A Comparison of Pre-operative Urine Culture with Intra-operative Stone Culture and Its Association with Post-procedural Sepsis: A Prospective Observational Study

A Comparison of Pre-operative Urine Culture with Intra-operative Stone Culture and Its Association with Post-procedural Sepsis: A Prospective Observational Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A Comparison of Pre-operative Urine Culture with Intra-operative Stone Culture and Its Association with Post-procedural Sepsis: A Prospective Observational Study Debansu Sarkar, Sanjay Singh, Raja Ray This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9193187/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background and Aim: Urosepsis is a dreaded complication following endourological procedures. Urinary calculi are known to harbour bacteria that may be released into the circulation during fragmentation, potentially leading to urosepsis. Thus, urosepsis may develop despite a sterile pre-operative mid-stream urine (MSU) culture. Stone culture is not routinely performed in endourological practice. This study aimed to evaluate (i) the relationship between pre-operative MSU culture and intra-operative stone culture, and (ii) their association with postoperative urosepsis. Materials and Methods: In this comparative observational study (March 2023 – May 2024), 143 patients who underwent percutaneous nephrolithotomy, ureteroscopic lithotripsy, or cystolithotripsy were evaluated. Pre-operative MSU cultures and intra-operative stone cultures were obtained and analysed for positivity, bacterial spectrum, and stone location. Postoperatively, all patients were monitored for sepsis, defined by standard Systemic Inflammatory Response Syndrome (SIRS) criteria in the presence of infection. Results: MSU cultures were positive in 15 patients (10.5 %), whereas stone cultures were positive in 40 patients (28 %), a significantly higher rate (p = 0.03). Escherichia coli was the predominant pathogen in both MSU (73.3%) and stone cultures (50 %). Concordant growth was observed in only 4 of 55 cases (7.3%). Nine patients (6.3 %) developed postoperative sepsis: 7 of 40 with positive stone cultures versus 2 of 103 with negative stone cultures (p = 0.002). Pre-operative MSU culture status was not significantly associated with sepsis (p = 0.24). Conclusion: The microbiological profile of intra-operative stone cultures differs significantly from that of pre-operative MSU cultures. Stone culture is a better predictor of postoperative urosepsis and, when positive, may guide targeted antimicrobial therapy at minimal extra cost. Routine stone culture and sensitivity testing should therefore be incorporated into endourological stone surgery practices. Urolithiasis Stone culture Pre-operative Mid-stream urine culture Urosepsis Figures Figure 1 Figure 2 Introduction Kidney and bladder stone disease has been a well-known clinical entity for centuries. Its incidence is influenced by geographical, climatic, ethnic, dietary, and genetic factors. [ ¹ ] Globally, prevalence rates range from 7 – 13 % in North America, 5 – 9 % in Europe, and 1 – 5 % in Asia. [ ² ] Before 1980, treatment was largely limited to open surgery; thereafter, extracorporeal shock-wave lithotripsy (ESWL) and endoscopic techniques—particularly laser lithotripsy and percutaneous nephrolithotomy (PCNL)—emerged as the dominant approaches. Urinary-tract infections are a frequent complication of endourological procedures and may progress to urosepsis. Post-operative infection affects up to 1.8 % of patients undergoing ureteroscopy with laser lithotripsy and 0.3 – 1.1 % of those treated with PCNL. [ ³ , ⁴ ] Notably, sepsis may develop despite prophylactic antibiotics, and patients with sterile pre-operative urine cultures can still become septic after stone manipulation, likely due to the release of bacteria during stone fragmentation. [ ⁴ ] Despite these risks, routine culture of stone fragments is uncommon; clinicians typically rely on pre-operative urine cultures to guide post-operative antimicrobial therapy. [ ⁵ ⁶] Accordingly, the present study aimed to find out (i) the relationship between pre-operative MSU culture and intra-operative stone culture in patients undergoing endourological procedures and (ii) how each culture source correlates with postoperative urosepsis. Ethics Approval and Consent to Participate The study was conducted in accordance with the ethical principles of the Declaration of Helsinki (2013 revision). Ethical approval was obtained from the Institutional Ethics Committee (IEC) of our institution (Approval No.: IPGME & R/IEC/2023/435). The study involved human participants, and all procedures were performed in accordance with institutional and international ethical standards. Methodology This was a comparative observational study conducted in the Department of Urology at a tertiary care centre from March 2023 to May 2024. Patients with urolithiasis who underwent surgery at this hospital during the aforementioned period were included in this study. In this study, we analysed pre-op MSU culture and intra-operative stone culture of 143 patients. The study excluded patients with urogenital malignancies, non-urological sources of sepsis, severe immunocompromise (such as HIV infection or ongoing chemotherapy), prior use of broad-spectrum antibiotics before urine culture sampling, current steroid therapy, congenital urologic anatomical anomalies, or prolonged catheterisation/ureteral stenting. Mid-stream urine (MSU) samples were collected 5–7 days before surgery. If the pre-operative MSU proved sterile, the patient received a single 1 gm intravenous dose of ceftriaxone 30 minutes before the procedure. For those with a positive culture, surgery was postponed while they completed a 7–10-day course of culture-directed antibiotics, after which a repeat MSU culture was obtained. Urine specimens were streaked onto MacConkey agar and incubated at 37 °C for 24 hours; absence of growth was reported as sterile. Colony morphology was reviewed at 48 hours, and antimicrobial susceptibility was assessed by the disc-diffusion method. Stone fragments were harvested under strict sterile conditions during each procedure and processed using the Nemoy–Stamey method. After sequential rinsing in five vials of sterile saline, the fragments in the fifth vial were crushed, and this suspension was submitted for culture and susceptibility testing [7] . Crushed fragments were inoculated onto chocolatized blood-agar plates and incubated at 37 °C for 48 hours. Bacterial species were identified by