Nitazoxanide, a potential drug for eradication of Helicobacter pylori with no cross-resistance to metronidazole

Nitazoxanide, a thiazolide compound, and its desacetyl derivative, tizoxanide, have antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. Because the treatment of Helicobacter pylori infection may be jeopardized by metronidazole resistance, nitazoxanide and tizoxanide were tested in vitro against these bacteria. The MICs of these two compounds were determined by agar dilution and were compared to those of metronidazole. Exposure to subinhibitory concentrations of nitazoxanide was also carried out by the method of Szybalski (W. Szybalski and V. Bryson, J. Bacteriol. 64:489-499, 1952). The MICs of nitazoxanide and tizoxanide for 103 strains ranged from 0.25 to 8 microg/ml, with the MIC at which 50% of strains are inhibited (MIC50) being 1 microg/ml and the MIC90 being 4 microg/ml, and no resistant strain was detected, whereas strains resistant to metronidazole were detected. When 10 strains were successively subcultured on medium containing nitazoxanide, no significant change in the MICs of this compound was observed. A pilot study of nitazoxanide for the treatment of H. pylori infection was carried out with 86 patients in association with 20 mg of omeprazole. An eradication rate of 83% (95% confidence interval, 64% to 94%) was obtained in a per-protocol analysis in the group receiving 1 g of nitazoxanide orally twice daily, and a few side effects were observed. The failures could not be explained by the selection of resistant strains since the MICs of nitazoxanide were similar for six pairs of isolates (proven to be the same strain by random amplified polymorphic DNA analysis in four cases) cultured before and after the treatment failure. Nitazoxanide exhibits good antimicrobial activity against H. pylori without the problem of acquired resistance which is encountered with metronidazole and has been demonstrated to have a satisfactory effect in a dose-ranging pilot study. It is therefore a good candidate to be included in treatment regimens aimed at the eradication of H. pylori.     

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.     

Antimicrobial activity of the new carbapenem biapenem compared to imipenem, meropenem and other broad-spectrum beta-lactam drugs

The in vitro activity of biapenem was compared to that of imipenem, meropenem and other broad-spectrum beta-lactams. A total of 716 isolates from recent cases of clinical septicemia and an additional 137 stock strains possessing known beta-lactamases or other well-characterized resistance mechanisms were tested. The minimal concentrations inhibiting 90% of strains (MIC90) of Enterobacteriaceae species were for biapenem 0.03 to 1 mg/l and for imipenem 0.25 to 2 mg/l. No member of the Enterobacteriaceae was found to be resistant to biapenem. Biapenem and meropenem were the most active drugs against Pseudomonas aeruginosa, with an MIC90 of 1 mg/l. Biapenem was more active than ceftazidime against most gram-negative and gram-positive bacteria tested. Biapenem was as potent as imipenem against anaerobic bacteria (including Bacteroides fragilis), with an MIC90 of 0.25 mg/l. High MICs of biapenem were demonstrated for Xanthomonas maltophilia, oxacillin-resistant Staphylococcus spp. and Enterococcus spp. These species have demonstrated resistance to other carbapenems and to most of the newer cephalosporins. The results of this study, coupled with previously documented favorable qualities of biapenem, endorse further investigation of this broad-spectrum antibacterial agent for clinical use.     

