Escherichia coli is one of the most common pathogens in urinary tract infections (UTIs), and antibiotic resistance in E. coli is becoming a serious problem in treating UTI. Efflux system overexpression is reported to contribute to E. coli resistance to several antibiotics. This study investigated the correlation of antibiotic susceptibilities with the overexpression of the efflux pump genes such as marA, yhiU, yhiV, and mdfA and with risk factors for antibiotic resistance in E. coli isolated from UTI patients. We examined the expression level of efflux pump genes using quantitative real-time reverse transcription-PCR (qRT-PCR). We also tested the in vitro susceptibilities to 12 kinds of antibiotics in 64 clinical strains of E. coli isolated from UTI patients. By multivariate analyses we revealed significant relationships between the overexpression of (i) marA and MICs of cefepime (FEP) and nalidixic acid (NAL), (ii) yhiV and MICs of minocycline (MIN), and (iii) mdfA and MICs of sitafloxacin (STX). In our investigation of the efflux pump genes, risk factors such as gender and the previous use of fluoroquinolones correlated with the overexpression of marA, and indwelling catheter use correlated with the overexpression of mdfA. In conclusion, we demonstrated that the increased expression of efflux pump genes such as marA and mdfA can lead to fluoroquinolone resistance in E. coli. These results contribute to our knowledge of the efflux system and raise the possibility of developing new agents, such as efflux pump inhibitors (EPIs), to antibiotic-resistant E. coli.There are many examples of multidrug resistance (MDR) in clinical isolates of Enterobacteriaceae, such as extended-spectrum ␤-lactamase (ESBL)-producing strains (6). The overexpression of efflux pumps was reported to contribute to MDR in E. coli (3,12). Almost all Gram-negative bacteria have genes for efflux pumps belonging to the resistance nodulation division (RND) family (3), and seven homologous RND-type pumps are known in E. coli. Five of these (AcrB, AcrF, MdtB, MdtC, and YhiV) are known to expel many kinds of drugs. Most of these efflux genes are not expressed or are expressed at low levels in clinical isolates (3). The tripartite efflux pump, AcrAB-TolC complex, contains AcrA, a fusion protein; AcrB, a cytoplasmic membrane transporter protein; and TolC, an outer membrane channel (12). The overexpression of this pump often is associated with the MDR phenotype in E. coli (3,15,27,32). YhiUV is regulated by the EvgAS, the twocomponent system (20), and helps expel doxorubicin and erythromycin by cooperating with TolC (3,7,10,14,20,21). A previous report showed that a point mutation in yhiV, coding for YhiV, was associated with differences in the MDR phenotype (3). The overexpression of efflux pump genes such as marA, yhiU, yhiV, and mdfA is related to antibiotic resistance, especially fluoroquinolones (3,12). This study investigated the relationship between the overexpression of these efflux pump genes and antibiotic resistance and risk factors for urin...

Ureteroscopic lithotripsy (UL), for renal or ureteral stones, is a standard technique for every urologist. However, the length of time the double J (DJ) stent needs to be kept in postoperatively is still controversial. This study investigated how the duration of DJ stenting after UL affects postoperative adverse events, especially infection and pain. One hundred and twenty-five patients were enrolled in this study and data were analyzed retrospectively. We set the median duration for keeping the DJ stent postoperatively as 14 days from median value in all cases and compared it to a longer duration group (>15 days) and a shorter duration group (<14 days) in terms of febrile complications, urinalysis, and the need to give antibiotics at the time of DJ stent removal. The duration of DJ stenting was from 3 to 61 (median 14) days. Thirteen patients had adverse events related to DJ stent removal (febrile complications, 11 patients; lumbago, 2 patients). Thirty-one patients were given antibiotics at the time of DJ stent removal. Patients with longer durations (>15 days) of DJ stenting had a significantly higher ratio of adverse events such as fever or lumbago (p = 0.041). In conclusion, this study demonstrated that shorter duration (<14 days) DJ stent use after UL may decrease adverse events and require less antibiotic use. Further prospective studies are needed to determine the optimal duration of DJ stent use after UL.

