0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Research Letter |

Trends in Neisseria gonorrhoeae Susceptibility to Cephalosporins in the United States, 2006-2014 FREE

Robert D. Kirkcaldy, MD, MPH1; Edward W. Hook III, MD2; Olusegun O. Soge, PhD3; Carlos del Rio, MD4; Grace Kubin, PhD5; Jonathan M. Zenilman, MD6; John R. Papp, PhD1
[+] Author Affiliations
1Division of STD Prevention, US Centers for Disease Control and Prevention, Atlanta, Georgia
2University of Alabama, Birmingham
3University of Washington, Seattle
4Emory University, Atlanta, Georgia
5Texas Department of State Health Services, Austin
6Johns Hopkins University, Baltimore, Maryland
JAMA. 2015;314(17):1869-1871. doi:10.1001/jama.2015.10347.
Text Size: A A A
Published online

Gonorrhea is a common sexually transmitted disease that, if untreated, can cause reproductive health complications. Treatments for gonorrhea have been repeatedly jeopardized by antimicrobial resistance. To ensure effective treatment, the US Centers for Disease Control and Prevention (CDC) periodically updates guidelines based on resistance trends. Following declining cephalosporin susceptibility in several countries, the CDC updated its treatment recommendation in 2010 from single-dose cephalosporin (injectable ceftriaxone or oral cefixime) to intensified combination therapy with either ceftriaxone (at a higher dose than previously recommended) or cefixime plus a second antimicrobial.1

The CDC updated the guidelines again in 2012 to recommend ceftriaxone-based combination therapy as the single recommended therapy.1 We describe recent gonococcal cephalosporin susceptibility trends, emphasizing changes following publication of these guidelines.

We analyzed 2006-2014 data from the CDC’s Gonococcal Isolate Surveillance Project (GISP), a sentinel system that monitors antimicrobial susceptibility in urethral isolates from consecutive men with gonorrhea treated at US public clinics for sexually transmitted disease.2 Jurisdictions competitively apply to participate. GISP is not designed to be nationally representative, but rather to detect emerging changes in susceptibility. Susceptibility is determined by agar dilution. Isolates with ceftriaxone minimum inhibitory concentrations of 0.125 µg/mL or greater or cefixime minimum inhibitory concentrations of 0.25 µg/mL or greater were categorized as exhibiting reduced susceptibility.

Trends were examined overall (and tested for significance [2-sided P < .05] by the Cochran-Armitage trend test) and stratified by region and sex of the sex partner. Analyses were conducted using SAS version 9.3 (SAS Institute Inc). GISP was determined by the Office of the Associate Director for Science, National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention, CDC to be a surveillance activity rather than human subject research. Isolates are collected during clinical care and separate consent is not required. Gonorrhea is notifiable; health departments have the authority to collect and transmit case data to the CDC.

During 2006-2014, 51 144 isolates were collected in 34 cities. Most isolates were collected in the West (36.6%) or South (32.2%); gay, bisexual, or other men who have sex with men contributed 28.1% of isolates. The percentage of participants treated with 250 mg of ceftriaxone intramuscularly increased from 8.7% (95% CI, 8.0%-9.5%) in 2006 to 96.6% (95% CI, 96.1%-97.1%) in 2014 (P < .001). The percentage of isolates with reduced cefixime susceptibility increased from 0.1% (95% CI, <0.1%-0.2%) in 2006 to 1.4% (95% CI, 1.1%-1.7%) in 2011, and then declined to 0.4% (95% CI, 0.3%-0.6%) in 2013 (P < .001) (Figure).

Place holder to copy figure label and caption
Figure.
Urethral Neisseria gonorrhoeae Isolates With Reduced Cefixime or Ceftriaxone Susceptibility by Year in the Gonococcal Isolate Surveillance Project, 2006-2014

Reduced cefixime susceptibility defined as minimum inhibitory concentrations of 0.25 µg/mL or greater. Reduced ceftriaxone susceptibility defined as minimum inhibitory concentrations of 0.125 µg/mL or greater. There was a trend in elevated cefixime minimum inhibitory concentrations from 2006-2011 (P < .001), 2011-2013 (P < .001), and 2013-2014 (P = .02; using the χ2 test). There was a trend in elevated ceftriaxone minimum inhibitory concentrations from 2006-2011 (P < .001), 2011-2013 (P < .001), and 2013-2014 (P = .13; using the χ2 test). Error bars indicate 95% confidence intervals.

aCefixime susceptibility was not tested in 2007 and 2008.

Graphic Jump Location

In 2014, the percentage of isolates was 0.8% (95% CI, 0.5%-1.0%). Among isolates from men who have sex with men, the percentage with reduced susceptibility peaked at 4.0% (95% CI, 3.1%-5.0%) and was 1.3% (95% CI, 0.8%-1.9%) in 2014 (Table). Among men who reported having sex exclusively with women, the percentage remained low. In regard to ceftriaxone, the annual overall percentage of isolates with reduced susceptibility fluctuated between 0.1% (95% CI, <0.1%-0.1%) and 0.4% (95% CI, 0.2%-0.6%) (Figure).

Table Graphic Jump LocationTable.  Urethral Neisseria gonorrhoeae Isolates With Reduced Cefixime Susceptibility by Year in the Gonococcal Isolate Surveillance Project, 2006-2014a

The prevalence of reduced cefixime susceptibility declined nearly 70% between 2011 and 2013, suggesting a halting of drift toward resistance. Although this improvement in susceptibility appears temporally correlated with treatment guideline changes, we cannot establish a causal relationship. Observed susceptibility trends mirror those in other countries, only some of which changed treatment guidance to ceftriaxone-based dual therapy.3,4 Other factors, such as mutation fitness costs or faltering transmission of a clone, might have contributed to improved susceptibility. The 2014 data, however, suggest that improvements in susceptibility may be short-lived.

