optimal antibiotic use during endoscopic kidney stone surgery

Davis P. Viprakasit, MD, FACSAssistant Professor

Department of UrologyUniversity of North Carolina at Chapel Hill

UNCUrology

Optimal Antibiotic Use During Endoscopic Kidney Stone Surgery

Disclosures

• None

Differences in Practice PatternsYes No

Require urinalysis prior to surgeryRequire urine culture prior to surgeryRoutinely send stone for culture for infection assessmentRoutinely use empiric Abx prior to URS

Routinely use empiric Abx prior to PCNL

Routinely use prolonged Abx after URS

Routinely use prolonged Abx after PCNL

Outline

• UTIs and Stone Disease• Guideline Recommendations• Antibiotic Stewardship• Antibiotics Regimens in URS• Antibiotics Regimens in PCNL• Limitations in UTI Diagnosis• New / Investigational Testing

Concurrent UTIs and Stone Disease

• Strong association• Can present chronically with recurrent cystitis or pyelonephritis

symptoms (prolonged nidus) • Can present acutely with evidence of fever and infection• May require prompt diagnosis and treatment with renal

decompression, particularly in setting of obstruction• Patients may develop infectious complications following

surgical treatment of stone

Stones as a consequence of UTI• 10-15% of all stones• Urease producers:

Proteus, Klebsiella, Pseudomonas, Staphylococcus

• ↑ risk with urine stasis and foreign bodies (ie. catheters)

• Prevention requires complete eradication of infection

Thomas and Tolley. Nat Clin Pract Urol 2008; 5:668.

UTI as a consequence of stones

Yoshimura et al. J Urol 2005; 173:458.

• Concomitant bladder or kidney infection with pre-existing metabolic stone

• Yoshimura et al – 10% of all hospital admissions for stone episodes are complicated by

infection requiring acute drainage• Lyons et al (AUA 2016)

– Retrospective review of patients with ureteral / obstructing renal stone– 15.4% (44/285) with documented UTI – 20% with UTI developed sepsis

Infection Complications Terminology

Kreydin and Eisner. Nat Clin Pract Urol 2013 10:598.

Infection Complications in Stone SurgeryURS PCNL

Fever 2.2 – 18.3% 15 - 30%SIRS 8.1% 9.8 - 38%Sepsis 7.4% 1 – 2%Mortality from sepsis 2 / 5000 patients

Martov et al. J Endourol 2015; 29:171.Zhong et al. J Endourol 2015; 29:25.Mitsuzuka et al. Urolithiasis 2016; 44:257.Blackmur et al. J Endourol 2016 June 17Dogan et al. Int Urol Nephrol 2007; 39:737.Korets et al. J Urol 2011; 186:1899.Kumar et al. Urol Res 2012; 40:79.De la Rosette et al. J Endourol 2011; 25:11.

Infection Complications in Stone Surgery

• Large residual bacteria can persist within stone despite sterilizing renal urine and multiple cycles of stone washing due to poor penetration within stone

Nemoy and Stamey. JAMA 1971; 215:1470.

Infection Complications in Stone Surgery

• May be related to endotoxins contained within stones• Release of lipopolysaccharides into circulation result in systemic response

McAleer et al. J Urol 2003; 169:1813.

Risk Factors For Infectious Complications

http://www.auanet.org/education/guidelines/antimicrobial-prophylaxis.cfmhttp://uroweb.org/wp-content/uploads/19-Urological-infections_LR2.pdf

Risk Factors for Infection after URS

J Endourol 2015; 29:171.J Endourol 2015; 29:25.J Urol 2016; 195:931.Urolithiasis 2016; 44:257.J Endourol 2016 June 17

Study n End Point Risk Factor

Martov et al (2015) 2650 UTI / Fever Female gender, Stone size, ASA II, Crohn / CV disease

Zhong et al (2015) 260 SIRS Stone size, Irrigation flow rate

Moses et al (2016) 550 UTI Preoperative stent, Operative time, Duration antibiotic prophylaxis

Mitsuzuka et al (2016) 153 Febrile UTI Preoperative pyuria, Pyelonephritis

Blackmur et al (2016) 462 Sepsis Positive bladder urine culture

Risk Factors for Infection after PCNL

Kreydin and Eisner. Nat Rev Urol 2013; 10:598.Acta Radiologica 1953; 39:37.

