Susceptibilities of clinical isolates to antibacterial agents. Focusing mainly on ofloxacin (first report). Reported by the Research Group for Testing Ofloxacin Susceptibility of Clinical Isolates

Susceptibility tests were carried out on a variety of clinically isolated pathogens using the susceptibility disc method at 197 hospitals in Japan between May, 1985 through March, 1986. These tests were organized by the Research Group for Testing Ofloxacin Susceptibility on Clinical Isolates, and the results were statistically analyzed. This paper describes a comparison of susceptibilities of clinical isolates including Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Neisseria gonorrhoeae, Escherichia coli, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Klebsiella pneumoniae subsp. pneumoniae, Proteus mirabilis, Morganella morganii, Serratia marcescens, Haemophilus influenzae, Pseudomonas aeruginosa, Acinetobacter calcoaceticus, Acinetobacter sp. and Campylobacter jejuni to ofloxacin (OFLX) and conventional antibacterial drugs. The results obtained were summarized as follows. 1. OFLX showed strong antibacterial activity against S. aureus, S. epidermidis, N. gonorrhoeae, E. coli, E. aerogenes, E. cloacae, C. freundii, K. pneumoniae subsp. pneumoniae, P. mirabilis, M. morganii, H. influenzae, A. calcoaceticus, Acinetobacter sp. and C. jejuni and only a few strains were resistant to OFLX. Moreover, OFLX has superior antibacterial activity against many species compared not only to norfloxacin but also to most of the conventional antibacterial drugs. 2. When studied by sampled materials such as sputum, urine, abscesses and otorrhea, OFLX occasionally showed different actions against the same species from different sources. Almost species from the urinary isolates were less sensitive than those from the sputum.     

Susceptibilities of clinical bacterial isolates to antimicrobial agents. A study mainly focused on imipenem. Reported by the Research Group for Testing Imipenem Susceptibility on Clinical Isolates

This study was conducted to investigate susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antibacterial agents at 64 hospital laboratories throughout Japan from September to December of 1988. In this study, identification and susceptibility testing were carried out at each laboratory and the tests were performed according to the disk dilution method recommended by NCCLS in which susceptibilities are classified into "S", "MS", "I" and "R". IPM showed markedly high in vitro activities against Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus faecalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Salmonella spp., Citrobacter freundii, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Moraxella (Branhamella) catarrhalis, Alcaligenes spp., Peptococcus spp./Peptostreptococcus spp., Bacteroides fragilis and Bacteroides spp. IPM also had strong activities against Achromobacter xylosoxidans and Pseudomonas aeruginosa, but less active against Flavobacterium spp., E. faecium, coagulase-negative staphylococci (CNS), Staphylococcus aureus and Pseudomonas cepacia. In a study in which activities of IPM against bacteria isolated from different clinical sources were compared, differences in susceptibilities were observed among S. aureus, CNS, A. calcoaceticus and P. aeruginosa, but such differences were not apparent among S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, C. freundii, S. marcescens or P. mirabilis.     

Susceptibilities of clinical bacterial isolates to antimicrobial agents. A study mainly focused on imipenem. Research Group for Testing Imipenem Susceptibility on Clinical Isolates

We investigated susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antimicrobial agents at 459 hospital laboratories throughout Japan from September to December of 1988. In this study, identification and susceptibility testing were performed at each hospital laboratory and the tests were carried out according to the 1-dilution or 3-dilution disc technique in which susceptibilities are classified into 4 grades: , ++, + and -. IPM had significantly high activity against Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Salmonella spp., Citrobacter freundii, Proteus mirabilis, Providencia rettgeri, Acinetobacter calcoaceticus, Moraxella catarrhalis, Alcaligenes spp., Peptococcus spp./Peptostreptococcus spp., Bacteroides fragilis and Bacteroides spp. and should slightly lower activities on coagulase-negative staphylococci (CNS), Enterococcus faecalis, Haemophilus influenzae, Serratia marcescens, Proteus vulgaris, Providencia stuartii and Pseudomonas aeruginosa than on the above mentioned bacteria. In a comparative study on activities of IPM against bacteria from different clinical sources, no remarkable differences were found due to different sources among S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, C. freundii, P. mirabilis or A. calcoaceticus, whereas slight differences were found among Staphylococcus aureus, CNS, S. marcescens and P. aeruginosa.     