We examined Enterococcus faecalis strains clinically isolated from 100 patients with urinary tract infections (UTIs) for their susceptibility to levofloxacin (LVX) by measuring the MIC and investigated amino acid mutations by direct DNA sequencing, which were then correlated with LVX resistance. Next, we studied risk factors for LVX resistance, such as age, gender, and previous fluoroquinolone use, and investigated the statistical correlation of these risk factors with each amino acid mutation and LVX resistance. Of the 100 isolates tested, 14 isolates showed LVX resistance and all of these isolates had amino acid mutations. We demonstrated that 2 out of 4 mutations (Ser83-to-Ile in gyrA and Ser80-to-Ile in parC) had a significant correlation with LVX resistance. There was a significant relationship between isolates with 2 or 3 amino acid mutations and LVX resistance. In addition, we found a significant correlation between the previous use of fluoroquinolones and LVX resistance or the presence of mutations and also demonstrated that previous use of other types of antibiotics was significantly related to the presence of mutations by multivariate analysis. In conclusion, we found significant correlation between amino acid mutations in E. faecalis, LVX resistance, and risk factors such as previous use of fluoroquinolones.Enterococcus faecalis is one of the most common pathogens in urinary tract infections (UTIs) (7). Recently, enterococcal infections have increased, and E. faecalis accounts for the majority of enterococcal infections (7). Fluoroquinolones have been frequently used to treat E. faecalis UTIs, and the emergence of fluoroquinolone-resistant E. faecalis (QREF) strains has recently been reported in several countries (12). In our institution, the proportion of QREF isolates gradually increased from 12/83 (14.4%) in 2004 to 10/49 (20.4%) in 2007, but this was not a statistically significant difference (P ϭ 0.3755). Rudy et al. demonstrated in analyses of 130 E. faecalis strains isolated from urine that all strains were sensitive to glycopeptides (vancomycin [VAN] and teicoplanin), 96% were sensitive to penicillin, 43% to ciprofloxacin, and 28% to tetracycline (22). Muratani et al. reported a 38% frequency of levofloxacin (LVX)-resistant E. faecalis isolates from UTIs (17).Mutations in the quinolone resistance-determining regions (QRDR) of gyrA coding for DNA gyrase and parC coding for DNA topoisomerase IV, the efflux system, antimicrobial-modifying resistance enzymes, and plasmid-mediated mechanisms are considered to contribute to resistance to fluoroquinolones (3,10,11,18,23,25,27). To our knowledge, no previous report has correlated risk factors with fluoroquinolone resistance and amino acid mutation in the QRDR in E. faecalis strains clinically isolated from the urine of UTI patients.Rattanaumpawan et al. investigated the risk factors for fluoroquinolone resistance in enterococcal UTIs and demonstrated that recent exposure to antibiotics such as fluoroquinolones, extended-spectrum cephalosporins, and c...

Nivolumab is effective for advanced renal cell carcinoma; however, reports are limited wherein nivolumab is combined with sequential therapy of angiogenesis inhibitors and metastasectomy. Case presentation: A 65-year-old man was diagnosed with left renal cell carcinoma of cT2aN0M1 with lung metastasis. The patient underwent nephrectomy and sequential therapy with interferon-a and angiogenesis inhibitors. Lung metastasis decreased by angiogenesis inhibitors, but new right adrenal gland metastasis appeared. Nivolumab as the fifth systemic therapy remarkably shrank the metastasis. After discontinuing nivolumab therapy, the metastasis continued to shrink. The patient underwent adrenalectomy, and pathological analysis revealed no remnant cancer cells in the specimen, confirming a pathological complete response. Twenty months postoperatively, he remains in good health without recurrence. Conclusion: We report a rare case with renal cell carcinoma of a pathological complete response by nivolumab after angiogenesis inhibitors.

A 77-year-old woman with liver cirrhosis was admitted to our hospital for marked hemorrhage in her ileal conduit stoma. She had a history of cystectomy and urinary diversion for bladder carcinoma 2 years ago. Contrast-enhanced CT demonstrated varices in the ileal conduit stoma. We accessed the varices via a recanalized paraumbilical vein to avoid pain from the transhepatic approach, and selectively embolized the varices with N-butyl cyanoacrylate (NBCA). We consider antegrade embolization of ileal conduit stomal varices with NBCA to be effective and feasible. Access via a paraumbilical vein is a useful alternative to the transhepatic approach.