative to the MIC were seen with other macrolides. After 48 h at the MIC, clindamycin was bactericidal against 8 strains, with 99 and 90% killing of 9 and 10 strains, respectively. After 24 h, 90% killing of 10 strains occurred at the MIC. The kinetics of clindamycin were similar to those of pristinamycin. After 48 h at the MIC, amoxicillin-clavulanate showed 99.9% killing of seven strains, with 99% killing of eight strains and 90% killing of nine strains. At four times the MIC, metronidazole was bactericidal against 8 of 10 strains tested after 48 h and against all 10 strains after 24 h; after 12 h, 99% killing of all 10 strains occurred.     

Susceptibility of anaerobic bacteria isolated from intra-abdominal infections to ofloxacin and interaction of ofloxacin with metronidazole.

The in vitro activities of ofloxacin alone and in combination with metronidazole against 177 anaerobic bacteria isolated from intra-abdominal infections, as determined by broth microdilution, showed that some Bacteroides fragilis strains were susceptible and that most other B. fragilis group species strains were resistant to ofloxacin. Isolates of other anaerobic species and genera, including those causing female genital tract disease, were generally susceptible to ofloxacin. Ofloxacin in combination with metronidazole usually showed an additive or indifferent interaction but no antagonism.     

Bactericidal activity of DU-6859a compared to activities of three quinolones, three beta-lactams, clindamycin, and metronidazole against anaerobes as determined by time-kill methodology.

The activities of DU-6859a, ciprofloxacin, levofloxacin, sparfloxacin, piperacillin, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 11 anaerobes were tested by the broth microdilution and time-kill methods. DU-6859a was the most active drug tested (broth microdilution MICs, 0.06 to 0.5 microg/ml), followed by imipenem (MICs, 0.002 to 4.0 microg/ml). Broth macrodilution MICs were within 3 (but usually 1) dilutions of the broth microdilution MICs. All compounds were bactericidal at the MIC after 48 h; after 24 h, 90% killing was shown for all strains when the compounds were used at four times the MIC. DU-6859a at < or = 0.5 microg/ml was bactericidal after 48 h.     

In Vitro Antimicrobial Susceptibility of Anaerobic Bacteria Isolated from Clinical Specimens

The minimal inhibitory concentrations of 601 clinical isolates of anaerobic bacteria to 10 different antimicrobial agents were determined by an agar-dilution technique. Nearly all strains were resistant to kanamycin and gentamicin, although moderate activity to both drugs was noted with Fusobacterium sp., anaerobic cocci, some strains of Bacteroides melaninogenicus, and nonsporeforming gram-positive bacilli. Chloramphenicol at 12.5 mug/ml inhibited all but three of the strains tested. Tetracycline at 6.25 mug/ml had high activity against all groups tested, with the exception that only 39% of strains of Bacteroides fragilis were inhibited at this concentration. Excluding certain species of Bacteroides, the majority of anaerobes were inhibited by penicillin at 3.1 mug/ml or less and by cephalothin at 12.5 mug/ml or less. Lincomycin at 6.2 mug/ml or less was active against nearly all strains. Erythromycin at a concentration of 3.1 mug/ml was active against B. fragilis; however, erythromycin was less active against the other groups. Most of the minimal inhibitory concentrations of lincomycin exceeded those of clindamycin by fourfold. Rifampin inhibited virtually all strains at 3.1 mug/ml.     

In Vitro Activity of Josamycin and Rosamicin Against Bacteroides fragilis Compared with Clindamycin, Erythromycin, and Metronidazole

The inhibitory and bactericidal activities of josamycin and rosamicin against 29 clinical isolates of Bacteroides fragilis were compared with those of clindamycin, erythromycin, and metronidazole by a broth dilution technique. Josamycin and rosamicin had similar inhibitory activity to metronidazole and clindamycin. Rosamicin had similar bactericidal activity to clindamycin but was less bactericidal than metronidazole (the most bactericidal agent tested). Josamycin was slightly more bactericidal than erythromycin (the least bactericidal agent tested), but less so than rosamicin and clindamycin.     

BMY28142, cefbuperazone (T-1982), and Sch 34343. Antimicrobial activity against 94 anaerobes compared to seven other antimicrobial agents

Three new beta-lactams were evaluated against 94 anaerobic strains representing 15 species using a Wilkins-Chalgren broth microdilution method. The penems, Sch 29482 and Sch 34343, were most active with all minimum inhibitory concentrations (MICs) at less than or equal to 4.0 micrograms/ml and MIC90s of less than or equal to 0.25 micrograms/ml. BMY 28142 had a more limited antianaerobic activity against Bacteroides fragilis with a MIC50 and MIC90 of 32 and 128 micrograms/ml, respectively. Cefbuperazone (T-1982) had low B. fragilis MICs (MIC90, 8.0 micrograms/ml), but potentially resistant range MIC90 results for the other species in the B. fragilis group and Clostridium species.     

肺炎链球菌192株对新喹诺酮类体外耐药性测定

目的：调查192株肺炎链球菌对青霉素、红霉素和环丙沙星等的耐药现状，并与新喹诺酮类进行比较。方法：根据美国国家I临床实验室标准委员会(NCCLS)2002年标准使用微量肉汤稀释法检测192株肺炎链球菌对青霉素、红霉素、克林霉素和喹诺酮类抗菌药物的最低抑菌浓度(MIC)。结果：肺炎链球菌对青霉素的耐药率(中介率 耐药率)已达42．7％，对红霉素的耐药率为77．6％，克林霉素、白霉素和环丙沙星的耐药率分别为66．7％、65．6％和57．3％，新喹诺酮类抗菌药物对之有较好的抗菌活性，敏感率皆大于90％；并与是否对青霉素、红霉素耐药无关。结论：在我国，肺炎链球菌对青霉素、红霉素的耐药率较高，新喹诺酮类抗生素有较好的抗菌活性。     

The comparative in-vitro activity of cefotetan against anaerobic bacteria

The in-vitro activity of cefotetan, a new cephamycin, was assessed against a total of 336 strains of anaerobic bacteria by means of an agar dilution procedure and compared with that of cefoxitin, mezlocillin, piperacillin, clindamycin and metronidazole. Overall clindamycin and metronidazole were the most active of the test compounds. Cefotetan showed good activity against anaerobic cocci and clostridia, except for Clostridium difficile (MIC90 = 16 mg/l), although it was comparatively less active than the other beta-lactams against anaerobic cocci. In the case of the Gram-negative anaerobes, cefotetan showed moderate activity comparable to that of cefoxitin; against the 120 test strains of Bacteroides fragilis both cefotetan and cefoxitin were markedly more active than the penicillins. In studies with antibiotic combinations, cefotetan + cefsulodin showed marked synergy (FIC index less than 0.3) against the majority of strains of Bact. fragilis tested.     

Antipneumococcal activity of ABT-773 compared to those of 10 other agents

MICs, time-kills, and postantibiotic effects (PAEs) of ABT-773 (a new ketolide) and 10 other agents were determined against 226 pneumococci. Against 78 ermB- and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s were 0.016 to 0.03 and 0.125 microgram/ml, respectively. Clindamycin was active only against macrolide-resistant strains containing mefE (MIC(50), 0.06 microgram/ml; MIC(90), 0.125 microgram/ml). Activities of pristinamycin (MIC(90), 0.5 microgram/ml) and vancomycin (MIC(90), 0.25 microgram/ml) were unaffected by macrolide or penicillin resistance, while beta-lactam MICs rose with those of penicillin G. Against 19 strains with L4 ribosomal protein mutations and two strains with mutations in domain V of 23S rRNA, ABT-773 MICs were 0.03 to 0.25 microgram/ml, while macrolide and azalide MICs were all >/=16.0 microgram/ml. ABT-773 was bactericidal at twice the MIC after 24 h for 8 of 12 strains (including three strains with erythromycin MICs greater than or equal to 64.0 microgram/ml). Kill kinetics of erythromycin, azithromycin, clarithromycin, and roxithromycin against macrolide-susceptible strains were slower than those of ABT-773. ABT-773 had longer PAEs than macrolides, azithromycin, clindamycin, or beta-lactams, including against ermB-containing strains. ABT-773, therefore, shows promising in vitro activity against macrolide-susceptible as well as -resistant pneumococci.     

