Clinical characteristics, management, and treatment outcomes of epididymo-orchitis among patients in a referral hospital in Southern Saudi Arabia

1. Introduction

Epididymo-orchitis (EO) is a prevalent genitourinary clinical syndrome in men, characterized by inflammation affecting both the epididymis and the corresponding testis, leading to pain and swelling [1, 2]. This inflammation typically arises as a result of infection spreading from the bladder, urethra, prostate, ejaculatory duct and vas deferens [3]. EO can affect individuals of all age groups and represents the most common cause of acute scrotal pain in outpatient healthcare settings [1]. In the United States, the reported annual incidence of EO reaches 600,000 cases, with 250 cases per 10,000 men reported in the United Kingdom [4, 5]. Notably, data from the US reveals that EO ranks as the fifth most frequent urological diagnosis among patients aged between 18 and 50 years attending outpatient facilities [6].

The inflammatory responses associated with EO typically arise from infectious agents or non-infectious factors, such as genitourinary trauma, iatrogenic bladder or urethral instrumentation, amiodarone usage, vasculitis and autoimmune disorders [1, 2]. Sexually transmitted pathogens are the predominant infectious agents responsible for EO in men under the age of 35, while Gram-negative bacteria are more commonly implicated in older men [5]. However, it is important to note that the diagnostic assessment and treatment approach may vary depending on the patient’s age [1].

EO is the most frequent complication of Brucella infection, with prevalence rates ranging from 1.4% to 25% among affected males [7]. The incidence of human brucellosis has become a significant public health concern in Saudi Arabia, leading to the implementation of various control measures since 1983 [8]. Presently, the hyperendemic nature of brucellosis remains a significant epidemiological challenge in the country, particularly in rural areas [9, 10, 11, 12]. Numerous studies have detailed the clinical features and risk factors associated with brucellosis in the southern region of Saudi Arabia [13, 14, 15]. Notably, it has been observed that EO is the most common genitourinary complication of brucellosis in endemic regions [2, 16, 17]. A prior investigation conducted in a tertiary care hospital in Riyadh reported EO in 1.6% of patients with brucellosis [18]. Additional studies in Saudi Arabia have documented complications of brucellosis, including testicular abscess [17] and non-caseating granulomatous EO, with a focus on necrosis [19]. Therefore, healthcare practitioners encountering EO cases in endemic areas should be vigilant regarding the potential association with brucellosis [18]. The differential diagnosis of an inflamed scrotum, a common urological emergency, remains a clinical challenge [2, 19, 20]. Nevertheless, it is crucial to highlight that delayed investigation and inappropriate management of EO can lead to various complications, including testicular abscess, atrophy, necrotizing orchitis, testicular infarction, atrophy and male infertility [2, 18].

Given these above considerations, in this present study, we aim to analyze the clinical and laboratory findings and treatment outcomes in patients diagnosed with EO at a referral hospital in southern Saudi Arabia.

2. Materials and methods

3. Results

Data was collected from 63 EO-diagnosed patients (Table 1). Their median age was 34 years (range 16–82 years), most were Saudi nationals (77.8%, n = 49), and approximately half were young adults and adults (54%, n = 34). Their median hospital stay was 7 days (IQR = 4 to 10 days), with 38 patients (60.3%) staying for 7 days or less, while 25 patients (39.7%) had admissions exceeding seven days. Among the patients, 55% were smokers, 34.9% had a history of animal contact, 25.4% had comorbidities, and 7.9% reported consuming raw milk.

3.2 Laboratory and radiological findings

Table 2 presents the results of admission laboratory tests for the patients. The average values from the complete blood count indicated an elevated total leukocyte count (TLC; median = 12, IQR (9–17)), an increased neutrophil count (median = 9.96, IQR (5.85–12.02)), and a normal platelet count (median = 274, IQR (230–330)). Anti-Brucella antibody titers (≥1:80) were detected in 22 cases (34.9%), with six of them showing positive blood cultures for Brucella species. Brucellosis was diagnosed in 11 of the 63 patients (17.5%) based on clinical symptoms, with titers of ≥160 and/or positive blood cultures.

