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Perioperative antibiotic prophylaxis for stone therapy

Schnabel, Marco J.a; Wagenlehner, Florian M.E.b; Schneidewind, Lailac

doi: 10.1097/MOU.0000000000000576
FUTURE OF KIDNEY STONE MANAGEMENT: Edited by Arkadiusz Miernik
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Purpose of review To give an overview about state-of-the-art antibiotic prophylaxis in urolithasis therapy and focus on recent publications in this field.

Recent findings The number of high-quality publications within the recent time is limited. Preoperative inflammatory blood parameters like C-reactive protein and erythrocyte-sedimentation rate might help in prediction of postoperative systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL). White blood cell count is nonpredictive for urinary tract infection (UTI) in patients with acute renal colic. In patients with low risk for infectious complications, antibiotic prophylaxis during shock-wave lithotripsy (SWL) is unnecessary and single-dose antibiotics are comparably effective as prolonged antibiotic usage during PCNL and ureterorenoscopy (URS).

Summary Current findings support the American Urological Association (AUA) and European Association of Urology (EAU) guideline recommendations for a risk-adapted minimal antibiotic usage. Single-dose antibiotic prophylaxis is sufficient for low-risk PCNL and URS. For SWL no antibiotic prophylaxis is needed.

aDepartment of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg

bDepartment of Urology, Paediatric Urology and Andrology, University Hospital Giessen, Giessen

cDepartment of Haematology/Oncology, University Medicine Greifswald, Greifswald, Germany

Correspondence to Marco J. Schnabel, MD, Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Landshuter Str. 65, 93053 Regensburg, Germany. Tel: +49 941 782 3510; e-mail: marco.schnabel@ukr.de

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STATE OF THE ART IN CURRENT UROLOGICAL GUIDELINES AND NEW DEVELOPMENTS

Use of antibiotic prophylaxis before urologic surgical procedures is a recognized strategy to prevent postoperative infections [1]. However, its use should be risk-adjusted according to the procedure and the patient's individual risk to ensure that antimicrobial stewardship (ABS) perspectives are followed [1,2]. The current EAU guideline recommends for antibiotic prophylaxis in invasive stone therapy: use antibiotic prophylaxis to reduce the rate of symptomatic urinary tract infections (UTIs) following ureteroscopy (weak evidence) as well as use single-dose antibiotic prophylaxis to reduce the rate of clinical urinary infection following percutaneous nephrolithotomy (PCNL) (strong evidence) [3]. Furthermore, the AUA guideline states that antimicrobial prophylaxis should be administered prior to invasive stone intervention and is based primarily on prior urine culture results, the local antibiotic susceptibility data, and in consultation with the current Best Practice Policy Statement on Urologic Surgery Antibiotic Prophylaxis (clinical principle) [4]. For noninvasive shock-wave lithotripsy (SWL) no routine antibiosis is recommended [4,5].

Nevertheless, state-of-the-art antibiotic prophylaxis cannot rule out postoperative infectious complications. For the less invasive ureterorenoscopy (URS) complications like sepsis (0.3%) or UTI (0.95%) are rarely reported [6]. For PCNL on the other hand, postoperative fever is common 10.5–32.1% [7,8], though sepsis rates are low 0.5% too [9]. Several risk factors for infectious complications after PCNL have been evaluated within the last years (Table 1) and can help to stratify patients prior and after the procedure to adapt their antibiotic therapy. The dilemma in PCNL is that the urine diagnostics of the lower urinary tract do not accurately reflect what is going on in the upper urinary tract [10].

Table 1

Table 1

A general extension of antibiotic prophylaxis for every patient seems to be tempting, but did not reduce infectious complication rates in two randomized controlled trials [24,25]. On the other hand, a prolonged duration of antibiotic administration after a surgical procedure without any infective indication encourages the development of multidrug-resistant organisms.

