Author's Accepted Manuscript Incidence of Infectious Complications after Extracorporeal Shock Wave Lithotripsy in Patients Without Associated Risk Factors A. Mira Moreno , M.D. Montoya Lirola , P.J. García Tabar , J.F. Galiano Baena , J.A. Tenza Tenza , J.J. Lobato Encinas

PII: DOI: Reference:

S0022-5347(14)03684-2 10.1016/j.juro.2014.05.091 JURO 11514

To appear in: The Journal of Urology Accepted Date: 19 May 2014 Please cite this article as: Mira Moreno A, Montoya Lirola MD, García Tabar PJ, Galiano Baena JF, Tenza Tenza JA, Lobato Encinas JJ, Incidence of Infectious Complications after Extracorporeal Shock Wave Lithotripsy in Patients Without Associated Risk Factors, The Journal of Urology® (2014), doi: 10.1016/j.juro.2014.05.091. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain. All press releases and the articles they feature are under strict embargo until uncorrected proof of the article becomes available online. We will provide journalists and editors with full-text copies of the articles in question prior to the embargo date so that stories can be adequately researched and written. The standard embargo time is 12:01 AM ET on that date.

ACCEPTED MANUSCRIPT

Incidence of Infectious Complications after Extracorporeal Shock Wave Lithotripsy in Patients Without Associated Risk Factors. Mira Moreno A, Montoya Lirola MD, García Tabar PJ, Galiano Baena JF, Tenza Tenza JA, Lobato Encinas JJ.

RI PT

Urology Department. General Hospital University of Alicante. Alicante, Spain.

Running head: Incidence of infectious complications after extracorporeal shock wave lithotripsy in patients without risk factors.

Corresponding Autor:

M AN U

SC

Keywords: Antibiotic prophylaxis, lithotripsy, urolithiasis, bacteriuria, risk factors.

Alejandra Mira Moreno. General Hospital University of Alicante. Pintor Baeza St, Alicante, Spain. Tel: +34 620653800

AC C

EP

TE D

Email: [email protected]

ACCEPTED MANUSCRIPT

ABSTRACT Purpose:

RI PT

To determine the incidence of infectious complications (asymptomatic bacteriuria, urinary tract infection and urosepsis) in subjects without associated risk factors treated with extracorporeal shock wave lithotripsy (SWL).

Material and methods:

M AN U

SC

An observational prospective cohort study was carried out between October 2010 and June 2013. We included all subjects without risk factors treated with SWL for kidney or ureteral lithiasis. All subjects underwent a urine culture five days prior the procedure and another one seven days after the SWL. None of the subjects included were treated with antibiotics.

Results:

TE D

366 subjects were initially enrolled. The mean age was 53+13 years. 64 subjects (17.5%) underwent SWL with previously placed double J stent. The urine culture post-SWL was positive in 20 patients (5.8%), 4 of them (1.2%) presented symptomatic urinary infection and the rest (4.6%) did not show any symptoms. None of the subjects developed urosepsis. In our case, the age has demostrate to be an independent risk factor for post-SWL bacteriuria.

Conclusions:

AC C

EP

The incidence of infectious complications after SWL in subjects without risk factors is very low, which leads us to conclude that, without defined risk factors, antibiotic prophylaxis is not justified. We also demonstrate that elderly subjects have more risk for development of post-SWL bacteriuria and therefore a possible infectious complication.

ACCEPTED MANUSCRIPT

INTRODUCTION

RI PT

Considered a safe and effective treatment, extracorporeal shock wave lithotripsy (SWL) is a widely used technique in the treatment of kidney and proximal ureteral lithiasis. However, this technique is not free of complications [1,2]. Some of these complications are infectious, such as asymptomatic bacteriuria, urinary tract infection or sepsis [3, 4, 5,6]. Variable incidences of infectious complications after SWL have been published [7, 8, 9].

M AN U

SC

Until September 2012, the American Urology Association (AUA) recommended the use of antibiotic prophylaxis in SWL, based on the metaanalysis of Pearle MS et al. [8]. New evidences emerged in the last years have led the change of these recommendations [10, 11, 12] . Now both, the AUA [13] and the EUA [14], agree in not recommending generalized antibiotic prophylaxis, although they do recommend it when associated factors exist that could increase the risk of infection. There is no agreement between AUA and EUA about the risk factors that should be considered for the prophylactic treatment.