standard biochemical techniques, and antibiotic sensitivities were determined with the disk-diffusion method. Surgical approaches varied by stone location: percutaneous nephrolithotomy (PCNL) for renal calculi, ureteroscopic pneumatic lithotripsy for ureteric stones, and transurethral cystolithotripsy for bladder stones. Post-operative sepsis was identified according to the 2001 International Sepsis Definitions Conference, which describes it as a systemic inflammatory response provoked by infection. Systemic inflammatory response syndrome (SIRS) was diagnosed when at least two of the following criteria were present: temperature > 38°C or 90 beats per minute; respiratory rate > 12 breaths per minute; or white-blood-cell count > 12,000 /mm³ or < 4,000 /mm³. Patients who developed sepsis were managed with broad-spectrum antibiotics and vasopressors to maintain haemodynamic stability. Statistical Analysis : - Continuous variables were presented as mean ± SD. Qualitative variables were presented as numbers and percentages of patients. Associations between variables were analysed using the Chi-square test. A p-value <0.05 was considered statistically significant. Results The study enrolled 143 patients, comprising 82 men (57.3 %) and 61 women (42.7 %). The mean age was 44.6 ± 14.5 years. Stratification by stone location produced three groups: Renal calculi: 127 patients (88.8%) underwent percutaneous nephrolithotomy (PCNL). Bladder calculi: 7 patients (4.9%) underwent transurethral mechanical cystolithotripsy. Ureteric calculi: 9 patients (6.3%) were treated with ureteroscopic lithotripsy. Table 1: - Demographic details of patient and stone location Mean ± SD Median (IQR) Age (years) Range 44.56 ± 14.51 4-75 45(18) Sex Number Percentage Male Female 82 61 57.3% 42.7% Site of stone Number Percentage Bladder calculus 7 4.9% Nephrolithiasis 127 88.8% Ureterolithiasis 9 6.3% Of the 143 patients, pre-operative mid-stream urine cultures were positive in 15 cases (10.5 %), whereas intra-operative stone cultures were positive in 40 cases (28 %). Figure 1 illustrates that Escherichia coli was the predominant uropathogen in both specimen types, appearing in 73 % of mid-stream urine (MSU) cultures and 50 % of stone cultures. In MSU specimens, the remaining isolates were mainly Klebsiella pneumoniae and Pseudomonas aeruginosa . Stone cultures, on the other hand, also yielded P. aeruginosa , K. pneumoniae , Enterococcus species, and Proteus mirabilis in addition to E. coli. These findings underscore a substantial difference in the microbial spectrum between urine and stone cultures. Figure 1: - Comparison between micro-organism growth in the mid-stream urine culture and stone culture- Table 2 shows that intra-operative stone cultures were positive far more often than pre-operative mid-stream urine (MSU) cultures (p = 0.03). Only nine patients had both specimens culture-positive; identical organisms were recovered in four of those cases, while the other five displayed divergent growth. Accordingly, true concordance was achieved in just 4 of 55 positive cultures (7.3 %). Overall, some form of mismatch—either growth in only one specimen or growth of different organisms in each—occurred in 42 of 143 patients (37 %). These findings suggest that pre-operative MSU culture is an unreliable surrogate for stone microbiology. Table 2: - Association between MSU culture and Stone Culture: - CULTURE INTRA-OPERATIVE STONE Total P-Value Positive Negative MSU Positive 9 (6.29%) 6 (4.2%) 15 (10.49%) 0.03 Negative 31 (21.67%) 97 (67.83%) 128 (89.51%) Total 40(27.97%) 103 (72.03%) 143 Subgroup analysis by stone location revealed a significant discrepancy between mid-stream urine (MSU) and intra-operative stone cultures only for renal calculi (p = 0.04; as shown in Table 3). Among patients with nephrolithiasis, stone cultures were positive in 28.3 % of cases, whereas pre-op MSU cultures were positive in only 9.45 %. No such difference was observed for bladder or ureteric stones. Table 3: - Comparison of pre-op MSU culture and intra-operative stone culture based on stone location: - Site of stone MSU Culture Positive (n=15) Stone culture Positive (n=40) p-value Bladder calculus (n=7) 2 3 0.14 Nephrolithiasis (n=127) 12 36 0.04 Ureterolithiasis (n=9) 1 1 1 Among the 143 patients studied, postoperative sepsis occurred in nine. Two of these nine had positive pre-op mid-stream urine (MSU) cultures before surgery, whereas seven showed positive stone cultures. The two patients with positive pre-operative MSU cultures also yielded positive stone cultures, but the organisms differed between the two specimens. Every patient who developed sepsis had undergone surgery for nephrolithiasis. Fig.2- Comparison of MSU culture and intra-operative stone culture based on association with post-operative sepsis. Table 4 outlines the relationship between postoperative sepsis and culture results. Of the 15 patients with a positive mid-stream urine (MSU) culture, 2 (13 %) developed sepsis, whereas 7 of the 128 patients (5.5 %) with a negative MSU culture became septic—an association that did not reach statistical significance (p = 0.24). In contrast, sepsis occurred in 7 of 40 patients (17.5 %) whose stone cultures were positive, compared with just 2 of 103 patients (1.94 %) whose stone cultures were negative, demonstrating a significant link between stone-culture positivity and postoperative sepsis (p = 0.002). Table-4: - Association between Sepsis and Stone & MSU Culture CULTURE SEPSIS Total P-value Positive Negative URINE Positive 2 (13.3%) 13 (86.7%) 15 0.24 Negative 7 (5.5%) 121 (94.5%) 128 Total 9 134 143 STONE Positive 7 (17.5%) 33 (82.5%) 40 0.002 Negative 2 (1.9%) 101 (98.1%) 103 Total 9 134 143 Discussion Nine of the 143 patients in our study developed postoperative sepsis—a 6.3 % rate comparable to earlier series [3,4] that likewise included vesical and ureteric lithotripsy alongside PCNL. None of these cases progressed to multi-organ failure, and all were managed conservatively. The patient who developed sepsis had undergone PCNL. PCNL exposes the kidney to uniquely high intrarenal pressures (IRP) and an open parenchymal tract , creating an efficient conduit for bacteria and endotoxin to enter the bloodstream. To keep the field clear, most PCNL systems deliver irrigation through a ­nephroscope at flow rates of 200–400 mL min. If the out-flow (sheath or nephrostomy tract) is even partly obstructed, IRP can climb far above normal renal-pelvic values (200 mmHg during routine PCNL, and the high-pressure cohort had a four-fold rise in SIRS/urosepsis