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In order to evaluate antimicrobial activity of cefozopran (CZOP), minimum inhibitory concentrations (MICs) of CZOP and control drugs were determined against Streptococcus pneumoniae from children that were isolated from October of 1995 to January of 1996. Determinations were made for the detection frequency of penicillin-insensitive or resistant strains in biovar utilizing hydrolysis products, and for the correlation of antibacterial susceptibility and macrolides (MLs)-resistant patterns. The results are summarized as follows; 1. MIC90 of CZOP wasor = 0.025 micrograms/ml against benzylpenicillin (PCG)-susceptible S. pneumoniae (PSSP, 50 strains). MIC distribution of CZOP against these strains was approximately equal to that of PCG, and showed stronger activities of CZOP than those of ceftazidime (CAZ), flomoxef (FMOX) and erythromycin (EM). 2. MIC90 of CZOP was 0.39 micrograms/ml against 50 strains of PCG-insensitive S. pneumoniae (PISP) and PCG-resistant S. pneumoniae (PRSP). Antimicrobial activities of CZOP against these strains were stronger than those of CAZ, FMOX, PCG and EM. 3. These isolated strains of PISP and PRSP did not show type III biovar, but showed types I and II. The detection frequency of MLs-constitutive resistant strains were high among type III PSSP and those of MLs-inductive resistant strains were high among types I and II PISP and PRSP. These data suggested that CZOP had strong antimicrobial activities against multiple drug resistant S. pneumoniae including penicillin-resistant strains. CZOP will be effective against S. pneumoniae which often are causative organisms in infections of children.

To evaluate antimicrobial activities of tosufloxacin (TFLX), minimum inhibitory concentrations (MICs) of TFLX and other drugs were determined against clinical isolates that were obtained in our laboratory from February of 1993 to January of 1994 (Period I), and from February of 1995 to January of 1996 (Period II). The results are summarized as follows: 1. Compared to MIC90's reported by others for TFLX in the 1980's, those obtained by us against beta-streptococci, Streptococcus pneumoniae, Peptostreptococcus spp., Haemophilus influenzae and Salmonella spp. were similar to, but those obtained against other bacteria were higher than those reported values. 2. Detection frequencies of resistant strains to TFLX were compared between Period I and Period II. MIC90's of TFLX against Staphylococcus spp., Morganella morganii, Providencia spp., Pseudomonas aeruginosa, beta-streptococci, S. pneumoniae and Peptostreptococcus spp. were lower in Period II than in Period I. TFLX-insensitive or -resistant H. influenzae were found among strains isolated in either of the Periods. 3. Most of the TFLX-resistant Gram-negative organisms tested were also resistant to other NQ's. 4. TFLX showed strong antimicrobial activities against penicillin-resistant S. pneumoniae.

We investigated antibacterial activities of combination uses of isepamicin (ISP) and beta-lactams in vitro against Pseudomonas aeruginosa, and the following conclusions were obtained. 1. ISP + piperacillin, ISP + ceftazidime, ISP + aztreonam, ISP + imipenem and ISP + panipenem against P. aeruginosa showed strong combined effects. 2. The minimum inhibitory concentrations (MICs) of these combinations were low and dependent on concentrations of ISP. And strong antibacterial activities were observed at ISP concentrations of sub-MIC levels. These results were similar to the results of previous reports, parts 1 and 2. 3. Concentrations of ISP sufficient to lower MIC90 values when by combined with beta-lactam agents were 4 approximately 8 micrograms/ml. These effects made it possible to lower the ISP dose to 400 mg at a single dose and the enhancement of activities by combinations resulted in strong antibacterial activities against multiple drug resistant stains at sub-MIC levels of ISP. Strong antibacterial activities were also obtained against beta-lactams-resistant strains of ISP-susceptible strains when ISP was combined with beta-lactam agents. 4. All results reported in parts 1 approximately 3 indicated that no antagonisms were produced by combining ISP + penicillins, ISP + cephems, ISP + monobactams and ISP + carbapenems against Staphylococcus aureus, Enterobacteriaceae and P. aeruginosa. These combinations showed strong antibacterial activities that were enhanced synergistically with wider spectra.

In order to evaluate the antimicrobial activity of meropenem (MEPM), minimum inhibitory concentrations (MICs) of MEPM and control drugs were determined against clinical isolates from blood and cerebrospinal fluid that were obtained from January, 1993 to December, 1994. The results are summarized as follows; 1. The MIC-range, 50% MIC (MIC50) and 90% MIC (MIC90) of MEPM were equal to those of imipenem (IPM) and panipenem (PAPM) against Streptococcus pneumoniae including benzylpenicillin (PCG)-insensitive or -resistant S. pneumoniae, Streptococcus agalactiae and Listeria monocytogenes which are Gram-positive strains, and were stronger than those of ampicillin (ABPC) and cefotaxime (CTX). 2. The MIC-range, MIC50 and MIC90 of these 3 drugs of carbapenems (MEPM, IPM and PAPM) were different against Escherichia coli and Haemophilus influenzae which are Gram-negative strains. The MIC90 of MEPM wasor = 0.025 microgram/ml and those of IPM and PAPM were 0.2 microgram/ml against E. coli. The MIC90 of MEPM was 0.1 microgram/ml, that of IPM was 25 micrograms/ml and that of PAPM was 6.25 micrograms/ml against H. influenzae. Thus, the antimicrobial activity of MEPM was stronger than those of IPM and PAPM. The MIC90's of IPM and PAPM against H. influenzae were high with the MIC of IPM at 12.5 approximately 25 micrograms/ml and the MIC of PAPM at 3.13 approximately 12.5 micrograms/ml against 3 IPM-resistant strains among 17 isolates. 3. The MIC90 of ABPC was 0.39 microgram/ml and that of CTX was 0.1 microgram/ml against 20 strains of S. pneumoniae including 6 strains of PCG-insensitive or resistant S. pneumoniae. The MIC90 of ABPC and CTX were higher than those of 3 carbapenem drugs. There were E. coli of 8 strains with ABPC-high resistance (the MIC of ABPC was100 micrograms/ml) and 2 strains for which MIC of CTX were 0.39 microgram/ml and 3.13 micrograms/ml. It was found that 29.4% of H. influenzae were beta-lactamase producing strains. 4. It appeared that antimicrobial activities of carbapenems, particularly MEPM were strong against clinical isolates from blood and cerebrospinal fluid. MEPM will be first choice drug by empiric therapy in infections including sepsis and purulent meningitis.

We investigated antibacterial activities of combination uses of isepamicin (ISP) and beta-lactams in vitro against Klebsiella pneumoniae and Enterobacter cloacae, and the following conclusions were obtained. 1. ISP+cefazolin, ISP+cefotiam and ISP+flomoxef against K. pneumoniae and ISP+piperacillin, ISP+ceftazidime, ISP+aztreonam, ISP+imipenem and ISP+panipenem against E. cloacae showed strong combined effects. 2. The minimum inhibitory concentrations (MICs) of these combinations were low due to the dependence of ISP concentrations. Strong antibacterial activities were observed at sub-MIC levels of ISP. These combined effects were stronger than those against Staphylococcus aureus described in the first report at sub-MIC levels of ISP. 1/4 MIC approximately 1/8 MIC of ISP showed enhanced activities of beta-lactams. Similarly strong combined effects were observed against both beta-lactam-sensitive and -resistant strains.

To examine the antimicrobial activity of clarithromycin (CAM) against strains clinically isolated from outpatients in 1994, minimum inhibitory concentrations (MICs) were determined for CAM and the control drugs. The results were as follows; 1. MIC50 and MIC90 of CAM were similar to those investigated in 1980's against many bacterial species. 2. CAM showed strong antimicrobial activities against beta-lactamase producing Moraxella subgenus Branhamella catarrhalis, Bordetella pertussis, Campylobacter jejuni subsp. jejuni and Peptostreptococcus spp. 3. It appears that resistance to MLs including CAM is increasing among Streptococcus pneumoniae.

