Endourology and Stones Analysis of the Utility of Stone Gram Stain in Urolithiasis Treated With Percutaneous Nephrolithotomy Patrick A. Cockerill, Marcelino E. Rivera, and Amy E. Krambeck OBJECTIVE METHODS
RESULTS
CONCLUSION
To define the sensitivity and specificity of stone gram stain for infected urolithiasis treated with percutaneous nephrolithotomy (PCNL). PCNL procedures performed at our institution were analyzed between January 2009 and May 2013. Stone fragments were sent in a sterile fashion for aerobic and fungal cultures. A gram stain and fungal smear were performed on the stones and reported within 24 hours of collection. A total of 228 patients underwent 248 PCNLs. Of the 248 stones, 81 (33%) had a positive stone culture. Stone gram stain was positive in 31 cases and negative in 50. There were 167 negative stone cultures, and in these cases, gram stain was positive in 5 and negative in 162. The calculated sensitivity and specificity of stone gram stain were 38% and 97%. The positive and negative predictive values were 86% and 76%, respectively. In the subset of 16 patients with positive stone fungal cultures, fungal smear was performed in 12 and was positive in 4, giving fungal smear a sensitivity of 33%. The results of this study suggest that stone gram stain cannot be relied on to detect a positive stone culture and may fail to detect up to 62% of infected stones. However, when positive, gram stain accurately predicts a positive stone culture in 86% of cases. UROLOGY -: -e-, 2014. 2014 Elsevier Inc.
T
he prevalence of urolithiasis in the United States has increased in the last 20 years from 5.2% to 8.8%.1 The use of percutaneous nephrolithotomy (PCNL) for the management of calculi has nearly doubled in parallel with the increasing incidence of urolithiasis.2 Although considered a minimally invasive procedure, the overall complication rate of PCNL has been estimated at 20.5%.3 Specifically, the risk of postoperative fever has been reported to be as high as 32%, with a 0.97%-4.7% risk of sepsis.4 The finding of a positive stone culture is a proven risk factor of fever and sepsis postoperatively; however, stone culture results have proven discordant with preoperative urine culture, and patients may have a positive stone culture despite a negative urine culture.5 Current antibiotic recommendations from the American Urological Association best practice statement call for 24 hours of antibiotics at the time of the PCNL procedure.6 However, early prediction of patients at risk of a positive stone culture, and, therefore, infectious complications, may allow for a more tailored approach to antibiotic prophylaxis postoperatively. Gram stain is a fast, simple laboratory test that performs very well in the setting of urinary tract infectious (UTIs) disease, with a
Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Urology, Mayo Clinic, Rochester, MN Reprint requests: Amy E. Krambeck, M.D., Department of Urology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905. E-mail: [email protected] Submitted: October 29, 2013, accepted (with revisions): December 24, 2013
ª 2014 Elsevier Inc. All Rights Reserved
sensitivity and specificity of 96% and 93%, respectively.7 At our institution, stone fragments are sent for gram stain and culture, with results of gram stain returning within 24 hours, whereas culture results take on average 5 days. Stone gram stain may provide an early predictor of infectious complications; however, there is lack of literature evaluating its ability to predict the final results of stone culture. In this study, we sought to define the predictive value of stone gram stain on final stone culture.
