World J Urol DOI 10.1007/s00345-013-1235-8
ORIGINAL ARTICLE
Chronic bacterial prostatitis in men with spinal cord injury Jo¨rg Krebs • Peter Bartel • Ju¨rgen Pannek
Received: 3 October 2013 / Accepted: 30 December 2013 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Recurrent urinary tract infections (UTI) are a major problem affecting spinal cord injury (SCI) patients and may stem from chronic bacterial prostatitis. We have therefore investigated the presence of chronic bacterial prostatitis and its role in the development of recurrent symptomatic UTI in SCI men. Methods This study is a prospective cross-sectional investigation of bacterial prostatitis in SCI men in a single SCI rehabilitation center. In 50 men with chronic SCI presenting for a routine urologic examination, urine samples before and after prostate massage were taken for microbiologic investigation and white blood cell counting. Furthermore, patient characteristics, bladder diary details, and the annual rate of symptomatic UTI were collected retrospectively. Results No participant reported current symptoms of UTI or prostatitis. In most men (39/50, 78 %), the microbiologic analysis of the post-massage urine sample revealed growth of pathogenic bacteria. The majority of these men (32/39, 82 %) also presented with mostly (27/39, 69 %) the same pathogenic bacteria in the pre-massage sample. There was no significant (p = 0.48) difference in the number of symptomatic UTI in men with a positive post-massage culture compared with those with a negative culture. No significant (p = 0.67) difference in the frequency distribution of positive versus negative post-massage cultures J. Krebs Clinical Trial Unit, Swiss Paraplegic Centre, Nottwil, Switzerland P. Bartel J. Pannek (&) Neuro-Urology, Swiss Paraplegic Centre, Guido A. Za¨ch Str. 1, 6207 Nottwil, Switzerland e-mail: [email protected]; [email protected]
was detected between men with recurrent and sporadic UTI. Conclusions Most SCI men are affected by asymptomatic bacterial prostatitis; however, bacterial prostatitis does not play a major role in the development of recurrent UTI. The indication for antibiotic treatment of chronic bacterial prostatitis in asymptomatic SCI men with recurrent UTI is questionable. Keywords Urinary tract infection Chronic bacterial prostatitis Microbiology Spinal cord injury
Introduction Neurogenic lower urinary tract dysfunction (NLUTD) following spinal cord injury (SCI) results in impaired storage and voiding function and subsequently an increased risk of urinary tract infections (UTI). Symptomatic UTI are a major cause of morbidity in individuals with SCI [1–3], with 20 % suffering from recurrent UTI [3]. Recurrent symptomatic UTI are bothersome for affected patients, and the associated symptoms, such as fever, incontinence, dysuria, increased spasticity, suprapubic pain, decreased bladder capacity, and impaired general well-being, lead to a decrease in quality of life [4]. Recurrent UTI in male SCI individuals may be the result of bacterial colonization of the prostate, which acts as a reservoir for uropathogens [5, 6]. Approximately 30 % of non-SCI men suffering from chronic bacterial prostatitis present with recurrent UTI [7], and bacterial infections of the prostate account for approximately 10 % of all cases of prostatitis [8], which is a common urologic disorder with a prevalence ranging between 2 and 10 % [9]. In SCI men, the prevalence of bacterial prostate infections may be
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considerably higher (i.e., 30 %) [10]. However, there are currently no data on the occurrence of bacterial prostatitis in SCI men with NLUTD. We have therefore prospectively investigated the presence of chronic bacterial prostatitis in men with NLUTD resulting from chronic ([12 months) SCI. Furthermore, the hypothesis was tested that SCI men affected by chronic bacterial prostatitis experience more symptomatic UTI compared to those not suffering from bacterial prostatitis.
Subjects and methods The present prospective study had been approved by the local ethics committee. All study participants provided written informed consent with guarantees of confidentiality. The study protocol had been registered with ClinicalTrials.gov (NCT01601041). Men with NLUTD resulting from chronic ([12 months) SCI, presenting for a routine urologic examination at the outpatient clinic of a single SCI rehabilitation center between December 2011 and December 2012 and using intermittent catheterization for bladder evacuation, were recruited for the study. Men suffering from a current symptomatic UTI, acute prostatitis, or medical conditions impairing the immune response, those under current or previous antibiotic treatment [28 days within the last 12 months, and those aged under 18 or older than 70 years were excluded. The prostate was examined by rectal palpation and ultrasonography in order to exclude contraindications for prostate massage (e.g., acute prostatitis, abscess). The participating men emptied their bladder completely by catheterization, and an urine sample aliquot was taken for microbiologic analysis and manual white blood cell (WBC) counting. Afterward, the prostate was massaged, and a second urine sample was collected by catheterization for microbiologic analysis (modified two-glass test [11]). Furthermore, the WBC count per high-power (1,0009 magnification) field (HPF) was determined semiquantitatively on gram-stained smears and classified as follows: 1–3 cells/HPF: (?), 4–10 cells/HPF: ?, 11–15 cells/HPF: ??, [15 cells/HPF: ???. The National Institutes of Health Classification System for prostatitis comprises four categories [12]. The diagnosis of chronic bacterial prostatitis (category II) is based on the detection of uropathogens in the cultures of expressed prostatic secretions and/or urine samples after prostate massage and an elevated WBC count [13, 14]. Typically, but not necessarily, the pre-massage urine sample is sterile [5, 13]. Clinically, chronic bacterial prostatitis is characterized by recurrent UTI and genitourinary discomfort and/ or pain in able-bodied men. Genitourinary discomfort and/
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or pain in the absence of bacteria localized to the prostate with or without inflammatory reaction is classified as chronic pelvic pain syndrome (category III). For the present investigation, a bacterial count of C103 colony-forming units/ml was considered clinically relevant in all microbiologic analyses [15]. The bacterium species with the greatest number of colony-forming units isolated from a post-massage sample was regarded to be the ‘‘main species.’’ Furthermore, a WBC count of C4/HPF in the postmassage urine sample and a count of [100/ll in the premassage sample were considered clinically relevant [14, 15]. Moreover, personal characteristics and bladder diary details were collected. The study participants were asked to report the number of symptomatic UTI they had experienced during the last 12 months. A symptomatic UTI was defined according to the published criteria: fever without another cause, dysuria, new onset of incontinence, suprapubic pain, impaired general well-being, decreased bladder capacity, increased general spasticity, hematuria without other causes, new onset of voiding problems [16]. According to the reported number of symptomatic UTI during the last 12 months, patients were categorized as suffering from frequent/recurrent ([2 UTI/year) or sporadic (B2 UTI/year) UTI. Data were calculated and presented as the median and the lower (LQ) and upper quartile (UQ). The differences between groups were tested with the Mann–Whitney U test. The Chi-square and Fisher’s exact test were used to test differences in the observed frequency distribution between groups. Statistical analyses were performed using the SPSS software (version 18.0.3, IBM, Somers, NY, USA). A p value of \0.05 was considered significant.
