Original Research
JOURNAL OF ENDOUROLOGY Volume 29, Number XX, XXXX 2015 ª Mary Ann Liebert, Inc. Pp. ---–--DOI: 10.1089/end.2014.0776
Multidrug Resistant Bacteriuria Before Percutaneous Nephrolithotomy Predicts for Postoperative Infectious Complications Nishant Patel, MD,1 William Shi,2 Michael Liss, MD,1 Omer Raheem, MD,1 David Wenzler, MD,1 Craig Schallhorn, BS,3 Linsday Kiyama, BS,3 Charles Lakin, MD,1 Michele Ritter, MD,1 and Roger L. Sur, MD1,4,5
Abstract
Background and Purpose: Multidrug resistant (MDR) uropathogens are increasing in prevalence and may contribute to significant morbidity after percutaneous nephrolithotomy (PCNL). We investigate the presence of MDR bacteriuria and occurrence of postoperative infectious complications in patients who underwent PCNL at our institution. Methods: Retrospective review was performed of 81 patients undergoing PCNL by a single surgeon (RLS) between 2009 and 2013. Patient demographics, comorbidities, stone parameters on imaging, and microbial data were compiled. MDR organisms were defined as resistant to three or more of the American Urological Association Best Practice Statement antimicrobial classes for PCNL. Postoperative complications were graded by Clavien score and European Association of Urology infection grade. Univariate comparisons were analyzed between patients with and without a postoperative infectious complication. Multivariate logistic regression was performed to determine significant predictor variables for postoperative infectious complications. Results: Of the 81 patients undergoing PCNL, 41/81 (51%) had positive preoperative urine culture, 24/81 (30%) had positive MDR urine culture, and 16/81 (19%) had a postoperative infectious complication. Multivariate analysis revealed a positive preoperative MDR urine culture significantly increased the risk of postoperative infectious complication (odds ratio [OR] = 4.89, 95% confidence interval [CI] 1.134–17.8, P = 0.016). The presence of more than one access tract during PCNL also predicted for infectious complications (OR = 7.5, 95% CI 2.13–26.4, P = 0.003) Of the 16 patients with a postoperative infection 3 (18%) had postoperative urine cultures discordant with the preoperative urine cultures. Conclusions: Our institution demonstrated a relatively high prevalence of MDR bacteriuria in patients undergoing PCNL and that MDR is a significant risk factor for postoperative infectious complications despite appropriate preoperative antibiotics. Further investigations regarding prophylaxis modalities and infection prevention strategies are needed. Infectious complications have been documented in 37% of patients undergoing PCNL, which include fever, systemic inflammatory response syndrome (SIRS), and urosepsis.3 Several previous studies have highlighted preoperative and intraoperative risk factors that may increase the risk of infection largely because of stone size, comorbidities, previous related procedures, and culture status. Moreover, the increasing prevalence of resistant bacteria has increased the complexity of antibiotic prophylaxis.4 Unfortunately, resistant bacteria are usually resistant to more than one antibiotic
Introduction
P
ercutaneous nephrolithotomy (PCNL) is the preferred treatment modality for patients with renal calculi ‡ 2 cm, complex or staghorn calculi according to the 2005 Report on Management of Staghorn Calculi.1 PCNL, however, has been associated with a 29.2% to 83% overall risk of perioperative complications.2,3 One area of concern is the increasing rate of infectious complications associated with PCNL coupled with increased trends of antimicrobial resistance. 1
Department of Urology, University of California San Diego Health System, San Diego, California. Bowdoin College, Brunswick, Maine. 3 University of California San Diego School of Medicine, San Diego, California. 4 Veterans Affairs San Diego Medical Center, San Diego, California. 5 Uniformed Services University of the Health Sciences, Bethesda, Maryland. 2
1
2
and are considered multidrug resistant (MDR) bacteria if they are resistant to at least one agent in three or more antimicrobial categories.5,6 We investigate both the prevalence of MDR uropathogens before PCNL and its association with postoperative infectious complications. The findings can be used to determine the strongest risk factors for postoperative complication for proper preoperative counseling, as well as further investigation regarding potential changes in antibiotic prophylaxis strategies. Methods
After Institutional Review Board approval, we retrospectively reviewed the records of 81 patients undergoing PCNL by a single surgeon (RLS) from September 2009 through August 2013. Any patient who did not have a preoperative urine culture (defined as within 30 days of PCNL) was excluded from the analysis. Urine samples were obtained from either bladder (midstream clean catch, catheterization) or kidney (existing nephrostomy drainage tube) samples. Demographic information was collected as well as stone size and presence or absence of staghorn calculus. Preoperative cross-sectional imaging was reviewed, and stone size was defined by the mean sum diameter of all calculi. A staghorn calculus was defined as a calculus within the renal pelvis that extended to at least two calices. An age-adjusted Charlson Comorbidity Index was also calculated for each patient.7 Before PCNL, all patients with positive urine cultures were treated with culture-specific antibiotics for 5 to 7 days preoperatively. Patients with negative cultures were given a regimen of first- or second-generation cephalosporin, ampicillin/clindamycin plus aminoglycoside or fluoroquinolone just before surgery per American Urological Association (AUA) best practice guidelines. Patients underwent standard prone PCNL with renal access obtained by the urologist. All patients had nephrostomy tube drainage postoperatively for 36 to 48 hours postoperatively and then had the tubes removed if a clamping trial was tolerated. Postoperative urine culture was collected when indicated in the presence of fever, SIRS, sepsis, or need for additional procedures (defined as 30 days post-PCNL). Postoperative data were collected including length of stay, presence of postoperative fever ( ‡ 100.4F), presence of SIRS, and presence of sepsis. SIRS was defined if two or more of the following clinical manifestations were present: (1) temperature ‡ 100.4F or £ 96.8F; (2) heart rate > 90 beats per minute; (3) tachypnea greater than 20 breaths per minute; (4) WBC of > 12,000 WBC/lL or < 4000 WBC/lL.8 Sepsis was defined as meeting criteria for SIRS with a positive urine culture within 30 days of the postoperative period. An infection severity grade was assigned according to the European Association of Urology (EAU) guidelines (grade 1: cystitis—dysuria, frequency, urgency, suprapubic pain; grade 2: mild to moderate pyelonephritis—temperature > 100.4F, flank pain; grade 3: severe pyelonephritis—grade 2 + nausea or vomiting; grade 4: urosepsis—temperature ‡ 100.4F or £ 96.8F, heart rate > 90 beats per minute, tachypnea greater than 20 breaths per minute, leukocytosis of > 12,000 white blood cells/lL or < 4000 white blood cells/lL; grade 5: severe urosepsis—grade 4 + organ dysfunction, hypoperfusion, or hypotension; grade 6: uroseptic shock—grade 5 + lactic
PATEL ET AL.
