Choosing the optimal antibiotic prophylaxis (AP) duration before common stone procedures requires balancing antimicrobial stewardship with minimizing postoperative infectious complications. A survey of 326 physicians found that roughly one-third of respondents prescribe prolonged antibiotics courses before endourology procedures despite negative preoperative urine cultures. Greater than two-thirds of the respondents were endourologists with over 10 years of experience who practiced in the United States at academic health centers.¹ Due to the large variation in practice and an absence of evidence supporting optimal antibiotic timing, several recent randomized controlled trials (RCTs) have been conducted specifically to address these questions in an evidence-based manner. Additionally, both the American Urological Association (AUA) and the European Association of Urology have released guidelines on this subject. Herein, we will review the most recent literature and summarize our corresponding clinical practice.

Percutaneous Nephrolithotomy

Previously, several prospective single institution studies demonstrated a significant decrease in sepsis with 1 week of AP before percutaneous nephrolithotomy (PCNL).² However, hypothesizing that the risk of sepsis varies significantly in patients undergoing PCNL, the Endourologic Disease Group for Excellence (EDGE) Research Consortium performed 2 separate multi-institutional RCTs wherein they stratified patients by high and low risk and tailored the AP intervention accordingly. Low risk was defined as negative urine culture within 2 weeks of surgery and no history of chronic kidney disease, existing external or internal nephroureteral stent, cirrhosis, hepatitis, pregnancy, severe hydronephrosis, antibiotic usage within 2 weeks of the PCNL, or history of fever/sepsis in the past 12 months associated with the stone. High risk was defined as a positive preoperative urine culture within 3 months of the procedure or an existing internal or external nephroureteral stent.^3,4 Low risk group patients were randomized to either 1 dose of intravenous (IV) antibiotics preoperatively or 7 d of oral AP + 1 dose of IV antibiotics preoperatively.⁴ High risk group patients received either 2 d of oral antibiotics + 1 dose of IV antibiotics preoperatively or 7 d of oral antibiotics AP + 1 dose of IV antibiotics preoperatively.⁴ The primary endpoint compared the rates of sepsis in each group as defined by the 2012 International Guidelines for Management of Severe Sepsis and Septic Shock.

For patients with a low risk of infection, 86 patients were randomized. The difference in sepsis rates was not statistically different between the AP arm (12%) and the no AP arm (14%, P = 1.0). Furthermore, the rates of septic shock were not different between cohorts (4.8% vs 0%, P = .24) This trial also showed equivalent outcomes and complications regardless of antibiotic administration for low-risk patients undergoing a PCNL.³

For patients with a high risk of infection, 123 patients were randomized. On univariate analysis, the difference in sepsis rate was not statistically significant between the prolonged AP (15%) arm and the brief AP arm (25%, P = 0.13); however, on multivariate analysis the odds ratio of sepsis rate was approximately 3 times higher for the 2-day antibiotic prophylactic cohort compared to the 7-day cohort (OR = 3.1, 95% CI 1.11-8.93, P = .031).⁴ Therefore, for low-risk patients we currently prescribe <24 h perioperative IV AP and reserve 7 d preoperative of AP for high-risk patients.

Ureteroscopy With Laser Lithotripsy

Per 2013 AUA Best Practice Policy Statement, all ureteroscopy (URS) patients should receive <24 h perioperative AP. However, the evidence for this publication includes literature >10 years old and, in fact, recommends ciprofloxacin as first-line antibiotics–despite the 6 black box warnings (tendon rupture, hypoglycemic coma, mental health side effects, myasthenia gravis, irreversible peripheral neuropathy, aortic aneurysm/dissection). Moreover, fluoroquinolones are now associated with high levels of drug resistance and do not treat known high rates of enterococcus infections.⁵

Nevertheless, there is substantial evidence supporting giving AP for URS to prevent infectious complications.^6,7 We recommend covering enterococcus and gram-negative pathogens. However, one significant risk factor for infectious complications following URS is dependent on whether patients have been pre-stented, in which case duration of indwelling stent tracks correlates closely with the risk of sepsis with durations of 1, 2, 3, and >3 months corresponding to a 1%, 4.9%, 5.5%, and 9.2% risk of sepsis, respectively.⁷ The duration of preoperative and postoperative AP is unclear given the paucity of research for high-risk patients. Therefore, balancing risk/benefits of AP is left to clinician judgment. Similar to how we risk stratify patients undergoing PCNL, we give 1 week of AP to patients who are deemed high risk (positive urine culture, history of prolonged indwelling ureteral stent, immunosuppression, multidrug resistant UTI, or recent febrile UTI/urosepsis).

More recent studies suggest that intra-renal pressures (eg, >30 mm Hg) might be contributing to sepsis and that efforts to correlate pressure with infectious complications are necessary. At a minimum, most agree to minimize intra-renal pressures to the extent that we can–judicious irrigation, possible access sheath (larger might be better), decreased operative time, staging URS for large stones. The authors are currently involved in a prospective observational trial using pressure sensing wires during URS to correlate it with infectious complications. Future ureteroscopes may incorporate this technology to guide surgeons on safe surgical pressures.

Extracorporeal Shock Wave Lithotripsy

Due to several RCTs and metanalyses, AUA and European Association of Urology Guidelines recommend that perioperative antibiotics are unnecessary in an index patient if the preoperative urine culture is negative.⁸

Cystoscopy With Stent Removal

In a recent randomized controlled trial of a single oral dose of AP or no AP, no patients in either group developed a symptomatic UTI.⁹ Similarly, providing antibiotics postoperatively after URS up until day of stent removal provides no benefit.¹⁰ Therefore, we do not recommend AP for routine cystoscopy with stent removal, unless risk factors exist (eg, immunosuppression, recent sepsis/fever).

In summary, though each patient is unique and may require an individualized treatment plan, many decisions regarding AP can be grounded in evidence-based literature. In order to mitigate the current antibiotic resistance threat, we offer a judicious approach to AP (see Table). PCNL, SWL, and cystoscopy with stent removal have been carefully studied, but there remains a literature gap with regard to duration of AP before and after URS in high-risk patients.