UNCLASSIFIED Levofloxacin: Is It Still Suitable as an Empirically Used Antibiotic During the Perioperative Period of Flexible Ureteroscopic Lithotripsy? A Single-center Experience with 754 Patients Ping Ao1, Ling Shu2, Zhenxing Zhang1, Dong Zhuo1*, Zhongqin Wei3 Purpose: To determine the empirical usage of antibiotics and analyze the pathogen spectrum during the perioper- ative period of flexible ureteroscopic lithotripsy (FURSL) with a focus on levofloxacin. Materials and Methods: This retrospective analysis included 754 patients who underwent FURSL successfully in our hospital from January 2015 to July 2019. All patients were sent for urine cultures and prescribed antibiotics during the perioperative period. Patients with negative preoperative urine cultures were divided into levofloxacin (LVXG) and non-levofloxacin groups (NLVXG) based on the empirical use of antibiotics. Operative time, the length of postoperative hospital stays and total hospital stays, total hospitalization costs, postoperative fever rate, and removal rate of stones were compared. Patients with positive urine cultures were analyzed for pathogen distri- bution and antibiotic resistance. Results: In the empirical use of antibiotics among 541 cases with negative urine cultures, the prescription rate of levofloxacin was 68.95%. Compared to that in NLVXG, LVXG had a lower cost of antibiotics but a higher post- operative fever rate and a longer hospital stay. There were no significant differences in operative time, the total hospitalization costs, and the removal rate of stones between the two groups. The top two common pathogens were Escherichia coli (36.11%) and Enterococcus faecalis (24.07%), with resistance rates of 74.36% and 71.15% to levofloxacin, respectively. Conclusion: Levofloxacin might be no longer suitable as the first-line choice of clinical experience when perform- ing FURSL in some centers. Keywords: flexible ureteroscopic lithotripsy; levofloxacin; urine culture INTRODUCTION Flexible ureteroscopic lithotripsy (FURSL) has been widely performed for the removal of kidney stones in several Chinese regional hospitals in recent years. The prevalence of kidney stones is about 5.88% in China and is higher in the South.(1) However, increas- ing cases of perioperative urinary tract infection (UTI) and even sepsis have been reported.(2,3) Asian urologists tend to prescribe antibiotics to reduce the risk of UTI during ureteroscopic lithotripsy, even in patients with negative preoperative urine cultures.(4) The appropri- ate use of antibiotics is a common concern of doctors and patients. Levofloxacin is a quinolone antibiotic commonly used in urology owing to its efficacy and low price. Recently, we observed that sometimes the anti-infective effect of levofloxacin was not satisfacto- ry. Studies have demonstrated typical pathogens with increased resistance to levofloxacin.(5-8) To date, there are few studies regarding the use of levofloxacin in the perioperative period of FURSL and the use of empirical antibiotics in ureteroscopic lithotripsy.(9) In this study, we aimed to evaluate whether levofloxacin is still suit- able as an empirically used antibiotic during the periop- erative period of FURSL. We conducted a case-control 1Department of Urology, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, China. 2Department of Operating Room, The First Affiliated Hospital of Wannan Medical College, Wuhu 241001, China. 3Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China. *Correspondence: Dong Zhuo, Department of Urology, The First Affiliated Hospital of Wannan Medical College, No. 2, Zheshan West Road, Jinghu District, Wuhu, 241001, China. Tel: +86-13705535953, E-mail: whzhuo2008@sina.com. Received February 2020 & Accepted October 2020 study to evaluate the pathogenic distribution in urine culture and analyze antibiotic resistance, which provid- ed a reference for the rational usage of antibiotics. MATERIALS AND METHODS After obtaining approval from the Institutional Review Board (No. WK2017F01), we conducted a retrospec- tive study on patients with a high incidence of stones who underwent FURSL successfully between January 2015 and July 2019, at the urology department of the First Affiliated Hospital of Wannan Medical College in Southern China. In all patients, the diagnosis of upper urinary calculi was confirmed using ultrasound, plain radiography, a computed tomography scan, and intra- venous pyelography. Surgical indications for FURSL were determined by analyzing the imaging data and clinical conditions, and a preoperative double-J stent was indwelt for 1- 4 weeks. In all patients, a routine preoperative urinalysis and urine culture were performed the morning before sur- gery, and re-examined based on the clinical condition after surgery. Patients with negative urine cultures were empirically treated using antibiotics during the peri- operative period of FURSL to prevent UTI. Empirical Urology Journal/Vol 18 No. 4/ July-August 2021/ pp. 445-451. [DOI: 10.22037/uj.v16i7.6033] Vol 18 No 4 July-August 2021 446 antibiotics, which we refer to as the antibiotics chosen by surgeons based on clinical experience when the pathogen test results were unknown or negative, were prescribed with a course of intravenous treatment that lasted 30-60 minutes preoperatively to 24-48 hours postoperatively in patients without risk factors for in- fection. Correspondingly, the course of antibiotics in patients with risk factors for infection (long history of lithiasis, severe hydronephrosis, chronic kidney disease, and diabetes mellitus) was prolonged from 24-48 hours preoperatively to 48-72 hours postoperatively. Based on the antibiotic regimen used, patients were divided into two groups, namely: levofloxacin group (LVXG) and non-levofloxacin group (NLVXG). Levofloxacin hydrochloride injection (Yangtze River Pharmaceutical Group, China) was usually used in LVXG at a dosage of 0.2 g twice daily. Perioperative characteristics and postoperative clinical outcomes, including patient gen- der, age, the side, location, size, and history of urinary stones were recorded. Additionally, conditions such as severe hydronephrosis, chronic kidney disease, diabetes mellitus, operative time, postoperative and total hospi- tal stay, the total cost of hospitalization, postoperative fever rate and removal rate of stones were recorded for each group. Operative time was defined as the time from ureteroscopy insertion to the placement of the ureteral stent. Axillary temperature above 38℃ was considered as postoperative fever, which indicated the diagnostic criteria of systemic inflammatory response syndrome. The definition of complete removal of stones by sur- gery was when no residual stones were observed in the kidney or if stone fragments less than 4mm were re- vealed upon imaging studies one month later. The clinical outcomes of FURSL were compared be- tween the two groups to evaluate the intervention effect of empirically used antibiotics focusing on levofloxa- cin. Pathogen distribution and their antibiotic sensitivities were obtained in patients with positive urine cultures. Urine samples from those patients were tested again af- ter they were administered anti-infective treatment us- ing sensitive antibiotics; FURSL was carried out when a negative culture report was obtained or when the leu- kocytes in their urine decreased. Endoscopic surgery apparatus and accessory tools such as modular flexible ureteroscope (PolyDiagnost, Germany), fiberoptic flex- ible ureteroscope (Storz, Germany), digital flexible ure- teroscope (Olympus, Japan), rigid ureteroscope (Wolf, Germany), holmium laser (Lumenis, USA), ureteral access sheath (Cook, USA) and nitinol