acidosis, refractory hypotension, oliguria, altered mental status, need for vasopressor support).9 The primary outcome for the purposes of this study was defined as any postoperative infection with an EAU urologic infection severity grade of ‡ 2 within 30 days of PCNL. Grade 1 infections were not included because the presence of a Foley catheter or ureteral catheter may mimic symptoms of cystitis. Secondary outcomes included postoperative infectious complications, defined as fever (temperature ‡ 100.4F), SIRS, or sepsis. MDR bacteriuria was defined as resistance to at least one agent in ‡ 3 classes of antibiotics per (AUA Best Practice Policy Statement on Urologic Surgery Antimicrobial Prophylaxis for percutaneous renal surgery: First or secondgeneration cephalosporin, aminoglycoside, metronidazole, clindamycin, ampicillin/sulbactam, or fluoroquinolone.5,10 Because Enterococcus species are intrinsically resistant to cephalosporins, penicillinase-susceptible penicillins, and low levels of aminoglycosides, only vancomycin-resistant Enterococcus was categorized as having MDR. Univariate comparisons were analyzed between patients with (group 1) and without (group 2) a postoperative infectious complication using appropriate testing as indicated (t test, chi-square test, Fisher exact test, and Mann-Whitney U test). Multivariate logistic regression was performed to assess for factors contributing to a postoperative infectious complication. The significance level was defined at P < 0.05. Statistical analysis was performed using SPSS version 21.0. Results
We analyzed the data of 81 patients after excluding 2 patients because of lack of preoperative urine culture within the 30-day period. Patient demographics are shown in Table 1. The mean body mass index (BMI) was 30.2 kg/m2, with 43%
Table 1. Patient Demographics (n = 81) Mean age, years (SD) Mean body mass index, kg/m2 (SD) Mean preoperative creatinine, mg/dL Sex Male Female History of tobacco Median Charlson Comorbidity Score Median stone number Mean sum diameter of calculi, mm (SD) Staghorn calculus Renal structural abnormality History of previous PCNL Diabetes Spinal cord injury Antibiotic within 30 days of urine culture Preoperative stent or nephrostomy Positive preoperative urine culture Positive preoperative MDR urine culture Infectious complications > 1 access tract Struvite composition Transfusion Stone free ( £ 2 mm fragments)
50.1 (14.0) 30.2 (7.9) 1.06 (0.57) 52% 48% 17 (21%) 2 2 35.7 (17) 23 (28%) 11 (14%) 29 (36%) 19 (23.5%) 3 (3.7%) 47 (58%) 44 (54.3%) 41 (51%) 24 (30%) 16 (19.8%) 31 (38.3%) 4 (4.9%) 3 (3.7%) 43 (53.1%)
SD = standard deviation; PCNL = percutaneous nephrolithotomy; MDR = multidrug resistant.
MULTIDRUG RESISTANT CULTURE BEFORE PCNL
3
FIG. 1. Isolated multidrug resistant (MDR) pathogens from preoperative urine culture.
of patients exhibiting a BMI > 30 kg/m2. Twenty-eight percent of patients harbored staghorn calculi, and the mean sum diameter of stone burden was 35.7 mm. Twenty-nine (36%) patients had a surgical history that included a previous PCNL. Forty-one of 81 (51%) patients had a positive preoperative urine culture. Twenty-four of 81 (30%) patients had MDR bacteriuria. Escherichia coli was most common organism
isolated with 28.9% (33/114 isolates) prevalence from preoperative culture. A total of 47 isolates were MDR, and the isolated MDR uropathogens are presented in Figure 1. Of all MDR isolates, E coli was the most prevalent MDR organism at 40.4% (19/47 isolates) with Enterobacter faecium (5/47 isolates) and Proteus mirabilis (5/47 isolates) representing the next most prevalent at 10.6% each. Of all E coli isolates, 57% (19/33) displayed MDR, all of which included resistance to ciprofloxacin. Nine of 24 (37.5%) patients with positive MDR urine culture went on have a postoperative infection develop, compared with 7 of 57 (12.3%) patients with a non-MDR or negative preoperative urine culture (chisquared, P = 0.009). Postoperatively, 19.8% (16/81) patients experienced an infectious complication. The majority of patients with an infectious complication had postoperative fever (75%, 12/ 16), and 62.5% (10/16) met the criteria for SIRS. Three patients experienced urosepsis and one patient died secondary to complications from urosepsis. Table 2 compares demographics and operative characteristics between those patients with and without postoperative infections complications. Patients in whom an infection developed had a significantly higher prevalence of staghorn calculi (50% vs 23.1%, P = 0.032), spinal cord injury (18.8% vs 0%, P < 0.0001), more than access tract during PCNL (75% vs 29.2%, P = 0.001), positive preoperative MDR urine culture (56.3% vs 23.1%, P = 0.009), and a longer mean hospital stay (15.6 days vs 5.2 days, P = 0.037). Postoperative urine culture was performed in 34 patients and was positive in 15 patients. MDR postoperative culture was present in 10 patients. Of the 15 positive cultures, 8 grew identical bacteria to preoperative culture while 7 displayed
Table 2. Comparison of Postoperative Infectious Complications
Mean age, years (SD) Mean body mass index, kg/m2 (SD) Mean preop creatinine, mg/dL Sex Male Female History of tobacco Median Charlson Comorbidity Score Median Stone Number Mean sum diameter of calculi, mm (SD) Staghorn calculus Preoperative nephrostomy Renal structural abnormality History of previous PCNL Diabetes Spinal cord injury Antibiotic within 30 days of urine culture Preoperative stent or nephrostomy Positive preoperative urine culture Positive preoperative MDR urine culture > 1 access tract Struvite composition Transfusion Stone free ( £ 2 mm fragments) Mean length of stay, days (SD)
Postoperative infection, group 1 (n = 16)
No postoperative infection, group 2 (n = 65)
46 (17) 28.0 (8.8) 1.05 (0.75)
51 (13) 30.7 (7.6) 1.06 (0.529)
50.0% 50.0% 18.8% 2 1 38.8 (16.4) 50.0% 25.0% 25.0% 37.5% 25% 18.8% 68.8% 56.3% 62.5% 56.3% 75.0% 25.0% 0% 56.3% 15.6 (18)
52.3% 47.7% 21.5% 3 2 35.0 (17.2) 23.1% 24.6% 10.8% 35.9% 23.1% 0% 55.4% 53.8% 47.7% 23.1% 29.2% 9.8% 4.6% 54.8% 5.2 (3.6)
P value 0.177 0.224 0.955 0.869 0.806 0.407 0.99 0.421 0.032 0.975 0.137 0.907 0.871 < 0.0001 0.332 0.863 0.289 0.009 0.001 0.260 0.381 0.919 0.037
4
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Table 3. Multivariate Analysis for Postoperative Infectious Complications
Mean body mass index, kg/m2 Positive preoperative urine culture Sum diameter of calculi (mm) Staghorn calculus Renal structure abnormality > 1 access tract Positive preoperative MDR urine culture
OR
95% CI
P value
0.95
0.87-1.04
0.25
2.082
0.59-7.5
0.260
1.02
0.98-1.06
0.392
2.53 3.17 7.5 4.89
0.74-8.66 0.77-12.97 2.13-26.4 1.134-17.8
0.140 0.109 0.003 0.016
OR = odds ratio; CI = confidence interval.