compared with patients kept below 80 mmHg. PCNL generates far higher renal pressures than ureteroscopic or trans-vesical lithotripsy, facilitating intravascular translocation of stone-bound bacteria. The percutaneous tract itself opens low-pressure venous and lymphatic channels, offering an additional conduit for bacteremia that ureteroscopy or cystolithotripsy does not create. This likely explains why only patients treated for renal stones developed sepsis. [13] Urosepsis still arose despite meticulous pre-operative preparation, likely because antibiotics penetrate calculi poorly, the organisms cultured from stones often differ from those in pre-operative urine, and endotoxins are released during fragmentation. Once the stone is broken, numerous venous and lymphatic channels opened by surgery—and the positive pressure of continuous irrigation—provide bacteria with ready access to the bloodstream, fostering intra-operative dissemination. Rao et al described preoperative and postoperative changes in endotoxins, namely bacterial cell wall lipopolysaccharides and tumor necrosis factor (TNF) in their series [9] . They observed that patients who were endotoxaemic yet afebrile before surgery faced a higher likelihood of postoperative bacteraemia, TNF elevation, and fever. These findings highlight that bacterial colonisation of stones and adjacent tissue—and the endotoxin surge released during lithotripsy—remain pivotal contributors to infectious complications. Numerous reports highlight the weak concordance between organisms isolated from stones and those found in bladder urine. Fowler et al. showed that while 77 % of stones yielded positive cultures, only 12.5 % of simultaneous bladder urine samples were positive [10] . Mariappan et al. similarly demonstrated this mismatch, with mid-stream urine (MSU) cultures positive in just 11.1 % of cases compared with 35.2 % positivity in stone cultures [5] . Devraj et al. (2016) echoed these findings, reporting stone-culture positivity in 30.1 % of patients versus 10.8 % for MSU cultures [7]. Consistent with these earlier series, our cohort showed intra-operative stone cultures positive in 28 % of cases, whereas only 10.5% of pre-op MSU cultures were positive. The bacteriology of urine and stone primarily involves gram negative micro-organisms. [9] In our study most common micro-organism isolated in both urine culture and stone culture was Escherichia coli > Pseudomonas aeruginosa. In this study bacteriological concordance was seen in just 2.8% (4/143) cases whereas bacteriological discordance (either growth only in one culture or both positive with different organism growth) was seen in 37% of cases (43/143). Therefore, microbiological picture of urine does not reflect that of stone and negative MSU culture does not rule out stone infection. Gram-negative organisms predominated in both urine and stone cultures [9] , with Escherichia coli being the most common isolate, followed by Pseudomonas aeruginosa . Exact concordance—i.e., the same organism recovered from both specimens—occurred in only 4 of 55 patients (7.3 %) . In contrast, some form of discordance (growth in just one sample or growth of different organisms in the two samples) was observed in 43 patients (37 %) . These data underscore that bladder-urine findings seldom mirror stone microbiology; a sterile pre-op MSU culture therefore, cannot be taken as evidence that the calculus itself is uninfected. Post-operative bacteraemia tends to emerge within the first six hours after surgery [12]; meanwhile, stone-culture reports are not available until about 48 hours later. As a result, culture findings cannot guide interventions to avert early SIRS, but they do become useful for directing therapy when fever persists beyond the two-day point. Limitations: - This study has several limitations. It did not account for potential confounding factors such as stone composition, stone burden, operative duration, or the presence of obstructed calyces. Additionally, antibiotic susceptibility patterns were not compared in cases with identical organisms. Finally, subgroup analysis showed significant differences only in nephrolithiasis, limiting generalizability. Conclusion The microbial milieu inside the calculus differs substantially from that of bladder urine. Intraoperative stone cultures are significantly associated with postoperative sepsis and outperform midstream urine cultures in predicting this complication. Moreover, the information they provide can steer targeted antibiotic therapy at little additional expense. Accordingly, we recommend obtaining a stone culture for every patient to enable prompt initiation of optimal antimicrobial treatment if sepsis arises after surgery. Declarations Funding The authors received no financial support for the research, authorship, and/or publication of this article. Author Contribution S.S.: Conceptualisation, Methodology, Data curation, Investigation, Writing – original draft.D.S.: Supervision, Methodology, Validation, Writing – review & editing.R.R.: Formal analysis, Data curation, Visualisation, Writing – review & editing.All authors read and approved the final manuscript References Miano R, Germani S, Vespasiani G (2007) Stones and urinary tract infections. Urol Int 79:32–36 Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y (2017) Epidemiology of stone disease across the world. World J Urol 35(9):1301–1320. 10.1007/s00345-017-2008-6 Epub 2017 Feb 17. PMID: 28213860 Knopf HJ, Graff HJ, Schulze H (2003) Perioperative antibiotic prophylaxis in ureteroscopic stone removal. Eur Urol 44:115 Draga RO, Kok ET, Sorel MR et al (2009) Percutaneous nephrolithotomy: factors associated with fever after the first postoperative day and systemic inflammatory response syndrome. J Endourol 23:921 Mariappan P, Smith G, Bariol SV, Moussa SA, Tolley DA (2005) 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 173:1610–1614 Walton-Diaz A, Vinay JI, Barahona J et al (2017) Concordance of renal stone culture: PMUC, RPUC, RSC and post-PCNL sepsis—a non-randomized prospective observation cohort study. Int Urol Nephrol 49:31–35 Devraj R, Tanneru K, Reddy B, Amancherla H, Chilumala R (2016) Renal stone culture and sensitivity is a better predictor of potential urosepsis than pelvic or midstream urine culture and sensitivity. J NTR Univ Health Sci 5:261 Nemoy NJ, Stamey TA Surgical, bacteriological and biochemical management of infection stones. JAMA, 215: 1470, 1971 Rao PN, Dube DA, Weightman NC, Oppenheim BA, Morris J (1991) Prediction of septicemia following endourological