In order to evaluate antibacterial activities of combination uses of isepamicin (ISP) and beta-lactams in vitro, minimum inhibitory concentrations (MICs) these drugs were examined singly and in combination against clinically isolated Staphylococcus aureus. The results are summarized as follows; 1. MICs of ISP + cefazolin (CEZ), ISP + cefotiam (CTM) and ISP + flomoxef (FMOX) were low and the activities against methicillin (DMPPC)-susceptible S. aureus (MSSA) were dependent on the concentration of ISP. Combined effects were observed when the concentrations of ISP were at sub-MIC levels (1/2 approximately 1/4 concentrations). 2. MICs of ISP + CEX, ISP + CTM, ISP + FMOX, ISP + imipenem and ISP + panipenem were low and the activities against DMPPC-resistant S. aureus (MRSA) were dependent on the concentration of ISP, and were similar to those against MSSA. Combined effects were observed when the concentrations of ISP were at sub-MIC levels of ISP. Lower MIC50 or MIC90 was observed at ISP concentrations of 4 approximately 16 micrograms/ml. 3. The blood Cmax of ISP exceeded 20 micrograms/ml at one-time administration of ISP 400 mg, and these results suggested that antibacterial activities of combination uses of ISP and beta-lactams was clinically effective against MRSA infections.

In order to evaluate antibacterial activities of combination uses of cefpirome (CPR) and various antibiotics in vitro, minimum inhibitory concentrations (MICs) of CPR alone and combinations of CPR+other drugs against freshly isolated clinical strains of Pseudomonas aeruginosa. The results are summarized as follows; 1. Combined effects of CPR+beta-lactams, piperacillin (PIPC), aztreonam (AZT), imipenem (IPM) showed wider antibacterial spectra and stronger antibacterial activities than CPR alone with drugs concentrations of CPR and other drugs at sub-MIC levels. At concentrations of sub-MIC levels, antibacterial effects of CPR+PIPC and CPR+AZT combination were strong but CPR+IPM was weaker than those of the former two combinations. It appeared that stronger effects were demonstrated by some combinations against strains that were susceptible to both drugs of combination, but little additive effects were shown against strains that were resistant to both drugs. Antibacterial effect of CPR+fosfomycin combination was the same as those of CPR+PIPC and CPR+AZT combinations. 2. Combined effects of CPR+aminoglycosides (AGs), gentamicin, tobramycin, amikacin showed wider antibacterial spectra and stronger antibacterial activities at sub-MIC levels of CPR or ATs. The effect against CPR-resistant strains was same. But the combined effect was weak against AGs-resistant strains. 3. Effectiveness of combinations of CPR+beta-lactams and CPR+AGs depended on drug susceptibilities of strains tested. We cannot estimate effects of those combinations without investigating drug susceptibility of bacteria being tested. 4. In none of the combinations tested, antagonism was observed.

In order to investigate antimicrobial activities of clavulanic acid/ticarcillin (CVA/TIPC) against Escherichia coli, Enterobacter spp. and Pseudomonas aeruginosa in 1992 and 1994, beta-lactamase activities were analyzed and minimum inhibitory concentrations (MICs) were determined including those of the control drugs. The results are as follows; 1. Compared to a report in 1980, the MIC distributions of CVA/TIPC against E. coli and P. aeruginosa did not show large differences. We found, however, that CVA/TIPC-resistant strains increased among Enterobacter spp. 2. Almost all of CVA/TIPC-resistant strains of Enterobacter spp. were also resistant to cephems and new quinolones, thus they were multiple drug resistant. 3. CVA/TIPC showed strong antimicrobial activities against penicillinase producing E. coli.

In order to evaluate antimicrobial activity of cefepime (CFPM), minimum inhibitory concentrations (MICs) of CFPM and other drugs were determined against clinical isolates that were obtained in 1994. 1. CFPM showed a wide antibacterial spectrum against Staphylococcus spp. and glucose non-fermentative Gram-negative rods ((G)NF-GNR). Antimicrobial activities of CFPM against Staphylococcus spp. were stronger than those of ceftazidime (CAZ) and somewhat stronger than those of cefotaxime (CTX), and antimicrobial activity of CFPM against Pseudomonas aeruginosa was same as that of CAZ. 2. Antimicrobial activities of CFPM against almost all of Enterobacteriaceae were stronger than those of CAZ and CTX. And CFPM showed strong antimicrobial activities against CAZ-resistant Escherichia coli, Citrobacter freundii and Enterobacter spp. 3. Antimicrobial activities of CFPM were weaker than those of CAZ against some of strains of Klebsiella oxytoca, beta-lactamase high producing strains of Moraxella subgenus Branhamella catarrhalis and than those of CTX against beta-lactamase high producing strains of Prevotella spp. 4. The feature of new cephems was demonstrated in that CFPM had wider antibacterial spectrum than cephems of previous genenations against Staphylococcus spp. and (G)NF-GNR and CFPM showed strong antimicrobial activities against almost all of oxacephem-resistant Enterobacteriaceae.

In order to investigate antimicrobial activities of clavulanic acid/amoxicillin (CVA/AMPC) against freshly isolated clinical strains obtained in 1995, beta-lactamase activities and minimum inhibitory concentration (MICs) were determined including those of the control drugs. The results are summarized as follows; 1. Detection frequencies of beta-lactamase producing strains were as follows: methicillin-susceptible Staphylococcus aureus subsp. aureus (MSSA, 90.0%), Haemophilus influenzae (22.0%), Moraxella subgenus Branhamella catarrhalis (100.0%), Escherichia coli (100.0%), Klebsiella pneumoniae subsp. pneumoniae (100.0%) and Neisseria gonorrhoeae (14.0%). It appeared that beta-lactamases produced by these strains were mostly penicillinase or enzyme of similar that. 2. Antimicrobial activities of CVA/AMPC against beta-lactamase producing strains were stronger than those of AMPC, and MIC90 of CVA/AMPC against benzylpenicillin (PCG)-insensitive or resistant Streptococcus pneumoniae was lower than those of sultamicillin, cefaclor and cefpodoxime. 3. CVA showed strong beta-lactamase inhibitory effect against M.(B.) catarrhalis of direct and indirect pathogenicity. We can expect CVA/AMPC to negate or decrease the influence of indirect pathogenicity.

A comparison was made for frequencies of isolation o glucose non-fermentative Gram-negative rods ((G)NF-GNR) from clinical specimens during a period from July, 1986 to June, 1987 (the first period) and that from January, 1994 to December, 1994 (the second period). Also, minimum inhibitory concentrations of principal drugs were determined against these isolates. The obtained results are summarized as follows: 1. Thirty four (34) species of (G)NF-GNR were found from 35,200 clinical specimens in the two periods. Numbers of strains of (G)NF-GNR obtained were 4,575 during the first period and 4,704 during the second period, thus no significant difference existed in numbers of strains isolated in the two periods. 2. Among the 34 species to which the 4,704 strains were classified into, Pseudomonas aeruginosa comprised 68.4%, Stenotrophomonas maltophilia 6.9%, Acinetobacter baumannii 5.6%, Burkholderia cepacia 3.1%, Acinetobacter Iwoffii 2.6%, Alcaligenes xylosoxidans subsp. xylosoxidans 2.4%, Flavobacterium indologenes 1.7%, Pseudomonas putida 1.1%, Acinetobacter junii 1.1% and Moraxella subgenus Moraxella lacunata 0.9%. When these frequencies of isolation were compared with those in the first period, it was found that B. cepacia decreased significantly (P0.01) and that S. maltophilia increased significantly (P0.001). 3. MIC determinations revealed multiple drug resistance strains in many different species of bacteria. Minocycline, however, were active against many such strains, and ofloxacin was found to have strong antibacterial activity against some strains.

A study was done to determine susceptibilities of Haemophilus influenzae that were obtained in our laboratory in 1994 to new quinolones (NQ) and other drugs. The results were as follows; 1. Among the 300 isolates, the detection frequency of NQ-resistant strains was 8.7% (26 strains), including isolates from chronic lower respiratory tract infections (22 strains) and those from middle meatus of nose (2 strains), etc. NQ-resistant strains were not isolated from children. 2. The cross resistance was studied for different NQs against NQ-resistant strains. Clavulanic acid/amoxicillin, cefteram, cefpodoxime, cefditoren, cefodizime (CDZM) and cefpirome showed strong antimicrobial activities against NQ-resistant strains. MIC90 of CEPs against all isolated strains including NQ-resistant strains and beta-lactamase producers was low. And the MIC90 of CDZM wasor = 0.025 microgram/ml, which was the lowest among all the antibiotics tested. 3. We found 47 strains (15.7%) of beta-lactamase producers among the 300 isolates, the frequency of beta-lactamase producing strains was high among strains obtained from children.

