Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1987). I. Susceptibility distribution

Since 1979, Ikemoto et al. have been retrospectively surveying the sensitivity of major species of bacteria isolated from patients with urinary tract infections to various antibacterial agents and antibiotics. Their findings for the past year are reported below. A total of 825 clinical strains of bacteria was investigated. Of this total, Gram-positive bacteria accounted for 28.0% (231 strains) and Gram-negative bacteria for 72.0% (594 strains). Taxonomically, Escherichia coli accounted for 34.7% (286 strains), Enterococcus faecalis for 14.3% (118), Pseudomonas aeruginosa for 11.0% (91), Klebsiella pneumoniae for 7.8% (64), and coagulase-negative staphylococci for 7.3% (60). Sensitivity spectra of these major bacteria to various drugs were as follows. 1. E. faecalis was sensitive to parenteral imipenem (IPM) and ampicillin and oral vancomycin. It was also sensitive to ofloxacin (OFLX) and ciprofloxacin (CPFX), which are new quinolones. Some strains were only slightly sensitive to second and third generation cephems cefmenoxime (CMX) and cefuzonam (CZON) aminoglycosides amikacin (AMK) and arbekacin (HBK), and erythromycin which is a macrolide. 2. Staphylococcus aureus was sensitive to dicloxacillin (MDIPC) which is a penicillin drug, cefotiam (CTM) which is a cephem, IPM, minocycline (MINO), and HBK. A fairly large number of strains were only slightly sensitive to cefazolin (CEZ), OFLX and CPFX. 3. Coagulase-negative staphylococci were sensitive to MDIPC which is a penicillin derivative, cephems CTM and CZON, IPM, HBK, clindamycin (CLDM) and MINO. Some strains, however, were only slightly sensitive to a majority of these drugs. 4. E. coli was sensitive to CTM, CMX, latamoxef (LMOX), ceftazidime (CAZ), CZON, and flomoxef (FMOX), all of which are second or third generation cephems. It was also sensitive to IPM, a carbapenem, carumonam (CRMN), a monobactam, and new quinolones, OFLX and CPFX. 5. K. pneumoniae was sensitive to cephems, viz. CTM, CAZ, CZON, FMOX and cefixime, CRMN which is a monobactam, IPM, a carbapenem and new quinolones, OFLX and CPFX. Some strains were only slightly sensitive to CTM, cefmetazole cefoperazone (CPZ), and FMOX. 6. Citrobacter freundii was sensitive to CRMN which is a monobactam, and new quinolones, OFLX and CPFX. Many strains were only slightly sensitive to cephems, viz. CEZ, CTM, CPZ and CAZ. 7. Enterobacter cloacae was sensitive to gentamicin and AMK which are aminoglycosides, but showed a bimodal pattern of sensitivity to CPZ, CAZ and CZON, all of which are cephems, and to quinolones, OFLX and CPFX.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). I. Susceptibility distribution]

Isolation frequencies and sensitivities to antibacterial and antibiotic agents were investigated on 801 bacterial strains isolated from patients with urinary tract infections in 9 hospitals during the period of June to November 1988. Of the above total bacterial population, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus spp. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. 1. Enterococcus faecalis: Vancomycin was most active with its MIC90 < or = 0.78 microgram/ml. Ampicillin, piperacillin, ofloxacin (OFLX), ciprofloxacin (CPFX) and imipenem (IPM) were also active. 2. Staphylococcus aureus: Arbekacin and minocycline were most active with their MIC90s 0.39 microgram/ml and 1.56 micrograms/ml, respectively. Among penicillins, dicloxacillin was the most active. Activities of cephems were considerably lower. 3. E. coli: Most of the agents were tested active. Particularly the second and third generation cephems were active in a range of < or = 0.10-0.20 microgram/ml. Carumonam (CRMN), IPM, OFLX and CPFX were also active with MIC90s < or = 0.10 microgram/ml. 4. Klebsiella pneumoniae CRMN and IPM were highly active. Penicillins generally showed lower activities. Cephems and new quinolones had high activities with their MIC90s in a range of 0.39-0.78 microgram/ml. 5. Proteus mirabilis: The third generation cephems were active with their MIC90s in a range of < or = 0.10-0.20 microgram/ml. CRMN, OFLX and CPFX were also active with their MIC90s < or = 0.10 microgram/ml, 0.39 microgram/ml and 0.20 microgram/ml, respectively. 6. Pseudomonas aeruginosa: IPM and tobramycin were active with their MIC90s 1.56 micrograms/ml and 3.13 micrograms/ml, respectively. CRMN and new quinolones showed MIC80s of 25-100 micrograms/ml. Most of penicillins and cephems were not active. 7. Other Gram-negative rods: Against Citrobacter freundii, Enterobacter cloacae and Serratia marcescens, IPM, CPFX and OFLX were active. Penicillins and cephems were not so active. CRMN was active against S. marcescens with its MIC80 at 6.25 micrograms/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)     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1985). I. Susceptibility distribution