Results Sixty men with NLUTD resulting from SCI and performing intermittent catheterization were included into the study. Ten men were excluded because the annual rate of UTI could not be determined (SCI \ 12 months) (n = 4), the age was [70 years (n = 1), urine samples after prostate massage were missing (n = 2), declined study participation (n = 2) or antibiotic treatment for[28 days within the previous 12 months (n = 1). Thus, the data of 50 men with a median age of 48.5 years (LQ 39.9 UQ 57.3 years) were analyzed. Spinal cord injury had occurred a median of 16.1 years (LQ 7.8 UQ 21.7 years) ago. The etiology of SCI was trauma (43/50, 86 %), tumor (3/50), myelomeningocele (3/ 50), or inflammatory process (1/50). There were four tetraand 46 paraplegic patients. In 19 and 31 patients, SCI was complete and incomplete, respectively.
World J Urol Table 1 Culture results and white blood cell counts of urine samples taken before and after prostate massage Post-massage sample
Pre-massage sample
Men
Culture
WBC count
Culture
B2 UTI/ year
Positivea
C4/HPF
Positivec
C100/ll
5
1
Positivec
\100/ll
9
0
Negatived
C100/ll
1
0
d
0
WBC count
\100/ll
1
Positivec
C100/ll
5
2
Positivec
\100/ll
6
3
Negatived
C100/ll
1
0
Negatived \100/ll
3
2
Negative Positivea
Negativeb
\4/HPF
C4/HPF
Negativeb \4/HPF
[2 UTI/ year
Positivec
C100/ll
2
0
Positivec
\100/ll
0
0
Negatived
C100/ll
0
0
Negatived \100/ll
0
0
Positivec
C100/ll
1
0
Positive \100/ll Negatived C100/ll
2 1
0 0
Negatived \100/ll
4
1
c
WBC white blood cells, UTI urinary tract infection, HPF high-power field a
C103 colony-forming units of uropathogenic bacteria/ml. b No growth or normal flora. c C103 colony-forming units of uropathogenic bacteria/ml. d no growth or \103 colony-forming units/ml
Thirteen men had implemented nonantibiotic UTI prophylaxis, i.e., cranberry products (n = 8), L-methionine (n = 3), or both (n = 2). No participant reported any current complaints of UTI or prostatitis. Nine patients had suffered from recurrent UTI (median 6 UTI/year, LQ 4 UQ 6 UTI/year). In the majority of men (39/50, 78 %), the microbiologic analysis of the post-massage urine sample revealed relevant growth of pathogenic bacteria (Table 1). However, an elevated WBC count in the post-massage sample was observed in only 17 of the 39 men with a positive culture. The majority of men (31/39, 79 %) with a positive post-massage culture also presented with C103 colony-forming units of pathogenic bacteria/ml in the premassage sample. In only eight men, the post-massage culture was positive, whereas the pre-massage culture was negative. Two of these eight men presented with recurrent UTI. There were two men with an elevated WBC count in the post-massage sample but a negative culture. In the premassage sample of 37 men (37/50, 74 %), C103 colonyforming units of pathogenic bacteria/ml were detected. The bacteria species identified in the pre- and post-massage samples are presented in Table 2. The following pathogens were identified most frequently in the post-massage samples: Escherichia coli, Klebsiella pneumoniae,
Enterobacter species, coagulase-negative Staphylococci and Streptococcus viridans. In most cases (27/39, 69 %), the main pathogen identified in the post-massage sample was also detected in the pre-massage sample. There was no significant (p = 0.48) difference in the number of symptomatic UTI in men with a positive postmassage culture compared with those with a negative culture (Fig. 1). More than 50 % (22/39) of the men with a positive post-massage culture had experienced no symptomatic UTI during the previous 12 months. No significant (p = 0.67) difference in the frequency distribution of positive versus negative post-massage cultures was detected between men with recurrent UTI and those with sporadic UTI (Table 1).
Discussion This is the first cross-sectional study on the occurrence of chronic bacterial prostatitis in men with chronic SCI and NLUTD. In approximately four of five men, the microbiologic analysis of the urine sample taken after prostate massage revealed growth of uropathogenic bacteria. However, no association between the presence of bacteria in the prostate and the occurrence of UTI was observed. The hypothesis that SCI men affected by chronic bacterial prostatitis experience more symptomatic UTI compared to those not suffering from bacterial prostatitis was rejected. Growth of pathogenic bacteria was observed in approximately 80 % of the post-massage sample cultures, but no study participant reported any genitourinary symptoms. The prostate of asymptomatic SCI men therefore seems to be commonly infested by bacteria, which is in contrast to the reported prevalence of chronic bacterial prostatitis of \10 % in able-bodied men [17]. However, in more than 50 % of the investigated men, the WBC count in the post-massage sample was not elevated. According to the official classification system, this would not represent chronic bacterial prostatitis (category II) [13, 14]. The lack of an elevated WBC count in many cases with a positive post-massage culture may have been the consequence of the method chosen for determining the WBC count in the post-massage sample. The sensitivity of counting WBC on gram-stained smears is reported to be low [18], resulting in false-negative WBC counts. Two of the investigated men presented with an elevated WBC count in the post-massage sample but a negative culture. These men can be diagnosed with abacterial, inflammatory prostatitis (corresponding to category III). However, this type of prostatitis was not the focus of the present investigation. Analogously, the pre-massage sample cultures revealed growth of pathogenic bacteria in[70 % of the investigated men. The prevalence of asymptomatic bacteriuria in SCI
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World J Urol Table 2 Bacteria species identified in the urine samples taken before and after prostate massage
Main speciesa
Concomitant species
E. coli
na, not applicable; spp, species; E. coli, Escherichia coli; H. parainfluenzae, Haemophilus parainfluenzae; S. agalactiae, Streptococcus agalactiae; K. pneumoniae, Klebsiella pneumoniae; E. cloacae, Enterobacter cloacae; coagulase-neg. Staph, coagulase-negative Staphylococc; P. aeruginosa, Pseudomonas aeruginosa; S. viridans group, Streptococcus viridans group; E. aerogenes/ cloacae, Enterobacter aerogenes/cloacae; S. aureus, Staphylococcus aureus; K. oxytoca, Klebsiella oxytoca; S. milleri, Streptococcus miller a
Bacterium species isolated from post-massage sample with greatest number of colonyforming units
Coagulase-neg. Staph.