Although sampling is systematic, participants and participating sites are not selected at random. Thus, prevalence data from participating sites are not expected to be nationally representative. However, data from the GISP have been found to reflect trends in other US settings and populations.5 Not all jurisdictions participated continuously during 2006-2014. GISP data cannot distinguish incident infections from repeated sampling of the same infection (although this is expected to be rare).

The increased prevalence of reduced cefixime susceptibility in 2014 highlights the need to maintain surveillance, search for new therapeutics, and ensure that gonorrhea is treated according to the CDC’s guidelines.

Section Editor: Jody W. Zylke, MD, Deputy Editor.

Corresponding Author: Robert D. Kirkcaldy, MD, MPH, Division of STD Prevention, US Centers for Disease Control and Prevention (CDC), 1600 Clifton Rd, Atlanta, GA 30329 (rkirkcaldy@cdc.gov).

Author Contributions: Dr Kirkcaldy had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Kirkcaldy, Hook, del Rio, Zenilman.

Acquisition, analysis, or interpretation of data: Kirkcaldy, Soge, del Rio, Kubin, Zenilman, Papp.

Drafting of the manuscript: Kirkcaldy.

Critical revision of the manuscript for important intellectual content: Hook, Soge, del Rio, Kubin, Zenilman, Papp.

Statistical analysis: Kirkcaldy.

Obtained funding: Soge, del Rio.

Administrative, technical, or material support: Kirkcaldy, Hook, Soge, Kubin, Zenilman, Papp.

Study supervision: Kirkcaldy, Zenilman.

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Hook reported receiving grants from Becton Dickinson, Hologic, Roche Molecular, and Cempra; serving as a consultant for Rib-X (Melinta) and Cempra; receiving honoraria from Becton Dickinson, Roche Molecular, and Cepheid; and receiving royalties from McGraw-Hill. No other disclosures were reported.

Funding/Support: The Gonococcal Isolate Surveillance Project is funded by the CDC, an agency of the US Department of Health and Human Services.

Role of the Funder/Sponsor: Staff from the CDC had a role in the design and conduct of the study; collection, management, analysis, and interpretation of data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC.

Centers for Disease Control and Prevention (CDC).  Update to CDC’s sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012;61(31):590-594.
PubMed
Centers for Disease Control and Prevention. Gonococcal Isolate Surveillance Project (GISP) protocol. http://www.cdc.gov/std/gisp/gisp-protocol-oct-2014.pdf. Accessed January 14, 2015.
Ison  CA, Town  K, Obi  C,  et al; GRASP Collaborative Group.  Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011. Lancet Infect Dis. 2013;13(9):762-768.
PubMed   |  Link to Article
European Centre for Disease Prevention and Control. Gonococcal antimicrobial susceptibility in Europe 2012. http://ecdc.europa.eu/en/publications/Publications/gonococcal-antimicrobial-susceptibility-surveillance-Europe-2012.pdf. Accessed May 8, 2015.
Kidd  S, Lee  MV, Maningas  E,  et al.  Gonococcal susceptibility to cephalosporins—Hawaii, 2003 to 2011. Sex Transm Dis. 2013;40(9):756-759.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure.
Urethral Neisseria gonorrhoeae Isolates With Reduced Cefixime or Ceftriaxone Susceptibility by Year in the Gonococcal Isolate Surveillance Project, 2006-2014

Reduced cefixime susceptibility defined as minimum inhibitory concentrations of 0.25 µg/mL or greater. Reduced ceftriaxone susceptibility defined as minimum inhibitory concentrations of 0.125 µg/mL or greater. There was a trend in elevated cefixime minimum inhibitory concentrations from 2006-2011 (P < .001), 2011-2013 (P < .001), and 2013-2014 (P = .02; using the χ2 test). There was a trend in elevated ceftriaxone minimum inhibitory concentrations from 2006-2011 (P < .001), 2011-2013 (P < .001), and 2013-2014 (P = .13; using the χ2 test). Error bars indicate 95% confidence intervals.

aCefixime susceptibility was not tested in 2007 and 2008.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable.  Urethral Neisseria gonorrhoeae Isolates With Reduced Cefixime Susceptibility by Year in the Gonococcal Isolate Surveillance Project, 2006-2014a

References

Centers for Disease Control and Prevention (CDC).  Update to CDC’s sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012;61(31):590-594.
PubMed
Centers for Disease Control and Prevention. Gonococcal Isolate Surveillance Project (GISP) protocol. http://www.cdc.gov/std/gisp/gisp-protocol-oct-2014.pdf. Accessed January 14, 2015.
Ison  CA, Town  K, Obi  C,  et al; GRASP Collaborative Group.  Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007-2011. Lancet Infect Dis. 2013;13(9):762-768.
PubMed   |  Link to Article
European Centre for Disease Prevention and Control. Gonococcal antimicrobial susceptibility in Europe 2012. http://ecdc.europa.eu/en/publications/Publications/gonococcal-antimicrobial-susceptibility-surveillance-Europe-2012.pdf. Accessed May 8, 2015.
Kidd  S, Lee  MV, Maningas  E,  et al.  Gonococcal susceptibility to cephalosporins—Hawaii, 2003 to 2011. Sex Transm Dis. 2013;40(9):756-759.
PubMed   |  Link to Article
CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

3,188 Views
3 Citations
×

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs