Approach Considerations
As discussed in the Workup section, females with diagnosed or suspected sexually transmitted diseases (STDs) should have a concomitant pregnancy test. This guides further care and allows treatment with medications that are not approved for use in pregnancy.
Identification and treatment of the patient's partner and any partners of the partner are important to prevent reinfection and complications.
Prevention of neonatal disease is with the use of silver nitrate, erythromycin, ciprofloxacin, gentamicin, or erythromycin eye drops.
Inpatient versus outpatient treatment
The main decision once a diagnosis of gonorrhea has been made, either definitively or presumptively, is whether to treat the patient as an outpatient or to hospitalize him or her.
For males, treatment is always outpatient for genital infection; however, admission may be necessary for complications such as disseminated gonococcal infection (DGI) or gonococcal arthritis.
In females, the decision is much more difficult, because the risk of complications is much higher. In light of high rates of noncompliance, reinfection, and poor follow-up, some clinicians advocate admitting a female patient whenever a question of a complication such as pelvic inflammatory disease (PID) is present, particularly in the adolescent population.
Many institutions have attempted to quantify abnormalities found on pelvic examination (ie, the PID score) in an attempt to admit those patients with a higher likelihood of complications.
In cases in which future fertility is at risk, most physicians are fairly aggressive, especially in situations in which the patient is very young or unfamiliar to them.
Many physicians admit patients who have corneal involvement for treatment with IV antibiotics. These patients can be discharged once the infection is under control and the corneal infection is improving.
Surgical care
Septic joints should be aspirated to make the initial diagnosis and to remove inflammatory exudate. Open drainage is rarely indicated, except in infections of the hip in children. Most authorities recommend removal of intrauterine devices in women with PID.
Pharmacologic Treatment Regimens
Uncomplicated urogenital, anorectal, and pharyngeal gonococcal infection
Treatment for uncomplicated urogenital, anorectal, and pharyngeal gonococcal infection is ceftriaxone 500 mg intramuscular (IM) given in a single dose.
Treatment for coinfection with Chlamydia trachomatis with oral doxycycline (100 mg twice daily for 7 days) should be administered when chlamydial infection has not been excluded. Ceftriaxone is safe and effective in pregnant women and probably destroys incubating syphilis. Its major drawback is the necessity for IM administration.
A review of the recommendations for antimicrobial treatment of uncomplicated gonorrhea in 11 East European countries showed ceftriaxone (250-1000 mg IM once) was a first-line antimicrobial in all of them. [57] (However, many of the second-line and alternative treatments were less than ideal, with regionally manufactured antimicrobials predominantly used.)
Data have indicated that the 400-mg oral dose of cefixime does not provide a bactericidal level that is as high or as sustained as that of the 250-mg dose of ceftriaxone and provided a lower cure rate for pharyngeal gonorrhea. The oral cephalosporins cefpodoxime and cefuroxime seem to be inferior and have less desirable pharmacodynamics. [58, 59] In addition, based on findings from the Gonococcal Isolate Surveillance Project (GISP), reported July 2011, from 2009-2010 a decreasing susceptibility to cefixime was found. [60] In response, the CDC issued revised guidelines that do not include oral cephalosporins as first-line treatment. [1]
Alternative treatment options or cephalosporin allergic
In patients who are cephalosporin allergic, a single 240 mg IM dose of gentamicin plus a single 2 g oral dose of azithromycin is an option. [1] Be aware of treatment-limiting adverse gastrointestinal adverse effects (eg, vomiting) of both of the cephalosporin-allergic regimens, 7.7% and 3.3%, respectively. A single 800 mg oral dose of cefixime is an alternative regimen. However, cefixime does not provide as high, or as sustained, bactericidal blood levels as does ceftriaxone and demonstrates limited treatment efficacy for pharyngeal gonorrhea.
Another alternative regimen for patients intolerant of cephalosporins include is spectinomycin (2 g IM). Spectinomycin may be costly and is currently unavailable in the United States.
