Ocular Gonorrhea in Adults

Ocular gonorrhea in an adult usually results from autoinoculation from an infected genital site. As in genital infection, the manifestations range from severe to occasionally mild or asymptomatic disease. The variability in clinical manifestations may be attributable to differences in the ability of the infecting strain to elicit an inflammatory response. Infection may result in a markedly swollen eyelid, severe hyperemia and chemosis, and a profuse purulent discharge. The massively inflamed conjunctiva may be draped over the cornea and limbus. Lytic enzymes from the infiltrating PMNs occasionally cause corneal ulceration and rarely cause perforation.

Prompt recognition and treatment of this condition are of paramount importance. Gram's stain and culture of the purulent discharge establish the diagnosis. Genital cultures should also be performed.

Harrison's Internal Medicine > Chapter 137. Gonococcal Infections 

Gonococcal Resistance to Antimicrobial Agents

It is no surprise that N. gonorrhoeae, with its remarkable capacity to alter its antigenic structure and adapt to changes in the microenvironment, has become resistant to numerous antibiotics. The first effective agents against gonorrhea were the sulfonamides, which were introduced in the 1930s and became ineffective within a decade. Penicillin was then employed as the drug of choice for the treatment of gonorrhea. By 1965, 42% of gonococcal isolates had developed low-level resistance to penicillin G. Resistance due to the production of penicillinase arose later. 

Gonococci become fully resistant to antibiotics either by chromosomal mutations or by acquisition of R factors (plasmids). Two types of chromosomal mutations have been described. The first type, which is drug specific, is a single-step mutation leading to high-level resistance. The second type involves mutations at several chromosomal loci that combine to determine the level as well as the pattern of resistance. Strains with mutations in chromosomal genes were first observed in the late 1950s. As recently as 2004, chromosomal mutations accounted for resistance to penicillin, tetracycline, or both in ~12% of strains surveyed in the United States. 

-Lactamase (penicillinase)–producing strains of N. gonorrhoeae (PPNG) carrying plasmids with the Pc^r determinant had rapidly spread worldwide by the early 1980s. N. gonorrhoeae strains with plasmid-borne tetracycline resistance (TRNG) can mobilize some -lactamase plasmids, and PPNG and TRNG occur together, sometimes along with strains exhibiting chromosomally mediated resistance (CMRNG). Penicillin, ampicillin, and tetracycline are no longer reliable for the treatment of gonorrhea and should not be used. Third-generation cephalosporins have remained highly effective as single-dose therapy for gonorrhea. Even though the minimal inhibitory concentrations (MICs) of ceftriaxone for certain strains may reach 0.015–0.125 mg/L (higher than the MICs of 0.0001–0.008 mg/L for fully susceptible strains), these levels are greatly exceeded in the blood, the urethra, and the cervix when the routinely recommended ceftriaxone and cefixime regimens are administered (see below). These regimens almost always result in an effective cure.

Quinolone-containing regimens were also recommended for treatment of gonococcal infections; the fluoroquinolones offered the advantage of antichlamydial activity when administered for 7 days. However, quinolone-resistant N. gonorrhoeae (QRNG) appeared soon after these agents were first used to treat gonorrhea; in the United States, quinolone-containing regimens are no longer routinely recommended for the treatment of gonorrhea.

QRNG is particularly common in the Pacific Islands (including Hawaii) and Asia, where, in certain areas, all gonococcal strains are now resistant to quinolones. At present, QRNG is also common in parts of Europe and the Middle East. In the United States, QRNG has been identified in midwestern and eastern areas as well as in states on the Pacific coast, where resistant strains were first seen. Alterations in DNA gyrase and topoisomerase IV have been implicated as mechanisms of fluoroquinolone resistance. 

Resistance to spectinomycin, which has been used in the past as an alternative agent, has been reported. Since this agent is usually not associated with resistance to other antibiotics, spectinomycin can be reserved for use against multiresistant strains of N. gonorrhoeae. Nevertheless, outbreaks caused by strains resistant to spectinomycin have been documented in Korea and England when the drug has been used for primary treatment of gonorrhea.

Harrison's Internal Medicine > Chapter 137. Gonococcal Infections 

Gonococcal Cervicitis

Mucopurulent cervicitis is the most common STI diagnosis in American women and may be caused by N. gonorrhoeae, C. trachomatis, and other organisms. Cervicitis may coexist with candidal or trichomonal vaginitis. N. gonorrhoeae primarily infects the columnar epithelium of the cervical os. Bartholin's glands occasionally become infected. 