discordant growth. In the 16 patients with a postoperative infection, 3 (18.7%) persons had postoperative culture with discordant growth while 4 (25%) had postoperative cultures with concordant growth and 9 (56.3%) had postoperative cultures with no growth. Blood cultures were positive in three (18.7%) patients who had postoperative infections, two of which were discordant and one was concordant growth. Table 3 shows a multivariate analysis of factors associated with a post operative infectious complication. After controlling for BMI, stone sum diameter, renal structure abnormalities, presence of any positive preoperative urine culture, and presence of staghorn calculus, having a positive preoperative MDR urine culture (OR = 4.89, 95% CI 1.134–17.8, P = 0.016) and more than one access tract during surgery (OR = 7.5, 95% CI 2.13–26.4, P = 0.003) were significantly associated with development of a postoperative infection. Discussion
The prevalence of MDR bacteria in preoperative urine cultures before PCNL was 30% and increased the risk of development of a post-PCNL infectious complication by nearly five-fold. Our overall infectious complications rate was 19.8%, which is within the range of 10% to 30% reported in other series.3,11–14 Our findings are concerning because MDR bacteriuria presents a growing challenge in the treatment of patients with nephrolithiasis given its significant impact on patient morbidity, length of stay, and hospital cost. From 2000 to 2009, a 50% to 300% increase in MDR gramnegative bacteria was seen during hospitalizations for urinary tract infection.4 A recent meta-analysis of inpatient populations demonstrated the presence of MDR gram-negative bacteria conferred a 1.5 risk of mortality compared with presence of non-MDR gram-negative bacteria.15 Furthermore, MDR Pseudomonas aeruginosa has been independently associated with 70% higher hospital costs compared with nonresistant strains.16 The problem is compounded by the lack of new antibiotic development by pharmaceutical industries, secondary to high costs and time commitment.17 Bladder urine cultures may not accurately depict the true microbial source in obstructed systems or infected stones and intraoperative stone and pelvic urine cultures more accurately predict urosepsis.18,19 Our study also confirms that positive preoperative urine culture does not significantly
predict infectious complications (OR = 1.74, 95% CI 0.54– 5.57, P = 0.357). These findings highlight the challenge that, at the time of operation, surgeons only have preoperative urine culture to guide antibiotic therapy and typically a minimum of 48 hours has transpired before care can be altered by stone and renal pelvic culture results. Our finding that a positive preoperative MDR culture increases the risk of postoperative infection complication therefore has strong clinical importance because it warns clinicians of a PCNL subset that warrants extra caution. Its presence is an addition to previously established variables associated with postoperative PCNL infectious complications: Staghorn calculi, hydronephrosis, preoperative stent or nephrostomy tube, previous PCNL, prolonged operative time, amount of irrigation, and number of tracts.12,14,18,20,21 Our study observed a 7.5 times risk of postoperative infection when multiple access tracts were used during PCNL (OR = 7.5, 95% CI 2.13–26.4, P = 0.003). Because multiple tracts are generally needed for complex, branched stones, this finding may potentially be considered a surrogate for staghorn or complex stones. In the multivariate model, however, staghorn calculus (OR 2.53, 95%CI 0.74–8.66, P = 0.140) and sum diameter of calculi (OR 1.02, 95% 0.98–1.06, P = 0.26) were nonsignificant. This suggests that multiple access tracts independently predict for postoperative infectious complications. Chen and associates14 demonstrated an usually high risk of SIRS after PCNL in patients with multiple access tracts (OR 22.41, 95% CI 3.91–128.53, P < 0.001), while the presence of staghorn calculus added no independent risk to the development of SIRS. The lingering question from this study remains: Why did patients with preoperative MDR who were treated appropriately still encounter postoperative infectious complications? The most likely answer is the known discordance between preoperative voided urine cultures and both stone and renal pelvic urine cultures that has been extensively documented in the literature. Positive postoperative urine cultures demonstrated 7 of 15 were positive for different pathogens supporting the known discordance of lower and upper tract cultures. Our results, however, also demonstrated that even when preoperative urine cultures were treated appropriately, the postoperative urine cultures still demonstrated that 8 of 15 patients were positive for the same pathogen with similar resistance, implying that the pathogen was either harbored inside the stone, needed longer preoperative treatment, or should have been treated with a different antibiotic regimen. For those 16 patients who experienced a postoperative urinary tract infection (UTI) complication (fever, SIRS, sepsis), 4 (25%) of the patients had concordant postoperative pathogens that had been treated preoperatively, highlighting our current problem: How do we minimize postoperative UTI complications in the face of appropriate treatment? Of note, 9 of these 16 patients did not demonstrate any growth suggesting antibiotics either suppressed bacterial growth or antibiotic-mediated lysing of bacterial cells resulted in endotoxin-related pyrexia. Do these findings alter our interpretation of current antibiotic treatment for PCNL? The latest update of the AUA Best Practice Statement recommends less than 24 hours of perioperative antibiotics, as is supported by Dogan and colleagues20 where their randomized study demonstrated that
MULTIDRUG RESISTANT CULTURE BEFORE PCNL
