Jonathan Masters

Escherichia coli Bloodstream Infection After Transrectal Ultrasound–Guided Prostate Biopsy: Implications of Fluoroquinolone-Resistant Sequence Type 131 as a Major Causative Pathogen

BACKGROUND Transrectal ultrasound-guided (TRUS) prostate biopsy is a commonly performed procedure, and fluoroquinolones are the most frequently given prophylactic antimicrobials. In the context of increasing fluoroquinolone resistance, and the international emergence of fluoroquinolone-resistant sequence type 131 (ST131) Escherichia coli, we describe a large series of E. coli bacteremia after TRUS biopsy. METHODS All male patients admitted with community-onset (CO) E. coli bacteremia from January 2006 through December 2010 were included. Patient characteristics, treatment outcomes, and rates of antimicrobial resistance were compared between patients with TRUS biopsy-related bacteremia and other male patients with CO E. coli bacteremia. Molecular typing was performed on E. coli isolates to determine phylogenetic group. RESULTS A total of 258 male patients were admitted with CO E. coli bacteremia. Of these, 47 patients (18%) were admitted after TRUS biopsy. Patients who had undergone TRUS biopsy were twice as likely to require intensive care admission (25% vs 12%) and had significantly higher rates of resistance to gentamicin (43%), trimethoprim-sulphamethoxazole (60%), and ciprofloxacin (62%) as well as all 3 agents in combination (19%). Thirty-six percent of post-TRUS biopsy patients did not receive active empirical antibiotic therapy. The ST131 clone accounted for 41% of all E. coli isolates after TRUS biopsy. CONCLUSIONS E. coli bacteremia can be a life-threatening complication of TRUS biopsy. Infecting strains are frequently multidrug-resistant and resistant to common empirical antibiotic agents. E. coli ST131 is an important cause of sepsis after TRUS biopsy. Further studies should evaluate colonization with fluoroquinolone-resistant E. coli as a risk factor for postbiopsy sepsis.

A Multigene Urine Test for the Detection and Stratification of Bladder Cancer in Patients Presenting with Hematuria

PURPOSE We investigated whether the RNA assay uRNA® and its derivative Cxbladder® have greater sensitivity for the detection of bladder cancer than cytology, NMP22™ BladderChek™ and NMP22™ ELISA, and whether they are useful in risk stratification. MATERIALS AND METHODS A total of 485 patients presenting with gross hematuria but without a history of urothelial cancer were recruited prospectively from 11 urology clinics in Australasia. Voided urine samples were obtained before cystoscopy. The sensitivity and specificity of the RNA tests were compared to cytology and the NMP22 assays using cystoscopy as the reference. The ability of Cxbladder to distinguish between low grade, stage Ta urothelial carcinoma and more advanced urothelial carcinoma was also determined. RESULTS uRNA detected 41 of 66 urothelial carcinoma cases (62.1% sensitivity, 95% CI 49.3-73.8) compared with NMP22 ELISA (50.0%, 95% CI 37.4-62.6), BladderChek (37.9%, 95% CI 26.2-50.7) and cytology (56.1%, 95% CI 43.8-68.3). Cxbladder, which was developed on the study data, detected 82%, including 97% of the high grade tumors and 100% of tumors stage 1 or greater. The cutoffs for uRNA and Cxbladder were prespecified to give a specificity of 85%. The specificity of cytology was 94.5% (95% CI 91.9-96.5), NMP22 ELISA 88.0%, (95% CI 84.6-91.0) and BladderChek 96.4% (95% CI 94.2-98.0). Cxbladder distinguished between low grade Ta tumors and other detected urothelial carcinoma with a sensitivity of 91% and a specificity of 90%. CONCLUSIONS uRNA and Cxbladder showed improved sensitivity for the detection of urothelial carcinoma compared to the NMP22 assays. Stratification with Cxbladder provides a potential method to prioritize patients for the management of waiting lists.

Prostate Disease Risk Factors among a New Zealand Cohort

Background: Prostate cancer is a leading public health burden worldwide, and in New Zealand it is the most commonly registered cancer and the third leading cause of cancer deaths among males. Genetic variability and its associations with diet, demographic and lifestyle factors could influence the risk of this disease. Methods: The single nucleotide polymorphisms (SNPs) within a group of antioxidant genes and related markers were tested between patient and control cohorts, adjusted for significant differences between basic lifestyle and demographic characteristics. Results: Increasing age, smoking and low serum selenium levels were significantly associated with an increased risk for prostate disease. Alcohol consumption increased the glutathione peroxidase (GPx) activity. A significant reduction in alcohol consumption was recorded with prostate disease. Three SNPs, namely GPx1 rs1050450, SEL15 rs5845 and CAT rs1001179, were significantly associated with prostate disease risk. A cumulative risk of prostate cancer was noted with 6 risk alleles. A lower GPx activity was recorded with prostate disease compared to the controls. However, the GPx1 rs1050450 allele T in association with prostate cancer recorded a significantly higher GPx activity compared to the controls. Conclusions: These data point to a possibility of identifying individuals at risk of prostate cancer for better management purposes.

