Gonorrhea, the second most commonly reported infectious disease in the United States, is increasing in incidence because Neisseria gonorrhoeae is progressively developing antibiotic resistance. Results of laboratory studies have provoked growing concern that cephalosporins, the only class of antibiotics that meets the current Centers for Disease Control and Prevention (CDC) efficacy standards, are also becoming ineffective in the treatment of gonorrhea.1
CDC updated its guidelines, as reported in Morbidity and Mortality Weekly Report (MMWR), recommending combination therapy with ceftriaxone and either azithromycin or doxycycline for uncomplicated gonorrhea. By revising the current treatment recommendations, the CDC hopes to delay cephalosporin resistance until new treatment options are developed.1
Gonorrhea is a major cause of pelvic inflammatory disease, which can lead to tubal infertility, ectopic pregnancy, and chronic pelvic pain. A pregnant woman with untreated gonorrhea has a higher risk for miscarriage, preterm birth, or premature rupture of membranes. An infected mother can transmit the disease to her child, with risk of blindness, joint infection, and sepsis in the baby.2 There is also strong epidemiologic and biologic evidence that N. gonorrhoeae infections enable HIV infection transmission.1,3
INCREASING INFECTION RATES
After a decline in reported gonorrhea rates to 98.1 cases per 100,000 population in 2009, the rate increased slightly in 2010 to 100.8 per 100,000, with 309,341 cases reported in the United States. In 2010, the reported gonorrhea rate for women was 106.5 per 100,000, slightly higher than for men (94.1 per 100,000). Reported gonorrhea rates were highest among adolescent girls ages 15 to19 years (570.9 per 100,000) and young women ages 20 to 24 years (560.7 per 100,000). The largest increases were observed among men and woman ages 20 to 24 years (4.9%) and 30 to 34 years (3.2%).3
“In the United States, about 300,000 cases of gonorrhea are reported each year, but because infected people often have no symptoms, the actual number of cases is probably closer to 700,000,” reported Gail Bolan, director of the CDC’s Sexually Transmitted Disease Prevention Division.4
GROWING CONCERN OVER RESISTANCE
Signs of growing resistance have only been seen in laboratory studies; there are no reported cases of treatment-resistant gonorrhea in the Unites States. However, the evidence of emerging cephalosporin resistance is following a similar pattern to that seen in 2007, when gonorrhea became fluoroquinolone-resistant.1,5
“The challenge is that there is not a well-studied second antibiotic we can turn to even when cephalosporin resistance does emerge,” said Robert D. Kirkcaldy, a medical epidemiologist at the CDC. “What we’ve been noticing is really since 2009 and 2010, it’s taking higher concentrations of antibiotic to kill the bacteria. This could mean resistance to the last antibiotic we have for gonorrhea could be on the horizon.”5
NEW CDC TREATMENT RECOMMENDATIONS
The CDC’s updated guidelines include treatment plans for uncomplicated disease; specific alternatives if ceftriaxone cannot be used; test-of-cure procedures; treatment failure strategies; and recommendations for sexual partners.1
To treat uncomplicated urogenital, anorectal, and pharyngeal gonorrhea, the CDC now recommends combination therapy with a single intramuscular dose of ceftriaxone 250 mg plus either a single dose of azithromycin 1 g orally or doxycycline 100 mg orally twice a day for 7 days.
Ceftriaxone, as a single 250-mg intramuscular injection, provides high and sustained bactericidal blood levels and is highly efficacious at all anatomic sites of N. gonorrhoeae infection currently circulating in the US. Clinical data are not available that support the use of an increased dose.
The percentage of isolates exhibiting tetracycline resistance was high but remained stable from 2006 (20.6%) to 2011 (21.6%).
When ceftriaxone cannot be used to treat urogenital or rectal gonorrhea, there are two options:
- if ceftriaxone is not readily available, give cefixime 400 mg orally plus either azithromycin 1 g orally or doxycycline 100 mg twice daily orally for 7 days
- if ceftriaxone cannot be given because of severe allergy, give azithromycin 2 g orally in a single dose.
A patient with gonorrhea treated with an alternative regimen should return 1 week after treatment for a test-of-cure at the infected anatomic site.
Test-of-cure—specimen culture is essential
The ideal test-of-cure is performed with culture or, if culture is not readily available, with a nucleic acid amplification testing (NAAT). If the NAAT is positive, make every effort to perform a confirmatory culture. All positive cultures for test-of-cure should undergo phenotypic antimicrobial susceptibility testing.
Unfortunately, the capacity of US laboratories to isolate N. gonorrhoeae by culture is declining rapidly because of the widespread use of NAATs for diagnosing gonorrhea. CDC reporters del Rio and colleagues write in MMWR:1