Neisseria gonorrhoeae
Authors: John S. Moran, MD, MPH, Andreas Tietz, M.D., Timothy A. Mietzner, Ph.D.
Monograph
Neisseria gonorrhoeae, the gonococcus, is a non-spore-forming, nonmotile bacterium that appears under the microscope as a Gram-negative coccus occurring in pairs (diplococci) with flattening of the adjacent sides. Gonococci are adapted to growth on mucous membranes and cannot tolerate drying. Their fragility limits their transmissibility to direct contact between mucous membranes or the direct exchange of infected secretions.
EPIDEMIOLOGY
The requirement for intimate contact to permit transmission makes gonorrhea a classic sexually transmitted infection. Sexual transmission via penile-vaginal, penile-rectal, or penile-pharyngeal contact accounts for the vast majority of cases. The most important means of non-sexual transmission is from mother to child during birth. The gonococcus is a survivor. Despite its being too fragile to be transmitted by food, water, air, or (with very rare exceptions) fomites, it remained a very common infection in most of the world in the preantibiotic era despite sometimes strenuous efforts to control it. The introduction of antimicrobials led to control of gonorrhea in some populations, but despite the natural susceptibility of the gonococci to low concentrations of a wide variety of antimicrobials, 75 years after the discovery of penicillin gonorrhea remains a common infection in much of the world. In the United States, gonorrhea remains one of the most commonly reported infectious diseases with 116 cases per 100,000 population reported in 2003 (7). It is most common among adolescents and young adults, with a peak incidence among females at 15 to 19 years of age (635/100,000 in 2003) and a peak incidence among males at 20 to 24 years of age (466/100,000 in 2003).
CLINICAL MANIFESTATIONS
In males, urethral infection may be asymptomatic or present as a painful but ultimately self-limited urethral inflammation. Acute gonococcal urethritis is characterized by an exuberant granulocytic inflammatory discharge. Fortunately, therapy with an appropriate dose of an antimicrobial agent active against the infecting strain will reliably eradicate infection, obviating the need for a test of cure. Eradication from the urethra is rapid with no viable bacteria recoverable 24 hours after a single dose of antimicrobial (27). Gonococcal orchitis and epidymitis are infrequent complications of urethral infection. Pharyngeal disease may be more common than previously appreciated and anal intercourse may lead to gonococcal proctitis; organisms that are increasingly resistant to conventional antibiotics have been isolated from rectal cultures.
In women, gonococci may cause asymptomatic or symptomatic endocervical infections, or upper genital tract disease. Gonococcal infections of women are closely associated with infertility and as a result, females disproportionately suffer the consequences of infection.
For both men and women, but more commonly in women, local gonococcal infection can progress to bacteremia with attendant septic arthritis. In fact, gonococcal arthritis is the most common etiology of arthritis in young people. When infection involves the eyes, especially in newborns, blindness can result if treatment is not prompt. Rarely, bacteremia results in dissemination to the joints, skin , endocardium or meninges.
LABORATORY DIAGNOSIS
The only rapid test for gonococcal infection is microscopic examination of stained secretions. Detection of polymorphonuclear leucocytes with intracellular Gram-negative diplococci in urethral exudates is reliable for the diagnosis of gonorrhea in men with symptomatic urethritis. It has a sensitivity and specificity comparable to culture isolation followed by oxidase testing and Gram staining of the isolate (10). The Gram stain of cervical secretions is less sensitive for the diagnosis of gonorrhea in women and specificity is inadequate except in skilled hands. The CDC does not recommend the use of Gram stain for the detection of gonococcal infection in asymptomatic men, in women, or at any site other than the urethra (10).
Definitive diagnosis of N. gonorrhoeae infection takes time. Either culture or DNA detection techniques can be used. Culture can be relatively inexpensive and is highly specific when confirmatory tests are used. It is also highly sensitive but only when specimen collection and transport are optimal. The DNA tests, especially the amplified DNA tests, can be highly sensitive and specific but, unlike culture, they provide no specimen for antimicrobial sensitivity testing.
Tests that are not highly specific are often sufficient for making treatment decisions. However, for making decisions about contact notification more specific tests should be used and in cases where the isolation of N. gonorhoeae may be evidence of crime, culture should be used for diagnosis with confirmatory testing and preservation of the isolate.
PATHOGENESIS
N. gonorrhoeae (and N. meningitidis) are obligate human pathogens. These organisms do not produce a specific product or "toxin" that accounts for the symptoms of gonorrhea. Rather it is the ability of these organisms to multiply on mucosal surfaces and avoid host defenses that incites the vigorous host immune response that ultimately causes the disease pathology. The capacity to multiply in vivo is a function of their ability to access growth-essential nutrients from the host, including efficiently scavenging growth-essential iron from human transferring, lactoferrin, or hemoglobin. These organisms evade host defenses by avoiding antigenic detection through the production of a capsule or antigenic variation of surface proteins. They also evade host defenses by invading columnar epithelial cells (e.g., endocervix, urethra, rectum, oropharynx, nasopharynx, and conjunctiva) (38a). Host factors can also contribute as individuals with complement deficiencies are predisposed to infection by pathogenic Neisseria spp.
Gonococci attach primarily to columnar and cuboidal epithelium. After 24-48 hours, they penetrate between and through the cells to reach the submucosal tissues where they stimulate a marked neutrophilic response resulting in sloughing of the epithelium, microabscess formation, and the exudation of pus (54).
Gonococcal infection facilitates transmission of HIV-1. In HIV infected individuals gonococcal urethritis greatly increases shedding of HIV in mucosal secretions and semen (29a). In HIV-negative individuals, gonococcal infection recruits cells and cytokines capable of enhancing acquisition of HIV, and facilitates breaks in mucosal integrity leading to increased virus infectivity.
SUSCEPTIBILITY IN VITRO AND IN VIVO
The gonococcus is a model of adaptability, having developed resistance to sulfonamides, penicillins, tetracyclines, and, recently, to fluoroquinolones. Nevertheless, any individual gonococcal strain has a high probability of being susceptible to single-dose treatment with any of several antimicrobials and all gonococci remain susceptible to single doses of certain cephalosporins.
In Vitro Data
Table 1 shows some recent MIC values from around the world for the antimicrobials most useful against N. gonorrhoeae. The data have many geographical gaps and few studies have differentiated between isolates from men who have sex with men (MSM) and isolates from heterosexuals. In the United States, fluoroquinolone resistance is much more common among MSM (8).
In Vivo Data
Relationship Between In Vitro Susceptibility and Clinical Outcome
Studies of human subjects experimentally infected withN. gonorrhoeae strains of known penicillin susceptibility and treated with varying doses of penicillin showed that eradication of urethral infections in men given single-dose therapy was associated with maintenance of plasma penicillin levels 3 to 4 times the MIC of the infecting strain for at least 7 to 10 hours (28). More recently it has been shown that high cure rates (>97.5%) in clinical trials of fluoroquinolones and cephalosporins for the treatment of urogenital and rectal infections are associated with serum or plasma antimicrobial concentrations of at least four times the MIC90 of the infecting strains persisting for at least 10 hours (42). For pharyngeal infection, high cure rates (≥80%) are associated with high serum or plasma antimicrobial levels that persist for at least 20 hours.
Results of Clinical Trials
Table 2 summarizes the results of clinical trials of the most effective antigonococcal regimens. Reference (42) offers a more comprehensive summary of 87 separate regimens.
ANTIMICROBIAL THERAPY
Uncomplicated Urogenital and Rectal Infections
Criteria for Choosing Regimens for Routine Use
It is important that only regimens with an effectiveness of >95% in clinical trials be used. Less effective regimens would permit onward transmission and obligate the prescriber to reexamine patients after treatment to ensure that they were no longer infectious. Such follow up would be expensive and, in many cases, impossible. Fortunately, there are safe, single-dose regimens that cure nearly 100% of infections, obviating the need for a test of cure. With several safe and effective antigonococcal regimens to choose from, it was proposed that the minimal standard for uncomplicated urogenital or rectal infections should be a proven efficacy of >95% in summed clinical trials with a 95% confidence interval that excludes values <95% (42). However, with resistance to flouroquinolones spreading, such a high standard may be untenable.
In the single-dose regimens used for the treatment of gonorrhea, the recommended antimicrobials are all very safe; hypersensitivity reactions are the greatest concern but even these appear to be rare. The main consideration is oral versus intramuscular administration. Avoiding injections is especially desirable in STD clinics where a substantial proportion of patients may be HIV- or hepatitis B surface antigen-positive.
The cephalosporins and spectinomycin have few contraindications. Fluoroquinolones, on the other hand, are generally considered to be contraindicated for children <18 years of age and for pregnant women. These contraindications are based on extrapolation from animal studies and not on human studies or clinical experience. Studies of children with cystic fibrosis treated with prolonged courses of fluoroquinolones have shown no evidence of toxicity (22, 23, 52).
Cost is an important consideration, especially for public STD clinics and increasingly for all providers. In general, the fluoroquinolones can be purchased for a lower per treatment cost than can the cephalosporins or spectinomycin.
Efficacy against incubating syphilis is no longer an important consideration in the United States because 1) incubating syphilis appears to be uncommon among gonorrhea patients in the United States (44), 2) patients treated for gonorrhea should, in general, be treated presumptively for Chlamydia trachomatis infection as well and the recommended antichlamydia regimens are likely to eradicate incubating syphilis.
Regimens Recommended for the Routine Treatment of Uncomplicated Gonococcal Infections of the Cervix, Urethra, and Rectum in Adult Heterosexuals Unlikely to have Acquired Their Infection from a Foreign Source or in Hawaii or California
Several single-dose regimens have been shown to be safe and highly effective for the treatment of cervical, urethral and rectal infections among adult men and women and are recommended by the CDC for the treatment of infections from a heterosexual, domestic U.S. source: ceftriaxone (125 mg i.m.), cefixime (400 mg p.o.), ciprofloxacin (500 mg p.o.), ofloxacin (400 mg p.o.), or levofloxacin (250 mg p.o.) (9). Fluoroquinolones should not be used in California or Hawaii, to treat MSM, or to treat infections that may have been acquired abroad. All of these regimens should routinely be accompanied with a regimen effective against uncomplicated Chlamydia trachomatis genital infection unless chlamydial infection has been ruled out.