Susceptibilities of clinical bacterial isolates to antimicrobial agents, 1989. A study mainly focused on imipenem. The Research Group for Testing Imipenem Susceptibilities of Clinical Isolates]

We investigated susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antimicrobial agents at hospital laboratories throughout Japan from September to December of 1989. The susceptibility testing was carried out according to the 1-dilution or 3-dilution disc technique in which susceptibilities are classified into 4 grades: (+++), (++), (+) and (-). IPM showed markedly high in vitro activities against Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Acinetobacter calcoaceticus, Bacteroides fragilis and had rather strong activities against Enterococcus faecalis, Haemophilus influenzae, Serratia marcescens, Proteus mirabilis, Morganella morganii, Pseudomonas aeruginosa and Achromobacter xylosoxidans, but was less active to Staphylococcus aureus, coagulase-negative staphylococci and Xanthomonas maltophilia. IPM has been found to have activities superior to those of other antibiotics tested against E. faecalis, E. cloacae, C. freundii, S. marcescens, P. aeruginosa and B. fragilis. No antibiotics tested showed good activities against MRSA except minocycline.     

Antimicrobial activity of dactimicin in vitro compared with that of dibekacin, netilmicin, sisomicin and micronomicin

Antimicrobial activity of dactimicin, a pseudo-disaccharide aminoglycoside antibiotic, was compared with those of dibekacin, netilmicin, sisomicin and micronomicin using clinical isolates of four Gram-positive and sixteen Gram-negative bacteria. Dactimicin was more active than the reference amino-glycosides against Serratia marcescens, especially gentamicin-resistant Serratia sp., Proteus vulgaris, P. rettgeri and Klebsiella oxytoca, but less active against Pseudomonas aeruginosa and P. mirabilis. Dactimicin was equally active as the references excepting netilmicin against Gram-positive bacteria and some Gram-negative bacteria including Escherichia coli, K. pneumoniae, Morganella morganii, Haemophilus influenzae, Citrobacter freundii, Enterobacter aerogens, E. cloacae, Acinetobacter calcoaceticus and Campylobacter jejunii. Dactimicin was active against resistant strains possessing various aminoglycoside-modifying enzymes including AAC(3)-1, by which dactimicin was acetylated.     

In vitro activity of aztreonam against gram negative bacteria from clinical specimens and its comparison with other commonly used antibiotics

A total of 755 gram negative bacteria isolated from clinical specimens were tested against aztreonam by the disc agar diffusion test. The strains of bacteria used in this study consisted of Escherichia coli (314), Enterobacter aerogenes (30), E. agglomerans (7), E. cloacae, (39), Citrobacter diversus (9), C. freundii (13), Hafnia alvei (3), Acinetobacter calcoaceticus (10), Klebsiella oxytoca (6), K. ozaenae (5), K. pneumoniae (107), Morganella morganii (3), Moraxella sp. (10), Pasteurella multocida (1), Proteus mirabilis (66), P. vulgaris (4), Providencia rettgeri (12), P. stuartii (5), Pseudomonas aeruginosa (85), P. fluorescens (2), P. maltophila (7), Salmonella sp. (1) and Serratia marcescens (17). In vitro activity against aztreonam was compared with amikacin, ampicillin, carbenicillin, cephalosporin, cefoxitin, chloramphenicol, gentamicin, nitrofurantoin, piperacillin, tetracycline, sulfamethoxazole-trimethoprim and tobramycin. Over 99% of E. coli and Enterobacter species were susceptible to aztreonam. All the 118 strains of Klebsiella, 87 strains of Proteus-Providencia and 17 strains of S. marcescens were also susceptible. Aztreonam also showed good activity against P. aeruginosa, inhibiting 90% of the 85 isolates tested.     

Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the bacteria were also evaluated with the bacterial resistance ratio calculated with the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of Moraxella (Branhamella) catarrhalis (n = 136), Haemophilus influenzae (n = 289), Escherichia coli (n = 276), Klebsiella pneumoniae (n = 192), Klebsiella oxytoca (n = 157), Enterobacter cloacae (n = 189), Enterobacter aerogenes (n = 93), Serratia marcescens (n = 172), Serratia liquefaciens (n = 24), Citrobacter freundii (n = 177), Citrobacter koseri (n = 70), Proteus mirabilis (n = 113), Proteus vulgaris (n = 89), Morganella morganii (n = 116), Providencia spp. (n = 41), Pseudomonas aeruginosa (n = 290), Pseudomonas fluorescens (n = 56), Pseudomonas putida (n = 63), Acinetobacter baumannii (n = 146), Acinetobacter lwoffii (n = 34), Burkholderia cepacia (n = 101), Stenotrophomonas maltophilia (n = 169), Bacteroides fragilis group (n = 196), and Prevotella/Porphyromonas (n = 173). An antibacterial activity of CZOP against E. coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with or more preferable than the study results obtained until the new drug application approval. MIC90 of CZOP against M.(B.) catarrhalis, C. koseri, and P. aeruginosa was not considerably changed and consistent with the study results obtained until the new drug application approval. MIC90 of CZOP against E. cloacae, E. aerogenes, and P. mirabilis increased year by year. The increase in MIC90 of CZOP against E. aerogenes and P. mirabilis, however, was not considered to be an obvious decline in susceptibility. In contract, the susceptibility of E. cloacae to CZOP was suspected to be decreasing because this species showed 20.6% resistance to CZOP. MIC90 of CZOP against C. freundii was variably changed or not one-sidedly, but was higher than the values obtained until the new drug application approval. Additionally, MIC90 of CZOP against H. influenzae was stable during 5 years except being higher in 1999, and, as a whole, was a little higher than the values obtained until the new drug application approval. An antibacterial activity of CZOP against P. fluorescens, P. putida, B. cepacia, S. maltophilia, B. fragilis group, and Prevotella/Porphyromonas was weak like the other cephems. Changes in MIC90 of CZOP against the other bacteria were 2 tubes or more through 5-year study period, but did not tend towards a unilateral direction as meaning a decline in susceptibility.     

Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2001--II. Gram-negative bacteria

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2001 were yearly evaluated and compared with those of other cephems, oxacephems and carbapenems. A total of 3,245 strains in 32 species of Gram-negative bacteria were isolated from the clinical materials annually collected from January to December, and consisted of Moraxella subgenus Branhamella catarrhalis, Escherichia coli, Citrobacter freundii, Citrobacter koseri, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Proteus mirabillis, Proteus vulgaris, Morganella morganii, Providencia spp. (P. alcalifaciens, P. rettgeri, P. stuartii), Pseudomonas aeruginosa, Pseudomonas putida, Burkholderia cepacia, Stenotrophomonas maltophilia, Haemophilus influenzae, Acinetobactor baumannii, Acinetobactor lwoffii, Bacteroides fragilis group (B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron), and Prevotella spp. (P. melaninogenica, P. intermedia, P. bivia, P. oralis, P. denticola). CZOP possessed stable antibacterial activities against M. (B.) catarrhalis, E. coli, C. freundii, C. koseri, K. pneumoniae, K. oxytoca, E. aerogenes, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris, M. morganii, Providencia spp., P. aeruginosa, and A. lwoffii throughout 6 years. The MIC90 of CZOP against those strains were consistent with those obtained from the studies performed until the new drug application approval. On the other hand, the MIC90 of CZOP against H. influenzae yearly obviously increased with approximately 64-time difference during the study period. The MIC90 of cefpirome, cefepime, and flomoxef against H. influenzae also yearly tended to rise. The present results demonstrated that CZOP had maintained the antibacterial activity against almost Gram-negative strains tested. However, the decrease in antibacterial activities of CZOP against B. cepacia, and H. influenzae was suggested.     

Antimicrobial activity of imipenem against 1386 clinical isolates

1386 isolates from clinical specimens were tested against imipenem by disc agar diffusion. The bacteria used in this study consisted of Escherichia coli, Enterobacter aerogenes, E. agglomerans, E. cloacae, Klebsiella pneumoniae, K. oxytoca, K. ozanae, Proteus mirabilis, P. vulgaris, Providencia stuartii, P. rettgeri, Acinetobacter calcoaceticus, Citrobacter diversus, C. freundii, Morganella morganii, Serratia liquefaciens, S. marcescens, Hafnia alvei, Aeromonas hydrophila, Pseudomonas aeruginosa, P. cepacia, P. maltophila, P. fluorescens, Staphylococcus aureus, S. epidermidis, S. saprophyticus, pneumococcus, Lancefield group A, B and D streptococci, viridans streptococci, diphtheroids and Bacillus species. In vitro activity of imipenem was compared with the following antibiotics: ampicillin, amikacin, carbenicillin, cefoperazone, cefoxitin, cephalothin, chloramphenicol, clindamycin, colistin, erythromycin, gentamicin, methicillin, penicillin, tetracycline, tobramycin, trimethoprim-sulfamethoxazole and vancomycin. Of the 819 strains of Enterobacteriaceae tested, 99.5% were susceptible to imipenem. Ninety-seven percent strains of P. aeruginosa were also susceptible to imipenem. All the 161 isolates of S. aureus and 116 of the 117 isolates of enterococci exhibited in vitro susceptibility to this antibiotic. All gram positive bacteria tested were inhibited by imipenem except 28% isolates of S. epidermidis and 5% isolates of S. agalactiae.     