The results of determinations of sensitivities of bacterial strains to various antibiotics are summarized as follows: 1. Against Escherichia coli, ofloxacin (OFLX) showed the strongest activity among oral antibacterial and antibiotic agents. Its MIC90 was below 0.10 micrograms/ml. The next strongest activity was found in mecillinam (MPC), cefaclor (CCL) and pipemidic acid (PPA); MIC90's of these agents 3.13 micrograms/ml. Cefotiam (CTM), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX) and latamoxef (LMOX) had MIC90 below 0.39 micrograms/ml. MIC90's of cefmetazole (CMZ) and cefoperazone (CPZ) were 1.56 micrograms/ml. Aztreonam (AZT) and carumonam (CRMN) in the monobactam group showed strong activities with MIC90's at 0.20 micrograms/ml. 2. Although Klebsiella pneumoniae had a strong resistance to ampicillin (ABPC) and showed relatively low sensitivities to other oral antibacterial and antibiotic agents, OFLX maintained high activity against this species and showed MIC90 of 0.39 micrograms/ml. Among injectable antibiotics, third generation cephems showed the strongest activity to this species with MIC90 of CZX below 0.10 micrograms/ml, of CTX and CMX 0.20 micrograms/ml, and of LMOX 0.78 micrograms/ml. MIC90 of CPZ was 6.25 micrograms/ml, which was the same as those of cefazolin (CEZ) and cefoxitin (CFX). CTM had similar MIC90 to LMOX, namely, 1.56 micrograms/ml. MIC90 of CMZ was 3.13 micrograms/ml. Monobactams AZT and CRMN showed strong activities to this species; their MIC90's were below 0.10 micrograms/ml and 0.20 micrograms/ml. 3. Although Citrobacter freundii generally exhibited low sensitivities to antibacterial and antibiotic agents examined, it showed high sensitivity to OFLX, at MIC80 of 0.78 micrograms/ml. This species showed low sensitivities to MPC, nalidixic acid (NA), PPA, and sulfamethoxazole-trimethoprim (ST). Among injectable antibiotics, LMOX and CMX had activities against this species; namely, MIC80's were 6.25 and 3.13 micrograms/ml, respectively. Among monobactams, AZT showed MIC80 of 12.5 micrograms/ml, and CRMN had that of 6.25 micrograms/ml. 4. Against Enterobacter cloacae, the strongest antibacterial activity was found with OFLX which had MIC90 of 0.39 micrograms/ml. A relatively strong activity was seen with MPC. MIC80 of MPC was 1.56 micrograms/ml. Except to CTM, this species had poor sensitivities to injectable first and second generation cephems, and their MIC80's were over 200 micrograms/ml. MIC80 of CTM was 25 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1985). III. Secular changes in susceptibility