Women infected with N. gonorrhoeae usually develop symptoms. However, the women who either remain asymptomatic or have only minor symptoms may delay in seeking medical attention. These minor symptoms may include scant vaginal discharge issuing from the inflamed cervix (without vaginitis or vaginosis per se) and dysuria (often without urgency or frequency) that may be associated with gonococcal urethritis. Although the incubation period of gonorrhea is less well defined in women than in men, symptoms usually develop within 10 days of infection and are more acute and intense than those of chlamydial cervicitis. 

The physical examination may reveal a mucopurulent discharge (mucopus) issuing from the cervical os. Because Gram's stain is not sensitive for the diagnosis of gonorrhea in women, specimens should be submitted for culture or a nonculture assay (see below). Edematous and friable cervical ectopy as well as endocervical bleeding induced by gentle swabbing are more often seen in chlamydial infection. Gonococcal infection may extend deep enough to produce dyspareunia and lower abdominal or back pain. In such cases, it is imperative to consider a diagnosis of pelvic inflammatory disease (PID) and to administer treatment for that disease (Chaps. 124 and 169). 

N. gonorrhoeae may be recovered from the urethra and rectum of women with cervicitis, but these are rarely the only infected sites. Urethritis in women may produce symptoms of internal dysuria, which is often attributed to "cystitis." Pyuria in the absence of bacteriuria seen on Gram's stain of unspun urine, accompanied by urine cultures that fail to yield >10⁵ colonies of bacteria usually associated with urinary tract infection, signifies the possibility of urethritis due to C. trachomatis. Urethral infection with N. gonorrhoeae may also occur in this context, but in this instance urethral cultures are usually positive. 