In order to evaluate antimicrobial activity of norfloxacin (NFLX), minimum inhibitory concentration (MICs) of NFLX and control drugs were determined against clinical isolates from ocular infections that were obtained in our laboratory from July, 1993 to December, 1994. The results are summarized as follows; 1. Compared to MIC distributions of NFLX against clinical isolates from ocular infections studied in 1986 and 1987, the MIC80 of NFLX against Corynebacterium spp., Enterobacter spp., Serratia spp., Burkholderia cepacia, Flavobacterium spp., Alcaligenes spp. increased 8 times. Almost all of NFLX-resistant strains among them were ofloxacin (OFLX)-resistant, new quinolones resistant strains, and a part of them were aminoglycosides, beta-lactams-resistant as well, thus all of these strains were multiple drug resistant. 2. MIC of NFLX against Pseudomonas aeruginosa were lower than that of OFLX. 3. NFLX showed strong antimicrobial activities against so-called "particular bacteria" including Staphylococcus aureus subsp. aureus, Moraxella spp., Haemophilus spp., and P. aeruginosa from ocular infections. And MIC80 of NFLX against these bacteria was 0.05-1.56 microgram/ml. We observed that NFLX eye drops was administered so that concentrations above the MIC against these clinical isolates were maintained.

We investigated clinical and bacteriological effects of cefetamet pivoxil (CEMT-PI) in community-acquired respiratory tract infections and obtained the following findings. 1. Of the 420 respiratory tract infection cases that were treated with CEMT-PI according to a same protocol at a total of 42 institutions in Tokyo, Kanagawa-ken, Saitama-ken and Chiba-ken from February to the beginning of April 1994, 359 cases in which clinical evaluations were considered possible were selected as the subjects of the clinical study. Regarding genders of patients, slightly more females (56.3%) than males were included. Diagnoses given to these patients included laryngopharygealitis (60.7%), tonsillitis (14.2%) and acute bronchitis (13.6). Outpatients accounted for 94.4% of the subjects. 2. For the bacteriological study, a written material describing the method of collecting specimens, storage and transport in detail was distributed to the above mentioned institutions. The isolation and identification of suspected causative bacteria, determination of minimum inhibitory concentrations (MIC) and investigation of beta-lactamase production were conducted all together. Suspected causative bacteria were detected from 238 (66.3%) out of the 359 cases. They included 85 strains of Haemophilus influenzae, 76 strains of Streptococcus pneumoniae, 20 strains of Streptococcus pyogenes and 17 strains of Moraxella subgenus Branhamella catarrhalis. 3. Clinical efficacy rates (the ratio of those excellent+good) among those who were treated with 1 CEMT-PI tablet (194 mg, titer) twice a day was 76.5% and among those who were given 2 tablets twice a day was 87.4%. The improvement rate of the latter was higher at a significant level of P0.05. 4. The clinical efficacies classified by suspected causative bacteria (single bacterium) were 93.3% against M.(B.) catarrhalis, 91.7% against beta-streptococci, 87.1% against H. influenzae and 78.4% against S. pneumoniae, etc. Though 7 (9.2%) of the 76 strains of S. pneumoniae were benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), the bacteriological efficacy was assessed either excellent or good in all of the 7 patients from whom PISP were detected. The clinical efficacy was assessed 100.0% in those from which a plural number of bacteria were detected. The 13 cases from which small numbers of Staphylococcus aureus was detected with other bacterium were also included in these cases.

In order to evaluate antimicrobial activity of cefmenoxime (CMX), minimum inhibitory concentrations (MICs) of CMX and control drugs were determined against clinical isolates from patients of sinusitis that were obtained in our laboratory from October of 1993 to March of 1994. The results are summarized as follows; 1. CMX showed strong antimicrobial activities against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis that were 3 major aerobic bacteria from sinusitis. Antimicrobial activities of CMX against benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and PCG-resistant S. pneumoniae (PRSP) were stronger than those of ampicillin (ABPC), and these strong activities suggested that CMX might have strong antimicrobial activities against beta-lactamase producing H. influenzae and M. (B.) catarrhalis. 2. Antimicrobial activities of CMX against microaerophiles, Streptococcus constellatus, Streptococcus intermedius and Gemella morbillorum and against Peptostreptococcus spp., from chronic sinusitis and odontogenic maxillary sinusitis, were stronger than those of most of the control drugs. 3. The MIC90's of CMX against isolates from patients of sinusitis wereor = 0.025-0.39 micrograms/ml. These values were lower than transitional concentrations in mucous membrane of maxillary sinus obtained when "1% CMX nasal solution" was used with nebulizer. It appears likely that sufficient concentrations exceeding MICs against main organisms would be obtained by nebulizer treatment using CMX nasal solution.

Antimicrobial activities were examined for sulbactam/ampicillin (SBT/ABPC) against clinically isolated microbial strains in 1987, 1990, 1994. Besides, the beta-lactamase productivity and MICs of these strains were measured, and the following conclusions were obtained. 1. The ratio of beta-lactamase producing strains were 90% of methicillin (DMPPC)-susceptible Staphylococcus aureus subsp. aureus (MSSA), about 80% of DMPPC-resistant S. aureus (MRSA), 100% of Escherichia coli, Klebsiella pneumoniae subsp. pneumoniae and Proteus mirabilis, 95% of Moraxella subgenus Branhamella catarrhalis and 15-20% of Haemophilus influenzae. Several kinds of beta-lactamase productivity were observed. 2. Antimicrobial activities of SBT/ABPC against beta-lactamase producing strains of MSSA, M. (B.) catarrhalis, H. influenzae, and almost all of Enterobacteriaceae were stronger than those of ampicillin (ABPC) and piperacillin (PIPC), but antimicrobial activities of SBT/ABPC were weak against MRSA and cephems (CEPs)-resistant strains detected in some of Enterobacteriaceae. 3. It appeared that benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) or PCG-resistant S. pneumoniae (PRSP) and CEPs-resistant Escherichia coli increased year by year. 4. Antimicrobial activities of SBT/ABPC were strong against Streptococcus pyogenes, S. pneumoniae, M. (B.) catarrhalis and H. influenzae including beta-lactamase producing strains. Additionally, beta-lactamase inhibiting effect of SBT was observed against beta-lactamase produced by S. aureus and K. pneumoniae which demonstrate indirect pathogenicity. Thus, SBT/ABPC is an injectable antibiotic that is expected to demonstrate clinical usefulness, especially as the first line drug for the respiratory tract infections that are community-acquired.

We examined beta-lactamase productions by clinically isolated strains of bacteria. The results were as follows; 1. It appears that beta-lactamases produced by strains of five species of Staphylococcus spp. are mostly penicillinase (90%). Source of beta-lactamase producing strains of Haemophilus influenzae (23%) and all of Moraxella subgenus Branhamella catarrhalis: strains (100%) are "HighLow producer" strains. 2. A large proportion of beta-lactamase producing strains of Enterobacteriaceae and Bacteroides fragilis group appeared to be "High producer" 3. beta-lactamase producing abilities are different among glucose non-fermentative Gram-negative rods. It appears that some of the strains appeared to be "High producers".

Clinical isolates from patients with otitis media and/or otitis externa were collected at otorhinology clinics nationwide and sent to us during 1989, 1991 and 1993. Minimum inhibitory concentrations (MICs) of fosfomycin (FOM) and of reference drugs against these strains were determined to investigate year-to-year antibacterial activity of FOM. A comparative analysis of the results revealed trends described below. 1. The MIC90 of FOM against Staphylococcus aureus subsp. aureus increased 4 times by 1993 as compared to those measured for strains isolated in 1984 and 1985, when FOM for otic use was under development. This was thought to be due to the recent increase in the detection frequency of methicillin-resistant S. aureus (MRSA) which is also resistant to FOM. 2. No annual changes were seen for MIC distribution of FOM against Proteus group and Pseudomonas aeruginosa. 3. Since there was no large annual change in the antibacterial activity of FOM against recent clinical isolates obtained from patients with otitis media and/or otitis externa, FOM may be considered as one of the useful drugs even now, in the mid-1990's.

