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Home , Abscess, Neisseria, Neisseria gonorrhoeae

Diagnosis and Treatment of gonorrhoeae KARL E. MILLER, M.D., University of Tennessee College of Medicine, Chattanooga Unit, Chattanooga, Tennessee

The most common site of is the urogenital tract. Men with this infection may experi- ence dysuria with penile discharge, and women may have mild vaginal mucopurulent discharge, severe pelvic pain, or no symptoms. Other N. gonorrhoeae infections include anorectal, conjunctival, pharyngeal, and ovarian/uterine. Infections that occur in the neonatal period may cause ophthalmia neonatorum. If left untreated, N. gonorrhoeae infec- tions can disseminate to other areas of the body, which commonly causes synovium and skin infections. Disseminated gonococcal infection presents as a few skin lesions that are limited to the extremities. These legions start as and progress into bullae, petechiae, and necrotic lesions. The most commonly infected joints include wrists, ankles, and the joints of the hands and feet. Urogenital N. gonorrhoeae infections can be diagnosed using culture or nonculture (e.g., the nucleic acid amplification test) techniques. When multiple sites are potentially infected, culture is the only approved diagnostic test. Treatments for uncomplicated urogenital, anorectal, or pharyngeal gonococcal infections include cepha- losporins and fluoroquinolones. Fluoroquinolones should not be used in patients who live in or may have contracted in Asia, the Pacific islands, or California, or in men who have sex with men. Gonorrhea infection should prompt physicians to test for other sexually transmitted diseases, including human virus. (Am Fam Physician 2006;73:1779-84, 1786. Copyright © 2006 American Academy of Family Physicians.)  Patient information: eisseria gonorrhoeae infections female infections A handout on gonorrhea, may present as a broad range In women, common symptoms include written by the author of this article, is provided of symptoms and can affect odorless vaginal discharge; vaginal bleeding, on page 1786. urogenital, anorectal, pharyn- particularly after intercourse; and dyspareu- geal,N and conjunctival areas. Severe cases can nia. Many women have no symptoms, how- lead to disseminated gonococcal infections, ever.2 Physical findings in women include , and ; and in women, with mucopurulent drainage from to pelvic inflammatory disease (PID). the os. The tends to bleed easily when Two methods for detecting N. gonorrhoeae rubbed with a cotton-tipped swab. Gonor- are culture and nonculture tests. Culture rhea infections do not cause , but techniques are considered the tests of choice; other concomitant infections may produce but nonculture techniques, vaginal findings. which are less labor-intensive Ten to 20 percent of women with gonor- Most rectal gonococcal and are similar in accuracy to rhea develop ascending infection that causes infections are subclinical, cultures, have replaced culture acute with or without endome- but symptoms can include techniques in some instances. tritis, also known as PID.2 Presentations anal pruritus and muco­ The newest nonculture tech- may range from no symptoms to severe purulent discharge. nique is the nucleic acid ampli- with a high . PID can fication test. This test has good negatively affect fertility, causing infertil- sensitivity (92 to 96 percent) and specificity ity in 15 percent of patients2; 50 percent of (94 to 99 percent) compared with cultures.1 patients who have three or more episodes of PID develop .2 Urogenital Infections The Centers for Disease Control and Pre- The most common site of N. gonorrhoeae vention (CDC) recommends that physicians infection is the urogenital tract. In women it maintain a low threshold for diagnosing can infect the endocervix and, if an ascend- PID because of significant negative sequelae ing infection develops, it can cause PID. Men associated with this infection.2 The CDC may develop and, occasionally, currently recommends empiric treatment . of PID in women with uterine and adnexal

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Evidence Clinical recommendation rating References

Uncomplicated gonococcal infections of the cervix, , C 2 or rectum should be treated with a single 125-mg dose of (Rocephin) administered intramuscularly. Oral regimens to treat pelvic inflammatory disease should C 2 continue for 14 days. Women younger than 25 years who are sexually active B 2, 12 should be screened annually for gonococcal infections. Fluoroquinolones should not be used to treat gonorrhea C 8 in men who have sex with men.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For more infor- mation about the SORT evidence rating system, see page 1687 or http://www.aafp.org/afpsort.xml.

