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Objectives: Acute epididymitis is often associated with urethritis. Mycoplasma genitalium and Ureaplasma urealyticum have been considered as pathogens of urethritis. The aim of the present study was to determine the prevalence of these microorganisms in men with acute epididymitis.
Method: A total of 56 men younger than 40 years-of-age with acute epididymitis were enrolled in the present study between January 2006 and June 2010. First-void urine specimens were subjected to culture of aerobic bacterial species, and examined for the presence of Chlamydia trachomatis, M. genitalium, M. hominis, U. parvum and U. urealyticum by polymerase chain reaction-based assays. Urethral swabs were cultured for Neisseria gonorrhoeae.
Results: The number and percentage of patients positive for each microorganism were as follows: Gram-negative bacilli, 2% and 3.6%; Gram-positive cocci, 23% and 41.1%; N. gonorrhoeae, 3% and 5.4%; C. trachomatis, 28% and 50.0%; M. genitalium, 5% and 8.9%; M. hominis, 6% and 10.7%; U. parvum, 6% and 10.7%; and U. urealyticum, 5% and 8.9%. Among 25 men with non-chlamydial non-gonococcal epididymitis, who were negative for Gram-negative bacilli, M. genitalium or U. urealyticum was detected in one man each (4.0%), and M. hominis and/or U. parvum was detected in five (20.0%).
Conclusion: In men younger than 40 years-of-age with acute epididymitis, C. trachomatis is a major pathogen. The prevalence of genital mycoplasmas and ureaplasmas are lower, and the role of genital mycoplasmas and ureaplasmas in the development of acute epididymitis remains to be determined.
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Acute epididymitis is a common inflammatory disease in men. It was historically assumed that epididymitis could be caused by chemical irritation from urine reflux.1 Now, however, most cases of epididymitis are thought to be a result of bacterial infection. Bacterial type varies with patient age.1 In men older than 35 years-of-age, epididymitis is often caused by Gram-negative bacilli responsible for UTI. In men younger than 35 years-of-age, epididymitis is often caused by pathogens associated with urethritis, including Neisseria gonorrhoeae and Chlamydia trachomatis.1 In addition, men presenting with epididymitis often have NGU, even in the absence of positive tests for C. trachomatis.2,3
Mycoplasma genitalium, first isolated from urethral cultures from two men with NGU in 1981,4 has been shown to be significantly associated with NGU in men.5,6 In addition, results of recent studies, which specifically identified Ureaplasma parvum and U. urealyticum in cases of NGU, suggested that U. urealyticum might be significantly associated with NGU.7–9 These pathogens associated with NGU, M. genitalium and U. urealyticum, might be likely to cause acute epididymitis similar to the etiological role of C. trachomatis. In contrast to many studies on the association of C. trachomatis with acute epididymitis, few studies exist on the roles of genital mycoplasmas and ureaplasmas in acute epididymitis.10
The purpose of the present study was to determine the prevalence of genital mycoplasmas and ureaplasmas in men with acute epididymitis. In addition to culturing for the presence of N. gonorrhoeae from urethral swabs, we examined FVU specimens from men younger than 40 years-of-age presenting with acute epididymitis. M. genitalium, M. hominis, U. parvum, U. urealyticum and C. trachomatis were sought by polymerase chain reaction-based assays, and their association with acute epididymitis was determined.
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This retrospective study was conducted in accordance with the Declaration of Helsinki. We enrolled all 56 Japanese patients younger than 40 years with a clinical diagnosis of acute epididymitis, who visited a urology clinic (iClinic) in Sendai, Japan, between January 2006 and June 2010, complaining of gradual onset of a painful swollen epididymis. However, all of them were examined by ultrasonography to confirm the diagnosis. All the patients had no history of direct trauma. None had an indwelling urethral catheter or a history of UTI complicated by genitourinary diseases, and none had taken any antibiotics in the month prior to attending the clinic.
