Tetsuro Matsumoto

Preventive Effect of Dapsone on Renal Scarring following Mannose-Sensitive Piliated Bacterial Infection

Renal scarring has been thought to occur in the later stages of chronic pyelonephritis. We previously reported that mannose-sensitive (MS) piliated bacteria promoted renal scarring, which was prevented by antioxidants. The preventive effect of diaphenylsulfone (dapsone), which has a scavenging activity on active oxygen species, on renal scarring was examined. Female Sprague-Dawley rats were inoculated with clinical isolates of Serratia marcescens which had both MS and mannose-resistant pili or with recombinant strains which had MS pili on their surface; they were then administered 20 mg/kg of dapsone or not. Dapsone significantly suppressed scarring following infection of the kidney. The bacterial counts in the kidneys were not different in dapsone-treated and nontreated rats. We conclude that dapsone is effective in preventing renal scarring, and it is suggested that the clinical use of this drug may prevent renal scar formation following pyelonephritis.

Distribution of a Methicillin-Resistance Gene in Urinary Isolates of Methicillin-Resistant Staphylococci Examined by Enzymatic Detection of the Polymerase Chain Reaction

We tried to examine the susceptibility to various antimicrobial agents and to detect the mec A gene using enzymatic detection of the polymerase chain reaction in methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive Staphylococcus aureus (MSSA) and Staphylococcus epidermidis isolated from patients with complicated urinary tract infections (UTIs). All the strains of MRSA and MSSA showed a low sensitivity to imipenem (IPM), ceftazidime (CAZ), flomoxef (FMOX), amikacin (AMK), ciprofloxacin (CPFX) and ofloxacin (OFLX). Although all the strains of MRSA had the mec A gene, none of the MSSA strains had it. 74% of S. epidermidis had the mec A gene and strains resistant to methicillin were seen in 72% of them. The mec A-positive S. epidermidis showed a lower susceptibility to IPM, CAZ, FMOX, AMK, CPFX and OFLX than the mec A-negative strains. These results suggest that methicillin resistance was due to the mec A gene in MRSA and methicillin-resistant S. epidermidis (MRSE), and that MRSEs were very common among the bacteria causing complicated UTI. When we try to control nosocomial infections due to MRSA, it should also be noted that MRSE can be a reservoir of the mec A gene.

Role of superoxide in pyelonephritis.

The role of superoxide in scar formation following renal infection caused by mannose-sensitive (MS) -piliated strains of bacteria was studied in the experimental pyclonephritis model using female Sprague-Dawley rats. The MS-piliated strain stimulated renal scarring to a significantly greater extent than either the non-piliated or mannose-resistant (MR) -piliated strains. Modification of leukocytes by administering cyclophosphamide to induce neutropenia and colchicine to inhibit leukocyte migration was effective in preventing renal scarring. Treatment with superoxide dismutase during the early stage of infection was also effective in preventing scar formation. Finally, the production of superoxide following stimulation by MS-piliated strain was larger amount than it following stimulation by either non-piliated or MR-piliated strains.These observations suggest that superoxide released from leukocytes plays an important role in the development of renal scarring following infection by MS-piliated strains.

Relation between renal scar formation and bacterial pili in the experimental chronic pyelonephritis model.

Renal scarring is thought to be end-stage of chronic pyelonephritis and one of important causes of renal insufficiency and renal hypertension. Significance of bacterial pili was examined in scar formation by the use of artificial variants which possessed either MR or MS pili of S. marcescens, and the result described below was obtained. MS piliated bacteria stimulated renal scarring more severely than MR piliated bacteria. This scarring mediated by MS piliated bacteria was prevented by superoxide dismutase.These findings suggested that the MS pili stimulated polymorphonuclear leukocytes to release large amount of superoxide and this superoxide damaged the renal tissue, resulted in the renal scar.