Strains with resistance to some antibiotics. 3 strains expressing extended-spectrum beta-lactamases
Premassage
Postmassage
10
5
5
0
2
na
2
H. parainfluenzae
0
1
na
1
S. agalactiae
1
1
0
0
7
9
7
9
E. cloacaec
1
2
1
2
Coagulase-neg. Staph. P. aeruginosa
0 0
2 1
na na
1 1
H. parainfluenzae
0
1
na
0
S. agalactiae
1
1
0
0
S. viridans group
1
1
0
0
Gardnerella vaginalis
0
1
na
0
1
6
1
6
0
1
na
1
Coagulase-neg. Staph. Enterococcus spp.
2
0
2
na
S. aureus
0
1
na
1
S. viridans group
1
1
0
0
K. oxytoca
0
1
na
1 2
1
2
1
na
na
na
na
3
3
3
3
Enterococcus spp.
1 3
0 3
0 0
na 0
E. coli
1
0
0
na
S. agalactiae
1
1
0
0
Coagulase-neg. Staph.
1
1
1
1
Gram neg. anaerobic cocci
0
1
na0
Prevotella bivia
0
1
na
0
Gardnerella vaginalis
0
1
na
0
1
3
1
2
H. parainfluenzae
0
1
na
0
Enterococcus spp.
1
0
1
na
1
1
1
1
0
1
na
0 1
None
S. viridans group
Corynebacterium spp.
Enterococcus spp. S. milleri Aerococcus None Prevotella bivia None
individuals has been reported to range between 30 and 80 % [19]. In the light of this high prevalence, it is not surprising that most (i.e., 79 %) of the investigated men with a positive post-massage sample culture also presented with a positive pre-massage culture. In the majority of men (i.e., approximately 70 %), the same main pathogenic bacteria were identified in both the pre- and the post-
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Postmassage
10
Proteus mirabilis
b
Premassage
Enterococcus spp.
K. pneumoniaec
E. aerogenes/ cloacaec
Count resistantb strains
Count
0
1
na
na
na
na
na
0
1
na
0
na
na
na
na
massage sample cultures. This supports the notion that ascending bacterial colonization of the prostate may occur after bladder infection, and in turn, bacteria may spread from the prostate into the urinary tract resulting in recurrent infections. We did not observe any association between the presence of bacteria in the prostate and the occurrence of UTI.
World J Urol Fig. 1 Box plots of annual symptomatic urinary tract infections (UTI) in spinal cord injury men with negative (n = 11) and positive (i.e., pathogenic bacteria) (n = 39) cultures of the urine samples taken after prostate massage
Men with bacterial colonization of the prostate had not experienced more UTI than men without, and both men with and without bacterial prostate colonization had suffered from recurrent UTI (i.e., [2 UTI/year). Furthermore, only two of the eight men with bacterial prostatitis and negative pre-massage urine cultures presented with recurrent UTI. Our results therefore do not support the notion that recurrent UTI are the result of bacterial colonization of the prostate in male SCI individuals. The pathogens identified most frequently in the prostatic fluid of the investigated SCI men (i.e., Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis) are also the main bacteria involved in chronic bacterial prostatitis in able-bodied men [5, 13, 20]. Apart from Enterococcus species, the role of gram-positive bacteria in chronic prostatitis is still being debated [21, 22]. Furthermore, Prevotella bivia and Gardnerella vaginalis were observed in the post-massage sample culture of two men each. In one of them, Prevotella bivia was the only bacteria identified in the post-massage sample. Prevotella bivia and Gardnerella vaginalis are normally associated with bacterial vaginitis, and men are typically asymptomatic carriers. However, there are case reports suggesting a uropathogenic potential in men [23, 24]. In other individuals, Aerococcus was the only pathogen identified in the post-massage sample (n = 1) or a concomitant pathogen in the pre-massage sample culture (n = 2). The clinical relevance of Aerococcus in the development of genitourinary infections remains to be determined [25]. Approximately 50 % (20/ 39) of the post-massage sample cultures revealed polymicrobial growth, and [70 % (29/39) of the main bacterial
species were multiresistant strains, which contributes to the complexity of managing UTI in SCI individuals [26]. The cross-sectional design pertains to the limitations of the present study. Chronic bacterial prostatitis is considered a persistent infection of the prostate with relapsing symptoms and UTI lasting more than 3 months [13, 14]. The duration of prostate infection is unknown in the investigated men. However, chronic asymptomatic bacterial colonization of the urinary tract is highly prevalent in SCI individuals [19]. Based on the isolated bacteria, relevant infections of the prostate were present, and there was no history of acute bacterial prostatitis. Acute bacterial prostatitis would manifest itself with symptoms such as fever and illness even in SCI individuals. The Meares–Stamey four-glass test is considered the gold standard for diagnosing prostatitis [13, 14]. However, this test cannot be performed in the majority of patients with NLUTD resulting from SCI. In the present investigation, a modified two-glass test was used. The urine samples before and after prostate massage were collected by intermittent catheterization. The two-glass test has been reported to provide results highly comparable with the four-glass test [27]. The serum concentration of prostate-specific antigen was not measured in the present investigation. Prostate-specific antigen levels are elevated in only approximately 20 % of men with chronic bacterial prostatitis [13], and thus, the determination of prostate-specific antigen levels is not recommended in chronic prostatitis because of the low sensitivity and specificity [28]. The retrospective collection of the annual rate of UTI and the mediocre accuracy (i.e., 66 %) [29] of patient self-prediction of UTI contribute to
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the uncertainty about the true number of annual symptomatic UTI. The true number of UTI may have been higher than reported by the participants. Apart from the limited sensitivity (i.e., 48 %) [29] of self-prediction, some study participants may not have remembered the correct number of UTI suffered during the previous 12 months. However, symptomatic UTI have a major impact on the quality of life of affected individuals, and thus, episodes of symptomatic UTI are not easily forgotten. Finally, there were only nine men with recurrent UTI (i.e., [2 UTI/year) in the present study. However, in the light of the high percentage of SCI men with bacterial colonization of the prostate, it is unlikely that a comparison between subjects with zero and subjects with more than two annual UTI would provide more evidence for the role of chronic bacterial prostatitis in the development of recurrent symptomatic UTI in SCI men. Based on the present results, most SCI men are affected by asymptomatic bacterial prostatitis and bacteriuria. The clinical relevance of bacterial colonization of the prostate in SCI men needs to be reconsidered. Commonly, SCI men presenting with recurrent UTI and growth of uropathogens in the post-massage urine or semen sample culture are treated for prostatitis with fluoroquinolones for 6 weeks according to current guidelines [15]. However, in the light of the present results, the justification for antibiotic treatment of asymptomatic chronic bacterial prostatitis in SCI men is highly questionable. Moreover, antibiotic treatment increases the selection pressure for resistant strains [30]. Conclusions Most SCI men are affected by asymptomatic bacterial prostatitis; however, bacterial prostatitis does not play a major role in the development of recurrent UTI. The indication for antibiotic treatment of chronic bacterial prostatitis in asymptomatic SCI men with recurrent UTI is questionable.
