Antibiotic Use in Hospital Urinary Tract Infections After FDA Regulation.

BACKGROUND: The FDA issued a "black box" warning regarding risks of fluoroquinolones in 2008 with updates in 2011, 2013, and 2016. OBJECTIVE: To examine antimicrobial use in hospital-treated UTIs from 2000 to 2020. DESIGN: Cross-sectional study with interrupted time series analysis. PARTICIPANTS: Patient encounters with a diagnosis of UTI from January 2000 to March 2020, excluding diagnoses of renal abscess, chronic cystitis, and infection of the gastrointestinal tract, lungs, or prostate. MAIN MEASURES: Monthly use of fluoroquinolone and non-fluoroquinolone antibiotics were assessed. Fluoroquinolone resistance was assessed in available cultures. Interrupted time series analysis examined level and trend changes of antimicrobial use with each FDA label change. KEY RESULTS: A total of 9,950,790 patient encounters were included. From July 2008 to March 2020, fluoroquinolone use declined from 61.7% to 11.7%, with similar negative trends observed in inpatients and outpatients, age ≥ 60 and < 60 years, males and females, patients with and without pyelonephritis, and across physician specialties. Ceftriaxone use increased from 26.4% encounters in July 2008 to 63.6% of encounters in March 2020. Among encounters with available culture data, fluoroquinolone resistance declined by 28.9% from 2009 to 2020. On interrupted time series analysis, the July 2008 FDA warning was associated with a trend change (-0.32%, < 0.001) and level change (-5.02%, p < 0.001) in monthly fluoroquinolone use. CONCLUSIONS: During this era of "black box" warnings, there was a decline in fluoroquinolone use for hospital-treated UTI with a concomitant decline in fluoroquinolone resistance and rise in ceftriaxone use. Efforts to restrict use of a medication class may lead to compensatory increases in use of a single alternative agent with changes in antimicrobial resistance profiles.

A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.

Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines carrying non-risk alleles of SNPs or deletion of the cis-regulatory region lower sensitivity to viral infection. Mechanistic studies indicated that loss/reduction of NDUFA4 causes mitochondrial stress, which leads to the leakage of mtDNA and thereby upregulation of type I interferon signaling. This study provides proof-of-principle for the application of iPSC arrays in GWAS and identifies NDUFA4 as a previously unknown susceptibility locus for viral infection.

Varicella-zoster virus and urologic practice: a case-based review.

INTRODUCTION: Each year, varicella-zoster virus (VZV) affects nearly one million people in the United States, often in the form of herpes zoster, or shingles. The urologic system is a rare but often debilitating target. This paper reviews the epidemiology, symptomatology, diagnosis, and management of VZV as it relates to urologic practice. MATERIALS AND METHODS: We performed a PubMed search using the query "herpes zoster" and "varicella-zoster virus" combined with multiple urological terms. RESULTS: Infection caused by VZV, specifically the resurgent clinical infection herpes zoster (HZ), is prevalent and increasing. It often affects older men and women and those in immunocompromised states and usually manifests as a painful cutaneous rash. However, urological conditions such as voiding dysfunction, erectile issues, and flank pain have also been noted in conjunction with an HZ infection. Additionally, urological procedures and treatments may incite an HZ outbreak. Awareness and prompt treatment can ameliorate the intensity and duration of this infection. CONCLUSIONS: An understanding of the atypical manifestations of HZ and disseminated VZV infection may aid urologic practitioners in avoiding misdiagnosis and delay of treatment.

Urinary tuberculosis: modern issues.

Tuberculosis remains an epidemic that affects one third of the world's population. The persistence of this disease is caused by a large pool of immune-compromised and lower socioeconomic populations. The advent of rapid transportation and migration has contributed to the persistence of this disease in developed and less developed nations. The emergence of drug-resistant strains has added an additional factor for the pervasiveness of tuberculosis. The genitourinary system is a primary target for hematogenous infections. This paper reviews the contemporary issues that affect the diagnosis and treatment of urinary tuberculosis.

An update on lower urinary tract tuberculosis.