In vitro activities of clindamycin, imipenem, metronidazole, and piperacillin-tazobactam against susceptible and resistant isolates of Bacteroides fragilis evaluated by kill kinetics

The aim of the present study was to investigate the activities of clindamycin, imipenem, metronidazole, and piperacillin-tazobactam against 12 Bacteroides fragilis isolates (resistant and susceptible strains) by kill kinetics over 24 h. In contrast to the other antimicrobial agents, clindamycin did not affect strains with MICs of >8.0 μg/ml. For those strains with MICs of ≤ 8.0 μg/ml, all employed antibiotics except clindamycin showed nearly bactericidal activity. Metronidazole proved to be the most active antimicrobial agent.     

Antipneumococcal activity of AZD2563, a new oxazolidinone,compared with nine other agents

The in vitro activity of AZD2563, a new oxazolidinone, was compared with that of linezolid, vancomycin, quinupristin/dalfopristin, amoxicillin, levofloxacin, penicillin, erythromycin, azithromycin and clindamycin against a range of pneumococci by microdilution and time-kill studies. Against 300 pneumococci (99 penicillin susceptible, 86 penicillin intermediate, 115 penicillin resistant, 185 erythromycin resistant, 35 quinolone resistant), both oxazolidinones remained active against isolates less susceptible to other agents, with MICs ranging between 0.125 and 2 mg/L; AZD2563 MICs were generally one dilution lower than those of linezolid. Both quinupristin/dalfopristin and vancomycin were active against all groups (MIC ranges 0.125-2 and 0.125-0.25 mg/L, respectively). Apart from 35 isolates with levofloxacin MICs > or= 8 mg/L, levofloxacin MICs were < or =0.25-4 mg/L. MICs of amoxicillin and erythromycin rose with penicillin G MICs; most macrolide-resistant isolates were either penicillin-intermediate or -resistant. Against 16 organisms with differing beta-lactam, macrolide and quinolone MICs, time-kill studies showed that AZD2563 was bactericidal (99.9% killing) at 4 x MIC against nine strains at 24 h, with 90% killing of all 16 strains at 2 x MIC after 12 h. Similar results were obtained with linezolid. Both oxazolidinones were bacteriostatic at the MIC against all 16 strains. Amoxicillin, levofloxacin and vancomycin, at 2 x MIC, were bactericidal against 15 of the 16 strains after 24 h. Quinupristin/dalfopristin yielded the most rapid killing, with bactericidal activity against 13 of 16 strains at the MIC after 3 h and against 15 strains at 2 x MIC after 24 h. Erythromycin was bactericidal against all 10 strains with MICs < or= 8 mg/L at 4 x MIC after 24 h.     

In vitro activity of the new ketolide telithromycin compared with those of macrolides against Streptococcus pyogenes: influences of resistance mechanisms and methodological factors

One hundred and seven clinical isolates of Streptococcus pyogenes, 80 susceptible to macrolides and 27 resistant to erythromycin A (MIC >0.5 microgram/ml), were examined. The erythromycin A-lincomycin double-disk test assigned 7 resistant strains to the M-phenotype, 8 to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLS(B)) phenotype, and 12 to the constitutive MLS(B) resistance (cMLS(B)) phenotype. MICs of erythromycin A, clarithromycin, azithromycin, roxithromycin, and clindamycin were determined by a broth microdilution method. MICs of telithromycin were determined by three different methods (broth microdilution, agar dilution, and E-test methods) in an ambient air atmosphere and in a 5 to 6% CO(2) atmosphere. Erythromycin A resistance genes were investigated by PCR in the 27 erythromycin A-resistant isolates. MICs of erythromycin A and clindamycin showed six groups of resistant strains, groups A to F. iMLS(B) strains (A, B, and D groups) are characterized by two distinct patterns of resistance correlated with genotypic results. A- and B-group strains were moderately resistant to 14- and 15-membered ring macrolides and highly susceptible to telithromycin. All A- and B-group isolates harbored erm TR gene, D-group strains, highly resistant to macrolides and intermediately resistant to telithromycin (MICs, 1 to 16 microgram/ml), were all characterized by having the ermB gene. All M-phenotype isolates (C group), resistant to 14- and 15-membered ring macrolides and susceptible to clindamycin and telithromycin, harbored the mefA gene. All cMLS(B) strains (E and F groups) with high level of resistance to macrolides, lincosamide, and telithromycin had the ermB gene. The effect of 5 to 6% CO(2) was remarkable on resistant strains, by increasing MICs of telithromycin from 1 to 6 twofold dilutions against D-E- and F-group isolates.     