MATERIALS AND METHODS After approval by the institutional review board, PCNLs performed by a single surgeon at our institution were analyzed between January 2009 and May 2013. Standard practice by the surgeon is to treat all patients with preoperative and postoperative antibiotics. Patients with a negative preoperative urine culture and no contraindication to taking the medication receive 7 days of Nitrofurantoin, 100 mg twice daily, whereas patients with a positive urine culture receive 10-14 days of targeted antibiotic therapy before PCNL. Postoperatively, patients with a negative stone culture and no contraindication to taking the medication receive 7 days of Nitrofurantoin, 100 mg twice daily. Patients with a positive stone culture and nonstruvite stone composition receive 4-6 weeks of postoperative antibiotic therapy on the basis of culture and sensitivity results, whereas patients with a positive stone culture and struvite composition receive 3 months of targeted postoperative antibiotic therapy. Stone fragments obtained through the percutaneous tract at the time of the procedure using a no touch technique were 0090-4295/14/$36.00 http://dx.doi.org/10.1016/j.urology.2013.12.043
1
sent for aerobic and fungal cultures. The no touch technique has been previously validated at our institution in 10 consecutive patients who demonstrated negative renal pelvic urine cultures after using the same stone retrieval instruments, thus demonstrating a sterile working environment with no contamination when stones are sent for culture. In the no touch technique, after initial lithotripsy, the first stone fragment for retrieval is grasped with sterile forceps and placed directly from the kidney into a vial with sterile saline to avoid contamination. The stone is not directly manipulated by the surgeon’s or the assistant’s hands. The stone fragments are sent to the microbiology laboratory in a vial with sterile saline. The laboratory pulverizes the stone within the same vial, performs a gram stain on the fragments and solution, and then incubates the fragments within the same vial. For bilateral PCNL cases, each kidney was cultured separately. The gram stain and fungal smear are reported within 24 hours of collection, before stone culture results were finalized. The results of stone gram stain and fungal smear were analyzed on the basis of final culture results to determine the sensitivity, specificity, negative predictive value, and positive predictive value of the tests.
RESULTS A total of 228 patients, 127 female and 101 male, underwent 248 PCNLs from January 2009 to May 2013 (Table 1). Median age at surgery was 58 years, and there were 15 bilateral procedures. Of 248 stones, 81 (33%) had a positive stone culture. Stone gram stain was positive in 31 cases and negative in 50. There were 167 negative stone cultures, and in these cases, gram stain was positive in 5 and negative in 162. The calculated sensitivity and specificity of stone gram stain were 38% and 97%, respectively. The positive and negative predictive values were 86% and 76%, respectively. The false positive rate of stone gram stain was 3%, and the false negative rate was 62%. In the subset of 16 patients with positive stone fungal cultures, fungal smear was performed in 12 and was positive in 4, giving fungal smear a sensitivity of 33% (Tables 2 and 3). In the 31 patients who had a positive gram stain and a positive stone culture, the gram stain accurately reflected the final organism on stone culture in all 31 tests. However, there was discordance between the 2 tests in 12 instances (39%), with either additional findings on gram stain not reflected in the final culture (n ¼ 5) or additional findings on stone culture (n ¼ 7) not reflected in the gram stain. In patients with a positive stone culture (81 total), 45 (56%) had a positive preoperative urine culture, and 31 (38%) had a negative preoperative urine culture, with 5 patients having only a negative urinalysis and not having a preoperative urine culture available. In patients with a positive stone gram stain (N ¼ 36), 15 (42%) had a positive preoperative urine culture, and 18 (50%) had a negative preoperative urine culture, with 3 patients not having a preoperative urine culture available for analysis. Of the 248 stones, 159 (64%) were of mixed composition, whereas 89 (36%) were not. Struvite was present 2
Table 1. Patient characteristics Characteristic
Value
Total number of patients Number of female Number of male Median age at surgery (y) Total number of unique tests
228 127 101 58 248
Table 2. Test characteristics Test Result
Stone Culture þ Stone Culture Total
Gram stain þ Gram stain
31 50 81
5 162 167
36 212 248
Table 3. Test characteristics Characteristic
Percentage
Sensitivity Specificity PPV NPV False positive rate False negative rate
38.3 97.0 86.1 76.4 3.0 61.7
NPV, negative predictive value; PPV, positive predictive value.
in 35 stones (14%). The predominant component in the remaining stones was calcium oxalate monohydrate in 105 (42%), apatite in 50 (20%), uric acid in 22 (9%), calcium oxalate dihydrate in 14 (6%), brushite in 13 (5%), cystine in 4 (2%), and ammonium urate, dihydroxyadenine, or sulfamethoxazole in 1 (0.4%). Stone composition was unavailable in 2 patients (Fig. 1). Of the 81 stones with a positive stone culture, 28 (35%) were struvite in composition, and the remaining 53 (66%) were calcium-based compositions (calcium oxalate or calcium phosphate).