References 1. Esclarin De Ruz A, Garcia Leoni E, Herruzo Cabrera R (2000) Epidemiology and risk factors for urinary tract infection in patients with spinal cord injury. J Urol 164(4):1285–1289 2. Wyndaele JJ (2002) Complications of intermittent catheterization: their prevention and treatment. Spinal Cord 40(10):536–541 3. Biering-Sorensen F, Nielans HM, Dorflinger T, Sorensen B (1999) Urological situation five years after spinal cord injury. Scand J Urol Nephrol 33(3):157–161 4. Goetz LL, Cardenas DD, Kennelly M, Bonne Lee BS, Linsenmeyer T, Moser C, Pannek J, Wyndaele JJ, Biering-Sorensen F (2013) International spinal cord injury urinary tract infection basic data set. Spinal Cord (Epub ahead of print)
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5. Nickel JC, Moon T (2005) Chronic bacterial prostatitis: an evolving clinical enigma. Urology 66(1):2–8 6. Wyndaele JJ (1985) Chronic prostatitis in spinal cord injury patients. Paraplegia 23(3):164–169 7. Habermacher GM, Chason JT, Schaeffer AJ (2006) Prostatitis/ chronic pelvic pain syndrome. Annu Rev Med 57:195–206 8. de la Rosette JJ, Hubregtse MR, Meuleman EJ, Stolk-Engelaar MV, Debruyne FM (1993) Diagnosis and treatment of 409 patients with prostatitis syndromes. Urology 41(4):301–307 9. Krieger JN, Lee SW, Jeon J, Cheah PY, Liong ML, DE Riley (2008) Epidemiology of prostatitis. Int J Antimicrob Agents 31(Suppl 1):S85–S90 10. Perrouin-Verbe B, Labat JJ, Richard I, Mauduyt de la Greve I, Buzelin JM, Mathe JF (1995) Clean intermittent catheterisation from the acute period in spinal cord injury patients. Long term evaluation of urethral and genital tolerance. Paraplegia 33(11):619–624 11. Nickel JC, Shoskes D, Wang Y, Alexander RB, Fowler JE Jr, Zeitlin S, O’Leary MP, Pontari MA, Schaeffer AJ, Landis JR, Nyberg L, Kusek JW, Propert KJ (2006) How does the premassage and post-massage 2-glass test compare to the Meares– Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome? J Urol 176(1):119–124 12. Krieger JN, Nyberg L Jr, Nickel JC (1999) NIH consensus definition and classification of prostatitis. JAMA 282(3):236–237 13. Lipsky BA, Byren I, Hoey CT (2010) Treatment of bacterial prostatitis. Clin Infect Dis 50(12):1641–1652 14. Sharp VJ, Takacs EB, Powell CR (2010) Prostatitis: diagnosis and treatment. Am Fam Physician 82(4):397–406 15. Grabe M, Bjerklund-Johansen TE, Botto H, C¸ek M, Naber KG, Pickard RS, Tenke P, Wagenlehner FM, Wullt B (2013) EAU guidelines on urological infections. Uroweb. http://www.uroweb. org/gls/pdf/18_Urological%20infections_LR.pdf. Accessed 30 July 2013 16. National Institute on Disability and Rehabilitation Research Consensus Validation Conference (1992) The prevention and management of urinary tract infections among people with spinal cord injuries. J Am Parapleg Soc 15(3):194–204 17. Schneider H, Ludwig M, Hossain HM, Diemer T, Weidner W (2003) The 2001 Giessen Cohort Study on patients with prostatitis syndrome—an evaluation of inflammatory status and search for microorganisms 10 years after a first analysis. Andrologia 35(5):258–262 18. Krieger JN, Ross SO, Deutsch LA, Fritsche TR, Riley DE (2003) Counting leukocytes in expressed prostatic secretions from patients with chronic prostatitis/chronic pelvic pain syndrome. Urology 62(1):30–34 19. Colgan R, Nicolle LE, McGlone A, Hooton TM (2006) Asymptomatic bacteriuria in adults. Am Fam Physician 74(6):985–990 20. Cai T, Mazzoli S, Meacci F, Boddi V, Mondaini N, Malossini G, Bartoletti R (2011) Epidemiological features and resistance pattern in uropathogens isolated from chronic bacterial prostatitis. J Microbiol 49(3):448–454 21. Nickel JC, Xiang J (2008) Clinical significance of nontraditional bacterial uropathogens in the management of chronic prostatitis. J Urol 179(4):1391–1395 22. Krieger JN, Ross SO, Limaye AP, Riley DE (2005) Inconsistent localization of gram-positive bacteria to prostate-specific specimens from patients with chronic prostatitis. Urology 66(4):721–725 23. Nalmas S, Bishburg E, Chan T (2007) Streptococcus constellatus and Prevotella bivia penile abscess. Sci World J 7:1631–1633 24. Maskell R (1981) Gardnerella vaginalis and prostatitis. Lancet 2(8246):581–582 25. Christensen JJ, Vibits H, Ursing J, Korner B (1991) Aerococcuslike organism, a newly recognized potential urinary tract pathogen. J Clin Microbiol 29(5):1049–1053
World J Urol 26. Biering-Sorensen F, Bagi P, Hoiby N (2001) Urinary tract infections in patients with spinal cord lesions: treatment and prevention. Drugs 61(9):1275–1287 27. Nickel JC (1997) The pre and post massage test (PPMT): a simple screen for prostatitis. Tech Urol 3(1):38–43 28. Nadler RB, Collins MM, Propert KJ, Mikolajczyk SD, Knauss JS, Landis JR, Fowler JE Jr, Schaeffer AJ, Alexander RB (2006) Prostate-specific antigen test in diagnostic evaluation of chronic prostatitis/chronic pelvic pain syndrome. Urology 67(2):337–342
29. Massa LM, Hoffman JM, Cardenas DD (2009) Validity, accuracy, and predictive value of urinary tract infection signs and symptoms in individuals with spinal cord injury on intermittent catheterization. J Spinal Cord Med 32(5):568–573 30. Hinkel A, Finke W, Botel U, Gatermann SG, Pannek J (2004) Increasing resistance against antibiotics in bacteria isolated from the lower urinary tract of an outpatient population of spinal cord injury patients. Urol Int 73(2):143–148
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ORIGINAL ARTICLE
Chronic bacterial prostatitis in men with spinal cord injury Jo¨rg Krebs • Peter Bartel • Ju¨rgen Pannek
Received: 3 October 2013 / Accepted: 30 December 2013 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Recurrent urinary tract infections (UTI) are a major problem affecting spinal cord injury (SCI) patients and may stem from chronic bacterial prostatitis. We have therefore investigated the presence of chronic bacterial prostatitis and its role in the development of recurrent symptomatic UTI in SCI men. Methods This study is a prospective cross-sectional investigation of bacterial prostatitis in SCI men in a single SCI rehabilitation center. In 50 men with chronic SCI presenting for a routine urologic examination, urine samples before and after prostate massage were taken for microbiologic investigation and white blood cell counting. Furthermore, patient characteristics, bladder diary details, and the annual rate of symptomatic UTI were collected retrospectively. Results No participant reported current symptoms of UTI or prostatitis. In most men (39/50, 78 %), the microbiologic analysis of the post-massage urine sample revealed growth of pathogenic bacteria. The majority of these men (32/39, 82 %) also presented with mostly (27/39, 69 %) the same pathogenic bacteria in the pre-massage sample. There was no significant (p = 0.48) difference in the number of symptomatic UTI in men with a positive post-massage culture compared with those with a negative culture. No significant (p = 0.67) difference in the frequency distribution of positive versus negative post-massage cultures J. Krebs Clinical Trial Unit, Swiss Paraplegic Centre, Nottwil, Switzerland P. Bartel J. Pannek (&) Neuro-Urology, Swiss Paraplegic Centre, Guido A. Za¨ch Str. 1, 6207 Nottwil, Switzerland e-mail: [email protected]; [email protected]