TE D

Knowing the exact incidence of bacteriuria and urinary tract infection after SWL in patients without risk factors allow us to reduce the use of antibiotics [15] and therefore minimize the consequences that result of its use, such as the development of resistant bacteria, the risk of adverse reactions and the economic cost of antibiotic treatment [16].

AC C

EP

Therefore, the principal objective of our study is to determine the incidence of infectious complications (asymptomatic bacteriuria, urinary tract infection and urosepsis) in patients without associated risk factors treated with SWL. The secondary objective is to determine the factors that are associated with increased risk of infectious complications.

ACCEPTED MANUSCRIPT

MATERIAL AND METHODS

RI PT

We designed an observational prospective cohort study carried out in the Lithiasis Section of the General Hospital University of Alicante.

SC

All subjects treated for kidney or ureteral lithiasis in our center between October 2010 and June 2013 were included. All subjects met the following criteria: at least 18 years old, negative urine culture prior to SWL, absence of external bladder catheter or nephrostomy tube, absence of a history of infectious stone or recurrent urinary tract infections prior to treatment with SWL.

M AN U

The following exclusionary criteria were employed: loss of subject for follow-up, no urinary culture within 7 days of the lithotripsy, endourological manipulation during or after the SWL. A urine culture was ordered for all patients 5 days before the procedure and a urinary tract x-ray was taken the day of the lithotripsy. Once 7 days had passed since the SWL, a new urine culture was carried out, and finally, the x-ray was repeated after 30 days and the final evaluation was carried out and data collection was completed.

AC C

EP

TE D

The variables collected at the beginning of the study were: prior pathology of the patient, size of the lithiasis (considering the largest diameter in the long axis), number and location of the lithiasis and whether the patient had a double J catheter prior to treatment with SWL (due to obstructive lithiasis or urinary sepsis). During the lithotripsy session, information was collected on the number of waves and energy employed and whether immediate fragmentation of the lithiasis was produced. In the final revision, the data collection was completed which included the following variables: fragmentation of the lithiasis, appearance of renal colic after the SWL session (defined as the presence of colic pain in the treated side that requires continued oral or intravenous analgesic), presence of stone residues largest than 5 millimeters (mm) in the control x-ray, result of the urine culture (the presence of more than 105 colony forming units per millimeter was considered as a positive culture), symptomatic urine infection (defined as the presence of dysuria, voiding frequency and/or urinary urgency with a positive urine culture) and urinary sepsis (defined as the presence of both symptomatic urine infection and systemic inflammatory response syndrome). In all of the cases the SWL was carried out in ambulatory care, under sedation and using the Dornier Lithotripter S II. Informed consent was obtained from all the patients. The statistical analysis was carried out using the statistical software program SPSS 19. Statistical significance was evaluated using the Chi Square method, Student´s t-test and multivariate linear logistic regression analysis. P values below 0.05 were considered statistically significant.

ACCEPTED MANUSCRIPT

RESULTS

RI PT

A total of 366 subjects were included in the study, 219 men (60%) and 147 women (40%). The mean age was 53 + 13 years. Regarding personal antecedents, 81 subjects (22%) had hypertension, 38 (10.4%) had diabetes mellitus and 34 (9.3%) had dyslipidemia. None of the included subjects had renal insufficiency (defined as a glomerular filtration rate below 60 ml/min/1.73 m2).

SC

64 subjects (17.5%) underwent SWL with previously placed double J stent.

M AN U

The mean size of the lithiasis treated was 1.3 + 0.6 centimeter (cm). The minimum and maximum size of the treated lithiasis was 0.5 and 2.7 cm, respectively. About the SWL session, a mean of 3099 + 571 shock waves per session were used. The average energy used was 2.6 + 0.3 mJ/mm2. No renal protective pause was used in any case. The characteristics of the lithiasis and the treatment are described in Table 1. After the initial phase, 21 subjects were excluded from the study, 19 due to lack of follow-up and 2 due to no control urine culture post-SWL. Therefore, the number of subjects that completed the study was 345.

TE D

The post-SWL urine culture was positive in 20 subjects (5.8%). In Table 2 isolated micro-organisms are specified.