Tuberculosis of the genitourinary tract presents with atypical manifestations. Only 20% to 30% of patients with genitourinary tuberculosis have a history of pulmonary infection. Tuberculosis often affects the lower genitourinary system rather than the kidney. Tuberculosis of the lower genitourinary tract most commonly affects the epididymis and the testis, followed by bladder, ureter, prostate, and penis. Use of bacillus Calmette-Guérin therapy for bladder cancer can cause symptomatic tubercular infections of the lower genitourinary tract. Tuberculosis of the lower genitourinary tract can present with irritative voiding symptoms, hematuria, epididymo-orchitis, prostatitis, and fistulas. Tuberculosis of the seminal vesicles, vas, fallopian tubes, and the uterus can cause infertility. Urinalysis may demonstrate sterile pyuria, hematuria, or albuminuria. Identification of acid-fast bacilli in culture or tissue or by polymerase chain reaction studies is diagnostic. Medical treatment may not result in resolution of symptoms. Surgical intervention and reconstruction of the urinary tract are frequently indicated.

Malignant melanoma of the prostate: a case report.

Primary genitourinary melanoma accounts for less than 1% of all cases of melanoma. Melanoma of prostatic origin is extremely rare. These patients are difficult to diagnose and carry a very poor prognosis. Aggressive surgical resection is the current treatment standard. We report a case of primary malignant melanoma of the prostate found during transurethral resection of the prostate.

How to diagnose and treat fungal infections in chronic prostatitis.

Epidemiologic changes that include immune-compromised patients and drug-resistant fungi have caused an increase in nosocomial infections by Candida albicans and non-albicans Candida species. Other fungi, aspergilla and Cryptococcus (environmental contaminants), are opportunistic invaders of the immune-compromised (transplant, HIV) patients. The environmental fungi Coccidioides immitis (dry arid areas), Histoplasma capsulatum (Avian-infested areas), and Blastomyces dermatitidis (aquatic areas) can cause infections in immune-competent and immune-deficient patients. Each fungus can cause changes in the prostate that mimic bacterial infection, benign prostatic hypertrophy, or neoplasm. Diagnosis can be established by urine cultures or needle biopsy of the prostate. Prostate surgery for carcinoma or benign enlargement may detect latent fungal infection. Different fungal species can have divergent clinical manifestations and require different treatment. In some cases, asymptomatic localized fungal prostatitis can be cured by removal of the infected gland. Symptomatic and disseminated infection may require prostatectomy and systemic antifungal therapy.

Physiological fatigue of smooth muscle contractions in rat urinary bladder.

OBJECTIVE: To characterize the physiological fatigue in bladder smooth muscles that can occur within 60 s of stimulation, which is closer to the duration of normal voiding. MATERIALS AND METHODS: Longitudinal and transverse strips of rat bladder were used; the muscles were mounted in an in vitro multi-muscle chamber, and the decline in contractile tension recorded during continuous electrical stimulation at frequencies of 5-30 Hz for 60 s. The effect of muscle length on fatigue was assessed by monitoring the decline in tension during 30 Hz stimulation at rest length, and at 60% and 100% stretched lengths of the bladder strips. To assess some of the factors involved in the development of fatigue, tension responses of fatigued muscles were monitored on exposure to 80 mm potassium or 1 microm bethanechol. RESULTS: In both longitudinal and transverse bladder strips stimulated at 30 Hz, peak contractile tension declined to 50% of original after approximately 33 s, and to 30% after 60 s of stimulation. After 10 s rest, 60% of the original tension was recovered. Increasing the frequency of fatigue stimulation from 5 to 30 Hz significantly increased the extent of the decline in tension and reduced the time to a 50% decrease in tension. Stretching the bladder strips from rest length to 100% stretched length significantly reduced the extent of tension decline and increased the time to a 50% decrease in tension. Exposure of fatigued muscles to high potassium or bethanechol generated more tension than electrical stimulation. CONCLUSION: Contractile fatigue occurs in both longitudinal and transverse strips of the bladder smooth muscles within the duration of normal voiding. Increasing the frequency of stimulation from 5 to 30 Hz increased the degree and rate of fatigue. Stretching the bladder strips from rest length by 60-100% reduced the degree and rate of fatigue. Bladder fatigue may be caused by decreased depolarization of the smooth muscle membranes, reduced release of acetylcholine from presynaptic nerve terminals, or by other yet undetermined mechanisms.