Table 2.Laboratory parameters for patients diagnosed with epididymo-orchitis.

Parameters	Frequency, n (%)
Routine urine test
Normal findings	50 (79.4)
Abnormal findings	13 (20.6)
	Only WBC	6 (9.5)
	WBC, RBC, protein and nitrate	3 (4.8)
	Only RBC	2 (3.2)
	Leucocyte and red blood cells	1 (1.6)
	WBC, RBC and protein	1 (1.6)
Positive urine culture	9 (14.3)
	Escherichia coli	6 (9.5)
	Klebsiella pneumoniae	3 (4.8)
Complete blood count
	Increased total leucocyte count	42 (66.7)
	Neutrophilia	41 (65.1)
	Platelets count
		Increased	0 (0.0)
		Normal	62 (98.3)
		Decreased	1 (1.6)
Positive anti-Brucella antibody titer	22 (34.9)
	1/80	2
	1/160	1
	1/320	8
	1/640	6
	1/1280	5
Blood culture
	*Brucella species	6/22 (27.3)
	**Klebsiella pneumoniae	1
*: Isolated from patients with positive anti-Brucella antibodies; **: Isolated from a patient with sepsis. WBC: white blood cells; RBC: red blood cells.

Routine urinalysis yielded abnormal findings in 13 cases (20.6%), while positive cultures were observed in 9 cases (14.3%). Among these, urine cultures were positive for 9 patients (14.3%), with Klebsiella pneumoniae identified in 6 cases and Escherichia coli in 3 cases.

Scrotal ultrasonography was performed for differential diagnosis of potential testicular abscesses and masses (Figs. 1,2). Increased vascularity was evident in both testes and epididymis in 49 patients (77.8%) (Fig. 1A), while 14 patients (22.2%) had increased vascularity in the epididymis alone (Fig. 1B). Complications of EO included reactive hydrocele in 15 patients (23.8%) and abscess formation in seven patients (11.1%) (3 testicular, 3 scrotal and 1 epididymal). Notably, one patient with a scrotal abscess subsequently developed K. pneumoniae sepsis. Additional complications comprised hypoechoic lesions in three patients (3.8%) (Fig. 2), epididymal thickening in two patients (3.1%), and one case of Fournier gangrene.

Fig. 1.Representative scrotal ultrasonography image of a patient with epididymo-orchitis. (A) Increased vascularity in both epididymis and testes, as observed in 77.8% of the patients. (B) Increased vascularity in the epididymis, as detected in 22.2% of the patients.

Fig. 2.Scrotal ultrasonography showed left epididymitis with the hypoechoic lesion as a complication of epididymo-orchitis in three (3.6%) of the 63 investigated patients.

3.3 Treatment and outcomes

Fig. 3 shows the various treatment regimens administered to the 63 EO patients. Empirical treatment was given to 48 patients, while those with positive urine culture results (n = 9) received treatment based on culture and sensitivity reports. Of the total, 55 patients (87.3%) responded favorably to the initial treatment course, and four patients (6.3%) achieved a cure following the second course. Additionally, EO complications were observed in three cases (4.8%), and one patient (1.6%) succumbed to septicemia. Among the 15 patients (23.8%) treated with a combination of ceftriaxone and ciprofloxacin, one patient did not respond to treatment and required orchiectomy due to a testicular abscess. Among the 10 patients (15.9%) treated with triple therapy (doxycycline, rifampicin and gentamicin), one experienced relapse after 6 months of completing treatment, characterized by the recurrence of EO symptoms in the absence of reinfection. Of the nine patients (14.3%) treated with ceftriaxone and co-trimoxazole, one did not respond to treatment, developed a testicular abscess, and underwent incision and drainage. Two patients (3.2%) did not respond to ceftriaxone monotherapy; therefore, one was switched to ciprofloxacin, and the other received a combination of ciprofloxacin and rifampicin. Levofloxacin monotherapy was modified to amikacin and amoxicillin/clavulanate in one patient (1.6%), and ciprofloxacin was replaced with amikacin in another. Overall, these changes led to complete resolutions, with all local symptoms disappearing and no clinical signs observed at six months.