EP

Despite the fact that 16 subjects indicated urinary tract symptoms such as dysuria and frequency, only 4 of them also presented a positive urine culture, therefore only 1.2% of the subjects presented symptomatic urinary infection. All the rest with positive urine culture, 16 subjects (4.6%), did not show any symptom. None of the patients developed urosepsis.

AC C

294 subjects (85.2%) had evidence of stone fragmentation in the x-ray at 30 days post-SWL. 196 (56.8%) were stone-free or had lithiasis below 5 mm after the session of SWL. During a month after SWL session 62 subjects (18%) suffered renal colic. We analyzed the risk factors that could be related to the appearance of a positive urine culture. We considered the following factors: sex, age, presence of diabetes mellitus, dyslipidemia or arterial hypertension, stone size, presence of double J stent, residual stone largest than 5 mm and stone location. In the univariate analysis we found that the risk of bacteriuria postSWL increases with the presence of a double J stent and in elderly subjects (the mean age in subjects with positive post-SWL urine culture was 59.9 + 13.4 years while in the negative urine culture group the mean age was 53 + 13.7 years, p=0.03)(Table 3). In the multivariate analysis (multiple linear regression), just the age showed to be an independent risk factor for post-

ACCEPTED MANUSCRIPT

SWL bacteriuria (p=0.048). The presence of double J stent did not show to be an independent risk factor (p=0.06). DISCUSSION

RI PT

Numerous studies have been published with the objective of estimating the incidence of infectious complications and therefore determining if the antibiotic prophylaxis is necessary[17, 18, 19, 20]. Variable incidences of infectious complications have been published.

M AN U

SC

Our study confirms the low incidence of bacteriuria after SWL in subjects without risk factors and with a negative urine culture prior to treatment. In our case the incidence of infectious complications is 5.8%, which 4.6% presented asymptomatic bacteriuria, 1.2% with a clinical profile of urinary tract infection and no case with sepsis. This incidence is similar to that published in the metaanalysis by Yang Lu et al. [10], which gives figures of about 5% for asymptomatic bacteriuria and 1% for sepsis. These data are somewhat greater than those published by Honey et al. [11], which refer an incidence of infectious complications of 3.1%. This result could be explained by the fact that in Honey et al. some of the study patients are treated prophylactically, while in our case, no patient is treated with antibiotics nor prophylactically, nor after the lithotripsy session. Therefore, it seems clear that for patients without associated risk factors and a negative urine culture pre-SWL, antibiotic prophylaxis is not indicated, coinciding with the recommendations of the AUA and EUA guidelines.

AC C

EP

TE D

On the other hand, there is not agreement in the literature about which factors should be considered risk factors for prophylactic treatment for this group of patients. Table 4 presents the risk factors that are considered by the AUA and EUA. There are few studies that directly analyze the factors associated with infection after SWL [21, 22]. In our study, the age has shown to be an independent risk factor for development of post-SWL bacteriuria, however the usefulness of antibiotic prophylaxis in elderly subjects would be up for discussion, since as mentioned before, the incidence of symptomatic infections and serious events is minimal. None of the other analyzed factors have shown to behave as an independent risk factor. The presence of double J stent is a risk factor in the univariate analysis but not in the multivariate. Perhaps increasing the population of the study we could demonstrate that the presence of double J stent prior to SWL is an independent risk factor for postSWL bacteriuria. We have found some limitations in our study. We do not have a comparasion group (a group with prophylactic antibiotic treatment), it would have been useful to demonstrate if the rates of bacteriuria and symptomatic urinary tract infection are or not similar. Moreover, we have not been able to demonstrate that the presence of double J stent prior to the SWL is an independent risk factor for bacteriuria post-SWL (despite this is considered a risk factor for the AUA and EUA). Maybe we should increase the population to demostrate that fact. Another limitation is that we could not determinate

ACCEPTED MANUSCRIPT

the risk factors associated with symptomatic infections and serious events; this analysis was not possible due to low incidence of these events.

CONCLUSIONS

AC C

EP

TE D

M AN U

SC

RI PT

In our study we show the low incidence of infectious complications after SWL in patients without risk factors, which leads us to conclude that without defined risk factors (positive urine culture prior to SWL, external bladder catheters or nephrostomy tube, and history of infectious stone or recurrent urinary tract infections), antibiotic prophylaxis is not justified. We also demonstrate that elderly subjects have more risk for development of postSWL bacteriuria and therefore a possible infectious complication.