short-term prophylaxis has no advantage over single-dose prophylaxis in preventing a postoperative infection. Although demographics of their patients are available, this study does not detail the comorbidity of their patients—e.g., presence of indwelling stent or nephrostomy tube, patients with previous fever, immunocompromised states (diabetes mellitus, human immunodeficiency virus), or MDR pathogens. Therefore, we do not know the complete generalizability of their recommendation for single-dose antibiotics. The AUA Best Practice Statement recommends antibiotics ‘‘extending beyond 24 hours from the conclusion of the procedure depending on patient-risk factors and the implications of infection-related morbidity for the patient’’— patient risk factors including colonization of foreign bodies. Treatment of preexisting bacteriuria is standard of care, but is there any benefit to pretreatment in higher risk groups who do not have preexisting bacteriuria? A level 2a prospectively controlled study by Mariappan and coworkers22 demonstrated that PCNL patients at higher risk for postoperative infection ( > 2 cm stone burden and/or hydronephrosis) had three times lower risk of SIRS if given 1 week of preoperative oral ciprofloxacin. What seems intuitive from these historic studies and our current study is that some patients need minimal perioperative antibiotics and others warrant longer courses. Better characterizing these cohorts is warranted by future studies— i.e., who is a high-risk PCNL patient? Furthermore, what is the appropriate duration of pretreatment antibiotics for these high-risk PCNL patients? Given the known discordance of upper and lower tract urine cultures, however, would it be feasible to obtain percutaneous renal pelvic culture 1 to 2 weeks before PCNL? This information would provide the opportunity to manage and subsequently mitigate infections, albeit it would necessitate an ancillary procedure. This admittedly time consuming and extra cost would have to be weighed against its potential benefit, however, much like renal biopsies have been recently advocated in renal-cell carcinoma. A pre-PCNL percutaneous renal pelvis culture in conjunction with future studies that better characterize patients who need pretreatment antibiotic courses could potentially decrease the infectious morbidity of PCNL. Regardless of future directions, what is increasingly clear is that guidelines need to detail which patients need more than the recommended < 24-hour perioperative antibiotic dose. This study and others highlight that differentiation is imperative— patients undergoing PCNL should be risk stratified for postoperative infectious complications. Antibiograms are available at individual hospital levels to optimize judicious antibiotic choice. Our institution’s antibiogram from September 2013 demonstrates an E coli ciprofloxacin resistance rate of 25%,23 and data from the 2010 California Antibiogram Project estimates a ciprofloxacin resistant rate of 17.6% within the state.24 Given these reports, it is concerning that we found our patients undergoing PCNL represented a much higher cohort of ciprofloxacin resistant E coli patients at 57%. This study suggests that urologists should cautiously use their hospital antibiogram data and instead consider evaluating their kidney stone patient antibiotic resistance rates. We no longer routinely use ciprofloxacin for PCNL, but preferentially use intravenous first-generation cephalosporin
5
and gentamicin when cultures do not otherwise guide alternatives. The recent Food and Drug Administration warning of permanent peripheral neuropathy further highlights the judicious use of fluoroquinolones.25 The limitations of this study include its retrospective design, small sample size, and high baseline prevalence of comorbid conditions. While the median Charlson score for the entire cohort was 2, there was no significant difference in Charlson scores. The length of stay was longer in the infectious group (15.6 days vs 5.2 days) because of issues with placement in these patients with significant comorbidities. The omission of intraoperative renal pelvic culture and stone culture data also limits our interpretation. Renal pelvis urine and stone cultures are therefore now routinely collected at our institution given its ability to alter our postoperative care. Conclusions
Our institution demonstrated a relatively high prevalence of MDR bacteriuria in patients undergoing PCNL. Moreover, MDR strongly predicted a postoperative infectious complication. The higher risk of complications associated with MDR bacteriuria should be provided to patients undergoing PCNL and warrants extra attention to postoperative care by urologists. Given that some PCNL patients represent a higher risk cohort for postoperative infectious complications, studies should seek methods to stratify and mitigate their risk. Disclosure Statement
No competing financial interests exist. References
1. Preminger GM, Assimos DG, Lingeman JE, et al. Chapter 1: AUA guideline on management of staghorn calculi: Diagnosis and treatment recommendations. J Urol 2005;173: 1991–2000. 2. Tefekli A, Ali Karadag M, Tepeler K, et al. Classification of percutaneous nephrolithotomy complications using the modified clavien grading system: Looking for a standard. Eur Urol 2008;53:184–190. 3. Michel MS, Trojan L, Rassweiler JJ. Complications in percutaneous nephrolithotomy. Eur Urol 2007;51:899–906. 4. Zilberberg MD, Shorr AF. Secular trends in gram-negative resistance among urinary tract infection hospitalizations in the United States, 2000–2009. Infect Control Hosp Epidemiol 2013;34:940–946. 5. Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrugresistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18:268–281. 6. Linhares I, Raposo T, Rodrigues A, Almeida A. Frequency and antimicrobial resistance patterns of bacteria implicated in community urinary tract infections: A ten-year surveillance study (2000–2009). BMC Infect Dis 2013;13:19. 7. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis 1987;40:373–383. 8. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/
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Society of Critical Care Medicine. Chest 1992;101:1644– 1655. Johansen TE, Botto H, Cek M, et al. Critical review of current definitions of urinary tract infections and proposal of an EAU/ESIU classification system. Int J Antimicrob Agents 2011;38(suppl):64–70. Wolf JS Jr, Bennett CJ, Dmochowski RR, et al. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol 2008;179:1379–1390. Gonen M, Turan H, Ozturk B, Ozkardes H. Factors affecting fever following percutaneous nephrolithotomy: A prospective clinical study. J Endourol 2008;22:2135–2138. Gutierrez J, Smith A, Geavlete P, et al. Urinary tract infections and post-operative fever in percutaneous nephrolithotomy. World J Urol 2013;31:1135–1140. Erdil T, Bostanci Y, Ozden E, et al. Risk factors for systemic inflammatory response syndrome following percutaneous nephrolithotomy. Urolithiasis 2013;41:395–401. Chen L, Xu QQ, Li JX, et al. Systemic inflammatory response syndrome after percutaneous nephrolithotomy: An assessment of risk factors. Int J Urol 2008;15:1025– 1028. Vardakas KZ, Rafailidis PI, Konstantelias AA, Falagas ME. Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: The study, the patient, the bug or the drug? J Infect 2013;66: 401–414. Morales E, Cots F, Sala M, et al. Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition. BMC Health Serv Res 2012;12:122. Rai J, Randhawa GK, Kaur M. Recent advances in antibacterial drugs. Int J Appl Basic Med Res 2013;3:3–10. 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. Korets R, Graversen JA, Kates M, et al. Post-percutaneous nephrolithotomy systemic inflammatory response: A prospective analysis of preoperative urine, renal pelvic urine and stone cultures. J Urol 2011;186:1899–1903.