Dip-slides are used as semiquantitative microbial sampling devices that are simple to use in routine testing of urine to detect the presence of bacteria, and are recommended for use in "Standard evaluation of drug efficacy in UTI". Bacterial growth on currently available dip-slides, however, may conceivably be influenced by the presence of antibacterial agents in urine. We studied clinical performance of, and effects of antibacterial agents on, such dip-slides, using two types of dip-slides, URICULTE and DIASLIDE, both of which are newly developed urine culture devices. The quantitative conventional culture method was also used as the control. 1. When single species of bacteria are present in urine specimens of patients, results obtained using URICULTE and DIASLIDE agreed very well, and they, in turn agreed well with results obtained using the quantitative, conventional culture method, also. 2. When urine specimens were spiked with Gram-negative rods and Gram-positive cocci together, URICULTE fail to provide quantitative results because colonies were not well separated and confluent growth often resulted because of a large sample volume this device employs. DIASLIDE which used a smaller amount of sample, on the other hand, provided quantitative results with adequate separation of colonies. 3. When three antibacterial agents were added to urine specimens that were spiked with bacteria, DIASLIDE produced significantly higher numbers of colonies than URICULTE. The difference probably are due to the difference in volumes of specimens used in the two devices, the former device employs approximately 1/100 as much volume of specimen as the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibacterial activities of cefetamet (CEMT) against clinically isolated strains from patients with community acquired respiratory tract infections were compared to those of other oral beta-lactam antibiotics in the period from January to March 1994. The following results were obtained. 1. CEMT showed strong antibacterial activities against three major pathogens causing community acquired respiratory tract infections, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae. However, antibacterial activities of CEMT against benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and PCG-resistant S. pneumoniae (PRSP) were slightly weaker than of those of some the reference antibiotics. 2. No MIC value changes of CEMT were observed from year to year against Moraxella subgenus Branhamella catarrhalis and Klebsiella pneumoniae.

To examine the antimicrobial activity of cefditoren (CDTR) against strains clinically isolated from outpatients at this hospital from November, 1993 to February, 1994, the minimum inhibitory concentrations (MICs) were determined including those of the control drugs. The results were as follows: 1. CDTR showed strong antimicrobial activities against Staphylococcus aureus subsp. aureus, Streptococcus pyogenes and Streptococcus pneumoniae. The MICs of CDTR against benzylpenicillin-insensitive or -resistant S. pneumoniae distributed in the lowest concentration range even compared to those of the control drugs. 2. CDTR showed strong antimicrobial activities against Haemophilus influenzae, Moraxella subgenus Branhamella catarrhalis, Escherichia coli, and Klebsiella spp. The MIC of CDTR against CEPs-resistant E. coli was lower than those of most control drugs. 3. Since the microbes described above the major pathogens for the community-acquired infections, CDTR will be effective against infectious diseases transmitted at outpatient visits.

In order to investigate antibacterial activities of new quinolones (NQs) against a number of clinical isolates obtained in our laboratory during a period from February, 1993 to January, 1994, minimum inhibitory concentrations (MICs) were determined using most of the NQs available in the market as of December, 1993. The obtained results are summarized as follows: 1. Noticeable differences were observed among the antibacterial activities of 8 different NQs tested against Gram-positive bacteria, i.e., there were large differences in their MIC distributions. Some differences were also observed among different NQs in ratios of NQ-resistant strains among Staphylococcus spp. From these results, it seems necessary to further study tolerance mechanisms of these Gram-positive bacteria toward different NQs and also to examine possible differences in antibacterial activities among different NQs against Gram-positive bacteria in clinical settings. 2. MIC distributions against Gram-negative bacteria were also different among the 8 NQs tested. Though elevated MICs were observed against NQ-resistant Gram-negative bacteria in many cases, and somewhat higher, though not exceedingly high, MIC values than those against NQ-sensitive bacteria were found in other cases, patterns of MIC values against different NQ-resistant Gram-negative bacteria were similar for all of the 8 NQs tested. This may explain the fact that most of NQ-resistant Gram-negative bacteria showed similar resistant patterns to the 8 NQs tested. 3. Among the NQ-resistant bacteria, were found Haemophilus influenzae and Neisseria gonorrhoeae strains. Ratios of resistant strains were approximately 10% or lower for the former and approximately 20% for the latter. 4. With MICs of ampicillin and cefaclor used as control, it appears that benzylpenicillin (PCG)-insensitive or PCG-resistant Streptococcus pneumoniae (PISP or PRSP) and CEPs-resistant Escherichia coli are increasing.

In order to examine antimicrobial activities of fosfomycin (FOM), the minimum inhibitory concentrations (MICs) of FOM and those of control drugs were determined against Streptococcus pneumoniae and Haemophilus influenzae isolated from sinusitis patients from September to November, 1993, and the following results were obtained. 1. Among 50 S. pneumoniae strains tested, there were 10 strains (20.0%) of benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) and 2 strains (4.0%) of PCG-resistant S. pneumoniae (PRSP); but the MIC distributions of FOM among the PISPs and the PRSPs were almost identical to those among the PCG-susceptible S. pneumoniae (PSSP). 2. There were 12 strains (24.0%) of beta-lactamase producing strains among 50 strains of H. influenzae tested, but the FOM's MIC distribution among these strains was almost identical to that among beta-lactamase non-producing strains. 3. The results obtained on the MIC90s of FOM against S. pneumoniae and H. influenzae suggest that the nebulization treatment with FOM nasal preparation satisfies the condition "above the MIC".

In order to evaluate antimicrobial activity of ciprofloxacin (CPFX), minimum inhibitory concentrations (MICs) of CPFX and other drugs were determined against clinical isolates that were obtained in our laboratory from January to December of 1991, and of 1993. The results are summarized as follows: 1. CPFX-resistant strains were on the increase in various strains, compared to those in the early 1980s. However, many of CPFX-resistant strains were multi-drug resistant including beta-lactams. In addition, they showed cross resistance to other fluoroquinolone agents. 2. MIC distribution of other drugs suggested that there were increased frequencies of benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) and CEPs-resistant Escherichia coli. However, MIC distribution of CPFX to these resistant strains were in a relatively low range. 3. When isolates of 1991 were compared to those of 1993, we confirmed that CPFX-resistant strains decreased among certain bacteria such as Staphylococcus aureus. Also we confirmed that fewer CPFX-resistant strains were found among bacteria that may be highly related to infections encountered in daily medical care.

To investigate antibacterial activities of isepamicin (ISP), MICs of ISP as well as other aminoglycosides (AGs) were determined against many strains of Gram-negative bacilli that were clinically isolated in 1993. 1. No ISP-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella spp., Enterobacter spp. or Proteus mirabilis. 2. ISP-resistant strains were observed among isolates of Citrobacter freundii, Serratia spp., Proteus vulgaris, Morganella morganii, Providencia spp. and Pseudomonas aeruginosa. The frequency of resistant strains in each species, however, was lower for ISP than other AGs. 3. When MIC90s were compared, antibacterial activities of ISP determined in this study were quite similar to those determined during the drug's development period (1980's) in Japan, suggesting no increase in the number of ISP-resistant strains over the years. 4. The number of clinically isolated Gram-negative bacilli resistant to multiple drugs are increasing in from year to year Japan. Our results in this study suggest that antibacterial activities of ISP may be potent enough against such Gram-negative bacilli resistant to multiple drugs.

Efficacies of combined uses of arbekacin(ABK) with other antibiotics against between 57 and 76 clinically isolated methicillin-resistant Staphylococcus aureus(MRSA) were examined. Other antibiotics tested were fosfomycin(FOM), 5 cephems(CEPs), 2 penicillins(PCs) and imipenem. Percentages of strains that grew at various combination of serially diluted drugs in a microdilution method were scored, and for each pair of drugsor = MIC50 oror = MIC90 was determined. FIC-indices were calculated ator = MIC50. Bacterial growth was inhibited by low concentrations of ABK dose-dependently, while most of the strains tested were resistant to 9 other drugs. FIC-indices with ABK were lowest when used together with ampicillin (ABPC) (0.516) followed by combinations with cefotiam (CTM) and cefuzonam (CZON) (each, 0.53), and FOM (0.625). When combined with 0.5 microgram/ml of ABK, 0.5 microgram/ml of ABPC inhibited more than 50% of MRSA strains. CTM or CZON in combination with the same amount of ABK to 2 micrograms/ml inhibited more than 50% of MRSA. Thus ABPC was found to be the most efficient in combined use with ABK to inhibit clinical MRSA strains.

