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)     

Comparison of in vitro activity of first, second and third generation cephem antibiotics against various pathogens isolated from clinical materials in 1983

In vitro susceptibilities of 3,286 strains of various pathogens isolated from clinical materials in 1983 to various cephem antibiotics were studied using the Showa disk diffusion test. The following antibiotics were evaluated: cephalexin (CEX), cephalothin (CET), cefazolin (CEZ), cefotiam (CTM), cefoxitin (CFX), cefmetazole (CMZ), cefotaxime (CTX), cefoperazone (CPZ), ceftizoxime (CZX), cefmenoxime (CMX) and latamoxef (LMOX). S. aureus: Susceptible strains to CET, CEZ, CTM, CFX and CMZ with MIC less than 15 micrograms/ml accounted for 93, 75, 93, 70 and 96% of the strains tested, while those to CTX, CPZ, CZX, CMX and LMOX for 89, 65, 61, 86 and 62%, respectively. Susceptible strains to CEX at MICs less than or equal to 20 micrograms/ml were 60%. Prevalence of bacterial resistance to CEX and CEZ, which have been used extensively, was greater than that to CET, CTM or CMZ, showing a bimodal distribution of MICs. The third generation cephems studied, in general, also showed bimodal distributions of MICs. S. pyogenes: All strains studied were susceptible to CET, CTX, CPZ, CZX, CMX and LMOX at MICs less than or equal to 15 micrograms/ml. However, susceptible strains to CEZ, CTM, CFX and CMZ accounted for 95, 95, 80 and 90%, respectively, while those to CEX at MICs less than or equal to 20 micrograms/ml for 79%. S. pneumoniae: At MICs less than 3 micrograms/ml, all strains were susceptible to all cephem antibiotics tested. S. faecalis: Only a very few strains were susceptible to these antibiotics. E. coli, K. pneumoniae and Proteus spp.: Susceptible strains of E. coli and K. pneumoniae to CEX at MICs less than or equal to 20 micrograms/ml accounted for 80 and 81% of the strains tested, while those of indole negative and positive Proteus for 69 and 4%, respectively. Strains of E. coli susceptible to CET, CEZ, CTM, CFX and CMZ at MICs less than or equal to 15 micrograms/ml were 78 to 96%, while those to CTX, CPZ, CZX, CMX and LMOX were 94 to 100%. Those of K. pneumoniae to these 2 groups of antibiotics were 81 to 95% and 94 to 100%, respectively. Susceptible strains of indole negative Proteus to the former group were 81 to 93% and those to the latter were 100%.(ABSTRACT TRUNCATED AT 400 WORDS)     

Distribution and changes in the susceptibility of bacteria isolated from clinical samples. II

In vitro activity of antimicrobial agents such as ABPC, SBPC, MPC, CEZ, CTM, CMZ, CTX, CMX, CZX, LMOX, CPZ, CFS and GM against major clinical isolates, S. aureus, S. pyogenes, E. coli, K. pneumoniae, P. mirabilis, C. freundii, Enterobacter spp., S. marcescens, P. vulgaris and P. aeruginosa, was examined. In this paper, we will report the susceptibility of S. aureus, S. pyogenes, E. coli, K. pneumoniae and P. mirabilis during a three-year period, 1981 to approximately 1983. CEZ- and GM-resistant S. aureus has markedly increased and occupied 24% and 18%, respectively, in 1983. CMZ and CFS have showed potent activity against CEZ-resistant S. aureus. It seems that the abuse of third generation-cephems and new oral cephalosporins is closely related with the increase of cephems-resistant S. aureus. The penicillin- and cephem-resistant strains of S. pyogenes could not be found in our study. Quite a few strains of E. coli, K. pneumoniae and P. mirabilis are resistant to penicillins, and also there is no appreciable change in susceptibility. Some strains of E. coli, K. pneumoniae and P. mirabilis showed low susceptibility to CPZ, but all strains showed high susceptibility and no change in susceptibility to third generations, and these strains showed no tendency to decrease in susceptibility to GM.     

