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.     

Susceptibilities of 97 strains of Xanthomonas maltophilia to antibiotics and the effect of beta-lactamase inhibitors

An agar dilution technique and the 'E' test were used to compare the antimicrobial activities of ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, meropenem, biapenem, imipenem, levofloxacin, ofloxacin, ciprofloxacin, ceftazidime and cefepime against 97 clinical isolates of Xanthomonas maltophilia. Intermediate susceptibility breakpoints for members of the family Enterobacteriaceae were used. Results were analysed as minimum inhibitory concentrations for 50 and 90% of the strains tested and as percentages of strains susceptible at the breakpoint. Good correlation between the two techniques was observed, with ticarcillin-clavulanate clearly the most active agent by both methods with 64 to 66% followed by levofloxacin with 63 to 65% of the strains being susceptible. Biapenem and imipenem showed weak activity with none of the strains being susceptible. Ceftazidime had better activity than cefepime when they were compared by the two methods. There was no significant difference in the results between the two susceptibility techniques used.     

Antimicrobial activity of carbapenem antibiotics against gram-negative bacilli

Antimicrobial activities of meropenem (MEPM), imipenem (IPM), panipenem (PAPM), ceftazidime (CAZ), cefozopran (CZOP), aztreonam (AZT), norfloxacin (NFLX) and tetracycline (TC) against clinically isolated Gram-negative bacilli [271 strains of Enterobacteriaceae and 242 strains non-fermentative Gram-negative bacteria (NFB)] were investigated. Among carbapenem antibiotics, MEPM showed the lowest MIC90, which activity was about four-hold higher than those of IPM and PAPM. The activity of IPM was equal or slightly superior to that of PAPM. Resistance to IPM (> 16 micrograms/ml) was observed in 3 strains of Enterobacteriaceae (1.1%) and 14 strains of NFB (5.8%). It is conceivable that these strains produce metallo-beta-lactamase. Referring to the correlation among MICs of MEPM, IPM and PAPM, 3 strains in 3 species of Enterobacteriaceae showed cross resistance to carbapenems; while 14 strains of NFB showed cross resistance to MEPM and IPM, 15 strains to MEPM and PAPM, and 29 strains to IPM and PAPM, and all of these strains were Pseudomonas aeruginosa. Fifteen of 29 strains of IPM-resistant and 77 of 92 strains of PAPM-resistant P. aeruginosa were susceptible to MEPM. Thirty-three strains (12%) of the Enterobacteriaceae were resistant to CAZ and AZT (> or = 32 micrograms/ml) and these were considered as ESBL-producing strains.     

Bactericide activity of sulbactam before bacteria belonging to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex

BACKGROUND: To evaluate the bactericidal activity of colistin, imipenem and sulbactam against 24 Acinetobacter calcoaceticus-Acinetobacter baumannii complex isolations. METHODS: Bactericidal activity was estimated by using killing curves method. The concentrations employed were: colistin 4 mg/l, imipenem 8 mg/l and sulbactam 8 and 32 mg/l. RESULTS: Colistin was bactericidal in 24 isolations after 6 hours of incubation. When we used 8 mg/l of imipenem we detected bactericidal activity at the susceptible strains (MIC < or = 4 mg/l). We found bactericidal effect in 15 of 18 strains susceptible to sulbactam when we used 8 mg/l in killing curves after 24 hours of incubation. Using 32 mg/l we detected the same effect in 18 strains with MIC < or = 8 mg/l. CONCLUSIONS: Considering the high incidence of resistance in Acinetobacter spp. to several antibiotics including imipenem, we consider that sulbactam could be an excellent therapeutic alternative because it presents bactericidal activity in susceptible 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.     

N-formimidoyl-thienamycin: in vitro activity in bacteria with resistance to beta-lactam antibiotics or gentamicin

The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of N-formimidoyl-thienamycin were determined for 25 strains each of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa which were resistant to gentamicin and/or acylureido penicillins or cefotaxime, cefoperazone or moxalactam, and for 38 strains of the group D streptococci. The drug was very active against the most frequently encountered gram-negative resistant causative organisms of nosocomial infections. The MIC ranged from 0.25-1 mg/l for multiresistant Enterobacteriaceae, and from 0.5-4 mg/l for multiresistant P. aeruginosa. The group D streptococci (enterococci) showed a low MIC (median: 0.75 mg/l); the median of the MBC was greater than 64 mg/l, however.     