Susceptibility of clinically isolated bacterial strains to imipenem/cilastatin sodium

In vitro antibacterial activities of imipenem/cilastatin sodium (imipenem) and other beta-lactams against clinically isolated 353 bacterial strains were investigated. The results obtained in this study are summarized as follows: 1. Imipenem (IPM) showed potent antibacterial activities against Gram-positive cocci such as Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus agalactiae. 2. IPM had inferior or equivalent antibacterial activities to beta-lactams against clinically isolated Enterobacteriaceae, that is, Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Serratia marcescens, Enterobacter cloacae, Enterobacter aerogenes and Proteus spp. 3. IPM showed potent antibacterial activities against clinically isolated Pseudomonas aeruginosa, Acinetobacter anitratus but not against Xanthomonas maltophilia.     

Antibacterial activities of sisomicin against fresh clinical isolates]

To investigate antibacterial activities of sisomicin (SISO), MICs of SISO as well as other aminoglycosides (AGs) were determined against many clinical isolates which were obtained in 1991. Results are summarized below: 1. No SISO-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Proteus mirabilis and Morganella morganii. 2. In comparison with the results of our previous study against isolates obtained in 1986, the rate of methicillin-resistant Staphylococcus aureus (MRSA) was higher, and SISO-resistant strains were observed at a high rate among the MRSA. Also, SISO-resistant strains of Serratia marcescens increased. However, the rate of SISO-resistant strains of Pseudomonas aeruginosa decreased, and among Citrobacter freundii, Enterobacter cloacae and Proteus vulgaris, SISO-resistant strains did not increase over the years. 3. MICs of SISO against Providencia rettgeri and Providencia stuartii were high, suggesting that antibacterial activities of SISO was weak against genus Providencia. 4. For comparison, according to MICs of ofloxacin and imipenem, new quinolone-resistant strains were observed at a high rate among various organisms, and carbapenem-resistant strains were observed at a high rate among S. marcescens and P. aeruginosa. 5. SISO is still one of the useful AGs in the 1990's since it maintains its strong antibacterial activities against most clinical isolates obtained in recent years and its potential as a combination drug with beta-lactams is being reported.     

A consideration on the results of nationwide surveillance of antimicrobial susceptibilities--gram-negative bacilli]

The results of the semi-annual nationwide surveillance of antimicrobial susceptibilities, conducted by the Japanese Ministry of Health and Welfare during the period of January 1993 to July 1995, were analyzed for typical Gram-negative bacilli in the purpose of provision of an index for antimicrobial selection. During these 3 years, Escherichia coli, Citrobacter freundii, Enterobacter aerogenes and Proteus mirabilis showed slightly increasing tendency in susceptibility to fosfomycin (FOM) and Citrobacter freundii. Klebsiella pneumoniae and Enterobacter aerogenes showed slightly increasing tendency to minocycline (MINO). While Haemophilus influenzae and Haemophilus parainfluenzae showed slightly decreasing tendency to cefmetazole (CMZ). However, these annual changes were almost negligible. Generally, these microorganisms showed relatively good susceptibilities, every year, to the principal antimicrobial agents being approved for use against Gram-negative bacilli. However, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens and Pseudomonas aeruginosa showed tendencies of decreased susceptibility to some of the antimicrobial agents. On the other hand, sulfamethoxazole-trimethoprim (ST), CMZ, latamoxef (LMOX), gentamicin (GM) and amikacin (AMK) showed good activities against some of the Gram-negative bacilli to which no indications are approved. In conclusion, bedside the identification of the causative microorganisms and the performance of antimicrobial susceptibility testing, such analyses (graphics of susceptibility tendency of clinical isolates to variety of antimicrobial agents) could be used as an index for selection of antimicrobial agents, when emergent and urgent selection of antimicrobial agents is necessary.     