Fig. 3.The antibiotic regimens used for treating patients with epididymo-orchitis. ǂ: Not improved, underwent orchiectomy (n = 1 patient); ¥: Relapse (n = 1 patient); ∥: Not improved, undergone abscess drainage procedure (n = 1 patient); ϔ: Developed sepsis and died (n = 1 patient); Δ: Improved after the second course of treatment (n = 4 patients).

One patient (1.6%) succumbed to sepsis following treatment with a combination of meropenem and tigecycline. This particular patient presented with fever lasting more than 7 days, along with lower urinary tract symptoms, left scrotal pain and swelling. He had multiple comorbidities, including diabetes, hypertension, ischemic heart disease and chronic renal failure requiring hemodialysis. Initial laboratory tests indicated an elevated TLC with neutrophilia and decreased platelet count, while anti-Brucella antibodies were not detected. Ultrasonography revealed increased vascularity in the left testicle and a para-testicular collection. An incision and drainage procedure was performed, and the patient was admitted to the intensive care unit, commencing empirical intravenous therapy with meropenem (500 mg, intravenous (IV) 8 hourly). Blood and urine cultures were obtained, both revealing K. pneumoniae isolates resistant to multiple antibiotics, except imipenem, meropenem, tigecycline and colistin. His treatment was then adjusted by adding tigecycline 100 mg, intravenous, 12 hourly for 6 weeks. However, the patient’s condition continued to deteriorate rapidly, with poor response to treatment, ultimately leading to his demise on the 35th day.

4. Discussion

EO represents a prevalent clinical syndrome in urological practice, necessitating accurate diagnosis and management to prevent severe complications. This study, to the best of our knowledge, constitutes the first investigation into the clinical and laboratory characteristics as well as treatment outcomes of EO in patients at a referral hospital in southern Saudi Arabia. The most frequently observed symptoms in EO cases were scrotal pain and swelling, closely followed by testicular pain. Fever was present in 24% of the patients. These symptoms align with previous findings in the scientific literature regarding EO cases [7, 20, 22]. Similarly, a study conducted at a tertiary hospital in Riyadh between 1983 and 2000 revealed that common symptoms in adult patients with Brucella-related EO included swollen and painful testicles, undulant fever, chills and arthralgia [18]. Likewise, scrotal pain, swelling, fever, erythema, malaise and arthralgia were frequently reported symptoms among patients with Brucella-related EO in Turkey [7, 23].

In our study, 35% of patients exhibited seropositivity for Brucella with titers ≥1:80. In Brucella-endemic regions, including our study area, a substantial number of individuals may possess anti-Brucella antibody titers ≥1:80 without necessarily having an active infection [24]. In a recent investigation examined the correlation between baseline Brucella antibody titers, culture positivity and clinical presentation in an area endemic for brucellosis, Alsubaie et al. [11] reported that Brucella serology was not significantly correlated with clinical outcomes at the end of therapy or with culture positivity at baseline. However, culture positivity was significantly associated with high antibody titers of ≥1:640. Thus, the diagnosis and monitoring of brucellosis patients should rely on clinical manifestations, epidemiological history, bacterial cultures and serological tests [24]. In this study, 17% of EO patients were confirmed to have active brucellosis, a percentage higher than the 9% incidence of brucellosis reported in EO patients in Egypt [25]. However, our findings align with those from Pakistan, where Brucella-related EO was reported in 16.7% (n = 23) of 138 EO cases [26]. Similarly, a study in China revealed that 30.7% of patients with confirmed brucellosis experienced EO complications [27]. Numerous studies have documented that EO can be a subsequent manifestation of systemic disease following a prior Brucella infection [2, 3, 24, 25]. In regions with a high incidence of brucellosis, clinicians should consider Brucella as a potential etiological agent of EO [24]. Nonetheless, Brucella-related EO can be differentiated by its gradual onset, longer duration, typical undulant fever, history of contact with animals or consumption of unpasteurized dairy products, serological testing and scrotal ultrasonography [2, 17]. Thus, early identification of brucellosis and the selection of appropriate therapy can lead to a favorable recovery without complications [2].