The antibacterial activity of new cephem antibiotics against clinical isolates. A comparison of the antibacterial activity of cefotaxime with 6 other antibiotics

During the period from May through July 1981, a comparative study was carried out on the antibacterial activities of cefotaxime (CTX) and ceftizoxime (CZX), cefoperazone (CPZ), latamoxef (LMOX), cefotiam (CTM), cefmetazole (CMZ) and cefazolin (CEZ). CTX and these other cephem antibiotics were tested against fresh clinical isolates which had been obtained from clinical materials by the laboratories of 14 participating medical institutions. 1. The clinical isolates were obtained from various clinical materials in the following decreasing order: urine, sputum and pus/discharge; 85.7% of the isolates came from these materials. 2. Concerning the sources of each species of clinical isolates, it was found that P. aeruginosa was isolated from the greatest number -9- of different clinical materials. This was followed by E. coli and E. cloacae, each isolated from 8 different clinical materials, and C. freundii and E. aerogenes, each found in 7 different clinical materials. 3. In relation to S. pyogenes, S. agalactiae and S. pneumoniae, CTX showed the best antibacterial activity; the second most potent antibiotic was CZX. CMZ and LMOX were found to show relatively high MIC values for those species. Against S. aureus, CEZ showed the best antibacterial activity, but 3 resistant strains had MICs of greater than 100 micrograms/ml. 4. With regard to Gram-negative bacteria, CTX and CZX showed the best antibacterial activities for all of the species, except for P. aeruginosa. These were followed, in order, by LMOX and CPZ. Compared with these 4 antibiotics, CTM, CMZ and CEZ were found to have inferior antibacterial activities against these bacteria. In relation to P. aeruginosa, the peak of the MIC distribution for CPZ was 6.25 micrograms/ml, and this was the best antibacterial activity detected with the various antibiotics tested. This was followed by CTX (25 micrograms/ml) LMOX (25 micrograms/ml) and CZX (50 micrograms/ml). CTM had an MIC of 100 micrograms/ml for 1 strain, and MICs of greater than 100 micrograms/ml for all of the other strains of P. aeruginosa, indicating them to be resistant to this antibiotic. All of the strains were resistant to CMZ and CEZ, showing MICs of greater than 100 micrograms/ml. 5. For each of the tested antibiotics, no correlation was found between the MIC and the serogroup for either P. aeruginosa or S. marcescens.     

Antimicrobial activity of sulbactam/cefoperazone. Comparison with other new cephems

Antimicrobial activities of sulbactam/cefoperazone (SBT/CPZ) against 50 fresh clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa were compared to those of CPZ, Cefotiam (CTM), Cefotaxime (CTX) and Latamoxef (LMOX). Minimal inhibitory concentrations (MIC's) of SBT and CPZ mixed in a ratio of 1:1 were determined by the dilution method using Mueller-Hinton agar and expressed by absolute concentrations of CPZ. Antimicrobial activities of SBT/CPZ against principally penicillinase (PCase) producing bacteria, i.e., S. aureus, E. coli, K. pneumoniae, P. mirabilis, were superior to those of CPZ alone. The presence of SBT in concentrations around 0.39 approximately 1.56 micrograms/ml clearly enhanced CPZ's antimicrobial activities against these PCase producing strains. The synergistic antimicrobial effects of SBT in combination with CPZ were less pronounced against principally cephalosporinase (CEPase) producing bacteria, i.e., C. freundii, Enterobacter spp., S. marcescens, P. vulgaris, and P. aeruginosa, and exerted with SBT at concentrations around 3.13 approximately 12.5 micrograms/ml. Comparative antimicrobial activities indicated by MIC80's of tested agents showed that SBT/CPZ had more stable activities against bacteria ranging from Gram-positive to Gram-negative bacteria than CTM, CTX and LMOX. MIC's of SBT/CPZ were higher than 25 micrograms/ml against 8% of S. aureus, 18% of C. freundii, 10% of Enterobacter spp., 26% of S. marcescens, 2% of P. vulgaris, and 18% of P. aeruginosa. These resistant strains against which the addition of SBT showed no synergism, may possess other mechanism of resistance than beta-lactamase production. It is concluded that the presence of CPZ resistant strains is an actual current problem and not an imaginary future problem, and that the number of resistant strains against other new cephems which have different chemical structure from CPZ is increasing. When these present bacteriological environments are considered, the appearance of SBT/CPZ in the clinical practice is timely and meaningful.     

