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Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2010:

Oral Cephalosporins No Longer a Recommended Treatment for

Gonococcal Infections

Gonorrhea is a major cause of serious reproductive com-

plications in women and can facilitate human immunodefi-

ciency virus (HIV) transmission (1) Effective treatment is a

cornerstone of U.S gonorrhea control efforts, but treatment

of gonorrhea has been complicated by the ability of Neisseria

gonorrhoeae to develop antimicrobial resistance This report,

using data from CDC’s Gonococcal Isolate Surveillance Project

(GISP), describes laboratory evidence of declining cefixime

susceptibility among urethral NV gonorrhoeae isolates collected

in the United States during 2006-2011 and updates CDC's

current recommendations for treatment of gonorrhea (2)

Based on GISP data, CDC recommends combination therapy

with ceftriaxone 250 mg intramuscularly and either azithro-

mycin 1 g orally as a single dose or doxycycline 100 mg orally

twice daily for 7 days as the most reliably effective treatment

for uncomplicated gonorrhea CDC no longer recommends

cefixime at any dose as a first-line regimen for treatment of

gonococcal infections, If cefixime is used as an alternative agent,

then the patient should return in 1 week for a test-of-cure at

the site of infection

Infection with N gonorrhoeae is a major cause of pelvic

inflammatory disease, ectopic pregnancy, and infertility, and

can facilitate HIV transmission (7) In the United States,

From 2006 to 2010, the minimum concentrations of cefixime needed to inhibit the growth in vitro of N gonorrhoeae strains

circulating in the United States and many other countries

increased, suggesting that the effectiveness of cefixime might

be waning (4) Reports from Europe recently have described patients with uncomplicated gonorrhea infection not cured by treatment with cefixime 400 mg orally (5-8)

GISP is a CDC-supported sentinel surveillance system that has monitored N gonorrhoeae antimicrobial susceptibilities since 1986, and is the only source in the United States of national and regional N gonorrhoeae antimicrobial suscep- tibility data During September-December 2011, CDC and five external GISP principal investigators, each with

N gonorrhoeae-specific expertise in surveillance, antimicro- bial resistance, treatment, and antimicrobial susceptibility testing, reviewed antimicrobial susceptibility trends in GISP through August 2011 to determine whether to update CDC’s

current recommendations (2) for treatment of uncomplicated

gonorrhea Each month, the first 25 gonococcal urethral iso- lates coll from men attending participating STD clinics

(approximately 6,000 isolates each year) were submitted for

antimicrobial susceptibility testin g, The minimum inhibitory

concentration (MIC), the lowest antimicrobial concentration

exhibited decreased susceptibility to ceftriaxone Because

increasing MICs can predict the emergence of resistance, lower

cephalosporin MIC breakpoints were established by GISP for

surveillance purposes to provide greater sensitivity in detecting

declining gonococcal susceptibility than breakpoints defined

by CLSI Cefixime MICs 20.25 g/mL and ceftriaxone MICs

20.125 vg/mL were defined as “elevated MICs.” CLSI does not

define azithromycin resistance criteria; CDC defines decreased

azithromycin susceptibility as 22.0 vg/mL

The percentage of isolates with elevated cefixime MICs

(MICs 20.25 g/mL) increased from 0.1% in 2006 to 1.5%

during January-August 2011 (Figure) In the West, the per-

centage increased from 0.2% in 2006 to 3.2% in 2011 (Table)

The largest increases were observed in Hea aa 8

; Minneapolis, Minnesota (0%

and San Diego,

ally, among MSM, isolates

reased from 0.2% in 2006

to 3.8% in 2011 In 2011, a higher proportion of isolates

from MSM had elevated cefixime MICs than isolates from

men who have sex exclusively with women (MSW), regardless

of region (Table)

The percentage of isolates exhibiting elevated ceftriaxone

MICs increased slightly, from 0% in 2006 to 0.4% in 2011

(Figure) The percentage increased from <0.1% in 2006 to

FIGURE Percentage of urethral Neisseria gonorrhoeae isolates (n = 32,794) with elevated cefixime MICs (20.25 g/mL) and ceftriaxone MICs (20.125 g/mL) — Gonococcal Isolate Surveillance

Project, United States, 2006-August 2011

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Abbreviation: MICs = minimum inhibitory concentrations