COMMENT In our cohort of patients, we establish the diagnostic ability of stone gram stain and fungal smear in infected urolithiasis. The overall sensitivity of 38% for gram stain and 33% for fungal smear reveals that many incidences of a positive stone culture would be missed if stone gram stain or smear alone was relied on. The poor sensitivity of gram stain in detecting a positive stone culture correlates poorly with its ability to detect UTIs when performed on clean catch or catheterized urine samples. In those instances, gram stain performs extremely well, with a sensitivity as high as 96%-98%.7,8 However, stone gram stain has a positive predictive value of 86%. We did note that when gram stain is positive, it is likely the final stone culture will be positive, which may be helpful to immediately identify patients who are at risk of postoperative infectious complications, as a positive stone culture is significantly associated with fever, the systemic inflammatory response syndrome (SIRS), and sepsis.9-11 UROLOGY
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Figure 1. Predominant stone composition. COD, calcium oxalate dihydrate; COM, calcium oxalate monohydrate; DHA, 2,8-dihydroxyadenine. (Color version available online.)
Unfortunately, a negative gram stain or fungal smear seems to be of no clinical benefit. The reason why stone gram stain is imprecise may be related to sampling error, as only a small portion of the stone is sent for gram stain, or secondary to inadequate bacterial load in the sample. Interestingly, in our cohort of patients, stone culture was positive in 81 patients (33%), despite only 28 (35%) of those patients having stones of struvite composition. In patients with nonstruvite stones who had a positive stone culture, there are 2 possibilities. The first is that these stones are secondarily infected, that is, the patient experienced a UTI of the upper tract causing colonization of the stone with bacteria. In this instance, the bacteria are not integral to the pathogenesis of stone formation. However, bacteria may be involved in stone pathogenesis in nonstruvite stones, and this hypothesis is the subject of ongoing investigation at our institution. Fever, SIRS, and sepsis remain complications of PCNL despite antibiotic prophylaxis. The incidence of fever has been reported as high as 32% after PCNL, and the incidence of sepsis as high as 4.7%.4,12 Numerous studies have shown that patients develop such infectious complications despite sterile preoperative urine samples. Eswara et al9 reviewed 274 patients who underwent ureteroscopy and 54 patients who underwent PCNL, all of whom had a negative preoperative urine culture or were treated with antibiotics before surgery. Despite sterile preoperative urine samples and the use of preoperative antibiotics, 3% developed sepsis. None of these patients had a positive preoperative urine culture, whereas 73% had a positive stone culture. Mariappan et al13 similarly showed that preoperative bladder urine is a poor predictor of postoperative infectious complications. In their series of 54 patients, positive bladder urine culture had a relative risk UROLOGY
-
(-), 2014
(RR) of sepsis of 1.6, which was not statistically significant (P ¼ .67). However, renal pelvic urine culture had a RR ¼ 4.27, and stone culture had a RR ¼ 4.48, both of which were statistically significant (P ¼ .009 and P ¼ .00009, respectively).13 These studies highlight that stone culture is a better predictor of actual bacterial colonization and postoperative infection risk than bladder urine. Currently, the American Urologic Association best practice statement on antibiotic prophylaxis for percutaneous renal surgery is 24 hours antibiotics for all patients.6 Gravas et al14 analyzed 162 patients who did not receive any antibiotic prophylaxis before PCNL and noted a significantly increased rate of postoperative fever from 2.5% to 7.4% (P ¼ .04) and postoperative complications from 1.9% to 22% (P 2 cm, and hydronephrosis.11 Stone culture is another factor obtained intraoperatively that can help guide antimicrobial therapy postoperatively. Gram stain of the stone identifies patients at risk of infectious complications in the early postoperative period. Gram stain has a positive predictive value of 86%, so those patients with a positive test are at risk for infectious complications and may warrant antimicrobial therapy beyond 24 hours postoperatively. In addition, the results of the stone gram stain can guide the broadening of antibiotic coverage to cover gram positive or negative organisms in the event the patient demonstrates signs of infection before the stone culture returns. However, in our experience, stone gram stain is unreliable and may miss up to 62% of cases of infected urolithiasis. Relying on this test alone to tailor antibiotic therapy postoperatively may risk undertreatment and expose patients to the morbidity of infectious complications. In our practice, it is the standard of care to perform a stone culture on all PCNL patients because of the unique infectious risks associated with the procedure. These risks include intermixing of urine and blood and the treatment of large stones, which are more likely to harbor bacteria, endotoxins, and higher risk of SIRS.13,18,19 After PCNL, all patients receive 1 week of antibiotic therapy, generally in the form of nitrofurantoin; however, if a stone culture is positive, the therapy is extended and the antibiotic changed to an appropriate culture specific drug. In this study, we found that 25% of patients with nonstruvite stones had a positive stone culture. It is our belief that by treating the positive stone culture we are preventing potential infectious complications and potentially limiting recurrent UTI.
