In females, N. gonorrhoeae most commonly infects the cervix, resulting in cervicitis. When female patients with gonococcal urogenital infections have symptoms, they may complain of vaginal discharge, dysuria, or pelvic pain.[1][13] Gonorrheal infection of the Bartholin’s glands adjacent to the vaginal introitus manifests as labial soft tissue swelling, abscess formation, and pain.[14] If cervicitis goes undetected and untreated, ascending gonococcal infection can result in upper reproductive tract involvement such as salpingitis and pelvic inflammatory disease. Pelvic inflammatory disease can manifest with pelvic pain, infertility, and increase the risk of ectopic pregnancy.[1][15] Gonococcal infections complicating pregnancy can lead to adverse pregnancy outcomes such as low birth weight newborns and transmission to newborns resulting in oropharyngeal or conjunctival infections.[15]

Although many females, more than 50%, will not manifest symptoms of their gonococcal cervix infections, most males, more than 90%, will manifest urogenital gonorrhea symptomatically.[4,13] The most common clinical manifestations of gonococcal disease in males include penile purulent discharge, dysuria, and testicular discomfort.[13] Male urogenital gonococcal complications include orchitis, epididymitis, penile lymphangitis, penile edema, and post-infectious urethral strictures. The prevalence of rectal and pharyngeal gonococcal infections have been increasing among populations of men who have sex with men.[3]

Like cervicitis, gonococcal infection of the pharynx, the rectum, and the female urethra often present asymptomatically or with subtle symptoms.[1] If left untreated, gonorrheal infection of the rectum can proceed to manifest with rectal pain, bleeding, discharge, and proctitis.[1] Uncommonly, N. gonorrhoeae manifest systemically as fever/septicemia, tenosynovitis, arthritis, and vasculitis.[15]

Diagnostic laboratory assays are essential to confirm the clinical suspicion of gonorrhea. Laboratory confirmation of the diagnosis of N. gonorrhoeae infection is made by direct detection of the gonococcal pathogen in urogenital, anorectal, pharyngeal, or conjunctival swab specimens or first-catch urine.[15] 

Populations that engage in anogenital sexual intercourse and/ or insertive oral sex will require screening for gonorrhea from the anus and pharynx in addition to urogenital screening.[3] Confirmation of the clinical suspicion of gonorrhea is established by detection of N. gonorrhoeae or its genetic signature in genital or extragenital samples by light microscopy of stained smears, culture, or nucleic acid amplification tests (NAATs).[4]

The routine utilization of NAATs to screen at-risk asymptomatic patients have demonstrated that pharyngeal and rectal gonococcal infections are not uncommon manifestations.[13] NAATs are generally more than 95% sensitive and specific in urethral and cervical swabs and first catch urine of males.[13] 

The development of commercially available point-of-care assays for N. gonorrhoeae infection has impacted time to treatment. However, while these point-of-care assays have few false-positive results, i.e., they demonstrate high levels of specificity, their sensitivity profiles range widely, with false-negative rates varying from 13% to greater than 90%.[16] Repeat laboratory screening after patient and partner treatment for gonococcal infection enhances eradication efforts.[16] Recently, the development of multiplex NAATs allows for screening of an extensive panel of STDs in addition to N. gonorrhoeae.[15]

Empiric therapy for gonococcal infections is often administered during the initial clinical visit based on historical factors such as sexual intercourse with a person with an STI, or a clinical exam suspicious for an STI, such as penile drip or abnormal vaginal discharge. Worldwide N. gonorrhoeae STD treatment for urogenital infections in males and females most commonly consists of dual therapy with a single intramuscular or intravenous dose of 250 to 500 mg of ceftriaxone in conjunction with a single oral dose of 1 to 2 g of azithromycin orally.[2][6] 

In Canada, an alternative antimicrobial regimen is favored for first-line N. gonorrhoeae treatment of urogenital infections, a single dose of oral cefixime 800 mg paired with a single dose of azithromycin 1 g.[6] Of note, 2 g of oral azithromycin and 800 mg of oral cefixime have notable gastrointestinal adverse effects, such as vomiting.[6]

For complicated gonococcal infections including pelvic inflammatory disease (PID), epididymitis, and proctitis, dual therapy with a single intramuscular or intravenous dose of 250 to 500 mg of ceftriaxone is paired with oral doxycycline 100 mg BID for seven days, rather than a single 1 g dose of azithromycin, because of doxycycline’s effectiveness against C. trachomatis and documented efficacy in treating epididymitis and proctitis.[3] Directly observed therapy, endorsed by the World Health Organization, of gonococcal therapy promotes adherence to therapy and limits treatment failures secondary to noncompliance.[17]