Ceftriaxone in a single injection of 125 mg provides sustained, high bactericidal levels in the blood. Extensive clinical experience indicates that it is safe and effective for the treatment of uncomplicated gonorrhea at all sites, curing 98.8% of uncomplicated urogenital and anorectal infections in published clinical trials. (A 250-mg dose is also acceptable, but so large a dose is unnecessary.)
Cefixime has an antimicrobial spectrum similar to that of ceftriaxone, but the 400-mg oral dose does not provide as high nor as sustained plasma levels as does 125 mg ceftriaxone. In published clinical trials, the 400 mg dose cured 97.3% of uncomplicated urogenital and anorectal infections. The advantage of cefixime is that it can be administered orally. An 800-mg dose may be slightly more effective but is less well tolerated.
Ciprofloxacin is very active against almost all strains of N. gonorrhoeae found in heterosexuals in the United States (excluding Hawaii and California) and, at a dose of 500 mg provides sustained bactericidal levels in the blood that have cured 99.8% of uncomplicated urogenital and anorectal infections in published clinical trials conducted in populations in which fluoroquinolone-resistant strains had not been reported. It is safe, relatively inexpensive, and can be administered orally. Numerous studies have shown that a 250-mg dose is also highly effective (curing 98.7% of uncomplicated urogenital and anorectal infections in published trials) and 250 mg is the dose approved by the Food and Drug Administration for the treatment of uncomplicated urethral and cervical gonorrhea. However, in view of the increasing spread of quinolone-resistant Neisseria gonorrhoeae (QRNG) and the fact that the 250-mg dose is not significantly safer, cheaper, or better tolerated than the 500-mg dose, the 500-mg dose is recommended (22). Because QRNG strains have become common in much of the world, quinolones should not be used to treat infections acquired from someone who may have been infected outside the United States. Quinolones should also not be used to treat infections in MSM.
Ofloxacin is also very active against most strains of N. gonorrhoeae and has favorable pharmacokinetics. The 400 mg oral dose has been very effective for the treatment of uncomplicated urogenital and anorectal infections, curing 98.6% in published clinical trials. Levofloxacin, the active l-isomer of ofloxacin, is twice as active as ofloxacin against N. gonorrhoeae in vitro. In vivo, a single 250-mg oral dose produces about the same peak serum concentration as does a 400-mg oral dose of ofloxacin (2.8 mg/mL compared with 2.9 mg/mL) and has a longer elimination half-life (7.3 hours compared with 4 to 5 hours). Levofloxacin can be used in place of ofloxacin (400 mg) in a single dose of 250 mg.
Patients who can tolerate neither cephalosporins nor fluoroquinolones, spectinomycin in a single 2-g i.m. dose is an acceptable alternative. Spectinomycin is expensive in the United States and must be given by intramuscular injection through a large bore (18 gauge) needle, but it has been effective in published clinical trials, curing 98.2% of uncomplicated urogenital and anorectal infections and resistance remains very rare in the United States (8) and uncommon elsewhere.
Pediatric Infection
Children have not been the subjects of recent clinical trials of gonorrhea therapy so the following recommendations from the CDC are based on clinical experience and expert opinion. Children who weigh 45 kg or more and have uncomplicated gonorrhea should be treated with one of the regimens recommended for adults. (Fluoroquinolones have not been recommended for person less than 18 years of age because they damage articular cartilage in young animals. However, in children treated with ciprofloxacin, no joint damage clearly attributable to quinolone therapy has been observed, even with multiple dose regimens (5). Children who weigh less than 45 kg who have uncomplicated vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis should be treated with a single dose of ceftriaxone (125 mg i.m.). If ceftriaxone cannot be given, an acceptable alternative is spectinomycin (40 mg/kg [maximum 2 g] i.m.) in a single dose but this treatment is unreliable for pharyngeal infections. Some experts use cefixime to treat gonococcal infections in children because it can be administered orally; however, there are no published reports of its safety or effectiveness for this purpose.
Pharyngeal Infections
Gonococcal infections of the pharynx are more difficult to eradicate than are infections at urogenital and anorectal sites (41). Few antigonococcal regimens can be relied upon to cure them more than 90% of the time. The most effective are single doses of ceftriaxone (125 [or 250] mg i.m.) and, for infections not acquired in Asia, the Pacific, Hawaii, or California, ciprofloxacin (500 mg p.o.).
Children weighing ≥ 45 kg, may be treated with one of the regimens recommended for adults. For children weighing <45 kg., the CDC recommends ceftriaxone (125 mg i.m.) or, if ceftriaxone cannot be used, spectinomycin (40mg/kg [maximum 2 g] i.m.). Spectinomycin is unreliable against pharyngeal infections; a culture should be performed 3-5 days after treatment to ensure that the infection has been eradicated.
Eye Infections
Conjunctivitis in Adults and Adolescents
Only one study of the treatment of gonococcal conjunctivitis among adults has been published in recent years (26). In that study, all 12 patients responded well to a single 1-g injection of ceftriaxone. The CDC recommends that a single, 1-g dose of ceftriaxone be administered intramuscularly and suggests that lavaging the eye once with saline be considered (9).
Ophthalmia Neonatorum
CDC recommends that gonococcal neonatal ophthalmia be treated with ceftriaxone (25 50 mg/kg i.v. or i.m.) in a single dose, not to exceed 125 mg. Ceftriaxone should be administered cautiously to hyperbilirubinemic infants, especially those born prematurely. Topical antibiotic therapy alone is inadequate and is unnecessary if systemic treatment is administered. Simultaneous infection with C. trachomatis should be considered when a patient does not respond satisfactorily (9).
Pelvic Inflammatory Disease
The syndrome of pelvic inflammatory disease (PID) results when infection ascends the reproductive tract from the cervix to the fallopian tubes and ovaries. Although PID is the most common complication of genital gonococcal infection, it can be caused by other microbes as well; therapy of PID should cover not only N. gonorrhoeae, but also C. trachomatis, anaerobes, Gram-negative facultative bacteria, and streptococci.
Pointing out the limited data comparing the efficacy of inpatient with outpatient treatment settings, the CDC proposes the following criteria for hospitalization based on observational data and theoretical concerns: surgical emergencies (e.g. appendicitis) cannot be excluded; the patient is pregnant; the patient does not respond clinically to oral antimicrobial therapy; the patient is unable to follow or tolerate an outpatient oral regimen; the patient has severe illness, nausea and vomiting, or high fever; or the patient has a tubo-ovarian abscess (9).
The DC recommends the following parenteral regimens for the treatment of PID: (a) cefotetan 2 g i.v. every 12 h) or cefoxitin (2 g i.v. every 6 h), either accompanied by doxycycline (100 mg p.o. or i.v. every 12 h) Parenteral therapy can be discontinued 24 hours after a patient improves clinically; continuing oral therapy should consist of doxycycline (100 mg p.o. twice a day) to complete a total of 14 days of therapy. When tubo-ovarian abscess is present, many health-care providers use clindamycin or metronidazole with doxycycline for continued therapy rather than doxycycline alone, because it provides more effective anaerobic coverage. (b) clindamycin (900 mg i.v. every 8 h) plus gentamicin (2 mg/kg i.v. or i.m. as a loading dose, followed by 1.5 mg/kg every 8 h) Parenteral therapy can be discontinued 24 hours after a patient improves clinically; continuing oral therapy should consist of doxycycline (100 mg p.o. twice a day) or clindamycin (450 mg p.o. four times a day) to complete a total of 14 days of therapy. When tubo-ovarian abscess is present, many health-care providers use clindamycin or metronidazole with doxycycline for continued therapy (9).
Alternative parenteral regimens are levofloxacin (500 mg i.v. once daily) or ofloxacin (400 mg i.v. every 12 h), plus doxycycline (100 mg p.o. or i.v. every 12 h). Either may be given with or without metronidazole (500 mg i.v. every 8 h) or ampicillin/sulbactam (3 g i.v. every 6 h).
The CDC also recommends the following mainly oral regimens: (a) levofloxacin (500 mg p.o. once daily) or ofloxacin (400 mg p.o. twice a day for 14 days); either may be given with or without metronidazole (500 mg p.o. twice a day for 14 days), (b) ceftriaxone 250 mg i.m. once or cefoxitin 2 g i.m. once in combination with probenecid 1 g p.o. in a single concurrent dose) or a single dose of another parenteral, third-generation cephalosporin (e.g., ceftizoxime or cefotaxime); to any of these regimens should be added doxycycline 100 mg orally twice a day for 14 days. The doxycycline may be given with metronidazole (500 mg p.o. twice a day for 14 days).
Of the antimicrobials recommended for the treatment of PID, the third-generation cephalosporins (especially ceftriaxone) and the fluoroquinolones are the most active against N. gonorrhoeae (except where fluoroquinolone-resistant N. gonorrhoeae are common). However, all regimens are likely to eradicate N. gonorrhoeae, since they include multiple doses and combinations of antimicrobials with activity against gonococci.
Disseminated Gonococcal Infection (DGI)
Disseminated gonococcal infection (DGI) results from gonococcal bacteremia, often resulting in petechial or pustular, acral skin lesions, asymmetrical arthralgias, tenosynovitis or septic arthritis, and is rarely complicated by perihepatitis and, very rarely, by endocarditis or meningitis. No studies of the treatment of DGI have been published in the past 24 years. The CDC recommendations for the treatment of DGI are based on the opinions of experts. Despite the lack of experimental or even observational studies of the efficacy of the recommended regimens, it is reassuring to note that no reports of treatment failures have been published since these recommendations were first made by the CDC in 1989.