Sensitivities to antimicrobial agents of Escherichia coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., Proteus spp., Pseudomonas aeruginosa and Serratia marcescens isolated from infected patients were evaluated and compared according to the types of their infections, i.e., simple and complicated urinary tract infections with or without indwelling catheter. There were no apparent decreases in the sensitivity of E. coli isolated from patients with simple urinary tract infections. When data obtained in 1982-1985 were summarized, it was found that a new quinoline derivative, ofloxacin (OFLX), showed the strongest activity among oral antimicrobial and antibiotic agents. This agent inhibited 100% of bacterial growth at MIC of 1.56 micrograms/ml. The next strongest activity was found with mecillinam (MPC) which showed 89.3% growth inhibition at the same concentration. Cefaclor (CCL) also showed 84.9% growth inhibition at the same concentration. When sensitivities of E. coli isolated from patients with complicated urinary tract infections with or without indwelling catheter to first and second generation cephems were determined, cefotiam (CTM), which inhibited 88.9%: 91.4% bacterial growth at MIC of 0.39 micrograms/ml, had the strongest activity among CTM, cefazolin (CEZ), cefoxitin (CFX) and cefmetazole (CMZ). Among third generation cephems, including cefmenoxime (CMX), latamoxef (LMOX), ceftizoxime (CZX), cefotaxime (CTX) and cefoperazone (CPZ), the strongest activity was observed with CZX, and the agent having the next strongest activity was CMX. LMOX and CPZ showed relatively low activities. Carumonam (CRMN) and aztreonam (AZT), monobactams, showed strong activities against E. coli. As for Klebsiella spp., activities of pencillins against these strains were low. When activities of oral cephems (cephalexin (CEX) and CCL) and of a quinoline derivative OFLX against these strains were determined, OFLX showed strong activity; i.e., the growth of Klebsiella spp. isolated from complicated urinary tract infections was inhibited at 87.2%: 82.1% at MIC of 0.20 micrograms/ml.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2002). III. Secular changes in susceptibility

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as urinary tract infections (UTIs) in 13 institutions in Japan were supplied between August 2002 and July 2003. The susceptibilities of these bacteria to various antimicrobial agents were examined. The bacteria were divided into 2 groups consisting of uncomplicated UTIs and complicated UTIs (with and without indwelling catheter) based on their isolation origins. The results were compared with those obtained between 1993 and 2001. The drug sensitivity of S. aureus in this year was similar to those in up to the previous year and S. aureus showed the best susceptibility to vancomycin. The drug sensitivity of E. faecalis in this year also was similar to those in up to the previous year. The drug sensitivity of E. coli in this year was generally good except penicillins and was similar to those in up to the previous year. Among cephems, cefozopran (CZOP) and cefpirome (CPR) showed the highest potency (MIC90: < or = 0.125 microg/mL). An antibacterial activity of cefotiam (CTM) was similar to it in 10 years ago and was fine (MIC90: < or = 1 microg/mL). The sensitivity of E. coli to carbapenems and carumonam (CRMN) also was good like to CZOP. However, the sensitivity of the complicated UTIs group to quinolones decreased after 2000 and was suggested to develop the resistance to the drug. The drug sensitivity of Klebsiella spp. in this year also was similar to those in up to the previous year. The bacteria showed good susceptibility (MIC: < or = 0.125 microg/mL) to cefmenoxime (CMX), CPR, cefixime (CFIX), flomoxef (FMOX), and CZOP among cephems. The drug sensitivity of P. aeruginosa was generally low. Most of the bacteria were little sensitive to cephems except CZOP and ceftazidime (CAZ). The sensitive bacteria to CZOP and ceftazidime (CAZ) were observed to be 26.8% (15/56 strains) and 39.3% (22/56 strains) in complicated UTIs group, respectively. The sensitivity profile of P. aeruginosa to the other tested drugs was not much different from that in up to the previous year. However, the sensitivity of the bacteria to carbapenems tended to decrease after 2000, and the low sensitive strains (MIC: > or = 256 microg/mL) were detected at 22.2% (2/9 strains) in the uncomplicated UTIs group and 3.6% (2/56 strains) in the complicated UTIs group.     

Antibiotic sensitivity of bacteria isolated from patients at 6 hospitals in Osaka

We examined MICs of 6 oral new quinolones and 4 oral cephems against bacteria isolated from patients at 6 hospitals in Osaka during the period from January to June in 1990, and the following results were obtained. 1. All species excluding Streptococcus pyogenes were more sensitive with less frequencies of resistance to new quinolones than to cephems. In new quinolones, tosufloxacin (TFLX) was the most active against Gram-positive cocci and ciprofloxacin (CPFX) and TFLX had the highest activities against Gram-negative rods. 2. Resistant (MIC of CPFX greater than or equal to 3.13 micrograms/ml) strains to new quinolones were observed at higher frequencies than 10% among Staphylococcus spp., Enterococcus faecalis, Citrobacter freundii, Morganella morganii, Providencia rettgeri, Serratia spp., Pseudomonas aeruginosa, Pseudomonas cepacia and Xanthomonas maltophilia. 3. The frequency of Staphylococcus aureus resistant to new quinolones isolated from in-patients or urine was significantly higher than that from out-patients or other sources. On the other hand, there was no significant difference in resistance frequencies of P. aeruginosa due to types of patients or sources. But, there were significant differences in frequencies of resistant organisms of either species to new quinolones among hospitals. 4. Twenty-seven strains (19.7%) of 137 S. aureus strains examined were methicillin-resistant, and they were similarly resistant to new quinolones also. Methicillin susceptible S. aureus were also similarly sensitive to new quinolones.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2002). I. Susceptibility distribution

