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.     

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)     

In vitro antimicrobial activity of various antibiotics against Haemophilus influenzae isolated from clinical specimens in 1983

In vitro susceptibilities of 73 strains of Haemophilus influenzae isolated from clinical specimens in 1983 to various antibiotics were studied. The following antibiotics were evaluated; ampicillin (ABPC), piperacillin (PIPC), cefotaxime (CTX), cefoperazone (CPZ), ceftizoxime (CZX), cefmenoxime (CMX), latamoxef (LMOX), tetracycline (TC), doxycycline (DOXY), minocycline (MINO), chloramphenicol (CP) and erythromycin (EM). Susceptible strains to ABPC and PIPC with MICs less than 3 micrograms/ml were 80.3 and 84.1%, respectively. With this break point of MIC, all strains showed susceptibility to CPZ, CZX, and CMX, but resistant strains were observed in 1.5% against CTX and LMOX. Susceptible strains to TC, DOXY and MINO at MICs less than 2 micrograms/ml were 86.3, 80, and 87.7%, respectively. Those to CP at MICs less than or equal to 4 micrograms/ml and to EM at MICs less than or equal to 1 microgram/ml were 86.2 and 71.9%.     

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)     

Comparison of antibacterial activity of cefmenoxime with other cephalosporins against clinically isolated bacteria (author's transl)

We examined the antibacterial activity of MX in comparison with those of other CEPs, using aerobic Gram-positive cocci, aerobic Gram-negative bacilli and anaerobic bacteria, 870 strains in total, all isolated from clinical specimens, in 1979 and 1980. Against Streptococcus, CMX showed superior antibacterial activity than those of CFX, CMZ, CXM and CTM. Against H. influenzae, CMX also showed superior antibacterial activity than those of CFX, CMX, CXM, CTM and CEZ. ABPC-and PIPC-resistant strains were sensitive to CMX. CTX, CPZ and CZX also showed antibacterial activities equivalent to that of CMX. Against enteric bacteria, E. coli, Klebsiella, E. cloacae, Serratia, C. freundii and Proteus, CMX showed superior antibacterial activity than those of CFX, CMZ, CXM, CTM and CEZ. Especially, against E. coli, Klebsiella, P. mirabilis, P. rettgeri and P. inconstans, CMX showed strong antibacterial activity. As to non-fermentation bacteria, CMX's antibacterial activity was relatively weak except P. putrefaciens, Alcaligenes and Comamonas. However, it was superior than that of CEZ. In comparison with other CEPs, the strength of CMX varied according to the kinds of bacteria. As to anaerobic bacteria, CMX showed strong antibacterial activity against Peptococcus, Peptostreptococcus, Lactobacillus, Propionibacterium, C. perfringens, Veillonella and Fusobacterium. However, its antibacterial activity against Bacteroides was similar to those of other CEPs.     

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).     

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.     

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.     

Antibacterial activities of various aminoglycosides against clinically isolated methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) were isolated from samples collected from various patients during 1986, and antibacterial activities of 6 aminoglycosides (AGs) (netilmicin (NTL), gentamicin (GM), sisomicin (SISO), dibekacin (DKB), tobramycin (TOB) and amikacin (AMK] and 4 beta-lactam antibiotics (cefazolin (CEZ), cefmetazole (CMZ), cloxacillin (MCIPC) and methicillin (DMPPC) against these MRSA were evaluated. Among these 6 AGs, NTL was the most potent, and its MIC50 and MIC80 were 1.56 and 3.13 micrograms/ml, respectively. Antibacterial activities of GM, SISO, DKB and TOB were weak, and MIC50's of GM and DKB were both 100 micrograms/ml, while those of SISO and TOB were 50 and greater than 100 micrograms/ml, respectively. Frequency of highly resistant specimens to AMK was rather low and its MIC50 and MIC80 were 12.5 and 25 micrograms/ml, respectively. As for antibacterial activities of the above 4 beta-lactam antibiotics, the MIC50 and MIC80 of CMZ were 6.25 and 12.5 micrograms/ml, respectively, and therefore, its antibacterial activity to MRSA is relatively good. However, MIC50's of CEZ, MCIPC and DMPPC were all greater than 100 micrograms/ml, showing poor antibacterial activities. Recently, MRSA became a problem in various fields of clinical practice, and a number of literatures reporting refractory infections caused by MRSA have been published. Since MRSA is featured as multiply resistant bacteria, it is known that MRSA is resistant to the majority of existing antibiotics (penicillins, cephems, macrolides, AGs, etc.). In 1985, we reported results of our study concerning the antibacterial activities of a number of CEPs and some of AGs against multiply resistant S. aureus including MRSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibiotic susceptibility of bacteria isolated from surgical infections (first report)