Adults
The CDC recommends hospitalization for initial therapy, especially for patients who cannot be relied on to comply with treatment, for those for whom the diagnosis is uncertain, and for those who have purulent synovial effusions or other complications. Patients should be examined for clinical evidence of endocarditis and meningitis. If endocarditis and meningitis are ruled out, patients should initially be treated with ceftriaxone 1 g i.m. or i.v. every 24 hours. Acceptable alternatives are cefotaxime (1 g i.v. every 8 hours),ceftizoxime (1 g i.v. every 8 hours), or spectinomycin (2 g i.m. every 12 hours). If the infecting organism is known to be susceptible to fluoroquinolones, ciprofloxacin (500 mg i.v. every 12 hours), ofloxacin (400 mg i.v. every 12 hours), or levofloxacin (250 mg i.v. daily), Parenteral treatment should be continued for 24 48 hours after improvement begins; then therapy may be switched to cefixime(400 mg p.o. 2 times a day) or ciprofloxacin (500 mg p.o. 2 times a day), ofloxacin (400 mg p.o. 2 times a day), or levofloxacin (500 mg p.o. once a day) to complete a full week of antimicrobial therapy. For gonococcal endocarditis or meningitis, initial therapy should be with 1 2 g of ceftriaxone (i.v. every 12 hours) and therapy should be continued for 10 14 days for meningitis and for at least 4 weeks for endocarditis.
Children
Children who have bacteremia or arthritis should be treated with ceftriaxone (50 mg/kg i.m. or i.v.) in a single dose daily for 7 days if they weigh >45 kg. If they weigh less, they should receive the same treatment except that the maximum daily dose should be no more than 1 g.
Underlying Diseases
HIV
Persons with HIV infection and gonococcal infection should receive the same treatment as persons not infected with HIV.
Pregnancy
There is no evidence that women respond less well to antigonococcal therapy during pregnancy. Two recent, randomized, controlled trials have addressed the treatment of gonococcal infection during pregnancy. In one trial, ceftriaxone (250 mg) cured 95.2% (95% CI 89.2% to 98.5%) of rectal and cervical infections and 100% (95% CI 54.1% to 100%) of pharyngeal infections while spectinomycin (2 g) cured 97.0% (95% CI 91.5% to 99.4%) of rectal and cervical infections and 83.3% (95% CI 35.9% to 99.6%) of pharyngeal infections (6). In the second trial, ceftriaxone (125 mg) cured 96.8% (95% CI 89.0% to 99.6%) of cervical and rectal infections and 100% (95% CI 47.8% to 100%) of pharyngeal infections; cefixime 400 mg cured 96.8% (95%CI 88.8% to 99.6%) of cervical and rectal infections and 100% (95% CI 54.1% to 100%) of pharyngeal infections (50). Because fluoroquinolones cause arthropathy in young animals their use is not recommended in pregnancy, although we found no reports of adverse effects of quinolones on pregnancy outcome in humans and a single, multicenter, prospective, controlled study of 200 exposed women found no evidence of adverse effects (34). Pregnant women infected with N. gonorrhoeae should be treated with a cephalosporin or, if they cannot tolerate a cephalosporin, with spectinomycin.
Allergy, Intolerance, or Adverse Reactions
Persons who cannot tolerate cephalosporins or quinolones should, in general, be treated with spectinomycin. Because spectinomycin is unreliable against pharyngeal infections (curing only 52% of infections in published studies), patients treated with spectinomycin and suspected or known to have pharyngeal infection should have a pharyngeal culture 3-5 days after treatment to verify eradication of infection.
Alternative Therapy
Alternative Cephalosporins
Single-dose alternatives to ceftriaxone and cefixime listed by the CDC are: ceftizoxime (500 mg i.m.), cefotaxime (500 mg i.m.), and cefoxitin (2 g i.m.) with probenecid (1 g p.o.). None of these regimens offers any advantage over ceftriaxone and there is less clinical experience with them for the treatment of uncomplicated gonorrhea. There are no acceptable oral cephalosporin alternatives to the 400-mg cefixime regimen. Neither cefuroxime axetil (1 g) nor cefpodoxime proxetil (200 mg) have been shown to cure more than 95% of uncomplicated urogenital and anorectal infections with a 95% confidence interval that excludes 95%.
Fluoroquinolones
Single-dose quinolone alternatives to ciprofloxacin, ofloxacin, and levofloxacin are gatifloxacin (400 mg p.o.), lomefloxacin (400 mg p.o.), and norfloxacin (800 mg p.o.). They are safe and effective for the treatment of uncomplicated gonorrhea but they are less well studied and none offers any advantage over the recommended fluoroquinolone regimens.
Macrolides
Azithromycin (2 gm p.o.) is highly effective against uncomplicated gonococcal infection but is expensive and too often causes gastrointestinal distress to be recommended for the treatment of gonorrhea. At an oral dose of one gram, azithromycin has cured 97.1% of subjects in published studies but is not recommended by the CDC because of concerns about the development of resistance.
Many other antimicrobials are also active against N. gonorrhoeae, but have no demonstrated advantage over those listed here.
Quinolone-Resistant N. gonorrhoeae (QRNG)
In the 17 years since strains of N. gonorrhoeae with decreased susceptibility to quinolones were first detected (29), strains with decreased susceptibility and strains resistant to quinolones (QRNG) have become common in parts of Asia and the Pacific, North America, and Europe. They appear to remain relatively rare in South America and Africa but surveillance is incomplete. In Asia, where strains with decreased susceptibility to the quinolones were first reported from the Philippines in 1988, QRNG made up 61% of 313 isolates tested in 1999, 54% of 399 tested in 2001 and 56% of 111 tested in 2003 (Table 3). Very high and increasing rates of QRNG are also reported in China, Vietnam, Japan, and Singapore (Table 3). In the nations of Oceania, the few surveillance data available indicate that 0 to 12% of isolates are resistant (Table 3). In most of Europe, surveillance for resistance has been less systematic than in Asia but a recent study found that of 1975 N. gonorrhoeae isolates collected in the United Kingdom 14.1% were fluoroquinolone-resistant and a further 1.6% showed decreased susceptibility (48). In the United States, QRNG remain relatively rare outside of California and Hawaii. Of the isolates collected by CDC's Gonococcal Isolate Surveillance Project (GISP) during 2003, 4.1% wereciprofloxacin resistant (minimum inhibitory concentrations (MICs) > 1.0 μg/mL to ciprofloxacin) but they were heavily concentrated in MSM (among whom 15% of isolates were resistant) and the states of California and Hawaii. Among isolates from heterosexuals outside of California and Hawaii, resistant isolates made up just 0.4% of the GISP sample (8). Elsewhere in the Western Hemisphere, QRNG is rarely reported. One fluoroquinolone-resistant isolate has been reported from South America (20).
Patients infected with QRNG will not necessarily fail to respond to a standard dose of a recommended fluoroquinolone. Resistance to ciprofloxacin, for example, is defined as exhibiting an MIC >1µg/mL but such patients are often cured by a single oral dose of 500 mg. The best data relating in vitro and in vivo susceptibility are from a population of female sex workers in the Philippines with a prevalence of ciprofloxacin resistance of 63%. Among 72 evaluable patients treated with 500 mg of ciprofloxacin, 24 (32%) failed therapy. Failure was related to pretreatment MICs: 2/18 (11%) for MICs <0.06 µg/mL, 0/4 for MICs of 0.125-0.5, 0/6 for MICs of 1-2, and 15/30 (50%) for MICs ≥4 (1).
Because of these and other data, quinolones are no longer recommended for the treatment of gonococcal infections in MSM, infections that may have been acquired in California, Hawaii, or outside the United States, or in sex partners of persons who may have acquired their infection from an MSM or in California, Hawaii, or outside the United States.
Combination Therapy
There are so many safe and effective single agent regimens that combination regimens, with their increased risk of adverse drug reactions, are unnecessary. For complicated infections, treatment with a higher dose of a single agent (e.g., 1 g instead of 125 mg of ceftriaxone for ophthalmia) or with multiple doses of a single agent (e.g., 4 weeks of therapy with ceftriaxone for endocarditis) is recommended, rather than adding a second antigonococcal agent.
Outcome
The anatomic site of infection is related to clinical outcome. A systematic review of published trials of various antimicrobial regimens for the biological cure of uncomplicated N. gonorrhoeae infection found that modern antigonococcal agents eradicate infections of the urethra, cervix and rectum more reliably than infection of the pharynx (41). Cure rates were 96.4% for the male urethra, 98.4% for the female urethra, 98.0% for the cervix, 97.9% for the female rectum, and 95.3% for the male rectum. Cure rates were significantly lower for infections of the pharynx: 83.7% in females and 79.2% in males. Nevertheless, there is a close relationship between efficacy at the pharynx and efficacy at other sites, so that the regimens most effective against urogenital and rectal infections generally are effective against pharyngeal infections as well. An exception to this relationship is spectinomycin (2 g i.m.) which is highly effective against urogenital and rectal infections but has poor efficacy against pharyngeal infection.
ADJUNCTIVE THERAPy
In the treatment of gonococcal ophthalmia, saline lavage of the affected eye may be considered in addition to definitive treatment with a parenteral antimicrobial.
For all gonococcal infections, the CDC recommends adding presumptive treatment for coexistent chlamydial infection to the antigonococcal regimen (see below).
ENDPOINTS FOR MONITORING THERAPY
The goals of therapy are to prevent complications and to render the individual non-infectious. For uncomplicated urogenital or rectal infections, the recommended regimens are so close to 100% effective that no follow up is needed if compliance is assured (i.e., treatment is directly observed) and symptoms resolve. For pharyngeal infections, only ciprofloxacin (500 mg) and (ceftriaxone 125 mg) are more than 90% effective (Table 2). However, most experts believe that pharyngeal infections are self-limited and not highly contagious so follow up cultures are not routinely recommended. For infections at other sites (e.g., the eye) and for disseminated infection, clinical resolution of signs and symptoms are used as endpoints since there is little concern about persistent, asymptomatic infection which would, in any case, not be readily transmissible.
Those persons with symptoms persisting after treatment should be evaluated by culture for N. gonorrhoeae, and any gonococci isolated should be tested for antimicrobial susceptibility. Infections detected after treatment with one of the recommended regimens are more likely to be reinfections than treatment failures.
VACCINES
No antigonococcal vaccine is commercially available or in phase III clinical trials. Study of the immune response to the gonococcus continues to be an area of active research (51, 45).
PREVENTION OR INFECTION CONTROL MEASURES
The acquisition of gonococcal infection is prevented by avoiding unprotected sexual contact with an infected person. Because many infected persons have no signs or symptoms, it is prudent for persons having sex outside of mutually monogamous relationships to use condoms in order to protect themselves and their partners.
