material responsible for acquisition of a penA allele may also
involve incorporation of a portion of the 110 tbpB locus.
The relatively low frequency (10.2%) of isolates with alert
value MIC for ciproﬂoxacin found in 2009 in this study was
of interest. In previous years, in San Francisco, particularly
2005–2007, frequencies of isolates with alert value cipro-
ﬂoxacin MIC ranged from 30% to 45% annually. It is un-
known whether the drop in frequency seen for alert value
MIC for ciproﬂoxacin is due to a shift in sequence types
located in San Francisco, or whether sequence types have
persisted over time, but have lost the mutations required for
resistance due to a lack of selective pressure. Experiments are
in progress to answer this question.
The data herein support that phenotypic markers of anti-
microbial resistance are associated with speciﬁc N. gonor-
rhoeae sequence types. These methods hold promise in
improving our ability to better monitor potential increases in
local transmission and the importation of resistant strains of
N. gonorrhoeae. Further characterization of the phenotypic,
genotypic, and epidemiologic characteristics of NG from
diverse geographic areas may be needed.
We thank the San Francisco Department of Public Health
STD Control branch and City Clinic for the acquisition of
GISP isolates. Antimicrobial phenotype testing was provided
by the CDC through the University of Washington Regional
GISP Laboratory in Seattle, WA. This research was sup-
ported in part by the Emerging Infectious Diseases (EID)
Fellowship Program administered by the Association of
Public Health Laboratories (APHL) and funded by the CDC.
No competing ﬁnancial interests exist.
1. Allen, V.G., D.J. Farrell, A. Rebbapragada, J. Tan, N. Tijet,
S.J. Perusini, L. Towns, S. Lo, D.E. Low, and R.G. Melano.
2011. Molecular analysis of antimicrobial resistance mecha-
nisms in Neisseria gonorrhoeae isolates from Ontario, Canada.
Antimicrob. Agents Chemother. 55:703–712.
2. Barry, P.M., and J.D. Klausner. 2009. The use of cephalo-
sporins for gonorrhea: the impending problem of resistance.
Expert Opin. Pharmacother. 10:555–577.
3. (CDC) Centers for Disease Control and Prevention. 2010.
Sexually Transmitted Disease Surveillance 2009. U.S. De-
partment of Health and Human Services, Atlanta, GA.
4. (CDC) Centers for Disease Control and Prevention. 2007.
Update to CDC’s sexually transmitted diseases treatment
guidelines, 2006: ﬂouorquinolones no longer recommended
for treatment of Gonococcal infections. MMWR 56:332–336.
5. Deguchi, T., et al. 2003. Treatment of uncomplicated Go-
nococcal urethritis by double-dosing of 200 mg ceﬁxime at a
6-h interval. J. Infect. Chemother. 9:35–39.
6. Dempsey, J.A., W. Litaker, A. Madhure, T.L. Snodgrass, and
J.G. Cannon. 1991. Physical map of the chromosome of Neis-
seria gonorrhoeae FA1090 with locations of genetic markers,
including opa and pil genes. J Bacteriol. 1991 173:5476–5486.
7. Felsenstein, J. 1981. Evolutionary trees from DNA se-
quences: a maximum likelihood approach. J. Mol. Evol. 17:
8. Hall, T.A. 1999. BioEdit: a user-friendly biological sequence
alignment editor and analysis program for Windows 95/98/
NT. Nucl. Acids. Symp. Ser. 41:95–98.
Available at www.cdc.gov/std/gisp/. (Online.)
10. Ison, C.A., J. Hussey, K.N. Sankar, J. Evans, and S. Alex-
ander. 2011. Gonorrhea treatment failures to ceﬁxime and
azithromycin in England, 2010. Euro Surveill. 16(14). pii:
11. Kirkcaldy, R.D., R.C. Ballard, and D. Dowell. 2011. Go-
nococcal resistance: are cephalosporins next? Curr. Infect.
Dis. Rep. 13:196–204.
12. Martin, I.M., C.A. Ison, D.M. Aanensen, K.A. Fenton, and
B.G. Spratt. 2004. Rapid sequence-based identiﬁcation of
gonococcal transmission clusters in a large metropolitan
area. J. Infect. Dis. 189:1497–1505.
13. Ochiai, S., H. Ishiko, M. Yasuda, and T. Deguchi. 2008.
Rapid detection of the mosaic structure of the Neisseria go-
norrhoeae penA gene, which is associated with decreased
susceptibilities to oral cephalosporins. J. Clin. Microbiol. 46:
14. Ohnishi, M., D. Golparian, K. Shimuta, T. Saika, S. Hos-
hina, K. Iwasaku, S. Nakayama, J. Kitawaki, and M. Un-
emo. 2011. Is Neisseria gonorrhoeae initiating a future era of
untreatable gonorrhea?: detailed characterization of the ﬁrst
strain with high-level resistance to ceftriaxone. Antimicrob.
Agents Chemother. 55:
15. Palmer, H.M., H. Young, C. Graham, and J. Dave. 2008.
Prediction of antibiotic resistance using Neisseria gonor-
rhoeae multi-antigen sequence typing. Sex. Transm. Infect.
16. Pandori, M., P.M. Barry, A. Wu, A. Ren, W.L.H. Whit-
tington, S. Liska, and J.D. Klausner. 2009. Mosaic penicil-
lin-binding protein 2 in Neisseria gonorrhoeae isolates
collected in 2008 in San Francisco, California. Antimicrob.
Agents Chemother. 53:4032–4034.
17. Takahata, S., N. Senju, Y. Osaki, T. Yoshida, and T. Ida.
2006. Amino acid substitutions in mosaic penicillin-binding
protein 2 associated with reduced susceptibility to ceﬁxime
in clinical isolates of Neisseria gonorrhoeae. Antimicrob.
Agents Chemother. 50:3638–3645.
18. Tapsall, J.W., F. Ndowa, D.A. Lewis, and M. Unemo. 2009.
Meeting the public health challenge of multidrug- and ex-
tensively drug resistant Neisseria gonorrhoeae. Exp. Rev.
Anti. Infect. Ther. 7:821–834.
19. Unemo, M., D. Golparian, G. Syversen, D.F. Vestrheim,
and H. Moi. 2010. Two cases of veriﬁed clinical failures
using internationally recommended ﬁrst-line ceﬁxime for
gonorrhoeae treatment, Norway, 2010. Euro. Surveil. 15(47).
20. Wu A, S. Buono, K.A. Katz, and M.W. Pandori. 2011.
Clinical Neisseria gonorrhoeae isolates in the United States
with resistance to azithromycin possess mutations in all 23S
rRNA alleles and the mtrR coding region. Microb. Drug
21. Yokioi, S., et al. 2007. Threat to ceﬁxime treatment of go-
norrhoeae. Emerg. Infect. Dis. 13:1275–1277.
Address correspondence to:
Mark W. Pandori, Ph.D.
San Francisco Department of Public Health Laboratory
101 Grove St. Room 419
San Francisco, CA 94102
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