CONCLUSION A positive stone culture has a strong association with postoperative infectious complications, so early prediction of the results is clinically useful, as culture may take up to 1 week to be finalized. In this study, we establish the sensitivity (38%) and specificity (97%) of stone gram stain in predicting the results of stone culture. Although the 4
positive predictive value of gram stain is 86%, it may miss up to 62% of cases of infected urolithiasis. Furthermore, fungal smears were of limited value in detecting stones harboring yeast. Thus, stone gram stain or fungal smear cannot be relied on to detect all patients with a positive stone culture who are at high risk of infectious complications. References 1. Scales CD, Smith AC, Hanley JM, et al. Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165. 2. Mirheydar HS, Palazzi KL, Derweesh IH, et al. Percutaneous nephrolithotomy use is increasing in the United States: an analysis of trends and complications. J Endourol. 2013;27:979-983. 3. Labate G, Modi P, Timoney A, et al. The percutaneous nephrolithotomy global study: classification of complications. J Endourol. 2011;25:1275-1280. 4. Michel MS, Trojan L, Rassweiler JJ. Complications in percutaneous nephrolithotomy. Eur Urol. 2007;51:899-906. 5. 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. 6. Wolf JS, Bennett CJ, Dmochowski RR, et al. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol. 2008;179:1379-1390. 7. Wiwanitkit V, Udomsantisuk N, Boonchalermvichian C. Diagnostic value and cost utility analysis for urine gram stain and urine microscopic examination as screening tests for urinary tract infection. Urol Res. 2005;33:220-222. 8. Olson ML, Shanholtzer CJ, Willard KE, et al. The slide centrifuge gram stain as a urine screening method. Am J Clin Pathol. 1991;96: 454-458. 9. Eswara JR, Sharif-Tabrizi A, Sacco D. Positive stone culture is associated with a higher rate of sepsis after endourological procedures. Urolithiasis. 2013;41:411-414. 10. Gonen M, Turan H, Ozturk B, et al. Factors affecting fever following percutaneous nephrolithotomy: a prospective clinical study. J Endourol. 2008;22:2135-2138. 11. Kreydin EI, Eisner BH. Risk factors for sepsis after percutaneous renal stone surgery. Nat Rev Urol. 2013;10:598-605. 12. Vorrakitpokatorn P, Permtongchuchai K, Raksamani EO, et al. Perioperative complications and risk factors of percutaneous nephrolithotomy. J Med Assoc Thai. 2006;89:826-833. 13. 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. 14. Gravas S, Montanari E, Geavlete P, et al. Postoperative infection rates in low risk patients undergoing percutaneous nephrolithotomy with and without antibiotic prophylaxis: a matched case control study. J Urol. 2012;188:843-847. 15. Dogan HS, Sahin A, Cetinkaya Y, et al. Antibiotic prophylaxis in percutaneous nephrolithotomy: prospective study in 81 patients. J Endourol. 2002;16:649-653. 16. Mariappan P, Smith G, Moussa SA, et al. One week of ciprofloxacin before percutaneous nephrolithotomy significantly reduces upper tract infection and urosepsis: a prospective controlled study. BJU Int. 2006;98:1075-1079. 17. Bag S, Kumar S, Taneja N, et al. One week of nitrofurantoin before percutaneous nephrolithotomy significantly reduces upper tract infection and urosepsis: a prospective controlled study. Urology. 2011;77:45-49. 18. Shigeta M, Hayashi M, Igawa M. A clinical study of upper urinary tract calculi treated with extracorporeal shock wave lithotripsy: association with bacteriuria before treatment. Urol Int. 1995;54:214-216. 19. McAleer IM, Kaplan GW, Bradley JS, et al. Endotoxin content in renal calculi. J Urol. 2003;169:1813-1814.