Susceptibility of anaerobic bacteria to 23 antimicrobial agents

The antimicrobial susceptibility of 492 anaerobic bacteria, the majority of which were recent clinical isolates, was determined by the agar dilution technique. Penicillin G was active against most of the strains tested at 32 U or less/ml, but only 72% of Bacteroides fragilis strains were susceptible at this level and 9% required 256 U or more/ml. Ampicillin was effective against most of the strains except B. fragilis at 16 mug or less/ml. Amoxicillin was active against only 31% of B. fragilis, 76% of other Bacteroides species, and 67% of Fusobacterium species at 8 mug/ml. Two new penicillins, mezlocillin and azlocillin, were similar to ampicillin in their activity. Carbenicillin and ticarcillin inhibited all but a few strains at 128 mug or less/ml. BLP 1654 was somewhat more active than penicillin G against B. fragilis but had similar activity against other anaerobes. Cephalothin was inactive against B. fragilis, and only 65% of other Bacteroides species were inhibited by 32 mug or less/ml. It was effective against all other anaerobes at that level. Cefamandole showed somewhat greater activity than cephalothin against B. fragilis but generally less activity against gram-positive organisms. Cefazaflur (SKF 59962) was comparable to cephalothin against B. fragilis. Cefoxitin was distinctly more active than cephalothin against B. fragilis. These latter two agents were less active than cephalothin against the gram-positive anaerobes. Chloramphenicol remains active against anaerobic bacteria at 16 mug or less/ml, with rare exceptions. Thiamphenicol was similar to chloramphenicol in its activity. Clindamycin was very active against most of the anaerobes at 8 mug or less/ml. Erythromycin and josamycin were also tested, with josamycin showing greater activity against B. fragilis than either erythromycin or clindamycin. A new oligosaccharide, everninomicin B, was less active than clindamycin against B. fragilis but more active against clostridia and some of the other strains tested. Most of the groups of bacteria tested demonstrated a trend toward resistance to tetracycline. Doxycycline and minocycline were somewhat more active than was tetracycline. Metronidazole was active against the majority of the anaerobes tested; resistance ws demonstrated by some of the gram-positive cocci and gram-positive, non-sporeforming bacilli.     

Comparative in-vitro and in-vivo activity of AM-1155 against anaerobic bacteria

The in-vitro activity of AM-1155, a 6-fluoro-8-methoxy quinolone, was compared with those of temafloxacin, sparfloxacin, tosufloxacin, ciprofloxacin, ofloxacin and cefmetazole, a cephamycin, against a variety of anaerobic bacteria. Although AM-1155 demonstrated only modest activity against the Bacteroides fragilis group and Prevotella bivia (MIC90s > or =3.13 mg/mL), 76% of the B. fragilis strains tested were inhibited at AM-1155 concentrations of 0.78 mg/L. AM-1155 was highly active against Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium spp., Clostridium perfringens and Mobiluncus spp. (MIC90s < or =0.39 mg/L). An in-vivo study using a mixed infection with AM-1155- and tosufloxacin-susceptible B. fragilis and Escherichia coli strains in rat granuloma pouch was performed. AM-1155 was effective against both organisms whereas tosufloxacin was effective only against E. coli. These results correlated well to the higher pouch levels of AM-1155 than those of tosufloxacin. Clostridium difficile overgrowth was found in the caecum of mice treated with ampicillin both 1 and 7 days after 5 days dosing, but not in AM-1155-treated mice. These results suggest that the clinical efficacy of AM-1155 against infections involving most anaerobic bacteria except for the B. fragilis group and P. bivia should be evaluated further.     

Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and importance

The agar dilution MIC method was used to test the activity of cefminox, a beta-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. Other beta-lactams were less active, with respective MIC50s and MIC90s of 2.0 and 64.0 microg/ml for cefoxitin, 2.0 and 128.0 microg/ml for cefotetan, 2.0 and 64.0 microg/ml for moxalactam, 4.0 and > 128.0 microg/ml for ceftizoxime, 16.0 and > 128.0 microg/ml for cefotiam, 8.0 and >128.0 microg/ml for cefamandole, and 4.0 and 128.0 microg/ml for cefoperazone. The clindamycin MIC50 and MIC90 were 0.5 and 8.0 microg/ml, respectively, and the metronidazole MIC50 and MIC90 were 1.0 and 4.0 microg/ml, respectively. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4x the MIC and cefoperazone at 8x the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2 x the MIC produced the most rapid effect, with 90% killing of all strains.     

In vitro activity of Bay 12-8039, a new 8-methoxyquinolone, compared to the activities of 11 other oral antimicrobial agents against 390 aerobic and anaerobic bacteria isolated from human and animal bite wound skin and soft tissue infections in humans