20. Dogan HS, Sahin A, Cetinkaya Y, et al. Antibiotic prophylaxis in percutaneous nephrolithotomy: Prospective study in 81 patients. J Endourol 2002;16:649–653. 21. Kreydin EI, Eisner BH. Risk factors for sepsis after percutaneous renal stone surgery. Nat Rev Urol 2013;10:598–605. 22. 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. 23. Ritter M, Dube DA, Weightman NC, et al. Antibiogram— Quarter 2, 2013. UC San Diego Health System Infection Control Committee. 2013. 24. Trivedi K, Oyong K, J H. California Antibiogram Project: Aggregate Susceptibiilty Data of Selected Pathogen, 2010. 2010. 25. US Food and Drug Administration. FDA drug safety communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection. Available at: www.fda.gov/Drugs/DrugSafety/ucm365050 .htm Accessed: December 9, 2014.
Address correspondence to: Roger L. Sur, MD UC San Diego Comprehensive Kidney Stone Center 200 W. Arbor Drive, MC 8897 San Diego, CA 92109 E-mail: [email protected]
Abbreviations Used AUA ¼ American Urological Association BMI ¼ body mass index EAU ¼ European Association of Urology MDR ¼ multidrug resistant PCNL ¼ percutaneous nephrolithotomy SIRS ¼ systemic inflammatory response syndrome UTI ¼ urinary tract infection
JOURNAL OF ENDOUROLOGY Volume 29, Number XX, XXXX 2015 ª Mary Ann Liebert, Inc. Pp. ---–--DOI: 10.1089/end.2014.0776
Multidrug Resistant Bacteriuria Before Percutaneous Nephrolithotomy Predicts for Postoperative Infectious Complications Nishant Patel, MD,1 William Shi,2 Michael Liss, MD,1 Omer Raheem, MD,1 David Wenzler, MD,1 Craig Schallhorn, BS,3 Linsday Kiyama, BS,3 Charles Lakin, MD,1 Michele Ritter, MD,1 and Roger L. Sur, MD1,4,5
Abstract
Background and Purpose: Multidrug resistant (MDR) uropathogens are increasing in prevalence and may contribute to significant morbidity after percutaneous nephrolithotomy (PCNL). We investigate the presence of MDR bacteriuria and occurrence of postoperative infectious complications in patients who underwent PCNL at our institution. Methods: Retrospective review was performed of 81 patients undergoing PCNL by a single surgeon (RLS) between 2009 and 2013. Patient demographics, comorbidities, stone parameters on imaging, and microbial data were compiled. MDR organisms were defined as resistant to three or more of the American Urological Association Best Practice Statement antimicrobial classes for PCNL. Postoperative complications were graded by Clavien score and European Association of Urology infection grade. Univariate comparisons were analyzed between patients with and without a postoperative infectious complication. Multivariate logistic regression was performed to determine significant predictor variables for postoperative infectious complications. Results: Of the 81 patients undergoing PCNL, 41/81 (51%) had positive preoperative urine culture, 24/81 (30%) had positive MDR urine culture, and 16/81 (19%) had a postoperative infectious complication. Multivariate analysis revealed a positive preoperative MDR urine culture significantly increased the risk of postoperative infectious complication (odds ratio [OR] = 4.89, 95% confidence interval [CI] 1.134–17.8, P = 0.016). The presence of more than one access tract during PCNL also predicted for infectious complications (OR = 7.5, 95% CI 2.13–26.4, P = 0.003) Of the 16 patients with a postoperative infection 3 (18%) had postoperative urine cultures discordant with the preoperative urine cultures. Conclusions: Our institution demonstrated a relatively high prevalence of MDR bacteriuria in patients undergoing PCNL and that MDR is a significant risk factor for postoperative infectious complications despite appropriate preoperative antibiotics. Further investigations regarding prophylaxis modalities and infection prevention strategies are needed. Infectious complications have been documented in 37% of patients undergoing PCNL, which include fever, systemic inflammatory response syndrome (SIRS), and urosepsis.3 Several previous studies have highlighted preoperative and intraoperative risk factors that may increase the risk of infection largely because of stone size, comorbidities, previous related procedures, and culture status. Moreover, the increasing prevalence of resistant bacteria has increased the complexity of antibiotic prophylaxis.4 Unfortunately, resistant bacteria are usually resistant to more than one antibiotic
Introduction
P
ercutaneous nephrolithotomy (PCNL) is the preferred treatment modality for patients with renal calculi ‡ 2 cm, complex or staghorn calculi according to the 2005 Report on Management of Staghorn Calculi.1 PCNL, however, has been associated with a 29.2% to 83% overall risk of perioperative complications.2,3 One area of concern is the increasing rate of infectious complications associated with PCNL coupled with increased trends of antimicrobial resistance. 1
Department of Urology, University of California San Diego Health System, San Diego, California. Bowdoin College, Brunswick, Maine. 3 University of California San Diego School of Medicine, San Diego, California. 4 Veterans Affairs San Diego Medical Center, San Diego, California. 5 Uniformed Services University of the Health Sciences, Bethesda, Maryland. 2
1
2
and are considered multidrug resistant (MDR) bacteria if they are resistant to at least one agent in three or more antimicrobial categories.5,6 We investigate both the prevalence of MDR uropathogens before PCNL and its association with postoperative infectious complications. The findings can be used to determine the strongest risk factors for postoperative complication for proper preoperative counseling, as well as further investigation regarding potential changes in antibiotic prophylaxis strategies. Methods