Prevention of acute allograft rejection by antibody targeting of TIRC7, a novel T cell membrane protein

The in vitro activity of trovafloxacin, a new fluoroquinolone, was compared with that of ciprofloxacin, ofloxacin, fleroxacin, ceftazidime, piperacillin/tazobactam, and meropenem against 613 consecutively recovered blood isolates from recently hospitalized patients. Susceptibility testing was performed by agar dilution according to NCCLS guidelines. Test strains included Acinetobacter species (n = 26), Escherichia coli (n = 137), Enterobacter species (n = 27), Klebsiella species (n = 42), Proteus species (n = 16), Pseudomonas aeruginosa (n = 28), Serratia marcescens (n = 13), Stenotrophomonas maltophilia (n = 7), enterococci (n = 54), coagulase-negative staphylococci (n = 38), Staphylococcus aureus (n = 137), Streptococcus pneumoniae (n = 27), beta-haemolytic streptococci (n = 13), and viridans group streptococci (n = 48). The overall respective MICs at which 50% and 90% of isolates were inhibited (MIC50s and MIC90s) were as follows: trovafloxacin, 0.06 and 1 mg/l; ciprofloxacin, 0.25 and 4 mg/l; ofloxacin, 0.5 and 4 mg/l; fleroxacin, 0.5 and 16 mg/l; ceftazidime, 2 and 128 mg/l; piperacillin/tazobactam, 2 and 8 mg/l; meropenem, 0.06 and 4 mg/l. For the quinolones, the rank order of activity against gram-negative microorganisms was ciprofloxacin > trovafloxacin > ofloxacin = fleroxacin, against gram-positive organisms, trovafloxacin > ciprofloxacin = ofloxacin > fleroxacin. Data obtained showed the similar activity of trovafloxacin and ciprofloxacin against gram-negative pathogens and the superior activity of trovafloxacin against gram-positive bacteria thus making it a potential candidate for the empiric treatment of patients with suspected bacteremia and sepsis.     

Comparative in vitro killing activities of meropenem, imipenem, ceftriaxone, and ceftriaxone plus vancomycin at clinically achievable cerebrospinal fluid concentrations against penicillin-resistant Streptococcus pneumoniae isolates from children with meningitis

The activities of meropenem, imipenem, ceftriaxone, and vancomycin were evaluated against 80 penicillin-susceptible and -resistant Streptococcus pneumoniae strains. Meropenem, imipenem, ceftriaxone, and vancomycin MICs at which 90% of the isolates are inhibited were 0.5, 0.25, 1, and 0.25 microg/ml, respectively. Against penicillin-resistant strains, the best killing activity at cerebrospinal fluid concentrations was obtained with imipenem and ceftriaxone-vancomycin. However, while the killing activity of imipenem was significantly greater than that of meropenem, no significant difference was observed between the activities of meropenem and ceftriaxone-vancomycin.     

Inter-observer reliability in the interpretation of coronary angiograms

The in vitro activity of the fluoroquinolone trovafloxacin (CP-99,219) against 257 blood isolates of Streptococcus pneumoniae obtained from Swedish hospitals was compared with those of commonly prescribed oral antibiotics and also with those of ciprofloxacin and ofloxacin against a collection of strains resistant (n = 6) or intermediately resistant (n = 22) to penicillin (Pc-R). The MICs of trovafloxacin for Pc-R strains of pneumococci ranged from 0.032 to 0.25 mg/l. No difference was seen between the clinical isolates and the Pc-R strains (MIC50 = 0.064 mg/l and MIC90 = 0.125 mg/l for both collections). For the Pc-R strains, the MIC50 and MIC90 values of ciprofloxacin were 0.5 and 1 mg/l, and those of ofloxacin 2 and 4 mg/l. The incidence of resistance in the two collections (clinical isolates/Pc-R strains) was 3%/39% for tetracycline, 1%/18% for macrolides, and 3%/57% for trimethoprim/sulfamethoxazole. The results of the current study suggest that the clinical efficacy of trovafloxacin in the treatment of pneumococcal infections should be investigated.     

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.     