stone baskets (Cook, USA) were used when required. In most cases, the procedure of FURSL was as follows: patients were general anesthesia in the lithotomy position. The dou- ble-J stent, placed preoperatively, was removed using ureteroscopy (8/9.8F), and the ureteroscope was drawn out leaving a retrograde safety guidewire. Subsequent- ly, a flexible ureteroscope was inserted after the ureteral access sheath (12/14F) had been placed under the guid- ance of wire. While locating the kidney stones, a 200- μm holmium laser fiber was prepared for fragmenting calculi using appropriate parameters (1.0J, 20Hz). Larg- er fragments were taken out using a nitinol stone basket and subjected to analysis using infrared spectroscopy Table 1. Empirical Use of Antibiotics with Negative Urine Cul- tures during Perioperative Period. Antibiotics Cases (n) Prescription rate (%) Levofloxacin 373 68.95 Cefoxitin sodium 79 14.60 Cefotaxime sodium 27 5.00 Piperacillin-sulbactam 19 3.51 Cefotaxime 22 4.07 Sulbacillin sodium 6 1.11 Clindamycin 3 0.55 Piperacillin-tazobactam 6 1.11 Ceftriaxone sodium 3 0.55 Etimicin sulfate 3 0.55 Total 541 100.00 Parameters Total LVXG NLVXG P Patients, n 541 373 168 Gender, n(%) 0.297 Male 371 (68.6) 261 (70.0) 110 (65.5) Female 170(31.4) 112 (30.0) 58 (34.5) Age in years, mean ± SD 49.57 ± 11.27 49.01 ± 10.68 50.82 ± 12.41 0.085 Stone side, n(%) 0.687 Left 256 (47.3) 181 (48.5) 75 (44.6) Right 256 (47.3) 173 (46.4) 83 (49.4) Bilateral 29 (5.4) 19(5.1) 10 (6.0) Stone location, n(%) 0.211 Kidey 477 (88.2) 335 (89.8) 142 (84.5) Upper ureteral 25 (4.6) 15 (4.0) 10 (6.0) Kidney and upper ureteral 39 (7.2) 23 (6.2) 16 (9.5) Stone size, mm, mean ± SD 18.87 ± 3.74 18.94 ± 3.79 18.69 ± 3.64 0.467 History of urinary stone, n(%) 0.493 Positive 208 (38.4) 147 (39.4) 61 (36.3) Negative 333 (61.6) 226 (60.6) 107 (63.7) Severe hydronephrosis, n(%) 0.832 Positive 18 (3.3) 12 (3.2) 6 (3.6) Negative 523 (96.7) 361(96.8) 162 (96.4) Chronic kidney disease, n(%) 0.494 Positive 30 (5.5) 19 (5.1) 11 (6.5) Negative 511 (94.5) 354(94.9) 157 (93.5) Diabetes mellitus, n(%) 0.894 Positive 47 (8.7) 32 (8.6) 15 (8.9) Negative 494 (91.3) 341(91.4) 153 (91.1) LVXG = levofloxacin group; NLVXG = non-levofloxacin group; n = number of patients; SD = standard deviation. Table 2. Preoperative Characteristics of Patients with Negative Urine Cultures. Levofloxacin during the Perioperation of FURSL- Ao et al. to evaluate the calculi composition. Lastly, 5F double-J stent and 16F catheter were retained. The research was approved by the Research Ethics Committee of The First Affiliated Hospital of Wannan Medical College. Informed consents were obtained from the participants. The leader of The First Affiliat- ed Hospital of Wannan Medical College and the ethics committees made an agreement on this research and ap- proved this consent procedure. Statistical Package for Social Sciences for Windows version 22.0 was used for comparing the perioperative characteristics and postoperative clinical outcomes be- tween the two groups using the independent sample t-test and Chi-squared test with two-sided p < 0.05 be- ing regarded as statistically significant. Multivariate logistic regression analysis was performed to confirm the role of risk factors of postoperative fever in patients with negative preoperative urine cultures. Furthermore, the pathogen spectrum determined from positive urine cultures and resistance rates of antibiotics were listed and analyzed. RESULTS During the perioperative period of FURSL, 541 patients with negative urine cultures were prescribed antibiot- ics, including quinolones, β-lactams, and lincosamides which were concerned mainly with the use of levo- floxacin and cephalosporins. The empirical utilization rate of levofloxacin was as high as 68.95% (373/541) (Table 1). The preoperative characteristics of all pa- tients