We evaluated 97 cases of infection by methicillin-resistant Staphylococcus aureus at the Fukuoka University Hospital, where this infection presents a serious problem. We evaluated the origin of specimens, coagulase typing, production of toxic shock syndrome toxin-1 (TSST-1) and susceptibility to various antimicrobial agents isolated at between February and May 1989. Specimens consisted primarily of sputum and pus. Sixty percent of all strains produced coagulase type VII. Only 4 strains produced TSST-1. Vancomycin, rifampicin, clindamycin, and sulfamethoxazole/trimethoprim showed good antibacterial activities against MRSA. Coagulase type VII strains were resistant to minocycline but sensitive to erythromycin and clindamycin as compared with those of type IV.

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Twelve species (4, 404 strains) of clinical isolates of bacteria were collected from 6 institutes during a five-year period from 1987 to 1991. We determined the susceptibility to ofloxacin and compared it with that to other antimicrobial agents. There were no significant changes in the MIC_50S of ofloxacin for any of the 12 species tested, though the MIC₉₀s for Staphylococcus aureus, Coagulase-negative staphylococci and Pseudomonas aeruginosa increased. Similar results were observed with ciprofloxacin and the other quinolones tested. The isolation frequency of methicillin-resisntant S. aureus (MRSA) among S. aureus in 1987 was almost the same as that in 1991, but that of ofloxacin-resistant S. aureus among MRSA increased considerably from 27% to 72%.

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We investigated the ability of six β-lactam antibiotics, ceftazidime (CAZ), cefoperazone (CPZ) cefsulodin (CFS), latamoxef (LMOX), aztreonam (AZT) and imipenem/cilastatin (IPM), to induce β-lactamase production in thirteen clinical isolates of Pseudomonas aeruginosa. We classified thirteen P. aeruginosa strains into three groups based on susceptibility to CAZ, and compared the six β-lactam antibiotics for rates of induction of β-lactamase. As a result, IPM was shown to have the highest inducing potential in the three strain groups. When induced by IPM, β-lactamase activity increased 330-fold in the CAZ-susceptible strains (S group), and 165-fold in the CAZ-low level resistant strains (LR group). However, neither CAZ, CPZ, CFS, LMOX nor AZT showed high inducing activities in the S or LR strain groups. In contrast, in the CAZ-high level resistant strains (HR group), all six β-lactam antibiotics showed low induction potential for β-lactamase. The MICs for strains in the S group measured after β-lactamase induction by IPM increased 18 times for CPZ, 12 times for CAZ, 8 times for CFS, 5 times for LMOX, 4 times for AZT. Uninduced and IPMinduced β-lactamase activities correlated with the MICs of CAZ, CPZ, CFS, LMOX and AZT, respectively.

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In vitro and in vivo bactericidal activities of five cephems [cefazolin (CEZ), cefotiam (CTM), cefmetazole (CMZ), cefotaxime (CTX), and cefoperazone (CPZ)] against Escherichia coli TK-16 R (a non-β-lactamase-producing strain) were studied in a mixed system with strains possessing inducibleti-lactamases (Enterobacter cloacae H-27, Proteus vulgaris T-178, Morganellamorganii T-211, Providencia rettgeri GN4430, and Serratia marcescens W-24). The following results were obtained.
1) In mixed cultures with strains possessing inducible β-lactamases, CEZ and CTM showed lower bactericidal activity against E. coli than that in pure cultures of E. coli. The bactericidal activity of CMZ was reduced in mixed cultures except for P. vulgaris. CTX was more active in mixed cultures than CEZ, CTM, or CMZ, but E. coli regrew in the presence of CTX in mixed cultures except for S. marcescens. Among the five cephems, CPZ was the most active agent in mixed cultures.
2) In mixed infections of rat pouches caused by E. coli and E. cloacae, the bactericidal activity of CMZ against E. coli was reduced, whereas, CPZ acted bactericidally on E. coli in pure and mixed infections.
3) In the β-lactamase inducibility tests, CMZ induced the largest amount of enzyme among the five cephems, followed by CTX, CTM and CEZ. In contrast to CMZ, CPZ caused little induction of β-lactamase production in any of the strains, tested.
4) Against the majority of enzymes tested, CEZ and CTM showed the largest V_max and Km values among the five cephems, followed by CPZ. CMZ or CTX tended to show the lowest V_max and Km (Ki) values. The V_max/Km or Ki values of these five cephems were similar, and the differences between them were less than the differences between the Vmax values.
5) These results suggest that the amount of β-lactamase induced by a cephem and β-lactamase lability of the cephem (Vmax and V_max/Km or Ki values) were important factors influencing in vitro and in vivo reduction of bactericidal activity of the cephem against E. coli in a mixed system with strains possessing inducible β-lactamases.

