Mina Kikuchi

Remarkable increase in fluoroquinolone-resistant Mycoplasma genitalium in Japan

OBJECTIVES We determined the prevalence of macrolide and fluoroquinolone resistance-associated mutations in Mycoplasma genitalium DNA specimens from men with non-gonococcal urethritis (NGU) and analysed their effects on antibiotic treatments of M. genitalium infections. METHODS In this retrospective study, we examined antibiotic resistance-associated mutations in the 23S rRNA, gyrA and parC genes of M. genitalium and the association of the mutations with microbiological outcomes of antibiotic treatments in men with M. genitalium-positive NGU. RESULTS No macrolide resistance-associated mutations in the 23S rRNA gene were observed in 27 M. genitalium DNA specimens in 2011 and in 24 in 2012. However, 5 of 17 in 2013 had 23S rRNA mutations. Three of 15 in 2011, 6 of 19 in 2012 and 8 of 17 in 2013 had fluoroquinolone resistance-associated alterations in ParC. Three in 2013 had both the antibiotic resistance-associated alterations coincidentally. In two men with M. genitalium harbouring 23S rRNA mutations, the mycoplasma persisted after treatment with a regimen of 2 g of extended-release azithromycin (AZM-SR) once daily for 1 day. All nine men with mycoplasma harbouring ParC alterations were microbiologically cured with a regimen of 100 mg of sitafloxacin twice daily for 7 days. CONCLUSIONS Macrolide- or fluoroquinolone-resistant M. genitalium appears to be increasing, and the increase in fluoroquinolone-resistant mycoplasmas is especially remarkable in Japan. Mycoplasmas harbouring 23S rRNA mutations would be resistant to the AZM-SR regimen, but those harbouring ParC alterations would still be susceptible to the sitafloxacin regimen.

Drug Resistance-Associated Mutations in Mycoplasma genitalium in Female Sex Workers, Japan

Mycoplasma genitalium was detected in 21 (14.1%) of 149 vaginal swab samples and in 1 (0.7%) of 149 throat washing samples from female sex workers during 2013–2014 in Japan. Prevalences of M. genitalium with macrolide resistance–associated 23S rRNA mutations and fluoroquinolone resistance–associated parC alterations were 47.1% and 36.8%, respectively.

Sitafloxacin: Antimicrobial activity against ciprofloxacin-selected laboratory mutants of Mycoplasma genitalium and inhibitory activity against its DNA gyrase and topoisomerase IV

A sitafloxacin regimen is highly effective on Mycoplasma genitalium infections, including those caused by the mycoplasmas harboring mutant topoisomerase IV with a quinolone resistance-associated amino acid change in ParC. In this study, we evaluated sitafloxacin antimicrobial activities against M. genitalium, including the mycoplasmas with decreased susceptibilities to quinolones, by determining minimum inhibitory concentrations (MICs) for the strain ATCC 33530 and its 3 ciprofloxacin-selected mutants, for which ciprofloxacin MICs were 8-16 times higher than that for their parent strain. We also evaluated inhibitory activities against the target enzymes of M. genitalium by determining concentrations required to inhibit 50% (IC50) of the supercoiling activity of the recombinant wild-type DNA gyrase and the decatenating activities of the recombinant wild-type topoisomerase IV and the 2 types of mutant topoisomerase IV with a single amino acid change in ParC. Sitafloxacin MICs were 0.125 for the parent strain and 0.125-0.25 μg/ml for the mutants. Sitafloxacin IC50s were 3.12 for the supercoiling activity of the wild-type DNA gyrase and 2.98 μg/ml for the decatenating activity of the wild-type topoisomerase IV. Its IC50s for the decatenating activity of the mutant topoisomerase IV harboring an amino acid change in ParC were 15.1 for Gly-81 → Cys and 7.92 μg/ml for Asp-87 → Tyr. Sitafloxacin was highly active against ciprofloxacin-selected mutants of M. genitalium and possessed intense inhibitory activities not only against wild-type DNA gyrase and topoisomerase IV but also against mutant topoisomerase IV containing ParC with a quinolone resistance-associated amino acid change. Sitafloxacin could be a promising agent for M. genitalium infections.