Antimicrobial activity of cefuroxime axetil (CXM-AX) was compared with those of other cephem antibiotics against clinically isolated strains obtained mainly from outpatients of our center in a period from January to September of 1990 and 1993. Minimum inhibitory concentrations were determined and the following results were obtained. 1. The results suggested that, compared with reports of studies conducted with clinical isolates in early 1980's, MIC80 of CXM were equal to or lower against Staphylococcus spp., Streptococcus pyogenes, Escherichia coli, Klebsiella spp., Proteus mirabilis, Haemophilus influenzae, Moraxella subgenus Branhamella catarrhalis, Neisseria gonorrhoeae, Peptostreptococcus spp., and Propionibacterium acnes, except for Streptococcus pneumoniae, MIC80 which was slightly higher. 2. MIC90 of comparator drugs reflected those of new resistant organisms recently appeared, such as benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), cephem-resistant E. coli and Klebsiella spp., new quinolone-resistant H. influenzae and N. gonorrhoeae. Methicillin-resistant Staphylococcus aureus (MRSA) was detected also from specimens of community acquired infections. From the nature of MRSA detected in those situations MRSA appeared to present a continuing problem. 3. MIC90 against strains obtained from patients with community acquired infections was a good index of increases of multidrug-resistant organisms in the past. Therefore, the determination of MIC90 is important in examining changes with time of sensitivities or resistances of clinically isolated strains to antimicrobial drugs. 4. Antimicrobial activities of CXM against recent clinical isolates showed the existence of problems as mentioned above. However, MIC of CXM as well as those of comparator drugs indicated that antimicrobial activities of CXM against Staphylococcus spp., Streptococcus spp., H. influenzae appeared to be relatively strong, and it is concluded that cefuroxime axetil still is one of the clinically useful oral antimicrobial drugs in the 1990's.

To investigate the antibiotic activity of cefteram (CFTM), the minimum inhibitory concentrations (MICs) of CFTM and of the control drugs were determined against clinically isolated strains received from November 1991 to April 1993 from 19 dental facilities throughout the country, as well as against clinically isolated strains from samples obtained at this center from patients with dental infectious diseases, and the following results were obtained. 1. 430 strains were detected in 198 cases but identified strains amounted to 425. They are comprised of 204 strains of oral streptococci (48.0%), 81 strains of Peptostreptococcus spp. (19.1%), 10 strains of Bacteroides spp. (2.4%), 23 strains of Prevotella spp. (5.4%), and 9 strains of Porphyromonas spp. (2.1%). The ratios of Gram-positive bacteria v.s. Gram-negative bacteria were 78.4% and 21.6%, respectively, and the Gram-positive bacteria were isolated at higher frequency than Gram-negative bacteria. 2. The MIC90's of CFTM against oral streptococci and Peptostreptococcus spp. were 0.10 microgram/ml and 0.05 microgram/ml, and year to year increases of incidences of resistance against CFTM were not observed. Some strains, however, appeared to have obtained resistance to CFTM. 3. Among Bacteroides spp., Prevotella spp., Porphyromonas spp. which used to belong to genus Bacteroides, there were some strains resistant to CFTM. As a whole, however, no year to year increases in the incidence of CFTM resistance among these strains also. 4. Two strains of 6 Staphylococcus aureus subsp. aureus were methicillin-resistant. 5. The above observations indicate that CFTM still shows strong antimicrobial activity against clinically isolated strains that may be involved in dental infections.

beta-Lactamase production and activities in sputa of patients with community-acquired lower respiratory tract infections (LRTI) were determined and following results were obtained: 1) Suspected causative organisms frequently isolated were H. influenzae and Streptococcus pneumoniae. Similar results were previously reported. 2) Various beta-lactamase producing indigenous bacteria were detected. In many cases these indigenous beta-lactamase producing strains were isolated even when suspected causative bacteria were not beta-lactamase producers. 3) beta-Lactamase activities were detected from 61.5% of the sputa tested. Remaining activities of antibiotics added to the sputa were highly correlated with detection of beta-lactamases produced by suspectedly causative and indigenous strains and with presence of beta-lactamase activities in the sputa. Sulbactam/cefoperazone was stable in sputa than other antibiotics tested. 4) We concluded that the beta-lactamase produced by indigenous strains can be one of the factors of indirect pathogenicity in the community-acquired LRTI.

We previously reported a part of the results we obtained regarding antibacteriological synergism between beta-lactams and vancomycin (VCM) against methicillin-resistant Staphylococcus aureus (MRSA). This paper reports an additional assessment we made subsequently to the previous report regarding antibacterial effects of different beta-lactams and VCM concurrently used against MRSA. Assessed in this study were bacteriological synergistic actions between flomoxef (FMOX) and VCM, latamoxef (LMOX) and VCM, cefpirome (CPR) and VCM and imipenem (IPM) and VCM against MRSA. 1. Synergistic enhancements of therapeutic activities were observed against MRSA with FMOX +VCM, CPR + VCM and IPM + VCM, but the activity of LMOX + VCM was low. 2. Concentration dependencies of actions of these antibiotic agents against MRSA were strong for beta-lactams, but weak for VCM. These observations were opposite of the results for beta-lactams and aminoglycosides, or beta-lactams and tetracyclines against MRSA we reported previously. 3. It appeared that strong synergistic antibacterial effects were obtained with FMOX or CPR concentrations between 8 and 32 micrograms/ml when used with VCM, and IPM concentrations between 4 and 16 micrograms/ml when used with VCM, hence, in the therapy using these combinations, concentrations and dose intervals of beta-lactams employed should be carefully considered. 4. When these antibiotics are used together in in vitro experiments, values of MIC and FIC-index may be different depending upon experimental systems used.

Evaluations were made for antibacterial activities of combination uses of flomoxef (FMOX) + vancomycin (VCM) against clinically isolated bacteria of family Enterobacteriaceae, and latamoxef (LMOX) + VCM, cefpirome (CPR) + VCM, and imipenem (IPM) + VCM against also clinically isolated Pseudomonas aeruginosa. The obtained results are summarized as follows. 1. FMOX and VCM appeared to act independently against Enterobacteriaceae without showing synergism or antagonism. 2. Regarding antibacterial effects of LMOX + VCM, or CPR + VCM against P. aeruginosa strains, MIC values under the combined uses were approximately 1 dilution (2 folds) higher than LMOX or CPR used alone, but we did not consider that these results meant the presence of antagonism between the beta-lactams and VCM. 3. Experimental results suggested that an antagonistic relationship was present between IPM and VCM against P. aeruginosa. The degree of the antagonism was dependent on VCM concentrations. In other words, when VCM is present at a concentration between 4 and 128 micrograms/ml, MIC values for IPM increased 2 to 4 dilutions (4 to 16 folds), whereas in the presence of 1 to 2 micrograms/ml VCM, MIC values for IPM were close to those of IPM alone. Further, some of this tendency was observed for FMOX against bacteria of family Enterobacteriaceae in the presence of VCM. 4. These results suggest that the dose level of VCM should be considered based on a low range when a combination therapy is considered between beta-lactams and VCM in the treatment of infections with MRSA alone or with Gram-negative rods with MRSA.

