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. 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.     

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.     

Susceptibilities of clinical isolates to antibacterial agents. A study mainly focused on ofloxacin (the second report). Reported by the Research Group for Testing ofloxacin Susceptibility on Clinical Isolates

Susceptibilities of various clinical isolates to ofloxacin (OFLX) and other antibacterial drugs were examined at 128 hospital laboratories in 36 prefectures throughout Japan between April, 1986 and March, 1987. The results were totalized with an emphasis mainly on OFLX and were compared with data obtained in the previous year. In this study, identification and susceptibility tests of the isolates were carried out at each hospital laboratory and the tests were performed according to the 1-dilution or 3-dilution disc method in which susceptibilities are classified into 4 grades: , ++, +, and -. Similarly to the study performed in the previous year, species showing susceptibilities to OFLX included Staphylococcus aureus (4,205 strains), Staphylococcus epidermidis (2,009 strains), Entercoccus faecalis (1,697 strains), Streptococcus pneumoniae (702 strains), Escherichia coli (4,097 strains), Klebsiella pneumoniae (1,375 strains), Enterobacter cloacae (762 strains), Enterobacter aerogenes (296 strains), Citrobacter freundii (406 strains), Proteus mirabilis (613 strains), Morganella morganii (320 strains), Serratia marcescens (869 strains), Haemophilus influenzae (1,282 strains), Pseudomonas aeruginosa (4,206 strains), Acinetobacter calcoaceticus (351 strains), Acinetobacter sp. (415 strains), and Campylobacter jejuni (151 strains). Neisseria gonorrhoeae (26 strains) were exceptional due to their smaller number this time than that of the previous year and only the susceptibility to OFLX was investigated with this species. As results, OFLX showed strong antibacterial activities (similar to the previous year) against S. aureus, S. epidermidis, N. gonorrhoeae, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, C. freundii, P. mirabilis, M. morganii, H. influenzae, A. calcoaceticus, Acinetobacter sp., and C. jejuni. However, when these susceptibilities shown in the present study were compared to those obtained in the previous year, many species showed decreases in the occurrence of or increases in -, though they were rather small changes. The following species were not totalized in the previous year due to their low numbers but were summarized in combination with those examined in this study: Streptococcus pyogenes (944 strains), Streptococcus agalactiae (815 strains), Enterococcus faecium (146 strains), Branhamella catarrhalis (135 strains), Citrobacter diversus (128 strains), Klebsiella oxytoca (873 strains), Proteus vulgaris (438 strains), Serratia liquefaciens (266 strains), Pseudomonas cepacia (433 strains), Pseudomonas putida (154 strains), Xanthomonas maltophilia (272 strains), Vibrio parahaemolyticus (120 strains), Bacteroides fragilis (98 strains),     

Changes in the antibacterial activity of chemotherapeutic agents (especially carbapenems) for 10 species of clinical isolates between 1994 and 1996. Surveillance group of the sensitivities of clinical isolates to antibacterial agents

During October and December of each year of from 1994 to 1996, 3,849 strains of 10 species of bacteria were isolated from clinical materials in 21 institutions nationwide. The minimum inhibitory concentrations (MICs) for these bacteria of four carbapenems (imipenem [IPM], panipenem [PAPM], meropenem [MEPM], and biapenem [BIPM]) and other representative antibacterial agents were measured to investigate annual changes in antibacterial activity. Carbapenems showed potent activity against methicillin-sensitive S. aureus (MSSA), S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, S. marcescens, and the B. fragilis group, with the activity being stable. However, these drugs showed weak activity against methicillin-resistant S. aureus (MRSA) and P. aeruginosa. The antibacterial activity (MIC90) against the tested organisms generally remained stable. Particularly, there was annual improvement of the MIC90 values of IPM and BIPM for S. pneumoniae, as well as the values of IPM and PAPM for H. influenzae, and those of IPM, PAPM, and BIPM for S. marcescens. On the other hand, the activity of carbapenems (including IPM) against MRSA was not necessarily strong, but there was annual improvement of MIC90 values.     