was detected between men with recurrent and sporadic UTI. Conclusions Most SCI men are affected by asymptomatic bacterial prostatitis; however, bacterial prostatitis does not play a major role in the development of recurrent UTI. The indication for antibiotic treatment of chronic bacterial prostatitis in asymptomatic SCI men with recurrent UTI is questionable. Keywords Urinary tract infection Chronic bacterial prostatitis Microbiology Spinal cord injury
Introduction Neurogenic lower urinary tract dysfunction (NLUTD) following spinal cord injury (SCI) results in impaired storage and voiding function and subsequently an increased risk of urinary tract infections (UTI). Symptomatic UTI are a major cause of morbidity in individuals with SCI [1–3], with 20 % suffering from recurrent UTI [3]. Recurrent symptomatic UTI are bothersome for affected patients, and the associated symptoms, such as fever, incontinence, dysuria, increased spasticity, suprapubic pain, decreased bladder capacity, and impaired general well-being, lead to a decrease in quality of life [4]. Recurrent UTI in male SCI individuals may be the result of bacterial colonization of the prostate, which acts as a reservoir for uropathogens [5, 6]. Approximately 30 % of non-SCI men suffering from chronic bacterial prostatitis present with recurrent UTI [7], and bacterial infections of the prostate account for approximately 10 % of all cases of prostatitis [8], which is a common urologic disorder with a prevalence ranging between 2 and 10 % [9]. In SCI men, the prevalence of bacterial prostate infections may be
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considerably higher (i.e., 30 %) [10]. However, there are currently no data on the occurrence of bacterial prostatitis in SCI men with NLUTD. We have therefore prospectively investigated the presence of chronic bacterial prostatitis in men with NLUTD resulting from chronic ([12 months) SCI. Furthermore, the hypothesis was tested that SCI men affected by chronic bacterial prostatitis experience more symptomatic UTI compared to those not suffering from bacterial prostatitis.
Subjects and methods The present prospective study had been approved by the local ethics committee. All study participants provided written informed consent with guarantees of confidentiality. The study protocol had been registered with ClinicalTrials.gov (NCT01601041). Men with NLUTD resulting from chronic ([12 months) SCI, presenting for a routine urologic examination at the outpatient clinic of a single SCI rehabilitation center between December 2011 and December 2012 and using intermittent catheterization for bladder evacuation, were recruited for the study. Men suffering from a current symptomatic UTI, acute prostatitis, or medical conditions impairing the immune response, those under current or previous antibiotic treatment [28 days within the last 12 months, and those aged under 18 or older than 70 years were excluded. The prostate was examined by rectal palpation and ultrasonography in order to exclude contraindications for prostate massage (e.g., acute prostatitis, abscess). The participating men emptied their bladder completely by catheterization, and an urine sample aliquot was taken for microbiologic analysis and manual white blood cell (WBC) counting. Afterward, the prostate was massaged, and a second urine sample was collected by catheterization for microbiologic analysis (modified two-glass test [11]). Furthermore, the WBC count per high-power (1,0009 magnification) field (HPF) was determined semiquantitatively on gram-stained smears and classified as follows: 1–3 cells/HPF: (?), 4–10 cells/HPF: ?, 11–15 cells/HPF: ??, [15 cells/HPF: ???. The National Institutes of Health Classification System for prostatitis comprises four categories [12]. The diagnosis of chronic bacterial prostatitis (category II) is based on the detection of uropathogens in the cultures of expressed prostatic secretions and/or urine samples after prostate massage and an elevated WBC count [13, 14]. Typically, but not necessarily, the pre-massage urine sample is sterile [5, 13]. Clinically, chronic bacterial prostatitis is characterized by recurrent UTI and genitourinary discomfort and/ or pain in able-bodied men. Genitourinary discomfort and/
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or pain in the absence of bacteria localized to the prostate with or without inflammatory reaction is classified as chronic pelvic pain syndrome (category III). For the present investigation, a bacterial count of C103 colony-forming units/ml was considered clinically relevant in all microbiologic analyses [15]. The bacterium species with the greatest number of colony-forming units isolated from a post-massage sample was regarded to be the ‘‘main species.’’ Furthermore, a WBC count of C4/HPF in the postmassage urine sample and a count of [100/ll in the premassage sample were considered clinically relevant [14, 15]. Moreover, personal characteristics and bladder diary details were collected. The study participants were asked to report the number of symptomatic UTI they had experienced during the last 12 months. A symptomatic UTI was defined according to the published criteria: fever without another cause, dysuria, new onset of incontinence, suprapubic pain, impaired general well-being, decreased bladder capacity, increased general spasticity, hematuria without other causes, new onset of voiding problems [16]. According to the reported number of symptomatic UTI during the last 12 months, patients were categorized as suffering from frequent/recurrent ([2 UTI/year) or sporadic (B2 UTI/year) UTI. Data were calculated and presented as the median and the lower (LQ) and upper quartile (UQ). The differences between groups were tested with the Mann–Whitney U test. The Chi-square and Fisher’s exact test were used to test differences in the observed frequency distribution between groups. Statistical analyses were performed using the SPSS software (version 18.0.3, IBM, Somers, NY, USA). A p value of \0.05 was considered significant.
