What is the likely cause and treatment of a penile specimen showing Gram-positive diplococci in pairs on a Gram stain?

Gram-Positive Diplococci in Penile Gram Stain: Likely Non-Gonococcal Etiology

Gram-positive diplococci in pairs on a penile/urethral Gram stain are NOT consistent with gonorrhea and likely represent normal skin flora or contaminants, as Neisseria gonorrhoeae characteristically appears as Gram-NEGATIVE intracellular diplococci. 1, 2

Critical Diagnostic Distinction

• Neisseria gonorrhoeae is a Gram-NEGATIVE diplococcus, not Gram-positive, and this is the defining microbiologic characteristic used for presumptive diagnosis of gonococcal urethritis 1, 3, 4
• Gram stain showing polymorphonuclear leukocytes with intracellular Gram-NEGATIVE diplococci in symptomatic men with urethral discharge is diagnostic for gonorrhea with specificity >99% and sensitivity >95% 2
• The presence of Gram-POSITIVE diplococci suggests organisms such as Enterococcus species or skin contaminants like Staphylococcus, which can appear as diplococci or clustered cocci 5

Differential Diagnosis for Gram-Positive Diplococci

• Enterococcus faecalis is a Gram-positive diplococcus that can form clustered cocci and may resemble Streptococcus pneumoniae in clinical specimens 5
• Normal skin flora contamination during specimen collection is a common source of Gram-positive cocci in urethral specimens 5
• If urethritis is present (>5 WBCs per oil immersion field), consider non-gonococcal urethritis (NGU) caused by Chlamydia trachomatis (15-55% of cases), Ureaplasma urealyticum, Mycoplasma genitalium, or Trichomonas vaginalis 1

Recommended Diagnostic Approach

• Obtain nucleic acid amplification tests (NAATs) for both N. gonorrhoeae AND C. trachomatis on urethral swab or first-void urine, as NAATs have superior sensitivity (>95%) and specificity (>99%) compared to Gram stain or culture 2
• Document urethritis by confirming >5 WBCs per oil immersion field on Gram stain of urethral secretions, or >10 WBCs per high power field on first-void urine microscopy 1
• Perform comprehensive STI screening including syphilis serology and HIV testing for all patients with suspected urethritis 1, 2

Treatment Recommendations

If urethritis is documented (>5 WBCs per oil immersion field) but Gram-negative diplococci are absent:

• Treat empirically for non-gonococcal urethritis with Azithromycin 1 g orally in a single dose OR Doxycycline 100 mg orally twice daily for 7 days 1
• Do NOT treat for gonorrhea based solely on Gram-positive diplococci, as this finding does not support gonococcal infection 1, 2
• If high-risk patient unlikely to return for follow-up, consider dual therapy covering both gonorrhea and chlamydia empirically, but this is based on epidemiologic risk, not the Gram stain finding 1

Critical Pitfalls to Avoid

• Do not confuse Gram-positive with Gram-negative diplococci - this is a fundamental error that would lead to incorrect diagnosis and treatment 1, 2, 4
• Do not rely on Gram stain alone to rule out infection in asymptomatic men, as sensitivity for non-gonococcal pathogens is very low (23% for C. trachomatis, 11% for U. urealyticum) 2, 6
• Avoid using Gram stain for endocervical, pharyngeal, or rectal specimens, as it is not sufficiently sensitive or specific for these sites 2
• Recognize that other Gram-negative diplococci (Moraxella catarrhalis, other Neisseria species, Acinetobacter baumannii) can mimic N. gonorrhoeae on Gram stain, requiring culture confirmation 1, 5

Partner Management

• If NAATs confirm N. gonorrhoeae or C. trachomatis infection, instruct patient to refer sex partners from the preceding 60 days for evaluation and treatment 1
• Partners should be treated presumptively for the same infection without waiting for their own test results 1