tenderness or cervical motion tenderness therefore, a higher chance of false negatives if they are at risk of sexually transmitted than do endocervical samples.1 diseases (STDs) and no other causes can be identified.2 Table 12 includes the CDC’s Male Infections criteria for diagnosing PID. Unlike women, men with urogenital infec- In women with urogenital disease, the tions are usually symptomatic. The normal nucleic acid amplification test can detect incubation period is two to six days after gonorrhea by endocervical or urine sample. exposure. Symptoms include purulent penile Urine samples have a lower sensitivity and, discharge and dysuria. The discharge may present at the meatus, which may be ery- thematous. Discharge may be expressed by Table 1 milking the penis. Diagnostic Criteria for PID N. gonorrhoeae may also cause epididy- mitis, which can present as unilateral tes- Minimal criteria ticular pain without discharge or dysuria. Cervical motion tenderness The patient may or may not have a fever. On Uterine or adnexal tenderness examination, the epididymis is swollen and Additional criteria* tender to palpation. Abnormal cervical or vaginal mucopurulent Culture or nonculture techniques can discharge diagnose urogenital gonorrhea in men.1 If Elevated C-reactive protein level the sample is obtained using a urethral swab, Elevated erythrocyte sedimentation rate the physician should milk the penis first. History of gonorrhea or infection Nucleic acid amplification tests using urine Oral temperature greater than 101˚F (38.3˚C) samples provide similar results to that of the White blood cells present on saline urethral swab technique.1 preparation of vaginal secretions Specific criteria Anorectal Infections Evidence of on endometrial biopsy Gonorrhea infections in the rectal area are Laparoscopic abnormalities consistent with PID most common in women and in men who Transvaginal ultrasonography or magnetic have sex with men (MSM). Perianal contam- resonance imaging shows thickened, fluid- ination from a cervical infection or a direct filled tubes with or without free pelvic fluid or tubo-ovarian complex. infection from anal intercourse can cause anorectal infections in women. In MSM, PID = pelvic inflammatory disease. the infection is caused by direct exposure *—Additional criteria may be used to enhance the through anal intercourse. Most rectal gono- specificity of minimal criteria. coccal infections are subclinical. If pres- Information from reference 2. ent, symptoms can include anal pruritus and mucopurulent discharge, usually with

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a bowel movement. Rectal pain, tenesmus, the globe of the eye and blindness. Infants and bleeding are more common in MSM. at risk of gonococcal are those Severe gonococcal rectal infections may be who did not receive prophylaxis for ophthal- difficult to differentiate from inflammatory mia neonatorum, those whose mothers had bowel disease. no prenatal care, and those whose mothers Although data suggest that nucleic acid have a history of STDs or substance abuse. amplification tests can detect rectal gonor- Common findings include of rhea infections,3 the CDC recommends the the conjunctiva and mucopurulent discharge culture technique for a diagnosis.2 How- from the eye. ever, one study 4 showed a high prevalence Testing neonates who have ophthalmia (7 percent) of asymptomatic rectal gonor- neonatorum for N. gonorrhoeae should rhea in MSM; therefore, it may be beneficial begin with a of the conjunctival to screen these patients using nucleic acid exudates. If intracellular gram-negative dip- amplification tests. lococci are present, N. gonorrhoeae infection is presumed and treatment should be initi- Pharyngeal Infections ated. Gonococcal cultures should confirm Pharyngeal infections caused by N. gonor- the diagnosis.2 rhoeae usually occur after orogenital expo- sure; symptoms are mild or absent. On sexual abuse physical examination, the pharynx may be Preadolescent children most commonly con- erythematous or have exudates. Anterior cer- tract gonococcal infections through sexual vical also may be pres- abuse.2 The common presentation is a girl ent. Most cases of pharyngeal infection will with vaginitis symptoms. Pharyngeal and spontaneously resolve with no treatment and rectal infections also may be present, but they usually do not cause adverse sequelae. Treat- are usually asymptomatic. ment should be initiated, however, to reduce A culture method should be used to test the potential for spreading the infection.2 children for N. gonorrhoeae.2 Nonculture The CDC currently recommends cultures to techniques should not be used alone because test patients who have suspected pharyngeal the U.S. Food and Drug Administration gonorrhea.2 has not approved them for use in children. Specimens from the , pharynx, ure- Infections in Children thra, or rectum should be used to isolate There are two distinct categories of gonococ- N. gonorrhoeae. cal infections in children. During the neona- tal period and the first year of life, gonorrhea Disseminated Infection infections can cause Disseminated infection is rare but can occur in (ophthalmia neonatorum); ; rec- 1 to 3 percent of adults who have gonorrhea.2 tal infections; and, in rare cases, . Septic emboli can cause polyar- These infections most commonly develop ticular and derma- Many experts advocate within two to five days after birth, because titis in these patients.2 Symptoms empiric treatment for the neonate is exposed to infected cervical of disseminated infection can chlamydia when treating exudates during delivery. Almost all new range from slight joint pain, a gonococcal infections in children older than few skin lesions, and no fever patients with gonorrhea. one year are caused by sexual abuse. to overt polyarthritis and a high fever. Patients with disseminated gonorrhea ophthalmia neonatorum usually have no urogenital symptoms. N. gonorrhoeae is not the most common cause The skin lesions typically are few and of ophthalmia neonatorum. However, iden- are limited to the extremities; they start as tifying and treating gonorrhea-related oph- papules and progress into hemorrhagic - thalmia neonatorum is important because, tules. Bullae, petechiae, or necrotic lesions if left untreated, it can cause perforation of also may be present. The skin lesions usually