Antibacterial activity of aztreonam: a synthetic monobactam. A comparative study with thirteen other antibiotics

The in vitro activity of aztreoman (SQ 26, 776), a new monocyclic beta-lactam antimicrobial agent, was determined against 1720 bacteria, all clinical isolates, and compared with that of thirteen beta-lactam and aminoglycoside antibiotics. Aztreonam inhibited 90% of Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, E. coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii, Proteus rettgeri, Proteus vulgaris and Salmonella sp. by less than or equal to 0.4 micrograms ml-1. This activity was superior to moxalactam, piperacillin, cefamandole, cefoperazone, cefoxitin, cefsulodin, ceftazidime and aminoglycoside antibiotics. Aztreonam was as active as moxalactam against Enterobacter aerogenes, Enterobacter cloacae and Shigella species. Pseudomonas aeruginosa strains resistant to moxalactam, piperacillin, cefamandole, cefoperazone, cefotaxime, cefoxitin, cefsulodin and ceftazidime were inhibited by aztreonam 50% by 6.3 micrograms ml-1 and 90% by 16 micrograms ml-1. Aztreonam was as active as ceftazidime against Serratia marcescens, all strains were inhibited by 3.1 micrograms ml-1 and 90% by 1.6 micrograms ml-1. There was no major difference between MBC and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU.     

Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2000--II. Gram-negative bacteria

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2000 were yearly evaluated and compared with those of other cephems, oxacephems, and carbapenems. Thirty-two species 2,697 strains of Gram-negative bacteria were isolated from the clinical materials annually collected from January to December, and consisted of Moraxella subgenus Branhamella catarrhalis (n = 125), Escherichia coli (n = 250), Citrobacter freundii (n = 153), Citrobacter koseri (n = 97), Klebsiella pneumoniae (n = 150), Klebsiella oxytoca (n = 100), Enterobacter aerogenes (n = 50), Enterobacter cloacae (n = 125), Serratia marcescens (n = 153), Proteus mirabillis (n = 103), Proteus vulgaris (n = 77), Morganella morganii (n = 141), Providencia spp. (P. alcalifaciens, P. rettgeri, P. stuartii; n = 154), Pseudomonas aeruginosa (n = 211), Pseudomonas putida (n = 49), Burkholderia cepacia (n = 102), Stenotrophomonas maltophilia (n = 101), Haemophilus influenzae (n = 210), Acinetobactor baumannii (n = 63), Acinetobactor Iwoffii (n = 30), Bacteroides fragilis group (B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron; n = 129), and Prevotella spp. (P. melaninogenica, P. intermedia, P. bivia, P. oralis, P. denticola; n = 124). CZOP possessed stable antibacterial activities against M. (B.) catarrhalis, E. coli, C. freundii, C. koseri, K. pneumoniae, K. oxytoca, E. aerogenes, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris, M. morganii, Providencia spp., P. aeruginosa, and A. lowffii throughout 5 years. The MIC90 of CZOP against those strains were consistent with those obtained from the studies performed until the new drug application approval. On the other hand, the MIC90 of CZOP against H. influenzae yearly obviously increased with approximately 65-time difference during study period. The MIC90 of cefpirome, cefepime, and flomoxef against H. influenzae also yearly tended to rise. The present results demonstrated that CZOP had maintained the antibacterial activity against almost Gram-negative strains tested. However, the decrease in the antibacterial activity of CZOP against H. influenzae was suggested.     