In our present study, patients diagnosed with EO displayed significantly high total leukocyte counts (TLC) and neutrophil counts, suggesting the presence of inflammation. However, platelet counts remained nearly within the normal range. It is recognized that neutrophils and lymphocytes may play pivotal roles in inflammatory processes, with lymphocyte counts showing transient changes during inflammatory conditions [22]. A recent study revealed that individuals with EO have significantly higher neutrophil counts but lower lymphocyte counts compared to those with Brucella-related EO [22], suggesting the potential utility of total and differential leukocyte parameters as differentiating factors between different types of EO [18].

In our current study, urinalysis revealed abnormal findings in 20.6% of the patients. Previous reports have documented UTIs in cases of acute right EO complicated by thrombosis of the pampiniform plexus [28]. Urine cultures yielded positive results for 14% of the patients, predominantly showcasing enteric Gram-negative pathogens such as E. coli and K. pneumoniae. It’s worth noting that all these positive cultures were obtained from freshly collected midstream voided-urine samples. Our findings are slightly lower than those reported in Iran, where bacterial pathogens were identified in 26% of EO patients via urine culture [29]. Similarly, a study conducted in the United States reported 20% positive urine cultures among men presenting with EO at emergency departments [1]. Enteric Gram-negative bacteria have been well-documented as infectious agents responsible for EO in adult patients, with E. coli being the most commonly implicated pathogen [1]. The hematogenous route, originating from the bladder or ascending from the urethra, vas deferens, prostate and ejaculation duct, is considered a potential path of infection in cases of infective EO or testicular abscess [30]. Therefore, routine urinalysis and culture hold significant diagnostic value in identifying infectious causes of EO [28, 31]. Noteworthily, one patient with EO was diagnosed with Neisseria gonorrhoeae, highlighting the importance of obtaining a sexual contact history to rule out sexually transmitted diseases (STDs) as potential contributors to EO.

Ultrasonography serves as a highly accurate imaging modality for diagnosing testicular and scrotal pathology and plays a crucial role in evaluating testicular vascularity [28]. It can be used to confirm the diagnosis of scrotal infections with testicular causes, such as malignancy, abscesses and testicular torsion, which may present with similar clinical findings [4, 19]. Furthermore, ultrasonography can reveal additional findings, including the presence of hydrocele, scrotal wall thickening, fistula formation, calcifications and abscess formation, which may manifest as avascular hypoechoic areas in the epididymis [20]. In our present study, patients diagnosed with EO exhibited increased vascularity in both the testes and epididymis, a characteristic indicative of infection. These findings are consistent with those reported in existing scientific literature [7, 31, 32, 33]. Additionally, our study identified scrotal abscesses and hypoechoic lesions on ultrasonography in seven and three cases, respectively. Notably, one patient with a testicular abscess that did not respond to treatment ultimately underwent orchiectomy, and this approach aligns with recommendations from other studies, which have advocated orchiectomy for patients with focal hypoechoic lesions in the testis, necrotizing orchitis, suspected malignancy and larger abscesses [17, 33].

To date, there is no specific recommended regimen for the treatment of EO, leading to the utilization of the same regimen for uncomplicated brucellosis [19]. Multiple treatment regimens have been proposed for EO, with their selection based on the individual patient’s baseline characteristics and clinical data [19, 31, 34]. Among the commonly prescribed antibiotic combinations for EO treatment, ceftriaxone is often combined with either a fluoroquinolone (such as ciprofloxacin, levofloxacin or ofloxacin), an aminoglycoside (such as amikacin, gentamicin or streptomycin), doxycycline, trimethoprim/sulfamethoxazole or rifampicin [34]. Various studies have used different combinations of medications for EO treatment, ranging from two to six regimens [2, 31, 35]. Fortunately, most therapy combinations administered to our EO patients proved to be effective. However, one case treated with the ceftriaxone and gentamicin regimen eventually underwent orchiectomy, resulting in a similarly low rate (3.8%) of orchiectomy reported among 53 cases of Brucella EO in previous studies [35]. Inadequate treatment can potentially prolong the infection and lead to testicular loss [18, 33]. Conversely, another case with a testicular abscess did not respond to empirical treatment. Ultimately, cure was achieved after an abscess incision and drainage, a preferable option for preserving the testicle compared to orchiectomy. It is essential to emphasize that appropriate source control encompasses draining abscesses and removing infected fluids, which can significantly improve patient outcomes and help in the selection of appropriate antimicrobial therapy [36]. Obtaining cultures from the abscess drainage site and urine samples from suspected UTIs is crucial for identifying possible pathogens and their resistance patterns, thus guiding the choice of antimicrobial therapy.