* Cefixime susceptibility not tested during 2007-2008

† January-August 2011

The 2010 CDC STD treatment guidelines (2) recommend that azithromycin or doxycycline be administered with a cepha-

losporin as treatment for gonorrhea The percentage of isolates

exhibiting tetracycline resistance (MIC 22.0 yg/mL) was high

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occurred initially in the West and predominantly among MSM

before spreading throughout the United States within several

years Thus, observed patterns might indicate early stages of

the development of clinically significant gonococcal resistance

to cephalosporins CDC anticipates that rising cefixime MICs

soon will result in declining effectiveness of cefixime for the

treatment of urogenital gonorrhea Furthermore, as cefixime

becomes less effective, continued use of cefixime might hasten

the development of resistance to ceftriaxone, a safe, well-

tolerated, injectable cephalosporin and the last antimicrobial

that is recommended and known to be highly effective in a

single dose for treatment of gonorrhea at all anatomic sites of

infection Maintaining effectiveness of ceftriaxone for as long

as possible is critical Thus, CDC no longer recommends the

routine use of cefixime as a first-line regimen for treatment of

gonorrhea in the United States

Based on experience with other microbes that have devel-

oped antimicrobial resistance rapidly, a theoretical basis exists

for combination therapy using two antimicrobials with dif-

ferent mechanisms of action to improve treatment efficacy

and potentially delay emergence and spread of resistance to

cephalosporins Therefore, the use of a second antimicrobial

(azithromycin as a single 1-g oral dose or doxycycline 100 mg

orally twice daily for 7 days) is recommended for administra-

tion with ceftriaxone The use of azi in as the second

Uncomplicated gonococcal infections of the cervix, urethra, and rectum

Recommended regimen Ceftriaxone 250 mg in a single intramuscular dose

PLUS

Azithromycin 1 g orally in a single dose

or doxycycline 100 mg orally twice daily for 7 days*

If ceftriaxone is not available:

Cefixime 400 mg in a single oral dose

PLUS

Azithromycin 1 g orally in a single dose

or doxycycline 100 mg orally twice daily for 7 days*

PLUS

Test-of-cure in 1 week

If the patient has severe cephalosporin allergy:

Azithromycin 2 g in a single oral dose

PLUS

Test-of-cure in 1 week

Uncomplicated gonococcal infections of the pharynx Recommended regimen

Ceftriaxone 250 mg in a single intramuscular dose

PLUS

Azithromycin 1 g orally in a single dose

or doxycycline 100 mg orally twice daily for 7 days*

Uncomplicated Gonococcal Infections of the Cervix, Urethra, and Rectum

Recommended Regimens

Ceftriaxone 250 mg IM ina single dose

OR, IF NOT AN OPTION

Cefixime 400 mg orally in a single dose

OR

Single-dose injectible cephalosporin regimens

PLUS

Azithromycin 1g orally in a single dose

OR

Doxycycline 100 mg orally twice a day for 7 days

cal Isolate

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To maximize compliance with recommended therapies, medications for gonococcal infections should be dispensed

on site Ceftriaxone in a single injection of 250 mg provides

sustained, high bactericidal levels in the blood Extensive clini-

cal experience indicates that ceftriaxone is safe and effective for the treatment of uncomplicated gonorrhea at all anatomic sites, curing 99.2% of uncomplicated urogenital and anorectal and 98.9% of pharyngeal infections in published clinical 1a (306.307) A250-mg dose of ceftriaxone is now recommended

over a 125-mg dose given the 1) increasingly wide geographic

distribution of isolates demonstrating aaa eT

to cephalosporins in vitro, 2) reports of ceftriaxone treatment

of ceftriaxone 250 mg

which is often unrecognized), and 4) the

aving a simple and consistent recommendation for treatment regardless of the anatomic site involved

CEFIXIME

® A 400-mg oral dose of cefixime: Cured

© 97.5% of uncomplicated urogenital and anorectal infections

© 92.3% of pharyngeal infections

e Providers should inquire:

e® C)ral sexual eXpOSUre

e Treat these patients with ceftriaxone: well documented efficacy in pharyngeal infection

OTHER CEPHALOSPORIN REGIMENS

Single-dose injectible cephalosporin regimens that are safe and highly effective:

° Ceftizoxime (500 mg, IM)

¢ Cefoxitin (2 g, IM with probenecid 1 g orally)

e Cefotaxime (500 mg, IM)