CO-EXISTING STDS
Dual Therapy for Gonorrhea and Chlamydial Infection
Persons with gonorrhea are generally at high risk of being infected with Chlamydia trachomatis as well. Recent studies in the United States and United Kingdom found concurrent C. trachomatis in 7–14% of homosexual men with gonorrhea, in 20–30% of heterosexual men, and in 40-50% of women (14,25,30,36,38). The CDC recommends that persons being treated for N. gonorrhoeaeinfection be routinely treated with a regimen effective against genital C. trachomatis infection as well. Recommended antichlamydial regimens include doxycycline (100 mg p.o. 2 times a day for 7 days and azithromycin (1 gram p.o. once). Routine dual therapy without testing can clearly be cost-effective because chlamydia therapy is safe and costs so little (e.g., ≥$0.50 to 1.50 for doxycycline) compared with the cost of testing. Some experts believe that the routine use of dual therapy has contributed to significant decreases in the prevalence of chlamydial infection. In addition to its value as a strategy for the control of chlamydial infection, dual therapy may have a secondary benefit. Because most gonococci in the United States are susceptible to the antimicrobial regimens recommended for the treatment of uncomplicated C. trachomatis infection, routine co-treatment may hinder the evolution and spread of antimicrobial resistant N. gonorrhoeae.
Since the introduction of dual therapy, chlamydial infection prevalence has dropped in some populations and testing for chlamydial infection has become quicker, more sensitive, and more widely available. Where rates of co-infection are low, some clinicians may prefer to use a highly sensitive test for chlamydia rather than treat presumptively. However, presumptive treatment is indicated for patients who may not return for test results.
Screening for Other Sexually Transmitted Diseases
Persons treated for gonorrhea are generally at increased risk for other STDs including HIV infection and should be counseled and screened as appropriate.
Disease Reporting
Gonorrhea is a reportable disease in all 50 states and the District of Columbia.
Management of Sex Partners
Recent sexual contacts of persons treated for gonorrhea and mothers of infected newborns should generally be tested for gonorrhea and treated presumptively. If found to be infected, they should be advised to refer their recent sex partners.
Resistance of N. gonorrhoeae to fluoroquinolones and other antimicrobials is expected to continue to spread which means that surveillance for antimicrobial resistance will continue to be important to guide therapy recommendations. The GISP, which samples approximately 3% of all gonococcal infections reported in men in the U.S. is a mainstay of surveillance. However, surveillance by clinicians is also important. Clinicians who diagnose N. gonorrhoeae infection in a person who was treated with a recommended regimen and who denies re-exposure should perform culture and susceptibility testing of relevant clinical specimens and should report the case to the local health department.
REFERENCES
1. Aplasca De Los Reyes MR, Pato-Mesola V, Klausner JD, Manalastas R, Wi T, Tuazon CU, Dallabetta G, Whittington WL, Holmes KK. A randomized trial of ciprofloxacin versus cefixime for treatment of gonorrhea after rapid emergence of gonococcal ciprofloxacin resistance in The Philippines. Clin Infect Dis 2001;32:1313-18. [PubMed]
2. Arreaza L, Salcedo C, Alcalá B, Berrón S, Martín E, Vázquez JA. Antibiotic resistance of Neisseria gonorrhoeae in Spain: trends over the last two decades. J Antimicrob Chemother 2003; 51:153-156. [PubMed]
3. Berron S, Vazquez JA, Gimenez MJ, de la Fuente L, Aguilar L. In vitro susceptibilities of 400 Spanish isolates of Neisseria gonorrhoeae to gemifloxacin and 11 other antimicrobial agents. Antimicrob Agents Chemother 2000;44:2543-44. [PubMed]
4. Bhuiyan BU, Rahman M, Miah MR, Nahar S, Islam N, Ahmed M, Rahman KM, Albert MJ. Antimicrobial susceptibilities and plasmid contents of Neisseria gonorrhoeae isolates from commercial sex workers in Dhaka, Bangladesh: emergence of high level resistance to ciprofloxacin. J Clin Microbiol 1999;37:1130-36. [PubMed]
5. Burstein GR, Berman SM, Blumer JL, Moran JS. Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: does the benefit outweigh the risk? Clin Infect Dis 2002;35(Suppl 2):S191-9. [PubMed]
6. Cavenee MR, Farris JR, Spalding TR, Barnes DL, Castaneda YS, Wendel GD Jr. Treatment of gonorrhea in pregnancy. Obstet Gynecol 1993;81:33-38. [PubMed]
7. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance, 2003. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, September 2004.
8. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2003 Supplement: Gonococcal Isolate Surveillance Project (GISP) Annual Report - 2003. Atlanta, Georgia: U.S. Department of Health and Human Services, November 2004.
9. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines 2002. MMWR 2002;51 (No. RR-6). [PubMed]
10. Centers for Disease Control and Prevention. Screening Tests To Detect Chlamydia trachomatis and Neisseria gonorrhoeae Infections — 2002. MMWR 2002;51(No. RR-15): 7.
11. Claeys G, Taelman H, Gichangi P, Tyndall M, Ombete J, Verschraegen G, Temmeperman M. Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from men with urethritis in Kenya. Sex Transm Infect 1998;74:294-95. [PubMed]
12. Clendennen TE, Echeverria P, Saengeur S, Kees ES, Boslego JW, Wignall FS. Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand. Antimicrob Agents Chemother 1992;36:1682-87. [PubMed]
13. Clendennen TE 3rd, Hames CS, Kees ES, Price FC, Rueppel WJ, Andrada AB, Espinosa GE, Kabrerra G, Wignall FS. In vitro antibiotic susceptibilities of Neisseria gonorrhoeae isolates in the Philippines. Antimicrob Agents Chemother 1992;36:277-82.[PubMed]
14. Creighton S, Tenant-Flowers M, Taylor CB, Miller R, Low N. Co-infection with gonorrhoea and chlamydia: how much is there and what does it mean? Int J STD AIDS 2003;14:109 -113.[PubMed]
15. Dillon JA, Rubabaza JP, Benzaken AS, Sardinha JC, Li H, Bandeira MG, dos Santos Fernando Filho E. Reduced susceptibility to azithromycin and high percentages of penicillin and tetracycline resistance in Neisseria gonorrhoeae isolates from Manaus, Brazil, 1998. Sex Transm Dis 2001;28:521-26. [PubMed]
16. Dillon JA, Li H, Sealy J, Ruben M, Prabhakar P, The Caribbean GASP Network. Gonococcal Antimicrobial Surveillance Program. Antimicrobial susceptibility of Neisseria gonorrhoeae isolates from three Caribbean countries: Trinidad, Guyana, and St. Vincent. Sex Transm Dis 2001;28:508-14. [PubMed]
17. Famiglietti A, Garcia SD, de Mier CA, Casco R, Belli L, Marcenac F, Vay C, de Torres RA. Evolution of Neisseria gonorrhoeae drug susceptibility in Buenos Aires, Argentina, 1985 99. Sex Transm Infect 2001;77:142. [PubMed]
18. Fekete T, Serfass DA, Lafredo SC, Cundy KR. Susceptibility to cephalosporins of penicillin susceptible and penicillin resistant strains of Neisseria gonorrhoeae from Philadelphia. Antimicrob Agents Chemother 1989;33:164-66. [PubMed]
19. Fekete T, Woodwell J, Cundy KR. Susceptibility of Neisseria gonorrhoeae to cefpodoxime: determination of MICs and disk diffusion zone diameters. Antimicrob Agents Chemother 1991;35:497-99. [PubMed]
20. Fiorito S, Galarza P, Pagano I, Oviedo C, Lanza A, Smayevsky J, Weltman G, Buscemi L, Sanjuan E. Emergence of high level ciprofloxacin resistant Neisseria gonorrhoeae strain in Buenos Aires, Argentina. Sex Transm Infect 2001;77:77. [PubMed]
21. Glatt AE, Cummings M, McCormack W. In vitro activity of temafloxacin compared with those of other agents against 100 clinical isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother 1992;36:1131-32. [PubMed]