Significantly, Cai et al.[26] demonstrated that adherence to EAU guidelines on antibiotic prophylaxis reduced antibiotic usage without increasing postoperative infection rate, lowered the prevalence of resistant uropathogens and is cost-effective as well. Therefore, adherence to guidelines on antibiotic prophylaxis is an important step to ABS which is also crucial in stone therapy, but improvement is still necessary.

In recent years, research seemed to focus on antibiotic prophylaxis in stone disease especially in PCNL, probably, because of the fear of septic complications.

To provide a current literature overview, a Medline search from 2017 until October 2018 was performed including the following terms: urolithiasis, SWL, URS, PCNL, antibiotic therapy, antibiotic prophylaxis.

On the whole, we try to summarize new aspects and developments in perioperative antibiotic prophylaxis in stone therapy.

The first section of this article will highlight current studies with focus on preoperative diagnostics. Here the value of the preoperative urine culture and inflammatory blood parameters will be discussed. The further course encompasses articles about antibiotic prophylaxis, subdivided in the specific method of stone therapy. An overview of these articles is presented in Table 2.

Table 2

Table 2

Box 1

Box 1

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PREOPERATIVE DIAGNOSTIC

Urinalysis and urine culture are part of the standard diagnostic prior stone treatment to provide an appropriate sensitive antibiotic therapy in case of an UTI [4,5]. Yet, infectious complications can occur even with sterile urine culture prior treatment [33]. The potential mismatch between a culture mid-stream urine and urine from the renal pelvis or a stone culture is a known issue [10,20]. In a recently published prospective, multicenter trial from Argentina and Chile with 122 PCNL patients the prior findings were confirmed. In this study was just a weak correlation (13%) between preoperative and intraoperative urine cultures seen. Postoperative infectious complications occurred in seven patients (5.7%) despite negative urine culture preoperatively, while four (57.1%) of these patients had a positive intrarenal urine or stone culture. In conclusion, the use of an intrarenal urine culture and stone culture was recommended to adapt antibiotic therapy in case of postoperative infectious complications [27▪].

Since the established preoperative diagnostic cannot provide complete certainty about the potential risk for postoperative infectious complications, more parameters are warranted.

In a recent study, Ganesan et al. evaluated preoperative blood and clinical parameters for postoperative SIRS in a cohort of 107 patients who underwent 30F Standard-PCNL retrospectively. A subgroup of 80 patients with negative preoperative urine culture was further analyzed for postoperative SIRS. Preoperative erythrocyte sedimentation rate (ESR) was significantly higher (P = 0.034) in SIRS group compared with patients without SIRS, C-reactive protein (CRP) values were higher too, but slightly missed statistical significance (P = 0.068). ESR more than 6.5 mm/h had a sensitivity of 70.4%, specificity of 61.5%, positive predictive value (PPV) of 48.7% and negative predictive value (NPV) of 80% for SIRS prediction. CRP more than 0.65 mg/dl had a sensitivity of 44.4%, specificity of 73%, PPV of 46.2% and NPV of 71.7% likewise. In addition, a prolonged operative time and positive urine culture were confirmed as risk factors [15].

Another study prospectively analyzed the value of CRP and white blood cell count for patients with acute renal colic pain presenting in the emergency department. 200 consecutive patients were enrolled in the study, prior antibiotic intake was an exclusion criteria. Although elevated CRP (42%) and leukocytosis (36%) were common, UTI proven by urine culture was seldom (13%). White blood cell count did not correlate with UTI in Receiver Operating Characteristic Curve (ROC Curve) curve analysis. In a multivariate model, suspicious urinalysis, five-fold increased CRP value and age at least 54 years were predictive for UTI. Especially in the subgroup of patients at least 54 years of age and not clearly suspicious urinalysis, a five-fold increased CRP was a significant predictor for UTI [odds-ratio (OR) 6.508; 95%-confidence interval (CI): 1.826–23.192]. Suspicious urinalysis was defined as either positive nitrite in dipstick or bacteria more than 20/hpf (high power field) or leukocytes more than 20/hpf in urine sediment. The authors concluded that a routine antibiotic usage is just necessary in colic patients with obvious suspicious urinalysis and CRP might be helpful in older patients with inconclusive urinalysis [28▪].

