"Gonorrhea is the second most commonly reported infectious disease in the
US, with about 340,000 cases reported in 2005," John M. Douglas, Jr., MD,
Director of the Division of Sexually Transmitted Diseases Prevention
(DSTD), National Center for HIV/AIDS, Viral Hepatitis, STD [sexually
transmitted disease], and TB Prevention (NCHHSTP), said in a CDC
teleconference. "Like most STDs, gonorrhea is underdiagnosed and
underreported, and we estimate that about twice that number of people were
affected. We've made substantial progress in reducing the burden of
gonorrhea over the years as a result of efforts to prevent, detect and
effectively treat the disease."
Rising rates of gonorrhea resistance to fluoroquinolones were first noted
in Hawaii and California, leading the CDC to recommend in 2000 and in
2002, respectively, that fluoroquinolones not be used to treat gonorrhea
infections in these states. In 2004, rising rates of gonorrhea resistance
to fluoroquinolones in men who have sex with men led the CDC to recommend
against using fluoroquinolones in this group.
"Part of our success in controlling this disease has been our ability to
treat the changing organism itself," Dr. Douglas says. "Gonorrhea has
proven to be quite efficient at navigating around the drugs we use to
combat it, with resistance first to penicillin, then tetracycline, then,
most recently, to fluoroquinolones.... We want a recommended treatment to
cure 95% or more of all gonorrhea infections, [and] we have reached a
level of resistance that threatens our ability to control the disease
across populations."
Data from CDC's Gonococcal Isolate Surveillance Project (GISP) in 26 US
cities showed that in the first half of 2006, 6.7% of gonorrhea cases in
heterosexual men were fluoroquinolone-resistant Neisseria gonorrhoeae
(QRNG), an 11-fold increase from 0.6% in 2001, and well above 5%, the
recognized threshold for changing treatment recommendations.
"As a result of these increases in fluoroquinolone resistance throughout
the country, CDC is no longer recommending that fluoroquinolones be used
to treat gonorrhea anywhere in the U.S.," Dr. Douglas says. "These
recommendations are critical to preserve the progress we've made in
controlling gonorrhea, one of the nation's most common STDs."
The overall proportion of gonorrhea cases that were QRNG increased from
less than 1% in 2001 to 13.3% in the first half of 2006, with dramatic
increases from 2004 to 2006 in Philadelphia (1.2% - 26.6%) and Miami (2.1%
- 15.3%). QRNG also continued to rise among men who have sex with men,
from 1.6% in 2001 to 38% in the first half of 2006.
"We do not have the full data yet from the last half of 2006," Hillard S.
Weinstock, MD, MPH, Medical Epidemiologist, DSTD, NCHHSTP, said in the
teleconference. "However, given the trends we have observed over the last
several years, we expect that the percentage of fluoroquinolone-resistant
cases will go up in the second half of 2006."
Therefore, the CDC no longer recommends fluoroquinolone antibiotics
(ciprofloxacin, ofloxacin, and levofloxacin) for treatment of gonorrhea in
the United States. Because gonorrhea resistance to penicillin, sulfa
drugs, and tetracycline is already widespread, this limits available
options for gonorrhea treatment to drugs in the cephalosporin class. The
United Kingdom preceded the United States by about 3 to 4 years in its
recommendation to switch from fluoroquinolones to cephalosporins in
gonorrhea treatment.
"There is an urgent need for new, effective medicines to treat gonorrhea,"
Kevin Fenton, MD, Director of CDC's National Center for HIV/AIDS, Viral
Hepatitis, STD, and TB Prevention, said in a news release. "We are running
out of options to treat this serious disease. Increased vigilance in
monitoring for resistance to all available drugs is essential."
Although significant resistance to cephalosporins has not been reported
thus far, CDC is collaborating with state and local health departments to
detect emerging cephalosporin resistance. Now that gonorrhea is largely
diagnosed by a convenient DNA test, many laboratories and providers no
longer have the capability of culturing N gonorrhoeae for drug resistance
testing. The CDC is urging health departments to maintain or develop this
capacity and to evaluate any gonorrhea treatment failures for possible
resistance.
"Importantly, with fluoroquinolones no longer recommended, only one class
of drugs remains recommended for treating gonorrhea: the antibiotics known
as cephalosporins," Dr. Douglas says. "Although the cephalosporins offer
several potential options for treating gonorrhea, the lack of additional
classes of antibiotics is a serious concern. There are currently no new
drugs for gonorrhea in the drug development pipeline."
To bolster international monitoring for the emergence of cephalosporin
resistance, CDC is also working with the World Health Organization (WHO)
and with government and industry partners to identify and evaluate new
drug regimens for gonorrhea treatment.
"While we have not seen any evidence of resistance to cephalosporins to
date, emergence of any resistance would be a serious public health
concern," Dr. Douglas said. "CDC will work with government and industry
partners to identify and evaluate promising alternative drug regimens for
treating gonorrhea. Ultimately, reducing the burden of gonorrhea will
require comprehensive and continued action on many fronts, as we work to
maintain and expand effective programs to prevent and control this disease
across the nation."