Distribution and changes in the susceptibility of bacteria isolated from clinical samples. III

This report presents data concerning in vitro activity of antimicrobial agents against Citrobacter freundii, Enterobacter spp., Serratia marcescens and Proteus vulgaris isolated from patients with complicated urinary tract infections and against Pseudomonas aeruginosa isolated from surgical wounds with postoperative infection and exudate from superficial abscesses. There was a marked increase of resistant strains of C. freundii, Enterobacter spp. and S. marcescens to penicillins, CEPs or GM. The isolates of these species obtained in 1983 showed MIC values of 100 micrograms/ml or more for the so-called new CEPs (CTX, CMX, CZX, LMOX and CPZ). The P. vulgaris isolates exhibited an increasing incidence of strains resistant to penicillins, and data on P. vulgaris isolates in 1983 indicated increase of strains resistant to CEPs. GM-resistant organisms were also noted to be increasing among the isolate of this species. The analysis did not reveal any appreciable change with calendar years among P. aeruginosa in respect of frequency of strains resistant to SBPC or CEPs (except CPZ). The data obtained in 1983, however, showed an indication of increasing incidence of organisms resistant to CPZ and GM. The increasing tendency of emergence of organisms resistant to new CEPs designed to expand activity against C. freundii, Enterobacter spp., S. marcescens and P. vulgaris, observed among the isolates of these species is considered probably to be the consequence of bacterial selective acquisition of R plasmid that carry drug resistant genes against CEPs. These are exactly reflected in the present data obtained in studies initiated in 1981 when the new CEPs became commonly prescribed in the daily clinics. It is concluded, accordingly, that organisms of these species resistant to CEPs have been increasing throughout the country.     

In vitro antibacterial activity of various cephems against clinical isolates from complicated urinary tract infections

In vitro antibacterial activity of several cephems (CEZ as the first generation (group A); CTM and CMZ as the second generation (group B); CMX, CPZ, LMOX, CTX and CZX as the third generation (group C)) against 8 species, each of 54 strains, of Gram-negative clinical isolates from complicated urinary tract infection was compared by determination of the MICs. The following results were obtained: The most sensitive drugs against each species in MIC80; CTX (MIC80 0.20 microgram/ml) against E. coli, CMX (1.56 microgram/ml) against K. pneumoniae, LMOX (0.39 microgram/ml) against P. mirabilis, LMOX (0.78 microgram/ml) against Indole (+) Proteus, CMX and CPZ (50 micrograms/ml) against E. cloacae, CMX and LMOX (50 micrograms/ml) against C. freundii, CMX (3.13 micrograms/ml) against S. marcescens and CPZ (25 micrograms/ml) against P. aeruginosa The most sensitive drugs against each species in MICS100; CMX (MIC100 3.13 micrograms/ml) against E. coli, CMX (6.25 micrograms/ml) against K. pneumoniae, CTX (0.78 microgram/ml) against P. mirabilis, LMOX (1.56 microgram/ml) against Indole (+) Proteus, CPZ (100 micrograms/ml) against E. cloacae, CMX (100 micrograms/ml) against C. freundii, CMX (12.5 microgram/ml) against S. marcescens and CPZ (50 micrograms/ml) against P. aeruginosa. In each species, the group C were most sensitive followed by those of the group B. Many isolates were highly resistant to the group A (especially in C. freundii, S. marcescens and P. aeruginosa).     