Our study revealed that only one case (1.6%) of relapse occurred after a 6-month treatment period, which is notably lower than the rates reported in Iran (26.3%) and Spain (25%) among EO patients [31, 34]. In the case of relapse, treatment was extended by two months, ultimately resulting in a successful cure. It has been suggested that patients experiencing treatment failure with any regimen at 45 days may achieve a cure by extending the treatment course to 2 months [35]. Moreover, several studies have recommended the exploration of alternative combination therapies to achieve the desired treatment outcome [2, 31, 34]. In our study, ciprofloxacin monotherapy demonstrated efficacy in treating two cases. Guidelines advocate for the empirical use of fluoroquinolones, including ciprofloxacin, in men over 35 years presenting with EO due to their favorable tissue penetration into the epididymis [18]. However, it is important to note that ciprofloxacin may not be effective when the causative microorganism exhibits resistance to quinolones [5]. Prior studies have documented an increased resistance rate to ciprofloxacin among Gram-negative pathogens in our local setting [37, 38, 39, 40]. Therefore, the selection of antibiotic therapy should be guided by local antibiogram patterns.

While most patients achieved recovery, it is essential to note that one patient succumbed to sepsis caused by multi-drug resistant (MDR) K. pneumoniae infection. MDR Gram-negative bacteria, such as K. pneumoniae, have emerged as a frequent cause of sepsis, leading to extended hospitalizations and elevated rates of morbidity and mortality [13, 41, 42]. Thus, a comprehensive understanding of local microbial data, encompassing prevalent pathogens and their resistance profiles, is important for facilitating effective empirical treatment and enhancing clinical outcomes.

5. Conclusions

In conclusion, EO remains a significant health concern among adult males, necessitating prompt investigation and treatment. Ultrasonography is invaluable in confirming the initial clinical diagnosis and ruling out abscesses or tumors for differential diagnosis. In regions endemic to Brucella, clinicians should remain vigilant regarding the potential involvement of brucellosis in EO cases. Nevertheless, a combination of clinical data, patient history and serological tests typically suffices for accurate diagnosis. Most EO cases can be effectively managed and completely resolved through appropriate antibiotic therapy. Notably, combination antibiotics featuring cefuroxime and/or ciprofloxacin from various drug classes have demonstrated efficacy in the treatment of most EO cases. However, in cases of uncomplicated EO that do not respond to standard therapy, an extended treatment duration of two months or an alternative regimen may be necessary.

Availability of data and materials

The raw data of the study are available upon reasonable request. All the data generated or analyzed during the study are included in this manuscript.

Author contributions

AA and MEI—designed the research study. AA, RA, SKS and SFR—collected the data. AA and RA—clinically supervised. AA, NZA, OBA and MEI—analyzed the data. AA, SKS, NZA, OBA and MEI—wrote the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Ethical approval for this study was granted by the Ethical Committee at King Abdullah Hospital, Bisha, Saudi Arabia (E-CTS REF no.BIS-23-00008-20062023) and adhered to the ethical principles outlined in the Helsinki Declaration. Informed consent was not sought as this is a retrospective study, and data were solely extracted from the hospital database.

Acknowledgment

The authors extend their appreciation to the Deanship of Scientific Research, University of Bisha, for funding this research through the promising program under grant number (UB-Promising-46-1445).

Funding

This research was funded by the Deanship of Scientific Research, University of Bisha, Bisha, Saudi Arabia, grant number (UB-Promising-46-1445).

Conflict of interest

The authors declare no conflict of interest.