Antibacterial activities of monobactams against fresh clinical isolates

Antibacterial activities of monobactam antibiotics (carumonam (CRMN) and aztreonam (AZT] against Gram-negative bacilli isolated from inpatients in the latter half of 1987 were investigated using penicillin (PC: piperacillin (PIPC], cephems (CEPs: ceftazidime (CAZ), cefotaxime (CTX), latamoxef (LMOX), cefsulodin (CFS], carbapenem (imipenem (IPM] and pyridonecarboxylic acids (norfloxacin (NFLX) and ofloxacin (OFLX] as reference antibiotics. A total of 400 strains of 13 species, i.e. Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Citrobacter freundii, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Pseudomonas aeruginosa and Haemophilus influenzae, were used as test strains. 1. CRMN and AZT, both monobactam antibiotics, were roughly comparable in their activities and no resistant strain to these antibiotics were found among isolates of E. coli, Klebsiella spp., Proteus spp., M. morganii, P. rettgeri or H. influenzae and few resistant strains were observed among isolates of S. marcescens. On the other hand, isolates of C. freundii, Enterobacter spp. and P. aeruginosa included rather numerous strains resistant to the monobactam antibiotics. Among these cases, whereas R strains, i.e. resistant strains showing MICs greater than or equal to 50 micrograms/ml, accounted for a large proportion of strains resistant to PC and CEPs, I strains, i.e. intermediately resistant strains showing MICs between 12.5 and 25 micrograms/ml, accounted for a large proportion of strains resistant to the monobactam antibiotics. 2. Strains resistant to PIPC, a PC, were detected with high and more or less uniform frequencies over the entire spectrum of the isolates examined. 3. Antibacterial activities of CEPs varied against different bacterial species. While strains resistant to CTX, CAZ and LMOX were commonly detected with high frequencies among isolates of C. freundii, Enterobacter spp. and S. marcescens, large percentages of LMOX-resistant strains of C. freundii and Enterobacter spp. were of the I type. CTX-resistant strains were also found among isolates of P. vulgaris and M. morganii. Proportions of CEP-resistant strains of P. aeruginosa were 28% for CFS and 12% for CAZ. 4. No or few strains among the isolates of 13 species investigated were resistant to IPM, a carbapenem antibiotic, which showed the most stable antibacterial activity, but it was less active than monobactam antibiotics and CEPs against Klebsiella spp., P. mirabilis and H. influenzae.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of combination of cefsulodin and mecillinam

The effect of cefsulodin in combination with mecillinam was examined against a wide range of bacterial species. The antibacterial spectrum was widened by the combination of cefsulodin and mecillinam in the ratio of 5:1 and 10:1. In overall observations, in the in vitro test, a synergistic effect against clinical isolates was found on Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, proteus mirabilis and Proteus vulgaris, and an additive effect was found on Staphylococcus aureus, Escherichia coli, Proteus morganii, Proteus rettgeri, Proteus inconstans and Pseudomonas aeruginosa. In in vivo tests, a synergistic effect was observed on S. marcescens TN 66 and K. pneumoniae DT infections and an additive effect was observed on S. aureus 308 A-1, E. coli O-111 and T-7, C. freundii TN 518, E. cloacae TN 603, P. vulgaris GN 4712, P. morganii Tn 373 and P. aeruginosa U 31 infections.     

Antibacterial activities of ofloxacin against recent isolates from patients with community-acquired infections

In order to survey antibacterial activities of ofloxacin (OFLX) against 1,440 bacterial strains isolated from patients with community-acquired infections in 1987 and 1990, minimum inhibitory concentrations (MICs) of the drug as well as those of other new quinolones and oral cephems were determined. The following conclusions were reached. 1. Comparison of the MIC distribution for strains isolated in 1987 with those in 1990 suggested a tendency toward an increase in the frequency of OFLX-resistant isolates with the passage of time of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Citrobacter spp., Klebsiella ssp., Enterobacter spp., Proteus vulgaris, Morganella morganii, Providencia spp., and Acinetobacter calcoaceticus. Most common elevations of MIC values against these bacteria were observed in MIC80 and MIC90 values, while no significant alteration was observed in MIC50 values. However, MIC50's of OFLX against Serratia marcescens and Pseudomonas aeruginosa were relatively high for strains isolated in both 1987 and 1990. Most of the OFLX-resistant strains of S. aureus seemed to be methicillin-resistant (MRSA). Furthermore, MIC80 of OFLX against coagulase-negative staphylococci was high in strains isolated in both 1987 and 1990. 2. Susceptibility of Streptococcus spp. was evaluated only in strains isolated in 1990. The results were comparable to those reported by others in the early 1980s. 3. Bacteria which showed no or infrequent emergence of OFLX-resistant strains even in 1990 were Proteus mirabilis, Haemophilus influenzae, Neisseria gonorrhoeae, Campylobacter spp. and Peptostreptococcus spp. 4. Recently isolated strains from patients with community-acquired infections showed a tendency toward an increase of the frequency of OFLX-resistant strains among many bacteria. However, the bacteria which contained high percentages of OFLX-resistant strains except for MRSA were so-called less-virulent bacteria, and in the other bacteria elevations of MIC values were only observed in MIC80 and MIC90. These results suggested that OFLX preserved a potent antibacterial activity against bacteria which were major causative pathogens in community-acquired infections.     