Principles of Antimicrobial Prophylaxis

• Periprocedural systemic administration of antimicrobial agent• Fundamental method to reduce risk of local and systemic

infections• Urinary procedures considered “clean-contaminated”• Urine culture recommended preoperatively to assess urinary

system

http://www.auanet.org/education/guidelines/antimicrobial-prophylaxis.cfm

Principles of Antimicrobial Prophylaxis

• First dose within 60 minutes of surgery• Duration ≤ 24 hours after procedure

– EXCEPTION:– Prosthetic material used– External catheter already present / placed– Documented bacteriuria / pre-existing infection

http://www.auanet.org/education/guidelines/antimicrobial-prophylaxis.cfm

Principles of Antimicrobial Prophylaxis

http://www.auanet.org/education/guidelines/antimicrobial-prophylaxis.cfm

Abx Prophylaxis in Stone Surgery

Mrkobrada et al. Can Urol Assoc J 2015; 9:13.

• Review of 5 RCT with 448 patients (349 URS, 99 PCNL)

• Incidence of UTI (33%) and fever (22%) in non-Abxgroup

Antibiotic Overuse

• Contributes to excess medication costs / health care burden• Development of health related complications:

– Allergic reactions– Drug interactions / side effects– Clostridium difficile colitis

• 250,000 illiness in US / year• 14,000 deaths in US / year

http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf

Antibiotic Resistance

• Emergence of microbial strains resistant to previously active agents through selection under antibiotic pressure and spread of resistant genes

http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf

Antibiotic Resistance

Antibiotic Resistance and UTIs• Review of Nationwide Inpatient

Sample Database

Zilberberg et al. Infect Control Hosp Epidemiol 2013; 34:940.

↑ 50%↑ 300%

Antibiotic Resistance and UTIs

http://www.eurekalert.org/pub_releases/2016-05/tumh-fdi052616.phphttp://www.cidrap.umn.edu/news-perspective/2016/06/news-scan-jun-14-2016

Abx Resistance Increases Complications• 81 PCNL patients (51% preop + UCx / 30% + MDR UCx)• 20% infectious complication

– 75% Fever - 19% Urospesis– 63% SIRS - 6% Death

Patel et al. J Endourol 2015; 29:531.

Antibiotic Stewardship: Strategies

• Curtailing habits that result in need for Abx– Reducing foley catheters– Maximizing nonabx means for simple UTI prevention

• Correct Abx prophylaxis choice / duration based on guidelines• When Abx needed:

– Use evidence-based prescribing rules– Consult local antibiograms for susceptibility patterns– Avoid empiric treatment in less severe infections– Switch to culture directed therapy

Wagenlehner et al. Eur Urol 2013; 64:358.

Overuse of Antibiotic Prophylaxis• Review of patient records in

Premier Perspectives Database • 10 GU surgeries (2007-2012)• Overall compliance with Abx

type / duration 53% (0.6-97%)• Overall compliance rate

increased over time (46% 2007 to 59% 2012)

Mossanen et al. J Urol 2015; 193:543.

So what is the optimal duration of antibiotics in endoscopic stone surgery?

Positive Preoperative Urine Culture

Wagenlehner et al. Eur Urol 2013; 64:358.

Negative Preop Urine Culture and URS

• Review of 97 URS patients• All received single preop Abx

dose• Group 1: 1-week Abx postop• Group 2: Single dose Abx at

stent removal• Excluded high risk patients

(diversion, preop stent)Ramaswamy and Shah. J Endourol 2012; 26:122.

Infection and URS

• Review of 550 URS patients• Abx compliance with AUA = 49%

– 82% Choice, 58% Duration• 3.4% infectious complication• Cipro most commonly used Abx• 68% complications due to non-

Gram negative organisism– 63% Gram positive – 5% Yeast Moses et al. J Urol 2016; 195:931.

Negative Preop Urine Culture and PCNL

• Review of 82 PCNL patients• All received single preop Abx

dose• Group 1: ≤ 24 hours of Abx• Group 2: 5-7 days postop Abx• Excluded high risk patients

(chronic catheter, UTI, cystitis, struvite stone)

Deshmukh et al. J Urol 2015; 194:992.

