Antibiotic resistant gonorrhea

# Overview
Gonorrhea treatment is complicated by the ability of Neisseria gonorrhoeae to develop resistance to antimicrobials. High-level resistance to expanded-spectrum cephalosporins and Azithromycin is now reported, and it seems that developing another effective treatment has become financially unattractive for pharmaceutical companies, though new combination antibiotic treatments are being evaluated. There are no affordable alternative therapeutic options currently available for the treatment of gonococcal disease, and it appears that even newly developed antibiotics will be only a short-term solution, as the bacterium may develop resistance to them as well.

# Antibiotic Resistant Gonorrhea
- Gonorrhea treatment is complicated by the ability of Neisseria gonorrhoeae to develop resistance to antimicrobials; accordingly, a combination therapy with Azithromycin and a cephalosporin is used to improve treatment efficacy and potentially slow the emergence and spread of antimicrobial resistance.
- High-level resistance to these expanded-spectrum cephalosporins is now reported, and it seems developing another effective treatment has become unaffordable.
- In the 1980s, penicillin and tetracycline were no longer recommended to treat gonorrhea.
- Since 1986, the United States Gonococcal Isolate Surveillance Project (GISP) has been monitoring antibiotic resistance to gonorrhea.
- In 2010, it was claimed that 27,000 per 100,000 gonorrhea samples were resistant to penicillin, tetracycline, ciprofloxacin, or some combination of these drugs.
- In 2009, the first extensively drug-resistant (XDR) gonococcal strain (H041) was isolated in Japan.
- In 2010 to 2011, a second gonococcal strain (F89) with high-level cefixime and ceftriaxone resistance was isolated in France and Spain.
- In 2012, the CDC updated its treatment guidelines, recommending combination therapy with ceftriaxone and azithromycin.
- In 2014, a ceftriaxone-resistant gonococcal strain with genetic similarities to H041 was reported in Australia.
- In 2015, ceftriaxone plus azithromycin became the only recommended treatment for treating gonorrhea.
In 2006, CDC had five recommended treatment options for gonorrhea. Currently, the U.S. has only one option remaining.
- Although new combination antibiotic treatments are being evaluated, there are currently no affordable alternative therapeutic options currently available for the treatment of gonococcal disease. Further, it seems even newly developed antibiotics will only be short-term solutions, as the bacterium may develop resistance to them as well.
- Drug resistance may be developed through the following mechanisms:
Chromosomal mutations
Acquisition of R factors (plasmids)
- Chromosomal mutations
- Acquisition of R factors (plasmids)

## Gonococcal Isolate Surveillance Project
Antimicrobial resistance remains an important consideration in the treatment of gonorrhea.
- In 1986, the CDC established the Gonococcal Isolate Surveillance Project (GISP). Data are collected from selected STD clinic sentinel sites and from regional laboratories in order to: 
Monitor antimicrobial susceptibility trends in the United States
Characterize male patients with gonococcal infection
Phenotypically characterize antimicrobial-resistant isolates of Niesseira gonorrhea
- Monitor antimicrobial susceptibility trends in the United States
- Characterize male patients with gonococcal infection
- Phenotypically characterize antimicrobial-resistant isolates of Niesseira gonorrhea

### Penicillin Susceptibility
Penicillin has not been a first-line treatment option for gonorrhea for several decades. However, it has been tested for surveillance purposes.
- In 2012, almost 13.1% of Neisseria gonorrhoeae from the GISP survey were resistant to penicillin, primarily through two mechanisms:
Chromosomal penicillin resistance (82.3%)
Penicillinase production (17.7%)
- Chromosomal penicillin resistance (82.3%)
- Penicillinase production (17.7%)

### Ceftriaxone Susceptibility
- In 1987, susceptibility testing for ceftriaxone began; it is still continued today.
- From 2008 to 2011, ceftriaxone Minimum inhibitory concentrations (MICs) increased from 0.1% to 0.4%.
- Five isolates with decreased ceftriaxone susceptibility (MIC 0.5 lg/ml) include:
San Diego, California (1987)
Cincinnati, Ohio (1992 and 1993)
Philadelphia, Pennsylvania (1997)
Oklahoma City, Oklahoma (2012)
- San Diego, California (1987)
- Cincinnati, Ohio (1992 and 1993)
- Philadelphia, Pennsylvania (1997)
- Oklahoma City, Oklahoma (2012)
- From 20062012, the prevalence of elevated ceftriaxone (MICs) was higher in isolates from Men Who have
Sex With Men (MSM) than those of Men Who have Sex With Women (MSW).

### Cefixime Susceptibility
- Cefixime susceptibility testing began in 1992 and was discontinued in 2007.
- In 2009, cefixime susceptibility testing was restarted due to drug supply shortages in the United States.
- From 2006 to 2010, ceftixim minimum inhibitory concentrations (MICs) increased from 0.1 to 1.4.
- From 20062012, the prevalence of elevated cefixime (MICs) was higher in isolates from Men Who have
Sex With Men (MSM) than from Men Who have Sex With women (MSW).

### Azithromycin Susceptibility
- In 1992, susceptibility testing for azithromycin began in the United States
- From 2010 to 2013, the percentage of isolates with reduced azithromycin susceptibility (MICs  2 g/ml) ranged from 0.3% to 0.6%
- Between 2013 and 2014, the percentage increased from 0.6% to 2.5%

### Susceptibility to Other Antimicrobials
- In 2014, 37.0% of isolates collected from GISP sites were resistant to penicillin, tetracycline, ciprofloxacin, or some combination of those antimicrobials.