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MASTER Home
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 Case Study:
December 2004
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Case Study - Neisseria gonorrhoeae
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MASTER Case Study
December 2004
Upon returning home to Nebraska, a 28 year old man who had vacationed in Thailand presented to the local emergency room (ER) complaining of painful urination and a purulent discharge from his penis. Urethral specimens were collected for detection of Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests (NAATs) and the patient was empirically given a single 500-mg dose of ciprofloxacin orally and a single 1-g dose of azithromycin. Subsequently, the NAATs were positive for N. gonorrhoeae, but negative for C. trachomatis. When the patient’s symptoms did not improve after two days, he again went to the local ER. The ER physician contacted the staff at the microbiology laboratory to determine if they could perform antimicrobial susceptibility testing of N. gonorrhoeae isolates. Although the laboratory’s routine procedure for diagnosis of gonococcal urethritis in adults involves direct detection using NAATs, the laboratory maintained the ability to perform culture for N. gonorrhoeae. A culture was submitted from the patient and N. gonorrhoeae was isolated. Following further discussion with the physician, the laboratory sent the isolate to a reference laboratory for antimicrobial susceptibility testing; the following report was ultimately issued.
Laboratory report
Urethral discharge
Neisseria gonorrhoeae isolated
| ceftriaxone | S | | ciprofloxacin | R | | tetracycline | S |
Question 1:
Why don’t clinical laboratories perform antimicrobial susceptibility tests routinely for N. gonorroheae?
Uncomplicated infections with N. gonorrhoeaeare treated empirically. CDC’s most recent “Sexually Transmitted Diseases Treatment Guidelines, 2002” list the following therapeutic regimens for uncomplicated gonococcal urethritis (see http://www.cdc.gov/STD/treatment/TOC2002TG.htm). Some additional updated information can be found at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5316a1.htm
Ceftriaxone 125 mg IM in a single dose
OR
Cefixime 400 mg orally in a single dose
OR
Ciprofloxacin 500 mg orally in a single dose*
OR
Ofloxacin 400 mg orally in a single dose*
OR
Levofloxacin 250 mg orally in a single dose*
PLUS,
IF CHLAMYDIAL INFECTION IS NOT RULED OUT
Azithromycin 1 g orally in a single dose
OR
Doxycycline 100 mg orally twice a day for 7 days.
*Fluoroquinolones should not be used for infections acquired in Asia or the Pacific, including Hawaii. In addition, use of fluoroquinolones is probably inadvisable for treating infections acquired in California and in other areas with increased prevalence of fluoroquinolone resistance.
Because of the increased prevalence of fluoroquinolone-resistant N. gonorrhoeae (FQRNG) in certain geographic areas, fluoroquinolones are no longer recommended for treating gonococcal infections acquired in those locations. Some of these areas include Asia, the Pacific Islands, England, and Wales. Similarly, there are several U.S. states (e.g., Hawaii, California, Massachusetts, and Washington) where the prevalence of FQRNG is sufficiently high that fluoroquinolones are not recommended as first-line agents for N. gonorrhoeae (see local FQRNG health alerts posted on http://www.cdc.gov/std/gisp/HealthAlerts.htm.) In addition, because of increased prevalence of FQRNG in men who have sex with men, CDC recommends that clinicians in the United States no longer use fluoroquinolones as a first-line treatment for gonorrhea in this group of patients. Before determining treatment for a patient suspected of having gonorrhea, clinicians should routinely ask all patients about their travel histories and male patients about the gender of their sex partners.
With the increasing prevalence of FQRNG, it is conceivable that additional antimicrobial susceptibility testing of an individual patient’s isolates will be necessary.
Question 2:
Why would the physician be interested in culture and antimicrobial susceptibility test results on this patient’s specimen?
The physician is interested in additional tests because the patient failed empiric therapy with ciprofloxacin. One reason for the patient’s failure to respond to ciprofloxacin may be due to infection with a FQRNG, and the inability of a single dose of azithromycin to completely eliminate the gonococcal infection. Susceptibility testing would be helpful to explore this possibility. Other potential reasons for clinical failure include the patient’s failure to take the ciprofloxacin as prescribed, or misdiagnosis of the etiologic agent(s) causing the patient’s infection, since there is a possibility of infection with multiple organisms.
Question 3:
If susceptibility testing is not routinely performed, how is resistance to fluoroquinolones and other antimicrobial agents monitored among N. gonorrhoeae isolated in the United States?
CDC conducts surveillance nationwide to determine the incidence of resistance among N. gonorrhoeae causing infections. As part of the Gonococcal Isolate Surveillance Project (GISP), N. gonorrhoeae isolates are collected from the first 25 men with urethral gonorrhea attending STD clinics each month in approximately 29 cities in the United States. There are five GISP regional laboratories, which determine antimicrobial susceptibilities by agar dilution for penicillin, tetracycline, spectinomycin, ciprofloxacin, ceftriaxone, cefixime, and azithromycin. Results from this surveillance system are used to help formulate empiric therapy recommendations and are available to public health and clinical practitioners (to review GISP data, please see http://www.cdc.gov/std/gisp/Default.htm). In addition to GISP, some state or local public health departments conduct local surveillance activities (to review these data, please see http://www.cdc.gov/std/gisp/NonGISP.htm).
Question 4:
How much resistance is there in the United States to the agents recommended for treating uncomplicated gonorrhea?