In vitro evaluation of activities of nitazoxanide and tizoxanide against anaerobes and aerobic organisms

The antibacterial activities of nitazoxanide and its main metabolite, tizoxanide, were tested against a broad range of bacteria, including anaerobes. Metronidazole, amoxicillin, amoxicillin-clavulanic acid, piperacillin, cefoxitin, imipenem, and clindamycin were used as positive controls. MICs were determined by reference agar dilution methods. The 241 anaerobes were all inhibited by nitazoxanide, with the MICs at which 90% of isolates are inhibited (MIC90S) being between 0.06 and 4 mg/liter with the exception of those for Propionibacterium species, for which the MIC90 was 16 mg/liter. The MIC90s of nitazoxanide were 0.5 mg/liter for the Bacteroides fragilis group (80 strains), 0.06 mg/liter for Clostridium difficile (21 strains), and 0.5 mg/liter for Clostridium perfringens (16 strains). Metronidazole showed a level of activity comparable to that of nitazoxanide except against Bifidobacterium species, against which it was poorly active, and Propionibacterium species, which were resistant to metronidazole. The other antibiotics showed various levels of activity against anaerobes, with imipenem along with nitazoxanide being the most active agents tested. Tizoxanide was less effective than nitazoxanide except against the B. fragilis group, against which its activity was similar to that of nitazoxanide. Under aerobic conditions, nitazoxanide demonstrated poor activity against members of the family Enterobacteriacae and Pseudomonas, Staphylococcus, and Enterococcus species. The same results were obtained when culture was performed under anaerobic conditions with the notable exception of the results against Staphylococcus aureus. The MICs of nitazoxanide were in the range of 2 to 4 mg/liter for 34 clinical isolates of S. aureus, 12 of which were methicillin resistant, while tizoxanide was not effective.     

In vitro activities of antimicrobial agents, alone and in combination, against Acinetobacter baumannii isolated from blood

In vitro activities of 15 antimicrobial agents against 90 strains of Acinetobacter baumannii isolated from blood cultures from hospitalized patients were determined using the agar dilution method. Imipenem, ofloxacin, and ciprofloxacin had the best antimicrobial activity with minimum inhibitory concentrations (MIC50s) of 0.25 mu g/ml and MIC90s of 0.5-1 mu g/ml. beta-lactam antibiotics other than imipenem had poor activity, with MIC50s ranging from 8 to 64 mu g/ml and MIC90s from 32 to > or = 256 mu g/ml. The checkerboard titration method was used to study the effects of combination of two antimicrobial agents. Combinations of ceftazidime, aztreonam, imipenem, or ciprofloxacin with amikacin showed either synergistic effects or partial synergistic effects for 40.9%-86.4% of 22 tested strains. The best in vitro activity was observed with the combination of imipenem and amikacin. No antagonistic effects were observed with the combination of imipenem and amikacin. Synergistic effects were confirmed by time-kill curve studies. In conclusion, imipenem, ofloxacin, and ciprofloxacin were the three most active agents against human blood isolates of A. baumannii. The combination of a beta-lactam or ciprofloxacin with amikacin was synergistic for some of the isolates.     

Salmonella bloodstream infections: report from the SENTRY Antimicrobial Surveillance Program (1997-2001)

Salmonella spp. are significant bloodstream pathogens and are routinely monitored for antimicrobial resistance by the SENTRY Antimicrobial Surveillance Program. Six hundred and one bloodstream infection (BSI) isolates of Salmonella spp., collected over a 5-year period (1997-2001) were tested for their susceptibility against 20 antimicrobial agents, comparing year and geographical region. Salmonella enterica serotype Typhi was the most frequently identified 'species' (43% of identified strains), although 'unspeciated' strains predominated overall (54.2%). The rank order for six selected drugs tested by their MIC(90) values and percentage susceptibility was: ceftriaxone (< or =0.25 mg/l; 99.5% susceptible)>ciprofloxacin (0.12 mg/l; 99.3%)> trimethoprim/sulphamethoxazole (< or =0.5 mg/l; 92.7%)>amoxycillin/clavulanate (16 mg/l; 89.7%)>ampicillin (>16 mg/l; 81.0%)>tetracycline (>8 mg/l; 79.4%). Most isolates remained highly susceptible to all 20 agents examined, with the exception of Salmonella Typhimurium (only 35.3% susceptible to tetracycline, 41.2% to ampicillin, and 61.8% to amoxycillin/clavulanate). DT104 resistance phenotypes were noted in 3.4 and nearly 60.0% of unspeciated Salmonella and S. Typhimurium, respectively. Unexpectedly, the highest overall susceptibility rates were recorded in Latin America. Fluoroquinolone resistance was observed and nalidixic acid screening MICs (< or =8 mg/l) predicted full susceptibility to ciprofloxacin. Five-year results from the SENTRY Program show no clear trend toward greater resistances in Salmonella spp. BSIs for the commonly used antimicrobial classes. With the exception of S. Typhimurium DT104, most Salmonella spp. remain highly susceptible to the tested antimicrobials that maybe utilized for Salmonella BSI.     

