|September 2012 · Vol. 24, No. 9
CDC: Stop using oral cephalosporins to treat gonorrhea
Start using combination therapy with ceftriaxone and either azithromycin or doxycycline because of increasing resistance to oral cephalosporins.
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
It is essential that culture capacity for N. gonorrhoeae be maintained to monitor antimicrobial resistance trends and determine susceptibility to guide treatment following treatment failure. To help control gonorrhea in the United States, health-care providers must maintain the ability to collect specimens for culture and be knowledgeable of laboratories to which they can send specimens for culture. Health-care systems and health departments must support access to culture, and laboratories must maintain culture capacity or develop partnerships with laboratories that can perform culture.
Clinicians treating a patient with persistent infection after treatment with the recommended therapy should culture relevant clinical specimens and perform antimicrobial susceptibility testing of N. gonorrhoeae isolates. Phenotypic antimicrobial susceptibility testing should be performed using disk diffusion, Etest (BioMerieux), or agar dilution. Data are limited on the use of NAAT-based antimicrobial susceptibility testing for genetic mutations.
Patients who experience treatment failure after treatment with alternative regimens should be treated with ceftriaxone 250 mg as a single intramuscular dose and azithromycin 2 g orally as a single dose and should receive infectious disease consultation.
Consult an infectious disease specialist, an STD/HIV Prevention Training Center, or the CDC for treatment advice, and report the case to the CDC through a health department within 24 hours of diagnosis. Conduct test-of-cure 7 days after re-treatment.
Clinicians should make every effort to ensure that the patient’s sex partners from the preceding 60 days are evaluated promptly and treated as indicated.
“Treatment of patients with gonorrhea with the most effective therapy will limit the transmission of the disease, prevent complications, and slow the emergence of resistance,” wrote CDC reporters. “However, resistance to cephalosporins, including ceftriaxone, is expected to emerge. Reinvestment in gonorrhea prevention and control is warranted. New treatment options for gonorrhea are urgently needed.”1
For the full MMWR article on new gonorrhea treatment guidelines, visit http://1.usa.gov/OxjuaQ
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1. del Rio C, Hall G, Holmes K, et al. Update to CDC’s Sexually Transmitted Diseases Treatment Guidelines, 2010: Oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR. 2012;61(31):590–594. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6131a3.htm. Published August 10, 2012. Accessed August 13, 2012.
2. Gonorrhea fact sheet. Womenshealth.gov. http://womenshealth.gov/publications/our-publications/fact-sheet/gonorrhea.cfm#h. Updated July 8, 2011. Accessed August 13, 2012.
3. Centers for Disease Control and Prevention. 2010 sexually transmitted diseases surveillance: Gonorrhea. CDC Web site. http://www.cdc.gov/std/stats10/gonorrhea.htm. Updated November 17, 2011. Accessed August 13, 2012.
4. The Washington Post. Only one gonorrhea drug remains for routine cases, CDC says. http://www.washingtonpost.com/national/health-science/gonorrhea-drug-is-becoming-less-effective-cdc-says/2012/08/09/874751e6-e256-11e1-ae7f-d2a13e249eb2_story.html. Published August 10, 2012. Accessed August 13, 2012.
5. Parker-Pope T. Worries about a gonorrhea “superbug”. NY Times Health Science. http://well.blogs.nytimes.com/2011/07/12/worries-about-a-gonorrhea-superbug/ Published July 12, 2011. Accessed August 13, 2012.
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