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are resolved if the gonorrhea continues to tion will detect more than 40,000 leukocytes disseminate. Skin lesions and blood cultures per mm3 (40 3 109 per L) and contain gram- usually are negative for N. gonorrhoeae. negative intracellular diplococci. Fluid cul- The joints most commonly affected by dis- tures usually do not grow the organism.2 seminated gonorrhea are the wrists, ankles, Disseminated gonorrhea also may pres- and the joints of the hands and feet. The axial ent as bacterial endocarditis, meningitis, skeleton rarely is involved. Initial aspiration and , although the incidences of of the joint may be negative for infection. If these presentations have declined with the untreated, however, the patient will develop advent of therapy. , which will most likely involve elbows, wrists, knees, or ankles. The joints Treatment will be swollen and warm, and a joint aspira- The CDC’s treatment guidelines for uncom- plicated gonococcal infections are included in Table 2.2 Despite findings that fluoroqui- Table 2 nolones have similar cure rates as ceftriax- Treatment Guidelines for one (Rocephin),5 N. gonorrhoeae has become Uncomplicated Gonococcal increasingly resistant to fluoroquinolones Infections* in some geographic areas. Therefore, the CDC advises against using fluoroquino- Cefixime (Suprax), 400 mg orally† lones to treat gonorrhea infection in patients Ceftriaxone (Rocephin), 125 mg intramuscularly who live or may have acquired infection in Ciprofloxacin (Cipro), 500 mg orally Asia, the Pacific islands (including Hawaii), Levofloxacin (Levaquin), 250 mg orally and California.2 The CDC recently noted (Floxin), 400 mg orally a substantial increase in fluoroquinolone- resistant N. gonorrhoeae in MSM, and it note: All medications are administered as a single dose; fluoroquinolones should not be used in geo- no longer recommends fluoroquinolones as graphic areas of high resistance or in men who have first-line treatment in these patients.6 Eng- sex with men. land, Wales, and Canada also have reported *—Cervical, urethral, rectal. fluoroquinolone-resistant N. gonorrhoeae.7,8 †—This medication has been unavailable at times. PID can be treated on an outpatient basis Information from reference 2. if the patient does not meet hospitalization criteria (Table 3).2 Outpatient treatment may include either of two equally effective oral regimens.2 If parenteral antibiotic therapy is Table 3 indicated, the preferred therapy is cefotetan Criteria for Hospitalizing (Cefotan), 2 g intravenously every 12 hours, Patients with PID or cefoxitin (Mefoxin), 2 g intravenously every six hours, plus (Vibramy- Patient does not respond to oral antimicrobial cin), 100 mg orally or intravenously every therapy. 12 hours. Doxycycline is best administered Patient is pregnant. orally because intravenous doxycycline can Patient has severe illness, and be painful and can adversely affect veins.2 vomiting, or high fever. Table 4 includes CDC treatment guidelines Surgical emergencies (e.g., ) 2 cannot be excluded. for PID. Patient has a tubo-ovarian . Pharyngeal gonococcal infections are Patient is unable to follow or tolerate an more difficult to treat than urogenital or outpatient oral drug regimen. anorectal infections because few antibiotic regimens can reliably cure this infection. The PID = pelvic inflammatory disease. CDC recommends ceftriaxone in a single Information from reference 2. 125-mg dose intramuscularly or ciprofloxa- cin (Cipro) in a single 500-mg dose orally,