The in vitro activity of Bay 12-8039, a new oral 8-methoxyquinolone, was compared to the activities of 11 other oral antimicrobial agents (ciprofloxacin, levofloxacin, ofloxacin, sparfloxacin, azithromycin, clarithromycin, amoxicillin clavulanate, penicillin, cefuroxime, cefpodoxime, and doxycycline) against 250 aerobic and 140 anaerobic bacteria recently isolated from animal and human bite wound infections. Bay 12-8039 was active against all aerobic isolates, both gram-positive and gram-negative isolates, at < or = 1.0 microg/ml (MICs at which 90% of isolates are inhibited [MIC90s < or = 0.25 microg/ml) and was active against most anaerobes at < or = 0.5 microg/ml; the exceptions were Fusobacterium nucleatum and other Fusobacterium species (MIC90s, > or = 4.0 microg/ml) and one strain of Prevotella loeschii (MICs, 2.0 microg/ml). In comparison, the other quinolones tested had similar in vitro activities against the aerobic strains but were less active against the anaerobes, including peptostreptococci, Porphyromonas species, and Prevotella species. The fusobacteria were relatively resistant to all the antimicrobial agents tested except penicillin G (one penicillinase-producing strain of F. nucleatum was found) and amoxicillin clavulanate.     

In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem

CS-834 is a novel oral carbapenem antibiotic. This compound is an ester-type prodrug of the active metabolite R-95867. The antibacterial activity of R-95867 was tested against 1,323 clinical isolates of 35 species and was compared with those of oral cephems, i.e., cefteram, cefpodoxime, cefdinir, and cefditoren, and that of a parenteral carbapenem, imipenem. R-95867 exhibited a broad spectrum of activity covering both gram-positive and -negative aerobes and anaerobes. Its activity was superior to those of the other compounds tested against most of the bacterial species tested. R-95867 showed potent antibacterial activity against clinically significant pathogens: methicillin-susceptible Staphylococcus aureus including ofloxacin-resistant strains, Streptococcus pneumoniae including penicillin-resistant strains, Clostridium perfringens, Neisseria spp., Moraxella catarrhalis, most members of the family Enterobacteriaceae, and Haemophilus influenzae (MIC at which 90% of strains are inhibited, < or =0.006 to 0.78 microg/ml). R-95867 was quite stable to hydrolysis by most of the beta-lactamases tested except the metallo-beta-lactamases from Stenotrophomonas maltophilia and Bacteroides fragilis. R-95867 showed potent bactericidal activity against S. aureus and Escherichia coli. Penicillin-binding proteins 1 and 4 of S. aureus and 1Bs, 2, 3, and 4 of E. coli had high affinities for R-95867. The in vivo efficacy of CS-834 was evaluated in murine systemic infections caused by 16 strains of gram-positive and -negative pathogens. The efficacy of CS-834 was in many cases superior to those of cefteram pivoxil, cefpodoxime proxetil, cefdinir, and cefditoren pivoxil, especially against infections caused by S. aureus, penicillin-resistant S. pneumoniae, E. coli, Citrobacter freundii, and Proteus vulgaris. Among the drugs tested, CS-834 showed the highest efficacy against experimental pneumonia in mice caused by penicillin-resistant S. pneumoniae.     

Susceptibilities of penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, compared with susceptibilities to 17 other agents

Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution, and results were compared with those of erythromycin, azithromycin, clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was very active against all strains tested, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.03 microg/ml for erythromycin-susceptible strains (MICs, < or =0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant strains (MICs, > or =1.0 microg/ml). All other macrolides yielded MIC90s of 0.03 to 0.25 and >64.0 microg/ml for erythromycin-susceptible and -resistant strains, respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant strains were < or =0.125 microg/ml. The MICs of pristinamycin for all strains were < or =1.0 microg/ml. The MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.5 microg/ml, respectively, and were unaffected by penicillin or erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at < or =1.0 microg/ml. The MICs of cefuroxime and cefotaxime rose with those of penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher in penicillin- and erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all macrolides tested against 11 erythromycin-susceptible and -resistant strains, with uniform bactericidal activity (99.9% killing) after 24 h at two times the MIC and 99% killing of all strains at two times the MIC after 12 h for all strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed significant activity, relative to the MIC, against erythromycin-susceptible strains only.     

