Gonorrhea Treatment & Management

Updated: Sep 07, 2018
  • Author: Brian Wong, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Treatment

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.

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Pharmacologic Treatment Regimens

Because of resistance with oral cephalosporins, only 1 regimen, dual treatment with ceftriaxone and azithromycin, is recommended for treatment of gonorrhea in the United States. Dual therapy with ceftriaxone and azithromycin should be administered together on the same day, preferably simultaneously and under direct observation. In addition, persons infected with N gonorrhoeae frequently are coinfected with C trachomatis; this finding has led to the longstanding recommendation that persons treated for gonococcal infection also be treated with a regimen that is effective against uncomplicated genital C trachomatis infection, further supporting the use of dual therapy that includes azithromycin. [1]

Combination with azithromycin, versus doxycycline, is preferred because of the more convenient dosing, likely better patient compliance, and reports of increasing resistance to tetracyclines in some Gonococcal Isolate Surveillance Project (GISP) samples.

Uncomplicated urogenital, anorectal, and pharyngeal gonococcal infection

First-line dual drug therapy regimen is as follows [1] :

  • Ceftriaxone 250 mg intramuscular (IM) single dose plus
  • Azithromycin 1 g PO single dose

The 250-mg IM dose of ceftriaxone is now recommended over the 125-mg dose, given concern for resistance, prior lower-dose ceftriaxone dose failures, and seemingly improved efficacy in pharyngeal infections. No benefit has been found for ceftriaxone dosing greater than 250 mg. 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. [61]

Because of the persistent increase in multidrug-resistant gonorrhea, the 2015 CDC treatment recommendations are as follows [1] :

  • Treat gonorrhea at any anatomic site with a single intramuscular injection of 250 mg ceftriaxone plus azithromycin 1 g PO as a single dose
  • If ceftriaxone is unavailable, patients can be given a single oral dose of cefixime 400 mg plus a single dose of azithromycin 1 g PO

Alternative treatment options

Per CDC guidelines, single-dose injectable cephalosporin regimens (other than ceftriaxone 250 mg IM) that are safe and generally effective against uncomplicated urogenital and anorectal gonococcal infections include ceftizoxime (500 mg IM), cefoxitin (2 g IM with probenecid 1 g PO), and cefotaxime (500 mg IM). [62] None of the above regimens offers any additional benefits for urogenital infection and may be more questionable in the treatment of pharyngeal infection. [58, 63]

In patients who are cephalosporin allergic, consider alternant dual therapy with single doses of gemifloxacin PO 320 mg plus azithromycin 2 g PO, or gentamicin 240 mg IM plus azithromycin 2 g PO. [64] Note that, while both of the above regimens seemed to have treated the few extragenital infections in the population studied, it was not powered to give reliable estimates of regimen efficacy. Be aware of treatment-limiting adverse gastrointestinal adverse effects (eg, vomiting) of both of the cephalosporin-allergic regimens, 7.7% and 3.3%, respectively.

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.

If azithromycin allergic, 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. However, be aware of the rising prevalence of tetracycline resistance among GISP isolates.

The CDC recommends that patients should return for a test of cure in 1 week. The CDC advises that clinicians should perform susceptibility testing in patients who fail to respond to treatment and notify their local public health STD program. [65]

Monotherapy with azithromycin is no longer 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. [66]

Investigational and future treatment options

In a clinical trial conducted by the CDC and NIH, 2 new antibiotic regimens successfully treated gonorrhea infections. The 2 regimens consist of gentamicin IV plus azithromycin PO, and gemifloxacin PO plus azithromycin PO. The study was conducted to identify new treatment options in the face of growing antibiotic resistance. [67, 68] While the study results offer successful treatment options, the CDC is not recommending a change in current guidelines due to the severe gastrointestinal side effects reported by trial participants. However, providers may consider using the regimens studied in this trial as alternative options when ceftriaxone cannot be used. [69]

The study of these antibiotic regimens included 401 men and women ranging in age from 15 years to 60 years. The combination treatments were highly effective in curing genital gonorrhea infections. The gentamicin plus azithromycin was found to be 100% effective and the gemifloxacin plus azithromycin was 99.5% effective. Both combinations cured 100% of gonococcal infections of the throat and rectum. [67, 68]

Although highly effective, the regimens frequently caused adverse GI effects. Of the 202 participants in the gentamicin plus azithromycin arm, 28% experienced nausea, 19% experienced diarrhea, and 7% experienced either abdominal discomfort/pain or vomiting. Of the 199 participants in the gemifloxacin plus azithromycin arm, 37% experienced nausea, 23% experienced diarrhea, and 11% experienced abdominal discomfort/pain. [67, 68]

Because of the emergence of multi-drug resistant (MDR) and extensively drug-resistant (XDR) N gonorrhoeae, combinations of available medications have been tested to maximize treatment response. Two combinations showed some promise in vitro: (1) gentamicin plus ertapenem and (2) gentamicin plus cefixime. Further investigation of these two combination regimens for treatment of drug-resistant gonorrhea is necessary prior to mainstream use. [70]

The novel experimental oral antibiotic ETX0914 (Entasis Therapeutics) was found to be safe and efficacious in treating uncomplicated urogenital gonorrhea in a phase 2 clinical trial. The FDA has designated ETX0914 a Qualified Infectious Disease Product and awarded the drug fast-track status. [26]

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 also are likely to be resistant to tetracyclines but susceptible to azithromycin. Consequently, only 1 regimen, dual treatment with ceftriaxone and azithromycin, is recommended for treatment of gonorrhea in the United States. [1]

In August 2012, the CDC announced changes to 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. [61]

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. [6]

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. [62]

Gonococcal conjunctivitis

Treatment recommendations for adults are single doses of ceftriaxone 1 g IM plus azithromycin 1 g PO with saline irrigation. [1, 71] 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). [72]

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. [62]

See the 2015 CDC STD treatment guidelines for treatment of gonococcal infection in children and newborns. [62]

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Consultations

The following consultations should be made in cases of gonococcal infections:

  • Gynecologist - Should be consulted for patients with severe pelvic inflammatory disease (PID) and for any pregnant patient with an STD

  • Pediatrician - Should be consulted for any child with an STD

  • Ophthalmologist - Should be consulted for every patient with gonococcal conjunctivitis, as this disease may progress rapidly and can cause permanent loss of vision

  • 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.

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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 rested 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.

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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. [73, 74]

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. [75]

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). [76, 77] While designed to prevent reinfection with chlamydia and gonorrhea, the recommendations can also be applied to other STDs. The ACOG recommendations include the following:

  • Expedited partner therapy to prevent reinfection, with legalization of expedited partner therapy
  • Counsel partners to undergo screening for HIV infection and other STDs
  • Expedited partner therapy contraindicated in cases of suspected abuse or compromised patient safety; pretreatment evaluation for abuse potential recommended
  • 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 women who are at increased risk for infection, including the following [78] :

  • Patients with previous gonorrheal infection

  • Patients with other STDs

  • Patients with new or multiple sex partners

  • Patients who engage in inconsistent condom use

  • Patients who engage in commercial sex work and drug use

  • 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.

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. [29]

PRO-2000, an antimicrobial gel for the potential prevention of HIV infection, is in phase III trial for the prevention of sexually transmitted infections, including HIV, herpes, chlamydia, and gonorrhea, in Africa. [79]

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HIV Infection

Patients with HIV infection should undergo the same medical and surgical therapy as patients without HIV infection.

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