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Table 4 Table 5 Treatment Guidelines for Patients Treatment Guidelines for with PID Disseminated Gonococcal Infections

Parenteral regimen Recommended parenteral regimen Cefotetan (Cefotan), 2 g IV every 12 hours Ceftriaxone (Rocephin), 1 g IV or IM every Cefoxitin (Mefoxin), 2 g IV every six hours 24 hours plus Alternative parenteral regimens Doxycycline (Vibramycin), 100 mg orally Cefotaxime (Claforan), 1 g IV every eight hours or IV every 12 hours Ciprofloxacin (Cipro), 400 mg IV every 12 hours Oral regimen A Levofloxacin (Levaquin), 250 mg IV once per day Ofloxacin (Floxin), 400 mg orally twice per day Ofloxacin (Floxin), 400 mg IV every 12 hours Levofloxacin (Levaquin), 500 mg once per day Spectinomycin (Trobicin), 2 g IM every 12 hours with or without Oral regimen* (Flagyl), 500 mg orally twice Cefixime (Suprax), 400 mg twice per day per day Ciprofloxacin, 500 mg twice per day Oral regimen B Levofloxacin, 500 mg once per day Ceftriaxone (Rocephin), single 250-mg dose IM Ofloxacin, 400 mg twice per day Cefoxitin, single 2-g dose IM administered concurrently with probenecid (Benemid), IV = intravenously; IM = intramuscularly. single 1-g dose orally *—Oral therapy should be initiated 24 to 48 hours plus after the patient begins to improve and should con- Doxycycline, 100 mg orally twice per day tinue for at least one week. with or without Information from reference 2. Metronidazole, 500 mg twice per day

PID = pelvic inflammatory disease; IV = intravenously; ceftriaxone, 1 g intravenously or intramus- IM = intramuscularly. cularly every 24 hours, for patients with dis- note: Parenteral regimen may be discontinued 24 hours 2 after clinical improvement. Duration of oral regimens seminated infections. Parenteral is 14 days. should be continued for 24 to 48 hours after Information from reference 2. clinical improvement begins and then oral regimens should begin.2 Fluoroquinolones and are because these regimens have been shown to contraindicated for pregnant women.2 If effectively treat pharyngeal gonorrhea.2 If the patient cannot tolerate , resistance to fluoroquinolone is a concern, the alternative therapy is spectinomycin ceftriaxone is the treatment of choice. (Trobicin), 2 g intramuscularly every 12 Children with ophthalmia neonatorum hours. Both of these regimens have similar or suspected gonococcal infection should be cure rates.9 Table 5 includes CDC treat- treated with ceftriaxone in a single 25- or ment guidelines for disseminated gonococ- 50-mg per kg dose intravenously or intra- cal infections.2 muscularly.2 Total dosage should not exceed 125 mg. Fluoroquinolones should be avoided Concomitant STDs in children who weigh less than 99 lb (45 kg), Ten to 30 percent of patients with gon- because they are at risk of articular cartilage orrhea will have a concomitant chlamydia damage.2 infection; therefore, many experts advocate Patients with suspected disseminated empirically treating chlamydia when treating gonococcal infection should be hospital- patients with gonorrhea.10 The CDC recom- ized initially.2 The evaluation should include mends (Zithromax) in a single examining for clinical signs of endocardi- 1-g dose orally, or doxycycline, 100 mg tis and meningitis. The CDC recommends twice a day for seven days, for patients with

