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

View full abstract

Antimicrobial activities of oral β-lactam antimicrobial agents against clinically isolated 131 strains ofHaemophilus influenzae were studied. The peak of MICs of ampicillin (ABPC) was 0.20μg/ml. Those ofcefaclor (CCL), cefotiam (CTM), cefteram (CFTM), cefpodoxime (CPDX), cefdinir (CFDN), cefditoren (CDTR), cefcapene (CFPN), and faropenem (FRPM) were 1.56, 0.39, 0.013, 0.05, 0.20, 0.013, 0.013, and0.39μg/ml, respectively. The antimicrobial activities of CFTM, CDTR and CFPN were superior to those of others.There was 74.8% of ABPC-sensitive strains, of which the MICs were below 0.78μg/ml. The percentages of β-lactamase-positive strains and β-lactamase-negative ABPC-resisitant H. influenzae (BLNAR) were 14.5% and 14%, respectively.

View full abstract

Investigations on emergence of vancomycin-resistant Enterococcus faecium (VREF) which has recentlybeen attracting attention, especially in the Western contries, have been conducted in Japan. A total of 1,239isolates of E. faecium were collected from 19 institutions during the period of April 1995 and June 1996, in thepurpose of evaluating susceptibilities to variety of antimicrobial agents, including RP59500 and vancomycin (VCM), and detecting vancomycin-resistant genes (van genes). Susceptibilities of penicillin-resistantStreptococcus pneumoniae (PRSP) and methicillin-resistant Staphylococcus aureus (MRSA) were also studied.
As a result, 2 isolates of E. faecium were found to be moderately resistant to VCM showing MIC of 8 μg/mlthough the final identification in species level and the detection of van genes by PCR method have not beencompleted. On the other hand, there detected no MRSA nor PRSP showing moderately resistant or resistant to VCM. It was concluded that RP59500 and VCM possessed favorable activity against clinically isolated E.faecium, PRSP and MRSA.
Among other species of enterococci, moderately resistant strains to VCM showing MIC of 8 μg/ml weredetected; 10 isolates of E. gallinarum, 4 of E. casseliflavus and 2 of E. flavescens. In those isolates, van C1 and van C2 were detected by PCR, and vanB was also detected in a isolates of E. gallinarum simultaneously.

View full abstract

We examined drug-resistance patterns, coagulase types, and MRSA-phage types of 125 MRSA strainsisolated from clinical specimens during the period of January 1990 and December 1994.
No vancomycin-resistant strain was isolated. Twenty one antibiotics were divided into three classes, low-, intermediate- and high-isolation-frequency class, based on isolation frequencies of resistant strains. Minocycline, chloramphenicol, streptomycin, and imipenem were found to be included in low-isolation-frequency class (16.8-40%). In intermediate-isolation-frequency class (45.6-62.9%), cefmetazole, amikacin, gentamicin, and tetracycline were included. Oxacillin, ampicillin, piperacillin, ceftizoxime, cefoperazone, cefazolin, erythromycin, oleandomycin, kitasamycin, clindamycin, kanamycin, tobramycin, and ofloxacin belonged to high-isolationfrequencyclass (97.6-100%). MIC₉₀s of vancomycin and minocycline (1.56 and 25 μg/ml) were lower than thatof other 13 drugs.
Comparing medical ward with dental ward, imipenem-, gentamicin-, and minocycline-resistant strains atmedical ward, chloramphenicol- and streptomycin-resistant strains at dental ward were isolated dominantly oneach ward. MRSA isolates were classified to 39 types by drug-resistance patterns.
The isolation frequencies of coagulase type II and type IV strains were 65.6% and 29.6%, respectively. Atdental ward, the isolation frequency of coagulase type IV strains was higher than that of coagulase type II strainsduring 1990-1992. However, coagulase type II strains were isolated considerably more than type IV strainsduring 1993-1994.
By MRSA-phage typing, MRSA isolates were grouped into 18 MRSA-phage types.
One hundred and twenty five MRSA isolates were divided into 56 types by using drug-resistance patterns, coagulase typing, and MRSA-phage typing.
It was considered that such classification in combination of three methods is useful to make decision ofepidemic by the same MRSA strain.