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Recently, theophylline products have been frequently used for bronchial asthma. However, their efficacy and safety are known to be restricted, and their pharmacokinetics change depending on what drugs they are co-prescribed with. We studied the effects of two macrolide antibiotics, erythromycin (EM) and roxithromycin (RXM), on serum theophylline concentration (STC). The subjects were 6 asthmatic children. A 200 mg dese of Theo-long^® was administered twice a day for one week, 300mg EM was concurrently administered three times a day from the 8th day for one week, and 150mg RXM was concurrently administered twice a day from the 22nd day for one week. Blood sampling was conducted every day from the days EM and RXM were first co-prescribed. On the 7th day after starting Theo-long^® administration and co-prescription of EM or RXM, we sampled blood and measured STC. The results indicated that STC started to increase from the 4th day after coprescription of EM, and an approximatly 30% increase was observed on the 7th day, compared to the values prior to co-prescription. On the other hand, STC did not increase after co-prescription of RXM. Significant increases of T_max and AUC were observed during the co-prescription period of EM compared with the period when only Theo-long^® was administered. However, there were no significant differences in C_max, T_max, AUC and t_1/2 during the co-prescription period of RXM. In conclusion, the effect of RXM on theophylline metabolism was very small compared to that of EM.

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Detection of Chlamydia trachomatis in first-void urine (FVU) by polymerase chain reaction (PCR) has been repoted to be a useful non-invasive test for diagnosing male urethritis caused by C. trachomatis. Although C. trachomatis is killed by antimicrobials therapy, its DNA may remain, and a highly sensitive PCR might give a positive result for C. trachomatis. To evaluate PCR as a method for posttveatment determination of the efficacy of antimicrobial drugs against chlamydial urethritis, test-of-cure analysis by PCR for detecting C. trachomatis in FVU was performed in 25 patients with nongonococcal urethritis, in whom C. trachomatis was detected in FVU by both PCR and IDEIA^® chlamydia. Six patients were treated with 200mg of DOXY for 7 days, and 19 were treated with 450mg of tosufloxacin (TFLX) for 7 days. After treatment, PCR and IDEIA^® were carried out for detection of C. trachomatis. IDEIA^® was negative in 24 patients, and positive in one patient. PCR was negative in all patients. Clinical symptoms resolved and FVU sediments normalized in all patients. In one patient, though, C. trachomatis was detected by IDEIA^® regardless of resolution of clinical symptoms and normalization of FVU sediments. The results with PCR were in complete agreement with the clinical results. Therefore, PCR may be useful for monitoring the clinical efficacy of chemotherapy against chlamydial urethritis.

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We investigated the pharmacokinetics and effects of imipenem cilastatin sodium (IPM/CS) administered in four divided doses per day in the treatment of patients with pulmonary infection. The results were as follows:
1) IPM/CS was given to 46 patients at 2.0g/day divided into four doses. In these 46 cases, the results were excellent in 15, good in 28, fair in 1, poor in 2. The clinical efficacy rate was 93.5%. Rash and epigastric discomfort were observed as adverse reactions in 1 case each.
2) With four divided doses, the concentration of imipenem (IPM) in serum and sputum remained high for a longer time than with twice daily administration.
3) The clinical efficacy rate was 70% on the fifth day and 92% on the seventh day. Mean duration of treatment was short, 10.9 days.
Based on these results, we conclude that daily administration of IPM in four divided doses provides excellent efficacy and safety, and reduces the required duration of treatment.

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