Negative Preop Urine Culture and PCNL

• Review of 115 PCNL patients• All with >2cm stone or hydro• Group 1: Standard periop Abx• Group 2: + 7-day Cipro preop• Excluded high risk patients

(catheter/stent, UTI, fever, DM, bladder path, CRI, previous Rx)

Mariappan et al. BJU Int 2006; 98:1075.

Extended Arm: 3x ↓ risk of SIRSHowever, 7 SIRS and 2 septic shock

Negative Preop Urine Culture and PCNL• 101 PCNL patients prospectively randomized• All with ≥2.5cm stone or hydro• Standard periop Abx vs. Standard Abx + 7-day NFT preop• High risk patients characteristics not described

Bag et al. Urology 2011; 77:45.

↓ postop fever in NFT (19%) group vs. control (49%)

Despite different antibiotic regimens, some patients will still develop infectious complications after endoscopic stone surgery…

Evaluation of Upper Tract Environment

• Guideline recommendations utilize bladder urine culture as:– Surrogate for the upper tract environment– For selection of antibiotic prophylaxis– To define infectious risks

Evaluation of Upper Tract Environment

• Prospective evaluation of 204 PCNL in 198 patients• Bladder urine culture 2 weeks prior

– Neg culture: Periop Abx for 24 hours– Pos culture: Periop Abx + 7 days culture specific Abx preop

• Intraop Renal pelvic culture• Intraop Stone culture• Excluded high risk patients: hx of paraplegia, urinary

diversion, neurogenic bladderKorets et al. J Urol 2011; 186:1899.

Evaluation of Upper Tract Environment• Postop SIRS 9.8%• Postop sepsis requiring ICU care 2.9%

Korets et al. J Urol 2011; 186:1899.

24%

10%16%

64%71%

75%

Evaluation of Upper Tract Environment

• Prospective evaluation of 204 PCNL in 198 patients• Bladder urine culture 2 weeks prior

– Neg culture: Periop Abx for 24 hours– Pos culture: Periop Abx + 7 days culture specific Abx preop

• Intraop Renal pelvic culture• Intraop Stone culture• Excluded high risk patients: hx of paraplegia, urinary

diversion, neurogenic bladderKorets et al. J Urol 2011; 186:1899.

Evaluation of Upper Tract Environment• Review of 328 PCNL / URS patients with routine stone cx• All received single preop Abx dose unless + preop cx• 11 patients (3%) readmitted with sepsis

– 9 after URS– 2 after PCNL

Eswara et al. Urolithiasis 2013; 41:411.

Evaluation of Upper Tract Environment

• Most common pathogens with + stone culture and sepsis were Gram + organisms and yeast

Eswara et al. Urolithiasis 2013; 41:411.

Evaluation of Upper Tract Environment

• Review of 219 PCNL patients• Group 1: Preplaced nephrostomy Drainage

– Acute infection, Hx recurrent UTI / pyelo, lower tract reconstruction / diversion, neurogenic bladder

– 7-10 days directed Abx based on renal urine culture• Group 2: Concurrent access with PCNL

– 7 days of fluoroquinolone or culture directed Abx based on bladder urine culture

Benson et al. J Urol 2014; 192:770.

Evaluation of Upper Tract Environment

Benson et al. J Urol 2014; 192:770.

Advances in Diagnostic Testing

PLoS One 2011; 2011 Feb 16;6(2):e17146. doi: 10.1371/journal.pone.0017146.

Summary• UTIs commonly associated with kidney stone disease and

unfortunately with endoscopic stone treatment

• Antibiotic prophylaxis is primary means of infection prevention

• Antibiotic stewardship important to minimizing population risks

• Patient / perioperative factors associated with ↑ individual risks

Summary• Preoperative bladder urine culture is current test of choice but

may be less optimal compared to renal pelvic / stone culture

• Short course, Guideline recommended antibiotics safe in most patients

• Prolonged antibiotics likely beneficial in select patients; determine on case by case basis

• Consider additional gram positive / yeast coverage

@UNCUrology