We previously demonstrated that 14-membered macrolides increase endogenous glucocorticoid levels in mice and suggested that the macrolides may modulate host biological responses. We therefore studied the effect of anti-tuberculous on serum glucocorticoid levels in mice. Intraperitoneal administration of rifampicin increased serum corticosterone levels in a dose-dependent manner in mice, as did isoniazid and D-cycloserine. However, the enhancing activities of isoniazid and D-cycloserine were weaker than that of rifampicin. The intraperitoneal administration of pyrazinamide did not affect serum corticosterone levels. The enhancing activity of rifampicin on serum corticosterone levels was completely suppressed by pre-treatment with dexamethasone. These results suggest that rifampicin enhances endogenous glucocorticoid production through the activation of the hypothalamo-pituitary-adrenocortical axis. Rifampicin may modulate host biological responses through the activation of this axis.

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We examined clinical isolates from urinary samples obtained at Nagasaki University Hospital between 1984 and 2000. Enterococcus species, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were the predominant pathogens. The incidence of isolation of Enterococcus species, S. aureus, and P. aeruginosa, which are resistant against several antibiotics in nature, has been gradually increasing. The susceptibility of P. aeruginosa and Serratia marcescens isolates to several antibiotics has improved from 1985 to 1999, whereas Enterobacter cloacae isolates have become more resistant during the same duration. Vancomycin-resistant enterococci, excluding isolates carrying vanC, have not been isolated from our hospital to date. In carbapenemase-producing bacteria associated with bla_IMP, P. aeruginosa was the major pathogen. In some patients with P. aeruginosa carrying bla_IMP, resistant bacteria disappeared following antibiotic administration; most such resistant bacteria were isolated from urinary tracts. Although gentamicin completely killed P. aeruginosa on the surface of MDCK cells within 2 hours, ceftazidime and meropenem did not kill any bacteria even if at concentrations up to 1, 600μg/mL.

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We studied the incidence of bacteriuria and the clinical response to and side effects from antimicrobial chemotherapy against symptomatic urinary tract infection in patients 85 years or older to determine appropriate antimicrobial chemotherapy against such infection. (1) The incidence of bacteriuria was screened in 80 patients who visited the Department of Urology and 849 healthy people who visited the Health Control Center of Jikei University School of Medicine for physical check-ups, between January and March 2001. Bacteriuria cases were classified into 3 groups: symptomatic urinary tract infection, asymptomatic urinary tract infection, and colonization. In men, the incidence of asymptomatic urinary tract infection rose with advancing age. In women, however, the incidence of bacteriuria did not change with age. (2) The incidence ofside effects from tosufuloxacin tosilate and imipenem/cilastatin in elderly patients was taken from the post marketing surveillance database. No significant differences were seen in the effectiveness and incidence of side effects between elderly and younger patients. These results indicated that antimicrobial chemotherapy for urinary tract infection in elderly patients need not differ from that in younger patlents.

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The pharmacokinetics of renally excreted β-lactams, aminoglycosides, and glycopeptides were studied in patients with renal dysfunction classified into 4 categories by 24-hour creatinine clearance (Ccr):(1) normal function (Ccr>70mL/minute), (2) minimum dysfunction (70>Ccr>50mL/minute), (3) moderate dysfunction (50>Ccr>30mL/minute), and (4) severe dysfunction (30mL/minute>Ccr). A significant correlation was seen between β and Ccr, generally implying that dosage regimens for renallv excreted drugs can be determined based on Ccr. In Ccr 50mL/minute, a half dosage at regular intervals or regular dosage at double intervals is recommended. In Ccr 30mL/minute, one third dosage at regular intervals or regular dosage at triple intervals is recommended. For drugs with narrow safety windows such as vancomycin and aminoglycosides, similar dosage regimens are apply, but doses carefully adjusted based on therapeutic drug monitoring is essential to ensure therapeutic effects and the prevention of side effects. Hepatic dysfunction induced by antimicrobial agents is often attributed to an allergic reaction. In such cases, antimicrobial agents with a different structural formula should be selected. For patients with hepatic dysfunction, agents with high bile excretion should be avoided.

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Upper urinary tract infections produce adverse renal consequences. Antibiotic prophylaxis prevents urinary tract infections; however, the appropriate indications for antibiotic prophylaxis are not well defined. Convincing evidence regarding the benefit of antibiotic prophylaxis in infants antenatally diagnosed as having hydronephrosis or hydroureteronephrosis has not yet been documented. We reviewed the medical records of patients who were antenatally diagnosed as having obstructive uropathy, or who experienced episodes of urinary tract infections after birth. Nine of 68 patients with hydronephrosis had urinary tract infections, while six of 14 patients with hydroureteronephrosis had urinary tract infections. We conclude that infants with hydroureteronephrosis are likely to have urinary tract infections, and antibiotic prophylaxis may be warranted.

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Beta lactams are basic to treating urinary tract infection in obstetrics and gynecology, especially during in pregnancy. Vaginal flora is highly associated with urinary tract infection. Since Lactobacillus species protect against abnormal growth of other bacteria, they mey be useful against bacterial vaginosis. Hormone replacement therapy is important perimenopausal therapy for urinary tract infection. The urethral syndrome caused by Chlamydia trachomatis is increasing.

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