manipulation for stones in the upper urinary tract. J Urol 146:955 Fowler JE (1984) Bacteriology of branched renal calculi and accompany ing urinary tract infection. J Urol 131:213–215 Lewi HJE, White A, Hutchinson AG, Scott R (1984) The bacteriology of the urine and renal calculi. Urol Res 12:107–109 O’Keeffe NK, Mortimer AJ, Sambrook PA et al (1993) Severe sepsis following percutaneous or endoscopic procedures for urinary tract stones. Br J Urol 72:277–283 Omar M, Noble M, Sivalingam S, El Mahdy A, Gamal A, Farag M, Monga M (2016) Systemic inflammatory response syndrome after percutaneous nephrolithotomy: a randomized single-blind clinical trial evaluating the impact of irrigation pressure. J Urol 196(1):109–114 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 04 May, 2026 Reviews received at journal 09 Apr, 2026 Reviewers agreed at journal 08 Apr, 2026 Reviewers invited by journal 06 Apr, 2026 Editor assigned by journal 02 Apr, 2026 Submission checks completed at journal 02 Apr, 2026 First submitted to journal 22 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9193187","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":620018189,"identity":"42938d6c-900e-484f-9037-4d3ccc5f3858","order_by":0,"name":"Debansu Sarkar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYHACxgNAggfCrgBiZuYGgnqQtJwBaWEkTgvUwjYwiV+Lwe3DBw58+HVYxpx/deLjynm10fztQC0/Krbh1nIuLeHgzL7DPJYz3m42PLvteO6Mw4wNjD1nbuPWcobH4DBvz2Eegxtnt0k2bjuW2wDUwszYRpyW7T8b5xzLnU+UFp4fQC3ne7cxNjbU5G4gpEXyDBvQLw3pQL/wbpZsOHYgdyNQy0F8fuE7w3zwwYc/1vbm/Gc3fmyoqcudd/7wwQc/KnBrAQPGtmYGA4kEEPMwWOAAfvUg8KeOwYAfrK6OsOJRMApGwSgYcQAAAbVm4IwAlPEAAAAASUVORK5CYII=","orcid":"","institution":"Institute of Post Graduate Medical Education and Research","correspondingAuthor":true,"prefix":"","firstName":"Debansu","middleName":"","lastName":"Sarkar","suffix":""},{"id":620018190,"identity":"6f1c1a53-5cd6-4cf1-8fb6-ec6ab7ac9c3c","order_by":1,"name":"Sanjay Singh","email":"","orcid":"","institution":"Institute of Post Graduate Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Sanjay","middleName":"","lastName":"Singh","suffix":""},{"id":620018191,"identity":"2ce12e22-5079-46b7-b7e0-cc47ae0472a7","order_by":2,"name":"Raja Ray","email":"","orcid":"","institution":"Institute of Post Graduate Medical Education and Research","correspondingAuthor":false,"prefix":"","firstName":"Raja","middleName":"","lastName":"Ray","suffix":""}],"badges":[],"createdAt":"2026-03-22 18:38:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9193187/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9193187/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106728739,"identity":"e8702850-d35a-4a83-ab8a-f4098eee8d63","added_by":"auto","created_at":"2026-04-12 18:44:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":18012,"visible":true,"origin":"","legend":"\u003cp\u003eComparison between micro-organism growth in the mid-stream urine culture and stone culture\u003c/p\u003e","description":"","filename":"f1.png","url":"https://assets-eu.researchsquare.com/files/rs-9193187/v1/977178dba26c8ba352e15937.png"},{"id":106702783,"identity":"4f4ab55f-ed40-4b09-a506-02d72c762c3d","added_by":"auto","created_at":"2026-04-12 07:36:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":17845,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of MSU culture and intra-operative stone culture based on association with post-operative sepsis.\u003c/p\u003e","description":"","filename":"f2.png","url":"https://assets-eu.researchsquare.com/files/rs-9193187/v1/0bc646e48e3b2dbc9c06874f.png"},{"id":108490906,"identity":"84f2dd49-e60c-400f-bbcc-a33b5b307692","added_by":"auto","created_at":"2026-05-05 09:49:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":253247,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9193187/v1/22bac89c-c1b8-4557-ada8-67cd15ff0f85.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eA Comparison of Pre-operative Urine Culture with Intra-operative Stone Culture and Its Association with Post-procedural Sepsis: A Prospective Observational Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eKidney and bladder stone disease has been a well-known clinical entity for centuries. Its incidence is influenced by geographical, climatic, ethnic, dietary, and genetic factors.\u003csup\u003e[\u003c/sup\u003e\u0026sup1;\u003csup\u003e]\u003c/sup\u003e Globally, prevalence rates range from 7 \u0026ndash; 13 % in North America, 5 \u0026ndash; 9 % in Europe, and 1 \u0026ndash; 5 % in Asia.\u003csup\u003e[\u003c/sup\u003e\u0026sup2;\u003csup\u003e]\u003c/sup\u003e Before 1980, treatment was largely limited to open surgery; thereafter, extracorporeal shock-wave lithotripsy (ESWL) and endoscopic techniques\u0026mdash;particularly laser lithotripsy and percutaneous nephrolithotomy (PCNL)\u0026mdash;emerged as the dominant approaches.\u003c/p\u003e\n\u003cp\u003eUrinary-tract infections are a frequent complication of endourological procedures and may progress to urosepsis. Post-operative infection affects up to 1.8 % of patients undergoing ureteroscopy with laser lithotripsy and 0.3 \u0026ndash; 1.1 % of those treated with PCNL.\u003csup\u003e\u0026nbsp;[\u003c/sup\u003e\u0026sup3;\u003csup\u003e,\u003c/sup\u003e ⁴\u003csup\u003e]\u003c/sup\u003e Notably, sepsis may develop despite prophylactic antibiotics, and patients with sterile pre-operative urine cultures can still become septic after stone manipulation, likely due to the release of bacteria during stone fragmentation. \u003csup\u003e[\u003c/sup\u003e⁴\u003csup\u003e]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eDespite these risks, routine culture of stone fragments is uncommon; clinicians typically rely on pre-operative urine cultures to guide post-operative antimicrobial therapy. \u003csup\u003e[\u003c/sup\u003e⁵ ⁶] Accordingly, the present study aimed to find out (i) the relationship between pre-operative MSU culture and intra-operative stone culture in patients undergoing endourological procedures and (ii) how each culture source correlates with postoperative urosepsis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eEthics Approval and Consent to Participate\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the ethical principles of the Declaration of Helsinki (2013 revision).\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained from the Institutional Ethics Committee (IEC) of our institution (Approval No.: IPGME \u0026amp; R/IEC/2023/435).\u003c/p\u003e\n\u003cp\u003eThe study involved human participants, and all procedures were performed in accordance with institutional and international ethical standards.