In vivo activities of amoxicillin and amoxicillin-clavulanate against Streptococcus pneumoniae: application to breakpoint determinations

The in vivo activities of amoxicillin and amoxicillin-clavulanate against 17 strains of Streptococcus pneumoniae with penicillin MICs of 0.12-8.0 mg/liter were assessed in a cyclophosphamide-induced neutropenic murine thigh infection model. Renal impairment was produced by administration of uranyl nitrate to prolong the amoxicillin half-life in the mice from 21 to 65 min, simulating human pharmacokinetics. Two hours after thigh infection with 10(5) to 10(6) CFU, groups of mice were treated with 7 mg of amoxicillin per kg of body weight alone or combined with clavulanate (ratio, 4:1) every 8 h for 1 and 4 days. There was an excellent correlation between the MIC of amoxicillin (0.03 to 5.6 mg/liter) and (i) the change in log10 CFU/thigh at 24 h and (ii) survival after 4 days of therapy. Organisms for which MICs were 2 mg/liter or less were killed at 1.4 to 4.2 and 1.6 to 4.1 log10 CFU/thigh at 24 h by amoxicillin and amoxicillin-clavulanate, respectively. The four strains for which MICs were >4 mg/liter grew 0.2 to 2.6 and 0.6 to 2. 3 logs at 24 h despite therapy with amoxicillin and amoxicillin-clavulanate, respectively. Infection was uniformly fatal by 72 h in untreated mice. Amoxicillin therapy resulted in no mortality with organisms for which MICs were 1 mg/liter or less, 20 to 40% mortality with organisms for which MICs were 2 mg/liter, and 80 to 100% mortality with organisms for which MICs were 4.0-5.6 mg/liter. Lower and higher doses (0.5, 2, and 20 mg/kg) of amoxicillin were studied against organisms for which MICs were near the breakpoint. These studies demonstrate that a reduction of 1 log10 or greater in CFU/thigh at 24 h is consistently observed when amoxicillin levels exceed the MIC for 25 to 30% of the dosing interval. These studies would support amoxicillin (and amoxicillin-clavulanate) MIC breakpoints of 1 mg/liter for susceptible, 2 mg/liter for intermediate, and 4 mg/liter for resistant strains of S. pneumoniae.     

Comparative in vitro activities of DU-6859a, levofloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against 387 aerobic and anaerobic bite wound isolates

The activities of DU-6859a, levofloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against bite wound isolates were determined by the agar dilution method. DU-6859a was the most active compound (MICs, < or = 0.125 microg/ml) against all Pasteurella species, Staphylococcus aureus, and streptococci; anaerobes were susceptible to < or = 0.5 microg/ml, except fusobacteria, which were susceptible to < or = 2 microg/ml. Against aerobes, levofloxacin was more active than ofloxacin (MIC at which 90% of isolates are inhibited [MIC90], < or = 1.0 microg/ml for both) and sparfloxacin and ciprofloxacin were also active (MIC90s, < or = 0.25 and < 1 microg/ml, respectively).     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1995). I. Susceptibility distribution]

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 704 bacterial strains isolated from patients with urinary tract infections (UTIs) in 11 hospitals during the period of June 1995 to May 1996. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.8% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.2% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) and imipenem (IPM) showed the highest activities against E. faecalis isolated from patients with UTIs. The MIC90S of them were 1 microgram/ml. Vancomycin (VCM) and piperacillin (PIPC) were also active with the MIC90S of 2 micrograms/ml and 4 micrograms/ml, respectively. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM showed the highest activities against S. aureus isolated from patients with UTIs. Its MIC90 was 1 microgram/ml against both S. aureus and MRSA. Arbekacin (ABK) was also active with the MIC90 of 2 micrograms/ml. The other except minocycline (MINO) had very low activities with the MIC90S of 64 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and MINO showed the strongest activities against S. epidermidis isolated from patients with UTIs. The MIC90S of them were 0.25 microgram/ml. VCM was also active with the MIC90 of 1 microgram/ml. The MIC90S of cephems ranged from 2 micrograms/ml to 16 micrograms/ml in 1994, but they ranged from 8 micrograms/ml to 128 micrograms/ml in 1995. These results indicated that some resistances existed among S. epidermidis to cephems. 4. Streptococcus agalactiae All drugs except gentamicin (GM) were active against S. agalactiae. ABPC, cefmenoxime (CMX), IPM, erythromycin (EM), clindamycin (CLDM) and clarithromycin (CAM) showed the highest activities. The MICs for all strains were lower than 0.125 microgram/ml. The MIC90S of the others were 2 micrograms/ml or below. 5. Citrobacter freundii IPM showed the highest activity against C. freundii isolated from patients UTIs. Its MIC90 was 1 microgram/ml. GM was also active with the MIC90 of 2 micrograms/ml. Cefpirome (CPR), cefozopran (CZOP) and amikacin (AMK) were also active with the MIC90S of 4 micrograms/ml. Penicillins and cephems except CMX, CPR and CZOP showed low activities with MIC90S of 256 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. MINO and tosufloxacin (TFLX) were also active with the MIC90S of 8 micrograms/ml. Penicillins and cephems except CPR and CZOP showed lower activities with the MIC90S of 256 micrograms/ml or above. 7. Escherichia coli. Most of the antimicrobial agents were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MICs for all strains were equal to or lower than 0.5 microgram/ml. CMX and TFLX were also active with the MIC90S of 0.125 microgram/ml or below. Penicillins were slightly active with MIC90S of 128 micrograms/ml or above. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with MIC90S of 2 micrograms/ml or below. Carumonam (CRMN) had the strongest activity against K. pneumoniae, the MICs for all strains were equal to or lower than 0.125 microgram/ml. Comparing with the result of 1994, the sensitivities of K. pneumoniae against all drugs had obviously changed into a better state. For example, the MIC90S of cephems ranged from 0.25 microgram/ml to 16 micrograms/ml in 1994, but they were all lower than 2 micrograms/ml in 1995. 9. Proteus mirabilis P. mirabilis was susceptible to a majority of drugs. CMX, ceftazidime (CAZ), cefixime (CFIX), and CRMN showed the highest activities against P. mirabilis isolated from patients with UTIs. MICs of CRMN for all     

