optimal antibiotic use during endoscopic kidney stone surgery
TRANSCRIPT
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
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