eMedicine Specialties > Infectious Diseases > Sexually Transmitted Diseases

Gonococcal Infections: Differential Diagnoses & Workup

Author: Brian Wong, MD, Assistant Professor of Medicine, Division of Infectious Diseases, Loma Linda University Medical Center
Coauthor(s): Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus; Renuka Heddurshetti, MD, Fellow in Infectious Diseases, Department of Internal Medicine, State University of New York at Brooklyn; Sanda Cebular, MD, Fellow, Department of Medicine, Section of Infectious Diseases, State University of New York at Brooklyn
Contributor Information and Disclosures

Updated: Apr 21, 2009

Differential Diagnoses

Workup

Laboratory Studies

Laboratory diagnosis of gonococcal infection depends on identification of N gonorrhoeae at an infected site.

• Smears with Gram stain
  • In men, urethritis can be diagnosed using either of two methods of Gram staining.
  • The first is via a urine sample. Preferably, examine the patient at least 2 hours after micturition or before his first morning void. The patient should provide a first-morning void, and the first 10-15 mL of the urine is saved. The urine is centrifuged so that the sediment may be analyzed microscopically under high power or oil immersion. The presence of 10 or more polymorphonuclear leukocytes (PMNs) seen under high power suggests urethritis.
  • The second method is a Gram stain of urethral exudate. The presence of 4 or more PMNs per oil-immersion field is diagnostic for urethritis. In symptomatic males, Gram staining of urethral exudate yields a sensitivity of 90%-98% and a specificity of 95%-98%. However, in asymptomatic males, the sensitivity of the Gram stain is only 60%. Therefore, culture studies are recommended if an asymptomatic gonococcal infection is suggested.
  • The presence of typical gram-negative intracellular diplococci after Gram stain establishes a diagnosis of gonorrhea. If these organisms are not observed, the patient is said to have nongonococcal urethritis. Results are considered equivocal if typical morphotypes not associated with neutrophils are present or if cell-associated but morphologically atypical organisms are observed. A simple Gram stain is probably the method of choice for the detection of gonorrhea in symptomatic males because it is much less expensive and much more rapid than the Gen-Probe method.
  • In women with positive cervical culture results, the Gram stain results from the endocervix are 50%-60% sensitive and 82%-97% specific. In addition, the presence of more than 10 PMNs per high-power field on an endocervical smear is consistent with cervicitis. In women who lack cervices because of hysterectomy, use urethral culture to make the diagnosis.
• Isolation through culture
  • This is the diagnostic criterion standard and should be used whenever practical. A single culture on most selective media yields a sensitivity of 95% or more for urethral specimens from men with symptomatic urethritis. A sensitivity rate of about 80%-90% is found for endocervical infections in women. For maximized yield in cervical specimens, simultaneous inoculation on selective and nonselective media is recommended. Culture may take several days to weeks.
  • Although the urethra is commonly infected in women with gonorrhea, culturing urethral specimens does not materially increase the diagnostic yield except in women who lack cervices because of hysterectomy.
  • Patients with possible DGI should have culture samples taken from all possible mucosal sites (ie, pharynx, urethra, cervix, rectum) and from blood and synovial fluid. Rectal and pharyngeal specimens are inoculated onto selective medium only.
  • When collecting specimens in males, any discharge present at the meatus can be easily recovered for examination. If no discharge is present at the meatus, urethral material must be recovered by inserting and rotating a small swab 2-3 cm into the urethra. A calcium alginate or Rayon swab on a metal shaft is recommended.
  • When collecting specimens in women, the exocervix is first wiped of exudate. A swab is then placed into the external os and rotated for several seconds. However, take care to avoid contact with vaginal mucosa or secretions, as vaginal fluids are inadequate.
  • A small percentage (approximately 5%) of isolated gram-negative diplococci from genital, rectal, and pharyngeal cultures are actually Neisseria meningitidis, which can cause clinical disease that is identical to gonococcal infections of the urethra, cervix, or rectum. Hence, speciation from samples from pharyngeal and rectal sites should be standard, while samples from genital sites are recommended.
  • Antimicrobial susceptibility testing is generally unnecessary except in cases of resistance surveillance testing or cases of disseminated infection.
• Isolation through other bodily fluid cultures
  • In patients who may have DGI, all possible mucosal sites should be cultured (eg, pharynx, cervix, urethra, rectum), as should blood and synovial fluid (in cases of septic arthritis). Three sets of blood cultures should also be obtained. Specimens from any mucosal site should be inoculated immediately in selective media for gonorrheal organisms, such as modified Thayer-Martin, or on chocolate agar at room temperature, which should be incubated in an enriched carbon dioxide environment. The growth of typical oxidase-positive colonies that consist of gram-negative diplococci strongly suggests gonorrhea.
  • Samples from normally sterile sites (eg, blood, CSF, synovial fluid) should be plated on nonselective and broth mediums. On the other hand, rectal and pharyngeal specimens, locations where commensal Neisseria may be present, should be inoculated onto selective medium only.
  • Synovial fluid aspirations in patients with septic arthritis usually yield greater than 50,000 leukocytes/µL, while synovial fluid culture is variably positive. Blood cultures, at this point, are often negative.
  • Gram stain and culture of vesicular or pustular skin lesions had a diagnostic yield of less than 5%. Immunofluorescent techniques may be used to achieve better results.
• No available serologic test is sufficiently sensitive and specific to merit use for screening or diagnostic purposes.