Methods of measuring susceptibility of anaerobic bacteria to trovafloxacin, including quality control parameters

Three methods approved by the National Committee for Clinical Laboratory Standards for testing the susceptibility of anaerobic bacteria were used to evaluate the fluoroquinolone, trovafloxacin. The methods gave essentially comparable results with 126 anaerobes and with three quality control strains. A collaborative study defined the quality control range for trovafloxacin MICs. Trovafloxacin had good in vitro activity against the more common anaerobes (MIC 90 < = or 2.0 micrograms/ml).     

In vitro activity of RP59500, an injectable streptogramin antibiotic, against vancomycin-resistant gram-positive organisms

The in vitro activity of RP59500, a streptogramin antibiotic, against 146 clinical isolates of vancomycin-resistant gram-positive bacteria was examined. Five strains of the species Enterococcus casseliflavus and Enterococcus gallinarum, for which the MIC of vancomycin was 8 micrograms/ml, were also studied. Twenty-eight vancomycin-susceptible strains of Enterococcus faecalis and Enterococcus faecium were included for comparison. The drug was highly active against Leuconostoc spp., Lactobacillus spp., and Pediococcus spp. (MICs, < or = 2 micrograms/ml). RP59500 was more active against vancomycin-susceptible strains of E. faecium than E. faecalis (MICs for 90% of the strains [MIC90s], 1.0 versus 32 micrograms/ml). Vancomycin-resistant strains of E. faecalis were as resistant to RP59500 as vancomycin-susceptible strains (MIC90, 32 micrograms/ml), but some vancomycin-resistant E. faecium strains were relatively more resistant to the new agent (MIC90, 16; MIC range, 0.5 to 32 micrograms/ml) than were vancomycin-susceptible organisms of this species.     

In vitro activity of biapenem against beta-lactamase producing Enterobacteriaceae