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)     

Comparison of antibacterial potencies of oral and parenteral antibiotic preparations against Escherichia coli, Klebsiella, Citrobacter, and Proteus isolated from urinary tract infections (3: 1981). 2. Changes in bacterial sensitivities

Since 1979 the antibacterial activity of antibiotics against E. coli, Klebsiella, Citrobacter and Proteus isolated from patients with urinary tract infections has been investigated. The serious transition of susceptibilities of E. coli and Klebsiella could not be recognized in these antibiotics (MPC, ABPC, NA, PPA, CEX, CEZ, CTM, CMZ and CFX). However, a few resistant organisms against the third generation's antibiotics (CTX, CMX, CZX, LMOX and CPZ) have already been appeared, we have to observe these results, continuously.     

Antibacterial activities of new cephems against clinically isolated organisms (author's transl)

The antibacterial activities of cefotaxime (CTX), cefoperazone (CPZ), ceftizoxime (CZX), cefmenoxime (CMX), latamoxef (LMOX), cefotiam (CTM), cefazolin (CEZ), gentamicin (GM) and cefsulodin (CFS) were investigated. All causative organisms were isolated from patients with urinary tract infections treated in Tokai University Hospital. The results were as follows. 1) The MICs of CMX, CTX, and CZX against most of clinically isolated strains of E. coli, K. pneumoniae, Indole (-) Proteus sp. were 0.1 microgram/ml and lower. And then CTM, LMOX and CPZ showed similar antibacterial activities. 2) LMOX and GM showed potent antibacterial activities against C. freundii which was considered to be causative organisms of infections in rare cases. 3) Against S. marcescens, CMX, CTX, CZX, and LMOX showed very potent antibacterial activities. 4) Against P. aeruginosa, CFS, GM and CPZ showed moderate antibacterial activities. 5) Against Enterobacter sp., GM and CMX showed potent antibacterial activities.     

Study on the drug sensitivity of multiple drug-resistant Staphylococcus aureus

Of clinically isolated Staphylococcus aureus showing resistance to multiple drugs among penicillins (PCs), cephem antibiotics (CEPs), aminoglycosides (AGs), minocycline (MINO) and fosfomycin (FOM), 64 strains were selected for the determination of MIC. Twenty-one drugs were used for the determination of MIC, with ampicillin (ABPC), cloxacillin (MCIPC), cephalothin (CET), cefazolin (CEZ), cefotiam (CTM), cefuroxime (CXM), cefamandole (CMD), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX), cefmetazole (CMZ), cefoxitin (CFX), latamoxef (LMOX), cefotetan (CTT), cefoperazone (CPZ), gentamicin (GM), dibekacin (DKB), tobramycin (TOB), amikacin (AMK), MINO, and FOM. MIC80 of each drug at 10(6) CFU/ml were: ABPC, MCIPC, CEZ, CTM, CXM, CTX, CZX, CMX, CFX, LMOX, CTT, CPZ, GM, DKB and TOB greater than 100 micrograms/ml; CET 50 micrograms/ml; CMD and AMK 25 micrograms/ml; CMZ 12.5 micrograms/ml; FOM 6.25 micrograms/ml; and MINO 0.78 micrograms/ml. The ratio of highly resistant strains with MIC greater than 100 micrograms/ml at 10(6) CFU/ml varied according to drug, and a difference tended to be seen in the degree of influence by resistant factors reflected upon MIC, e.g. drugs for which a high resistance of more than 50% was confirmed were ABPC, CXM, CZX, LMOX and TOB, and 20 approximately 30% MCIPC, CTM, CTX, CMX and CFX. MIC on MCIPC which has a correlation of structural activity with methicillin correlated with cephems (CEPs) resistance to a high degree, but many of the so-called new CEPs showed resistance even to the strains with a low MIC on MCIPC. It was assumed that CEPs resistant strains have multiple drug resistant factors based on the fact that such strains showed multiple drug resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Susceptibilities of uropathogenic bacteria to ampicillin, cefazolin, cefmetazole and gentamicin. Nine-year survey of changing patterns of susceptibilities