After Institutional Review Board approval, we retrospectively reviewed the records of 81 patients undergoing PCNL by a single surgeon (RLS) from September 2009 through August 2013. Any patient who did not have a preoperative urine culture (defined as within 30 days of PCNL) was excluded from the analysis. Urine samples were obtained from either bladder (midstream clean catch, catheterization) or kidney (existing nephrostomy drainage tube) samples. Demographic information was collected as well as stone size and presence or absence of staghorn calculus. Preoperative cross-sectional imaging was reviewed, and stone size was defined by the mean sum diameter of all calculi. A staghorn calculus was defined as a calculus within the renal pelvis that extended to at least two calices. An age-adjusted Charlson Comorbidity Index was also calculated for each patient.7 Before PCNL, all patients with positive urine cultures were treated with culture-specific antibiotics for 5 to 7 days preoperatively. Patients with negative cultures were given a regimen of first- or second-generation cephalosporin, ampicillin/clindamycin plus aminoglycoside or fluoroquinolone just before surgery per American Urological Association (AUA) best practice guidelines. Patients underwent standard prone PCNL with renal access obtained by the urologist. All patients had nephrostomy tube drainage postoperatively for 36 to 48 hours postoperatively and then had the tubes removed if a clamping trial was tolerated. Postoperative urine culture was collected when indicated in the presence of fever, SIRS, sepsis, or need for additional procedures (defined as 30 days post-PCNL). Postoperative data were collected including length of stay, presence of postoperative fever ( ‡ 100.4F), presence of SIRS, and presence of sepsis. SIRS was defined if two or more of the following clinical manifestations were present: (1) temperature ‡ 100.4F or £ 96.8F; (2) heart rate > 90 beats per minute; (3) tachypnea greater than 20 breaths per minute; (4) WBC of > 12,000 WBC/lL or < 4000 WBC/lL.8 Sepsis was defined as meeting criteria for SIRS with a positive urine culture within 30 days of the postoperative period. An infection severity grade was assigned according to the European Association of Urology (EAU) guidelines (grade 1: cystitis—dysuria, frequency, urgency, suprapubic pain; grade 2: mild to moderate pyelonephritis—temperature > 100.4F, flank pain; grade 3: severe pyelonephritis—grade 2 + nausea or vomiting; grade 4: urosepsis—temperature ‡ 100.4F or £ 96.8F, heart rate > 90 beats per minute, tachypnea greater than 20 breaths per minute, leukocytosis of > 12,000 white blood cells/lL or < 4000 white blood cells/lL; grade 5: severe urosepsis—grade 4 + organ dysfunction, hypoperfusion, or hypotension; grade 6: uroseptic shock—grade 5 + lactic
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acidosis, refractory hypotension, oliguria, altered mental status, need for vasopressor support).9 The primary outcome for the purposes of this study was defined as any postoperative infection with an EAU urologic infection severity grade of ‡ 2 within 30 days of PCNL. Grade 1 infections were not included because the presence of a Foley catheter or ureteral catheter may mimic symptoms of cystitis. Secondary outcomes included postoperative infectious complications, defined as fever (temperature ‡ 100.4F), SIRS, or sepsis. MDR bacteriuria was defined as resistance to at least one agent in ‡ 3 classes of antibiotics per (AUA Best Practice Policy Statement on Urologic Surgery Antimicrobial Prophylaxis for percutaneous renal surgery: First or secondgeneration cephalosporin, aminoglycoside, metronidazole, clindamycin, ampicillin/sulbactam, or fluoroquinolone.5,10 Because Enterococcus species are intrinsically resistant to cephalosporins, penicillinase-susceptible penicillins, and low levels of aminoglycosides, only vancomycin-resistant Enterococcus was categorized as having MDR. Univariate comparisons were analyzed between patients with (group 1) and without (group 2) a postoperative infectious complication using appropriate testing as indicated (t test, chi-square test, Fisher exact test, and Mann-Whitney U test). Multivariate logistic regression was performed to assess for factors contributing to a postoperative infectious complication. The significance level was defined at P < 0.05. Statistical analysis was performed using SPSS version 21.0. Results
We analyzed the data of 81 patients after excluding 2 patients because of lack of preoperative urine culture within the 30-day period. Patient demographics are shown in Table 1. The mean body mass index (BMI) was 30.2 kg/m2, with 43%
Table 1. Patient Demographics (n = 81) Mean age, years (SD) Mean body mass index, kg/m2 (SD) Mean preoperative creatinine, mg/dL Sex Male Female History of tobacco Median Charlson Comorbidity Score Median stone number Mean sum diameter of calculi, mm (SD) Staghorn calculus Renal structural abnormality History of previous PCNL Diabetes Spinal cord injury Antibiotic within 30 days of urine culture Preoperative stent or nephrostomy Positive preoperative urine culture Positive preoperative MDR urine culture Infectious complications > 1 access tract Struvite composition Transfusion Stone free ( £ 2 mm fragments)
50.1 (14.0) 30.2 (7.9) 1.06 (0.57) 52% 48% 17 (21%) 2 2 35.7 (17) 23 (28%) 11 (14%) 29 (36%) 19 (23.5%) 3 (3.7%) 47 (58%) 44 (54.3%) 41 (51%) 24 (30%) 16 (19.8%) 31 (38.3%) 4 (4.9%) 3 (3.7%) 43 (53.1%)
SD = standard deviation; PCNL = percutaneous nephrolithotomy; MDR = multidrug resistant.
MULTIDRUG RESISTANT CULTURE BEFORE PCNL
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FIG. 1. Isolated multidrug resistant (MDR) pathogens from preoperative urine culture.