N. gonorrhoeae has evolved antimicrobial resistance utilized for its treatment since the first use of sulfonamides in the 1930s. In some parts of Asia and Europe, gonococcal isolates exhibiting elevated mean inhibitory concentrations to ceftriaxone have been identified, and ceftriaxone treatment failures have been reported. When there is a high suspicion or confirmation of N. gonorrhoeae resistance to standard therapy based on culture and sensitivity results, treatment of urogenital infection with a single dose of gentamicin 240 mg IM with a single dose of azithromycin 1 g orally can be administered. [18] 

In patients with a documented life-threatening allergy to cephalosporins or B-lactam allergy, aztreonam monotherapy can be utilized to treat N. gonorrhoeae infections. Aztreonam 1g administered intravenously treats urogenital gonorrhea and may have efficacy for pharyngeal and rectal gonococcal infection as well when utilizing a 2g dose.[2]

Urogenital symptoms induced by gonorrhea can be observed with other sexually transmitted diseases, as well as non-sexually transmitted illnesses.  Sexually transmitted illnesses that can cause dysuria, penile discharge, abnormal vaginal discharge, and pelvic pain include Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, Mycoplasma genitalium, and herpes simplex virus.[3]

Acute gonococcal infection can impact multiple organ systems. Infectious and noninfectious diseases can cause urethritis, cervicitis, proctitis, conjunctivitis, pharyngitis, and arthritis. Autoimmune, neoplastic, traumatic, and toxicologic etiologies must be considered when evaluating patients presenting with symptoms suspicious for gonorrhea. The gonococcal infection itself can have autoimmune manifestations such as reactive arthritis in association with urethritis and conjunctivitis.[1]

Gonorrhea morbidity has risen over the last 20 years secondary to the progression of antimicrobial resistance.[2]

Complications from gonorrhea result in substantial morbidity and socioeconomic consequences. If the gonorrhea infections are not detected or appropriately treated, they can induce serious complications with reproductive health complications in women, including pelvic inflammatory disease, chronic pelvic pain, infertility, first-trimester abortion, and ectopic pregnancy.[6] Uncommonly, the disseminated gonococcal infection will manifest as septic arthritis or endocarditis. Gonorrheal infection can cause Fitz-Hugh-Curtis syndrome, liver capsule inflammation with resultant intra-abdominal adhesions, in women and male infertility.

Complications specific to males include epididymitis, prostatitis, and proctitis.[1] Immune-mediated, systemic complications following gonorrhea infection can result in the triad of reactive arthritis, urethritis, and conjunctivitis.[1] Gonorrheal infection can complicate obstetrical delivery by infecting newborns via eye contact with genital secretions during the puerperal period and can result in gonococcal conjunctivitis that can progress onto blindness. Gonorrheal infection increases the risk of sexual transmission of HIV-AIDS.[1][13]

The development of N. gonorrhoeae with antimicrobial resistance is a complication that has societal implications. Generally, the development of antimicrobial resistance corresponds to local, regional, and national antibiotic use; populations in countries such as Holland with lower utilization of cephalosporins, macrolides, and fluoroquinolones have a lower incidence of gonococcal resistance than high antibiotic consumption nations.[18]

When treating individuals with suspected or confirmed cephalosporin resistance, clinicians are recommended to consult an infectious disease consultant and report treatment failure to the Centers for Disease Control within 24 hours of laboratory culture confirmation of the diagnosis of antimicrobial-resistant N. gonorrhoeae.[18]

Public health control of gonorrhea depends upon suitable antimicrobial therapy, in tandem with generalized and targeted prevention interventions, use of accurate diagnostic assays, partner notification procedures, and epidemiological surveillance. Antibiotic administration should resolve individual cases to decrease the risk of complications and avert further transmission of the infection.[4]

Patients should abstain from sexual activity for at least 1 week following initiation of antibiotic therapy. Patients should be counseled regarding the necessity to microbiologically confirm a cure of N. gonorrhoeae if they are treated with alternative therapy if significant comorbidities are present, including HIV, or if symptoms persist. Retesting can provide antibiotic susceptibilities that can avoid further treatment failure. Infected patients with gonorrhea are also at increased risk of contracting other STIs, including HIV. Up to 27% of patients diagnosed with HIV have a diagnosis of gonorrhea within 12 months of HIV diagnosis.[19]

The Centers for Disease Control and Prevention advocates for screening pregnant women and women with STI risk factors for N. gonorrhoeae infection. STI risk factors include prior STI diagnoses, non-Latino African American ethnicity, young age, sparse condom use, and multitudinous sexual partners.[16] An interprofessional team consisting of primary care providers, epidemiologists, infectious disease specialists, community health nurses, and pharmacists can improve patient outcomes.