Harrison's Internal Medicine > Chapter 137. Gonococcal Infections 

Gonococcal Infections: Treatment

Treatment failure can lead to continued transmission and the emergence of antibiotic resistance. The importance of adequate treatment with a regimen that the patient will adhere to cannot be overemphasized. Thus highly effective single-dose regimens have been developed for uncomplicated gonococcal infections. The updated 2006 treatment guidelines for gonococcal infections from the Centers for Disease Control and Prevention are summarized in Table 137-1; the recommendations for uncomplicated gonorrhea apply to HIV-infected as well as HIV-uninfected patients. Table 137-1 Recommended Treatment for Gonococcal Infections: 2006 Guidelines of the Centers for Disease Control and Prevention (Updated in 2007) Diagnosis Treatment of Choice Uncomplicated gonococcal infection of the cervix, urethra, pharynx, or rectuma    First-line regimens Ceftriaxone (125 mg IM, single dose) or Cefixime (400 mg PO, single dose) plus Treatment for Chlamydia if chlamydial infection is not ruled out: Azithromycin (1 g PO, single dose) or Doxycycline (100 mg PO bid for 7 days)   Alternative regimens Ceftizoxime (500 mg IM, single dose) or Cefotaxime (500 mg IM, single dose) or Spectinomycin (2 g IM, single dose)b,c or Cefotetan (1 g IM, single dose) plus probenecid (1 g PO, single dose)b or Cefoxitin (2 g IM, single dose) plus probenecid (1 g PO, single dose)b Epididymitis See Chap. 124 Pelvic inflammatory disease See Chap. 124 Gonococcal conjunctivitis in an adult Ceftriaxone (1 g IM, single dose)d   Ophthalmia neonatorume   Ceftriaxone (25–50 mg/kg IV, single dose, not to exceed 125 mg) Disseminated gonococcal infectionf     Initial therapyg       Patient tolerant of -lactam drugs Ceftriaxone (1 g IM or IV q24h; recommended) or Cefotaxime (1 g IV q8h) or Ceftizoxime (1 g IV q8h)     Patients allergic to -lactam drugs Spectinomycin (2 g IM q12h)c   Continuation therapy Cefixime (400 mg PO bid) Meningitis or endocarditis See texth   aTrue failure of treatment with a recommended regimen is rare and should prompt an evaluation for reinfection or consideration of an alternative diagnosis. bSpectinomycin, cefotetan, and cefoxitin, which are alternative agents, currently are unavailable or in short supply in the United States. cSpectinomycin may be ineffective for the treatment of pharyngeal gonorrhea. dPlus lavage of the infected eye with saline solution (once). eProphylactic regimens are discussed in the text. fHospitalization is indicated if the diagnosis is uncertain, if the patient has frank arthritis with an effusion, or if the patient cannot be relied on to adhere to treatment. gAll initial regimens should be continued for 24–48 h after clinical improvement begins, at which time therapy may be switched to one of the continuation regimens to complete a full week of antimicrobial treatment. Treatment for chlamydial infection (as above) should be given if this infection has not been ruled out. hHospitalization is indicated to exclude suspected meningitis or endocarditis. Single-dose regimens of the third-generation cephalosporins ceftriaxone (given IM) and cefixime (given orally) are the mainstays of therapy for uncomplicated gonococcal infection of the urethra, cervix, rectum, or pharynx. Quinolone-containing regimens are no longer recommended in the United States as first-line treatment because of widespread resistance to these agents. Because co-infection with C. trachomatis occurs frequently, initial treatment regimens must also incorporate an agent (e.g., azithromycin or doxycycline) that is effective against chlamydial infection. Pregnant women with gonorrhea, who should not take doxycycline, should receive concurrent treatment with a macrolide antibiotic for possible chlamydial infection. A single 1-g dose of azithromycin, which is effective therapy for uncomplicated chlamydial infections, results in an unacceptably low cure rate (93%) for gonococcal infections and should not be used alone. Spectinomycin has been an alternative regimen for the treatment of uncomplicated gonococcal infections in penicillin-allergic persons. However, spectinomycin is not available in the United States at this time. A single 2-g dose of azithromycin is effective against sensitive strains, but this drug is expensive, causes gastrointestinal distress, and is not recommended for routine or first-line treatment of gonorrhea. Persons with uncomplicated infections who receive a recommended regimen do not need a test of cure. Cultures for N. gonorrhoeae should be performed if symptoms persist after therapy with an established regimen, and any gonococci isolated should be tested for antimicrobial susceptibility. Symptomatic gonococcal pharyngitis is more difficult to eradicate than genital infection. Persons who cannot tolerate cephalosporins and those in whom quinolones are contraindicated may be treated with spectinomycin if it is available, but this agent results in a cure rate of 52%. Persons given spectinomycin should have a pharyngeal sample cultured 3–5 days after treatment as a test of cure. A single 2-g dose of azithromycin may be used in areas where rates of resistance to azithromycin are low.  Treatments for gonococcal epididymitis and PID are discussed in Chap. 124. Ocular gonococcal infections in older children and adults should be managed with a single dose of ceftriaxone combined with saline irrigation of the conjunctivae (both undertaken expeditiously), and patients should undergo a careful ophthalmologic evaluation that includes a slit-lamp examination.  DGI may require higher dosages and longer durations of therapy (Table 137-1). Hospitalization is indicated if the diagnosis is uncertain, if the patient has localized joint disease that requires aspiration, or if the patient cannot be relied on to comply with treatment. Open drainage is necessary only occasionally—e.g., for management of hip infections that may be difficult to drain percutaneously. Nonsteroidal anti-inflammatory agents may be indicated to alleviate pain and hasten improvement of affected joints. Gonococcal meningitis and endocarditis should be treated in the hospital with high-dose IV ceftriaxone (1–2 g every 12 h); therapy should continue for 10–14 days for meningitis and for at least 4 weeks for endocarditis. All persons who experience more than one episode of DGI should be evaluated for complement deficiency.

Prevention and Control Condoms, if properly used, provide effective protection against the transmission and acquisition of gonorrhea as well as other infections that are transmitted to and from genital mucosal surfaces. Spermicidal preparations used with a diaphragm or cervical sponges impregnated with nonoxynol 9 offer some protection against gonorrhea and chlamydial infection. However, the frequent use of preparations that contain nonoxynol 9 is associated with mucosal disruption that paradoxically may enhance the risk of HIV infection in the event of exposure. All patients should be instructed to refer sex partners for evaluation and treatment. All sex partners of persons with gonorrhea should be evaluated and treated for N. gonorrhoeae and C. trachomatis infections if their last contact with the patient took place within 60 days before the onset of symptoms or the diagnosis of infection in the patient. If the patient's last sexual encounter was >60 days before onset of symptoms or diagnosis, the patient's most recent sex partner should be treated. Partner-delivered medications or prescriptions for medications to treat gonorrhea and chlamydial infection diminish the likelihood of reinfection (or relapse) in the infected patient. In states where it is legal, this approach is an option for partner management. Patients should be instructed to abstain from sexual intercourse until therapy is completed and until they and their sex partners no longer have symptoms. Greater emphasis must be placed on prevention by public health education, individual patient counseling, and behavior modification. Sexually active persons, especially adolescents, should be offered screening for STIs. For males, a NAAT on urine or a urethral swab may be used for screening. Preventing the spread of gonorrhea may help reduce the transmission of HIV. No effective vaccine for gonorrhea is yet available, but efforts to test several candidates are under way.

Harrison's Internal Medicine > Chapter 137. Gonococcal Infections