of patients exhibiting a BMI > 30 kg/m2. Twenty-eight percent of patients harbored staghorn calculi, and the mean sum diameter of stone burden was 35.7 mm. Twenty-nine (36%) patients had a surgical history that included a previous PCNL. Forty-one of 81 (51%) patients had a positive preoperative urine culture. Twenty-four of 81 (30%) patients had MDR bacteriuria. Escherichia coli was most common organism
isolated with 28.9% (33/114 isolates) prevalence from preoperative culture. A total of 47 isolates were MDR, and the isolated MDR uropathogens are presented in Figure 1. Of all MDR isolates, E coli was the most prevalent MDR organism at 40.4% (19/47 isolates) with Enterobacter faecium (5/47 isolates) and Proteus mirabilis (5/47 isolates) representing the next most prevalent at 10.6% each. Of all E coli isolates, 57% (19/33) displayed MDR, all of which included resistance to ciprofloxacin. Nine of 24 (37.5%) patients with positive MDR urine culture went on have a postoperative infection develop, compared with 7 of 57 (12.3%) patients with a non-MDR or negative preoperative urine culture (chisquared, P = 0.009). Postoperatively, 19.8% (16/81) patients experienced an infectious complication. The majority of patients with an infectious complication had postoperative fever (75%, 12/ 16), and 62.5% (10/16) met the criteria for SIRS. Three patients experienced urosepsis and one patient died secondary to complications from urosepsis. Table 2 compares demographics and operative characteristics between those patients with and without postoperative infections complications. Patients in whom an infection developed had a significantly higher prevalence of staghorn calculi (50% vs 23.1%, P = 0.032), spinal cord injury (18.8% vs 0%, P < 0.0001), more than access tract during PCNL (75% vs 29.2%, P = 0.001), positive preoperative MDR urine culture (56.3% vs 23.1%, P = 0.009), and a longer mean hospital stay (15.6 days vs 5.2 days, P = 0.037). Postoperative urine culture was performed in 34 patients and was positive in 15 patients. MDR postoperative culture was present in 10 patients. Of the 15 positive cultures, 8 grew identical bacteria to preoperative culture while 7 displayed
Table 2. Comparison of Postoperative Infectious Complications
Mean age, years (SD) Mean body mass index, kg/m2 (SD) Mean preop creatinine, mg/dL Sex Male Female History of tobacco Median Charlson Comorbidity Score Median Stone Number Mean sum diameter of calculi, mm (SD) Staghorn calculus Preoperative nephrostomy Renal structural abnormality History of previous PCNL Diabetes Spinal cord injury Antibiotic within 30 days of urine culture Preoperative stent or nephrostomy Positive preoperative urine culture Positive preoperative MDR urine culture > 1 access tract Struvite composition Transfusion Stone free ( £ 2 mm fragments) Mean length of stay, days (SD)
Postoperative infection, group 1 (n = 16)
No postoperative infection, group 2 (n = 65)
46 (17) 28.0 (8.8) 1.05 (0.75)
51 (13) 30.7 (7.6) 1.06 (0.529)
50.0% 50.0% 18.8% 2 1 38.8 (16.4) 50.0% 25.0% 25.0% 37.5% 25% 18.8% 68.8% 56.3% 62.5% 56.3% 75.0% 25.0% 0% 56.3% 15.6 (18)
52.3% 47.7% 21.5% 3 2 35.0 (17.2) 23.1% 24.6% 10.8% 35.9% 23.1% 0% 55.4% 53.8% 47.7% 23.1% 29.2% 9.8% 4.6% 54.8% 5.2 (3.6)
P value 0.177 0.224 0.955 0.869 0.806 0.407 0.99 0.421 0.032 0.975 0.137 0.907 0.871 < 0.0001 0.332 0.863 0.289 0.009 0.001 0.260 0.381 0.919 0.037
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Table 3. Multivariate Analysis for Postoperative Infectious Complications
Mean body mass index, kg/m2 Positive preoperative urine culture Sum diameter of calculi (mm) Staghorn calculus Renal structure abnormality > 1 access tract Positive preoperative MDR urine culture
OR
95% CI
P value
0.95
0.87-1.04
0.25
2.082
0.59-7.5
0.260
1.02
0.98-1.06
0.392
2.53 3.17 7.5 4.89
0.74-8.66 0.77-12.97 2.13-26.4 1.134-17.8
0.140 0.109 0.003 0.016
OR = odds ratio; CI = confidence interval.
discordant growth. In the 16 patients with a postoperative infection, 3 (18.7%) persons had postoperative culture with discordant growth while 4 (25%) had postoperative cultures with concordant growth and 9 (56.3%) had postoperative cultures with no growth. Blood cultures were positive in three (18.7%) patients who had postoperative infections, two of which were discordant and one was concordant growth. Table 3 shows a multivariate analysis of factors associated with a post operative infectious complication. After controlling for BMI, stone sum diameter, renal structure abnormalities, presence of any positive preoperative urine culture, and presence of staghorn calculus, having a positive preoperative MDR urine culture (OR = 4.89, 95% CI 1.134–17.8, P = 0.016) and more than one access tract during surgery (OR = 7.5, 95% CI 2.13–26.4, P = 0.003) were significantly associated with development of a postoperative infection. Discussion
The prevalence of MDR bacteria in preoperative urine cultures before PCNL was 30% and increased the risk of development of a post-PCNL infectious complication by nearly five-fold. Our overall infectious complications rate was 19.8%, which is within the range of 10% to 30% reported in other series.3,11–14 Our findings are concerning because MDR bacteriuria presents a growing challenge in the treatment of patients with nephrolithiasis given its significant impact on patient morbidity, length of stay, and hospital cost. From 2000 to 2009, a 50% to 300% increase in MDR gramnegative bacteria was seen during hospitalizations for urinary tract infection.4 A recent meta-analysis of inpatient populations demonstrated the presence of MDR gram-negative bacteria conferred a 1.5 risk of mortality compared with presence of non-MDR gram-negative bacteria.15 Furthermore, MDR Pseudomonas aeruginosa has been independently associated with 70% higher hospital costs compared with nonresistant strains.16 The problem is compounded by the lack of new antibiotic development by pharmaceutical industries, secondary to high costs and time commitment.17 Bladder urine cultures may not accurately depict the true microbial source in obstructed systems or infected stones and intraoperative stone and pelvic urine cultures more accurately predict urosepsis.18,19 Our study also confirms that positive preoperative urine culture does not significantly
predict infectious complications (OR = 1.74, 95% CI 0.54– 5.57, P = 0.357). These findings highlight the challenge that, at the time of operation, surgeons only have preoperative urine culture to guide antibiotic therapy and typically a minimum of 48 hours has transpired before care can be altered by stone and renal pelvic culture results. Our finding that a positive preoperative MDR culture increases the risk of postoperative infection complication therefore has strong clinical importance because it warns clinicians of a PCNL subset that warrants extra caution. Its presence is an addition to previously established variables associated with postoperative PCNL infectious complications: Staghorn calculi, hydronephrosis, preoperative stent or nephrostomy tube, previous PCNL, prolonged operative time, amount of irrigation, and number of tracts.12,14,18,20,21 Our study observed a 7.5 times risk of postoperative infection when multiple access tracts were used during PCNL (OR = 7.5, 95% CI 2.13–26.4, P = 0.003). Because multiple tracts are generally needed for complex, branched stones, this finding may potentially be considered a surrogate for staghorn or complex stones. In the multivariate model, however, staghorn calculus (OR 2.53, 95%CI 0.74–8.66, P = 0.140) and sum diameter of calculi (OR 1.02, 95% 0.98–1.06, P = 0.26) were nonsignificant. This suggests that multiple access tracts independently predict for postoperative infectious complications. Chen and associates14 demonstrated an usually high risk of SIRS after PCNL in patients with multiple access tracts (OR 22.41, 95% CI 3.91–128.53, P < 0.001), while the presence of staghorn calculus added no independent risk to the development of SIRS. The lingering question