Data regarding sexual orientation, urethritis symptoms (discharge, dysuria, urethral burning or irritation), and lower UTI symptoms (dysuria, frequency and urgency of urination) were obtained from all subjects. All subjects underwent genital examination. Their urethral smears were examined for the existence of Gram-negative intracellular diplocci, and their urethral swabs were cultured for N. gonorrhoeae. A FVU sample, which was the first 20 to 30 mL of the initial flush of urine after not having urinated for at least 2 h, was collected from all subjects. A portion of each FVU specimen was examined for quantification of WBC with automated quantitative urine particle analyzers (UF-50 or UF-1000i, Sysmex Corporation, Tokyo, Japan) according to manufacturer instructions.11,12 Another portion of each specimen was subjected to culture of aerobic bacterial species. Another portion was sent to a laboratory (Mitsubishi Chemical Medience Corporation, Tokyo, Japan) for evaluation of microbial etiology. The urine specimens were tested for C. trachomatis by an AMPLICOR STD-1 (Roche Diagnostics, Basel, Switzerland) or APTIMA Combo2 (Gen-Probe Incorporated, San Diego, CA, USA) assay, and for M. genitalium, M. hominis, U. parvum, and U. urealyticum by polymerase chain reaction-microtiter hybridization assay with species-specific oligonucleotide probes, as reported previously.13
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The 56 men ranged in age from 17 to 39 years (average age 27.8 years), and 47 (83.9%) men were younger than 35 years. Bacterial species detected in the FVU specimens from the men are shown in Table 1. Two species of Gram-negative bacilli, Escherichia coli and Serratia marcescens, were respectively isolated from one man each. Gram-positive cocci, including six bacterial species, were cultured in 23 men. N. gonorrhoeae and/or C. trachomatis were detected in 29 (51.8%) of 56 men. Genital mycoplasmas and/or ureaplasmas were detected in 16 men (28.6%).
Table 1. Prevalence of bacterial species detected in men with acute epididymitis
|Bacterial species||No. men (%)|
|Gram-negative bacilli||2 (3.6)|
| E. coli||1 (1.8)|
| S. marcescens||1 (1.8)|
|Gram-positive cocci||23 (41.1)|
| S. aureus||3 (5.4)|
| α-streptococci||6 (10.7)|
| β-streptococci||1 (1.8)|
| S. agalactiae||4 (7.1)|
| E. faecalis||6 (10.7)|
| Coagulase-negative staphylococci||6 (10.7)|
|N. gonorrhoeae||3 (5.4)|
|C. trachomatis||28 (50.0)|
|M. genitalium||5 (8.9)|
|M. hominis||6 (10.7)|
|U. parvum (biovar 1)||6 (10.7)|
|U. urealyticum (biovar 2)||5 (8.9)|
In the present study, the 56 patients with acute epididymitis were diagnosed as having gonococcal epididymitis, chlamydial non-gonococcal epididymitis, or non-chlamydial non-gonococcal epididymitis on the basis of the presence or absence of N. gonorrhoeae or C. trachomatis in FVU. Of three men from whom N. gonorrhoeae was isolated from the urethra, all the men showed symptoms and signs of gonococcal urethritis (Table 2). Two men were infected with C. trachomatis. Genital mycoplasmas or ureaplasmas were not detected, but 106 cfu/mL of S. agalactiae was cultured from the FVU of one man. Of the 53 men who were negative for N. gonorrhoeae, 26 (49.1%) were positive for C. trachomatis in their FVU specimens (Table 2). Of these 26 men, 20 (76.9%) did not complain of urethritis symptoms, and 19 (73.1%) showed no pathogenic urethral discharges on examinations, though 25 men (96.2%) showed pyuria of ≥10 WBC/µL in their FVU.14 In seven men (26.9%), one or two species of Gram-positive cocci were cultured in the FVU specimens, but the bacterial loads were <105 cfu/mL. A total of 10 men (38.5%) were infected with one or two species of genital mycoplasmas and ureaplasmas. One man (3.8%) was infected with M. genitalium and U. urealyticum. Three men (11.5%) were infected with M. genitalium, and another three men (11.5%) were infected with U. urealyticum.