In vitro activities of several antimicrobial agents against bacterial pathogens isolated from patients with primary and postoperative infections were investigated in 1982 and 1983. Antimicrobial agents examined were as follows: sulbenicillin (SBPC), piperacillin (PIPC), cephalothin (CET), cefazolin (CEZ), cefmetazole (CMZ), cefotiam (CTM), cefoperazone (CPZ), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX), latamoxef (LMOX), lincomycin (LCM), gentamicin (GM) and amikacin (AMK). Specimens for bacterial isolation included plus, fluid drawn by centesis, or bile. Blood samples of septicemia were excluded. The antimicrobial activities of these drugs were determined by the agar plate dilution method of the Japanese Society of Chemotherapy. There were 123 strains obtained in the 1982 survey and 252 strains in the 1983 survey. Little or no differences were seen in frequencies of isolation between the isolates of principal species in 1982 and those in 1983. Isolation frequencies of pathogens in primary infections were, in an order of decreasing frequency, E. coli (25.6%), anaerobes (21.1%), Streptococcus sp. (14.3%), Staphylococcus sp. (11.3%); in postoperative infections, Streptococcus sp. was most frequent (28.6%), followed by Pseudomonas sp. (17.6%), anaerobes (12.6%), E. coli (10.9%), Staphylococcus (10.1%). Against S. aureus, CEZ, CTM, LCM and GM had similar degree of activity with CET being somewhat more active. CMX was the most active drug among the third generation cephems tested against S. aureus. No strain was CTM, CEZ, and LCM-resistant at the same time. Over 90% of E. coli, were sensitive to CTX, CZX and CMX, inhibited by 0.10 microgram/ml, while E. coli were slightly less susceptible to CPZ and LMOX. Penicillins were not very active against K. pneumoniae, and only 60% of K. pneumoniae were inhibited by PIPC at concentrations of 12.5 micrograms/ml. Third generation cephems, CTX, CMX and CZX, proved highly active against K. pneumoniae; over 90% of K. pneumoniae was inhibited by CTX, CMX and CZX at a concentration of 0.10 microgram/ml. About 60% of P. aeruginosa was inhibited by 3.13 micrograms/ml of PIPC and GM but was resistant to SBPC. This survey should be very useful for the selection of an appropriate drug for prophylaxis if the frequencies of incidences of pathogens in postoperative infections are taken into account in selecting the most active antibiotic agent(s) against the most frequent genus, genera and species of pathogens.     

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 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.     

Bacterial species recently isolated from urinary tract infections and their antibiotic susceptibility, with special reference to acute cystitis

Numbers of the strains of each bacterial species isolated from urinary tract infections were summed and their incidences were calculated for each a half year from the second half of 1980 to the first half of 1982. The incidences of Escherichia coli strains were found to be greatly reduced and those of Streptococcus faecalis strains were greatly increased. Those of Staphylococcus epidermidis strains were also increased. This trend was thought to be caused by the extensive and exclusive use of cephalosporin derivatives. Minimal inhibitory concentrations of gentamicin (GM), amikacin (AMK), ampicillin (ABPC), cefazolin (CEZ), ceftizoxime (CZX), latamoxef (LMOX) and minocycline (MINO) against these isolated strains were estimated. The most sensitive drugs for E. coli were found to be CZX, LMOX, GM and AMK, CZX and MINO for Klebsiella, CZX and LMOX for Proteus, and GM for Pseudomonas aeruginosa. All Gram-positive cocci were found generally to be most susceptible to MINO, but S. faecalis and other Pseudomonas were also sensitive to ABPC. Exclusive use of cephalosporins for the treatment may induce selective increases of the resistant species in normal flora. Since these flora could be the causative agents for various infections, these selections caused by the exclusive use of the monotype drugs are not preferable, and various different drugs should be used for the suitable cases.     