22. Green SD. Indications and restrictions of fluoroquinolone use in children. Br J Hosp Med 1996;56:420-23. [PubMed]
23. Burstein GR, Berman SM, Blumer JL, et al. Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: does the benefit outweigh the risk? Clin Infect Dis 2002;35(suppl 2):191-199.[PubMed]
24. Guoming L, Qun C, Shengchun W. Resistance of Neisseria gonorrhoeae epidemic strains to antibiotics: report of resistant isolates and surveillance in Zhanjiang, China: 1998 to 1999. Sex Transm Dis. 2000;27:115-18. [PubMed]
25. Habib AR, Fernando R Efficacy of azithromycin 1g single dose in the management of uncomplicated gonorrhoea. Int J STD AIDS. 2004;15:240-2.[PubMed]
26. Haimovici R, Roussel TJ. Treatment of gonococcal conjunctivitis with single-dose intramuscular ceftriaxone. Am J Ophthalmol 1989;107:511-14. [PubMed]
27. Haizlip J, Isbey SF, Hamilton HA, Jerse AE, Leone PA, Davis RH, Cohen MS. Time required for elimination of Neisseria gonorrhoeae from the urogenital tract in men with symptomatic urethritis: comparison of oral and intramuscular single-dose therapy. Sex Transm Dis 1995;22:145-48. [PubMed]
28. Jaffe HW, SchroeterAL, Reynolds GH, Zaidi AA, Martin JE, Thayer JD. Pharmacokinetic determinants in penicillin cure of gonococcal urethritis. Antimicrob Agents Chemother 1979;15:587-91. [PubMed]
29. Joyce MP, Aying BB, Vaughan GH, Herip DS, Hayes CG, Espinosa G, Andrada A, Daily OP, Laughlin LW. In vitro sensitivity of Neisseria gonorrhoeae to fluoroquinolone antibiotics in the Republic of the Philippines. Presented at the 6th International Pathogenic Neisseria Conference; Callaway Gardens, GA, Oct 16-21, 1988; Abstract E19. [PubMed]
29a. Kaul R, Rowland-Jones SL, Gillespie G, Kimani J, Dong T, Kiama P, Simonsen JN, Bwayo JJ, McMichael AJ, Plummer FA. Gonococcal cervicitis is associated with reduced systemic CD8+ T cell responses in human immunodeficiency virus type 1-infected and exposed, uninfected sex workers. J Infect Dis 2002;185(10):1525-9. Epub 2002 Apr 30. [PubMed]
30. Kent CK, Chaw JK, Wong W, Liska S, Gibson S, Hubbard G, Klausner JD. Prevalence of rectal, urethral, and pharyngeal chlamydia and gonorrhea detected in 2 clinical settings among men who have sex with men: San Francisco, California, 2003. Clin Infect Dis. 2005;41:67-74. [PubMed]
31. Korting HC, Abeck D. One-shot treatment of uncomplicated gonorrhoea with third generation cephalosporins with differing serum half life. Results of a controlled trial with ceftriaxone and cefotaxime. Chemotherapy 1989;35:441- 48. [PubMed]
32. Lesmana M, Lebron CI, Taslim D, Tjaniadi P, Subekti D, Wasfy MO, Campbell JR, Oyofo BA. In vitro antibiotic susceptibility of Neisseria gonorrhoeae in Jakarta, Indonesia. Antimicrob Agents Chemother. 2001;45:359-62. [PubMed]
33. Lewis DA, Ison CA, Livermore DM, Chen HY, Hooi AY, Wisdom AR. A one-year survey of Neisseria gonorrhoeae isolated from patients attending an east London genitourinary medicine clinic: antibiotic susceptibility patterns and patients= characteristics. Genitourin Med 1995:71:13-17. [PubMed]
34. Loebstein R, Addis A, Ho E, Andreou R, Sage S, Donnenfeld AE, Schick B, Bonati M, Moretti M, Lalkin A, Pastuszak A, Koren G. Pregnancy outcome following gestational exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob Agents Chemother 1998;42:1336-39. [PubMed]
35. Lkhamsuren E, Shultz TR, Limnios EA, Tapsall JW. The antibiotic susceptibility of Neisseria gonorrhoeae isolated in Ulaanbaatar, Mongolia. Sex Transm Infect 2001;77:218-19. [PubMed]
36. Lyss SB, Kamb ML, Peterman TA, Moran JS, Newman DR, Bolan G, Douglas JM Jr, Iatesta M, Malotte CK, Zenilman JM, Ehret J,Gaydos C, Newhall WJ, Project RESPECT Study Group. Chlamydia trachomatis among patients infected with and treated for Neisseria gonorrhoeae in sexually transmitted disease clinics in the United States. Ann Intern Med 2003;139:178 -185.[PubMed]
37. Mbwana J, Mhalu F, Mwakagile D, Masesa J, Moshiro C, Sandstrom E. Susceptibility pattern of Neisseria gonorrhoeae to antimicrobial agents in Dar es Salaam. East Afr Med J 1999;76:330-34. [PubMed]
38. McMillan A, Manavi K, Young H. Concurrent gonococcal and chlamydial infections among men attending a sexually transmitted diseases clinic. Int J STD AIDS. 2005;16:357-61. [PubMed]
38a. Mietzner TA, Morse SA. Neisseria. In: Borriello sp et al (ed). Topley and Wilson’s Microbiology and Microbial Infections, 10thedition. Bacteriology Vol 2. London. Hoader Arnold. [PubMed]
39. Moodley P, Pillay C, Goga R, Kharsany AB, Sturm AW. Evolution in the trends of antimicrobial resistance in Neisseria gonorrhoeae isolated in Durban over a 5 year period: impact of the introduction of syndromic management. J Antimicrob Chemother 2001:48:853-59. [PubMed]
40. Moodley P, Sturm AW. Ciprofloxacin resistance in Neisseria gonorrhoeae. Lancet 2001;357:1295-96. [PubMed]
41. Moran JS. Treating Uncomplicated Neisseria gonorrhoeae infections: Is the anatomic site of infection important? Sex Transm Dis 1995;22:39-47. [PubMed]
42. Moran JS, Levine WC. Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin Infect Dis 1995;20(Suppl 1):S47-65. [PubMed]
43. Moran JS. Ciprofloxacin for gonorrhea--250 mg or 500 mg? Sex Transm Dis 1996;23:165-67. [PubMed]
44. Peterman TA, Zaidi AA, Lieb S, Wroten JE. Incubating syphilis in patients treated for gonorrhea: a comparison of treatment regimens. J Infect Dis 1994;170:689-92. [PubMed]
45. Plante M, Jerse A, Hamel J, Couture F, Rioux CR, Brodeur BR, Martin D. Intranasal immunization with gonococcal outer membrane preparations reduces the duration of vaginal colonization of mice by Neisseria gonorrhoeae.. J Infect Dis 2000;182:848-55.[PubMed]
46. Plourde PJ, Tyndall M, Agoki E, Ombette J, Slaney LA, D'Costa LJ, Ndinya-Achola JO, Plummer FA. Single-dose cefixime versus single-dose ceftriaxone in the treatment of antimicrobial-resistant Neisseria gonorhoeae infection. J Infect Dis 1992;166:919-22.[PubMed]
47. Portilla I, Lutz B, Montalvo M, Mogabgab WJ. Oral cefixime versus intramuscular ceftriaxone in patients with uncomplicated gonococcal infections. Sex Transm Dis 1992;19:94-98.[PubMed]
48. GRASP Steering Group. The Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) Year 2004 report. London: Health Protection Agency 2004. http://www.hpa.org.uk/infections/topics_az/hiv_and_sti/sti-gonorrhoea/publications/grasp_report_20043.pdf
49. Rahman M, Alam A, Nessa K, Nahar S, Dutta DK, Yasmin L, Monira S, Sultan Z, Khan SA, Albert MJ. Treatment failure with the use of ciprofloxacin for gonorrhea correlates with the prevalence of fluoroquinolone-resistant Neisseria gonorrhoeae strains in Bangladesh. Clin Infect Dis 2001 Mar 15;32:884-89. [PubMed]
50. Ramus RM, Sheffield JS, Mayfield JA, Wendel GD Jr. A randomized trial that compared oral cefixime and intramuscular ceftriaxone for the treatment of gonorrhea in pregnancy. Am J Obstet Gynecol 2001;185:629-32. [PubMed]
51. Russell MW, Hedges SR, Wu HY, Hook EW 3rd, Mestecky J. Mucosal immunity in the genital tract: prospects for vaccines against sexually transmitted diseases--a review. Am J Reprod Immunol 1999;42:58-63. [PubMed]
52. Schaad UB. Use of quinolones in children and articular risk. Arch Pediatr 1996;3:183-84. [PubMed]
53. Schäfer V, Enzensberger R, Schneider C, Rickmann J, Nitschke-Özbay H, Brade V. Epidemiology of penicillin-resistant Neisseria gonorrhoeae in Frankfurt, Germany. Eur J Clin Microbiol Infect Dis 1995;14:914-18. [PubMed]
54. Sparling PF, Handsfield HH. Neisseria gonorrhea. In: Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. Churchill Livingstone, Philadelphia, PA, 6th Edition 2004.[PubMed]
55. Swanston WH, Ali C, Mahabir BS, Prabhakar P, Basraj S, George J. Antibiotic Susceptibility of Neisseria gonorrhoeae in Trinidad and Tobago. WI Med J 1997;46:107-110. [PubMed]