with negative urine cultures are described in Ta- ble 2. No significant differences in the characteristics between the characteristics of LVXG and NLVXG are seen, which indicates good comparability. Table 3 demonstrates that NLVXG has similar postoperative clinical outcomes compared to that of LVXG in terms of operative time, the total cost of hospitalization, and the removal rate of stones. On the other hand, LVXG has a lower cost of antibiotics (53.83 ± 10.17 vs 68.28 ± 13.81 USD, p = 0.000) but a higher postoperative fever rate (9.4% vs 4.2%, p = 0.036), longer postoperative hospital stay (2.74 ± 1.36 vs 2.38 ± 1.62, p = 0.007), and total hospital stay (8.51 ± 3.25 vs 7.83 ± 2.68, p = 0.011) compared to that in NLVXG. Perioperative urine culture was positive in 213 pa- tients, including 80 males (37.56%) and 133 females (62.44%). A total of 216 positive isolates were detected, which comprised 115 types of Gram-negative bacteria, 82 types of Gram-positive bacteria, and 19 variants of fungi. The most common pathogen isolated was Es- cherichia coli (36.11%) followed by Enterococcus fae- calis (24.07%) (Table 4). After investigating the drug sensitivity test reports of pathogens to antibiotics, it was found that the common Gram-negative bacteria that are sensitive to cefoperazone sulbactam, piperacillin-tazo- bactam, cefotetan, amikacin, imipenem etc., had high resistance to ampicillin, cefazolin, ceftriaxone, levo- floxacin and aztreonam (Table 5). Similarly, the typical Parameters Total LVXG NLVXG P Patients, n 541 373 168 Operative time, min, mean ± SD 90.49 ± 37.66 89. 42 ± 36.23 92.85 ± 40.68 0.328 Postoperative hospital stay, d, mean ± SD 2.63 ± 1.45 2.74 ± 1.36 2.38 ± 1.62 0.007 Total hospital stay, d, mean ± SD 8.30 ± 3.01 8.51 ± 3.25 7.83 ± 2.68 0.011 Total cost of antibiotics, USD, mean ± SD 58.32 ± 13.23 53.83 ± 10.17 68.28 ± 13.81 0.000 Total cost of hospitalization, USD, mean ± SD 2704 ± 522.3 2692 ± 508.5 2731 ± 552.1 0.415 Postoperative fever, n(%) 0.036 Positive 42 (7.8) 35 (9.4) 7 (4.2) Negative 499 (92.2) 338 (90.6) 161 (95.8) Stone removal, n(%) 0.521 Complete 412 (76.2) 287 (76.9) 125 (74.4) Incomplete 129 (23.8) 86 (23.1) 43 (25.6) Table 3. Postoperative Clinical Outcomes in LVXG Versus NLVXG. LVXG = levofloxacin group; NLVXG = non-levofloxacin group; n = number of patients; SD = standard deviation; USD = United States dollar (Converted from CNY at the exchange rate on October 22, 2019). Isolated pathogens Isolates (n) Constituent Ratio (%) Gram-negative 115 53.24 Escherichia coli 78 36.11 Proteus mirabilis 18 8.33 Klebsiella pneumoniae 9 4.17 Pseudomonas aeruginosa 3 1.39 Acinetobacter junii 3 1.39 Serratia marcescens 2 0.93 Aeromonas hydrophila 2 0.93 Gram-positive 82 37.96 Enterococcus faecalis 52 24.07 Staphylococcus epidermidis 12 5.56 Streptococcus agalactiae 9 4.17 Staphylococcus haemolyticus 6 2.78 Staphylococcus saprophyticus 1 0.46 Staphylococcus aureus 2 0.93 Fungus 19 8.80 Candida albicans 11 5.09 Candida glabrata 8 3.70 Table 4. Distribution and Constituent Ratio of Pathogens in Urine Cultures during Perioperative Period. Levofloxacin during the Perioperation of FURSL- Ao et al. Unclassified 447 Vol 18 No 4 July-August 2021 448 Gram-positive bacteria, that are sensitive to vancomy- cin, linezolid, furantoin etc., had high resistance to tet- racycline, clindamycin, erythromycin, gentamycin and levofloxacin (Table 6). Remarkably, our study showed high resistance rate for levofloxacin for E. coli, Pro- teus mirabilis and Klebsiella pneumoniae with values of 74.36%, 61.11% and 66.67% respectively, while the corresponding values were determined to be 71.15%, 83.33%, and 66.67% for E. faecalis, Staphylococcus epidermidis and Streptococcus agalactiae. In the multivariate logistic regression analysis, the use of levofloxacin, moderate to severe hydronephrosis, and history of diabetes were independent risk factors for postoperative fever in preoperative urine culture-nega- tive patients (P < 0.05) (Table 7). DISCUSSION It is well known that the treatment of large upper uri- nary tract stones, especially kidney stones, relied on open surgery in the past. Currently, minimally invasive percutaneous nephrolithotripsy (PCNL) and FURSL are the primary choices.