In order evaluate antimicrobial activities of cefodizime (CDZM), minimum inhibitory concentrations (MIC's) of CDZM and other control drugs were determined against various clinical isolates, that were sent to our center from nation-wide medical institutions or were isolated and identified in our laboratory from various specimens of infected patients. The followings are a summary of the results: 1. Bacterial species with no or few strains resistant to cephems including CDZM included Streptococcus pyogenes, Haemophilus influenzae, Citrobacter diversus, most of Klebsiella pneumoniae and Proteus mirabilis. Some strains of Klebsiella oxytoca were resistant to cephems increases in beta-lactams resistant Streptococcus pneumoniae and cephem resistant Escherichia coli seemed likely. Among Citrobacter freundii, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii and Providencia spp. belonging to a category of so-called "mildly toxic bacteria", high portions of the strains examined were resistant to cephems including CDZM and these strains were also resistant to new quinolones, thus they showed multiple drug resistance. 2. MIC90's of CDZM against Streptococcus spp., H. infleunzae, Moraxella subgenus Branhamella catarrhalis, E. coli, Klebsiella spp. and P. mirabilis, frequently found in daily treatment of infections, were less thanor = 0.025 to 1.56 micrograms/ml. This indicates that CDZM would be expected to have enough antibiotic activity in infections caused by above mentioned bacteria. However, cautions are needed in the treatment of infections by beta-lactam resistant S. pneumoniae, cephem resistant E. coli and cephem resistant K. oxytoca with CDZM. 3. Among the above mentioned "mildly toxic bacteria", many multiple drug resistant strains exist. Therefore, we evaluated an usefulness of concomitant use of CDZM with aminoglycosides in the treatment of infections by these bacteria, using other reports which indicates the usefulness in vitro and in vivo. 4. Antibacterial activities of CDZM we observed in this study seem to indicate that CDZM concentrations in infected areas are maintained at above MIC levels for relatively long periods of time.

Minimum inhibitory concentrations (MICs) were determined for polymyxin B (PL-B), gentamicin, ofloxacin and norfloxacin against clinically isolated microbial strains collected since November 1992, and the following conclusions were obtained: 1. Judging from the MIC distribution of PL-B against the studied strains including multi-drug resistant organisms of major strains of family Enterobacteriaceae, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., and Pseudomonas aeruginosa, it appeared that no PL-B resistant strains were detected among those Gram-negative organisms within the antimicrobial spectrum of PL-B. 2. MICs of PL-B against most strains including methicillin resistant Staphylococcus aureus and coagulase-negative staphylococci were distributed between 100 and 800 micrograms/ml. These results supported reports of other investigators that the eradication of Staphylococcus spp. including MRSA (methicillin-resistant S. aureus) was possible by the use of PL-B at 1 mg/ml. 3. MIC distribution of PL-B against organisms of the Bacteroides fragilis group was almost the same as the results described above.

Bacteria clinically isolated from patients of otitis media and otitis externa were collected from various medical facilities across Japan during years 1988, 1990 and 1992, and minimum inhibitory concentrations (MICs) of cefmenoxime and of reference drugs were determined against these strains. A comparative analyses of the obtained results revealed some trends described below. 1. Methicillin-resistant Staphylococcus aureus (MRSA), multiple drug resistant Coagulase-negative staphylococci (CNS) and multiple drug resistant Proteus spp. showed a year to year trend toward a steady increasing. Relative frequencies of occurrence of MRSA in these years, however, remained comparable to that of early 1980's. 2. A year to year trend toward increasing was also found for resistant or insensitive Streptococcus pneumoniae to penicillins and cephems. 3. Multiple drug-resistant Pseudomonas aeruginosa strains were also detected but they showed no trend toward increasing.

Minimum inhibitory concentrations (MICs) were determined for sultamicillin (SBTPC), and for other major oral beta-lactam agents against clinically isolated strains collected from outpatients during a period from August, 1992 to February, 1993, and the following conclusions were obtained. 1. The ratio of penicillinase (PCase)-producing strains of Staphylococcus aureus was 96.0% and that of methicillin-resistant S. aureus (MRSA) was 12.0%. MIC90 of SBTPC against S. aureus including MRSA was 6.25 micrograms/ml. No increasing tendency was observed for S. aureus resistant to SBTPC. 2. No resistant strains were found among Streptococcus pyogenes and Enterococcus faecalis against penicillins (PCs) including SBTPC. But PCs and cephems (CEPs) insensitive or resistant Streptococcus pneumoniae were observed in 22.0% among all the strains of S. pneumoniae. 3. 100% of the tested both strains of Escherichia coli and Proteus mirabilis were beta-lactamase producers. 12.0% of the tested strains of Haemophilus influenzae and 16.0% of the strains of Neisseria gonorrhoeae were also beta-lactamase producers. SBTPC showed strong antimicrobial activity against most of these beta-lactamase producing strains. However, in our study of beta-lactamase productivity using plural substrates and test methods, it appeared that a part of strains of E. coli might produce beta-lactamase of "Extended broad-spectrum". MICs of SBTPC and CEPs against those strains were distributed rather in a high range. 4. The results of the study suggested that the resistant strains of S. pneumoniae against PCs and CEPs might be increasing year by year. Some of strains of E. coli, resistance against the 2 agents were observed. It is important to keep observing changes in resistance of such organisms in the future. 5. The antimicrobial activities of SBTPC against clinically isolated strains in this study indicated potential problems such as those mentioned above. It is, however, also confirmed that SBTPC shows still strong antimicrobial activities against most of beta-lactamase producing strains found in daily medical examinations. Taking into consideration of the strong activities of SBTPC against so-called indirect pathogenicity caused by beta-lactamase producing indigenous bacteria reported lately, SBTPC may be a useful antibiotic for community acquired infections in the 1990's.

In order to examine antibiotic activities of cefteram (CFTM), its minimum inhibitory concentrations (MIC's) and those of other cephem drugs were determined against clinically isolated strains received from July 1990 to June 1991 and from July 1992 to February 1993 from medical facilities throughout the country and against clinically isolated strains detected in our laboratory in samples from patients with various infectious diseases. The obtained results are summarized below. 1. No CFTM-resistant strains were found among beta-streptococci, Klebsiella spp., Proteus mirabilis, Haemophilus influenzae, and Neisseria gonorrhoeae or even when found, they were present in extremely low proportions. 2. It appeared that Streptococcus pneumoniae insensitive or resistant to beta-lactams, as well as cephems-resistant strains of Escherichia coli were increasing. The former included benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) of PCG-resistant S. pneumoniae (PRSP), and the presence of the latter suggests the possibility of the existence of "Extended broad-spectrum beta-lactamase" producing strains. The MIC's of beta-lactams against the above PISP or PRSP, and against cephems-resistant E. coli tended to be high, but those of CFTM were relatively low (in most cases). 3. Proportions of strains resistant to cephems, including CFTM among Citrobacter spp., Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii, and Providencia rettgeri were high, and in addition, the existence of these cephem resistant species suggests an increase in multiple drug resistant strains that show resistance to new quinolone drugs. 4. As mentioned above, CFTM is by no means a perfect drug or utility drug and its antimicrobial activities do not cover some recent isolates with multiple drug resistance. Except problems encountered with so-called "attenuated" strains of bacteria, increases in resistance can only be observed at a level of MIC90's, and as far as MIC80's are concerned, CFTM still is as active as before and may be used in the treatment of most infections we encounter in normal medical practices.

Aiming at measuring the antimicrobial activities of arbekacin (ABK) against the strains of methicillin-resistant Staphylococcus aureus (MRSA), isolated from pediatrics patients in 1992, the minimum inhibitory concentration (MIC) of 8 antibiotics including ABK was determined and the coagulase types of those strains were also examined. The obtained results are summarized as follows. 1. Among coagulase types of a total of 78 strains, Type II, Type IV and Type VII were 84.6%, 12.8% and 2.6%, respectively. No clear difference in coagulase types were observed among their origins of isolation. 2. MIC90 of ABK against 42 strains isolated from the air passage of suspected pneumoniae patients and 36 strains isolated from the blood of suspected septicemia patients were 1.56 micrograms/ml and 3.13 micrograms/ml, respectively, and MIC90 of ABK against the 78 strains was 1.56 micrograms/ml, which was equal to that of vancomycin (VCM). 3. Most of these strains exhibited resistance against multiple antibiotic agents including cefmetazole (CMZ), imipenem (IPM), fosfomycin (FOM) and minocycline. Strains isolated from the blood were mostly resistant to multiple agents, and most of them were especially highly resistant to CMZ and IPM. ABK, however, showed potent antimicrobial activities even to those strains. These results were similar to the results obtained several years ago. 4. Considering the fact that ABK demonstrates not only potent antimicrobial activities against MRSAs isolated from the pediatric patients, but also shows remarkable clinical effects with concomitant use with beta-lactams or FOM, the prospect of ABK use in MRSA infectious diseases of children is excellent.