Imaging Studies

• Plain radiography
  • Chest radiography may show elevation of hemidiaphragm in Fitz-Hugh-Curtis syndrome.
  • Joint plain films to evaluate septic joints are often unrevealing but may help to rule out fracture or other disease processes.
• Ultrasonography or CT scan
  • Pelvic ultrasonography or CT scans may show thick dilated fallopian tubes or abscess formation.
  • PID is uncommon in pregnancy. Therefore, ultrasonography is the preferred method used to evaluate for ectopic pregnancy whenever a pregnant patient has signs and symptoms of possible PID.
  • Vaginal ultrasonography and CT scanning may also help to define the cause of pelvic pain syndromes.
  • Abdominal imaging may give indications of peri-hepatic adhesions or abdominal loculated fluid collections or help to exclude other diagnoses.

Other Tests

• Various tests can be used, if available, to detect the antigen or the genome of gonococci in exudates.
  • Nucleic acid amplification tests (NAAT) amplify genetic sequences (DNA or RNA) from a few copies to millions in a short period of time. Variations of this process include ligase chain reaction tests and strand displacement amplification. These tests are very sensitive but expensive, and results must be interpreted carefully because of false-positive results in certain settings.⁹ Some studies have been showing promise of DNA polymerase chain reaction (PCR) of porA pseudogene detection, possibly even in nongenital sites.¹⁰ The CDC recommends careful review of product inserts to be certain appropriate specimens types are collected and the product is used appropriately.
  • DNA probes use a DNA sequence to locate ribosomal RNA of gonorrhea. Cost and availability are limiting factors.
  • Nucleic acid probe signal amplification (NAPSA) detects DNA sequences using RNA probes. Located sequences are then coated with detection antibodies, which then allow detection. One commercial product uses a single test to detect both gonorrhea and chlamydia. More study is needed to evaluate the sensitivity of this technique compared to that of NAAT.
  • Consider verifying positive urogenital nucleic acid detection test results (PCR, ligase chain reactions, strand displacement amplification, ribosomal RNA or DNA sequence amplification tests) when false-positive results are likely. In 2002, the CDC recommended testing a second specimen with a different test to confirm the positive results.¹¹ Australia and the United Kingdom have proposed guidelines to test the initial specimen with supplementary tests using different target sequences. The recommendations were that a result was reported as positive only if both test results were positive.¹²
• Rapid tests/point of care
  • Immunochromatographic strip test (IST) combines antibodies from a patient’s specimen (secretions or urine) and N gonorrhoeae antigens on a nitrocellulose strip. One study showed that this technique yielded a sensitivity of 70% and specificity of 97%.¹³
  • Optical immunoassay (OIA) also uses antigen-antibody reactions (monoclonal), but on a silicon wafer; a positive reaction is evidenced by a color change. A sensitivity of 60% and specificity of 90% was reported. Both rapid tests yield results within 30 minutes and require minimal training to use. Initial test results show some promise, but additional verification of their utility in appropriate settings is still needed.¹⁴

Procedures

• In PID, culdocentesis may demonstrate free purulent exudate and may provide material for Gram staining and culture.
• In DGI, Gram stain of material from unroofed skin lesions may show typical organisms.
• In septic arthritis cases, arthrocentesis may show purulence and/or causative organisms.
• Rarely would CSF fluid yield positive results in cases of meningitis secondary to gonorrhea.

Histologic Findings

Exudate of PMNs is typical. In PID, loss of ciliated columnar epithelium from the fallopian tubes may occur. Tubes, pelvic mesentery, and ovaries may be bound together with dense fibrosis and abscess formation.

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