(10,11) Clinical studies have con- firmed that FURSL is effective in treating renal calculi that are around 2 cm in size.(12-15) In such cases, FURSL is more popular than PCNL as the former involves less trauma, is a safer procedure and is associated with fast- er patient recovery(16). However, there are still some serious complications in the perioperative period of FURSL, such as postoperative UTI, urosepsis, and even septic shock. These could be caused by factors such as preoperative UTI, obstruction due to renal calculi, high intrarenal pressure, kidney injury, pathogens invading the blood after lithotripsy, and prolonged surgical dura- tion.(8,17,18) Despite generally attaching importance to the FURSL procedure, knowledge regarding the prevention of infection and selection of antibiotics during the peri- operative period of FURSL is limited. Routine urine cultures during the perioperative period are of great value to prevent UTI and help select suit- able antibiotics.(19) In our institution, urine culture and drug susceptibility testing should be performed at least once before FURSL. Surgery can only be carried out if the urine culture is negative. Studies have shown that positive urine cultures, hydronephrosis, large stones, infectious stones, high renal pressure, and diabetes are risk factors for postoperative infection of the upper uri- nary tract in patients who have undergone endoscopy. (20,21) However, preoperative urine cultures may not ac- curately reflect the infection status of patients with re- nal obstruction and those in whom the Double-J stent is not appropriately placed in the renal pelvis.(21) In such patients, pyelouria or core fragments of the stone can be used for culture and antibiotic susceptibility tests. Fur- thermore, a postoperative urine culture should also be repeated to prevent changes in pathogens. Calculi generally obstruct the urinary tract, which may Antibiotics Escherichia coli (n = 78) Proteus mirabilis (n = 18) Klebsiella pneumoniae (n = 9) Isolates (n) Resistance Rate (%) Isolates (n) Resistance Rate (%) Isolates (n) Resistance Rate (%) Ampicillin 66 84.62 13 72.22 9 100.00 Ampicillin-sulbactam 55 70.51 7 38.89 7 77.78 Cefoperazone-sulbactam 0 0.00 0 0.00 0 0.00 Piperacillin-tazobactam 6 7.69 0 0.00 0 0.00 Ciprofloxacin 61 78.21 7 38.89 7 77.78 Levofloxacin 58 74.36 11 61.11 6 66.67 Cefazolin 66 84.62 7 38.89 4 44.44 Cefotaxime 6 7.69 0 0.00 0 0.00 Ceftazidime 49 62.82 4 22.22 4 44.44 Cefatriaxone 64 82.05 3 16.67 3 33.33 Cefepime 52 66.67 3 16.67 0 0.00 Compound sulfamethoxazole 38 48.72 13 72.22 7 77.78 Tobramycin 26 33.33 4 22.22 0 0.00 Aztreonam 55 70.51 4 22.22 0 0.00 Gentamicin 32 41.03 10 55.56 0 0.00 Amikacin 14 17.95 0 0.00 0 0.00 Nitrofurantoin 6 7.69 17 94.44 4 44.44 Imipenem 3 3.85 3 16.67 0 0.00 Table 5. Resistance Rates of Common Gram-negative Pathogens to Antibiotics Antibiotics Enterococcus faecalis (n = 52) Staphylococcus epidermidis (n = 12) Streptococcus agalactiae (n = 9) Isolates (n) Resistance Rate (%) Isolates(n) Resistance Rate (%) Isolates (n) Resistance Rate (%) Ampicillin 3 5.77 10 83.33 0 0.00 Clindamycin 35 67.31 11 91.67 8 88.89 Ciprofloxacin 12 23.08 11 91.67 6 66.67 Erythromycin 29 55.77 11 91.67 7 77.78 Gentamicin 23 44.23 1 8.33 6 66.67 Tetracycline 38 73.08 5 41.67 5 55.56 Vancomycin 0 0.00 0 0.00 0 0.00 Levofloxacin 37 71.15 10 83.33 6 66.67 Penicillin 6 11.54 11 91.67 1 11.11 Linezolid 0 0.00 0 0.00 0 0.00 Moxifloxacin 12 23.08 10 83.33 5 55.56 Nitrofurantoin 0 0.00 0 0.00 0 0.00 Tegafycline 0 0.00 0 0.00 0 55.56 Table 6. Resistance Rates of Common Gram-positive Pathogens to Antibiotics. Levofloxacin during the Perioperation of FURSL- Ao et al. result in bacteriuria or infection following lithotripsy. Studies have shown that prophylactic antibiotics can reduce the incidence of bacteriuria after ureteroscopic lithotripsy, but can not reduce the risk of postoperative UTI.