UROLOGY
-
(-), 2014
RESULTS
CONCLUSION
To define the sensitivity and specificity of stone gram stain for infected urolithiasis treated with percutaneous nephrolithotomy (PCNL). PCNL procedures performed at our institution were analyzed between January 2009 and May 2013. Stone fragments were sent in a sterile fashion for aerobic and fungal cultures. A gram stain and fungal smear were performed on the stones and reported within 24 hours of collection. A total of 228 patients underwent 248 PCNLs. Of the 248 stones, 81 (33%) had a positive stone culture. Stone gram stain was positive in 31 cases and negative in 50. There were 167 negative stone cultures, and in these cases, gram stain was positive in 5 and negative in 162. The calculated sensitivity and specificity of stone gram stain were 38% and 97%. The positive and negative predictive values were 86% and 76%, respectively. In the subset of 16 patients with positive stone fungal cultures, fungal smear was performed in 12 and was positive in 4, giving fungal smear a sensitivity of 33%. The results of this study suggest that stone gram stain cannot be relied on to detect a positive stone culture and may fail to detect up to 62% of infected stones. However, when positive, gram stain accurately predicts a positive stone culture in 86% of cases. UROLOGY -: -e-, 2014. 2014 Elsevier Inc.
T
he prevalence of urolithiasis in the United States has increased in the last 20 years from 5.2% to 8.8%.1 The use of percutaneous nephrolithotomy (PCNL) for the management of calculi has nearly doubled in parallel with the increasing incidence of urolithiasis.2 Although considered a minimally invasive procedure, the overall complication rate of PCNL has been estimated at 20.5%.3 Specifically, the risk of postoperative fever has been reported to be as high as 32%, with a 0.97%-4.7% risk of sepsis.4 The finding of a positive stone culture is a proven risk factor of fever and sepsis postoperatively; however, stone culture results have proven discordant with preoperative urine culture, and patients may have a positive stone culture despite a negative urine culture.5 Current antibiotic recommendations from the American Urological Association best practice statement call for 24 hours of antibiotics at the time of the PCNL procedure.6 However, early prediction of patients at risk of a positive stone culture, and, therefore, infectious complications, may allow for a more tailored approach to antibiotic prophylaxis postoperatively. Gram stain is a fast, simple laboratory test that performs very well in the setting of urinary tract infectious (UTIs) disease, with a
Financial Disclosure: The authors declare that they have no relevant financial interests. From the Department of Urology, Mayo Clinic, Rochester, MN Reprint requests: Amy E. Krambeck, M.D., Department of Urology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905. E-mail: [email protected] Submitted: October 29, 2013, accepted (with revisions): December 24, 2013
ª 2014 Elsevier Inc. All Rights Reserved
sensitivity and specificity of 96% and 93%, respectively.7 At our institution, stone fragments are sent for gram stain and culture, with results of gram stain returning within 24 hours, whereas culture results take on average 5 days. Stone gram stain may provide an early predictor of infectious complications; however, there is lack of literature evaluating its ability to predict the final results of stone culture. In this study, we sought to define the predictive value of stone gram stain on final stone culture.
MATERIALS AND METHODS After approval by the institutional review board, PCNLs performed by a single surgeon at our institution were analyzed between January 2009 and May 2013. Standard practice by the surgeon is to treat all patients with preoperative and postoperative antibiotics. Patients with a negative preoperative urine culture and no contraindication to taking the medication receive 7 days of Nitrofurantoin, 100 mg twice daily, whereas patients with a positive urine culture receive 10-14 days of targeted antibiotic therapy before PCNL. Postoperatively, patients with a negative stone culture and no contraindication to taking the medication receive 7 days of Nitrofurantoin, 100 mg twice daily. Patients with a positive stone culture and nonstruvite stone composition receive 4-6 weeks of postoperative antibiotic therapy on the basis of culture and sensitivity results, whereas patients with a positive stone culture and struvite composition receive 3 months of targeted postoperative antibiotic therapy. Stone fragments obtained through the percutaneous tract at the time of the procedure using a no touch technique were 0090-4295/14/$36.00 http://dx.doi.org/10.1016/j.urology.2013.12.043
1
sent for aerobic and fungal cultures. The no touch technique has been previously validated at our institution in 10 consecutive patients who demonstrated negative renal pelvic urine cultures after using the same stone retrieval instruments, thus demonstrating a sterile working environment with no contamination when stones are sent for culture. In the no touch technique, after initial lithotripsy, the first stone fragment for retrieval is grasped with sterile forceps and placed directly from the kidney into a vial with sterile saline to avoid contamination. The stone is not directly manipulated by the surgeon’s or the assistant’s hands. The stone fragments are sent to the microbiology laboratory in a vial with sterile saline. The laboratory pulverizes the stone within the same vial, performs a gram stain on the fragments and solution, and then incubates the fragments within the same vial. For bilateral PCNL cases, each kidney was cultured separately. The gram stain and fungal smear are reported within 24 hours of collection, before stone culture results were finalized. The results of stone gram stain and fungal smear were analyzed on the basis of final culture results to determine the sensitivity, specificity, negative predictive value, and positive predictive value of the tests.