We analyzed antibiotic susceptibilities of urinary isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, and Indole (+) Proteus group to ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ) and gentamicin (GM) in 69 laboratories in 1988 and also studied changing patterns of susceptibilities from 1980 to 1988. Minimal inhibitory concentrations were determined using the agar dilution method (MUELLER-HINTON agar, BBL) with inoculation of 10(6) cfu/ml of bacteria. Ninety to 99% of the strains of E. coli, Klebsiella spp. and P. mirabilis were inhibited at a concentration of 6.25 micrograms/ml of CEZ and CMZ and of 1.56 micrograms/ml of GM. Approximately 80% of the strains of Indole (+) Proteus group were inhibited at concentrations of 6.25 micrograms/ml of CMZ and of 1.56 micrograms/ml of GM. However, resistance to ABPC and CEZ was high, with 83% and 81% of the strains being not inhibited at a concentration of 50 micrograms/ml of ABPC and CEZ, respectively. No significant changes in susceptibilities of the 4 bacteria to the above 4 antibiotics were observed over the 9 year period. No increase was found in the incidence of the resistant strains of the 4 bacteria to CMZ and GM, nor of E. coli and Klebsiella spp. to CEZ.     

A nationwide study of the antimicrobial susceptibility of clinical isolates of Klebsiella sp. in Japan

We have reported the antimicrobial susceptibility of clinical isolates of Escherichia coli in 1983 and 1984 to 4 antibiotics, ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ) and gentamicin (GM), in the previous report. In this paper, we described the antimicrobial susceptibility of Klebsiella sp. to the same antibiotics during the same period reported for E. coli before. Numbers of isolates tested were 1,671 strains in 1983 and 1,374 strains in 1984. We determined MICs of the 4 antibiotics against isolates by the standard method of the Japan Society of Chemotherapy. The most effective agent was GM among the 4 antibiotics. CMZ had a similar antimicrobial activity to GM. Resistance rates were low for both agents. CEZ had a fairly good antimicrobial activity, but it was less active than GM and CMZ. ABPC was not effective. There was neither significant annual change of antimicrobial activity of each agent against isolates nor an increasing tendency of resistant strains in the last 5 years. Depending on isolates from clinical materials, differences in the susceptibility were noted and there was a high ratio of resistant organisms among isolates from urine.     

Comparative studies of antimicrobial agents against causative organisms isolated from urinary tract infections (1984). I. Susceptibility distribution

Our research group was engaged for 3 years (1979-1981) in a study on sensitivities to antibiotics of 4 bacterial groups including representative pathogenic bacteria found in cases of urinary tract infections; i.e. E. coli, Klebsiella spp., Citrobacter spp., and Proteus spp. Since 1982, all the bacterial strains isolated by our group from patients with urinary tract infections and deemed by doctors in charge as pathogens were sent to the Laboratory of Clinical Pathology of Juntendo University, where they were refixed and subjected to MIC determination. This is the third year of the new study. E. coli was detected most frequently from patients with urinary tract infections and the detection frequency was 28% (323/1,153) this year (1984), whereas it was 35.3% (304/860) last year, showing a 7% decline from last year to this year. E. faecalis was next frequent organism (12.7% or 147/1,153) followed by P. aeruginosa (10.8% or 124/1,153). This order, however, was reversed from last year. Other pathogens, in a decreasing order of isolation frequencies following the above three, were as follows: Proteus spp. (9.5% or 109/1,153), S. marcescens (6.2% or 71/1,153), S. epidermidis (5.4% or 62/1,153), K. pneumoniae (4.9% or 56/1,153), Enterobacter spp. (2.4% or 28/1,153) and Citrobacter spp. (2.3% or 27/1,153). The results of the determination of the sensitivity of bacterial strains to the antibiotics are described below. Of all the oral antibacterial and antibiotic agents used against E. coli, mecillinam (MPC), cefaclor (CCL) and pipemidic acid (PPA) proved to have high antibacterial potency, and their MIC90 (the concentration to inhibit growths of 90% of the objective bacteria) was 3.13 micrograms/ml. The MIC90's of cefotiam (CTM), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX) and latamoxef (LMOX) were less than 0.39 microgram/ml. The MIC90's of cefmetazole (CMZ) and cefoperazone (CPZ) were invariably 1.56 micrograms/ml. K. pneumoniae was not sensitive to ampicillin (ABPC) and did not show much sensitivity to other oral antibacterial and antibiotic agents also. Of all the injectable preparations of antibiotics, cephem antibiotics of the third generation showed the most potent antibacterial effects against K. pneumoniae, and their MIC90's were lower than 0.10 microgram/ml for CZX, 0.20 microgram/ml for CTX, 0.39 microgram/ml for CMX, and 0.78 microgram/ml for LMOX, while MIC90's of CPZ was 6.25 micrograms/ml, which was equal to that of CMZ. The MIC90 of CTM was 0.78 microgram/ml which was identical to that of LMOX.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). III. Secular changes in susceptibility]

