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Although gonorrhea has afflicted humans for centuries, and the causative bacterium, Neisseria gonorrhoeae, was identified more than a century ago, gonorrhea remains a public health problem in the United States. Before the 1930s, gonorrhea often was treated with patent medicines or intraurethral irrigations with compounds such as merbromin (Mercurochrome) or other antiseptics. Cephalosporins remained the foundation of gonorrhea treatment in the 2010 CDC STD treatment guidelines (4). Unsuccessful treatment of gonorrhea with oral cephalosporins, such as cefixime, was identified in East Asia, beginning in the early 2000s, and in Europe within the past few years.
Challenges in detecting and responding to the emergence of multidrug-resistant gonorrhea also exist.
Several steps taken now might delay the emergence of cephalosporin-resistant strains, mitigate the public health consequences of expanded resistance, and prevent a return to the era of untreatable gonorrhea. Within several years, molecular assays for detecting genetic mutations associated with resistance might be available and could enhance surveillance and clinical management. Alternate Text: The figure above shows the prevalence of ciprofloxacin resistance in urethral Neisseria gonorrhoeae isolates collected from men in the United States, by location, during 1990-2007, according to the Gonococcal Isolate Surveillance Project.
Alternate Text: The figure above shows the prevalence of ciprofloxacin resistance in urethral Neisseria gonorrhoeae isolates collected from men in the United States, by gender of sex partner, during 1999-2007, according to the Gonococcal Isolate Surveillance Project. Alternate Text: The figure above shows the percentage of urethral Neisseria gonorrhoeae isolates with elevated cefixime minimum inhibitory concentrations (MICs) and elevated ceftriaxone MICs during 2006-2011, according to the Gonococcal Isolate Surveillance Project. The introduction of sulfonamide antimicrobials in the 1930s ushered in an era of effective antimicrobial therapy for gonorrhea. These updated guidelines increased the recommended dosage of ceftriaxone to 250 mg and included broadened recommendations for combination therapy: a cephalosporin, preferably ceftriaxone 250 mg as a single intramuscular dose, should be administered with a second antimicrobial. Based on surveillance trends, CDC recently updated its treatment recommendations: gonorrhea at any anatomic site should be treated with a single 250 mg intramuscular dose of ceftriaxone plus either 1 g of azithromycin as a single oral dose or 100 mg of doxycycline orally twice daily for 7 days (8). When a suspected cephalosporin-resistant infection is detected, local public health authorities should interview the patient and ensure adequate treatment and ensure that all recent partners are evaluated and treated appropriately.
Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections.

High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain. Update to CDC's sexually transmitted diseases treatment 2010 guidelines: oral cephalosporins no longer a recommended treatment for gonococcal infections. Men who have sex with men were and remain disproportionately affected by fluoroquinolone-resistant N. In the United States, health inequities persist; the incidence of reported gonorrhea among blacks is 17 times the rate among whites, likely because of structural socioeconomic factors (1,2). However, most cases of gonorrhea are asymptomatic, particularly cervical, pharyngeal, and rectal infections.
During this period, fluoroquinolones were widely used for treatment of gonorrhea because they were safe, effective, inexpensive, and available in oral forms. Previously recommended antimicrobials likely cannot again be routinely prescribed for empiric gonorrhea treatment.
At this time, only one new antimicrobial is undergoing clinical study (NCT01591447) as a potential treatment for gonorrhea. Clinicians can help prevent sequelae and spread of gonorrhea by eliciting sexual histories from their patients, screening sexually active MSM and high-risk sexually active women for gonorrhea at least annually at exposed anatomic sites, and treating appropriately (4). If this recommended regimen cannot be used, two alternative treatment options exist for urogenital or rectal gonorrhea: 1) if ceftriaxone is not available, clinicians can consider cefixime 400 mg as a single oral dose and either azithromycin 1 g as a single oral dose or doxycycline 100 mg orally twice daily for 7 days, or 2) if the patient is cephalosporin-allergic, clinicians can consider azithromycin 2 g as a single oral dose.
Clinicians can strengthen surveillance by maintaining vigilance for treatment failures, collecting isolates for susceptibility testing from such patients, and promptly notifying the local public health STD program. However, experience and current data suggest that public health actions outlined in this report provide the best chance of averting the unfavorable outcome of multidrug-resistant gonorrhea, greater disease burden, heightened risk for sequelae, and greater health-care costs. At regional laboratories, the susceptibilities of these isolates to penicillin, tetracycline, spectinomycin, ciprofloxacin, ceftriaxone, cefixime, and azithromycin are determined by agar dilution. Untreated or inadequately treated gonorrhea can facilitate human immunodeficiency virus (HIV) transmission and cause serious reproductive complications in women, such as pelvic inflammatory disease, ectopic pregnancy, and infertility.

Penicillin was then found to be effective for gonorrhea treatment and became the therapy of choice for several decades.
The National Institute for Allergy and Infectious Diseases, in collaboration with CDC, is conducting a clinical trial (NCT00926796) to study the efficacy of two combinations of existing antimicrobials.
Clinicians also can counsel sexually active adults, particularly those living in high prevalence areas, to engage in mutually monogamous partnerships with uninfected partners and to consistently and correctly use latex condoms, which can reduce transmission. Carolyn Deal, PhD, National Institute for Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland. During this time, however, the gonococcus acquired genetic mutations that conferred increasing penicillin resistance, necessitating increasingly higher doses of penicillin to ensure treatment success.
The National Institutes of Health currently supports 137 basic science research grants on gonorrhea, including translational research to identify targets for antimicrobial development.
CDC will continue to update treatment recommendations based on surveillance data and clinical research.
By 1976, through further mutations, the gonococcus became able to produce beta-lactamase, an enzyme that destroys penicillin; strains that produce this enzyme are highly resistant to penicillin.
Men who have sex with men (MSM) were and remain disproportionately affected by QRNG (Figure 2).
Antimicrobial susceptibility testing generally is not routinely available in clinical practice, and early diagnosis and effective antimicrobial treatment of patients and their partners has been the mainstay of gonorrhea control and prevention; thus, gonococcal antimicrobial resistance poses a grave challenge. During the 1980s, penicillin- and tetracycline-resistant strains became widespread in the United States, complicating gonorrhea therapy. The acquisition of a mosaic penA gene encoding a remodeled penicillin binding protein (PBP2) and overproduction of an efflux pump in N. Local and state health departments are encouraged to promptly notify CDC of suspected treatment failures or isolates with elevated cephalosporin MICs.

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