In vitro study of the antibacterial activity of ofloxacin against recent clinical isolates

The in vitro activity of ofloxacin, a new broad-spectrum antimicrobial agent, was studied by a standardized single disc method. A total of 990 clinical isolates were tested, including 20 strains of anaerobic bacteria. Ofloxacin was highly active against 683 strains (70.41%), had intermediate activity against 109 (11.23%) and had no activity against 178 (18.35%). Ofloxacin was highly active against E. coli, Klebsiella sp., Citrobacter sp., Proteus mirabilis, Proteus morganii, Salmonella sp., Campylobacter jejuni, Haemophilus influenzae, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Eubacterium sp., Propionibacterium acnes and Streptococcus sp. Pseudomonas sp., Serratia sp. and Proteus vulgaris had percentages of resistance to ofloxacin of 37.11%, 32% and 33.33% respectively. High percentages of resistance to ofloxacin were found only for Providencia sp., Proteus rettgeri and Bacteroides fragilis. With regard to Streptococcus faecalis, the results obtained with the disc procedure were not reliable and MIC determination was necessary to assess the behaviour of the drug.     

Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among bacteria were also evaluated with the bacterial resistance ratio calculated from the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter Iwoffii, Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group, and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against M. (B.) catarrhalis (MIC90: 4 micrograms/mL) and showed comparable activity to carbapenems against H. influenzae (MIC90: 1 microgram/mL). The antibacterial activity of CZOP against E. coli was preferable (MIC90: 0.125 microgram/mL) and comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The MIC90 of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 microgram/mL, respectively. The MIC90 of CZOP against E. cloacae increased during 6 years (32 to 128 micrograms/mL). The antibacterial activity of CZOP against E. aerogenes was preferable (MIC90: 1 microgram/mL). The antibacterial activities of CZOP against S. marcescens and S. liquefaciens were relatively potent (MIC90: 0.5 and 0.25 microgram/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP preserved comparable antibacterial activity to CPR against C. freundii and C. koseri (MIC90: 8 and 0.125 micrograms/mL). The MIC90 of CZOP against P. mirabilis, P. vulgaris, and M. morganii was 0.25, 16, and 2 micrograms/mL, respectively. The antibacterial activity of CZOP against Providencia spp. was moderate (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against P. aeruginosa was the most potent (MIC90: 16 micrograms/mL) among the test agents and comparable to those CFPM, IPM, and MEPM. CZOP had low activity against P. fluorescens and P. putida (MIC90: 128 micrograms/mL). The antibacterial activity of CZOP against A. baumannii was comparable to those of ceftazidime (CAZ), CPR and CFPM (MIC90: 32 micrograms/mL) and against A. lwoffii was moderate (MIC90: 64 micrograms/mL). Most of the test agents including CZOP had low antibacterial activity against B. cepacia, S. maltophilia, and B. fragilis group. The MIC90 of CZOP against Prevotella/Porphyromonas was 64 micrograms/mL. Bacterial cross-resistance ratio between CZOP and other agents was low in most of the species, ranging from 0.0 to 15.1%. In non-glucose fermentative bacteria, however, the bacterial cross-resistance ratio between CZOP and CFPM, CAZ, CPR, or IPM was high, being 36.8%, 28.0%, 38.7%, or 31.1%, respectively. In conclusion, the 6-year duration study suggested that the antibacterial activity of CZOP against E. cloacae possible decreased, but against other Gram-negative bacteria was consistent with the study results obtained until the new drug application approval.     

Susceptibility of clinically isolated strains to aztreonam

In vitro antibacterial activities of aztreonam (AZT) and cephems against clinically isolated 334 strains were investigated. The results obtained in the study are summarized as follows: 1. AZT showed excellent antibacterial activities against clinically isolated 334 strains. 2. AZT showed potent activities against Escherichia coli, Klebsiella pneumoniae, Proteus spp., Enterobacter aerogenes and Citrobacter freundii. 3. Antibacterial activities of AZT were superior against Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa to those of cephems.