Studies on phage type, beta-lactamase activity and sensitivity of multiple drug-resistant Staphylococcus aureus isolated from clinical specimens to cefmetazole

The 868 strains of S. aureus were isolated at the Department of Pediatrics, Third Hospital and Aoto Hospital, The Jikei University, School of Medicine and the Kanagawa Prefectural Nursing and Hygienic School Hospital during 6 months from May to October in 1981. From them 66 strains not sensitive to CEZ were selected by a 3-concentration disk method. A total number of 54 strains except for 12 isolated from the same infant patient was examined for their MIC's for 6 drugs, CMZ, CEZ, CTM, CXM, MCIPC and GM. Moreover, phage typing and beta-lactamase activity determination were carried out in them. 1. Antibacterial activity Sixty-six (7.6) of 868 strains were not sensitive to CEZ. The MIC's of CMZ against these resistant strains were between 1.56 and 50 micrograms/ml with a peak between 3.13 and 6.25 micrograms/ml when the 10(5) cells/ml bacterial suspension were inoculated. CMZ was superior in antibacterial activity to CEZ and CXM by about 4 degrees and to CTM by about 3 degrees. MCIPC and GM has higher antibacterial activity against a few strains than CMZ. However, the number of strains with MIC higher than or equal to 50 micrograms/ml was 17 for MCIPC and 40 for GM, but only 2 for CMZ. Thus, the former 2 drugs were far inferior to the latter one. 2. Phage type (1) Nineteen strains (35.2%) had MIC's for CEZ greater than 50 micrograms/ml and CMZ less than 6.25 micrograms/ml. Seventeen of them belonged to the nontypable. (2) Fourteen (25.9%) had MIC's for CEZ greater than 100 micrograms/ml. Of them 9 were allocated to the group III, 3 to the mixed (I + II + III, I + III) group and 2 to the nontypable. (3) Of 20 strains (37.0%) which had MIC's for CEZ greater than 100 micrograms/ml and CMZ less than 6.25 micrograms/ml 5 belonged to the group I, 3 to the group III and 12 to the nontypable. (4) Five strains classified into the group I were all isolated at the Kanagawa Perfectural Nursing and Hygienic School Hospital. (5) Eleven of 15 strains belonging to the group III were isolated at the Third Hospital, The Jikei University, School of Medicine. (6) Seventeen of 21 strains isolated at the Aoto Hospital, The Jikei University, School of Medicine belonged to the nontypable. (7) Phage type was considered to be influenced by difference in areas, infection within hospitals, etc., 3. beta-Lactamase activity beta-Lactamase activity was demonstrated at levels between 0.07 and 3.26 mumol/min/mg in all 54 strains. There was no correlation between MIC for CEZ or CEZ and beta-lactamase activity. It was suggested that beta-lactamase might not contribute to mechanism of resistance of S. aureus to each drug examined.     

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)     

In vitro susceptibility of Escherichia coli and Klebsiella sp. to antibiotics

A nationwide susceptibility survey of clinical isolates of Escherichia coli and Klebsiella pneumoniae initiated in 1980 was continued for the 8th consecutive year. A total of 4,421 strains of E. coli and 2,825 strains of K. pneumoniae isolated mainly from urine, sputum and pus, were obtained from 69 hospitals throughout Japan during the 2 years (1986-1987). MICs were determined using the agar plate dilution method (Mueller-Hinton agar, BBL) with inoculation of 10(8)CFU/ml bacteria. Antibiotics tested in this survey were 2 penicillins, 7 cephems and 2 aminoglycosides. Most of the strains of the two species of bacteria were susceptible to ceftizoxime (CZX), cefotetan (CTT), latamoxef (LMOX), cefotiam (CTM) and cefmetazole (CMZ) and also gentamicin (GM) and netilmicin (NTL) were active against both species of bacteria. About 90% of the E. coli strains were inhibited at a concentration of 0.20 micrograms/ml of CZX, 0.39 micrograms/ml of LMOX, 0.78 micrograms/ml of CTT, 1.56 micrograms/ml of CTM or NTL, or 3.13 micrograms/ml of CMZ or GM. Most of the strains were resistant to ampicillin (ABPC) and piperacillin. For the strains of K. pneumoniae, similar results were obtained. Yearly changes in susceptibility of E. coli and K. pneumoniae were not obvious with ABPC, cefazolin, CMZ or GM. No significant differences were observed during 1986-1987 in susceptibilities of the isolates of both species of bacteria due to different clinical specimens. These results suggest that the 2nd and the 3rd generation cephems and aminoglycosides, alone or in combination, may be efficacious in treating infections due to E. coli and K. pneumoniae.     