ACCEPTED MANUSCRIPT

REFERENCES [1] Skolarikos A, Alivizatos G, de la Rosette J. Extracorporeal shock wave lithotripsy 25 years later: complications and their prevention. Eur Urol 2006;50:981-90.

RI PT

[2] Vakalopoulos I, Paraskevopoulos S, Radopoulos D. Is urinary tract infection after shock wave lithotripsy an aggravating factor for renal damage? Arch Esp Urol 2010;63(6):454-9.

[3] Rahav G, Strul H, Pode D, et al. Bacteriuria following extracorporeal shock-wave

SC

lithotripsy in patients whose urine was sterile before the procedure. Clin Infect Dis 1995;20:1317-20.

[4] Raz R, Zoabi A, Sudarsky M, et al. The incidence of urinary tract infection in

M AN U

patients without bacteriuria who underwent extracorporeal shock wave lithotripsy. J Urol 1994;151:329-30.

[5] Dinçel Ç, Özdiler E, Özenci H, et al. Incidence of urinary tract infection in patients without bacteriuria undergoing ESWL: comparison of stone types. J Endourol 1998;12(1):1-3.

[6] Westh H, Knudsen F, Hedengran AM, et al. Extracorporeal shock wave lithotripsy

1990;144(1):15-6.

TE D

of kidney stones does not induce transient bacteraemia. A prospective study. J Urol

[7] Bierkens AF, Hendrikx AJ, Ezz el Din KE, et al. The value of antibiotic prophylaxis during extracorporeal shock wave lithotripsy in the prevention of urinary tract infections

EP

in patients with urine proven sterile prior to treatment. Eur Urol 1997;31:30-5. [8] Pearle MS, Roehrborn CG. Antimicrobial prophylaxis prior to shock wave lithotripsy in patients with sterile urine before treatment: a meta-analysis and cost-

AC C

effectiveness analysis. Urology 1997;49(5):679-86. [9] Ilker Y, Türkeri LN, Korten V, et al. Antimicrobial prophylaxis in management of urinary tract stones by extracorporeal shock-wave lithotripsy: is it necessary? Urology 1995;46(2):165-7.

[10] Lu Y, Tianyong F, Ping H, et al. Antibiotic prophylaxis for shock wave lithotripsy in patients with sterile urine befote treatment may be unnecessary: a systematic review and meta-analysis. J Urol 2012;188(2):441-8.

ACCEPTED MANUSCRIPT

[11] Honey RJ, Ordon M, Ghiculete D, et al. A prospective study examining the incidente of bacteriuria and urinary tract infection post-shockwave lithotripsy with targeted antibiotic prophylaxis. J Urol 2013;189(6):2112-7. [12] Wiesenthal JD, Ghiculete D, Ordon M, et al. A prospective study examining the

against universal antibiotic prophylaxis. J Urol 2011;185(4s):e472.

RI PT

incidence of bacteriuria and urinary tract infection post-shockwave lithotripsy: the case

[13] Wolf JS, Bennett CJ, Dmochowski RR, et al. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol 2008 (Updated 2012)

[14] Turk C, Knoll T, Petrik A, et al. Guidelines on Urolithiasis. EAU 2013;25-7.

SC

[15] Robles JE, de Castro F, Frades MC, et al. Antibioterapia profiláctica en la litotricia extracorpórea por ondas de choque (LEOC): estudio prospectivo y randomizado. Actas

M AN U

Urol Esp 1991;15:442-5.

[16] Foxman B. Epidemiolgy of urinary tract infections: incidente, morbidity, and economic costs. AM J Med 2002;113(1A):5S-13S.

[17] Deliveliotis C, Giftopoulos A, Koutsokalis G, et al. The necessity of prophylactic antibiotics during extracorporeal shock wave lithotripsy. Int Urol Nephrol 1997;29:51721.