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SHOCK-WAVE LITHOTRIPSY

According to the guidelines a routine antibiotic prophylaxis for SWL is unnecessary when preinterventional urinalysis is unremarkable [4,5]. This is supported by a retrospective multicenter study from New Zealand, which encompasses a period of 20 years and 10 809 patients. Antibiotic prophylaxis was delivered according to local hospital policy or urologist's preference (6710 patients, 62.1%). Patients who received antibiotics (group 1) had a higher proportion of ureteral stones (21.7 vs. 16.2%, P < 0.0001) and bigger stones (10.1 vs. 9.6 mm, P < 0.0001). Occurrence rate of symptomatic UTI after SWL was low (126 patients, 1.2%) and not different between the groups (group 1: 1.1 vs. 1.3%, P = 0.335). Neither were the rate of urinary sepsis (0.04 vs. 0.15%, P = 0.075), nor the readmission rate to the hospital due to infectious complications (0.3 vs. 0.5%, P = 0.211) different in both groups. In a multivariate model female sex (OR:2.281, CI:1.592–3.267), stone size (OR:0.944, CI:0.920–0.969) and every 1000 additional shocks delivered during SWL (OR:0.836, CI:0.734–0.951) increased the risk of post-SWL UTI. Therefore, the authors concluded that a routine antibiotic prophylaxis does not reduce risk of post-SWL UTI [29].

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URETERORENOSCOPY

AUA best practice guidelines recommend intravenous antibiotics for 24 h or less in patients undergoing URS. Chew et al. analyzed the impact of prolonged antibiotic therapy postoperatively in a double center cohort, retrospectively. Out of 42 patients who received preoperative single-dose antibiotics, two developed an UTI within a 4-month period postoperatively (4.8%). This was compared with 39 patients who received an additional postoperative antibiotic therapy at surgeon's discretion and encountered four UTIs (10.2%). Epidemiological and perioperative parameter were balanced in both groups. In conclusion, single-dose antibiotics prior URS are supposed to be sufficient and a prolonged antibiotic intake postoperatively not beneficial for UTI prevention [30].

These results are supported by a recent retrospective trial with 1068 patients undergoing a URS in four academics hospitals. Patients with positive or missing preoperative urine culture were excluded. 337 patients with a single-dose antibiotic (group 1) were compared with 731 patients with supplemental antibiotics (group 2). Although the BMI was slightly higher in group 2 (29.6 vs. 30.5; P = 0.039), the rate of postoperative ureteral stent placement was higher in group 1 (40.1 vs. 32.4%; P = 0.0149), otherwise the groups were balanced. Within a 30-days follow-up a difference was neither seen in the postoperative UTI rate (3.6 vs. 2.9%, P = 0.546), nor in the unplanned hospital encounters (27.0 vs. 23.7%, P = 0.240). In multivariate analysis only culture-proven UTI within 1 year prior URS correlated significantly with a postoperative UTI, irrespective of antibiotic group (OR 10.8, P < 0.0001) [31▪].

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PERCUTANEOUS NEPHROLITHOTOMY

An intravenous single-dose antibiotic is recommended for all patients prior PCNL with an unremarkable urine culture and no other risk factors [4,5]. In the past, a pretreatment of 1 week with Ciprofloxacin 250 mg twice daily was an established procedure, since this reduced the risk of postoperative SIRS three times [34]. A recent randomized controlled trial of Chew et al. analyzed perioperative antibiotics prior to PCNL in a low infection risk population. 43 patients were randomized to nitrofurantoin 100 mg twice daily for 7 days preoperatively while a control arm of 43 patients received no oral antibiotics. All participants received perioperative doses of ampicillin and gentamicin. Prone PCNL was performed by urologists blinded to randomization. The primary outcome was the development of sepsis. The sepsis rate was not statistically different between the treatment and control groups (12 and 14%, respectively, 95% CI −0.163–0.122, P = 1.0). The authors concluded that there is no advantage providing 1 week of preoperative oral antibiotics in patients at low risk for infectious complications who undergo PCNL [32▪▪]. On the whole, this methodically profound study showed that reducing antibiotic usage is possible and save which is an important approach to ABS.