Table 2. Demographic characteristics of the study population
|Characteristic||No. patients (%) or mean ± SD or mean (median)|
|Gonococcal (n = 3)||Chlamydial non-gonococcal (n = 26)||Non-chlamydial non-gonoccocal (n = 25†)|
|Age (years)||26.0 ± 6.6||27.7 ± 6.6||27.6 ± 6.2|
| <35 years||3 (100)||22 (84.6)||20 (80.0)|
|Heterosexual||3 (100)||26 (100)||25 (100)|
|Previous urethritis||0||2 (7.7)||3 (11.5)|
|Self-reported dysuria|| || || |
| None||0||20 (76.9)||25 (100)|
| Mild||1 (33.3)||5 (19.2)||0|
| Moderate to sever||2 (66.7)||1 (3.8)||0|
|Self-reported urethral discharge||3 (100)||1 (3.8)||1 (3.8)|
|Urethral discharge on examination|| || || |
| None/normal||0||19 (73.1)||22 (88.0)|
| Mucoid/mucoprulent||3 (100)||7 (26.9)||3 (12.0)|
|Self-reported urethral burning or irritation||1 (33.3)||4 (15.4)||0|
|Body temperature||37.5 ± 0.6||37.1 ± 0.5||37.3 ± 0.6|
|Epididymo-orchitis||2 (66.7)||2 (7.7)||2 (8.0)|
|White blood cells in first-void urine (/µL)||1890.2–4502.3 (2759.3)||3.6–3979.4 (501.6)||1.0–2009.9 (11.0)|
| <10/µL||0||1 (3.8)||12 (48.0)|
| ≥10/µL||3 (100)||25 (96.2)||13 (52.0)|
|Aerobic culture|| || || |
| No growth||2 (66.7)||19 (73.1)||12 (48.0)|
| <105 cfu/mL||0||7 (26.9)||12 (48.0)|
| ≥105 cfu/mL||1 (33.3)||0||1 (4.0)|
|N. gonorrhoeae||3 (100)||0||0|
|C. trachomtis||2 (66.7)||26 (100)||0|
|M. genitalium||0||4 (15.4)||1 (4.0)|
|M. hominis||0||2 (7.7)||4 (16.0)|
|U. parvum||0||1 (3.8)||5 (20.0)|
|U. urealyticum||0||4 (15.4)||1 (4.0)|
Of the 27 men with non-chlamydia non-gonococcal epididymitis, two men were positive for Gram-negative bacilli. One man from whom E. coli was isolated was negative for genital mycoplasmas and ureaplasmas, and had a bacterial load of 107 cfu/mL. He had bilateral epididymo-orchitis with a high fever of 39.3°C and showed 275.3 WBC/µL in his FVU. This case of acute epididymitis could be associated with UTI. In the other man from whom S. marcescens was isolated, Enterococcus faecalis was simultaneously cultured from his FVU specimen with a total bacterial load of 104 cfu/mL, but he showed no symptoms of UTI and no pyuria. Of the remaining 25 men with non-chlamydia non-gonococcal epididymitis, 24 (96.0%) reported no urethritis symptoms, and 22 (88.0%) showed no pathological urethral discharges on examinations (Table 2). However, 13 men (52.0%) showed pyuria in FVU.14 One or two species of Gram-positive cocci were cultured in the FVU specimens in 13 (52.0%) men. In one man, 106 cfu/mL of α-streptococci were isolated, but in other men, the bacterial loads were <105 cfu/mL. Seven men (26.9%) were infected with one or two species of genital mycoplasmas and ureaplasmas. In one man (4.0%), M. genitalium and E. faecalis were detected in his FVU. He had 11.0 WBC/µL in his FVU, but had no symptoms or signs related to acute urethritis and UTI. In another man (4.0%), U. urealyticum and 103 cfu/mL of α-streptococci were isolated from his FVU. He did not complain of any symptoms of urethritis, but had mucoid urethral discharge on genital examination and 489.2 WBC/µL in his FVU. Five other men (20.0%) were positive for M. hominis and/or U. parvum. Four of them had no symptoms or signs related to UTI and urethritis. One man who was positive for M. hominis and U. parvum had 31.0 WBC/µL in his FVU, but did not complain of urethritis symptoms.
In 9 men (16.1%) of the 57 men with acute epididymitis, no investigated bacterial specimens were detected. All of them had no symptoms or signs related to UTI and urethritis, but five men had pyuria of ≥10 WBC/µL in their FVU.14
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Most cases of acute epididymitis in heterosexual men under 35 years-of-age are associated with urethritis. In the present study, in just two of the 56 enrolled patients younger than 40 years with acute epididymitis, of whom 83.9% were younger than 35 years, Gram-negative bacilli were isolated from urine specimens. N. gonorrhoeae and C. trachomatis were detected in 5.4% and 50.0%, respectively. The acute epididymitis in these patients could be associated with urethritis. However, more than 70% of men positive for C. trachomatis did not complain of symptoms and showed no signs of acute urethritis, though typical symptoms and signs of acute gonococcal urethritis were found in all the men positive for N. gonorrhoeae. C. trachomatis might reach the epididymis through the urethra and cause acute epididymitis without prominent inflammation of the urethra.
In the present study, M. genitalium was detected in 8.9%, M. hominis in 10.7%, U. parvum in 10.7% and U. urealyticum in 8.9% of the patients. Regarding the prevalence of genital mycoplasmas and ureaplasmas, only one report exists.15 That study, in which, in addition to aerobic culture of midstream urine specimens, urethral swab specimens from 158 men older than 40 years with acute epididymitis were examined for the presence of C. trachomatis, M. genitalium, M. hominis, and Ureaplasma spp. showed that 34.8% of men were positive for E. coli, 1.3% for C. trachomatis, 1.9% for M. genitalium, 1.9% for M. hominis and 15.2% for Ureaplasma spp. The high prevalence of E. coli and the low prevalence of C. trachomatis suggested that the acute epididymitis in most patients older than 40 years enrolled in that study might be associated with UTI. The prevalence of genital mycoplasmas and ureaplasmas in men younger than 40 years found in the present study was higher than that in men older than 40 years. This higher prevalence could be related to the higher proportion of urethritis-associated epididymitis seen in younger men.