Results Sixty men with NLUTD resulting from SCI and performing intermittent catheterization were included into the study. Ten men were excluded because the annual rate of UTI could not be determined (SCI \ 12 months) (n = 4), the age was [70 years (n = 1), urine samples after prostate massage were missing (n = 2), declined study participation (n = 2) or antibiotic treatment for[28 days within the previous 12 months (n = 1). Thus, the data of 50 men with a median age of 48.5 years (LQ 39.9 UQ 57.3 years) were analyzed. Spinal cord injury had occurred a median of 16.1 years (LQ 7.8 UQ 21.7 years) ago. The etiology of SCI was trauma (43/50, 86 %), tumor (3/50), myelomeningocele (3/ 50), or inflammatory process (1/50). There were four tetraand 46 paraplegic patients. In 19 and 31 patients, SCI was complete and incomplete, respectively.
World J Urol Table 1 Culture results and white blood cell counts of urine samples taken before and after prostate massage Post-massage sample
Pre-massage sample
Men
Culture
WBC count
Culture
B2 UTI/ year
Positivea
C4/HPF
Positivec
C100/ll
5
1
Positivec
\100/ll
9
0
Negatived
C100/ll
1
0
d
0
WBC count
\100/ll
1
Positivec
C100/ll
5
2
Positivec
\100/ll
6
3
Negatived
C100/ll
1
0
Negatived \100/ll
3
2
Negative Positivea
Negativeb
\4/HPF
C4/HPF
Negativeb \4/HPF
[2 UTI/ year
Positivec
C100/ll
2
0
Positivec
\100/ll
0
0
Negatived
C100/ll
0
0
Negatived \100/ll
0
0
Positivec
C100/ll
1
0
Positive \100/ll Negatived C100/ll
2 1
0 0
Negatived \100/ll
4
1
c
WBC white blood cells, UTI urinary tract infection, HPF high-power field a
C103 colony-forming units of uropathogenic bacteria/ml. b No growth or normal flora. c C103 colony-forming units of uropathogenic bacteria/ml. d no growth or \103 colony-forming units/ml
Thirteen men had implemented nonantibiotic UTI prophylaxis, i.e., cranberry products (n = 8), L-methionine (n = 3), or both (n = 2). No participant reported any current complaints of UTI or prostatitis. Nine patients had suffered from recurrent UTI (median 6 UTI/year, LQ 4 UQ 6 UTI/year). In the majority of men (39/50, 78 %), the microbiologic analysis of the post-massage urine sample revealed relevant growth of pathogenic bacteria (Table 1). However, an elevated WBC count in the post-massage sample was observed in only 17 of the 39 men with a positive culture. The majority of men (31/39, 79 %) with a positive post-massage culture also presented with C103 colony-forming units of pathogenic bacteria/ml in the premassage sample. In only eight men, the post-massage culture was positive, whereas the pre-massage culture was negative. Two of these eight men presented with recurrent UTI. There were two men with an elevated WBC count in the post-massage sample but a negative culture. In the premassage sample of 37 men (37/50, 74 %), C103 colonyforming units of pathogenic bacteria/ml were detected. The bacteria species identified in the pre- and post-massage samples are presented in Table 2. The following pathogens were identified most frequently in the post-massage samples: Escherichia coli, Klebsiella pneumoniae,
Enterobacter species, coagulase-negative Staphylococci and Streptococcus viridans. In most cases (27/39, 69 %), the main pathogen identified in the post-massage sample was also detected in the pre-massage sample. There was no significant (p = 0.48) difference in the number of symptomatic UTI in men with a positive postmassage culture compared with those with a negative culture (Fig. 1). More than 50 % (22/39) of the men with a positive post-massage culture had experienced no symptomatic UTI during the previous 12 months. No significant (p = 0.67) difference in the frequency distribution of positive versus negative post-massage cultures was detected between men with recurrent UTI and those with sporadic UTI (Table 1).
Discussion This is the first cross-sectional study on the occurrence of chronic bacterial prostatitis in men with chronic SCI and NLUTD. In approximately four of five men, the microbiologic analysis of the urine sample taken after prostate massage revealed growth of uropathogenic bacteria. However, no association between the presence of bacteria in the prostate and the occurrence of UTI was observed. The hypothesis that SCI men affected by chronic bacterial prostatitis experience more symptomatic UTI compared to those not suffering from bacterial prostatitis was rejected. Growth of pathogenic bacteria was observed in approximately 80 % of the post-massage sample cultures, but no study participant reported any genitourinary symptoms. The prostate of asymptomatic SCI men therefore seems to be commonly infested by bacteria, which is in contrast to the reported prevalence of chronic bacterial prostatitis of \10 % in able-bodied men [17]. However, in more than 50 % of the investigated men, the WBC count in the post-massage sample was not elevated. According to the official classification system, this would not represent chronic bacterial prostatitis (category II) [13, 14]. The lack of an elevated WBC count in many cases with a positive post-massage culture may have been the consequence of the method chosen for determining the WBC count in the post-massage sample. The sensitivity of counting WBC on gram-stained smears is reported to be low [18], resulting in false-negative WBC counts. Two of the investigated men presented with an elevated WBC count in the post-massage sample but a negative culture. These men can be diagnosed with abacterial, inflammatory prostatitis (corresponding to category III). However, this type of prostatitis was not the focus of the present investigation. Analogously, the pre-massage sample cultures revealed growth of pathogenic bacteria in[70 % of the investigated men. The prevalence of asymptomatic bacteriuria in SCI
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World J Urol Table 2 Bacteria species identified in the urine samples taken before and after prostate massage
Main speciesa
Concomitant species
E. coli
na, not applicable; spp, species; E. coli, Escherichia coli; H. parainfluenzae, Haemophilus parainfluenzae; S. agalactiae, Streptococcus agalactiae; K. pneumoniae, Klebsiella pneumoniae; E. cloacae, Enterobacter cloacae; coagulase-neg. Staph, coagulase-negative Staphylococc; P. aeruginosa, Pseudomonas aeruginosa; S. viridans group, Streptococcus viridans group; E. aerogenes/ cloacae, Enterobacter aerogenes/cloacae; S. aureus, Staphylococcus aureus; K. oxytoca, Klebsiella oxytoca; S. milleri, Streptococcus miller a
Bacterium species isolated from post-massage sample with greatest number of colonyforming units
Coagulase-neg. Staph.