56. Talbot H, Romanowski B. In vitro activities of lomefloxacin, tetracycline, penicillin, spectinomycin, and ceftriaxone against Neisseria gonorrhoeae and Chlamydia trachomatis. Antimicrob Agents Chemother 1989;33:2049-51. [PubMed]
57. Tanaka M, Matsumoto T, Kobayashi I, Uchino U, Kumazawa J. Emergence of in vitro resistance to fluoroquinolones in Neisseria gonorrhoeae isolated in Japan. Antimicrob Agents Chemother 1995;39:2367-370. [PubMed]
58. Tanaka M, Nakayama H, Haraoka M, Saika T, Kobayashi I, Naito J. Antimicrobial resistance of Neisseria gonorrhoeae and high prevalence of ciprofloxacin resistant isolates in Japan, 1993 to 1998. J Clin Microbiol 2000;38:521-5. [PubMed]
59. Van Dyck E, Crabbé F, Nzila N, Bogaerts J, Munyabikali JP, Ghys P, Diallo M, Laga M. Increasing resistance of Neisseria gonorrhoeae in West and Central Africa: Consequences on therapy of gonococcal infection. Sex Transm Dis 1997;24:32-37.[PubMed]
60. Van Dyck E, Karita E, Abdellati S, Dirk VH, Ngabonziza M, Lafort Y, Laga M. Antimicrobial susceptibilities of Neisseria gonorrhoeae in Kigali, Rwanda, and trends of resistance between 1986 and 2000. Sex Transm Dis 2001 Sep;28(9):539-45. [PubMed]
61. Wenling C, Xibao Z, Shi F, Minchang W, Ping L, Debiao W, Jinlan Y. Analysis of the antibiotic sensitivity of Neisseria gonorrhoeae in Guangzhou, Peoples Republic of China. Sex Transm Dis. 2000;27:480-2. [PubMed]
62. Wagner J, Tebbe B, Hornle R, Chahin M, Arvand M, Wendt C, Orfanos CE, Hahn H. Antibiotikaempfindlichkeit von Neisseria gonorrhoeae Isolaten in Berlin (Antibiotic sensitivity of Neisseria gonorrhoeae isolates in Berlin) Hautarzt 2000;51:666-69. [PubMed]
63. West B, Changalucha J, Grosskurth H, Mayaud P, Gabone RM, Ka-Gina G, Mabey D. Antimicrobial susceptibility, auxotype and plasmid content of Neisseria gonorrhoeae in Northern Tanzania: emergence of high level plasmid mediated tetracycline resistance. Genitourin Med 1995;71:9-12. [PubMed]
64. Youssef RZ, Murray M, Holmes B, Mogabgab WJ. Cefotetan therapy for gonococcal urethritis and cervicitis. Sex Transm Dis 1990;17:99-101. [PubMed]
Table 1 - In Vitro Activities of Selected Antimicrobials against Neisseria gonorrhoeae
Antimicrobial | MIC50(mg/L) | MIC90(mg/L) | MIC range (mg/L) | Number of strains | Source of isolates (country and year)* | Reference |
---|---|---|---|---|---|---|
Cephalosporins | ||||||
Cefixime | 0.008 | 0.030 | 6552 | USA 2003 | CDC 2003 (7) | |
<0.002 | 0.008 | <0.002-0.06 | 150 | Germany 1988-92 | Schäffer 1995 | |
<0.015 | <0.015 | <0.0015-0.12 | 104 | London, United Kingdom n.r. >95 | Lewis 1995 | |
<0.001 | 0.03 | <0.001-8.0 | 328 | Thailand 1990 | Clendennen 1992a | |
0.015 | 0.06 | 0.008-0.12 | 164 | Nairobi, Kenya 1989-90 | Plourde 1992 | |
0.03 | 0.25 | 0.002-0.5 | 211 | Fukuoka City, Japan 2002 | Tanaka 2004 | |
Cefotaxime | <0.015 | 0.03 | <0.0015-0.12 | 104 | London, United Kingdom n.r. >95 | Lewis 1995 |
0.001 | 0.004 | 0.001-0.016 | 122 | Indonesia 1996 | Lesmana 2001 | |
0.031 | 0.125 | 0.004-0.25 | 79 | Japan 1992-93 | Tanaka 1995 | |
0.03 | 0.06 | <0.001-8.0 | 333 | Thailand 1990 | Clendennen 1992a | |
0.03 | 1 | 0.002->8 | 134 | Philippines 1989 | Clendennen 1992b | |
0.008 | 0.015 | 0.004-0.06 | 130 | Mwanza, Tanzania 1992 | West 1995 | |
Cefotetan | - | 0.5 | 0.03-8 | 150 | New Orleans, Louisiana, USA 1989 | Youssef 1990 |
Cefoxitin | 0.5 | 1 | 0.5-1.0 | 129 | Philadelphia, USA 1987 | Fekete 1989 |
1.0 | 2 | 0.03-4 | 400 | Spain 1992-99 | Berron 2000 | |
0.250 | 1 | 0.016-2.0 | 122 | Indonesia 1996 | Lesmana 2001 | |
1 | 2 | 0.060-8.0 | 332 | Thailand 1990 | Clendennen 1992a | |
1 | 4 | 0.06->8 | 134 | Philippines 1989 | Clendennen 1992b | |
Cefpodoxime | 0.008 | 0.03 | 0.001-0.125 | 77 | USA (n.r.) >91 | Fekete 1991 |
0.03 | 0.125 | <0.004->4.0 | 331 | Thailand 1990 | Clendennen 1992a | |
0.03 | 2 | 0.002->4 | 134 | Philippines 1989 | Clendennen 1992b | |
Ceftizoxime | 0.004 | 0.016 | 0.001-0.016 | 89 | Germany (n.r.) >89 | Korting 1989 |
0.015 | 0.03 | <0.001->4.0 | 333 | Thailand 1990 | Clendennen 1992a | |
0.008 | 0.25 | <0.001->4 | 137 | Philippines 1989 | Clendennen 1992b | |
Ceftriaxone | 0.004 | 0.015 | 6552 | USA 2003 | CDC 2003 (7) | |
0.004 | 0.008 | 0.00025-0.016 | 81 | Manaus, Brazil 1998 | Dillon 2001a | |
0.001 | 0.001 | 0.001 - 0.008 | 81 | Buenos Aires, Argentina 1995-96 | Famiglietti 2001 | |
0.004 | 0.016 | 0.002-0.064 | 507 | Trinidad, Trinidad and Tobago1992 | Swanston 1997 | |
0.003 | 0.01 | 0.0005-0.12 | 400 | Spain 1992-99 | Berron 2000 | |
<0.007 | <0.007 | <0.007-0.030 | 85 | Berlin, Germany 1995-97 | Wagner 2000 | |
0.03 | 2 | 0.016-2.048 | 91 | Zhanjiang, China 1998-99 | Guoming 2000 | |
0.0312 | 0.125 | 0.25-0.002 | 203 | Guangzhoou, China 1997-98 | Wenling 2000 | |
0.015 | 0.06 | 0.004-0.5 | 94 | Dhaka, Bangledesh 1997 | Bhuiyan 1999 | |
0.001 | 0.002 | 0.001-0.008 | 122 | Jakarta, Indonesia 1996 | Lesmana 2001 | |
0.008 | 0.03 | <0.001-1.0 | 333 | Thailand 1990 | Clendennen 1992a | |
0.008 | 0.06 | <0.001->1.0 | 134 | Philippines 1989 | Clendennen 1992b | |
0.004 | 0.008 | 0.002-0.060 | 139 | Kigali, Rwanda 1999-2000 | Van Dyck 2001 | |
<0.007 | 0.015 | <0.007 - 0.06 | 354 | Durban, South Africa 1997-2000 | Moodley 2001a | |
<0.002 | 0.004 | <0.002-0.032 | 177 | Nairobi, Kenya 1995-96 | Claeys 1998 | |
0.015 | 0.06 | 0.002-0.25 | 110 | Guanzhou, China 2001 | Zheng 2005 | |
0.004 | 0.032 | <0.001-0.063 | 91 | Cuba 1995-98 | Sosa 2003 | |
0.015 | 0.06 | 0.002-0.12 | 211 | Fukuoka City, Japan 2002 | Tanaka 2004 | |
0.004 | 0.016 | 0.004-0.03 | 413 | New Zealand 2002 | Heffernan 2004 | |
<0.001 | 0.008 | <0.001-0.032 | 936 | London, U.K. 2003 | GRASP 2004 | |
0.02 | 0.004 | <0.001-0.032 | 1039 | England and Wales excluding London, U.K. 2003 | GRASP 2004 | |
Cefuroxime | 0.032 | 0.125 | 0.001 - 0.5 | 81 | Buenos Aires, Argentina 1995-96 | Famiglietti 2001 |
0.064 | 0.128 | 0.008-1 | 506 | Trinidad, Trinidad and Tobago1992 | Swanston 1997 | |
0.03 | 0.125 | <0.002-0.5 | 150 | Germany 1988-92 | Schäffer 1995 | |
0.5 | 1 | 0.06-4.0 | 94 | Dhaka, Bangladesh 1977 | Bhuiyan 1999 | |
0.5 | 1 | <0.030->4.0 | 333 | Thailand 1990 | Clendennen 1992a | |
0.125 | 2 | 0.015->8.0 | 135 | Philippines 1989 | Clendennen 1992b | |
0.03 | 0.5 | 0.016-256 | 199 | Dar es salaam, Tanzania 1993-95 | Mbwana 1999 | |
0.06 | 0.25 | 0.008-1 | 130 | Mwanza, Tanzania 1992 | West 1995 | |
Quinolones | ||||||
Ciprofloxacin | 0.004 | 0.008 | 6552 | USA 2003 | CDC 2003 (7) | |
0.004 | 0.008 | 0.004-0.25 | 81 | Manaus, Brazil 1998 | Dillon 2001a | |
0.008 | 0.032 | 0.001 - 0.5 | 81 | Buenos Aires, Argentina 1995-1996 | Famiglietti 2001. | |
0.003 | 0.01 | 0.001-0.25 | 400 | Spain 1992-99 | Berron 2000 | |
0.007 | 4 | <0.0015-64 | 81 | Spain, 2001 | New reference ARREAZA 2005 | |
<0.007 | <0.007 | <0.007-8.0 | 84 | Berlin, Germany 1995-97 | Wagner 2000 | |
<0.004 | 0.008 | <0.004-0.06 | 104 | London, United Kingdom n.r. >95 | Lewis 1995 | |
<0.03 | 1.0 | <0.03-4.0 | 56 | Ulaanbaatar, Mongolia n.r. (2001) | Lkhamsuren 2001 | |
2 | 2 | 0.032-2.048 | 91 | Zhanjiang, China 1998-99 | Guoming 2000 | |
0.015 | 1.0 | 0.004-4.0 | 94 | Dhaka, Bangladesh 1997 | Bhuiyan 1999 | |
2 | 8 | 0.008-64 | 115 | Philippines 1996-97 | Aplaxca 2001 | |
0.004 | 0.016 | 0.001-0.016 | 122 | Jakarta, Indonesia 1996 | Lesmana 2001 | |
0.004 | 0.008 | <0.001-2.0 | 329 | Thailand 1990 | Clendennen 1992a | |
0.004 | 0.25 | <0.001->2.0 | 135 | Philippines 1989 | Clendennen 1992b | |
0.004 | 0.008 | 0.002-0.15 | 139 | Kigali, Rwanda 1999-2000 | Van Dyck 2001 | |
<0.007 | 0.015 | <0.007 - 0.06 | 354 | Durban, South Africa 1997-2000 | Moodley 2001a | |
<0.007 | 0.03 | <0.007-0.06 | 204 | Durban (urban), South Africa 1999 | Moodley 2001b | |