[18] Islam MA, Shameem IA, Ahasan DN, et al. Necessity of antibiotics prophylaxis

TE D

during extracorporeal shock wave lithotripsy. Mymensingh Med J 2005;14(1):58-60. [19] Cochran JS, Robinson SN, Crane VS, et al. Extracorporeal shock wave lithotripsy. Use of antibiotics to avoid postprocedural infection. Postgrad Med 1988;89(6):199-204. [20] Jikke AM, Laguna MP, Geerlings SE, et al. Antibiotic prophylaxis in urologic

EP

procedures: a systematic review. Eur Urol 2008;54:1270-86. [21] Duvdevani M, Lorber G, Gofrit O, et al. Fever after shockwave lithotripsy-risk

AC C

factors and indications form prophylactic antimicrobial treatment. J Endourol 2010;24(2):277-81.

[22] Fujita K, Mizuno T, Ushiyama T, et al. Complicating risk factors for pyelonephritis alter extracorporeal shock wave lithotripsy. Int J Urol 2000;7(6):224-30.

RI PT

ACCEPTED MANUSCRIPT

LEGENDS SWL: extracorporeal shock wave lithotripsy AUA: American Urology Association

SC

EUA: European Urology Association mm: millimeter

M AN U

cm: centimeter

AC C

EP

TE D

mJ: millijoules

ACCEPTED MANUSCRIPT

TABLES n=366 Stone location

RI PT

43,2% 30,9% 18,6% 7,4%

SC

66,9% 33,1% 38,3% 53,3% 8,5% 1,6% 19,7% 61,5% 17,2% 28,2% 69,1% 7,7%

M AN U

Calyx 158 Renal pelvis 113 Ureter 68 Multiple 27 Number of stones Single stone 245 Multiple stones 121 Size 0,5 - 1 cm 140 1,1 - 2 cm 195 > 2 cm 31 Number of shock wave 0 - 1500 6 1501 - 2500 72 2501 - 3500 225 > 3500 63 Energy 1,65-2,4 mJ/mm2 85 2,41-2,7 mJ/mm2 253 >2,7 mJ/mm2 28

TE D

Table 1. Stone and treatment characteristics

AC C

EP

Negative urine culture Positive urine culture Escherichia coli Klebsiella pneumoniae Proteus Staphylococcus aureus Staphylococcus saprophyticus Serratia liquefaciens Varios microorganismos Total

Table 2. Urine culture results

325

94,20%

14 1 1 1 1 1 1 345

4% 0,3% 0,3% 0,3% 0,3% 0,3% 0,3%

ACCEPTED MANUSCRIPT

Positive urine culture

RR (IC 95%)

p

Sex 3,8% 8,8%

(8/208) (12/137)

0,44 1

(0,18 - 1,04)

> 65 years < 65 years Diabetes Mellitus Yes No Dyslipidemia Yes No Arterial hypertension Yes No Stone size > 2 cm < 2 cm Double J stent Yes No Residual stone >5 mm Yes No Stone location Renal Ureteral

11% 4,4%

(8/73) (12/272)

2,48 1

(1,06 - 5,85)

8,3% 5,5%

(3/36) (17/309)

1,52 1

(0,47 - 4,92)

6,3% 5,8%

(2/32) (18/313)

1,09 1

(0,26 - 4,47)

0,71

7,5% 5,3%

(6/80) (14/265)

1,42 1

(0,56 - 3,57)

0,42

3,4% 6%

(1/29) (19/316)

0,06 1

(0,08 - 4,13)

1

11,5% 4,6%

(7/61) (13/284)

2,5 1

(1,04 - 6,02)

0,036

4% 7,6%

(6/151) (14/185)

0,53 1

(0,21 - 1,33)

0,17

(15/280) (5/65)

0,7 1

(0,26-1,85)

0,47

M AN U

TE D 5,4% 7,7%

0,046

0,45

SC

Age

0,056

RI PT

Male Female

EP

Table 3. Risk factors of bacteriuria, univariate analysis

AC C

AUA Advanced age Anatomic anomalies of the urinary tract Poor nutritional status Smoking Chronic corticosteroid use Inmunodeficiency Externalized catheters Colonized endogenous/ exogenous material Distant coexistent infections Prolonged hospitalization

Table 4. Risk factors considered by AUA and EUA

EAU Internal stent placement Indwelling catheter Nephrostomy tube Infectious stone

Incidence of infectious complications after extracorporeal shock wave lithotripsy in patients without associated risk factors.

We determined the incidence of infectious complications (asymptomatic bacteriuria, urinary tract infection and urosepsis) in patients without associat...
133KB Sizes 0 Downloads 4 Views