None of the injectible cephalosporins:

e Any advantage over ceftriaxone for urogenital infection

e Efficacy for pharyngeal infection is less certain

AZITHROMYCIN 2 G

e Effective against uncomplicated infection (99.2%)

e Azithromycin 1 g meets alternative regimen criteria (97.6%)

e Not recommended because of treatment failures

e Concerns about possible emergence of antimicrobial resistance

e Not adequately susceptible to penicillins, tetracyclines, and older macrolides (e.g., erythromycin)

MMWR August 4, 2006

alternative nonquinolone regimens in this report should be

considered

Similar to ciprofloxacin, ofloxacin is no longer universally

effective against NV gonorrhoeae in the United States The 400

mg oral dose of ofloxacin has been effective for treatment of

L uncomplicated urogenital and anorectal infections; in clini-

cal trials, 98.6% of infections were cured (140) Levofloxacin,

the active Lisomer of ofloxacin, can be used in place of

in ofloxacin as a single dose of 250 mg

Alternative Regimens

Spectinomycin 2 g in a single IM dose

OR Single-dose cephalosporin regimens

Single-dose quinolone regimens

SPECTINOMYCIN

e Useful in persons who cannot tolerate cephalosporins

e Curing 98.2% of uncomplicated urogenital and anorectal infections

e Poor efficacy against pharyngeal infection (51.8%)

e Expensive, not available in the United States

OTHERS

e Cefpodoxime 400mg orally:

e Some evidences: an alternative treatment

e Pharyngeal site: poor

e Cefuroxime axetil 1 g orally:

e Pharmacodynamics: less favorable than cefpodoxime, cefixime, or ceftriaxone

e Minimum efficacy as an alternative regimen

e Treating pharyngeal infection is poor (56.9%)

ask their patients about oral sexual exposure; 1T reported,

patients should be treated with a regimen with acceptable

efficacy against pharyngeal infection Chlamydial coinfection

of the pharynx is unusual; however, because coinfection at genital sites sometimes occurs, treatment for both gonorrhea

and chlamydia is recommended

Recommended Regimens

Ceftriaxone 250 mg IM ina single dose

PLUS

Azithromycin 1g orally in a single dose

OR

Doxycycline 100 mg orally twice a day for 7 days

Y TẾ TPHCM

Bệnh viện Da Liễu

Khoa Xét nghiệm

TONG KET KHANG SINH ĐỒ NĂM 2012

Azm

100.0 0.0 0.0

98.4 0.0 1.6

0.0 0.0 100.0

Cc 100.0 0.0 0.0

Er

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Chú thích :

Er Erythromycin CIP Ciprofloxacin CRO Ceftriazone

Dx Doxycycline P Penicilline TE Tetracycline

Bt Bactrim NA Nalidixic acid CFM Cefixime

SPT Spectinomycin c Chioramphenicol AZM Azithromycin

A

Bénh vién Da

Khoa Xét nghiém

TONG KET KHANG SINH DO 6 THANG DAU NAM 2013

Chú thích :

Er Erythromycin CIP Ciprofloxacin CRO Ceftriazone

Dx Doxycycline P Penicilline TE Tetracycline

Bt Bactrim NA Nalidixic acid CFM Cefixime

SPT Spectinomycin c Chloramphenicol AZM Azithromycin

Điều trị lậu (đề nghị)

e Niéu sinh duc va hau mon truc trang:

e Cefixime 400mg (U), hoac

e Spectinomycin 2g (TB), hoac

e Chloramphenicol (U) ?

e Hau hong (quan hé đường miệng):

se Ceftriaxone 250mg (TB)

e Tai kham sau 1 tuan

e Diéu tri kem Chlamydia:

e Azithromycin 1g (U), hoac

e® Doxycycline 100mg 2 lan/ngay x 7 ngay (U)

Mot so dé nghi

Tái khám sau 1 tuần: Cefixime, Ceftriaxone Cay va lam khang sinh do:

Còn triệu chứng

Trước khi điều trị Ceftriaxone 2

Tăng số mẫu giám sát

Cong tac CDT:

Khuyén cáo định kỳ cho khu vực phía Nam Khuyén cao:

e Cay va làm kháng sinh đồ tất cả trường hợp không đáp ứng

e Chuyén tuyén trén

Chân thành cám ơn quý đồng nghiệp