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.     

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.     

Survey of the sensitivities of clinical isolates to antibacterial agents (annual report)]

Research groups were formed in 21 institutions nationwide to investigate carbapenem resistance. The activities of various antibacterial agents, principally carbapenems, were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MIC) of 17 antibacterial agents for 1,241 strains of 11 bacterial species isolated at all institutions between October and December 1996. The results were as follows: Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae and showed low activities against MRSA. Their activities against Enterococcus faecalis were comparable to that of ampicillin and piperacillin. The carbapenems showed high activities against Haemophilis influenzae, Escherichia coli, Klebsiella pneumoniae. Enterobacter cloacae. Serratia marcescens and Bacteroides fragilis group. Their activities were greater than that exhibited by other beta-lactam antibacterial agents, but some resistant strains of Serratia marcescens were detected. The antibacterial activity of carbapenems against Pseudomonas aeruginosa was comparable to that of CAZ, and there were some resistant strains.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1997). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 560 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1997 to May 1998. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. Susceptibilities 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 VCM and arbekacin (ABK) showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90s of them were 1 microgram/ml. The others except minocycline (MINO) had low activities with the MIC90s of 32 micrograms/ml or above. More than a half of S. aureus strains (including MRSA) showed high susceptibilities to gentamicin (GM) and MINO, the MIC50s of 0.25 microgram/ml or 0.5 microgram/ml. 3. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. The MIC90s of ciprofloxacin (CPFX) and tosufloxacin (TFLX) were 1 microgram/ml, the MIC90s of amikacin (AMK) and ofloxacin (OFLX) were 4 micrograms/ml, the MIC90 of GM was 16 micrograms/ml. Among E. cloacae strains, those with low susceptibilities to quinolones have decreased in 1997, compared with those in 1996. But the other drugs were not so active in 1997 as 1996. 4. Escherichia coli All drugs except penicillins were active against E. coli with the MIC90s of 8 micrograms/ml or below. Particularly, flomoxef (FMOX), cefmenoxime (CMX), cefpirome (CPR), cefozopran (CZOP), IPM, CPFX and TFLX showed the highest activities against E. coli with the MIC90s of 0.125 microgram/ml or below. 5. Klebsiella pneumoniae K. pneumoniae was susceptible to almost all the drugs except penicillins. Carumonam (CRMN) had the strongest activity with the MICs for all strains equal to or lower than 0.125 microgram/ml. FMOX, CPR, CZOP, CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. The MIC90s of quinolones had changed into a better state in 1997, compared with those in 1996. 6. Proteus mirabilis Almost all the drugs except ABPC and MINO showed high activities against P. mirabilis. CMX, ceftazidime (CAZ), latamoxef (LMOX), CPR, cefixime (CFIX), cefpodoxime (CPDX) and CRMN showed the highest activities against P. mirabilis. The MICs of them for all strains were equal to or lower than 0.125 microgram/ml. CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. 7. Pseudomonas aeruginosa The MIC90 of GM was 8 micrograms/ml, the MIC90s of AMK, IPM and meropenem (MEPM) were 16 micrograms/ml. The others were not so active against P. aeruginosa with the MIC90s of 32 micrograms/ml or above. The MIC90s of quinolones had changed into a lower state in 1997, compared with those in 1996. 8. Serratia marcescens IPM showed the highest activity against S. marcescens. Its MIC90 was 2 micrograms/ml. GM was also active with the MIC90 of 4 micrograms/ml. The MIC90s of the others were 16 micrograms/ml or above. The MIC50s of CRMN was 0.125 microgram/ml or below, the MIC50s of CPR and CZOP were 0.25 microgram/ml.     