A test-of-cure is unnecessary for persons with uncomplicated infection, except for persons with pharyngeal gonorrhea, a test-of-cure is recommended using culture or nucleic acid amplification tests 7–14 days after initial treatment, regardless of the treatment regimen. CDC advises that clinicians should perform susceptibility testing in patients who fail to respond to treatment and notify their local public health STD program. [61]
Monotherapy with azithromycin is not recommended because of concerns over the ease with which N gonorrhoeae can develop resistance to macrolides, and because several studies have documented azithromycin treatment failures. Strains of N gonorrhoeae circulating in the United States are not adequately susceptible to penicillins, tetracyclines, or older macrolides (eg, erythromycin); thus, use of these antimicrobials cannot be recommended. [1]
Gonococcal pharyngeal infections may be more challenging to eradicate than infections involving urogenital and anorectal areas. [62]
Drugs that are not primary treatment options
Prior to 2007, fluoroquinolones were the preferred class of antimicrobials for the treatment of gonorrhea; however, reports surfaced of N gonorrhoeae infection with decreasing susceptibilities and frank resistance. In addition, United States gonococcal strains with elevated MICs to cefixime are likely to be resistant to tetracyclines but susceptible to azithromycin.
In August 2012, the CDC announced changes to the 2010 sexually transmitted disease guidelines for gonorrhea treatment. The Gonococcal Isolate Surveillance Project (GISP) described a decline in cefixime susceptibility among urethral N gonorrhoeae isolates in the United States during 2006-2011. Because of cefixime’s susceptibility, new guidelines were issued that no longer recommend oral cephalosporins for first-line gonococcal infection treatment. [63]
In April 2007, the CDC updated treatment guidelines for gonococcal infection and associated conditions. Fluoroquinolone antibiotics were no longer recommended to treat gonorrhea in the United States. The recommendation was based on analysis of new data from the CDC's aforementioned GISP. The data showed the proportion of gonorrhea cases in heterosexual men that were fluoroquinolone-resistant (QRNG) reached 6.7%, an 11-fold increase from 0.6% in 2001. [1]
However, if a patient has an absolute contraindication to cephalosporin and other viable antibiotic options are limited, a fluoroquinolone may still have a role in treatment. In these situations, sensitivity testing would be necessary in the event of treatment failure.
Tetracyclines are no longer acceptable first-line therapy for gonorrhea because of the prevalence of tetracycline-resistant strains. Doxycycline 100 mg PO BID for 7 days can be used in place of azithromycin as an alternative second antimicrobial when used in combination with ceftriaxone or cefixime (also second-line therapy). Furthermore, as cefixime becomes less effective, continued used of cefixime might hasten the development of resistance to ceftriaxone, a safe, well-tolerated, injectable cephalosporin and the last antimicrobial known to be highly effective in a single dose for treatment of gonorrhea at all anatomic sites of infection. Other oral cephalosporins (eg, cefpodoxime and cefuroxime) are not recommended because of inferior efficacy and less favorable pharmacodynamics. The frequency of such gonococcal strains is increasing, having climbed to 5-15% in various US cities. [1]
Gonococcal arthritis
Recommended therapy is with ceftriaxone at 1 g daily IV/IM plus a single dose of azithromycin 1 g PO. Initial IV/IM treatment should be continued for 1-2 days after symptoms improve.
Alternative regimens include cefotaxime or ceftizoxime 1 g IV every 8 hours plus a single dose of azithromycin 1 g PO. [1]
When treating an arthritis-dermatitis syndrome, CDC guidelines allow for switch to an oral antibiotic, when guided by susceptibility testing, after 1-2 days of significant clinical improvement is documented to complete a total course of at least 7 days. [64]
Gonococcal conjunctivitis
Treatment recommendations for adults are single doses of ceftriaxone 1 g IM plus azithromycin 1 g PO with saline irrigation. [1, 65] Topical antibiotic solutions may also be considered. If the cornea is involved or if corneal involvement cannot be excluded due to lid swelling or chemosis, some physicians treat with a 3-day course of IV antibiotics (eg, ceftriaxone 1 g IV q12-24h). [66]
Gonorrhea contributing to pelvic inflammatory disease
All regimens used to treat PID should also be effective against N gonorrhoeae and C trachomatis because endocervical screening that is negative for these organisms does not rule out upper-reproductive–tract infection.
The preferred regimen is a single dose of ceftriaxone 2 g IM plus doxycycline 100 mg PO BID for 14 days with or without metronidazole 500 mg PO BID for 14 days.
Other regimens are also effective and should take into consideration severity of PID and if tubo-ovarian abscess is present. [1]
Gonococcal epididymitis
Recommended therapy includes ceftriaxone 250 mg IM as a single dose with doxycycline 100 mg orally twice daily for a total of 10 days.