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003eThis was a comparative observational study conducted in the Department of Urology at a tertiary care centre from March 2023 to May 2024.\u003c/p\u003e\n\u003cp\u003ePatients with urolithiasis who underwent surgery at this hospital during the aforementioned period were included in this study. In this study, we analysed pre-op MSU culture and intra-operative stone culture of 143 patients.\u003c/p\u003e\n\u003cp\u003eThe study excluded patients with urogenital malignancies, non-urological sources of sepsis, severe immunocompromise (such as HIV infection or ongoing chemotherapy), prior use of broad-spectrum antibiotics before urine culture sampling, current steroid therapy, congenital urologic anatomical anomalies, or prolonged catheterisation/ureteral stenting.\u003c/p\u003e\n\u003cp\u003eMid-stream urine (MSU) samples were collected 5\u0026ndash;7 days before surgery. If the pre-operative MSU proved sterile, the patient received a single 1 gm intravenous dose of ceftriaxone 30 minutes before the procedure. For those with a positive culture, surgery was postponed while they completed a 7\u0026ndash;10-day course of culture-directed antibiotics, after which a repeat MSU culture was obtained. Urine specimens were streaked onto MacConkey agar and incubated at 37 \u0026deg;C for 24 hours; absence of growth was reported as sterile. Colony morphology was reviewed at 48 hours, and antimicrobial susceptibility was assessed by the disc-diffusion method.\u003c/p\u003e\n\u003cp\u003eStone fragments were harvested under strict sterile conditions during each procedure and processed using the Nemoy\u0026ndash;Stamey method. After sequential rinsing in five vials of sterile saline, the fragments in the fifth vial were crushed, and this suspension was submitted for culture and susceptibility testing \u003csup\u003e[7]\u003c/sup\u003e. Crushed fragments were inoculated onto chocolatized blood-agar plates and incubated at 37 \u0026deg;C for 48 hours. Bacterial species were identified by standard biochemical techniques, and antibiotic sensitivities were determined with the disk-diffusion method.\u003c/p\u003e\n\u003cp\u003eSurgical approaches varied by stone location: percutaneous nephrolithotomy (PCNL) for renal calculi, ureteroscopic pneumatic lithotripsy for ureteric stones, and transurethral cystolithotripsy for bladder stones.\u003c/p\u003e\n\u003cp\u003ePost-operative sepsis was identified according to the 2001 International Sepsis Definitions Conference, which describes it as a systemic inflammatory response provoked by infection. Systemic inflammatory response syndrome (SIRS) was diagnosed when at least two of the following criteria were present: temperature \u0026gt; 38\u0026deg;C or \u0026lt; 36\u0026deg;C; heart rate \u0026gt; 90 beats per minute; respiratory rate \u0026gt; 12 breaths per minute; or white-blood-cell count \u0026gt; 12,000 /mm\u0026sup3; or \u0026lt; 4,000 /mm\u0026sup3;. Patients who developed sepsis were managed with broad-spectrum antibiotics and vasopressors to maintain haemodynamic stability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStatistical Analysis\u003c/u\u003e\u003c/strong\u003e\u003cstrong\u003e: -\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eContinuous variables were presented as mean \u0026plusmn; SD. Qualitative variables were presented as numbers and percentages of patients. Associations between variables were analysed using the Chi-square test. A p-value \u0026lt;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study enrolled 143 patients, comprising 82 men (57.3 %) and 61 women (42.7 %). The mean age was 44.6 \u0026plusmn; 14.5 years. Stratification by stone location produced three groups:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eRenal calculi:\u003c/strong\u003e 127 patients (88.8%) underwent percutaneous nephrolithotomy (PCNL).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eBladder calculi:\u003c/strong\u003e 7 patients (4.9%) underwent transurethral mechanical cystolithotripsy.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eUreteric calculi:\u003c/strong\u003e 9 patients (6.3%) were treated with ureteroscopic lithotripsy.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eTable 1: - Demographic details of patient and stone location\u003c/p\u003e\n\u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMedian (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003cp\u003eRange\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e44.56 \u0026plusmn; 14.51\u003c/p\u003e\n \u003cp\u003e4-75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e45(18)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePercentage\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e57.3%\u003c/p\u003e\n \u003cp\u003e42.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSite of stone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePercentage\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBladder calculus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNephrolithiasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e88.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eUreterolithiasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eOf the 143 patients, pre-operative mid-stream urine cultures were positive in 15 cases (10.5 %), whereas intra-operative stone cultures were positive in 40 cases (28 %).\u003c/p\u003e\n\u003cp\u003eFigure 1 illustrates that \u003cstrong\u003eEscherichia coli\u003c/strong\u003e was the predominant uropathogen in both specimen types, appearing in 73 % of mid-stream urine (MSU) cultures and 50 % of stone cultures. In MSU specimens, the remaining isolates were mainly \u003cstrong\u003eKlebsiella pneumoniae\u003c/strong\u003e and \u003cstrong\u003ePseudomonas aeruginosa\u003c/strong\u003e. Stone cultures, on the other hand, also yielded \u003cstrong\u003eP. aeruginosa\u003c/strong\u003e, \u003cstrong\u003eK. pneumoniae\u003c/strong\u003e, \u003cstrong\u003eEnterococcus\u003c/strong\u003e species, and \u003cstrong\u003eProteus mirabilis\u003c/strong\u003e in addition to E. coli. These findings underscore a substantial difference in the microbial spectrum between urine and stone cultures.