Beside preoperative factors which might increase the risk of postoperative infectious complications, several intraperative and postoperative risk factors are known (Table 1). In a prospective single center cohort study the impact of residual stone fragments after 30F PCNL on the occurrence of postoperative SIRS was assessed. Antibiotic prophylaxis was started directly with surgery and given until the 14F nephrostomy tube was removed after 2–3 days. Patients with UTI in preoperative urine culture received sensitive antibiotics for at least 7 days prior surgery. 94 (13%) of 729 patients developed SIRS postoperatively. Positive intrarenal urine or stone culture were more common in the SIRS group (26.6 vs. 12.3%, P = 0.003), so were residual fragments (37.2 vs. 26.5%, P = 0.03) assessed by radiograph or computed tomography scan [11▪].

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FUTURE PROSPECTS

More high-quality studies are warranted to select patients on risk for infectious complications and to optimize their perioperative antibiotic therapy. Furthermore, such data is needed to safely cut down antibiotic usage for patients undergoing urolithiasis therapy.

Improved diagnostics like DNA sequencing and the growing knowledge about the human microbiome might improve our antibiotic strategy in the future [35].

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CONCLUSION

Preinterventional urinalysis and urine culture are mandatory prior stone therapy, if the sample is suspicious for UTI start appropriate sensitive antibiotic therapy and decompress obstructed and infected upper urinary tract if necessary. Use single-dose antibiotics for PCNL and URS, but no antibiotics for SWL, in low-risk patients with unremarkable preinterventional urine sample. Take a mismatch of mid-stream urine culture and intrarenal urine or stone culture into account. Sample stones and intrarenal urine for culture during invasive stone therapy. Prolong antibiotic therapy just in case of infectious complications, deescalate therapy according to intraoperative culture results. Current guideline recommendations as well as levels of evidences are summarized in Table 3.

Table 3

Table 3

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Acknowledgements

M.J.S.: Advisory board: Ipsen. Financial support as guest speaker: Janssen, Bristol-Myers-Squibb, Novartis, medac, Bayer, Roche, Dornier.

F.M.E.W.: Advisory boards: Achaogen, Astra Zeneca, Bionorica, MSD, Rempex, Pfizer, Rosen-Pharma, Shionogi und Vifor. Study support by Achaogen, Astellas, Astra Zeneca, Bionorica, Calixa, Cerexa, Leo-Pharma, Merlion, MSD, Cubist, Rempex, Rosen-Pharma, Shionogi, Vifor.

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Financial support and sponsorship

None.

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Conflicts of interest

There are no conflicts of interest.

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REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest
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REFERENCES