In the present study, seven (26.9%) of the 26 men with chlamydial epididymitis were infected with M. genitalium and/or U. urealyticum. Because C. trachomatis was likely to be a pathogen in these cases, the pathogenic roles of M. genitalium and U. urealyticum in acute epididymitis could not be determined. Clinically, the findings suggested that, in men with acute chlamydial epididymitis associated with urethritis, co-infection by M. genitalium and/or U. urealyticum would not be rare and should be taken into consideration when managing such patients.
In men with non-chlamydial non-gonococcal epididymitis, the prevalence of M. genitalium (3.8%) or U. urealyticum (3.8%) appeared to be lower compared with that (15.4%) in men with chlamydial non-gonococcal epididymitis. Chlamydial epididymitis is a sexually transmitted infection of the epididymis, where C. trachomatis ascends through the urethra. The patients with chlamydial epididymitis could have had higher risks of exposure to pathogens related to NGU, including M. genitalium and U. urealyticum, whereas those with non-chlamydial non-gonococcal epididymitis could have had lower risks. In addition, no investigated bacterial species were detected in nine patients with non-chlamydial non-gonococcal epididymitis. The category of non-chlamydial non-gonococcal epididymitis might include some patients with other diseases that are not as a result of bacterial infections. Therefore, the prevalence of M. genitalium and U. urealyticum could be lower in patients with non-chlamydial non-gonococcal epididymitis.
In one man with non-chlamydial non-gonococcal epididymitis in the present study, M. genitalium and E. faecalis were detected. In a case report from Japan, M. genitalium was detected in the FVU from a 30-year-old man with acute epididymitis in whom the FVU was negative for N. gonorrhoeae, C. trachomatis, U. parvum and U. urealyticum, and bacterial culture of the urine was also negative.16 In these cases, including ours, the possible association of M. genitalium in the urethra with acute epididymitis could be assumed, but there are no studies in which M. genitalium was detected in epididymal aspirates directly obtained from the inflamed epididymis. In another man with non-chlamydial and non-gonococcal epididymitis, U. urealyticum and 103 cfu/mL of α-streptococci were detected from his FVU. In a previous study in which U. parvum and U. urealyticum were not distinguished from each other, recovery of ureaplasmas from percutaneous aspirates of the inflamed epididymis was reported in one patient with a greater than fourfold serological antibody response.17 In another previous study, however, no patients were positive for ureaplasmas in their epididymal aspirates, although ureaplasmas were recovered from some of their urethral swabs.18 Thus, the pathogenic roles of M. genitalium and U. urealyticum would be inconclusive.
The prevalence of M. hominis (15.4%) or U. parvum (19.2%), both of which have been assumed to be a colonizer in the urethra, appeared to be higher in comparison with those (7.7% or 3.8%, respectively) in men with chlamydial non-gonococcal epididymitis. In a previous study, M. hominis was isolated from the epididymal aspirate of one patient with acute epididymitis.19 However, M. hominis and U. parvum are often recovered from the urethra of asymptomatic men. The prevalence of these bacterial species in asymptomatic men was reported to be ∼22%, respectively.13,20 The pathogenic roles of M. hominis and U. parvum also would be inconclusive.
In conclusion, C. trachomatis was a major pathogen in acute epididymitis in men younger than 40 years-of-age. The prevalence of genital mycoplasmas and ureaplasmas were low, and the crucial association of genital mycoplasmas and ureaplasmas with acute epididymitis was inconclusive. To verify causal roles of genital mycoplasmas and ureaplasmas in acute epididymitis, further studies are needed, including studies of a large number of men positive only for a single species of genital mycoplasmas or ureaplasmas, an examination of epididymal aspirates directly obtained from the inflamed epididymis for the presence of genital mycoplasmas or ureaplasmas, and the determination of antibodies against these microorganisms. Nevertheless, this is the first study to our knowledge to report the prevalence of genital mycoplasmas and ureaplasmas in younger men with acute epididymitis. It provides some new findings on the bacterial etiology of acute epididymitis in younger men, suggesting that the prevalence of genital mycoplasmas and ureaplasmas would be lower and that these microorganisms might play only a minor pathogenic role, if any, in acute epididymitis in comparison with that of C. trachomatis.