Most cases of gonorrhea in women are asymptomatic and untreated. However,
failure to treat gonorrhea aggressively and early may result in pelvic
inflammatory disease with associated infertility, chronic pelvic pain,
and/or ectopic pregnancy. In men, rare complications of untreated
gonorrhea may include epididymitis, rarely associated with infertility.
Even when asymptomatic, inflammation of the male genitourinary tract
associated with gonorrhea may increase susceptibility to HIV infection.
Rarely, untreated gonorrhea may be associated with serious sequelae such
as infectious arthritis, meningitis or endocarditis.
Updated recommended treatment regimens for gonorrhea infection are as
follows:
For uncomplicated gonococcal infections of the cervix, urethra, and
rectum, recommended treatments are 125 mg of ceftriaxone in a single
intramuscular (IM) dose or 400 mg of cefixime (not available in the United
States) in a single oral dose, plus treatment of Chlamydia if chlamydial
infection is not ruled out. Although 400-mg tablets of cefixime are not
available in the United States, and it is only available in a suspension
formulation, Dr. Douglas said that the CDC has approached the Food and
Drug Administration regarding this, and they are hopeful that oral tablets
will soon be an option in the United States.
"While we only have this single class of recommended antibiotics, the
cephalosporins, and the vigilance we've talked about today is a key public
health priority, we've been using this class of drugs for the treatment of
gonorrhea since the early 1980s, and fortunately, so far, there has not
been any documentation of emergence of resistance," Dr. Douglas says. "I
don't want to present an injectable antibiotic as an insurmountable
obstacle, because we used it for years with penicillin; it's more of a
bump in the road in terms of how providers will be caring for patients
with gonorrhea."
Alternative regimens for uncomplicated gonococcal infections of the
cervix, urethra, and rectum are 2 g of spectinomycin (not available in the
United States) in a single IM dose or cephalosporin single-dose regimens
(ceftizoxime, 500 mg IM; or cefoxitin, 2 g IM, administered with
probenecid, 1 g orally; or cefotaxime, 500 mg IM).
For uncomplicated gonococcal infections of the pharynx, recommended
regimens are 125 mg of ceftriaxone in a single IM dose, plus treatment of
Chlamydia if chlamydial infection is not ruled out. There are currently no
recommended alternatives for pharyngeal infection.
For disseminated gonococcal infection, pelvic inflammatory disease,
epididymitis, and treatment of gonorrheal infections in patients with
documented severe allergic reactions to penicillins or cephalosporins,
updated treatment regimens are available at
http://www.cdc.gov/std/treatment.
A limitation of findings from GISP, which is conducted in publicly funded
clinics and includes only male urethral isolates, is that they might not
be representative of the entire US population infected with gonorrhea.
"We've looking hard for resistance for the duration of the GISP project,
and we've never seen gonorrhea that we would consider to be resistant to
cephalosporins," Dr. Douglas said. "Based on global surveillance, we have
not documented any strains resistant to cephalosporins at all. That's
comforting, of course, but because of the genetic versatility of the
organism, it's not something we feel completely complacent about.
Although test of cure is not recommended routinely for uncomplicated
gonorrhea treated with recommended or alternative regimens, persons with
persistent symptoms of gonococcal infection or whose symptoms recur
shortly after treatment with a recommended or alternative regimen should
be reevaluated by culture for N gonorrhoeae. Positive isolates should be
tested for antimicrobial susceptibility, and clinicians and laboratories
should report treatment failures or resistant gonococcal isolates to the
CDC at the telephone number: 1-404-639-8373, through state and local
public health authorities.
"In [other] Gram-negative bacteria, very highly resistant strains even to
these third generation cephalosporin antibiotics have occurred," Dr.
Douglas concluded. "It's just very hard to know if that could happen [for
N gonorrheae], and when it could happen, but it's certainly not
implausible. Can it happen? Absolutely."
Morbid Mortal Wkly Rep. 2007;56:332-336.
http://www.cdc.gov/std/treatment
http://www.cdc.gov/std/gonorrhea/arg/
Clinical Context
In the United States, gonorrhea is the second most frequently reported
notifiable disease, with 339,593 cases documented in 2005. Although
fluoroquinolones (ciprofloxacin, ofloxacin, or levofloxacin) are highly
effective, readily available, and convenient as single-dose oral therapy
and have been used since 1993 for gonorrhea treatment, prevalence of
fluoroquinolone resistance in N gonorrhoeae has been increasing and is now
widespread.
Beginning in 2000, fluoroquinolones were no longer recommended for
treatment of gonorrhea acquired in Asia or the Pacific Islands (including
Hawaii); in 2002, this recommendation was extended to California; and in
2004, CDC recommended that fluoroquinolones not be used in the United
States to treat gonorrhea in men who have sex with men. This Morbidity and
Mortality Weekly Report article summarizes findings from the GISP and
updates CDC's Sexually Transmitted Diseases Treatment Guidelines, 2006
regarding the treatment of N gonorrhoeae infections.
Disclaimer : Medicines and the cure for gonococal urethritis or Tulo may differ from person to person and it is always advisable to consult a physician whenever possible.