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)     

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.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). I. Susceptibility distribution

The frequencies of bacterial isolation and susceptibilities to antimicrobial agents were investigated on 538 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1998 to May 1999. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.3% and Gram-negative bacteria accounted for 69.7%. Susceptibilities of several isolated bacteria to antimicrobial agents were as follows; against Enterococcus faecalis isolated from patients with UTIs, vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) had strong activities. Among E. faecalis strains, those with low susceptibilities to all drugs have increased in 1998, compared with those in 1997. VCM showed the highest activity against MRSA isolated from patients with UTIs. The MICs of VCM for all 34 strains were equal to or lower than 2 micrograms/ml. Arbekacin (ABK) was also active against MRSA with the MIC90s of 2 micrograms/ml. Against Escherichia coli and Klebsiella pneumoniae, all drugs except penicillins were active. Particularly, meropenem (MEPM) showed the highest activity with the MICs of 0.125 micrograms/ml or below. Almost all the drugs except minocycline (MINO) showed high activities against Proteus mirabilis. Against Pseudomonas aeruginosa, all drugs were not so active, with the MIC90s of 16 micrograms/ml or above. MEPM, IPM and gentamicin (GM) showed high activities against Serratia marcescens. Generally, it seemed that resistant strains of S. marcescens had decreased since 1996.     

Antibacterial activity of cephem antibiotics against isolates from clinical specimens at the Yokohama City University Hospital

Minimum inhibitory concentrations (MICs) of cephem antibiotics against 405 strains belonging to 17 species of clinical isolates were investigated using the standard method of the Japanese Congress of Chemotherapy. The results obtained are summarized below. Cephem antibiotics showed weak antibacterial activities against Enterococcus sp., B. fragilis and S. marcescens. S. pneumoniae, S. agalactiae, E. coli, K. pneumoniae and P. mirabilis were susceptible to cephem antibiotics. Cephem antibiotics of the 1st and the 2nd generations showed weak antibacterial activity against Citrobacter sp. and E. cloacae, while cephem antibiotics of 3rd generation had a good antibacterial activity against these species. Cephem antibiotics of the 2nd and the 3rd generations showed high antibacterial activity against H. influenzae and indole positive Proteus group. Cefoperazone showed high antibacterial activity against P. aeruginosa. Resistance to latamoxef, ceftizoxime and cefoxitin was observed among Staphylococcus sp., while the MICs of other antibiotics against Staphylococcus sp. were fairly low. Number of strains resistant to the 3rd cephem antibiotics seems to be increasing because the 3rd generation of cephem antibiotics have been used frequently. Further investigation will be required on resistant organism to these antibiotics including beta-lactamase producing strains.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). I. Susceptibility distribution

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of September and December 2001. Then, the susceptibilities of them to a variety of antimicrobial agents were investigated. The number of them were 496 strains. The breakdown of these strains was Gram-positive bacteria as 29.6% and Gram-negative bacteria as 70.4%. Susceptibilities of these bacteria to antimicrobial agents were as follows; against Staphylococcus aureus, vancomycin (VCM) showed a strong activity, and this drug also had a strong activity against MRSA in preventing growth of all strains at 1 microgram/mL. In addition, arbekacin (ABK) showed strong activity with the MIC90 of 2 micrograms/mL against MRSA and prevented growth of all strains at 4 micrograms/mL. ABK also showed a strong activity against Staphylococcus epidermidis in preventing growth of all strains at 0.5 microgram/mL. Ampicillin (ABPC) and cefozopran (CZOP) showed a relatively strong activity against S. epidermidis (MIC90: 8 micrograms/mL). ABPC, imipenem (IPM), and VCM showed strong activities against Enterococcus faecalis. No increase of low-susceptible strains in E. faecalis was observed against these antimicrobial agents. Against Escherichia coli, carbapenems showed the highest activities: meropenem (MEPM) prevented growth of all strains at 0.25 microgram/mL; IPM prevented growth of all strains at 0.5 microgram/mL. CZOP and cefotiam (CTM) also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/mL; MIC90 of CTM was within 0.5 microgram/mL. Quinolone-resistant E. coli was detected at frequency of 9.3%, which was lower than that in the last year, and was higher level than those in up to 1999. MEPM showed the strongest activity against Citrobacter freundii in preventing growth of all strains at 0.125 microgram/mL. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125 microgram/mL. Against Serratia marcescens, the MIC90 of gentamicin (GM) was the lowest value being 2 micrograms/mL, and those of IPM and carumonam were 8 and 16 micrograms/mL, respectively. Against Pseudomonas aeruginosa, almost all drugs were not so active. The MIC90 of GM was 8 micrograms/mL, those of IPM and amikacin were 16 micrograms/mL, and those of all other drugs were over than 32 micrograms/mL.     

