In the JournalsPerspective

Gonorrhea resistance to AZM reaches 5% threshold among Seattle MSM

A three-dimensional computer-generated image of drug-resistant Neisseria gonorrhoeae diplococcal bacteria.
A computer-generated image of drug-resistant gonorrhea.
Source: CDC

In Seattle, an increasing number of gonorrhea infections in men who have sex with men have demonstrated reduced susceptibility to azithromycin — one of two drugs recommended to treat the increasingly drug-resistant STD.

According to researchers from the Seattle and King County public health department, the CDC has set an azithromycin “alert value” minimum inhibitory concentration (MIC) level of 2 µg/mlL or greater for Neisseria gonorrhea.

WHO and the CDC recommend single doses of intramuscular ceftriaxone (250 mg) and oral azithromycin (1 g) to treat gonorrhea, but both also recommend removing an antimicrobial from treatment when more than 5% of circulating isolates are resistant to the drug or it becomes less than 95% effective. Between 2014 and 2016, 5% of gonorrhea cases identified in MSM in Seattle had azithromycin alert-value MICs, the researchers reported.

“If we consider alert value isolates resistant, we are now at that threshold among MSM in King County,” Lindley A. Barbee, MD, MPH, instructor in the division of allergy and infectious diseases at the University of Washington and assistant director of the HIV/STD program in the local health department, and colleagues wrote in Clinical Infectious Diseases. “This occurrence raises the issue of whether [azithromycin] should continue to be part of standard gonorrhea treatment.”

The CDC has designated gonorrhea as one of the three most urgent antibiotic-resistant threats in the United States, behind only Clostridium difficile and carbapenem-resistant Enterobacteriaceae (CRE). According to recent WHO data, the number of countries that reported drug-resistant gonorrhea infections increased between 2009 and 2014. Most countries that reported data to WHO saw resistance to both ceftriaxone and azithromycin, underscoring the need for new antibiotics to treat gonorrhea.

Barbee and colleagues evaluated antimicrobial susceptibility profiles and clinical data of

gonococcal isolates collected at the Seattle and King County health department’s STD clinic from 2012 to 2016. They compared cases that had azithromycin alert-value MICs with those that had MIC levels of 1 µg/mL or lower.

None of the 263 gonorrhea infections reported in 2012 or 2013 had organisms with alert-value MICs. However, between 2014 and 2016, 4.4% of 926 total gonorrhea cases, including 5% of the 765 cases reported among MSM, showed reduced susceptibility to azithromycin.

Barbee and colleagues said there were no treatment failures between 2014 and 2016 in patients whose gonorrhea infections were treated with regimens containing ceftriaxone. But they said regimens containing azithromycin — which was added to gonorrhea regimens to treat concurrent, undiagnosed chlamydia — are “problematic” for several reasons.

They said little clinical data exist to support using azithromycin to treat gonorrhea, which may actually be promoting resistance. Moreover, because azithromycin’s half-life is longer than ceftriaxone’s, infections that are not eradicated in the first 30 hours following treatment may be exposed to azithromycin monotherapy for up to 14 days, Barbee and colleagues noted.

“Further research is needed to understand how antibiotic use affects the development of resistance in N. gonorrhoeae at both the individual and population level, and to develop new gonorrhea treatment options,” they concluded. – by Gerard Gallagher

Disclosure: Barbee reports receiving research support from Hologic, Inc.

A three-dimensional computer-generated image of drug-resistant Neisseria gonorrhoeae diplococcal bacteria.
A computer-generated image of drug-resistant gonorrhea.
Source: CDC

In Seattle, an increasing number of gonorrhea infections in men who have sex with men have demonstrated reduced susceptibility to azithromycin — one of two drugs recommended to treat the increasingly drug-resistant STD.

According to researchers from the Seattle and King County public health department, the CDC has set an azithromycin “alert value” minimum inhibitory concentration (MIC) level of 2 µg/mlL or greater for Neisseria gonorrhea.

WHO and the CDC recommend single doses of intramuscular ceftriaxone (250 mg) and oral azithromycin (1 g) to treat gonorrhea, but both also recommend removing an antimicrobial from treatment when more than 5% of circulating isolates are resistant to the drug or it becomes less than 95% effective. Between 2014 and 2016, 5% of gonorrhea cases identified in MSM in Seattle had azithromycin alert-value MICs, the researchers reported.

“If we consider alert value isolates resistant, we are now at that threshold among MSM in King County,” Lindley A. Barbee, MD, MPH, instructor in the division of allergy and infectious diseases at the University of Washington and assistant director of the HIV/STD program in the local health department, and colleagues wrote in Clinical Infectious Diseases. “This occurrence raises the issue of whether [azithromycin] should continue to be part of standard gonorrhea treatment.”

The CDC has designated gonorrhea as one of the three most urgent antibiotic-resistant threats in the United States, behind only Clostridium difficile and carbapenem-resistant Enterobacteriaceae (CRE). According to recent WHO data, the number of countries that reported drug-resistant gonorrhea infections increased between 2009 and 2014. Most countries that reported data to WHO saw resistance to both ceftriaxone and azithromycin, underscoring the need for new antibiotics to treat gonorrhea.

Barbee and colleagues evaluated antimicrobial susceptibility profiles and clinical data of

gonococcal isolates collected at the Seattle and King County health department’s STD clinic from 2012 to 2016. They compared cases that had azithromycin alert-value MICs with those that had MIC levels of 1 µg/mL or lower.

None of the 263 gonorrhea infections reported in 2012 or 2013 had organisms with alert-value MICs. However, between 2014 and 2016, 4.4% of 926 total gonorrhea cases, including 5% of the 765 cases reported among MSM, showed reduced susceptibility to azithromycin.

Barbee and colleagues said there were no treatment failures between 2014 and 2016 in patients whose gonorrhea infections were treated with regimens containing ceftriaxone. But they said regimens containing azithromycin — which was added to gonorrhea regimens to treat concurrent, undiagnosed chlamydia — are “problematic” for several reasons.

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They said little clinical data exist to support using azithromycin to treat gonorrhea, which may actually be promoting resistance. Moreover, because azithromycin’s half-life is longer than ceftriaxone’s, infections that are not eradicated in the first 30 hours following treatment may be exposed to azithromycin monotherapy for up to 14 days, Barbee and colleagues noted.

“Further research is needed to understand how antibiotic use affects the development of resistance in N. gonorrhoeae at both the individual and population level, and to develop new gonorrhea treatment options,” they concluded. – by Gerard Gallagher

Disclosure: Barbee reports receiving research support from Hologic, Inc.

    Perspective

    Photo of Jeanne Marrazzo

    The finding that 5% of MSM with gonorrhea in Seattle had reduced susceptibility to azithromycin is alarming, considering that macrolides are one of only two remaining drug classes with reliable activity against this ever-evolving pathogen. This finding aligns with the CDC’s recent report that nationally, reduced susceptibility to azithromycin increased during 2013-2015 from 0.6% to 2.6%. The Global Antibiotic Research and Development Partnership (GARDP), launched by WHO in 2016, has developed a plan to address next steps in securing new antibiotics for this infection, a truly urgent global need. In the near term, this study raises more proximate concern about inclusion of azithromycin in routine treatment of gonorrhea. Is it time to walk it back?

    Jeanne Marrazzo, MD, MPH

    Director, division of infectious diseases
    University of Alabama at Birmingham School of Medicine

    Disclosure: Marrazzo reports being an investigator on an NIH-funded trial of an experimental new antibiotic for gonorrhea supplied by Entasis.