The bacterial strains isolated from 491 patients diagnosed as having urinary tract infections (UTIs) in 13 institutions in Japan were supplied between August 2002 and July 2003. The susceptibilities of them to many kinds of antimicrobial agents were investigated. Of them, 578 strains were estimated as causative bacteria and used for the investigation. The number of them was 578 strains consisting of 177 gram-positive bacterial strains (30.6%) and 401 gram-negative bacterial strains (69.4%). Against Staphylococcus aureus, vancomycin (VCM) showed a strong activity and prevented the growth of all strains with 1 microg/mL. The susceptibility of Staphylococcus epidermidis to cephems including cefotiam (CTM) was relatively good. Against Enterococcus faecalis, ampicillin (ABPC), imipenem (IPM), and VCM showed the strongest antibacterial activity (MIC90: 2-4 microg/mL). In addition, the low sensitive strains (MIC: > or = 256 microg/mL) to clarithromycin (CAM) were detected at 48.3% but none to cefozopran (CZOP). The antibacterial activity of cephems to Escherichia coli was generally good, and especially CZOP and cefpirome (CPR) showed the highest activity (MIC90: < or = 0.125 microg/mL). Quinolone resistant E. coli was detected at frequency of 13.5%, which was higher than that in the last year. The antibacterial activity of cephems to Citrobacter freundii was generally low but CZOP and CPR had a strong acitivity (MIC90: 0.25 and 0.5 microg/mL, respectively). The antibacterial activity of cephems to Klebsiella pneumoniae was good and especially cefmenoxime (CMX), cefixime (CFIX), flomoxef (FMOX), CPR, and CZOP showed stronger activity (MIC90: < or = 0.125 microg/mL). Against Serratia marcescens, meropenem (MEPM) had the highest antibacterial activity followed by CPR and CZOP. Against Proteus mirabilis, CMX, ceftazidime (CAZ), CPR, MEPM, carumonam (CRMN), and levofloxacin (LVFX) showed the strongest activity (MC90: < or = 0.125 microg/mL). Among other cephems, CZOP and CFIX were also strong (MIC90: 0.25 microg/mL). The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs were ranged from 64 to > or = 256 microg/mL except IPM and amikacin (AMK) having 16 microg/mL. The antibacterial activity of CZOP was relatively good (MIC50: 8 microg/mL).     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004). I. Susceptibility distribution

The bacterial strains isolated from 490 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of them to many kinds of antimicrobial agents were measured. Of them, 577 strains were estimated as causative bacteria and used for the measurement. The strains consisted of 156 gram-positive bacterial strains (27.0%) and 421 gram-negative bacterial strains (73.0%). Against Staphylococcus aureus, arbekacin (ABK), vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Enterococcus faecalis, ampicillin (ABPC) and VCM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially cefozopran (CZOP) and cefpirome (CPR) showed the strongest activity (MIC90: < or = 125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): > or = 4 microg/mL] was detected at frequency of 18.8%, which was higher than that in the last year. Against Klebsiella pneumoniae, CZOP, meropenem (MEPM), and carumonam (CRMN) showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. The antibacterial activity of the other cephems was relatively good, and decrease in their activity observed in the last year study was not recognized. Against Serratia marcescens, imipenem (IPM) and gentamicin (GM) had the strongest antibacterial activity. Against Proteus mirabilis, CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. MEPM prevented the growth of all strains with 0.25 microg/mL. Next, cefmenoxime (CMX), ceftazidime (CAZ), CZOP, cefixime (CFIX), cefpodoxime (CPDX), and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to > 128 microg/mL except IPM and MEPM having 16 microg/mL. The antibacterial activities of CZOP and CAZ were considered to be relatively good on MIC50 comparison (MIC50: 2 microg/mL).     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2004). III. Secular changes in susceptibility