Sensitivities to various antibacterial and antibiotic agents of strains of Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Serratia marcescens and Pseudomonas aeruginosa isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June to November 1988 were compared with those in the same period of previous year according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. No remarkable changes were found in sensitivities of E. coli, Proteus spp., Citrobacter spp. and S. marcescens. The sensitivity of Klebsiella spp. to cephems decreased in complicated UTI without indwelling catheter and increased in complicated UTI with indwelling catheter. The sensitivity of Enterobacter spp. to third generation cephems decreased in complicated UTI with indwelling catheter. Sensitivities of P. aeruginosa to aspoxicillin and cefsulodin increased. The number of resistant strains to new quinolones increased slightly.     

In vitro susceptibilities of clinical isolates of Staphylococcus aureus

In vitro susceptibilities of 350 strains of Staphylococcus aureus to ampicillin (ABPC), methicillin (DMPPC), cloxacillin (MCIPC), cefazolin (CEZ), cefmetazole (CMZ), cefmenoxime (CMX), latamoxef (LMOX) and 5 non-beta-lactam antimicrobial agents were determined according to the standard method of Japan Society of Chemotherapy. Frequencies of the appearance of resistant organisms (MIC greater than or equal to 12.5 micrograms/ml) to beta-lactam antibiotics were 45% for ABPC, 27% for DMPPC, 11% for MCIPC, 24% for CEZ, 15% for CMZ, 36% for CMX and 51% for LMOX. To non-beta-lactam antimicrobial agents, resistant strains appeared at 31% to gentamicin, 15% to amikacin, 0.6% to minocycline (MINO), 1% to norfloxacin (NFLX) and 65% to fosfomycin (FOM). More than 80% of DMPPC-resistant strains were also resistant to LMOX, CMX, ABPC, FOM, and CEZ, but most of those were susceptible to MINO and NFLX. Incidence of DMPPC-CEZ resistant S. aureus was 23% of the 350 strains tested. As stated above, multiply resistant strains of S. aureus are present throughout different hospitals in Okinawa.     