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uncomplicated infections of the cervix, ure- Chattanooga, TN 37403 (e-mail: karl.miller@erlanger. thra, and rectum and possible concomitant org). Reprints are not available from the author. chlamydia infections.2 Author disclosure: Nothing to disclose. Physicians should strongly consider test- ing patients who have confirmed gonococcal REFERENCES infections for other STDs, including human immunodeficiency virus, using CDC guide- 1. Cook RL, Hutchinson SL, Ostergaard L, Braithwaite RS, Ness RB. Systematic review: noninvasive testing for lines for STD testing and treatment, which and Neisseria gonorrhoeae. Ann are available online at http://www.cdc.gov/ Intern Med 2005;142:914-25. std/treatment/.2 Unfortunately, compliance 2. Workowski KA, Levine WC. Sexually transmitted dis- 11 eases treatment guidelines 2002. Centers for Dis- with these guidelines is low. In one study ease Control and Prevention. MMWR Recomm Rep of an emergency department, compliance 2002;51(RR-6)1-78. Accessed online September 14, ranged from 14 to 79 percent with respect 2005, at: http://www.cdc.gov/std/treatment/. to history taking, physical examination, 3. Koumans EH, Johnson RE, Knapp JS, St Louis ME. Labo- ratory testing for Neisseria gonorrhoeae by recently diagnostic testing, treatment, and coun- introduced nonculture tests: a performance review seling about . Less than one third with clinical and public health considerations. Clin of patients included in this study received Infect Dis 1998;27:1171-80. CDC-recommended antibiotics. 4. Young H, Manavi K, McMillian A. Evaluation of ligase chain reaction for the non-cultural detection of rectal and pharyngeal gonorrhea in men who have sex with Screening men. Sex Transm Infect 2003;79:484-6. According to the CDC, all sexually active 5. Hook EW 3d, Jones RB, Martin DH, Bolan GA, Mroc- zkowski TF, Neumann TM, et al. Comparison of cip- women younger than 25 years should be rofloxacin and ceftriaxone as single-dose therapy screened annually for gonorrhea. Women for uncomplicated gonorrhea in women. Antimicrob 25 years of age or older should be screened Agents Chemother 1993;37:1670-3. annually if they have a new sexual partner 6. Centers for Disease Control and Prevention. Increases 2 in fluoroquinolone-resistant Neisseria gonorrhoeae or a history of multiple partners. The U.S. among men who have sex with men — United States, Preventive Services Task Force (USPSTF) 2003, and revised recommendations for gonorrhea recommends that all sexually active women, treatment, 2004. MMWR Morb Mortal Wkly Rep 2004;53:335-8. including those who are pregnant, receive 7. Fenton KA, Ison C, Johnson AP, Rudd E, Soltani M, routine screening if they are at increased Martin I, et al., for the GRASP collaboration. Ciprofloxa- risk of infection.12 Risk factors include age cin resistance in Neisseria gonorrhoeae in England and younger than 25 years, history of an STD, Wales in 2002. Lancet 2003;361:1867-9. 8. Sarwal S, Wong T, Sevigny C, Ng LK. Increasing inci- new or multiple sexual partners, inconsistent dence of ciprofloxacin-resistant Neisseria gonorrhoeae use, and history of prostitution or infection in Canada. CMAJ 2003;168:872-3. drug use.12 The CDC and the USPSTF do 9. Brocklehurst P. Antibiotics for gonorrhoea in pregnancy. not recommend routine screening for men Cochrane Database Syst Rev 2002;(2):CD000098. because they usually are symptomatic.2,12 10. Lyss SB, Kamb ML, Peterman TA, Moran JS, Newman DR, Bolan G, et al, for the Project RESPECT Study Group. Chlamydia trachomatis among patients infected with and treated for Neisseria gonorrhoeae in sexually The Author transmitted disease clinics in the United States. Ann KARL E. MILLER, M.D., is professor in the Department of Intern Med 2003;139:178-85. Family Medicine at the University of Tennessee College 11. Kane BG, Degutis LC, Sayward HK, D’Onofrio G. of Medicine, Chattanooga Unit. He received his medical Compliance with the Centers for Disease Control and degree from the Medical College of Ohio at Toledo and Prevention recommendations for the diagnosis and completed a family practice residency at Flower Memorial treatment of sexually transmitted diseases. Acad Emerg Hospital, Sylvania, Ohio. Dr. Miller is an assistant medical Med 2004;11:371-7. editor for American Family Physician and is editor of the 12. U.S. Preventive Services Task Force. Screening for gon- “Letters to the Editor” department for Family Medicine. orrhea: recommendation statement. AHRQ Publication No. 05-0579-A. Rockville, Md.: Agency for Healthcare Address correspondence to Karl E. Miller, M.D., Research and Quality, May 2005. Accessed online Department of Family Medicine, University of Tennessee June 7, 2005, at: http://www.ahrq.gov/clinic/uspstf05/ College of Medicine, Chattanooga Unit, 1100 E. Third St., gonorrhea/gonrs.htm.

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