from this study remains: Why did patients with preoperative MDR who were treated appropriately still encounter postoperative infectious complications? The most likely answer is the known discordance between preoperative voided urine cultures and both stone and renal pelvic urine cultures that has been extensively documented in the literature. Positive postoperative urine cultures demonstrated 7 of 15 were positive for different pathogens supporting the known discordance of lower and upper tract cultures. Our results, however, also demonstrated that even when preoperative urine cultures were treated appropriately, the postoperative urine cultures still demonstrated that 8 of 15 patients were positive for the same pathogen with similar resistance, implying that the pathogen was either harbored inside the stone, needed longer preoperative treatment, or should have been treated with a different antibiotic regimen. For those 16 patients who experienced a postoperative urinary tract infection (UTI) complication (fever, SIRS, sepsis), 4 (25%) of the patients had concordant postoperative pathogens that had been treated preoperatively, highlighting our current problem: How do we minimize postoperative UTI complications in the face of appropriate treatment? Of note, 9 of these 16 patients did not demonstrate any growth suggesting antibiotics either suppressed bacterial growth or antibiotic-mediated lysing of bacterial cells resulted in endotoxin-related pyrexia. Do these findings alter our interpretation of current antibiotic treatment for PCNL? The latest update of the AUA Best Practice Statement recommends less than 24 hours of perioperative antibiotics, as is supported by Dogan and colleagues20 where their randomized study demonstrated that
MULTIDRUG RESISTANT CULTURE BEFORE PCNL
short-term prophylaxis has no advantage over single-dose prophylaxis in preventing a postoperative infection. Although demographics of their patients are available, this study does not detail the comorbidity of their patients—e.g., presence of indwelling stent or nephrostomy tube, patients with previous fever, immunocompromised states (diabetes mellitus, human immunodeficiency virus), or MDR pathogens. Therefore, we do not know the complete generalizability of their recommendation for single-dose antibiotics. The AUA Best Practice Statement recommends antibiotics ‘‘extending beyond 24 hours from the conclusion of the procedure depending on patient-risk factors and the implications of infection-related morbidity for the patient’’— patient risk factors including colonization of foreign bodies. Treatment of preexisting bacteriuria is standard of care, but is there any benefit to pretreatment in higher risk groups who do not have preexisting bacteriuria? A level 2a prospectively controlled study by Mariappan and coworkers22 demonstrated that PCNL patients at higher risk for postoperative infection ( > 2 cm stone burden and/or hydronephrosis) had three times lower risk of SIRS if given 1 week of preoperative oral ciprofloxacin. What seems intuitive from these historic studies and our current study is that some patients need minimal perioperative antibiotics and others warrant longer courses. Better characterizing these cohorts is warranted by future studies— i.e., who is a high-risk PCNL patient? Furthermore, what is the appropriate duration of pretreatment antibiotics for these high-risk PCNL patients? Given the known discordance of upper and lower tract urine cultures, however, would it be feasible to obtain percutaneous renal pelvic culture 1 to 2 weeks before PCNL? This information would provide the opportunity to manage and subsequently mitigate infections, albeit it would necessitate an ancillary procedure. This admittedly time consuming and extra cost would have to be weighed against its potential benefit, however, much like renal biopsies have been recently advocated in renal-cell carcinoma. A pre-PCNL percutaneous renal pelvis culture in conjunction with future studies that better characterize patients who need pretreatment antibiotic courses could potentially decrease the infectious morbidity of PCNL. Regardless of future directions, what is increasingly clear is that guidelines need to detail which patients need more than the recommended < 24-hour perioperative antibiotic dose. This study and others highlight that differentiation is imperative— patients undergoing PCNL should be risk stratified for postoperative infectious complications. Antibiograms are available at individual hospital levels to optimize judicious antibiotic choice. Our institution’s antibiogram from September 2013 demonstrates an E coli ciprofloxacin resistance rate of 25%,23 and data from the 2010 California Antibiogram Project estimates a ciprofloxacin resistant rate of 17.6% within the state.24 Given these reports, it is concerning that we found our patients undergoing PCNL represented a much higher cohort of ciprofloxacin resistant E coli patients at 57%. This study suggests that urologists should cautiously use their hospital antibiogram data and instead consider evaluating their kidney stone patient antibiotic resistance rates. We no longer routinely use ciprofloxacin for PCNL, but preferentially use intravenous first-generation cephalosporin
5
and gentamicin when cultures do not otherwise guide alternatives. The recent Food and Drug Administration warning of permanent peripheral neuropathy further highlights the judicious use of fluoroquinolones.25 The limitations of this study include its retrospective design, small sample size, and high baseline prevalence of comorbid conditions. While the median Charlson score for the entire cohort was 2, there was no significant difference in Charlson scores. The length of stay was longer in the infectious group (15.6 days vs 5.2 days) because of issues with placement in these patients with significant comorbidities. The omission of intraoperative renal pelvic culture and stone culture data also limits our interpretation. Renal pelvis urine and stone cultures are therefore now routinely collected at our institution given its ability to alter our postoperative care. Conclusions
Our institution demonstrated a relatively high prevalence of MDR bacteriuria in patients undergoing PCNL. Moreover, MDR strongly predicted a postoperative infectious complication. The higher risk of complications associated with MDR bacteriuria should be provided to patients undergoing PCNL and warrants extra attention to postoperative care by urologists. Given that some PCNL patients represent a higher risk cohort for postoperative infectious complications, studies should seek methods to stratify and mitigate their risk. Disclosure Statement
No competing financial interests exist. References
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20. Dogan HS, Sahin A, Cetinkaya Y, et al. Antibiotic prophylaxis in percutaneous nephrolithotomy: Prospective study in 81 patients. J Endourol 2002;16:649–653. 21. Kreydin EI, Eisner BH. Risk factors for sepsis after percutaneous renal stone surgery. Nat Rev Urol 2013;10:598–605. 22. 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. 23. Ritter M, Dube DA, Weightman NC, et al. Antibiogram— Quarter 2, 2013. UC San Diego Health System Infection Control Committee. 2013. 24. Trivedi K, Oyong K, J H. California Antibiogram Project: Aggregate Susceptibiilty Data of Selected Pathogen, 2010. 2010. 25. US Food and Drug Administration. FDA drug safety communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection. Available at: www.fda.gov/Drugs/DrugSafety/ucm365050 .htm Accessed: December 9, 2014.
Address correspondence to: Roger L. Sur, MD UC San Diego Comprehensive Kidney Stone Center 200 W. Arbor Drive, MC 8897 San Diego, CA 92109 E-mail: [email protected]
Abbreviations Used AUA ¼ American Urological Association BMI ¼ body mass index EAU ¼ European Association of Urology MDR ¼ multidrug resistant PCNL ¼ percutaneous nephrolithotomy SIRS ¼ systemic inflammatory response syndrome UTI ¼ urinary tract infection