RESULTS A total of 228 patients, 127 female and 101 male, underwent 248 PCNLs from January 2009 to May 2013 (Table 1). Median age at surgery was 58 years, and there were 15 bilateral procedures. Of 248 stones, 81 (33%) had a positive stone culture. Stone gram stain was positive in 31 cases and negative in 50. There were 167 negative stone cultures, and in these cases, gram stain was positive in 5 and negative in 162. The calculated sensitivity and specificity of stone gram stain were 38% and 97%, respectively. The positive and negative predictive values were 86% and 76%, respectively. The false positive rate of stone gram stain was 3%, and the false negative rate was 62%. In the subset of 16 patients with positive stone fungal cultures, fungal smear was performed in 12 and was positive in 4, giving fungal smear a sensitivity of 33% (Tables 2 and 3). In the 31 patients who had a positive gram stain and a positive stone culture, the gram stain accurately reflected the final organism on stone culture in all 31 tests. However, there was discordance between the 2 tests in 12 instances (39%), with either additional findings on gram stain not reflected in the final culture (n ¼ 5) or additional findings on stone culture (n ¼ 7) not reflected in the gram stain. In patients with a positive stone culture (81 total), 45 (56%) had a positive preoperative urine culture, and 31 (38%) had a negative preoperative urine culture, with 5 patients having only a negative urinalysis and not having a preoperative urine culture available. In patients with a positive stone gram stain (N ¼ 36), 15 (42%) had a positive preoperative urine culture, and 18 (50%) had a negative preoperative urine culture, with 3 patients not having a preoperative urine culture available for analysis. Of the 248 stones, 159 (64%) were of mixed composition, whereas 89 (36%) were not. Struvite was present 2
Table 1. Patient characteristics Characteristic
Value
Total number of patients Number of female Number of male Median age at surgery (y) Total number of unique tests
228 127 101 58 248
Table 2. Test characteristics Test Result
Stone Culture þ Stone Culture Total
Gram stain þ Gram stain
31 50 81
5 162 167
36 212 248
Table 3. Test characteristics Characteristic
Percentage
Sensitivity Specificity PPV NPV False positive rate False negative rate
38.3 97.0 86.1 76.4 3.0 61.7
NPV, negative predictive value; PPV, positive predictive value.
in 35 stones (14%). The predominant component in the remaining stones was calcium oxalate monohydrate in 105 (42%), apatite in 50 (20%), uric acid in 22 (9%), calcium oxalate dihydrate in 14 (6%), brushite in 13 (5%), cystine in 4 (2%), and ammonium urate, dihydroxyadenine, or sulfamethoxazole in 1 (0.4%). Stone composition was unavailable in 2 patients (Fig. 1). Of the 81 stones with a positive stone culture, 28 (35%) were struvite in composition, and the remaining 53 (66%) were calcium-based compositions (calcium oxalate or calcium phosphate).