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.     

Recent trend of incidence of respiratory pathogenic bacteria and its susceptibility to antimicrobial agents: studies in the year 1984-1986

Based on a quantitative analysis of sputum cultures, pathogenic bacteria in respiratory ailments isolated in our laboratory during 1984 to 1986 were classified and analyzed. During the study period, the most frequently isolated agent was Haemophilus influenzae followed by Pseudomonas aeruginosa, Branhamella catarrhalis and Streptococcus pneumoniae. They together consisted of 70 approximately 74% of all the respiratory pathogenic bacteria isolated in our study. Susceptibilities of above pathogens to antimicrobial agents were investigated using the agar dilution method. Results are summarized as follows. 1. Ratio of proportion of beta-lactamase producing strains among non beta-lactamase producing strains of H. influenzae markedly decreased in 1986 (6/70, 8.6%) as compared to previous years (11/73, 15.1% in 1984 and 8/49, 16.3% in 1985). In consequence, MIC90 values for penicillins reduced considerably in 1986. Among the antibiotics examined cefmenoxime (CMX) and cefotaxime (CTX) were the most active agents against H. influenzae. A development of resistance to other cephems and new quinolones (norfloxacin, ofloxacin, ciprofloxacin) was not evident during the 3-year survey. 2. Against S. pneumoniae, benzylpenicillin was still the most active agent despite gradual increase of frequency of isolation. Ampicillin (ABPC), piperacillin (PIPC), CMX and CTX were also potent against S. pneumoniae. S. pneumoniae were frequently isolated from patients treated with new quinolones or minocycline (MINO). This phenomenon may be explained by higher MIC values of these agents against S. pneumoniae. 3. Of B. catarrhalis strains isolated, more than 80% were beta-lactamase positive, although MIC90 were not so high (1.56 micrograms/ml for ABPC and 0.20 micrograms/ml for PIPC). Among the antibiotics tested, latamoxef was the most active agent against B. catarrhalis and inhibited all the strains at a concentration of 0.05 micrograms/ml or less. No resistant strains were observed against cephems, new quinolones, erythromycin or MINO. 4. P. aeruginosa appeared to be rapidly developing resistance against new quinolones in patients with chronic P. aeruginosa respiratory infections who had been treated with these agents. In treating chronic respiratory infection due to P. aeruginosa, one must be watchful of rapid development of resistance by the organism or its replacement with S. pneumoniae.     

Evaluation of in vitro antibacterial potencies of oral antibiotics against sputum isolates

Susceptibility of 162 sputum isolates to oral antibiotics was measured by an agar dilution method. The sputum isolates included S. pneumoniae 25 strains, S. aureus 30 strains, H. influenzae 37 strains, K. pneumoniae 51 strains and E. coli 19 strains. Minimal inhibitory concentration (MIC) values of cefaclor (CCL), cephalexin (CEX), ampicillin (ABPC) and minocycline (MINO) were measured for each strains. Eighty percent of S. pneumoniae strains were inhibited at 0.024 to 0.05 micrograms/ml of ABPC, 0.39 to 0.78 micrograms/ml of CCL, and 1.56 to 3.13 micrograms/ml of CEX and MINO. ABPC, CCL and CEX were considered to be effective clinically when they were used with the usual dosage. However, about 30% of strains were resistant to the usual dosage of orally administrated MINO. Eighty percent of S. aureus strains were inhibited at 0.20 to 0.39 microgram/ml of MINO and 3.13 to 6.25 micrograms/ml of the other 3 drugs. MINO is the most effective with the usual dosage. Twenty to 40% of strains showed resistance to CCL, CEX and ABPC. Eighty percent of H. influenzae strains were inhibited at 0.39 micrograms/ml of ABPC, 0.78 to 1.56 micrograms/ml of MINO, 3.13 micrograms/ml of CCL and 12.5 to 25 micrograms/ml of CEX. ABPC should be selected as the first choice antibiotic. However, there were 2 ABPC-resistant strains that were highly susceptible to CCL. Eighty percent of K. pneumoniae strains were inhibited at 0.39 to 0.78 micrograms/ml of CCL, 3.13 to 6.25 micrograms/ml of MINO and CEX, and 12.5 to 25 micrograms/ml of ABPC. CCL seemed to be only effective oral antibiotic for K. pneumoniae infection.(ABSTRACT TRUNCATED AT 250 WORDS)