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2004 and July 2005. The susceptibilities of these bacteria to various antimicrobial agents were measured. The bacteria were divided into 2 groups consisting of uncomplicated UTIs and complicated UTIs (with and without indwelling catheter) based on their isolation origins. The results were compared with those obtained between 1995 and 2003. The drug sensitivity of S. aureus in this year was similar to those in up to the previous year and S. aureus showed the best susceptibility to vancomycin (VCM) and arbekacin (ABK). The drug sensitivity of E. faecalis in this year also was similar to those in up to the previous year. The susceptibility of E. coli to cephems in this year was generally good and was similar to those in up to the previous year. MIC90 of cefozopran (CZOP) was the most stable and 0.125 microg/mL or less since 1995. The susceptibility of E. coli to cefpirome (CPR) and cefotiam (CTM) also was good but to cefaclor (CCL), cefixime (CFIX), and cefpodoxime (CPDX) was largely decreased in complicated UTI groups. The sensitivity of E. coli to carbapenems also was good but to carumonam (CRMN) tended to decrease. The susceptibility of E. coli to quinolones, however, has largely changed and has decreased since 2003 in uncomplicated UTIs and 2000 in complicated UTIs. That was suggested the development of the resistance to the drug. The susceptibility of Klebsiella spp. to cefazolin (CEZ), CTM, CCL, CPDX, and cefditoren (CDTR) decreased in the previous year and recovered to the year before the previous year in this year. The susceptibility of Klebsiella spp. to other cephems was stable since 1995, especially against CZOP, the highest sensitivity (MIC90: < or = 0.125 microg/mL) was maintained. The susceptibility of Klebsiella spp. to carbapenems and CRMN also was good. The susceptibility of Klebsiella spp. to aminoglycosides was lower than to CZOP but was stable since 1995. The susceptibility of P. aeruginosa was generally low and has largely changed against the majority of the agents since 1995. The susceptibility of P. aeruginosa isolated from uncomplicated UTIs has largely changed against ceftazidime (CAZ), cefsulodin (CFS), CZOP, imipenem (IPM), meropenem (MEPM), aztreonam (AZT), CRMN, gentamicin (GM), and tobramycin (TOB). The susceptibility of P. aeruginosa isolated from complicated UTIs has largely changed against CSF, CZOP, MEPM, GM, and ciprofloxacin (CPFX). The susceptibility of P. aeruginosa isolated from complicated UTIs has been stable against amikacin (AMK). For annual changes in MIC50, TOB and IPM had a relatively stable and high activity (MIC50: 0.5-2 microg/mL).     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1986). I. Susceptibility distribution

Susceptibilities to various antibacterial and antibiotic agents of bacterial strains isolated from urinary tract infections at 8 hospitals in Japan from July to October in 1986 are summarized as follows. 1. Enterococcus faecalis was susceptible to sulfamethoxazole/trimethoprim (ST) and imipenem (IPM) with MIC90s of 0.78 and 1.56 microgram/ml. Minocycline had the strongest activity against Staphylococcus aureus; the MICs for all strains tested were lower than 0.39 microgram/ml. The MIC80s of dicloxacillin, and arbekacin (HBK) were 0.20 and 0.78 microgram/ml, respectively. Among the cephems, the MIC80 of flomoxef was 25 micrograms/ml, whereas those of cefmenoxime (CMX) and cefotiam (CTM) were 50 micrograms/ml. 2. Escherichia coli was most susceptible to ofloxacin (OFLX) among the oral antibacterial and antibiotic agents tested. OFLX showed the minimum inhibitory concentration against 90% (MIC90) of the 274 strains of E. coli tested to be lower than 0.10 microgram/ml. The antibacterial activities of the third generation cephems such as CMX and latamoxef (LMOX) were the strongest among the injectable antibiotics tested. The MIC90s of CMX and LMOX were lower than 0.10 and 0.20 microgram/ml, respectively. CTM and cefmetazole, the second generation cephems, were also highly active against E. coli with MIC90s of 0.39 and 1.56 micrograms/ml, respectively. 3. Among the oral antibacterial and antibiotic agents tested, OFLX was the most active against Klebsiella pneumoniae. Its MIC90 was 0.78 microgram/ml. Among the injectable antibiotics tested, CMX was the strongest with an MIC90 of 0.20 microgram/ml; MIC90 of CTM and LMOX were 0.39 microgram/ml. 4. The tested antibacterial and antibiotic agents were generally less active against Citrobacter freundii than against other bacteria. The MIC80 of OFLX was 0.39 microgram/ml. Gentamicin (GM) and ST were slightly active against C. freundii. Among the cephems, CMX had the MIC80 of 25 micrograms/ml. 5. Enterobacter cloacae was less susceptible to the cephems tested. OFLX, GM, and mecillinam were active against this bacteria with MIC80s of 0.78, 0.78 and 1.56 micrograms/ml, respectively. 6. Among the oral antibacterial and antibiotic agents and penicillins examined, piperacillin (PIPC) was the most active against Proteus mirabilis. Its MIC90 was 0.39 microgram/ml. Those of sulbenicillin, cefaclor, ampicillin, OFLX, and ST were 0.78, 0.78, 1.56, 3.13 and 3.13 micrograms/ml, respectively. CMX was highly active against P. mirabilis with an MIC90 of less than or equal to 0.10 microgram/ml; LMOX followed with an MIC90 of 0.20 microgram/ml among the injectable antibiotics tested. CTM was also active against this bacterium; the MIC90 was 0.39 microgram/ml. 7. The antibacterial and antibiotic agents were generally only slightly active against Proteus vulgaris.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2003). I. Susceptibility distribution