The activity of biapenem was compared with that of imipenem and cefotaxime against 108 strains of beta-lactamase producing Enterobacteriaceae. Biapenem and imipenem were very active, inhibiting 90% of the strains at a concentration of 0.5 microgram/ml. Both carbapenems were very active against plasmidic beta-lactamase producers, with MIC90s below 1 microgram/ml. However, the MIC90 of biapenem for cephalosporinase producers was 1 microgram/ml. Against strains producing extended-spectrum beta-lactamases, biapenem exhibited better activity against TEM-type producers (MIC90 0.25 microgram/ml) than against SHV-type producers (MIC90 0.5 microgram/ml). Overall, the in vitro antibacterial activity of biapenem is similar to that of imipenem.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1996). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 680 bacterial strains isolated from patients with urinary tract infections (UTIs) in 10 hospitals during the period of June 1996 to May 1997. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.4% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 69.6% and most of them were Escherichia coli. Susceptabilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90S of 2 micrograms/ml. The others had low activities with the MIC90S of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA Arbekacin (ABK) and VCM showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90S of them were 1 or 2 micrograms/ml. The others except minocycline (MINO) had low activities with the MIC90S of 32 micrograms/ml or above. 3. Staphylococcus epidermidis ABK and VCM showed the strongest activities against S. epidermis isolated from patients with UTIs. The MICs for all strains were equal to or lower than 2 micrograms/ml. Cefazolin (CEZ), cefotiam (CTM) and cefozopran (CZOP) were also active with the MIC90S of 4 micrograms/ml. Compared with antimicrobial activities of cephems is 1995, the MIC90S of them had changed into a better state. They ranged from 4 micrograms/ml 16 micrograms/ml in 1996. 4. Streptococcus agalactiae All drugs except MINO were active against S. agalactiae. ABPC, CZOP, IPM, and clarithromycin (CAM) showed the highest activities. The MICs for all strains were equal to or lower than 0.125 micromilligrams. Tosufloxacin (TFLX) and VCM were also active with the MIC90S of 0.5 micromilligrams. 5. Citrobacter freundii Gentamicin (GM) showed the highest activity against C. freundii isolated from patients with UTIs. Its MIC90 was 0.5 micrograms/ml. IPM and amikacin (AMK) were also active with the MIC90S of 1 microgram/ml and 2 micrograms/ml, respectively. Cefpirome (CPR) and CZOP were also active with the MIC90S of 8 micrograms/ml. The MIC90S of the others were 16 micrograms/ml or above. 6. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 0.5 microgram/ml. The MIC90S of ciprofloxacin (CPFX) and TFLX were 1 microgram/ml, the MIC90 of AMK was 2 micrograms/ml, the MIC90S of CZOP, GM and ofloxacin (OFLX) were 4 micrograms/ml. The MIC50S of cephems except CEZ, cefmetazole (CMZ) and cefaclor (CCL) had changed into a better state in 1996, compared with those in 1995. 7. Escherichia coli All drugs except penicillins and MINO were active against E. coli. Particularly CPR, CZOP and IPM showed the highest activities against E. coli. The MIC90S of them were 0.125 microgram/ml or below. Among E. coli strains, those with low susceptibilities to cephems except CEZ, cefoperazone (CPZ), latamoxef (LMOX) and CCL have increased in 1996, compared with those in 1995. 8. Klebsiella pneumoniae K. pneumoniae was susceptible to all drugs except penicillins, with the MIC90S of 2 micrograms/ml or below. CPR had the strongest activity, the MICs for all strains were equal to or lower than 0.25 microgram/ml. Flomoxef (FMOX), cefixime (CFIX), CZOP and carumonam (CRMN) were also active with the MIC90S of 0.125 microgram/ml or below. 9. Pseudomonas aeruginosa All drugs except quinolones were not so active against P. aeruginosa with the MIC90S were 32 micrograms/ml or above. Quinolones were more active in 1996 than 1995. The MIC90S of them were between 4 micrograms/ml and 8 micrograms/ml, and the MIC50S of them were between 1 microgram/ml and 2 micrograms/ml. 10. Serratia marcescens GM showed the highest activity against S. marcescens. Its MIC90 was 1 micro     

Intraocular pressure in snorkling and diving (author''s transl)]

The in vitro susceptibility of 145 anaerobic clinical isolates and 96 gram-positive aerobic clinical isolates to josamycin, a new macrolide antibiotic, was studied using the agar dilution technique. Ninety-five of the aerobes were susceptible to 1.56 mug or less of josamycin per ml. The median minimal inhibitory concentration of these organisms was 相似文献   

In vitro antimicrobial activity of fluoroquinolones against clinical isolates obtained in 1989 and 1990