In order to study antibacterial activities of ofloxacin (OFLX), minimum inhibitory concentrations (MICs) of OFLX were determined against clinical isolates obtained from ophthalmic institutes all over the country and those isolated and identified from patients with various ocular infections during three years from September 1989 until August 1992, and the results were compared with those of the control drugs. The following results were obtained. 1. Compared with the reports by others presented from 1984 through 1986, increases were observed for strains with moderate or low susceptibilities to OFLX such as Staphylococcus spp., Corynebacterium spp., Serratia spp., and glucose-nonfermentative Gram-negative rods ((G) NF-GNR). 2. Although incidence of resistance to OFLX increased among the above strains, remarkably low frequencies was observed for the occurrence of highly resistant strains to OFLX with MIC value100 micrograms/ml. 3. The antibacterial spectrum of OFLX covered (G)NF-GNR, and the activity of OFLX was superior to those of aminoglycosides, penicillins and cephems used as the control drugs. 4. Low incidence of highly resistant strains to OFLX and its broad antibacterial spectrum suggested the usefulness of a 0.3% OFLX ophthalmic solution in achieving concentrations exceeding MIC for a prolonged period of time.

The Antimicrobial activity of aspoxicillin (ASPC) in terms of minimum inhibitory concentration (MICs) was compared with those of other penicillin antibiotics (PCs) against clinical isolates sent to us from medical institutions throughout Japan in 1988, 1990 and 1992 and strains isolated and identified from samples collected from patients with various infections. 1. The MIC80's of ASPC against Staphylococcus aureus, Enterococcus spp., Escherichia coli, Bacteroides fragilis group were almost the same as those against these isolates in 1985 to 1986. 2. A trend for increasing susceptibility to PCs including ASPC was observed in the isolates of S. aureus and Haemophilus influenzae. This trend in S. aureus was attributed to the appearance of non beta-lactamase producing strains associated with the development of highly resistant strains among the methicillin-resistant S. aureus (MRSA) as well as to a tendency toward yearly decreasing frequency of MRSA. The trend for the increased susceptibility in H. influenzae was related to the decrease in the number of beta-lactamase production strains. 3. The frequency of the strains highly resistant to PCs including ASPC increased. 4. No PCs-resistant strains were observed among the so-called beta-streptococci, while among alpha-streptococci and Streptococcus pneumoniae there was a trend for decreasing frequency of strains with lower susceptibility to PCs or those with resistant to PCs. These strains may be variants which were also resistant to cephems and had penicillin-binding proteins (PBPs). Meanwhile, a high frequency of highly PCs-resistant strains were noted among Enterococcus faecium. In view of the fact that the PCs-resistance of E. faecium is known to be related to PBPs, the pattern of the susceptibility of the recent clinical isolates to beta-lactams is considered to be multimodal.

Against 200 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from 1990 to 1991, minimum inhibitory concentrations (MICs) of a total of 15 antibacterial agents including arbekacin (ABK) were determined. In addition coagulase types of the tested strains were determined and classified according on their origins. 1. Among the coagulase types of 200 strains, type II were 63.5%, type IV 18.5%, type VII 11.0% and the other types 7.0%. Type II strains were prevailing among those isolated from the respiratory tract specimens and type IV among those from the surgical specimens. These results were in agreement with other recent reports including our previous ones. 2. The MIC50 of methicillin, 6 cephalosporins (CEPs), imipenem, fosfomycin (FOM), gentamicin, tobramycin and clindamycin for 200 strains ranged from 50 to100 micrograms/ml. On the other hand, MIC50 and MIC90 of ABK, minocycline (MINO) and vancomycin (VCM) were 0.78 and 3.13 micrograms/ml for ABK, 0.39 and 50 micrograms/ml for MINO, and 0.78 and 1.56 micrograms/ml for VCM. 3. The MIC90 of ABK against coagulase type IV strains was rather high, 12.5 micrograms/ml. However, the strains inhibited by 6.25 to 12.5 micrograms/ml of ABK were isolated even in our studies performed in 1986, 1988 and 1989. Further studies are therefore required to confirm whether appearance of these strains used in the present study inhibited at relatively high concentrations of ABK is due to the use of ABK. 4. It is reported that, at present, most of the MRSAs spreading in Japan are acceleratedly acquiring resistance to many drugs, and especially, they are developing high resistance against beta-lactams. ABK showed potent antibacterial activities even against these strains. Since ABK has been shown to display potent activities against MRSA in combination with beta-lactams or FOM, we believe ABK is one of the useful aminoglycoside antibiotics for the treatment of MRSA infections.

We assessed the bacteriological efficacies of cefotiam (CTM) plus imipenem (IPM) and CTM plus vancomycin (VCM) therapies against methicillin-resistant Staphylococcus aureus (MRSA) in an in vitro system. The results are summarized as follows. 1. It appeared that the bacteriological efficacies of CTM+IPM therapy against MRSA strains were different against different target MRSA strains. In other words, the FIC indices of CTM+IPM were distributed in a wide range ofor = 0.5-2.0. The strains showing MIC levels ofor = 8 micrograms/ml in IPM concentrations showed a strong correlation with FIC index values ofor = 0.5, and the strains showing the MIC level ofor = 128 micrograms/ml in IPM concentration showed a strong correlation with FIC index values of2.0. Hence, the strains showing FIC indicesor = 0.5 were considered to be newborn strains with penicillin-binding protein 2' (PBP-2'), those showing FIC indices0.5-or = 2.0 were considered to be strains with increasing production in PBP-2', and those showing FIC indices2.0 were considered to be strains with increasing productions in both PBP-2' and PBP-m2. In strains with FIC indices higher than 2.0, the 2 drugs may possibly share the action mechanism and the activity center thus they compete with each other.(ABSTRACT TRUNCATED AT 250 WORDS)

We assessed the bacteriological efficacies of cefotiam (CTM) plus arbekacin (ABK) and CTM plus minocycline (MINO) therapies against methicillin-resistant Staphylococcus aureus (MRSA) in an in vitro system. The results are summarized as follows. 1. Both of CTM+ABK and CTM+MINO demonstrated almost perfect antibacterial activities against MRSA strains at ABK and MINO concentrations of MIC levels as clinically expected plasma ABK or MINO levels, and also showed antibacterial activities at ABK or MINO concentrations of sub-MIC levels. But no results suggesting antagonism were obtained. 2. The potent antibacterial effect of CTM+ABK or CTM+MINO against MRSA strains was considered to be the result of damage to the cellular membrane of target strains by ABK or MINO with ABK or MINO concentrations at MIC or sub-MIC levels and by the subsequent antibiotic effect of CTM. 3. A combination of drugs which are different from each other in mechanisms of action and points of action is likely to show a consistent antibacterial effect, but a combination of drugs which are competitive to each other because they share mechanism and point of action possibly cause antagonism.

Investigations were made on effects of a combination therapy consisting of arbekacin (ABK) and ampicillin (ABPC) against methicillin-resistant Staphylococcus aureus (MRSA). The following conclusions were drawn. 1. A frequency of FIC index to beor = 0.5 upon a combination therapy consisting of ABK and ABPC against MRSA was 48.7%, hence this therapy showed better antibacterial effects than the other 8 combination therapies consisting of ABK and other antibiotics previously studied. 2. A combination therapy consisting of ABK and ABPC against MRSA was better than any other combination therapy because ABPC had a higher binding affinity with penicillin-binding protein 3 of MRSA, and because a high antibacterial activity of ABPC was maintained during the combination therapy. ABPC did not lose antibacterial activity largely because MRSA dose not produce beta-lactamase, or most of MRSA produces little beta-lactamase activity. 3. Our data indicate that the success of a combination therapy against MRSA depends upon the effects of the drug under sub MIC concentrations.