The bacterial strains isolated from 565 patients diagnosed as having urinary tract infections (UTIs) in 14 institutions in Japan were collected between August 2003 and July 2004. The susceptibilities of them to many kinds of antimicrobial agents were investigated. Of them, 701 strains were estimated as prophlogistic bacteria and used for the investigation. The strains consisted of 258 Gram-positive bacterial strains (36.8%) and 443 Gram-negative bacterial strains (63.2%). Against Staphylococcus aureus, vancomycin (VCM) showed the strongest activity and prevented the growth of all strains with 2 microg/mL. Against Streptococcus agalactiae, ampicillin (ABPC), cefozopran (CZOP), imipenem (IPM), and clarithromycin (CAM) showed a strong activity and the MIC90 was 0.125 microg/mL or less. Against Enterococcus faecalis, VCM, ABPC, and IPM showed a strong antibacterial activity. The antibacterial activity of cephems to Escherichia coli was generally good, and especially CZOP and cefpirome (CPR) showed the strongest activity (MIC90: < or = 0.125 microg/mL). Quinolone resistant E. coli [MIC of ciprofloxacin (CPFX): > or =4 microg/mL] was detected at frequency of 15.7%, which was higher than that in the last year. Against Klebsiella pneumoniae, meropenem (MEPM) showed the strongest activity and next, the antibacterial activity of CRMN and CZOP was good. The antibacterial activity of the other cephems, however, significantly decreased, compared with that evaluated in last year. Against Serratia marcescens, MEPM had the strongest antibacterial activity. Against Proteus mirabilis, MEPM and CRMN showed the strongest activity and prevented the growth of all strains with 0.125 microg/mL or less. Nest, cefmenoxime (CMX), ceftazidime (CAZ), cefixime (CFIX), cefpodoxime (CPDX), CPR, CZOP, and cefditoren (CDTR) showed a strong activity. The antibacterial activity of the drugs to Pseudomonas aeruginosa was generally low, and MIC90 of all the drugs was ranged from 32 to < or = 256 microg/mL except IPM and amikacin (AMK) having 16 microg/mL. The antibacterial activity of CZOP was relatively good (MIC50: 2 microg/mL).     

Comparison of in vitro antibacterial activities of new cephems against clinical organisms (isolated between June 1983 and January 1984)

We compared the in vitro antibacterial activities of ceftizoxime (CZX), cefotaxime (CTX), cefmenoxime (CMX), cefoperazone (CPZ), ceftazidime (CAZ), latamoxef (LMOX) and cefotetan (CTT) against 2,729 strains of 11 organisms freshly isolated from 10 medical institutions in Japan between June 1983 and January 1984 and obtained the following results: Against S. pyogenes, LMOX and CTT, which have the methoxy group at the 7 position, were less active than the other drugs. LMOX inhibited 80% of S. pyogenes at 0.78 micrograms/ml; CTT, at 1.56 micrograms/ml; but CZX and CTX inhibited 100% at 0.025 micrograms/ml or lower; CMX, at 0.05 micrograms/ml; and CPZ and CAZ, at 0.20 micrograms/ml. Against H. influenzae, E. coli, K. pneumoniae, P. mirabilis and indole-positive Proteus, these test antibiotics, especially CZX, CTX and CMX, which have the aminothiazolyl methoxyimino group, were potently active. Against S. marcescens CZX and CAZ were more active than the other drugs and against P. aeruginosa CAZ was more active than the other drugs. The test organisms did not tend to acquire resistance to these cephems when our results were compared with the results obtained at the development period.     

Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2000--I. Gram-positive 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, carbapenems, and penicillins. Fifteen species, 1,062 strains, of Gram-positive bacteria were isolated from the clinical materials annually collected from January to December, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA; n = 127), methicillin-resistant Staphylococcus aureus (MRSA; n = 123), Staphylococcus epidermidis (n = 104), Staphylococcus haemolyticus (n = 58), Streptococcus pyogenes (n = 100), Streptococcus agalactiae (n = 50), Streptococcus pneumoniae (n = 125), Enterococcus faecalis (n = 150), Enterococcus faecium (n = 50), Enterococcus avium (n = 50), and Peptostreptococcus spp. (P. anaerobius, P. asaccharolyticus, P. magnus, P. micros, P. prevotii; n = 125). CZOP possessed stable antibacterial activities against all strains tested throughout 5 years. The MIC90 of CZOP against MRSA and S. haemolyticus tended to decrease while against S. pneumoniae and Peptostreptococcus spp., tended to increase year by year. However, the MIC90 just changed a little and were consistent with the results from the studies performed until the new drug application approval. Increases in the MIC90 against S. pneumoniae were also observed with cefpirome (CPR), cefepime (CFPM), flomoxef (FMOX), sulbactam/cefoperazone (SBT/CPZ), and imipenem (IPM). Increases in the MIC90 against Peptostreptococcus spp. were also observed with ceftazidime (CAZ), CPR, CFPM, FMOX, SBT/CPZ, and IPM. The decreases in the sensitivities were not always considered to depend upon generation of resistant bacteria because the annual MIC range of each antibacterial agent was almost generally wide every year and the annual sensitivity of each strain to the agents extremely varied. In conclusion, the annual antibacterial activities of CZOP against the Gram-positive bacteria did not considerably change. It, therefore, was suggested that CZOP had maintained high antibacterial activity during 5 years of post-marketing.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). III. Secular changes in susceptibility

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June 1998 to May 1999, and the results were compared with those obtained during the same period from 1990 to 1997 in uncomplicated UTIs and complicated UTIs. Among E. faecalis strains, those with low susceptibilities to almost drugs have increased in the latest period. All 5 S. aureus strains isolated from uncomplicated UTIs were the most susceptible to gentamicin (GM). Over 50% of S. aureus strains isolated from complicated UTIs were susceptible to GM, and on the contrary the resistant strains have increased with the MIC90 of 256 micrograms/ml or above. Among S. aureus strains isolated from complicated UTIs, those with low susceptibilities to arbekacin (ABK) have increased in the latest period compared to those during period of 1996-1997, and the MIC90s of them have changed into the lower state from 1 microgram/ml in 1996-1997 to 4 micrograms/ml in 1998. S. aureus strains have continued high susceptibilities to vancomycin (VCM). The susceptibilities to minocycline (MINO) of E. coli showed MIC90: 4 micrograms/ml in 1997, but those have returned in the latest period in uncomplicated UTIs. The MIC90s of ofloxacin (OFLX) to E. coli isolated from uncomplicated and complicated UTIs have been lower 2-3 classes in the latest period than those in 1997. Among Klebsiella spp. strains isolated from uncomplicated UTIs, those with low susceptibilities to almost cephems had increased in 1997, but few of them were detected in the latest study. The sensitive strains of P. aeruginosa to almost drugs have increased during the latest period. The MIC50s of cefozopran (CZOP) and OFLX against P. aeruginosa were the best in our history. The sensitive strains of P. aeruginosa to ceftazidime (CAZ) have increased and its percentage was 30%. Piperacilline (PIPC), cefoperazone (CPZ), GM and OFLX resistant P. aeruginosa strains have increased in the latest period.     

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.     