Disseminated gonococcal infection
In disseminated infection, it is important to evaluate for evidence of meningitis and endocarditis. Inpatient management and consultation with an infectious disease specialist to decide upon initial regimen are recommended, especially in patients who may be noncompliant with therapy, in whom the diagnosis is uncertain, who have purulent arthritis, or who have other complications.
Gonococcal meningitis and endocarditis
Current recommendations in the treatment of gonococcal meningitis and endocarditis are to use ceftriaxone 1-2 g IV every 12-24 hours plus azithromycin 1 g PO for 1 dose. The exact duration of therapy and any alteration in antibiotics should be discussed with an infectious disease specialist. Of key importance are antimicrobial susceptibility testing and the patient's clinical response to empiric therapy. The 2015 CDC guidelines recommend 10-14 days of parenteral therapy for meningitis and at least 4 weeks of parenteral therapy for endocarditis. [64]
See the 2015 CDC STD treatment guidelines for treatment of gonococcal infection in children and newborns. [64]
Consultations
The following consultations should be made in cases of gonococcal infections:
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Gynecologist - Should be consulted for patients with severe pelvic inflammatory disease (PID) and for any pregnant patient with an STD
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Pediatrician - Should be consulted for any child with an STD
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Ophthalmologist - Should be consulted for every patient with gonococcal conjunctivitis, as this disease may progress rapidly and can cause permanent loss of vision
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Infectious disease specialist - May be of benefit in cases of disseminated gonococcal infection (DGI) or complicated disease courses
In cases of suspected rape or abuse in pediatric patients, seeking specialist help (in the form of specialist nurses or physicians) to interview and collect specimens (if necessary) for testing is prudent. Careful documentation of physical findings, even if apparently normal, is crucial for medicolegal reasons. Notification of child-protective services is required if abuse is suspected.
Monitoring
Per the 2015 CDC Sexually Transmitted Diseases Treatment Guidelines, a test-of-cure is no longer needed for patients with uncomplicated urogenital or rectal gonorrhea who are treated with recommended or alternative regimens.
However, patients with pharyngeal gonorrhea treated with an alternative regimen should be tested for 14 days after treatment and be tested for cure with NAAT assay or culture. Confirmatory testing of the repeat NAAT assays that are positive and further antimicrobial susceptibility testing may be needed.
In many cases, "treatment failure" may result from reinfection from sexual partners who have not received appropriate therapy.
Reevaluation 3 months after treatment is recommended by the CDC. This is distinct and different from immediate test of cure. If 3-month retesting is not possible, the patient should undergo repeat screening at the next medical encounter, within 12 months of treatment.
Instruct patients with uncomplicated gonococcal infections to follow up with a primary care physician or public health provider to reduce the risk of future infection.
Early follow-up care and culture with antibiotic sensitivities are indicated in patients with unresolved or recurrent symptoms despite therapy.
Patients with disseminated gonococcal infection (DGI) or pelvic inflammatory disease (PID) who are treated in an outpatient setting must receive follow-up care within 24 hours.
Deterrence and Prevention
In an effort to minimize transmission of gonorrhea, patients should refrain from all sexual activity for at least 7 days after treatment, and all sexual partners should also undergo appropriate treatment.
The prevention of gonococcal infections is based on education, mechanical or chemical prophylaxis, and early diagnosis and treatment. Condoms offer partial protection, while effective antibiotics taken in therapeutic doses immediately before or soon after exposure can mediate an infection. Several studies have shown that male circumcision status had no statistically significant impact on susceptibility to or acquisition of gonorrhea. [67, 68]
The US Preventive Services Task Force (2008) found that behavioral counseling interventions in multiple sessions conducted in STD clinics and primary care settings effectively reduces the occurrence of STDs in at-risk adults and adolescents. However, they determined that additional studies are needed for evaluation of lower-intensity behavioral counseling interventions and behavioral counseling in lower-risk patient populations. [69]
Preventive measures also include attention to partner notification. Patients should be encouraged to notify their sexual partners of their exposure and encourage them to seek medical care; this is patient referral. If patients are unwilling or unable to notify their partners, then the assistance of state and local departments of public health can be enlisted; this is provider referral.