Strains with resistance to some antibiotics. 3 strains expressing extended-spectrum beta-lactamases
Premassage
Postmassage
10
5
5
0
2
na
2
H. parainfluenzae
0
1
na
1
S. agalactiae
1
1
0
0
7
9
7
9
E. cloacaec
1
2
1
2
Coagulase-neg. Staph. P. aeruginosa
0 0
2 1
na na
1 1
H. parainfluenzae
0
1
na
0
S. agalactiae
1
1
0
0
S. viridans group
1
1
0
0
Gardnerella vaginalis
0
1
na
0
1
6
1
6
0
1
na
1
Coagulase-neg. Staph. Enterococcus spp.
2
0
2
na
S. aureus
0
1
na
1
S. viridans group
1
1
0
0
K. oxytoca
0
1
na
1 2
1
2
1
na
na
na
na
3
3
3
3
Enterococcus spp.
1 3
0 3
0 0
na 0
E. coli
1
0
0
na
S. agalactiae
1
1
0
0
Coagulase-neg. Staph.
1
1
1
1
Gram neg. anaerobic cocci
0
1
na0
Prevotella bivia
0
1
na
0
Gardnerella vaginalis
0
1
na
0
1
3
1
2
H. parainfluenzae
0
1
na
0
Enterococcus spp.
1
0
1
na
1
1
1
1
0
1
na
0 1
None
S. viridans group
Corynebacterium spp.
Enterococcus spp. S. milleri Aerococcus None Prevotella bivia None
individuals has been reported to range between 30 and 80 % [19]. In the light of this high prevalence, it is not surprising that most (i.e., 79 %) of the investigated men with a positive post-massage sample culture also presented with a positive pre-massage culture. In the majority of men (i.e., approximately 70 %), the same main pathogenic bacteria were identified in both the pre- and the post-
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Postmassage
10
Proteus mirabilis
b
Premassage
Enterococcus spp.
K. pneumoniaec
E. aerogenes/ cloacaec
Count resistantb strains
Count
0
1
na
na
na
na
na
0
1
na
0
na
na
na
na
massage sample cultures. This supports the notion that ascending bacterial colonization of the prostate may occur after bladder infection, and in turn, bacteria may spread from the prostate into the urinary tract resulting in recurrent infections. We did not observe any association between the presence of bacteria in the prostate and the occurrence of UTI.
World J Urol Fig. 1 Box plots of annual symptomatic urinary tract infections (UTI) in spinal cord injury men with negative (n = 11) and positive (i.e., pathogenic bacteria) (n = 39) cultures of the urine samples taken after prostate massage
Men with bacterial colonization of the prostate had not experienced more UTI than men without, and both men with and without bacterial prostate colonization had suffered from recurrent UTI (i.e., [2 UTI/year). Furthermore, only two of the eight men with bacterial prostatitis and negative pre-massage urine cultures presented with recurrent UTI. Our results therefore do not support the notion that recurrent UTI are the result of bacterial colonization of the prostate in male SCI individuals. The pathogens identified most frequently in the prostatic fluid of the investigated SCI men (i.e., Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis) are also the main bacteria involved in chronic bacterial prostatitis in able-bodied men [5, 13, 20]. Apart from Enterococcus species, the role of gram-positive bacteria in chronic prostatitis is still being debated [21, 22]. Furthermore, Prevotella bivia and Gardnerella vaginalis were observed in the post-massage sample culture of two men each. In one of them, Prevotella bivia was the only bacteria identified in the post-massage sample. Prevotella bivia and Gardnerella vaginalis are normally associated with bacterial vaginitis, and men are typically asymptomatic carriers. However, there are case reports suggesting a uropathogenic potential in men [23, 24]. In other individuals, Aerococcus was the only pathogen identified in the post-massage sample (n = 1) or a concomitant pathogen in the pre-massage sample culture (n = 2). The clinical relevance of Aerococcus in the development of genitourinary infections remains to be determined [25]. Approximately 50 % (20/ 39) of the post-massage sample cultures revealed polymicrobial growth, and [70 % (29/39) of the main bacterial
species were multiresistant strains, which contributes to the complexity of managing UTI in SCI individuals [26]. The cross-sectional design pertains to the limitations of the present study. Chronic bacterial prostatitis is considered a persistent infection of the prostate with relapsing symptoms and UTI lasting more than 3 months [13, 14]. The duration of prostate infection is unknown in the investigated men. However, chronic asymptomatic bacterial colonization of the urinary tract is highly prevalent in SCI individuals [19]. Based on the isolated bacteria, relevant infections of the prostate were present, and there was no history of acute bacterial prostatitis. Acute bacterial prostatitis would manifest itself with symptoms such as fever and illness even in SCI individuals. The Meares–Stamey four-glass test is considered the gold standard for diagnosing prostatitis [13, 14]. However, this test cannot be performed in the majority of patients with NLUTD resulting from SCI. In the present investigation, a modified two-glass test was used. The urine samples before and after prostate massage were collected by intermittent catheterization. The two-glass test has been reported to provide results highly comparable with the four-glass test [27]. The serum concentration of prostate-specific antigen was not measured in the present investigation. Prostate-specific antigen levels are elevated in only approximately 20 % of men with chronic bacterial prostatitis [13], and thus, the determination of prostate-specific antigen levels is not recommended in chronic prostatitis because of the low sensitivity and specificity [28]. The retrospective collection of the annual rate of UTI and the mediocre accuracy (i.e., 66 %) [29] of patient self-prediction of UTI contribute to
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the uncertainty about the true number of annual symptomatic UTI. The true number of UTI may have been higher than reported by the participants. Apart from the limited sensitivity (i.e., 48 %) [29] of self-prediction, some study participants may not have remembered the correct number of UTI suffered during the previous 12 months. However, symptomatic UTI have a major impact on the quality of life of affected individuals, and thus, episodes of symptomatic UTI are not easily forgotten. Finally, there were only nine men with recurrent UTI (i.e., [2 UTI/year) in the present study. However, in the light of the high percentage of SCI men with bacterial colonization of the prostate, it is unlikely that a comparison between subjects with zero and subjects with more than two annual UTI would provide more evidence for the role of chronic bacterial prostatitis in the development of recurrent symptomatic UTI in SCI men. Based on the present results, most SCI men are affected by asymptomatic bacterial prostatitis and bacteriuria. The clinical relevance of bacterial colonization of the prostate in SCI men needs to be reconsidered. Commonly, SCI men presenting with recurrent UTI and growth of uropathogens in the post-massage urine or semen sample culture are treated for prostatitis with fluoroquinolones for 6 weeks according to current guidelines [15]. However, in the light of the present results, the justification for antibiotic treatment of asymptomatic chronic bacterial prostatitis in SCI men is highly questionable. Moreover, antibiotic treatment increases the selection pressure for resistant strains [30]. Conclusions Most SCI men are affected by asymptomatic bacterial prostatitis; however, bacterial prostatitis does not play a major role in the development of recurrent UTI. The indication for antibiotic treatment of chronic bacterial prostatitis in asymptomatic SCI men with recurrent UTI is questionable.