Evaluation of the in vitro activity of NVP-LMB415 against clinical anaerobic isolates with emphasis on the Bacteroides fragilis group

OBJECTIVES: To compare the in vitro activity of NVP-LMB415 (formerly referred to as NVP-PDF 713) with that of other agents with anti-anaerobe activity against clinical anaerobic isolates, with emphasis on the Bacteroides fragilis group. METHODS: The MICs for 405 B. fragilis group and 102 Gram-positive anaerobic isolates were determined using NCCLS-recommended procedures. The activity of NVP-LMB415 was compared with that of cefoxitin, clindamycin, imipenem, garenoxacin, linezolid, moxifloxacin and tigecycline. Vancomycin was included in the evaluation of the Gram-positive organisms. RESULTS: NVP-LMB415 showed excellent in vitro activity against all the species of the B. fragilis group isolates (MIC range < or = 0.03-0.5 mg/L and MIC(90) 0.5 mg/L). NVP-LMB415 was active against B. fragilis group strains resistant to beta-lactams, quinolones or clindamycin, and the MICs were much lower than those of newer agents such as linezolid, tigecycline and garenoxacin. The MICs of NVP-LMB415 ( > or = 4 mg/L) for Clostridium species were higher than the MICs for other anaerobes. CONCLUSIONS: Given the frequency of isolation of anaerobic bacteria and their increasing resistance to all classes of antibiotics, NVP-LMB415 is an ideal agent for potential use against mixed infections caused by resistant anaerobic pathogens such as of B. fragilis and Gram-positive aerobic strains such as methicillin-resistant staphylococci, streptococci and enterococci.     

Comparison of in vitro antibiograms of Bacteroides fragilis group isolates: differences in resistance rates in two institutions because of differences in susceptibility testing methodology.

With 120 clinical isolates of the Bacteroides fragilis group, a comparison of rates of resistance to selected antimicrobial agents by using two susceptibility tests was performed in two medical institutions. The broth microdilution method produced MICs significantly lower than those determined by the agar dilution method. With ceftizoxime and cefoxitin, 88 and 18%, respectively, of the MICs were greater than or equal to 2 twofold dilutions apart. These differences in MIC results produced major interpretive discrepancies for ceftizoxime and cefoxitin, whereas no significant differences in resistance rates were noted for clindamycin and metronidazole.     

Antimicrobial susceptibility of anaerobic bacteria in Australia.

The susceptibilities of 900 clinical isolates of anaerobic bacteria to 14 antimicrobial agents were determined by an agar dilution technique. Chloramphenicol, imipenem and metronidazole were found to be active against virtually all of the strains; only a single Bacteroides fragilis isolate was resistant to both imipenem and metronidazole. The addition of clavulanic acid to amoxycillin and ticarcillin potentiated the activities of these agents against all anaerobes including members of the B. fragilis group. Ampicillin/sulbactam and clindamycin were the next most active agents, 91 and 89% of isolates respectively being susceptible. Seventy-three per cent of the bacteria tested were susceptible to cefoxitin and 65% to cefotetan, with the MICs of almost 50% of the isolates clustering between 16 and 32 mg/L. There was also clustering around the breakpoint (64 mg/L) of piperacillin. Azithromycin exhibited poor activity against the B. fragilis group; only 18% of isolates were susceptible to < or = 4 mg/L. However, 92% of non-B. fragilis Bacteroides group strains were susceptible to this agent. We conclude that imipenem, metronidazole, chloramphenicol, ticarcillin/clavulanate, co-amoxiclav and, to a lesser extent, ampicillin/sulbactam are suitable as empirical therapy for infections caused by anaerobic bacteria.     