1. Sasse A, Mertens R, Sion JP, et al. Surgical prophylaxis in Belgian hospitals: estimate of costs and potential savings. J Antimicrob Chemother 1998; 41:267–272.
2. Çek M, Tandoğdu Z, Naber K, et al. Antibiotic prophylaxis in urology departments, 2005–2010. Eur Urol 2013; 63:386–394.
3. Bonkat G, Pickard R, Bartoletti R, et al. EAU guidelines on urological infections. 2018; Arnhem, The Netherlands: EAU Guidelines Office, Available at: http://uroweb.org/guideline/urological-infections. [Accessed 29 September 2018].
4. Assimos D, Krambeck A, Miller NL, et al. Surgical management of stones: American Urological Association/Endourological Society Guideline, PART I. J Urol 2016; 196:1153–1160.
5. Türk C. EAU guidelines on urolithiasis. 2018; Arnhem, The Netherlands: EAU Guidelines Office, Available at: http://uroweb.org/guideline/urolithiasis. [Accessed 29 September 2018].
6. Somani BK, Giusti G, Sun Y, et al. Complications associated with ureterorenoscopy (URS) related to treatment of urolithiasis: the Clinical Research Office of Endourological Society URS Global study. World J Urol 2017; 35:675–681.
7. de La Rosette J, Assimos D, Desai M, et al. The Clinical Research Office of the Endourological Society Percutaneous Nephrolithotomy Global Study: indications, complications, and outcomes in 5803 patients. J Endourol 2011; 25:11–17.
8. Michel MS, Trojan L, Rassweiler JJ. Complications in percutaneous nephrolithotomy. Eur Urol 2007; 51:899–906. discussion 906.
9. Seitz C, Desai M, Häcker A, et al. Incidence, prevention, and management of complications following percutaneous nephrolitholapaxy. Eur Urol 2012; 61:146–158.
10. Mariappan P, Smith G, Bariol SV, et al. Stone and pelvic urine culture and sensitivity are better than bladder urine as predictors of urosepsis following percutaneous nephrolithotomy: a prospective clinical study. J Urol 2005; 173:1610–1614.
11▪. Degirmenci T, Bozkurt IH, Celik S, et al. Does leaving residual fragments after percutaneous nephrolithotomy in patients with positive stone culture and/or renal pelvic urine culture increase the risk of infectious complications? Urolithiasis 2018; [Epub ahead of print].

The prospective trial underlines the importance of the stone-free status after percutaneous nephrolithotomy (PCNL) to prevent infectious complications postoperatively.

12. Chen L, Xu Q-Q, Li J-X, et al. Systemic inflammatory response syndrome after percutaneous nephrolithotomy: an assessment of risk factors. Int J Urol 2008; 15:1025–1028.
13. Gonen M, Turan H, Ozturk B, Ozkardes H. Factors affecting fever following percutaneous nephrolithotomy: a prospective clinical study. J Endourol 2008; 22:2135–2138.
14. Gutierrez J, Smith A, Geavlete P, et al. Urinary tract infections and postoperative fever in percutaneous nephrolithotomy. World J Urol 2013; 31:1135–1140.
15. Ganesan V, Brown RD, Jiménez JA, et al. C-reactive protein and erythrocyte sedimentation rate predict systemic inflammatory response syndrome after percutaneous nephrolithotomy. J Endourol 2017; 31:638–644.
16. Sharifi Aghdas F, Akhavizadegan H, Aryanpoor A, et al. Fever after percutaneous nephrolithotomy: contributing factors. Surg Infect 2006; 7:367–371.
17. Fernandez A, Foell K, Nott L, et al. Percutaneous nephrolithotripsy in patients with urinary diversions: a case–control comparison of perioperative outcomes. J Endourol 2011; 25:1615–1618.
18. Draga ROP, Kok ET, Sorel MR, et al. Percutaneous nephrolithotomy: factors associated with fever after the first postoperative day and systemic inflammatory response syndrome. J Endourol 2009; 23:921–927.
19. Dogan HS, Guliyev F, Cetinkaya YS, et al. Importance of microbiological evaluation in management of infectious complications following percutaneous nephrolithotomy. Int Urol Nephrol 2007; 39:737–742.
20. Korets R, Graversen JA, Kates M, et al. Postpercutaneous nephrolithotomy systemic inflammatory response: a prospective analysis of preoperative urine, renal pelvic urine and stone cultures. J Urol 2011; 186:1899–1903.
21. Zhong W, Zeng G, Wu K, et al. Does a smaller tract in percutaneous nephrolithotomy contribute to high renal pelvic pressure and postoperative fever? J Endourol 2008; 22:2147–2151.
22. AlSmadi J, Fan J, Zhu W, et al. The influence of super-mini percutaneous nephrolithotomy on renal pelvic pressure in vivo. J Endourol 2018; 32:819–823.
23. Kreydin EI, Eisner BH. Risk factors for sepsis after percutaneous renal stone surgery. Nat Rev Urol 2013; 10:598–605.
24. Seyrek M, Binbay M, Yuruk E, et al. Perioperative prophylaxis for percutaneous nephrolithotomy: randomized study concerning the drug and dosage. J Endourol 2012; 26:1431–1436.
25. Tuzel E, Aktepe OC, Akdogan B. Prospective comparative study of two protocols of antibiotic prophylaxis in percutaneous nephrolithotomy. J Endourol 2013; 27:172–176.
26. Cai T, Verze P, Brugnolli A, et al. Adherence to European Association of Urology Guidelines on Prophylactic Antibiotics: an important step in antimicrobial stewardship. Eur Urol 2016; 69:276–283.
27▪. Walton-Diaz A, Vinay JI, Barahona J, et al. Concordance of renal stone culture: PMUC, RPUC, RSC and post-PCNL sepsis – a nonrandomized prospective observation cohort study. Int Urol Nephrol 2017; 49:31–35.