View full abstract

Clinical and bacteriological evaluation was performed as follows on ceftriaxone (CTRX) at a dose of 50mg/kg once daily to pediatric patients with community-acquired pneumonia.
Of 48 subject patients, CTRX was markedly effective in 36 (75.0%), effective in 9 (18.7%), slightly effectivein 2 (4.2%), and failure in 1 (2.1%), indicating the overall effective rate of 93.7%. In 47 (97.9%) patients with theexception of 1, it was observed during the period of administration that fever was resolved and clinical symptomsas well as radiographically abnormal shadows were found relieved or improved.
Patients infected by an isolated strain accounted for 34 (70.8%), while those by multiple strains 14 (29.2%), indicating that either Streptococcus pneumoniae or ^{Haemophilus influenzae}, or both were detected in almost allpatients (45 cases).
Of the 48 patients, bacteriological effect was eliminated in 44 (91.7%), and replacement of the bacteria inthe remaining 4 (8.3%).
MIC₉₀ of CTRX against detected bacteria was 0.2μg/ml with H. influenzae, ≤0.025μg/ml with PSSP, 0.1μg/ml with PISP, and 0.39μg/ml with PRSP.
Blood concentration of CTRX at 50mg/kg upon completion of 1-hour drip intravenous infusion was89.7±25.2μg/ml, and 6.6±0.9μg/ml at 24 hours after the completion, indicating that the concentrations hadbeen well above the levels of MIC₉₀ throughout the 24 hours.
Abnormal symptoms, which were most likely adverse drug reactions, were not observed in any patients, andno abnormal changes were noted in patients, whose clinical lab values were taken before or after the administration.
Situations may differ by region in Japan, however, infants under 3 are generally exempted from medical paymentregardless of inpatients or outpatients. When hospitalized, psychological burden upon pediatric patientswithout guardians attended must be enormous. If they are over 3, there is a difference in medical costs betweeninpatients and outpatients, with greater economic burden on inpatients. Thus, it was considered worth attemptingthe outpatient treatment as one of new therapies for community-acquired pneumonia, though the outpatient treatmentshould not be encouraged without due consideration.
Based on these results, CTRX dosed once daily to pediatric patients with community-acquired pneumonia isclinically and bacteriologically superior in usefulness. Further review may be necessary, however, it is consideredthat outpatient treatment can also serve as one of the options, if safety of once-a-day administration of CTRX can be established.

View full abstract

The results of the semi-annual nationwide surveillance of antimicrobial susceptibilities, conducted by the Japanese Ministry of Health and Welfare during the period of January 1993 to July 1995, were analyzed for typical Gram-negative bacilli in the purpose of provision of an index for antimicrobial selection.
During these 3 years, Escherichia coli, Citrobacter freundii, Enterobacter aerogenes and Proteus mirabilisshowed slightly increasing tendency in susceptibility to fosfomycin (FOM) and Citrobacter freundii, Klebsiellapneumoniae and Enterobacter aerogenes showed slightly increasing tendency to minocycline (MINO). WhileHaemophilus influenzae and Haemophilus parainfluenzae showed slightly decreasing tendency to cefmetazole (CMZ). However, these annual changes were almost negligible.
Generally, these microorganisms showed relatively good susceptibilities, every year, to the principal antimicrobialagents being approved for use against Gram-negative bacilli. However, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens and Pseudomonas aeruginosa showed tendencies of decresed susceptibilityto some of the antimicrobial agents.
On the other hand, sulfamethoxazole-trimethoprim (ST), CMZ, latamoxef (LMOX), gentamicin (GM) andamikacin (AMK) showed good activities against some of the Gram-negative bacilli towhich no indications areapproved.
In conclusion, bedside the identification of the causative microorganisms and the performance of antimicrobialsusceptibility testing, such analyses (graphics of susceptibility tendency ofclinical isolates to variety ofantimicrobial agents) could be used as an index for selection of antimicrobial agents, when emergent and urgent selection of antimicrobial agents is necessary.

View full abstract