We obtained bacterial strains which were clinically isolated and identified from outpatients with various infections in medical institutions throughout Japan. Possible antibacterial activities of rokitamycin (RKM) were examined against these isolates. Minimum inhibitory concentrations (MICs) were determined through a comparative study with reference drugs. The results of the study are summarized as follows. 1. Resistance patterns of 400 isolates which were highly resistant to macrolides (MLs) with MIC values100 micrograms/ml were classified into 55 patterns. Staphylococcus spp. showed cross resistance to 14-membered ring MLs with 100% cross resistance observed between erythromycin (EM) and clarithromycin (CAM), and 85.2% between EM and oleandomycin (OL). Fewer isolates showed strong resistance to 16-membered ring MLs than to 14-membered ring MLs. Cross resistances observed among the Staphylococcus isolates were 100% between acetylmidecamycin (MDM-AC) and kitasamycin (leucomycin (LM)), 93.9% between MDM-AC and josamycin (JM), and 53.3% between MDM-AC and RKM. Streptococcus spp. and Peptococcus spp. showed very similar resistance patterns to both 14- and 16-membered ring MLs, but resistance patterns to RKM were quite different. Most of anaerobic streptococci and Bacteroides fragilis group had similar resistance patterns to 14- and 16-membered ring MLs, but in some cases a pattern similar to that of Staphylococcus spp. was observed. 2. When ML-resistant bacteria isolated during 1975 to 1980 were compared to those isolated in 1986 and 1989, it was observed that resistance of Staphylococcus aureus remained almost unchanged, that of Streptococcus pyogenes was lower in the later years than during 1975 to 1980, but that of Streptococcus pneumoniae increased. 3. Most of ML-resistances of the resistant isolates were inducible, but extents of induction varied depending on drugs tested. Strong inductions were observed when 14-membered ring MLs were used, but inductions were minimal with 16-membered ring MLs. RKM appeared to induce resistance to the least extent. From these results, it appears that the RKM is quite useful clinically even in the 1990s.

The authors studied antimicrobial activities of cefetamet (CFMT) and other leading oral antimicrobials of beta-lactam class against clinically isolated strains from urban respiratory tract infection (RTI) patients from January to March, 1992. 1. CFMT showed potent antimicrobial activities against "3 primary pathogens" of RTIs i.e., Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, but the drug had a slightly higher MIC than those of a few oxime-type cephems already on the market. 2. CFMT was as stable as cefixime to beta-lactamase, generated by Moraxella subgenus Branhamella catarrhalis, which reduces the antimicrobial activity of cephems. 3. Blood concentrations of CFMT after administering cefetamet pivoxil (CFMT-PI), an oral form of the drug, exceeded the MIC80 against the "3 primary pathogens" as well as M. (B) catarrhalis and Klebsiella pneumoniae, for a duration of approximately 9 and 11 hours, respectively, after single doses of 250 and 500 mg. This suggests that CFMT could remain above the MICs for a sufficient time period with twice daily dosages of normal dose levels. 4. It is concluded that CFMT-PI will be useful for treating urban RTIs.

Antimicrobial activity of ceftazidime (CAZ) was compared with those of other cephem antibiotics against clinically isolated strains sent to us by medical institutions throughout Japan in 1989 and 1991. Those strains separated and identified from samples collected from patients with various infections were also examined, and the following results were obtained. 1. The results suggested that, compared with reports of studies conducted with clinical isolates in early 1980's, MIC90 of CAZ in 1991 were markedly higher against Staphylococcus spp., Streptococcus pneumoniae, Escherichia coli, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii, and Pseudomonas aeruginosa. Also, among other bacteria such as Providencia rettgeri, Providencia stuartii, Xanthomonas maltophilia, and Bacteroides fragilis group, strains resistant to CAZ were observed in high proportions. However, large time-course changes were not observed in microbial activities of CAZ on Streptococcus pyogenes, Klebsiella spp, Proteus mirabilis, Pseudomonas cepacia, Acinetobacter calcoaceticus, Haemophilus influenzae and Anaerobic GPC (Gram-positive cocci). 2. Among the strains used in the study, methicillin-resistant Staphylococcus aureus (MRSA), Benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), cephamycin and oxime type cephem-resistant Gram-negative bacilli of Enterobacteriaceae and new quinolone-resistant organisms were observed in high proportions. It appears therefore, that CAZ failed to exert sufficient antimicrobial activities to these strains because of combination of resistance in these strains. 3. Antimicrobial activities of CAZ on recent clinical isolates showed problems as mentioned above. However, it was also demonstrated that CAZ maintained effective antimicrobial activities against most of the clinical isolates which could be causative organisms of infectious diseases in the clinical practice. When it is additionally taken into account that CAZ is one of those limited drugs with activity against P. aeruginosa, and it has excellent permeability through outer membrane, it is concluded that CAZ still is one of the clinically useful cephem drugs in 1990's.

Antibacterial effects of combination use of arbekacin (ABK) with cefmetazole (CMZ) or flomoxef (FMOX) were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and the following results were obtained. 1. Antibacterial effects of combinations of ABK with CMZ and with FMOX were equally potent against MRSA at clinically expected 1 MIC of ABK in blood. However, at a sub MIC of ABK different effects were observed between the 2 combinations. The former combination was slightly less effective than the latter. 2. In either combination the potency of the antibacterial activity was less dependent on the concentration of CMZ or FMOX, but was strongly dependent on ABK concentrations. These results suggest that antibacterial effects of the combinations were highly dependent on antibacterial potency and concentration of ABK as previously reported for combinations of ABK with other drugs. 3. It appears that the antibacterial activity of the combination of the sub MIC of ABK with a beta-lactam is an important point in considering the effectiveness of a combination therapy.

Antibacterial effects of combination use of arbekacin (ABK) with cefotiam (CTM) or cefuzonam (CZON) were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and the following results were obtained. 1. Antibacterial effects of combinations of ABK with CTM and with CZON were equally potent against MRSA at clinically expected 1 MIC of ABK in blood. However, at a sub MIC of ABK the different effects were observed between the 2 combinations. The antibacterial effect of the former was strong and that of the latter was a little weak. 2. In either combination the potency of the antibacterial activity was less dependent on the concentration of CTM or CZON, but was strongly dependent on ABK concentrations. These results suggest that antibacterial effects of the combinations were highly dependent on antibacterial potency and concentration of ABK as previously reported for combinations of ABK with other drugs. 3. The combination use of ABK with CTM appears to be useful in cases of infection by MRSA alone while the combination use of ABK with CZON appears to be useful in cases of double infection with MRSA and Gram-negative bacterium.

Clinical trials of ofloxacin (OFLX) otic solution, such as an early phase II study, a dose-finding study, a phase III double-blind comparative study and open studies, were conducted in the period from February 1988 to October 1989. In these studies, organisms were isolated from secretions of middle ear in patients with chronic otitis media and acute exacerbation of chronic otitis media, and from secretions of external ear in patients with external otitis. These organisms were subjected to identification, followed by determination of susceptibilities to OFLX and the other antibacterials. Results obtained are summarized as follows: 1. In total, 746 organisms were defined as the presumable causative organisms in 439 patients with otitis media and 80 with external otitis. Among the isolates, aerobic Gram-positive organisms were most prevalent, with an isolation rate of 66.9%, followed by aerobic Gram-negative organisms (32.4%), and obligate anaerobes (0.7%). Staphylococcus aureus and Pseudomonas aeruginosa were the organisms isolated most frequently among aerobic Gram-positive and Gram-negative bacteria, respectively. 2. The MIC90 of OFLX against the above 746 strains was 6.25 micrograms/ml. At this level, OFLX was 8 times more potent than cefmenoxime (CMX), and 32 times more potent than fosfomycin (FOM) and fradiomycin (FRM). It was postulated that OFLX retained higher local level than the MIC90 of the drug at 2 hours after topical adaptation of the otic solution, and had enough "above the MIC" and "time above MIC". 3. The MIC90 of OFLX against glucose-nonfermentative Gram-negative rods (GNF-GNR) including P. aeruginosa, which were isolated in 32.6% of the 519 patients, was superior to those of CMX, FOM, and FRM. The well-balanced antibacterial activity of OFLX was thought to be one of the properties of OFLX otic solution. 4. Previously-reported post antibiotic effect of OFLX was thought to be another property of OFLX otic solution. In conclusion, OFLX otic solution appeared to be clinically useful, because it possessed advantageous properties beyond other clinically-available otic solutions.