Can a patient have a sexually transmitted infection (STI) and scrotal pain with negative Urine Microscopy and Culture (mcs) and negative C-Reactive Protein (CRP) tests?

STI Can Cause Scrotal Pain with Negative Urine MCS and CRP Tests

Yes, a patient can have a sexually transmitted infection (STI) causing scrotal pain despite negative urine microscopy and culture (MCS) and negative C-reactive protein (CRP) tests. 1

Diagnostic Considerations for Scrotal Pain with Negative Tests

STIs as a Cause of Scrotal Pain

• Epididymitis in sexually active men under 35 years is most commonly caused by Chlamydia trachomatis or Neisseria gonorrhoeae, which may present with scrotal pain 1
• These infections can be present even when standard urine tests are negative 1
• Sexually transmitted epididymitis is often accompanied by urethritis, which can be asymptomatic 1

Why Tests May Be Negative

• Urine MCS tests primarily detect bacterial urinary tract infections but may miss STIs 2
• CRP may not be significantly elevated in early or localized infections 3
• A study found no significant association between STIs and positive urine cultures, suggesting they can exist independently 2
• Standard urine cultures do not detect common STI pathogens like Chlamydia and Gonorrhea 1, 4

Recommended Diagnostic Approach

For Suspected STI with Scrotal Pain

• Perform a Gram-stained smear of urethral exudate or intraurethral swab to detect urethritis (>5 polymorphonuclear leukocytes per oil immersion field) 1
• Obtain nucleic acid amplification tests (NAAT) specifically for N. gonorrhoeae and C. trachomatis, either on intraurethral swab or first-void urine 1, 4
• Consider testing for other pathogens such as Mycoplasma genitalium, Ureaplasma urealyticum, and Trichomonas vaginalis 4
• Examine first-void uncentrifuged urine for leukocytes if urethral Gram stain is negative 1

Rule Out Other Causes

• Consider testicular torsion, especially if pain onset is sudden and severe 1, 5
• Ultrasound with Doppler is recommended to evaluate blood flow and rule out torsion 1
• Consider non-infectious causes if all STI tests are negative 6

Treatment Recommendations

Empiric Treatment for Suspected STI Epididymitis

• For patients under 35 years with scrotal pain and suspected STI, even with negative urine MCS and CRP, empiric treatment is recommended with ceftriaxone 250 mg IM in a single dose PLUS doxycycline 100 mg orally twice a day for 10 days. 1
• For patients over 35 years or those with suspected enteric organisms: ofloxacin 300 mg orally twice daily for 10 days or levofloxacin 500 mg orally once daily for 10 days 1
• Adjunctive measures include bed rest, scrotal elevation, and analgesics until inflammation subsides 1

Follow-Up

• Reevaluate if no improvement within 3 days of starting treatment 1
• Persistent swelling or tenderness after completing antibiotics requires comprehensive evaluation 1
• Partner notification and treatment is essential if STI is confirmed or suspected 1

Important Clinical Pearls

• Negative urine MCS and CRP do not rule out STI as a cause of scrotal pain 3, 2
• Chronic scrotal pain syndrome is often treated with antibiotics despite limited evidence supporting bacterial etiology 6
• In one study, only 22% of patients with chronic scrotal pain had clinically relevant bacteria detected 6
• The differential diagnosis for persistent scrotal pain includes tumor, abscess, infarction, testicular cancer, TB, and fungal epididymitis 1