The prospective multicenter study from South America supports the clinical importance of intraoperative culture from urine of renal pelvis and stones, as these information can be helpful in case of postoperative infectious complications.

28▪. Rosenhammer B, Spachmann PJ, Burger M, et al. Prospective evaluation of predictive parameters for urinary tract infection in patients with acute renal colic. J Emerg Med 2018; 55:319–326.

The prospective cohort study clarifies that raised white blood cell count is common in patients with acute renal colic but nonpredictive for urinary tract infection (UTI), though a five-fold increased C-reactive protein protein can be sign for UTI.

29. Alexander CE, Gowland S, Cadwallader J, et al. Routine antibiotic prophylaxis is not required for patients undergoing shockwave lithotripsy: outcomes from a national shockwave lithotripsy database in New Zealand. J Endourol 2016; 30:1233–1238.
30. Chew BH, Flannigan R, Kurtz M, et al. A single dose of intraoperative antibiotics is sufficient to prevent urinary tract infection during ureteroscopy. J Endourol 2016; 30:63–68.
31▪. Greene DJ, Gill BC, Hinck B, et al. American Urological Association antibiotic best practice statement and ureteroscopy: does antibiotic stewardship help? J Endourol 2018; 32:283–288.

The retrospective multicenter study supports the sufficiency of single-dose antibiotic prophylaxis during ureterorenoscopy, an prolonged antibiotic intake was not beneficial for UTI prevention.

32▪▪. Chew BH, Miller NL, Abbott JE, et al. A randomized controlled trial of preoperative prophylactic antibiotics prior to percutaneous nephrolithotomy in a low infectious risk population: a report from the EDGE Consortium. J Urol 2018; 200:801–808.

The methodically profound randomized controlled trial supports a single-dose antibiotic prophylaxis to be sufficient for low-risk patients undergoing PCNL.

33. Gravas S, Montanari E, Geavlete P, et al. Postoperative infection rates in low risk patients undergoing percutaneous nephrolithotomy with and without antibiotic prophylaxis: a matched case control study. J Urol 2012; 188:843–847.
34. Mariappan P, Smith G, Moussa SA, Tolley DA. One week of ciprofloxacin before percutaneous nephrolithotomy significantly reduces upper tract infection and urosepsis: a prospective controlled study. BJU Int 2006; 98:1075–1079.
35. Mouraviev V, McDonald M. An implementation of next generation sequencing for prevention and diagnosis of urinary tract infection in urology. Can J Urol 2018; 25:9349–9356.
Keywords:

antibiotic prophylaxis; percutaneous nephrolithotomy; shock-wave lithotripsy; stone therapy; ureterorenoscopy; urolithiasis

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