<0.007 | 0.015 | <0.007-1.0 | 156 | KwaZulu/Natal (rural), South Africa 1999 | Moodley 2001b | |
0.002 | 0.012 | 0.002-32 | 199 | Dar es salaam, Tanzania 1993-95 | Mbwana 1999 | |
0.004 | 0.008 | 0.002-0.015 | 251 | Abidjan, Côte d=Ivoire 1992-93 | Van Dyck 1997 | |
0.004 | 0.015 | 0.002-0.06 | 952 | Kinshasa, Congo 1988-1993 | Van Dyck 1997 | |
0.015 | 0.015 | 0.001-0.03 | 40 | Nairobi, Kenya 1989-90 | Plourde 1992 | |
0.004 | 0.015 | 0.001-0.06 | 1085 | Kigali, Rwanda 1989-90 | Van Dyck 1997 | |
2 | 8 | 0.03-32 | 110 | Guangzhou, China 2001 | Zheng 2005 | |
0.008 | 0.016 | 0.004-0.063 | 91 | Cuba 1995-98 | Sosa 2003 | |
4 | 32 | 0.002-64 | 211 | Fukuoka City, Japan 2002 | Tanaka 2004 | |
0.004 | 0.06 | 0.004-4 | 413 | New Zealand 2002 | Heffernan 2004 | |
Enoxacin | 0.25 | 2 | 0.008-8.0 | 79 | Japan 1992-93 | Tanaka 1995 |
lomefloxacin | 0.016 | 0.032 | <0.008-0.063 | 196 | Canada PCN-sensitive 1988 | Talbot 1989 |
0.125 | 1.0 | 0.004-2.0 | 79 | Japan 1992-93 | Tanaka 1995 | |
Norfloxacin | 0.016 | 0.032 | 0.008-0.128 | 507 | Trinidad, Trinidad and Tobago1992 | Swanston 1997 |
0.003 | 0.006 | 0.001-4 | 400 | Spain 1992-99 | Berron 2000 | |
0.25 | 16 | 0.016-32 | 157 | Fukuoka City, Japan 1997-98 | Tanaka 2000 | |
0.03 | 0.06 | 0.016-0.5 | 122 | Jakarta, Indonesia 1996 | Lesmana 2001 | |
0.06 | 0.125 | <0.015->4.0 | 332 | Thailand 1990 | Clendennen 1992a | |
<0.016 | 0.016 | 0.016-0.125 | 177 | Nairobi, Kenya 1995-96 | Claeys | |
0.06 | 0.125 | 0.008-0.25 | 130 | Mwanza, Tanzania 1992 | West 1995 | |
Ofloxacin | 0.0039 | 0.0078 | 0.002-0.015 | 100 | Brooklyn, New York, USA (n.r.) >92 | Glatt 1992 |
0.016 | 0.032 | 0.002 - 0.5 | 81 | Buenos Aires, Argentina 1995-1996 | Famiglietti 2001 | |
0.03 | 0.03 | 0.002-1 | 400 | Spain 1992-99 | Berron 2000 | |
0.008 | 0.03 | <0.002-0.25 | 150 | Germany 1988-92 | Schäffer 1995 | |
0.125 | 1 | 0.002-2.0 | 79 | Japan 1992-93 | Tanaka 1995 | |
0.038 | 0.075 | <0.005-2.5 | 333 | Thailand 1990 | Clendennen 1992a | |
0.038 | 0.625 | 0.005->5.0 | 139 | Philippines 1989 | Clendennen 1992b | |
0.015 | 0.03 | <0.007 - 4 | 354 | Durban, South Africa 1997-2000 | Moodley 2001a | |
0.008 | 0.012 | 0.004-0.032 | 177 | Nairobi, Kenya 1995-96 | Claeys 1998 | |
Levofloxacin |
0.007 | 0.003 | 0.002-0.5 | 400 | Spain 1992-99 | Berron 2000 |
4 | 8 | 0.004-32 | 211 | Fukuoka City, Japan 2002 | Tanaka 2004 | |
Gatifloxacin |
1 | 2 | <0.001-8 | 211 | Fukuoka City, Japan 2002 | Tanaka 2004 |
Miscellaneous | ||||||
Azithromycin | 0.125 | 0.25 | 6552 | USA 2003 | CDC 2003 (7) | |
0.125 | 0.25 | 0.032-0.5 | 81 | Manaus, Brazil 1998 | Dillon 2001a | |
0.125 | 0.5 | 0.063-8.0 | 67 | St. Vincent 1996 | Dillon 2001b | |
0.032 | 0.125 | 0.016 - 2 | 81 | Buenos Aires, Argentina 1995-1996 | Famiglietti 2001 | |
0.25 | 2.0 | 0.063-8.0 | 69 | Georgetown, Guyana 1994-1995 | Dillon 2001b | |
0.25 | 0.5 | <0.007-1.0 | 85 | Berlin, Germany 1995-97 | Wagner 2000 | |
0.023 | 0.047 | <0.016-0.19 | 177 | Nairobi, Kenya 1995-96 | Claeys 1998 | |
0.25 | 0.5 | 0.063-4.0 | 91 | Cuba 1995-98 | Sosa 2003 | |
0.5 | 1 | 0.06-2 | 130 | Mwanza, Tanzania 1992 | West 1995 | |
0.12 | 0.25 | 0.008-2 | 211 | Fukuoka City, Japan 2002 | Tanaka 2004 | |
0.125 | 0.25 | 0.03-4 | 936 | London, U.K. 2003 | GRASP 2004 | |
0.125 | 0.5 | 0.03-2 | 1039 | England and Wales excluding London, U.K. 2003 | GRASP 2004 | |
Spectinomycin | 16 | 16 | 187 | USA 1989-90 | Portilla 1992 | |
8 | 16 | 16-16 | 81 | Manaus, Brazil 1998 | Dillon 2001a | |
8 | 16 | 2 - 16 | 81 | Buenos Aires, Argentina 1995-1996 | Famiglietti 2001 | |
32 | 32 | 0.5-32 | 507 | Trinidad, Trinidad and Tobago1992 | Swanston 1997 | |
16 | 16 | 4-32 | 400 | Spain 1992-99 | Berron 2000 | |
8 | 16 | 0.06-32 | 85 | Berlin, Germany 1995-97 | Wagner 2000 | |
16 | 128 | 8-128 | 90 | Zhanjiang, China 1998-99 | Guoming 2000 | |
8 | 16 | 4-16 | 197 | Fukuoka City, Japan, 1997-98 | Tanaka 2000 | |
8.0 | 16.0 | 4.0-32.0 | 94 | Dhaka, Bangladesh 1977 | Bhuiyan 1999 | |
64 | 64 | 8-128 | 305 | Thailand 1990 | Clendennen 1992a | |
32 | 32 | 16->128 | 117 | Philippines 1989 | Clendennen 1992b | |
32 | 32 | 16-32 | 139 | Kigali, Rwanda 1999-2000 | Van Dyck 2001 | |
8 | 32 | <0.007 - >64 | 354 | Durban, South Africa 1997-2000 | Moodley 2001a | |
4 | 8 | 3-12 | 177 | Nairobi, Kenya 1995-96 | Claeys | |
8 | 32 | 8-32 | 199 | Dar es salaam, Tanzania 1993-95 | Mbwana 1999 | |
8 | 16 | 4-16 | 110 | Guangzhou, China 2001 | Zheng 2005 | |
16 | 16 | 8-16 | 91 | Cuba 1995-98 | Sosa 2003 | |
8 | 16 | 4-16 | 211 | Fukuoka City, Japan 2002 | Tanaka 2004 | |
16 | 32 | 2-64 | 936 | London, U.K. 2003 | GRASP 2004 | |
16 | 32 | 2-64 | 1039 | England and Wales excluding London, U.K. 2003 | GRASP 2004 | |
8 | 16 | 2-16 | 413 | New Zealand 2002 | Heffernan 2004 |
** indicates that lower limit of MIC range was not reported.
Table 2 - Aggregated Results of Clinical Trials
Pharyngeal infections | Urogenital & rectal infections | |||||
---|---|---|---|---|---|---|
Drug regimen | % cured | 95% C I | % cured | 95% C I | ||
Ceftriaxone 250 mg | 99.0 | 94.4 | 100 | 99.2 | 98.8 | 99.5 |
Ciprofloxacin 500 mg* | 97.2 | 85.5 | 99.9 | 99.8 | 98.7 | 100 |
Ciprofloxacin 250 mg | 88.5 | 81.8 | 95.2 | 98.7 | 98.0 | 99.4 |
Ceftriaxone 125 mg | 94.1 | 85.6 | 98.4 | 98.9 | 97.9 | 99.8 |
Ceftizoxime 500 mg | 100 | 15.8 | 100 | 99.2 | 97.8 | 99.8 |
Ofloxacin 400 mg | 88.7 | 68.8 | 97.8 | 98.6 | 97.8 | 99.4 |
Gatifloxacin 600 mg | 100 | 82.3 | 100 | 99.6 | 97.7 | 100 |
Spectinomycin 2 g | 51.8 | 38.7 | 64.9 | 98.2 | 97.6 | 99.9 |
Azithromycin 2 g | 100 | 82.3 | 100 | 99.2 | 97.2 | 99.9 |
Gatifloxacin 400 mg | 100 | 63.1 | 100 | 99.2 | 97.1 | 99.9 |
Cefoxitin 2g + probenecid 1 g | 99.2 | 97.1 | 99.9 | |||
Cefotaxime 500 mg | 45.4 | 16.7 | 76.2 | 97.9 | 96.7 | 99.1 |
Norfloxacin 800 mg | 80.0 | 28.4 | 99.5 | 98.0 | 96.7 | 99.2 |
Azithromycin 1 g | 100 | 39.8 | 100 | 97.1 | 95.2 | 99.0 |
Cefixime 800 mg | 80.0 | 51.9 | 95.7 | 98.4 | 95.9 | 99.6 |
Cefixime 400 mg | 92.3 | 74.9 | 99.1 | 97.4 | 95.9 | 98.6 |
Cefuroxime axetil 1 g | 56.9 | 43.3 | 70.5 | 96.2 | 94.8 | 97.5 |
Cexpodoxime proxetil 200 mg | 78.9 | 54.5 | 94.0 | 96.5 | 94.3 | 98.5 |
Table 3 - Quinolone Resistance in Strains of Neisseria gonorrhoeae Isolated in Asia and Oceania in 1999, 2001, and 2003
Number tested | Number less susceptible (%) | Number resistant (%) | |||||||
---|---|---|---|---|---|---|---|---|---|
Country | 1999 | 2001 | 2003 | 1999 | 2001 | 2003 | 1999 | 2001 | 2003 |
ASIA | |||||||||
Brunei | 53 | 52 | 50 | 4 (7.5) | 1 (2.0) | 5 (10.0) | 5 (9.4) | 10 (19.0) | 31 (62.0) |
China | 591 | 748 | 1254 | 131 (22.1) | 83 (11.1) | 332 (52.8) | 650 (86.9) | 1171 (93.4) | |
Hong Kong SAR | 2482 | 2575 | 3378 | 697 (28.1) | 235 (9.1) | 165 (4.9) | 1653 (66.6) | 2270 (88.2) | 3167 (93.7) |
Japan | 246 | 300 | 200 | 80 (32.5) | 42 (14.0) | 17 (12.8) | 56 (22.8) | 192 (64.0) | 154 (77.0) |
Korea | 86 | 177 | 212 | 61 (71.0) | 94 (53.1) | 39 (18.4) | 14 (16.0) | 70 (39.5) | 166 (78.3) |
Laos | 187 | 11 (5.9) | 42 (22.5) | ||||||
Malaysia | 54 | 30 | 0 (0) | 2 (6.7) | 0 (0) | 7 (23.3) | |||
Mongolia | 56 | 5 (8.9) | 14 (25.0) | ||||||
Philippines | 313 | 399 | 111 | 8 (2.5) | 1 (0.2) | 11 (9.9) | 191 (61.0) | 217 (54.3) | 62 (55.9) |
Singapore | 768 | 741 | 200 | 37 (4.8) | 35 (4.7) | 9 (4.5) | 131 (17.0) | 207 (27.9) | 103 (51.5) |
Vietnam | 194 | 168 | 27 (13.9) | 33 (19.6) | 69 (35.6) | 71 (42.3) | |||
OCEANIA | |||||||||
Australia | 3658 | 3641 | 3772 | 500 (13.7) | 149 (4.1) | 77 (2.0) | 128 (3.5) | 489 (13.4) | 452 (12.0) |
New Caledonia | 53 | 57 | 53 | 0 (0) | 0 (0) | 0 (0) | 3 (5.7) | ||
New Zealand | 638 | 765 | 1113 | 8 (1.3) | 20 (2.6) | 31 (2.8) | 14 (2.2) | 77 (10.0) | 96 (8.6) |
Papua New Guinea | 343 | 96 | 96 | 1 (0.3) | 0 (0) | 0 (0) | 5 (1.5) | 0 (0) | 0 (0) |
