Current Evidence for Antibiotic Stewardship in Urology and Urinary Tract Infections
A total of 17 primary new research studies were included. Search of the Cochrane Central Register of Controlled Trials identified 43 registered ongoing clinical trials of ABS in urology indicating the latest increase in attention and importance of this topic. The 17 published studies were chosen to extract information on ABS in outpatients, inpatients, specific procedures (e.g. transurethral resection of the prostate, TUR-P) and new developments. We further explored the implications of these work on future research. Highly relevant articles with novel work and potential to impact future research are summarized in Table 1.
Antibiotic Stewardship in the Outpatient Setting
Five studies on ABS programs in the outpatient setting were identified. All of these studies were retrospective. Within the outpatient setting at the USA. Wattengel et al. identified that 68% of community onset UTI patients were treated with inappropriate antibiotics. In their analysis indwelling urinary catheters and advanced age were risk factors for both recurrent infections and inappropriate antibiotic usage. The authors concluded that outpatient antibiotic prescription for UTIs is suboptimal and stewardship programs should focus on patients with indwelling catheters and advanced age.
Another retrospective cohort study dealt with the significance of urine culture in uncomplicated UTIs in young women managed in community. All patients in this cohort presented with UTI symptoms but in 43% of cases the urine culture did not show any pathogens. Moreover, 6% of the patients received fluoroquinolones for upfront treatment. Symptom duration of patients with or without microbiological proof of infections was similar. Authors of this paper have changed their practice to start symptomatic treatment until urine culture results are available, which would be anticipated with a decrease in inappropriate antibiotic usage. The diagnostic power of urine cultures is a topic of further debate, but the approach adopted by the authors is similar to the published randomized clinical trials for antibiotics vs. nonsteroid anti-inflammatory medication for uncomplicated cystitis. We recognize this as an area that ABS can obtain large benefits. Yet, further in-depth analysis of the data for the studies are awaited as there is a risk of certain subpopulations to progress to severe infections such as pyelonephritis.
Pharmacists play an important role in improving and implementing ABS in the outpatient setting. In their retrospective analysis McCormick et al. confirmed that appropriate antibiotic usage increased from 37% to 71.6% in a population of uncomplicated cystitis and pyelonephritis treated in community by involvement of pharmacists. Largest increment of benefit was obtained through improving the duration of therapy.
The elderly population living in care homes who develop UTIs are a distinct group of patients than the above-mentioned groups. A recent study identified that a concerning rate of 67% of the male population in this group with UTIs received suboptimal antibiotic treatment. In 46% of their cohort patients received an antibiotic that potentially did not provide coverage or was resistant by the causative pathogen. The identified predictors for suboptimal antibiotic prescription were prior fluoroquinolone exposure, chronic renal disease, age of 85 years or older, prior skin infection, recent high white blood cell count and genitourinary disorder. Authors suggest that predictors of suboptimal prescriptions should be targeted with ABS interventions to improve UTI treatment.
The benefits of ABS in outpatient setting have been confirmed by Kissler et al. by analyzing the antibiotic prescription trends from the Massachusetts outpatient database between 2011 and 2015. Yet always, a decline in antibiotic prescription in population might not necessarily relate to better patient outcomes. In a study from the UK, of patients over the age of 65 seen in community for UTI, delay in antibiotics or no antibiotic treatment translated into 60-day mortality rates of 2.8% and 5.4% respectively in comparison to 1.6% in patients who received immediate antibiotics. Therefore, ABS programs in outpatient settings cannot be administered as a blanket rule but instead better patient stratification tools are necessary as well as improved diagnostic tools.
Antibiotic Stewardship in Emergency Departments
Only one retrospective study focused on ABS in emergency departments. Patel et al. describe a poor adherence to evidence-based guidelines and overuse of broad-spectrum antibiotics. Additionally, fluoroquinolones were prescribed for longer than the recommended duration in 60% of the cases. The level of guideline adherence declined if the condition was more severe (i.e. cystitis vs. pyelonephritis); however, results were not adjusted for confounders.
Antibiotic Stewardship During Inpatient Treatment
We identified one prospective, single-institutional (Spain) observational study with the topic of carbapenem de-escalation in complicated UTIs within an ABS program during inpatient treatment. De-escalation strategy with guidance from the hospital pharmacist was associated with significant decrease in hospitalization by 5 days and also reduced crude hospital mortality from 29.3% to 7.4%. The de-escalation study was not a randomized study and selection bias is one of the major concerns of these results. The main message from this study is that by involvement of multidisciplinary teams for ABS at a local level patient-specific decisions can help improve outcomes.
Institutional Aspects of Antibiotic Stewardship
Three studies were identified for this section. Uda et al. performed a retrospective, single-institutional analysis asking the question: How does ABS affect inappropriate antibiotic therapy in urological patients? At that institution 11.4% inappropriate antibiotic use (not according to national guideline) was documented, but it significantly decreased during the study period by ABS programs (P = 0.012). Consequently, the authors concluded that their findings suggest that urologists have probably become more familiar with infectious disease management through ABS interventions, leading to a decrease in inappropriate antibiotic use and an increase in urine culture submissions. Furthermore, Goebel et al. conducted a survey on organizational readiness for ABS for asymptomatic bacteriuria, for which they identified as local leadership and inadequate resources as the limiting factors for success. Despite evidence to the contrary, many practitioners continue to inappropriately screen for and treat bacteria in the urine of clinically asymptomatic patients. Watson et al. performed a multicenter quasi-experimental study, before and after intervention, whereby they introduced additional questions in the electronic health system for requesting urine cultures. Clinicians were asked for the clinical indication of the urine culture request. After their intervention the number of performed urine cultures decreased (40.4% reduction; P < 0.01) and also the antibiotic days of therapy decreased (15.2%: P < 0.01). Additionally, the authors estimated the yearly savings following their intervention and they calculated 535 181 USD yearly savings. Overall, adoption of clinical decision aids via electronic health systems can provide improvement in ABS.