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.     

In vitro antimicrobial activity of a novel aminothiazolylglycylcephalosporin, MT0703S, compared with that of ceftazidime, cefoperazone and aztreonam

The antibacterial activity of a novel aminothiazolylglycylcephalosporin, MT0703S, possessing a dihydroxypyridone moiety was compared in vitro with the activity of ceftazidime, cefoperazone, aztreonam and other beta-lactam antibiotics using seven bacterial species of a clinical origin. MT0703S showed the most potent activity against P. aeruginosa, including the ceftazidime-resistant strains, E. coli, K. pneumoniae and C. freundii. MT0703S was comparable to aztreonam but more active than ceftazidime and cefoperazone in its activity against K. oxytoca and E. cloacae, and comparable to ceftazidime against S. aureus and S. marcescens. MT0703S was more active than cefoperazone against S. marcescens but less active against S. aureus. The stability of MT0703S against various beta-lactamases appeared to be intermediate between the stability of ceftazidime and that of cefoperazone. The antimicrobial activity of MT0703S increased in a low-iron environment and decreased in a high ferric ion concentration.     

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.     

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 activity of ciprofloxacin against fresh clinical isolates from superficial suppurative foci

The minimum inhibitory concentrations (MICs) of 5 drugs (ciprofloxacin (CPFX), and 4 drugs used as standard) were determined to investigate antibacterial potencies of CPFX against bacterial strains isolated in 1989 from superficial suppurative foci. The clinical isolates tested included 375 strains from 11 aerobic bacterial species, and 50 strains from 2 anerobic bacterial genera (group) for a total of 425 isolates. Interpreting MIC level distributions of these drugs as the expression of antibacterial potencies, the results are as follows. 1. When activities of new-quinolone antibiotics were tested, we found that, CPFX expressed far superior antibacterial potency to ofloxacin (OFLX) and norfloxacin (NFLX) against coagulase-negative staphylococci, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Pseudomonas aeruginosa and Peptostreptococcus spp., although the activity of CPFX against Bacteroides fragilis group was weaker than that of OFLX, and CPFX had similar activity against Staphylococcus aureus to OFLX. 2. In comparison to beta-lactam antibiotics, CPFX was inferior to amoxicillin (AMPC) against E. faecalis and inferior to AMPC and cefaclor (CCL) against Peptostreptococcus spp. Against all other bacterial species, however, CPFX expressed superior antibacterial potency to AMPC and CCL. 3. Scattered findings of low sensitivity or resistance to CPFX were observed among the S. aureus, E. faecalis, E. faecium, P. vulgaris, M. morganii, P. aeruginosa and B. fragilis (group) species, but with an exception of E. faecium, the incidence of resistance strains was low.     

Metronidazole-quinolone combination: antibacterial activity in vitro

Combination of metronidazole and oxolinic or pipemidic acid were tested in vitro against some of the bacteria most commonly responsible for genito-urinary infections (E. coli, K. pneumoniae, Enterob. cloacae, Serratia marcescens, Pr. mirabilis, Pr. morganii, Str. faecalis and 3 strains of Ps. aeruginosa). The metronidazole-oxolinic acid combination was found to be additive or synergistic against E. coli, K. pneumoniae, Enterob. cloacae and Serratia marcescens. The results show that subinhibitory concentrations of oxolinic acid may reveal an activity of metronidazole against aerobic and facultative anaerobic bacteria, under aerobic conditions.