Phototoxicity studies of pazufloxacin mesilate,a novel parenteral quinolone antimicrobial agent--in vitro and in vivo studies

Phototoxicity of pazufloxacin mesilate (PZFX mesilate), a novel parenteral quinolone antimicrobial agent, were evaluated in vitro and in vivo studies. In vitro, phototoxicity for cultured cells of PZFX, which is active principle of PZFX mesilate, was studied, and stability for long-wavelength ultraviolet (UVA) was examined. In vivo, phototoxicity tests in guinea pigs and rats, and photoallergenicity tests in guinea pigs were conducted. In the phototoxicity test on cultured cells, CHL/IU cells were irradiated UVA of 300-3000 mJ/cm2 in the presence of PZFX, ofloxacin (OFLX), lomefloxacin (LFLX) or sparfloxacin (SPFX) at 10 micrograms/mL. Phototoxic potencies for cultured cells of the quinolones tested were SPFX > LFLX > OFLX > PZFX. In addition, changes in ultraviolet absorption spectrum and residual rate of PZFX, OFLX, LFLX and SPFX were examined after UVA irradiation of 300-3000 mJ/cm2 to each solution. PZFX was stable for UVA compared with OFLX and LFLX. In the phototoxicity test of guinea pigs, each quinolone was administered intraperitoneally daily for 7 days, and UVA of about 11 J/cm2 was irradiated at 30 minutes after the last administration. Dose levels of each quinolone were 65 and 130 mg/kg of PZFX mesilate (dose levels converted to PZFX: 50 and 100 mg/kg), 50 and 100 mg/kg of nalidixic acid (NA), 100 mg/kg of OFLX, enoxacin (ENX), ciprofloxacin (CPFX), LFLX and SPFX. Grade of skin reaction (erythema) at 24 hours after UVA irradiation decreased in the order: SPFX > CPFX > NA > ENX = OFLX > LFLX > PZFX mesilate. Thus, PZFX mesilate was found to have the weakest phototoxicity. In the maximum plasma concentration of quinolones from 0.5 to 2.5 hours after administration, corresponding to the time of UVA irradiation, the concentration of the group administered PZFX mesilate was about 4.1 times higher than that of CPFX group, and about 1.3 times higher than that of SPFX group. The area under the blood concentration-time curve (AUC0.5-2.5) of the group administered PZFX mesilate was the same as that of SPFX group, and about 3.2 times larger than that of CPFX group. These data showed that phototoxicity of PZFX mesilate was also weaker than that of CPFX or SPFX in consideration of AUC0.5-2.5. In the phototoxicity test of rats injected intravenously, no phototoxicity was observed at 130 mg/kg of PZFX mesilate. In the photoallergenicity test of guinea pigs, no photoallergenicity was observed by PZFX mesilate. As mentioned above, from in vitro studies PZFX was found to be stable for UVA irradiation compared with OFLX and LFLX, and phototoxicity for cultured cells of PZFX was weaker than that of SPFX, LFLX or OFLX. In addition, from in vivo studies phototoxicity of PZFX mesilate was found to be weaker than that of NA, OFLX, ENX, CPFX, LFLX or SPFX, and no photoallergenicity was observed. Therefore, photosensitive potency of PZFX mesilate might be less than that of other quinolones.     

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.     

Quinolone antibacterial-agent-induced cutaneous phototoxicity: ear swelling reactions in Balb/c mice

The phototoxic potentials of quinolone derivatives and the possibility of free radical contribution to their phototoxicity were investigated by measuring increments in ear thickness. Balb/c mice, fasted overnight, were orally administered ofloxacin (OFLX), lomefloxacin (LMFX), enoxacin (ENX), ciprofloxacin (CPFX) and DR-3355 (the s-isomer of OFLX), and immediately exposed to ultraviolet-A light (UVA: 320-400 nm) for 4 h (21.6 joules/cm2). Measurement of ear thickness was carried out 0, 24 and 48 h after the end of irradiation. The time-course profiles of ear thickness varied with both the doses and the quinolone used, but linear dose-response curves were obtained from the data 24 h after irradiation ended. The 50% ear thickness increment-inducing doses of LMFX, ENX, OFLX, CPFX and DR-3355 were calculated as 24.8, 81.9, 428.0, 457.9 and 526.6 mg/kg, respectively. The phototoxic potential of these quinolones coincided with the data obtained previously by measuring the incidence of erythema on the ears. Pretreatment with butylated hydroxtoluene, a free radical scavenger, almost completely prevented all swelling reactions induced by the quinolones. These results suggest that the degree of phototoxicity induced by the quinolones used could depend on the balance between the generation of free radicals and the effectiveness of the defense systems against toxic radicals.