\u003c/p\u003e\n\u003cp\u003eFigure 1: - Comparison between micro-organism growth in the mid-stream urine culture and stone culture-\u003c/p\u003e\n\u003cp\u003eTable 2 shows that intra-operative stone cultures were positive far more often than pre-operative mid-stream urine (MSU) cultures (p = 0.03). Only nine patients had both specimens culture-positive; identical organisms were recovered in four of those cases, while the other five displayed divergent growth. Accordingly, true concordance was achieved in just 4 of 55 positive cultures (7.3 %). Overall, some form of mismatch\u0026mdash;either growth in only one specimen or growth of different organisms in each\u0026mdash;occurred in 42 of 143 patients (37 %). These findings suggest that pre-operative MSU culture is an unreliable surrogate for stone microbiology.\u003c/p\u003e\n\u003cp\u003eTable 2: - Association between MSU culture and Stone Culture: -\u003c/p\u003e\n\u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eCULTURE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eINTRA-OPERATIVE STONE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eP-Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u0026nbsp;MSU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9 (6.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6 (4.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15 (10.49%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e31 (21.67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e97 (67.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e128 (89.51%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40(27.97%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e103 (72.03%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSubgroup analysis by stone location revealed a significant discrepancy between mid-stream urine (MSU) and intra-operative stone cultures only for renal calculi (p = 0.04; as shown in Table 3). Among patients with nephrolithiasis, stone cultures were positive in 28.3 % of cases, whereas pre-op MSU cultures were positive in only 9.45 %. No such difference was observed for bladder or ureteric stones.\u003c/p\u003e\n\u003cp\u003eTable 3: - Comparison of pre-op MSU culture and intra-operative\u0026nbsp;stone culture based on\u0026nbsp;stone location: -\u003c/p\u003e\n\u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSite of stone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eMSU Culture Positive (n=15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eStone culture Positive (n=40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBladder calculus (n=7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e2\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e3\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNephrolithiasis (n=127)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e12\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e36\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.04\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eUreterolithiasis (n=9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e1\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e1\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAmong the 143 patients studied, postoperative sepsis occurred in nine. Two of these nine had positive pre-op mid-stream urine (MSU) cultures before surgery, whereas seven showed positive stone cultures. The two patients with positive pre-operative MSU cultures also yielded positive stone cultures, but the organisms differed between the two specimens. Every patient who developed sepsis had undergone surgery for nephrolithiasis.\u003c/p\u003e\n\u003cp\u003eFig.2- Comparison of MSU culture and intra-operative stone culture based on association with post-operative sepsis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 outlines the relationship between postoperative sepsis and culture results. Of the 15 patients with a positive mid-stream urine (MSU) culture, 2 (13 %) developed sepsis, whereas 7 of the 128 patients (5.5 %) with a negative MSU culture became septic\u0026mdash;an association that did not reach statistical significance (p = 0.24). In contrast, sepsis occurred in 7 of 40 patients (17.5 %) whose stone cultures were positive, compared with just 2 of 103 patients (1.94 %) whose stone cultures were negative, demonstrating a significant link between stone-culture positivity and postoperative sepsis (p = 0.002).\u003c/p\u003e\n\u003cp\u003eTable-4: - Association between Sepsis and Stone \u0026amp; MSU Culture\u003c/p\u003e\n\u003ctable \u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003eCULTURE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eSEPSIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eURINE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (13.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13 (86.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (5.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e121 (94.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e128\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eSTONE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e33 (82.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003cp\u003e(98.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e134\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eNine of the 143 patients in our study developed postoperative sepsis\u0026mdash;a 6.3 % rate comparable to earlier series\u003csup\u003e\u0026nbsp;[3,4]\u003c/sup\u003e that likewise included vesical and ureteric lithotripsy alongside PCNL. None of these cases progressed to multi-organ failure, and all were managed conservatively. The patient who developed sepsis had undergone PCNL. PCNL exposes the kidney to uniquely \u003cstrong\u003ehigh intrarenal pressures (IRP) and an open parenchymal tract\u003c/strong\u003e, creating an efficient conduit for bacteria and endotoxin to enter the bloodstream. To keep the field clear, most PCNL systems deliver irrigation through a \u0026shy;nephroscope at flow rates of 200\u0026ndash;400 mL min.\u003csup\u003e\u0026nbsp;\u003c/sup\u003eIf the out-flow (sheath or nephrostomy tract) is even partly obstructed, IRP can climb far above normal renal-pelvic values (\u0026lt;10 mmHg). A 2016 prospective study that directly measured IRP showed peaks \u003cstrong\u003e\u0026gt;200 mmHg\u003c/strong\u003e during routine PCNL, and the high-pressure cohort had a four-fold rise in SIRS/urosepsis compared with patients kept below 80 mmHg. PCNL generates far higher renal pressures than ureteroscopic or trans-vesical lithotripsy, facilitating intravascular translocation of stone-bound bacteria. The percutaneous tract itself opens low-pressure venous and lymphatic channels, offering an additional conduit for bacteremia that ureteroscopy or cystolithotripsy does not create. This likely explains why only patients treated for renal stones developed sepsis.