PROCAARE: Treatment of chancroid

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Reference: Schmid, G.P. (1999).  Treatment of chancroid, 1997.  Clin.
Infect. Dis. 28(Suppl 1): S14-20.

This article reviews recommendations for the treatment of chancroid based
upon articles published between 1992-1996. 

Ceftriaxone and other cephalosporins: Several studies indicate that
ceftriaxone is highly active against H. ducreyi isolates.  Isolates from
the United States, Thailand (Antimicrob. Agents Chemother. 37: 1552 and
37: 1986), Rwanda (Clin. Infect. Dis. 20: 924), and Saudi Arabia
(Microbios 74: 103) were all uniformly susceptible to cetriaxone.  Good in
vitro activity has also been observed for ceftizoxime, ceftazidime, and
cepfirome as well.  Clinical efficacy of ceftriaxone (250 mg IM, once) has
generally be in the range of 97-100%.  One exception was a study from
Kenya which reported only a 35% efficacy among 133 men (73% for
HIV-negative individuals), despite sensitivity of isolates to ceftriaxone
(J. Infect. Dis. 167: 469).  The reasons for the high rates of clinical
failure observed in this study remain unclear, but highlight the need for
continued vigilance on clinical reponse to treatment.

Macrolides and azalides: Erythromycin and azithromycin have generally high
activity against H. ducreyi isolates, although strains resistant to
erythromycin have been reported.  A study in Nairobi, Kenya on 45 men
reported a cure rate of 91% with erythromycin 500 mg PO qid for 7 days and
89% for azithromycin at 1 gm PO once (Sex. Transm. Dis. 21: 231).  In
general, single-dose azithromycin regimens appear to be highly effective,
with studies from South Africa (Int. J. STD AIDS 7(Suppl 1): 9) and the
United States (Clin. Infect. Dis. 21: 409) reporting efficacies of
92-100%.  A study from Malawi reported a clinical failure rate of 13% for
erythromycin 250 mg PO tid and 8% for erythromycin 500 mg PO tid (J.
Infect. Dis. 171: 451).  While this difference was not statistically
significant,  in view of the associated failure rates in the study of 19%
for a trimethoprim-sulfamethoxazole-based regimen, and 0-8% for multiple
or single-dose quinolone regimens, respectively, the 500 mg-based regimen
of erythromycin appears preferable over 250 mg.

Quinolones: Quinolones have generally displayed excellent in vitro
activity against H. ducreyi, although there are concerns of increasing
quinolone resistance.  Ciprofloxacin, ofloxacin, norfloxacin, fleroxacin,
enoxacin, and sparfloxacin have all demonstrated high in vitro activity.
The most recent trials of single-dose ciprofloxacin (500 mg once) reported
response rates ranging from 73% in a study from Rwanda (Clin. Infect. Dis.
20: 924) to 92% in a South African study (Ballard et al., abstract no. 116
from the 10th meeting of the International Society for Sexually
Transmitted Diseases).  Pooling results from a number of studies of
single-dose ciprofloxacin (including early studies in 1988 demonstrating
high efficacy in Thailand) revealed a 89% pooled effectiveness rate.  This
rate appears lower than those observed for older studies of higher
single-dose ciprofloxacin regimens (1 gm PO once: Genitourin. Med. 65:
54), 500 mg PO bid for one day (Antimicrob. Agents Chemother. 32: 723),
500 mg PO bid for 3 days (Am. J. Med. 82(suppl) 317), or a more recent
study of 250 mg PO qD for 7 days (J. Infect. Dis. 171: 451), which were
associated with clinical response rates of 98-100%.

Trimethoprim/ sulfamethoxazole (TMP-SMX): Disappointing efficacy rates
have been observed for TMP-SMX, including a 53% failure rate in Rwanda for
a single dose of 640 mg TMP/3200 mg SMX, and a 19% failure rate in Malawi
for 7 days of therapy.

Amoxicillin/clavulanic acid: Significant rates of in vitro resistance have
been reported for this agent.  No new trials on clinical efficacy have
been reported.

In general, these antimicrobial agents were well-tolerated, and adverse
effects tended to be minor.  Nausea and abdominal discomfort were of
course relatively frequent with erythromycin and azithromycin-based
regimens, but the great majority of patients were able to complete their
treatment course.

The author proposes either azithromycin (1 gm PO, once), ceftriaxone (250
mg IM, once), or erythromycin (500 mg PO qid for 7 days) for the treatment
of chancroid (these recommendations are geared for the United States).
Single-dose ciprofloxacin (500 mg PO, once) has an acceptable cure rate as
high as 92%, but higher dose regimens appear to be more efficacious.
Further studies are required to determine which of the regimens of 1 gm PO
once, 500 mg PO bid for one day, or 500 mg PO bid for 3 days is most
effective.  For now, the most conservative recommendation for quinolone
use would be ciprofloxacin at 500 mg PO bid for 3 days. 

HIV status: Three studies since 1993 have addressed cure rates for
chancroid among HIV-positive and HIV-negative patients.  Only one has
shown a statistically significant decrease in efficacy for HIV-positive
individuals (Sex. Transm. Dis. 21: 231).  This study compared azithromycin
1 gm once vs. erythromycin 500 mg qid for 7 days, and reported a 79% cure
rate among HIV-positive patients, compared to 94% among HIV-negative
individuals.  A second study of azithromycin therapy  (with small numbers
of patients) reported a cure rate of 85% and 92% in HIV-positive and
negative patients, respectively, a difference which did not reach
statistical significance.  Nonetheless, it would appear prudent to more
closely monitor clinical response to therapy in HIV-infected individuals.

Circumcision status: Uncircumcised males appear to have an increased
chance for clinical failure.  In one study, an efficacy for ceftriaxone of
only 18% was reported for uncircumcised HIV-positive men, versus 58% for
circumcised men (p=0.08).  Other studies have shown statistically
significant differences in outcome depending on circumcision status with
small numbers of patients (e.g. 16/27 uncircumcised men cured vs. 16/17
circumcised men , p<0.05--Clin. Infect. Dis. 21: 409).

Management of fluctuant lymph nodes: A small randomized trial compared
needle aspiration to incision and drainage of inguinal buboes (Sex.
Transm. Dis. 22: 217).  11 patients received incision and drainage, versus
12 who underwent needle aspiration.  None of the patients receiving
incision and drainage required further intervention, while 6 of 12 in the
needle aspiration group required additional aspiration.  However, incision
and drainage is of course a more invasive procedure, requiring surgical
packing.  Further study is needed to provide parameters which most favor
incision and drainage (e.g. size of nodes, stage of suppuration).

Keywords: clinical science, sexually transmitted disease, STD, chancroid,
Haemophilus ducreyi, treatment, ceftriaxone, erythromycin, azithromycin,
trimethoprim, sulfamethoxazole, amoxicillin, circumcision, bubo, drainage.

Summarized by: Albert Shaw <ashaw@usa.healthnet.org>



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