The in vitro activity of 4 carbapenem antibiotics, i. e., biapenem (BIPM), meropenem (MEPM), imipenem (IPM), and panipenem (PAPM), ampicillin, 2 cephalosporins, and vancomycin (VCM), was determined by the agar dilution method against 200 strains of Streptococcus pneumoniae isolated from patients with respiratory tract infections, acute otitis media, and purulent meningitis. Based on penicillin-binding proteins (PBPs) gene analysis by polymerase chain reaction, the prevalence of PSSP (penicillin-susceptible S. pneumoniae), PISP (penicillin-intermediate resistant S. pneumoniae), and PRSP (penicillin-resistant S. pneumoniae) was 51, 71 and 78 strains. MICs₅₀, and MICs₉₀, were as follows: 2 and 4, μg/mL ampicillin, 1 and 1, μg/mL cefotaxime (CTX), 4 and 8, μg/mL cefotiam, 0.125 and 0.25, μg/mL IPM, 0.063 and 0.125, μg/mL PAPM, 0.5 and 0.5, μg/mL MEPM, 0.25 and 0.5, μgmL BIPM, and 0.25 and 0.5, μg/mL VCM. Th bactericidal activity of carbapenems against 2 PRSP strains was significantly higher than that of cephalosporins. There was little difference among the activities of 4 carbapenems at concentrations lower than the breakpoint (1-2, μg/mL) recommended by the Japanese Society of Chemotherapy. PRSP strain ME-19 (serotype 19 F) was examined under a scanning electron microscope after exposure to BIPM, MEPM, or CTX at the MIC for 3 h. Peptidoglycan synthesis in the direction of the long axis and constriction in the septal region were inhibited by BIPM and MEPM. Cell lysis was observed near the septum as if a part of the cell wall was pulled apart. CTX inhibited septal synthesis and, as a result, filamentous cells were formed. Peptidoglycan synthesis in the long axis was almost normal, and only a few cells were lysed by short-term observation. From these results, we speculate that the clinical effect of the 4 carbapenems against pneumonia and sepsis cases caused by PRSP can be expected at the same level of activity when a host does not have a risk factor.

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Drug compliance is an especially important issue in infectious disease therapy. We studied the compliance of oral medicine consumption in patients with uterine cervicitis caused by Chlamydia trachomatis. Among students and office employees, the lack of compliance was high, especially after breakfast and lunch. Among housewives, the lack of compliance was very low. The major reasons for lack of compliance were lack of breakfast and transporting action. The ideal frequency of oral medicine in students and office employees with uterine cervicitis is single therapy, and in housewives, twice a day. Guidance in drug compliance is important in therapy for sexually transmitted diseases.

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No method of therapeutic drug monitoring (TDM) of teicoplanin (TEIC) has been established. We compared the predictivity of different TDM strategies. Four dosing calculation were evaluated in 7 patients treated with TEIC. Based on initial determined drug concentrations, the drug concentration in a steady state was predicted by the Sawchuck-Zaske (Zaske) and extrapolated Vd (volume of distribution) methods. Initial blood samples were obtained at the baseline, 2 or 6 h after administration, and just before the next dose on day 3 or 4. Steady-state samples were obtained just before administration on days 7 to 10. Analytical procedures for initial dosing calculation using different sets of blood concentrations were as follows: Zaske method. Clearance (CL) and Vd were calculated using 3 concentrations: trough, 2 or 6 h, and the next trough. Extrapolated Vd method. CL was calculated from the fixed Vd to 1 L/kg and the trough. In the 5 cases where an almost steady state concentration was reached at initial dosing calculation, the extrapolated Vd method had better prediction precision than the Zaske method, although no significant differences were seen in prediction accuracy and prediction bias. The correlation (r=0.83) between the concentration predicted by the Zaske method and concentrations obtained at a steady state decreased to r=0.67 in all 5 cases. Estimation by the Zaske method in a non steady state did not seem justified. Vd (0.44 L/kg) calculated by the Zaske method using 2 h was less than half the at reported (1 L /kg). CL calculated by both methods was larger than the at reported (0.008 L/h/kg), although no significant differences were seen between the Zaske method (0.018-0.022 L/h/kg) and extrapolated Vd method (0.024-0.026 L/h/kg). We concluded that the Zaske method may be inadequate for TEIC TDM. The authenticity of parameters estimated by both methods in initial dosing calculation is low, and additional studies may be needed to obtain better predictive performance. When comparing different combinations of time samples, 1-point approaches at 3 or 4 days and also at a steady state are recommended.

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Antimicrobial susceptibility of 80 clinical isolates of Streptococcus pneumoniae isolated from pediatric patients in the Republic of Korea (Korea) from 1995 to 1997 was evaluated and compared to that of 53 Japanese strains isolated from 1996 to 1998 using bebzylpenicillin, quinolones, oral cephems, minocycline, and clarithromycin. The rate of penicillin-intermediately resistant/-resistant strains with MICs exceeding 0.125 μg/mL for bebzylpenicillin in Korean strains was 72.5%, that was greater than that in Japanese strains (49.1%). Oral cephem-susceptible strains (MIC for cefteram <0.0313 μg/mL) were found more frequently in Korean than Japanes strains. Minocycline susceptibility of strains from both countries was similar. There were more strains with high resistance to clarithromycin in Korea than in Japan. Neither country had fluoroquinolone-resistant strains.

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A 68-year-old woman with right-side lumbago was found to have a right adrenal tumor, which we resected in December 1999. The pathological diagnosis was adrenocortica adenoma. A tumor hump along the surgical incision appeared in June 2000. Needle biopsy indicated local recurrence of adrenocortical carcinoma. Mitotane therapy was started from August 2000, and tumors decreased markedly in size. Adrenocortical carcinoma is comparatively rare disease, found as a convalescence defective disease occurring in both men and women in all ages. Surgery remains the primary, definitive, single potentially curative treatment for adrenocortical carcinoma. Incomplete resection has an extremely poor prognosis. Our administration of mitotane in a case with local recurrence clearly reduced tumor size.

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A 59-year-old woman with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis treated using teicoplanin (TEIC) had moderate chronic renal failure, so she was treated carefully with therapeutic drug monitoring (TDM) of TEIC. At first, she was treated with vancomycin (VCM) by intravenous infusion and VCM bead replacement therapy. Short-term remission was achieved, but only 2 months of treatment for renal failure was exacerbated, so the interruption of treatment led her osteomyelitis to recur. TEIC has 2 advantages over other anti-MRSA drugslittle influence on the kidneys, and good treatment of bone-so we chose TEIC for this patient, using TDM to set the adequate dose and interval. TEIC can be used in long-term medication without reducing kidney function and can be used safely and effectively with TDM, meaning TEIC is a possible alternative in treating MRSA osteomyelitis.

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