COMMENT In our cohort of patients, we establish the diagnostic ability of stone gram stain and fungal smear in infected urolithiasis. The overall sensitivity of 38% for gram stain and 33% for fungal smear reveals that many incidences of a positive stone culture would be missed if stone gram stain or smear alone was relied on. The poor sensitivity of gram stain in detecting a positive stone culture correlates poorly with its ability to detect UTIs when performed on clean catch or catheterized urine samples. In those instances, gram stain performs extremely well, with a sensitivity as high as 96%-98%.7,8 However, stone gram stain has a positive predictive value of 86%. We did note that when gram stain is positive, it is likely the final stone culture will be positive, which may be helpful to immediately identify patients who are at risk of postoperative infectious complications, as a positive stone culture is significantly associated with fever, the systemic inflammatory response syndrome (SIRS), and sepsis.9-11 UROLOGY
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(-), 2014
Figure 1. Predominant stone composition. COD, calcium oxalate dihydrate; COM, calcium oxalate monohydrate; DHA, 2,8-dihydroxyadenine. (Color version available online.)
Unfortunately, a negative gram stain or fungal smear seems to be of no clinical benefit. The reason why stone gram stain is imprecise may be related to sampling error, as only a small portion of the stone is sent for gram stain, or secondary to inadequate bacterial load in the sample. Interestingly, in our cohort of patients, stone culture was positive in 81 patients (33%), despite only 28 (35%) of those patients having stones of struvite composition. In patients with nonstruvite stones who had a positive stone culture, there are 2 possibilities. The first is that these stones are secondarily infected, that is, the patient experienced a UTI of the upper tract causing colonization of the stone with bacteria. In this instance, the bacteria are not integral to the pathogenesis of stone formation. However, bacteria may be involved in stone pathogenesis in nonstruvite stones, and this hypothesis is the subject of ongoing investigation at our institution. Fever, SIRS, and sepsis remain complications of PCNL despite antibiotic prophylaxis. The incidence of fever has been reported as high as 32% after PCNL, and the incidence of sepsis as high as 4.7%.4,12 Numerous studies have shown that patients develop such infectious complications despite sterile preoperative urine samples. Eswara et al9 reviewed 274 patients who underwent ureteroscopy and 54 patients who underwent PCNL, all of whom had a negative preoperative urine culture or were treated with antibiotics before surgery. Despite sterile preoperative urine samples and the use of preoperative antibiotics, 3% developed sepsis. None of these patients had a positive preoperative urine culture, whereas 73% had a positive stone culture. Mariappan et al13 similarly showed that preoperative bladder urine is a poor predictor of postoperative infectious complications. In their series of 54 patients, positive bladder urine culture had a relative risk UROLOGY
-
(-), 2014
(RR) of sepsis of 1.6, which was not statistically significant (P ¼ .67). However, renal pelvic urine culture had a RR ¼ 4.27, and stone culture had a RR ¼ 4.48, both of which were statistically significant (P ¼ .009 and P ¼ .00009, respectively).13 These studies highlight that stone culture is a better predictor of actual bacterial colonization and postoperative infection risk than bladder urine. Currently, the American Urologic Association best practice statement on antibiotic prophylaxis for percutaneous renal surgery is 24 hours antibiotics for all patients.6 Gravas et al14 analyzed 162 patients who did not receive any antibiotic prophylaxis before PCNL and noted a significantly increased rate of postoperative fever from 2.5% to 7.4% (P ¼ .04) and postoperative complications from 1.9% to 22% (P 2 cm, and hydronephrosis.11 Stone culture is another factor obtained intraoperatively that can help guide antimicrobial therapy postoperatively. Gram stain of the stone identifies patients at risk of infectious complications in the early postoperative period. Gram stain has a positive predictive value of 86%, so those patients with a positive test are at risk for infectious complications and may warrant antimicrobial therapy beyond 24 hours postoperatively. In addition, the results of the stone gram stain can guide the broadening of antibiotic coverage to cover gram positive or negative organisms in the event the patient demonstrates signs of infection before the stone culture returns. However, in our experience, stone gram stain is unreliable and may miss up to 62% of cases of infected urolithiasis. Relying on this test alone to tailor antibiotic therapy postoperatively may risk undertreatment and expose patients to the morbidity of infectious complications. In our practice, it is the standard of care to perform a stone culture on all PCNL patients because of the unique infectious risks associated with the procedure. These risks include intermixing of urine and blood and the treatment of large stones, which are more likely to harbor bacteria, endotoxins, and higher risk of SIRS.13,18,19 After PCNL, all patients receive 1 week of antibiotic therapy, generally in the form of nitrofurantoin; however, if a stone culture is positive, the therapy is extended and the antibiotic changed to an appropriate culture specific drug. In this study, we found that 25% of patients with nonstruvite stones had a positive stone culture. It is our belief that by treating the positive stone culture we are preventing potential infectious complications and potentially limiting recurrent UTI.