In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal carbapenem

ER-35786 is a new parenteral 1 beta-methyl carbapenem with a broad antibacterial spectrum and a potent antipseudomonal activity. It showed high in vitro activity, comparable to those of meropenem and a new carbapenem, BO-2727, against methicillin-susceptible Staphylococcus aureus and streptococci, with MICs at which 90% of strains tested are inhibited (MIC90S) of < or = 0.39 microgram/ml. Against methicillin-resistant S. aureus, ER-35786 was the most active among the compounds tested, yet its MIC90 was 12.5 micrograms/ml. Against members of the family Enterobacteriaceae, Moraxella catarrhalis, and Haemophilus influenzae, ER-35786 inhibited 90% of strains tested at a concentration of < or = 1.56 micrograms/ml. The MIC90 of ER-35786 for Pseudomonas aeruginosa was 3.13 micrograms/ml, and the compound was more active than meropenem. In addition, the activity of ER-35786 against imipenem-, meropenem-, cefclidin-, or ceftazidime-resistant P. aeruginosa was equal to or higher than that of the most active reference compound. The in vivo activity of ER-35786 was consistent with this in vitro activity. The in vivo activity of ER-35786 was highest for systemic infection models with methicillin-resistant S. aureus and beta-lactam-resistant P. aeruginosa strains. In acute pneumonia caused by P. aeruginosa, ER-35786 produced a greater reduction in the viable cell count in the lungs than did imipenem-cilastatin or meropenem.     

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.     

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 vitro activity of fleroxacin against multiresistant gram-negative bacilli isolated from patients with nosocomial infections

In order to evaluate the in vitro activity of fleroxacin against nosocomial gram-negative organisms, 263 multiresistant gram-negative bacilli (203 Enterobacteriaceae and 60 non-fermenting gram-negative bacilli) were isolated from adult patients with nosocomial infections. The different patterns of resistance to eight different antimicrobial agents (ampicillin, carbenicillin, piperacillin, cephalothin, cefamandole, ceftazidime, gentamicin and amikacin) were determined by minimum inhibitory concentration (MIC), using the agar dilution method. The most prevalent multiresistant species isolated were Klebsiella pneumoniae (28.9%), Escherichia coli (24%) and Pseudomonas aeruginosa (12.2%). All these bacterial strains showed three to five resistance patterns to at least three different antibiotics. Resistance to ceftazidime was observed in at least one of the resistance patterns of isolated bacteria. The activity of fleroxacin against multiresistant enteric bacteria was excellent; these strains showed a susceptibility of 79-100%. The susceptibility of P. aeruginosa to antipseudomonal agents was low; however, the activity of fleroxacin against these strains was higher than 60% (MIC < or = 2 microg/ ml), broadly comparable with ciprofloxacin. The resistance to fluoroquinolones detected in this study was no cause for alarm (3%). Consequently, fleroxacin maintains a remarkable activity against Enterobacteriaceae and remains highly active against other gram-negative bacilli. Nevertheless, actions directed at preventing or limiting resistance will be crucial to maintain the viability of fluoroquinolones as important therapeutic agents.     

Antimicrobial activity of ofloxacin against recent clinical isolates from otitis media and otitis externa]

In order to evaluate the annual changes of susceptibility, minimum inhibitory concentrations (MICs) of ofloxacin (OFLX) and 4 control drugs were determined against clinical isolates that were obtained from patients with otitis media and otitis externa during the periods between January and December 1993, and the periods between October 1996 and March 1997. The results are summarized as follows: 1. No annual changes were seen for MIC50 of OFLX, but MIC80 and MIC90 of that rose against methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci (CNS) and Pseudomonas aeruginosa from 1993 to 1996. It appears that resistance to OFLX is increasing among these bacteria. Detection frequency of highly resistant strains to OFLX (MIC > 100 micrograms/ml) was lower than to other control drugs. 2. No annual changes were seen of MIC50, MIC80 and MIC90 of OFLX against methicillin-susceptible S. aureus (MSSA), Streptococcus spp., Proteus spp. and Haemophilus influenzae. OFLX showed strong antimicrobial activities against these bacteria. 3. Since there was no large annual changes in the antimicrobial activity of OFLX against clinical isolates that were obtained from patients with otitis media and otitis externa, OFLX otic solution was considered as one of the clinically useful drugs even now.     

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.     

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