Antibiotic Stewardship in Special Urological Procedures
This section includes three retrospective and one prospective study about ABS for different urological procedures.
Antibiotic prophylaxis and prolonged antibiotic administration for penile prosthesis implantation was retrospectively reviewed by Dropkin et al.. Device infection leading to explanation was not required in any of the patients with no risk factors who did not receive any additional antibiotics after implantation. Whereas explanation rate went up to 4% in patients with risk factors and infection rates in high risk population with prolonged antibiotics was 5%. In the light of these findings prolonged antibiotic administration following penile prosthesis is unlikely to provide protection from infections leading to explanation.
Fox et al. validated the best practice-policy statement on urodynamic antibiotic prophylaxis for the high-risk patient in the era of ABS, retrospectively. Overall, they concluded that especially elevated post void residual and neurogenic lower urinary tract dysfunction were significant predictors for posturodynamic UTI. Morbidity associated with UTI was low, so antimicrobial prophylaxis for these conditions should be reconsidered in the era of ABS.
The prospective cohort study in this section was conducted by Baten et al. in patients undergoing TUR-P. Their data showed a low infectious complication rate (2.9%) in patients without a preoperative catheter or pyuria, undergoing TUR-P without antibiotic prophylaxis. Authors concluded that their findings warrant challenging the use of routine antibiotic prophylaxis in TUR-P for low risk patients they identified. These results are not generalizable and certainly have not accounted for the multiple confounders that could impact the outcomes (e.g. preoperative urine culture, duration of surgery or the local resistance rates). Future studies to identify the relationship of prophylaxis and postoperative surgical infections should account for the confounders and designed carefully to account for the disease process complexity.
Identifying New Targets for Antibiotic Stewardship
So far, it is understood that the independent activities in defining the benefit of antibiotic stewardship (ASB) in urology have been limited. Therefore, it is essential to identify the areas of research and development required to improve the benefits of ASB in urology without creating any harm. Furthermore, two of these studies have used mathematic modelling. Füri et al. published the article 'The potential negative impact of antibiotic pack on ABS in primary care in Switzerland: a modelling study'. Interestingly, they also considered other uncomplicated infections, like otitis media, in their analysis, but the conclusion is also very meaningful for UTI: Fixed antibiotic packs often do not match recommended treatment regimens, especially for children, potentially resulting in longer than necessary treatments and leftover doses in the community. As part of national stewardship, a move to exact pill-count system, including for child-appropriate solid formulations, should be considered. Unfortunately, this approach might lead to a big political discussion and will not find agreement from the pharmacological industry. Tandogdu et al. considered a condition-specific surveillance in healthcare-associated urinary tract infections (HAUTI) as a strategy to improve empirical antibiotic treatment as a target to ABS in their modelling study. Finally, they came to the conclusion that their estimates illustrate that antibiotic choices can be different between HAUTI conditions, like cystitis, pyelonephritis or urosepsis, and their findings can improve empirical antibiotic selection towards a personalized approach, but this should be validated in local surveillance studies. Of note, both of these studies include predictive mathematical modelling, and their validation will be subject to further studies. Obtaining evidence through clinical trials for infections is very costly and are rarely generalizable due to disparate geographical epidemiology of postsurgical infections pathogens and their susceptibility. A timely alternative is to use rigorous local epidemiological data to inform mathematical models in supporting ABS.
Wathne et al. tried to identify targets for ABS interventions through analysis of the antibiotic prescribing process in hospitals in a multicenter observational study, also including other infectious diseases, e.g. lower respiratory tract infections, skin, or soft tissue infections. Interestingly, they identified five key targets for ABS interventions in hospitals, which are all shown in Table 2. Additionally, the authors concluded that analyzing the process of antibiotic prescribing in hospitals with patient-level data identified important targets for ABS interventions and this should be done in the different institutions. The most important of these key items is adherence to local, valid, patient focused guidelines for antibiotic prescription. Kranz et al. aimed to identify barriers for nonadherence to guidelines in UTI in their survey in German urologists. Main reasons for nonadherence on the physicians' side were 23.4% personal experience and lacking practicality of UTI guidelines on the individual complex patient. On the open questions urologists mostly stated (11.7%) that the main reason on the physician side for nonadherence is ignorance. Therefore they, in open questions, suggest to promote guidelines more in meetings and more designed practically with shortcuts and simple layout. Furthermore, German urologists stated that guidelines should also have a patient section, where the main recommendations are explained in plain language. The authors concluded that their results might help to improve the design of guideline and therefore help to improve guideline adherence.
Curr Opin Urol. 2021;31(4):285-290. © 2021 Wolters Kluwer Health, Inc.