Fundamental and clinical evaluation on ceftriaxone in the pediatric field

Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed. CTRX was compared with CEZ, CMZ, CTX and LMOX in the antibacterial activity against the clinical isolates such as S. aureus, E. coli, P. mirabilis, K. pneumoniae and S. marcescens. Against S. aureus, the MIC of CTRX ranged from 0.2 to greater than 100 micrograms/ml with a peak of 3.13 micrograms/ml, showing that CTRX was almost equal to CTX in activity, slightly superior to LMOX and much inferior to CMZ and CEZ, although some strains were not susceptible to CEZ. Against the intestinal strains of E. coli, K. pneumoniae and P. mirabilis, the MIC distribution of CTRX was similar to that of CTX and LMOX while CTRX showed the MIC as high as 3.13 micrograms/ml or above against 44% of all strains including the beta-lactamase producing strains of E. coli and K. pneumoniae, indicating a slight tendency of their becoming resistant. The MIC peaks against E. coli, K. pneumoniae and P. mirabilis were less than or equal to 0.1, 0.39 and less than or equal to 0.1 microgram/ml, respectively. As to S. marcescens which is drawing attention as a causative agent for infections inside of hospitals or those among young infants, CTRX inhibited 84% of the strains at 3.13 micrograms/ml, showing a definite superiority to CEZ and CMZ and a slight superiority to CTX and LMOX. The serum concentration after a single intravenous injection with 40 mg/kg reached a mean peak of 168.8 micrograms/ml at the first blood sampling (at 30 minutes) and gradually decreased to 137.5 micrograms/ml at 1 hour, 30.9 micrograms/ml at 6 hours, 12.6 micrograms/ml at 12 hours and 3.8 micrograms/ml at 24 hours, while the half-life time was 6.0 hours. The comparison of the serum level by 1 hour intravenous drip infusion between the dosage groups of 20 mg/kg and 40 mg/kg revealed that the former group reached a peak of 85.4 micrograms/ml at the termination of drip while the latter's peak was 176.6 micrograms/ml observed during the drip (30 minutes after the initiation of drip). The respective levels of the 2 groups were 15.4 and 32.1 micrograms/ml at 6 hours, 5.1 and 15.0 micrograms/ml at 12 hours, and 1.6 and 4.1 micrograms/ml at 24 hours, indicating a distinct dose-response 2 hours after the initiation of drip administration. The half-life times were 4.9 and 6.2 hours, respectively, which are the longest among the cephalosporins presently being developed.(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)     

Evaluation of in vitro antimicrobial activity of cefazolin alone and in combination with cefmetazole or flomoxef using agar dilution method and disk diffusion method]

Antimicrobial activities of cefazolin (CEZ) against 251 strains of various clinical isolates obtained during 1989 and 1990 were determined using the Mueller-Hinton agar dilution method at an inoculum level 10(6) CFU/ml. The reliability of the disk susceptility test was also studied using Mueller-Hinton agar and various disks at inoculum levels of 10(3-4) CFU/cm2 in estimating approximate values of MICs. In addition, antimicrobial activities of CEZ and cefmetazole (CMZ) or flomoxef (FMOX) in combination were investigated against methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA) using the checkerboard agar dilution MIC method and the disk diffusion test either with the disks contained CEZ, CMZ, and FMOX alone, or CEZ, and CMZ or FMOX in combination. In this study, the MICs of CEZ against S. aureus were distributed with the 3 peak values at 0.39 microgram/ml, 3.13 micrograms/ml and > 100 micrograms/ml. MICs against MSSA were 0.39 microgram/ml to 0.78 microgram/ml, whereas those against MRSA were greater than 0.78 microgram/ml. MICs against majority of strains of Enterococcus faecalis were 25 micrograms/ml. Over 90% of strains of Escherichia coli and Klebsiella pneumoniae were inhibited at the level of 3.13 micrograms/ml. About 60% of isolates of indole negative Proteus spp. were inhibited at the levels of less than 3.13 micrograms/ml and 100% at 6.25 micrograms/ml, but MICs against indole positive Proteus spp., Serratia spp. and Pseudomonas aeruginosa were over 100 micrograms/ml. The antimicrobial activities of CEZ against these clinical isolates were not significantly different compared to those reported about 15-20 years ago, except for S. aureus. Highly resistant strains of S. aureus to CEZ were more prevalent in this study. The inhibitory zones obtained with the disk test were compared with MICs. The results of CEZ disk susceptibility test with 30 micrograms disk (Showa) or 10 micrograms disk (prepared in this laboratory) were well correlated with MICs (r = -0.837 and -0.814, respectively), showing the reliavility of the disk method in estimating approximate values of MICs. In the 4 category classification system currently used in Japan, break points in MIC values proposed are () MIC < or = 3 micrograms/ml, (++) > 3-15 micrograms/ml, (+) > 15-60 micrograms/ml, (-) > 60 micrograms/ml. The results obtained with 30 micrograms disks showed false positive in 7.7% and false negative in 6.8% of the samples. The disk results with E. faecalis showed a higher ratio of false positive results.(ABSTRACT TRUNCATED AT 400 WORDS)