Efficacy of combination therapy with tamsulosin and zolpidem on nocturia in patients with benign prostatic hyperplasia

Introduction We examined the efficacy of combination therapy with α1-blocker tamsulosin and hypnotic zolpidem in patients who had suffered from sleep disturbance associated with nocturia. Material and methods A total of 35 patients diagnosed with nocturia with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) were studied. After treatment with tamsulosin for 4 weeks, 16 patients dissatisfied with nocturia (nocturiaquality of life index ≥4) and suspected to have sleep disturbance (Athens Insomnia Scale ≥6) received additional treatment with tamsulosin and zolpidem for 2 weeks. Outcomes were evaluated by the International Prostate Symptom Score (IPSS) and quality of life index (QOL), Athens Insomnia Scale (AIS) and nocturia-quality of life index (nocturia-QOL). Results After monotherapy with tamsulosin, significant reductions in IPSS (18.9 ±3.8 to 9.9 ±3.0, p <0.001), QOL (4.5 ±0.9 to 3.2 ±0.9, p <0.001) and nocturia episodes (3.4 ±0.7 to 2.6 ±1.0, p <0.001) were observed. However 20 patients were dissatisfied with nocturia (nocturia- QOL ≥4). Among 20 patients, 16 patients were suspected to have sleep disturbances (AIS ≥6). In these patients, additional therapy with tamsulosin and zolpidem significantly reduced nocturia episodes (3.3 ±0.8 to 1.9 ±0.7, p <0.001), AIS (10.6 ±2.9 to 6.8 ±25, p <0.001) and nocturia – QOL (5.6 ±0.5 to 3.6 ±1.1, p <0.001) compared with patients after treatment with tamsulosin only. Conclusions Combination therapy with tamsulosin and zolpidem may be useful for patients with BPH dissatisfied with nocturia and suspected to have sleep disturbance.

Postoperative infectious complications in patients undergoing holmium laser enucleation of the prostate: Risk factors and microbiological analysis

To examine the incidence of postoperative bacteriuria and febrile complications, and to investigate bacterial strains in the urine of patients undergoing holmium laser enucleation of the prostate.

ALK Gene Translocation in Inflammatory Myofibroblastic Tumor of the Urinary Bladder: A Case Report.

A 26-year-old woman with gross hematuria was seen in a previous hospital. Magnetic resonance imaging (MRI) showed a tumor at the dome of the urinary bladder with invasion outside of the bladder wall. The patient underwent transurethral resection of the bladder tumor (TUR-BT). From the result of the pathological examination, the tumor was suggested to be carcinosarcoma of the bladder. The patient was then referred to our hospital for treatment. We performed radical cystectomy and ileal conduit diversion. Pathological examination of the excised specimen revealed an inflammatory myofibroblastic tumor as the basis for immunostaining of anaplastic lymphoma kinase (ALK).

Thyroidization in renal allografts

Abstract:  Thyroidization (thyroid‐like appearance) in renal tissue which is made up of a colloid‐like hyaline cast formation of Tamm‐Horsfall glycoprotein (THP) is a common finding in chronic pyelonephritis and obstructive nephropathy. This type of pathological change is sometimes observed in renal allograft specimens. We examined allograft specimens for thyroidization and other pathological findings related to thyroidization to characterize the conditions causing such changes. One‐hundred three patients who underwent renal transplantation between January 2006 and April 2008 at Gifu University Hospital (251 renal allograft biopsy specimens) were enrolled in this study. Sixteen patients had thyroidization (11 mild, 4 moderate, and 1 severe). In four patients, THP reflux on Bowman’s capsule was found, and in three patients interstitial THP deposits were observed. In four patients, tubulointerstitial nephritis was diagnosed. Fifteen of 16 patients were examined for vesicoureteral reflux (VUR) with voiding cystourethrography. Three of 15 patients had VUR. In the past medical histories of the 16 patients with thyroidization, three had low capacity bladders, two had prostate diseases, and six had previous urinary tract infections. In cases of thyroidization with additional findings, including THP reflux into Bowman’s space and interstitial THP deposits, we need to examine the patients for the presence of urinary tract diseases. In cases of thyroidization and tubulointerstitial nephritis urinary tract infections were suspected. Such subclinical urological diseases in the grafts might affect the prognosis of renal function. Therefore, appropriate management of urinary tract diseases is required.