References 1. Esclarin De Ruz A, Garcia Leoni E, Herruzo Cabrera R (2000) Epidemiology and risk factors for urinary tract infection in patients with spinal cord injury. J Urol 164(4):1285–1289 2. Wyndaele JJ (2002) Complications of intermittent catheterization: their prevention and treatment. Spinal Cord 40(10):536–541 3. Biering-Sorensen F, Nielans HM, Dorflinger T, Sorensen B (1999) Urological situation five years after spinal cord injury. Scand J Urol Nephrol 33(3):157–161 4. Goetz LL, Cardenas DD, Kennelly M, Bonne Lee BS, Linsenmeyer T, Moser C, Pannek J, Wyndaele JJ, Biering-Sorensen F (2013) International spinal cord injury urinary tract infection basic data set. Spinal Cord (Epub ahead of print)
123
5. Nickel JC, Moon T (2005) Chronic bacterial prostatitis: an evolving clinical enigma. Urology 66(1):2–8 6. Wyndaele JJ (1985) Chronic prostatitis in spinal cord injury patients. Paraplegia 23(3):164–169 7. Habermacher GM, Chason JT, Schaeffer AJ (2006) Prostatitis/ chronic pelvic pain syndrome. Annu Rev Med 57:195–206 8. de la Rosette JJ, Hubregtse MR, Meuleman EJ, Stolk-Engelaar MV, Debruyne FM (1993) Diagnosis and treatment of 409 patients with prostatitis syndromes. Urology 41(4):301–307 9. Krieger JN, Lee SW, Jeon J, Cheah PY, Liong ML, DE Riley (2008) Epidemiology of prostatitis. Int J Antimicrob Agents 31(Suppl 1):S85–S90 10. Perrouin-Verbe B, Labat JJ, Richard I, Mauduyt de la Greve I, Buzelin JM, Mathe JF (1995) Clean intermittent catheterisation from the acute period in spinal cord injury patients. Long term evaluation of urethral and genital tolerance. Paraplegia 33(11):619–624 11. Nickel JC, Shoskes D, Wang Y, Alexander RB, Fowler JE Jr, Zeitlin S, O’Leary MP, Pontari MA, Schaeffer AJ, Landis JR, Nyberg L, Kusek JW, Propert KJ (2006) How does the premassage and post-massage 2-glass test compare to the Meares– Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome? J Urol 176(1):119–124 12. Krieger JN, Nyberg L Jr, Nickel JC (1999) NIH consensus definition and classification of prostatitis. JAMA 282(3):236–237 13. Lipsky BA, Byren I, Hoey CT (2010) Treatment of bacterial prostatitis. Clin Infect Dis 50(12):1641–1652 14. Sharp VJ, Takacs EB, Powell CR (2010) Prostatitis: diagnosis and treatment. Am Fam Physician 82(4):397–406 15. Grabe M, Bjerklund-Johansen TE, Botto H, C¸ek M, Naber KG, Pickard RS, Tenke P, Wagenlehner FM, Wullt B (2013) EAU guidelines on urological infections. Uroweb. http://www.uroweb. org/gls/pdf/18_Urological%20infections_LR.pdf. Accessed 30 July 2013 16. National Institute on Disability and Rehabilitation Research Consensus Validation Conference (1992) The prevention and management of urinary tract infections among people with spinal cord injuries. J Am Parapleg Soc 15(3):194–204 17. Schneider H, Ludwig M, Hossain HM, Diemer T, Weidner W (2003) The 2001 Giessen Cohort Study on patients with prostatitis syndrome—an evaluation of inflammatory status and search for microorganisms 10 years after a first analysis. Andrologia 35(5):258–262 18. Krieger JN, Ross SO, Deutsch LA, Fritsche TR, Riley DE (2003) Counting leukocytes in expressed prostatic secretions from patients with chronic prostatitis/chronic pelvic pain syndrome. Urology 62(1):30–34 19. Colgan R, Nicolle LE, McGlone A, Hooton TM (2006) Asymptomatic bacteriuria in adults. Am Fam Physician 74(6):985–990 20. Cai T, Mazzoli S, Meacci F, Boddi V, Mondaini N, Malossini G, Bartoletti R (2011) Epidemiological features and resistance pattern in uropathogens isolated from chronic bacterial prostatitis. J Microbiol 49(3):448–454 21. Nickel JC, Xiang J (2008) Clinical significance of nontraditional bacterial uropathogens in the management of chronic prostatitis. J Urol 179(4):1391–1395 22. Krieger JN, Ross SO, Limaye AP, Riley DE (2005) Inconsistent localization of gram-positive bacteria to prostate-specific specimens from patients with chronic prostatitis. Urology 66(4):721–725 23. Nalmas S, Bishburg E, Chan T (2007) Streptococcus constellatus and Prevotella bivia penile abscess. Sci World J 7:1631–1633 24. Maskell R (1981) Gardnerella vaginalis and prostatitis. Lancet 2(8246):581–582 25. Christensen JJ, Vibits H, Ursing J, Korner B (1991) Aerococcuslike organism, a newly recognized potential urinary tract pathogen. J Clin Microbiol 29(5):1049–1053
World J Urol 26. Biering-Sorensen F, Bagi P, Hoiby N (2001) Urinary tract infections in patients with spinal cord lesions: treatment and prevention. Drugs 61(9):1275–1287 27. Nickel JC (1997) The pre and post massage test (PPMT): a simple screen for prostatitis. Tech Urol 3(1):38–43 28. Nadler RB, Collins MM, Propert KJ, Mikolajczyk SD, Knauss JS, Landis JR, Fowler JE Jr, Schaeffer AJ, Alexander RB (2006) Prostate-specific antigen test in diagnostic evaluation of chronic prostatitis/chronic pelvic pain syndrome. Urology 67(2):337–342
29. Massa LM, Hoffman JM, Cardenas DD (2009) Validity, accuracy, and predictive value of urinary tract infection signs and symptoms in individuals with spinal cord injury on intermittent catheterization. J Spinal Cord Med 32(5):568–573 30. Hinkel A, Finke W, Botel U, Gatermann SG, Pannek J (2004) Increasing resistance against antibiotics in bacteria isolated from the lower urinary tract of an outpatient population of spinal cord injury patients. Urol Int 73(2):143–148
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