The in vitro activity of nine fluoroquinolones, enoxacin, norfloxacin, ofloxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin, fleroxacin and levofloxacin, and two earlier quinolones, nalidixic acid and pipemidic acid, against 1,346 bacterial strains isolated clinically between 1989 and 1990, was evaluated by agar dilution method. The bacteria studied were Staphylococcus aureus (including methicillin-susceptible and -resistant strains), Staphylococcus epidermidis, Enterococcus species (including high-level gentamicin-resistant strains), Escherichia coli, Salmonella species, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Citrobacter spp., Pseudomonas aeruginosa, Pseudomonas cepacia, Acinetobacter baumannii, and Bacteroides fragilis. In contrast to the moderate to poor activity of two earlier quinolones, the fluoroquinolones acted well against most Enterobacteriaceae and A. baumannii. The minimum inhibitory concentrations for 90% of the drug strains (MIC90s) were < 1 microgram/mL against most tested species. Ciprofloxacin, tosufloxacin, sparfloxacin, and levofloxacin were more effective against multi-drug-resistant nosocomial pathogens. All fluoroquinolones assayed were very active against methicillin-susceptible S. aureus, with MIC90s < or = 1 microgram/mL. For methicillin-resistant strains, on the other hand, the MIC90s were > or = 4 micrograms/mL. There was no significant difference in fluoroquinolone susceptibility between methicillin-susceptible and -resistant S. epidermidis. Sparfloxacin, tosufloxacin, ciprofloxacin and levofloxacin were more active against enterococci. Most fluoroquinolones were relatively inactive against B. fragilis, with the exception of tosufloxacin, sparfloxacin and levofloxacin. The MIC90s of most quinolones assayed against K. pneumoniae, Citrobacter spp., E. cloacae, S. aureus and S. epidermidis were at least four-fold higher in our study. Therefore, it is important for physicians to use fluoroquinolones carefully so as to prevent or delay the emergence of resistant strains.     

Antimicrobial activity of RU-66647, a new ketolide

A new macrolide subclass called ketolides, possess a mode of action similar to the macrolide-lincosamide-streptogramin (MLS) compounds. Utilizing reference in vitro tests, the in vitro activity of RU-66647 (a ketolide) was compared to other MLS compounds against 376 Gram-positive organisms and over 400 representative strains of Gram-negative bacilli. The ketolide's spectrum was most similar to clindamycin and an earlier drug in the series (RU-64004 or RU-004) against staphylococci and streptococci. However, RU-66647 was more active than erythromycin and azithromycin against oxacillin-resistant Staphylococcus spp. and vancomycin-resistant enterococci. Ketolide activity was more potent than other MLS drugs against vancomycin-susceptible enterococci (MIC90, 0.25-4 micrograms/ml) and all streptococci (MICs, < or = 0.25 microgram/ml). Erythromycin-resistant (constitutive) strains were generally inhibited by < or = 2 micrograms RU-66647/ml (staphylococci, 31 to 36%; streptococci, 100%; enterococci, 72%). RU-66647 was active against Haemophilus influenzae (MIC90, 2 micrograms/ml), Moraxella catarrhalis (MIC90, 0.12 microgram/ml), and pathogenic Neisseria spp. (MIC90 0.5 microgram/ml). The ketolide failed to inhibit Enterobacteriaceae, nonfermentative Gram-negative bacilli, and Bacteriodes fragilis group strains. RU-66647 was observed to be a promising new compound directed toward some organisms resistant to other MLS-class drugs.     

Autoimmune thyroid disease and insulin-dependent diabetes mellitus during pregnancy and post partum

The in-vitro antimicrobial activity of HSR-903, a new fluoroquinolone, was tested against 51 clinical Neisseria gonorrhoeae isolates in comparison with ciprofloxacin, levofloxacin and sparfloxacin. The MICs of HSR-903 for 11 isolates with alterations in both GyrA and ParC, for 19 isolates with alterations only in GyrA and for 21 isolates without alterations in either GyrA or ParC ranged from 0.03 mg/L to 1.0 mg/L (MIC90 = 0.25 mg/L), from 0.03 mg/L to 0.5 mg/L (MIC90 = 0.125 mg/L) and from < or = 0.001 mg/L to 0.008 mg/L (MIC90 = 0.004 mg/L), respectively. Levofloxacin and ciprofloxacin were the least active of the four quinolones tested, particularly against the mutant strains. Sparfloxacin was more active, but HSR-903 exhibited the most potent in-vitro activity against the clinical N. gonorrhoeae isolates, including those harbouring quinolone-resistance-associated alterations in GyrA and ParC.