The American College of Obstetricians and Gynecologists (ACOG) has released guidelines on expedited partner therapy for chlamydial and gonorrheal sexually transmitted diseases (STDs). [70, 71] While designed to prevent reinfection with chlamydia and gonorrhea, the recommendations can also be applied to other STDs. The ACOG recommendations include the following:
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Expedited partner therapy to prevent reinfection, with legalization of expedited partner therapy
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Counsel partners to undergo screening for HIV infection and other STDs
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Expedited partner therapy contraindicated in cases of suspected abuse or compromised patient safety; pretreatment evaluation for abuse potential recommended
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Expedited partner therapy medications and protocols based on CDC, state, and/or local guidelines
Screening
Because of the health risks from asymptomatic gonorrhea, the US Preventive Services Task Force recommends gonorrhea screening of women who are at increased risk for infection, including the following [72] :
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Patients with previous gonorrheal infection
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Patients with other STDs
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Patients with new or multiple sex partners
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Patients who engage in inconsistent condom use
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Patients who engage in commercial sex work and drug use
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Patients living in communities with a high prevalence of disease
Because the prevalence of asymptomatic gonorrhea in men is low, evidence was insufficient for the task force to either recommend or not recommend routine screening of men at increased infection risk.
Doxycycline post-exposure prophylaxis
CDC is evaluating doxycycline post-exposure prophylaxis (doxy-PEP) to prevent gonorrhea, chlamydia, and syphilis following unprotected anal sex in gay and bisexual men and transgender women. [75]
Doxycycline post-exposure prophylaxis was tested in an a randomized open-label trial among men who have sex with men and transgender women living with HIV or on PrEP who had N gonorroheae (GC), C trachomatis (CT), or early syphilis in the past year. Patients were randomized 2:1 to either doxycycline 200 mg PO within 72 hours of condomless sex or no doxycycline with STI testing at enrollment, quarterly, and when symptomatic. Among 360 on PrEP, 65 STI endpoints (29.5%) occurred in controls and 47 (9.6%) in doxy-PEP participants (p < 0.0001). [76]
In an earlier study, participants in a randomized, controlled trial were assigned to take a single oral 200-mg dose of doxycycline PEP (n = 116) within 24 hour after sex or no prophylaxis (n = 116) and followed for a median of 8.7 months.
There were 73 participants who presented with a new STI during follow-up, 28 in the PEP group (9-month probability 22%) and 45 in the no-PEP group (42; p = 0.007). Occurrence of a first STI in participants taking PEP was lower than in those not taking PEP (hazard ratio 0.53; p = 0.008). Similar results were observed for the occurrence of a first episode of chlamydia (HR 0.30; p = 0.006) and of syphilis (HR 0.27; p = 0·047). For a first episode of gonorrhea, results did not differ significantly (HR 0.83; p = 0.52). [77]
Prophylaxis in neonates
All infants born to mothers with untreated gonococcal infection should be treated prophylactically with a single dose of ceftriaxone (25-50 mg/kg IV/IM, not to exceed 125 mg). All neonates should undergo prophylaxis for ophthalmia neonatorum with silver nitrate (1%) aqueous solution in both eyes once or erythromycin (0.5%) ophthalmic ointment in both eyes once.
Research
Several factors, including the lack of an animal model and the diverse antigenic variability of gonorrhea, have made creation of a gonococcal vaccine difficult. Based on rabbit studies, a pilin target was the most likely vaccine candidate. Early tests in military recruits and in volunteers met with some success, but protection was strain-limited, once again because of high antigenic variation of pili. A vaccine toward porins was also evaluated, but induced anti-porin antibodies were not bactericidal. [28]
PRO-2000, an antimicrobial gel for the potential prevention of HIV infection, is in phase 3 trials for the prevention of sexually transmitted infections, including HIV, herpes, chlamydia, and gonorrhea, in Africa. [73]
HIV Infection
Patients with HIV infection should undergo the same medical and surgical therapy as patients without HIV infection.
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This patient presented with gonococcal urethritis, which became systemically disseminated, leading to gonococcal conjunctivitis of the right eye. Courtesy of the CDC/Joe Miller, VD.
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Gonorrhea rates, United States, 1941-2016. Courtesy of the Centers for Disease Control and Prevention (CDC).
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Gonorrhea rates by race/ethnicity, United States, 2012-2016. Courtesy of the Centers for Disease Control and Prevention (CDC).
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Rates of gonococcal infection per 100,000 by state and outlying regions (2016). Courtesy of the Centers for Disease Control and Prevention (CDC).
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Disseminated gonococcemia, acral pustules.
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Cytologic smear of cutaneous acral pustule showing gram-negative, intracellular diplococci.
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Rates of reported gonorrhea cases by age group and sex, United States, 2016. Courtesy of the Centers for Disease Control and Prevention (CDC).
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