TRAVEL-ASSOCIATED EXTENDED-SPECTRUM β-LACTAMASE-PRODUCING ESCHERICHIA COLI BLOODSTREAM INFECTION FOLLOWING TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BIOPSY

Sir, Recent case series describe infectious complications after TRUS-guided prostate biopsy due to extended-spectrum β -lactamase (ESBL)-producing Escherichia coli . However, few studies have specifi cally evaluated potential risk factors for postbiopsy isolation of ESBL-producing E. coli . We read with interest the timely article by Patel et al . [ 1 ] describing the association between recent international travel and post-biopsy infections with multi-resistant E. coli .

Seasonal variation in the acute presentation of urinary calculi over 8 years in Auckland, New Zealand

Study Type – Symptom prevalence (retrospective cohort)
Level of Evidence 2b

Perceived barriers and facilitators to physical activity in men with prostate cancer: possible influence of androgen deprivation therapy

While physical activity is beneficial for men with prostate cancer, too few perform sufficient activity for such benefit. This study examined perceptions of men with prostate cancer of their barriers and facilitators to physical activity, and how androgen deprivation therapy (ADT) may influence these perceptions. Two focus groups were conducted, involving six ADT and eight non-ADT patients respectively. Data were transcribed verbatim and themes developed using a general inductive thematic approach. Facilitators to physical activity common to both groups of cancer survivors included clinician and spousal involvement, with pre-existing co-morbidities and increased age cited as barriers by both groups. The ADT subgroup cited personal involvement as a facilitator to physical activity, with fatigue, reduced motivation and a relative lack of specific advice from their clinician as additional barriers. The non-ADT subgroup had no additional facilitators to physical activity but cited time constraints as a barrier. These results highlight the important role that cancer clinicians and spouses play in promoting physical activity for men with prostate cancer and how ADT may influence their other facilitators and barriers. As physical activity is beneficial for prostate cancer survivors, especially those on ADT, cancer clinicians should regularly discuss physical activity with their patients.

Effects of bariatric surgery on untreated lower urinary tract symptoms: a prospective multicentre cohort study

To evaluate the effects of bariatric surgery on lower urinary tract symptoms (LUTS) in a prospective cohort study.

Quality of life effects of androgen deprivation therapy in a prostate cancer cohort in New Zealand: can we minimize effects using a stratification based on the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?

BackgroundAndrogen deprivation therapy (ADT) is an effective palliation treatment in men with advanced prostate cancer (PC). However, ADT has well documented side effects that could alter the patient’s health-related quality of life (HRQoL). The current study aims to test whether a genetic stratification could provide better knowledge for optimising ADT options to minimize HRQoL effects.MethodsA cohort of 206 PC survivors (75 treated with and 131 without ADT) was recruited with written consent to collect patient characteristics, clinical data and HRQoL data related to PC management. The primary outcomes were the percentage scores under each HRQoL subscale assessed using the European Organisation for Research and Treatment of Cancer Quality of Life questionnaires (QLQ-C30 and PR25) and the Depression Anxiety Stress Scales developed by the University of Melbourne, Australia. Genotyping of these men was carried out for the aldo-keto reductase family 1, member C3 (AKR1C3) rs12529 single nucleotide polymorphism (SNP). Analysis of HRQoL scores were carried out against ADT duration and in association with the AKR1C3 rs12529 SNP using the generalised linear model. P-values <0 · 05 were considered significant, and were further tested for restriction with Bonferroni correction.ResultsIncrease in hormone treatment-related effects were recorded with long-term ADT compared to no ADT. The C and G allele frequencies of the AKR1C3rs12529 SNP were 53·4 % and 46·6 % respectively. Hormone treatment-related symptoms showed an increase with ADT when associated with the AKR1C3 rs12529 G allele. Meanwhile, decreasing trends on cancer-specific symptoms and increased sexual interest were recorded with no ADT when associated with the AKR1C3 rs12529 G allele and reverse trends with the C allele. As higher incidence of cancer-specific symptoms relate to cancer retention it is possible that associated with the C allele there could be higher incidence of unresolved cancers under no ADT options.ConclusionsIf these findings can be reproduced in larger homogeneous cohorts, a genetic stratification based on the AKR1C3 rs12529 SNP, can minimize ADT-related HRQoL effects in PC patients. Our data additionally show that with this stratification it could also be possible to identify men needing ADT for better oncological advantage.