Table 4 - Recommended Regimens for the Treatment of Gonococcal Infections in the United States
Diagnosis | Population | Treatment of choice | Alternative Regimen |
---|---|---|---|
Uncomplicated urogenital or rectal infection | Heterosexual adults and children >45 kg likely to have acquired infection from a U.S. domestic source outside California or Hawaii | Ceftriaxone 125 mg IM in a single dose
ORCefixime 400 mg orally in a single doseORCiprofloxacin 500 mg orally in a single doseOROfloxacin 400 mg orally in a single doseORLevofloxacin 250 mg orally in a single dosePLUS treatment for Chlamydia if chlamydial infection is not ruled out |
Spectinomycin 2 g IM in a single dose
PLUS treatment for Chlamydia if chlamydial infection is not ruled out |
|
Homosexual adults and children >45 kg or adults and children>45 kg who may have acquired infection from a California, Hawaii, or foreign source | Ceftriaxone 125 mg IM in a single dose
ORCefixime 400 mg orally in a single dosPLUS treatment for Chlamydia if chlamydial infection is not ruled out |
Spectinomycin 2 g IM in a single dose
PLUS treatment for Chlamydia if chlamydial infection is not ruled out |
Children who weigh <45 kg | Ceftriaxone 125 mg IM in a single dose | Spectinomycin 40 mg/kg (maximum dose: 2 g) IM in a single dose | |
Pharyngeal infection | Heterosexual adults and children >45 kg likely to have acquired infection from a U.S. domestic source outside California or Hawaii | Ceftriaxone 125 mg IM in a single dose
ORCiprofloxacin 500 mg orally in a single dosePLUS treatment for Chlamydia if chlamydial infection is not ruled out |
|
|
Homosexual adults and children >45 kg or adults and children ≥45 kg who may have acquired infection from a California, Hawaii, or foreign source | Ceftriaxone 125 mg IM in a single dose
PLUS treatment for Chlamydia if chlamydial infection is not ruled out |
|
Children who weigh <45 kg | Ceftriaxone 125 mg IM in a single dose | Spectinomycin 40 mg/kg (maximum dose: 2 g) IM in a single dose may be used, but this therapy is unreliable and should be followed with a test of cure | |
Eye infection | Adults | Ceftriaxone 1 g IM as a single dose | |
|
Infants | Ceftriaxone 25–50 mg/kg IV or IM in a single dose, not to exceed 125 mg. |
|
Pelvic Inflammatory Disease | Parenteral therapy | Cefotetan 2 g IV every 12 h OR Cefoxitin 2 g IV every 6 h) PLUS Doxycycline 100 mg orally or IV every 12 h
ORClindamycin 900 mg IV every 8h PLUS Gentamicin loading dose IV or IM (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kg) every 8 h (Single daily dosing may be substituted.) |
Ofloxacin 400 mg IV every 12 hours
OR Levofloxacin 500 mg IV once daily WITH OR WITHOUT Metronidazole 500 mg IV every 8 hORAmpicillin/Sulbactam 3 g IV every 6 hPLUS Docycycline 100 mg orally or IV every 12 h) |
|
Oral therapy | Levofloxacin 500 mg orally once daily for 14 days OR Ofloxacin 400 mg orally twice a day for 14 days
WITH OR WITHOUT Metronidazole 500 mg orally twice a day for 14 daysORCeftriaxone 250 mg IM in a single dose OR Cefoxitin 2 g IM in a single dose and Probenecid 1 g orally administered concurrently as a single dose OR other parenteral third generation cephalosporine PLUS Doxycycline 100 mg orally twice a day for 13 days WITH OR WITHOUT Metronidazole 500 mg orally twice a day for 14 days |
|
Disseminated infection | Adults and children >45 kg infected with organisms known to be susceptible to fluoroquinolones. | Ceftriaxone 1 g IM or IV every 24 hours Parenteral treatment should be continued for 24-48 hours after improvement begins;
then therapy may be switched to cefixime 400 mg orally twice a day OR Ciprofloxacin 500 mg orally twice a day OR Ofloxacin 400 mg orally twice a day OR Levofloxacin 500 mg orally once a day to complete a full week of antimicrobial therapy. |
Cefotaxime 1 g IV every 8 hours
ORCeftizoxime 1 g IV every 8 hoursORCiprofloxacin 500 mg IV every 12 hoursOROfloxacin 400 mg IV every 12 hoursORLevofloxacin 250 mg IV dailyORSpectinomycin 2 g IM every 12 hours.Parenteral treatment should be continued for 24-48 hours after improvement begins; then therapy may be switched toCefixime 400 mg orally twice a dayORCiprofloxacin 500 mg orally twice a dayOROfloxacin 400 mg orallyl twice a dayORLevofloxacin 500 mg orally once a day to complete a full week of antimicrobial therapy. |
|
Adults and children >45 kg who may be infected with fluoroquinolone-resistant organisms | Ceftriaxone 1 g IM or IV every 24 hours. Parenteral treatment should be continued for 24-48 hours after improvement begins;
then therapy may be switched to cefixime 400 mg orally twice a day to complete a full week of antimicrobial therapy. |
Cefotaxime 1 g IV every 8 hours
ORceftizoxime 1 g IV every 8 hoursORSpectinomycin 2 g IM every 12 hours.Parenteral treatment should be continued for 24-48 hours after improvement begins; then therapy may be switched toCefixime 400 mg orally twice a day to complete a full week of antimicrobial therapy. |
|
Newborns | Ceftriaxone 25–50 mg/kg/day IV or IM in a single daily dose for 7 days, with a duration of
10–14 days, if meningitis is documented ORCefotaxime 25 mg/kg IV or IM every 12 hours for 7 days, with a duration of 10–14 days, if meningitis is documented.
|
|
What's New
Kirkcaldy RD, et al. Cephalosporin-Resistant Gonorrhea in North America. JAMA 2013;309:185-187.
Schumacher CM, Ghanem KG. Retreatment rates for uncomplicated gonorrhea infection: comparing ceftriaxone and azithromycin versus ceftriaxone and doxycycline.Sex Transm Dis. 2013;40:539-45.
Bolan GA, et al. The emerging threat of untreatable gonococcal infection. NEJM. 2012;366(6):485-7.
Mehta SD, Moses S, et al. Adult Male Circumcision Does Not Reduce the Risk of Incident Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis Infection: Results from a Randomized, Controlled Trial in Kenya.J Infect Dis. 2009 Aug 1;200:370-378.
Moncada J, Donegan E, et al. Evaluation of CDC-Recommended Approaches for Confirmatory Testing of PositiveNeisseria gonorrhoeae Nucleic Acid Amplification Test Results. J Clin Microbiol 2008;46:1614-1619.
GUIDED MEDLINE SEARCH FOR
Reviews
Baron EJ. Neisseria spp.
CDC. Quinolones not recommended in the U.S.
Nie S, et al. Gonococcal endocarditis: a case report and literature review. Eur J Clin Microbiol Infect Dis 2014;33:23-27.
Newman LM, Moran JS, Workowski KA. Update on the Management of Gonorrhea in Adults in the United States. Clin Infect Dis 2007;44:S84-101.
CDC. Cost minimizing strategies for treatment of gonorrhea. Emerg Infect Dis, Aug 2005.
GUIDED MEDLINE SEARCH FOR RECENT REVIEWS
History
Benedek TG: Biography of Neisser
Benedek TG. History of the Medical Treatment of Gonorrhea.
Benedek TG. Gonorrhea and the beginnings of clinical research ethics. Perspect Biol Med. 2005 Winter;48(1):54-73.
GUIDED MEDLINE SEARCH FOR HISTORICAL ASPECTS
Table of Contents
- Monograph
- Epidemiology
- Clinical Manifestations
- Laboratory Diagnosis
- Pathogenesis
- Susceptibility in Vitro and in Vivo
- Antimicrobial Therapy
- Uncomplicated Urogenital and Rectal Infections
- Criteria for Choosin
g Regime
ns for Routine Use - Regime
ns Recom
mended for the Rotuine Treatme
nt of Uncomp
licated Gonoco
ccal Infection
s of the Cervix, Urethra, and Rectum in Adult Heteros
exuals Unlikely to have Acquire
d their Infection from a Foreign Source or in Hawaii or Californi
a - Pediatri
c Infection
- Criteria for Choosin
- Pharyngeal Infections
- Eye Infections
- Pelvic Inflammatory Disease
- Disseminated Gonococcal Infection (DGI)
- Underlying Diseases
- Alternative Therapy
- Quinolone-Resistant N. gonorrhoeae (QRNG)
- Combination Therapy
- Outcome
- Uncomplicated Urogenital and Rectal Infections
- Adjunctive Therapy
- Endpoints for Monitoring Therapy
- Vaccines
- Prevention of Infection Control Measures
- Co-Existing STDS