CONCLUSION A positive stone culture has a strong association with postoperative infectious complications, so early prediction of the results is clinically useful, as culture may take up to 1 week to be finalized. In this study, we establish the sensitivity (38%) and specificity (97%) of stone gram stain in predicting the results of stone culture. Although the 4
positive predictive value of gram stain is 86%, it may miss up to 62% of cases of infected urolithiasis. Furthermore, fungal smears were of limited value in detecting stones harboring yeast. Thus, stone gram stain or fungal smear cannot be relied on to detect all patients with a positive stone culture who are at high risk of infectious complications. References 1. Scales CD, Smith AC, Hanley JM, et al. Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165. 2. Mirheydar HS, Palazzi KL, Derweesh IH, et al. Percutaneous nephrolithotomy use is increasing in the United States: an analysis of trends and complications. J Endourol. 2013;27:979-983. 3. Labate G, Modi P, Timoney A, et al. The percutaneous nephrolithotomy global study: classification of complications. J Endourol. 2011;25:1275-1280. 4. Michel MS, Trojan L, Rassweiler JJ. Complications in percutaneous nephrolithotomy. Eur Urol. 2007;51:899-906. 5. 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. 6. Wolf JS, Bennett CJ, Dmochowski RR, et al. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol. 2008;179:1379-1390. 7. Wiwanitkit V, Udomsantisuk N, Boonchalermvichian C. Diagnostic value and cost utility analysis for urine gram stain and urine microscopic examination as screening tests for urinary tract infection. Urol Res. 2005;33:220-222. 8. Olson ML, Shanholtzer CJ, Willard KE, et al. The slide centrifuge gram stain as a urine screening method. Am J Clin Pathol. 1991;96: 454-458. 9. Eswara JR, Sharif-Tabrizi A, Sacco D. Positive stone culture is associated with a higher rate of sepsis after endourological procedures. Urolithiasis. 2013;41:411-414. 10. Gonen M, Turan H, Ozturk B, et al. Factors affecting fever following percutaneous nephrolithotomy: a prospective clinical study. J Endourol. 2008;22:2135-2138. 11. Kreydin EI, Eisner BH. Risk factors for sepsis after percutaneous renal stone surgery. Nat Rev Urol. 2013;10:598-605. 12. Vorrakitpokatorn P, Permtongchuchai K, Raksamani EO, et al. Perioperative complications and risk factors of percutaneous nephrolithotomy. J Med Assoc Thai. 2006;89:826-833. 13. 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. 14. Gravas S, Montanari E, Geavlete P, et al. Postoperative infection rates in low risk patients undergoing percutaneous nephrolithotomy with and without antibiotic prophylaxis: a matched case control study. J Urol. 2012;188:843-847. 15. Dogan HS, Sahin A, Cetinkaya Y, et al. Antibiotic prophylaxis in percutaneous nephrolithotomy: prospective study in 81 patients. J Endourol. 2002;16:649-653. 16. Mariappan P, Smith G, Moussa SA, et al. One week of ciprofloxacin before percutaneous nephrolithotomy significantly reduces upper tract infection and urosepsis: a prospective controlled study. BJU Int. 2006;98:1075-1079. 17. Bag S, Kumar S, Taneja N, et al. One week of nitrofurantoin before percutaneous nephrolithotomy significantly reduces upper tract infection and urosepsis: a prospective controlled study. Urology. 2011;77:45-49. 18. Shigeta M, Hayashi M, Igawa M. A clinical study of upper urinary tract calculi treated with extracorporeal shock wave lithotripsy: association with bacteriuria before treatment. Urol Int. 1995;54:214-216. 19. McAleer IM, Kaplan GW, Bradley JS, et al. Endotoxin content in renal calculi. J Urol. 2003;169:1813-1814.
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