Perceptions of physically active men with prostate cancer on the role of physical activity in maintaining their quality of life: possible influence of androgen deprivation therapy

The primary aim of this study was to examine the perceptions of older men with prostate cancer regarding their quality of life and physical activity post‐diagnosis, and the potential benefits and risks associated with being physically active. A secondary aim was to gain some preliminary insight into how these perceptions may differ as a function of androgen deprivation therapy (ADT).

Rectal colonization with New Delhi metallo-β-lactamase-1-producing Escherichia coli prior to transrectal ultrasound (TRUS)-guided prostate biopsy

Sir, The global spread of New Delhi metallo-b-lactamase (NDM)producing Enterobacteriaceae is of significant public health concern. To date, NDM-producing Enterobacteriaceae have been isolated from numerous geographical regions, including Europe, North America, Australia and New Zealand. In addition to hydrolysing carbapenems, NDM-producing organisms display resistance to a broad range of antimicrobial classes, primarily due to the presence of additional acquired plasmid-associated resistance genes. As a result, infections caused by these organisms pose a considerable therapeutic challenge. Transrectal ultrasound (TRUS)-guided prostate biopsy is a commonly performed urological outpatient procedure, with 1000000 biopsies performed annually in the USA. A variety of infectious complications have been reported following TRUS biopsy, ranging from urinary tract infection through to bacteraemia and sepsis. Of note, the incidence of infectious complications following TRUS biopsy is reportedly increasing, with clinical and economic consequences. The most common pathogen in the setting of post-biopsy sepsis is Escherichia coli, with causative strains probably originating from the patient’s own endogenous flora. Over the past decade, the prevention and management of TRUS-biopsy infections due to E. coli has become more complicated due to increasing antimicrobial resistance in this organism. Currently, the most common resistance profiles encountered in this setting are fluoroquinolone resistance and/or extendedspectrum b-lactamase (ESBL) production. Recent studies suggest that pre-biopsy screening for such resistant pathogens with subsequent ‘tailored’ prophylaxis based on antimicrobial susceptibility results may be an effective way to reduce infectious complications. To date, however, there are no reports describing pre-TRUS biopsy isolation of carbapenemase-producing E. coli. Here, we describe the isolation of NDM-1-producing E. coli from a patient undergoing rectal screening prior to TRUS biopsy. In early 2013, an elderly New Zealand male attended the urology outpatient clinic for a pre-biopsy rectal screen. A TRUS biopsy 15 months earlier had demonstrated the presence of lowgrade prostatic carcinoma, and the patient was being monitored by regular measurement of prostate-specific antigen (PSA) levels and outpatient clinic assessments. In order to assess possible progression of his carcinoma, a repeat biopsy was recommended. In the month before attending for pre-biopsy rectal screening, the patient had returned from visiting relatives in India. He had no known healthcare contact during this trip. Rectal screening for pre-TRUS biopsy carriage of fluoroquinolone-resistant E. coli was introduced in Auckland City Hospital, New Zealand in March 2012. Where possible, rectal swabs obtained from patients pre-TRUS biopsy are incubated aerobically overnight in MacConkey broth containing 1 mg/L ciprofloxacin. Isolates growing in this broth are then subcultured onto MacConkey agar containing 1 mg/L ciprofloxacin. Any E. coli isolates growing after 24 h are identified using the Bruker MALDI-TOF system, and antimicrobial susceptibility testing is performed using agar dilution according to CLSI guidelines. The patient’s pre-biopsy rectal swab grew a fluoroquinoloneresistant E. coli that was also resistant to penicillins, extendedspectrum cephalosporins, carbapenems, piperacillin/tazobactam, aztreonam, aminoglycosides and trimethoprim/sulfamethoxazole. The isolate tested susceptible to fosfomycin and nitrofurantoin. Double-disc synergy testing using meropenem or ertapenem with either EDTA or dipicolinic acid as inhibitors was positive, but the modified Hodge test was negative. PCR analysis and DNA sequencing demonstrated the presence of the blaNDM-1 and blaCTX-M-15 genes. In addition, the isolate was also found to harbour the aac-6′-Ib and rmtC genes. Multilocus sequence typing (MLST) analysis was performed as previously described (http://mlst.ucc.ie/ mlst/dbs/Ecoli), and revealed sequence type (ST) 101. Given the risk of a post-biopsy infection with extremely limited treatment options, along with the patient’s advanced age and the low-grade nature of his carcinoma, a decision was made not to proceed with biopsy. This case illustrates the increasingly complex challenges caused by antimicrobial resistance in the context of TRUS biopsy. Although for many patients colonized with fluoroquinolone-resistant E. coli, pre-biopsy screening and ‘targeted’ prophylaxis may be a useful preventative strategy, for patients colonized with extremely resistant organisms such as NDM-producing E. coli, options for targeted prophylaxis and potential treatment may be so limited that the benefit of proceeding with biopsy may itself need to be called into question. Although fosfomycin has shown initial efficacy