To date, resistance to either cefixime or ceftriaxone has not been reported, although reduced susceptibility to cefixime (MIC 0.25 - 1.0 ug/ml) has been noted in a few isolates from Hawaii. The prevalence of fluoroquinolone resistance varies considerably by location within the United States and in 2003 ranged from 0-21%, with higher prevalence in California and Hawaii and increasing prevalence in cities in the Midwest and Northeast. Fluoroquinolone resistance in some parts of Asia is as high as 60%.
Question 5:
According to the fluoroquinolone therapy recommendations, either ciprofloxacin, ofloxacin, or levofloxacin can be used for treating N. gonorrhoeae. If an isolate is intermediate or resistant to one of these is it likely to be resistant to the others?
Yes, it is likely to be intermediate or resistant since cross resistance among these fluoroquinolones is common. Because NCCLS does not have interpretive criteria for levofloxacin, an isolate that is intermediate or resistant to either ciprofloxacin or ofloxacin should be considered to have corresponding levels of resistance to levofloxacin.
Question 6:
If a laboratory performs culture for gonococci and isolates N. gonorrhoeae, should a beta-lactamase test routinely be performed on the isolate?
No, this is not necessary. The beta-lactamase test detects production of an enzyme that destroys penicillin. Because of the increasing incidence of penicillin resistance in N. gonorrhoeae, penicillin is no longer recommended as a primary agent for treatment of gonorrhea. Plasmid-mediated beta-lactamase production is only one mechanism of penicillin resistance; some strains of N. gonorrhoeae are penicillin resistant due to altered penicillin binding proteins. In such isolates, penicillin resistance can be detected by disk diffusion or MIC tests. Beta-lactamase or penicillinase-producing N. gonorrhoeae are sometimes referred to by the acronym PPNG. Isolates that are penicillin and tetracycline resistant (but beta-lactamase negative) are referred to as chromosomally mediated resistant N. gonorrhoeae or CMRNG. The genes encoding penicillin and tetracycline resistance in CMRNG are located on the chromosome.
Question 7:
Should clinical laboratories offer culture for N. gonorrhoeae in addition to direct detection tests such as NAATs?
Yes, in most settings. Rapid NAATs for N. gonorrhoeae are useful for the majority of specimens received in the clinical laboratory. However, NAATs are inappropriate for detecting N. gonorrhoeae in cases of sexual abuse. In addition, many of the NAAT kits are approved for testing only genitorurinary specimens so culture remains the test of choice for specimens from other anatomic sites (e.g., rectal or pharyngeal specimens). In complicated infections or where clinical failure occurs after what is presumed to be appropriate therapy, culture may be useful, as in the case described here. If a laboratory offers culture for N. gonorrhoeae and it is infrequently requested, a practical strategy would be to submit these tests to a reference laboratory.
In addition to NCCLS documents that describe standard procedures for antimicrobial susceptibility testing of N. gonorrhoeae, some additional references (all available from the GISP webpage, http://www.cdc.gov/std/gisp) that may be useful for clinical or public health laboratorians include:
References:
1. Centers for Disease Control and Prevention. 2004. Increases in fluoroquinolone-resistant Neisseria gonorrhoeae among men who have sex with men--United States, 2003, and revised recommendations for gonorrhea treatment, 2004. MMWR;53:335-8.
2. Centers for Disease Control and Prevention. 2002. Sexually transmitted diseases treatment guidelines 2002. MMWR 51(No. RR-6).
3. Centers for Disease Control and Prevention. 2003. Sexually Transmitted Disease Surveillance 2002 Supplement: Gonococcal Isolate Surveillance Project (GISP) Annual Report 2002. Atlanta, Georgia: U.S. Department of Health and Human Services, CDC.
4. Dicker, L.W., D.J. Mosure, R. Steece, and K.M. Stone. 2004. Laboratory tests used in U.S. Public Health Laboratories for sexually transmitted disease. Sexually Transmitted Diseases. 31:259-264.
5. Katz, A.R., M.V. Lee, R.G. Ohye, P.M. Whiticar, and P.V. Effler. 2003. Ciprofloxacin resistance in Neisseria gonorrhoeae: trends in Hawaii, 1997-2002. Lancet. 362:495.
6. NCCLS. 2003. Performance standards for antimicrobial disk susceptibility tests, eighth edition, approved standard. M2-A8, NCCLS, Wayne, PA.
7. NCCLS. 2003. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, sixth edition, approved standard. M7-A6. NCCLS, Wayne, PA.
8. NCCLS. 2004. Performance standards for antimicrobial susceptibility testing, fourteenth informational supplement. M100-S14. NCCLS, Wayne, PA.
9. Newman, L.M., S.A. Wang, R.G. Ohye, N. O'Connor, M.V. Lee, and H.S. Weinstock. 2004. The epidemiology of fluoroquinolone-resistant Neisseria gonorrhoeae in Hawaii, 2001. Clin. Infect. Dis. 38:649-54.
10. Shigemura, K., H. Okada, T. Shirakawa, K. Tanaka, S. Arakawa, S. Kinoshita, A. Gotoh, and S. Kamidono. 2004. Susceptibilities of Neisseria gonorrhoeae to fluoroquinolones and other antimicrobial agents in Hyogo and Osaka, Japan. Sexually Transmitted Infect. 80:105-7.
11. Wang, S.A., M.V. Lee, N. O'Connor, C.J. Iverson, R.G. Ohye, P.M. Whiticar, J.A. Hale, D.L. Trees, J.S. Knapp, P.V. Effler, and H.S. Weinstock. 2003. Multidrug-resistant Neisseria gonorrhoeae with decreased susceptibility to cefixime-Hawaii, 2001. Clin. Infect. Dis. 37:849-52.
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This page last reviewed: 7/12/2004
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