(22-24) A reduction in the incidence of bacteriuria should reduce the risk of infection; however, the actu- al situation may be complicated and depend on several factors, including damage to the ureteral wall during the procedure, location of the stone, and pressure of the irrigation fluid, which may increase the chances of post- operative infection in the urinary tract. Most urologists recommend the use of prophylactic antibiotics before ureteroscopic lithotripsy.(24) The use of the ureteroscope, especially during lithotripsy, causes varying degrees of ureteral-wall injury. The extent of damage depends on the clinical experience of the surgeon. Generally, com- plicated renal calculi treated using ureteroscopic litho- tripsy pose higher risks of infection. Therefore, even if urine cultures are negative in patients who have been in- dicated lithotripsy, empirical antibiotic treatment is still necessary.(25) In this study, 541 patients with negative urine cultures were empirically prescribed antibiotics to prevent UTI. The commonly prescribed antibiotics in our department are levofloxacin and cephalosporins. Compared to NLVXG, patients in LVXG had similar clinical outcomes, such as operative time, the total cost of hospitalization, and complete stone removal rate, but lower total cost of antibiotics, higher postoperative fe- ver rate, and longer hospitalization. Although levoflox- acin is inexpensive and a frequently prescribed drug in China, our study shows that levofloxacin use did not significantly reduce the total cost incurred by patients, but rather increased postoperative fever rate and pro- longed the hospital stay, leading to increased costs. This may be related to the false-negative results of urine cul- tures and levofloxacin resistance, both of which result- ed in an unsatisfactory anti-infective effect. To a certain extent, our study reveals that there is no obvious value or advantage in prescribing levofloxacin empirically during the perioperative period of FURSL. After analyzing the pathogen spectrum and drug-sus- ceptibility results from positive cultures, we found that E. coli (36.11%) and E. faecalis (24.07%) were the top two bacteria that were highly resistant to levofloxacin. (7,8,26) The most accepted method to determine an an- tibiotic regimen is to select appropriate and sensitive anti-infective agents based on culture results. Howev- er, since laboratory reports are obtained relatively late, the norm is to first prescribe antibiotics empirically and then titrate the regimen based on laboratory findings and patient condition. Prolonged delays and waiting for culture results may adversely affect the efficacy of drug therapy, especially in patients with high-risk of UTIs; therefore, it is particularly essential to choose suitable antibiotics during the perioperative period. The rate of levofloxacin resistance in bacteria was more than 60% and as high as 74.36% in the case of E. coli in our in- vestigation, which suggested that this antibiotic was Table 7. Multivariate analysis of fever after FURSL in patients with preoperative urine culture Negative Cases P value OR 95%CI Use of levofloxacin < 0.001 8.901 2.633～30.095 Moderate to severe hydronephrosis 0.001 7.381 2.305～23.632 Operative time (≥60min) 0.342 0.561 0.170～1.851 history of diabetes(yes) 0.015 4.437 1.338～14.714 not efficacious and, therefore, unsuitable for empirical use. Our clinical study reveals the experiential rate of levofloxacin to be 68.95%, which is inappropriate. On the other hand, if high-grade antibiotics such as ceftri- axone, imipenem, and vancomycin are used directly to achieve anti-infective effect when culture studies are not indicated, patients are treated by supposed safe medication with the suspicion of abusing antibiotics which may lead to more resistant pathogens and even super-bacteria in the long run. The increasing insensi- tivity of ceftriaxone to pathogens for UTI treatment is a problem that has been faced in recent years.(27,28) Based on the data from our study, we believe that the empirical utilization of levofloxacin should be reduced in the perioperative period of FURSL. In line with our analysis, antibiotics, such as cefotetan, piperacillin-ta- zobactam, and amikacin, or similar drugs (cefoxitin, piperacillin sulbactam, etimicin,etc.) , with low re- sistance to common bacteria may be used instead of levofloxacin. Eventually, these antibiotics can be ad- justed based on the results of drug-susceptibility tests. In addition, easy-to-use tools, for instance, “Excel” spreadsheets for monitoring and standardizing the man- agement of antibiotics and, summarizing the pathogens spectra and antibiotic sensitivity, thereby reducing the irrational use of antibiotics in clinical work.(29) In the long run, such measures may not only improve the safe- ty and effectiveness of the procedure, but also accel- erate the postoperative rehabilitation of patients There- fore, this would be in accordance with the concept of enhanced recovery after surgery.(30) Our study had some limitations. In addition to the lim- itations of the retrospective study itself, several sur- geons were involved in performing FURSL. At times, the choice of antibiotic inevitably depended on the sur- geon’s preference or the clinical knowledge of antibi- otic-resistance profiles of microorganisms, which may have resulted in different surgical outcomes. In this single-center investigation, FURSL procedures were performed by qualified senior endoscopic specialists of our department, and we believe that this difference may have had minimal impact on standardized FURSL. Owing to the increase in surgical steps and associated costs, we did not consider urine from the renal pelvis or the core part of the stone for pathogen cultures. How- ever, it has been reported that the discordance between the results of urine and stone cultures carries a high risk of postoperative systemic inflammatory response syndrome.(21,31) Therefore, this study needs further im- provement and our future work will be directed toward a multicenter prospective cohort study to obtain more convincing data that could serve as a powerful refer- ence for the rational use of antibiotics during the peri- operative period of FURSL. CONCLUSIONS This study determined that levofloxacin, which is fa- miliar to surgeons, was used empirically in the periop- Levofloxacin during the Perioperation of FURSL- Ao et al. Unclassified 449 Vol 18 No 4 July-August 2021 450 erative period of FURSL and often used excessively. Despite it being inexpensive, levofloxacin was found to be unsatisfactory in clinical practice and displayed an inordinate resistance rate. When FURSL is performed in areas with a high incidence of urinary calculi, levo- floxacin might no longer be suitable as an empirically used antibiotic in our center; therefore, a decrease in the use of levofloxacin and using alternative sensitive antibiotics based on the findings from urine culture is recommended. CONFLICT OF INTEREST None declared. REFERENCES 1. Zeng G, Mai Z, Xia S, et al. Prevalence of kidney stones in China: an ultrasonography based cross-sectional study. BJU Int. 2017;120:109-16. 2. Komori M, Izaki H, Daizumoto K, et al. 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