\u003csup\u003e\u0026nbsp;[13]\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eUrosepsis still arose despite meticulous pre-operative preparation, likely because antibiotics penetrate calculi poorly, the organisms cultured from stones often differ from those in pre-operative urine, and endotoxins are released during fragmentation. Once the stone is broken, numerous venous and lymphatic channels opened by surgery\u0026mdash;and the positive pressure of continuous irrigation\u0026mdash;provide bacteria with ready access to the bloodstream, fostering intra-operative dissemination.\u003c/p\u003e\n\u003cp\u003eRao et al described preoperative and postoperative changes in endotoxins, namely bacterial cell wall lipopolysaccharides and tumor necrosis factor (TNF) in their series\u003csup\u003e\u0026nbsp;[9]\u003c/sup\u003e.\u003csup\u003e\u0026nbsp;\u003c/sup\u003eThey observed that patients who were endotoxaemic yet afebrile before surgery faced a higher likelihood of postoperative bacteraemia, TNF elevation, and fever. These findings highlight that bacterial colonisation of stones and adjacent tissue\u0026mdash;and the endotoxin surge released during lithotripsy\u0026mdash;remain pivotal contributors to infectious complications.\u003c/p\u003e\n\u003cp\u003eNumerous reports highlight the weak concordance between organisms isolated from stones and those found in bladder urine. Fowler et al. showed that while 77 % of stones yielded positive cultures, only 12.5 % of simultaneous bladder urine samples were positive \u003csup\u003e[10]\u003c/sup\u003e. Mariappan et al. similarly demonstrated this mismatch, with mid-stream urine (MSU) cultures positive in just 11.1 % of cases compared with 35.2 % positivity in stone cultures \u003csup\u003e[5]\u003c/sup\u003e. \u0026nbsp;Devraj et al. (2016) echoed these findings, reporting stone-culture positivity in 30.1 % of patients versus 10.8 % for MSU cultures \u003csup\u003e[7].\u003c/sup\u003e Consistent with these earlier series, our cohort showed intra-operative stone cultures positive in 28 % of cases, whereas only 10.5% of pre-op MSU cultures were positive.\u003c/p\u003e\n\u003cp\u003eThe bacteriology of urine and stone primarily involves gram negative micro-organisms.\u003csup\u003e[9]\u0026nbsp;\u003c/sup\u003eIn our study most common micro-organism isolated in both urine culture and stone culture was Escherichia coli \u0026gt; Pseudomonas aeruginosa. In this study bacteriological concordance was seen in just 2.8% (4/143) cases whereas bacteriological discordance (either growth only in one culture or both positive with different organism growth) was seen in 37% of cases (43/143). Therefore, microbiological picture of urine does not reflect that of stone and negative MSU culture does not rule out stone infection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGram-negative organisms predominated in both urine and stone cultures \u003csup\u003e[9]\u003c/sup\u003e, with Escherichia coli being the most common isolate, followed by \u003cstrong\u003ePseudomonas aeruginosa\u003c/strong\u003e. Exact concordance\u0026mdash;i.e., the same organism recovered from both specimens\u0026mdash;occurred in only \u003cstrong\u003e4 of 55 patients (7.3 %)\u003c/strong\u003e. In contrast, some form of discordance (growth in just one sample or growth of different organisms in the two samples) was observed in \u003cstrong\u003e43 patients (37 %)\u003c/strong\u003e. These data underscore that bladder-urine findings seldom mirror stone microbiology; a sterile pre-op MSU culture therefore, cannot be taken as evidence that the calculus itself is uninfected.\u003c/p\u003e\n\u003cp\u003ePost-operative bacteraemia tends to emerge within the first six hours after surgery \u003csup\u003e[12];\u0026nbsp;\u003c/sup\u003emeanwhile, stone-culture reports are not available until about 48 hours later. As a result, culture findings cannot guide interventions to avert early SIRS, but they do become useful for directing therapy when fever persists beyond the two-day point.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eLimitations: -\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. It did not account for potential confounding factors such as stone composition, stone burden, operative duration, or the presence of obstructed calyces. Additionally, antibiotic susceptibility patterns were not compared in cases with identical organisms. Finally, subgroup analysis showed significant differences only in nephrolithiasis, limiting generalizability.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe microbial milieu inside the calculus differs substantially from that of bladder urine. Intraoperative stone cultures are significantly associated with postoperative sepsis and outperform midstream urine cultures in predicting this complication. Moreover, the information they provide can steer targeted antibiotic therapy at little additional expense. Accordingly, we recommend obtaining a stone culture for every patient to enable prompt initiation of optimal antimicrobial treatment if sepsis arises after surgery.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eS.S.: Conceptualisation, Methodology, Data curation, Investigation, Writing \u0026ndash; original draft.D.S.: Supervision, Methodology, Validation, Writing \u0026ndash; review \u0026amp; editing.R.R.: Formal analysis, Data curation, Visualisation, Writing \u0026ndash; review \u0026amp; editing.All authors read and approved the final manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMiano R, Germani S, Vespasiani G (2007) Stones and urinary tract infections. Urol Int 79:32\u0026ndash;36\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y (2017) Epidemiology of stone disease across the world. World J Urol 35(9):1301\u0026ndash;1320. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00345-017-2008-6\u003c/span\u003e\u003cspan address=\"10.1007/s00345-017-2008-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003eEpub 2017 Feb 17. PMID: 28213860\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKnopf HJ, Graff HJ, Schulze H (2003) Perioperative antibiotic prophylaxis in ureteroscopic stone removal. Eur Urol 44:115\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDraga RO, Kok ET, Sorel MR et al (2009) Percutaneous nephrolithotomy: factors associated with fever after the first postoperative day and systemic inflammatory response syndrome. J Endourol 23:921\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMariappan P, Smith G, Bariol SV, Moussa SA, Tolley DA (2005) 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 173:1610\u0026ndash;1614\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalton-Diaz A, Vinay JI, Barahona J et al (2017) Concordance of renal stone culture: PMUC, RPUC, RSC and post-PCNL sepsis\u0026mdash;a non-randomized prospective observation cohort study. Int Urol Nephrol 49:31\u0026ndash;35\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevraj R, Tanneru K, Reddy B, Amancherla H, Chilumala R (2016) Renal stone culture and sensitivity is a better predictor of potential urosepsis than pelvic or midstream urine culture and sensitivity. J NTR Univ Health Sci 5:261\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNemoy NJ, Stamey TA Surgical, bacteriological and biochemical management of infection stones. JAMA, 215: 1470, 1971\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRao PN, Dube DA, Weightman NC, Oppenheim BA, Morris J (1991) Prediction of septicemia following endourological manipulation for stones in the upper urinary tract. J Urol 146:955\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFowler JE (1984) Bacteriology of branched renal calculi and accompany ing urinary tract infection. J Urol 131:213\u0026ndash;215\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLewi HJE, White A, Hutchinson AG, Scott R (1984) The bacteriology of the urine and renal calculi. Urol Res 12:107\u0026ndash;109\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO\u0026rsquo;Keeffe NK, Mortimer AJ, Sambrook PA et al (1993) Severe sepsis following percutaneous or endoscopic procedures for urinary tract stones. Br J Urol 72:277\u0026ndash;283\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOmar M, Noble M, Sivalingam S, El Mahdy A, Gamal A, Farag M, Monga M (2016) Systemic inflammatory response syndrome after percutaneous nephrolithotomy: a randomized single-blind clinical trial evaluating the impact of irrigation pressure. J Urol 196(1):109\u0026ndash;114\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"african-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"afju","sideBox":"Learn more about [African Journal of Urology](http://link.springer.com/journal/12293)","snPcode":"12301","submissionUrl":"https://submission.springernature.com/new-submission/12301/3","title":"African Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Urolithiasis, Stone culture, Pre-operative Mid-stream urine culture, Urosepsis","lastPublishedDoi":"10.21203/rs.3.rs-9193187/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9193187/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and Aim:\u003c/strong\u003e Urosepsis is a dreaded complication following endourological procedures. Urinary calculi are known to harbour bacteria that may be released into the circulation during fragmentation, potentially leading to urosepsis. Thus, urosepsis may develop despite a sterile pre-operative mid-stream urine (MSU) culture. Stone culture is not routinely performed in endourological practice. This study aimed to evaluate (i) the relationship between pre-operative MSU culture and intra-operative stone culture, and (ii) their association with postoperative urosepsis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods:\u003c/strong\u003e In this comparative observational study (March 2023 – May 2024), 143 patients who underwent percutaneous nephrolithotomy, ureteroscopic lithotripsy, or cystolithotripsy were evaluated. Pre-operative MSU cultures and intra-operative stone cultures were obtained and analysed for positivity, bacterial spectrum, and stone location. Postoperatively, all patients were monitored for sepsis, defined by standard Systemic Inflammatory Response Syndrome (SIRS) criteria in the presence of infection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e MSU cultures were positive in 15 patients (10.5 %), whereas stone cultures were positive in 40 patients (28 %), a significantly higher rate (p = 0.03). Escherichia coli was the predominant pathogen in both MSU (73.3%) and stone cultures (50 %). Concordant growth was observed in only 4 of 55 cases (7.3%). Nine patients (6.3 %) developed postoperative sepsis: 7 of 40 with positive stone cultures versus 2 of 103 with negative stone cultures (p = 0.002). Pre-operative MSU culture status was not significantly associated with sepsis (p = 0.24).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The microbiological profile of intra-operative stone cultures differs significantly from that of pre-operative MSU cultures. Stone culture is a better predictor of postoperative urosepsis and, when positive, may guide targeted antimicrobial therapy at minimal extra cost. Routine stone culture and sensitivity testing should therefore be incorporated into endourological stone surgery practices.\u003c/p\u003e","manuscriptTitle":"A Comparison of Pre-operative Urine Culture with Intra-operative Stone Culture and Its Association with Post-procedural Sepsis: A Prospective Observational Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-12 07:35:57","doi":"10.21203/rs.3.rs-9193187/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"186046368366645900846544573997417834739","date":"2026-05-04T20:57:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-09T04:24:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"124297734591581287171895897342380125265","date":"2026-04-08T07:13:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-06T04:17:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-02T05:45:07+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-02T05:44:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"African Journal of Urology","date":"2026-03-22T18:21:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"african-journal-of-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"afju","sideBox":"Learn more about [African Journal of Urology](http://link.springer.com/journal/12293)","snPcode":"12301","submissionUrl":"https://submission.springernature.com/new-submission/12301/3","title":"African Journal of Urology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8f932ef1-f04b-4b9c-9425-289e9ad821e6","owner":[],"postedDate":"April 12th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"186046368366645900846544573997417834739","date":"2026-05-04T20:57:25+00:00","index":24,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-12T07:35:58+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-12 07:35:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9193187","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9193187","identity":"rs-9193187","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}