Multicenter survey of the changing in vitro antimicrobial susceptibilities of clinical isolates of Bacteroides fragilis group, Prevotella, Fusobacterium, Porphyromonas, and Peptostreptococcus species

In vitro surveys of antimicrobial resistance among clinically important anaerobes are an important source of information that can be used for clinical decisions in the choice of empiric antimicrobial therapy. This study surveyed the susceptibilities of 556 clinical anaerobic isolates from four large medical centers using a broth microdilution method. Piperacillin-tazobactam was the only antimicrobial agent to which all the isolates were susceptible. Similarly, imipenem, meropenem, and metronidazole were highly active (resistance, <0.5%), whereas the lowest susceptibility rates were noted for penicillin G, ciprofloxacin, and clindamycin. For most antibiotics, blood isolates were less susceptible than isolates from intra-abdominal, obstetric-gynecologic, and other sources. All isolates of the Bacteroides fragilis group were susceptible to piperacillin-tazobactam and metronidazole, while resistance to imipenem and meropenem was low (<2%). For these same isolates, resistance rates (intermediate and resistant MICs) to ampicillin-sulbactam, cefoxitin, trovafloxacin, and clindamycin were 11, 8, 7, and 29%, respectively. Among the individual species of the B. fragilis group, the highest resistance rates were noted among the following organism-drug combinations: for clindamycin, Bacteroides distasonis and Bacteroides ovatus; for cefoxitin, Bacteroides thetaiotaomicron, B. distasonis, and Bacteroides uniformis; for ampicillin-sulbactam, B. distasonis, B. ovatus, and B. uniformis; and for trovafloxacin, Bacteroides vulgatus. For the carbapenens, imipenem resistance was noted among B. fragilis and meropenem resistance was seen among B. fragilis, B. vulgatus, and B. uniformis. With few exceptions all antimicrobial agents were highly active against isolates of Prevotella, Fusobacterium, Porphyromonas, and Peptostreptococcus. These data further establish and confirm that clinically important anaerobes can vary widely in their antimicrobial susceptibilities. Fortunately most antimicrobial agents were active against the test isolates. However, concern is warranted for what appears to be a significant increases in resistance to ampicillin-sulbactam and clindamycin.     

Comparative in vitro activities of pristinamycin, its components, and other antimicrobial agents against anaerobic bacteria.

Using an agar dilution technique, we compared the activities of pristinamycin and its components PIA and PIIA with those of penicillin G, cefoxitin, chloramphenicol, metronidazole, and clindamycin against 200 strains of anaerobic bacteria isolated from suppurative lesions. The antimicrobial activity of pristinamycin was similar to that of chloramphenicol. On the basis of these results and because of its antistaphylococcal and antistreptococcal activities and its absence of toxicity, pristinamycin might be a valuable therapeutic agent for treating mixed aerobic-anaerobic cutaneous infections.     

Synergism between penicillin, clindamycin, or metronidazole and gentamicin against species of the Bacteroides melaninogenicus and Bacteroides fragilis groups

Clinical isolates of the Bacteroides melaninogenicus and Bacteroides fragilis groups were tested for in vitro and in vivo susceptibility to penicillin, clindamycin, and metronidazole, used singly or in combination with gentamicin. The in vitro tests consisted of determinations of minimal inhibitory concentrations (MICs) carried out with or without constant amounts of gentamicin. When used alone, gentamicin had negligible effects on the bacteria but significantly reduced the MICs of penicillin, clindamycin, and metronidazole against 11, 10, and 3, of the 15 strains of the B. melaninogenicus group, respectively. The 15 strains of the B. fragilis group were all beta-lactamase producers and were highly resistant to penicillin or the combination of penicillin and gentamicin. However, gentamicin reduced the MICs of clindamycin and metronidazole against 1 and 7 strains of this group, respectively. The in vivo tests were carried out in mice and consisted of measurements of the effects of the antimicrobial agents on the sizes and bacterial content of abscesses induced by subcutaneous injection of bacterial suspensions. The results of the in vivo tests were generally consistent with those obtained in vitro with strains of the B. melaninogenicus group. Synergism between gentamicin and penicillin, clindamycin, or metronidazole was shown in 13, 10, and 3 strains of this group, respectively. In vivo synergism was not clearly demonstrated with the strains of the B. fragilis group, possibly because clindamycin and metronidazole used alone were highly efficacious. We suggest that the synergistic effect of gentamicin is due to its increased transport into the bacterial cell in the presence of penicillin and, possibly, other antimicrobial agents. The newly recognized in vitro and in vivo synergism between penicillin and other antimicrobial agents and an aminoglycoside in B. melaninogenicus may have clinical implications that deserve to be investigated.