In vitro susceptibilities of isolates of Haemophilus ducreyi from Thailand and the United States to currently recommended and newer agents for treatment of chancroid

Knapp, Joan S.; Back, Arthur F.; Babst, Anna; Taylor, David N.; Rice, Roselyn J.

doi:10.1128/aac.37.7.1552

Cited by 32 publications

(14 citation statements)

References 14 publications

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“…Although H. ducreyi is thought to be universally susceptible to third-generation cephalosporins, macrolides, and quinolones, reports of resistance to or treatment failures with these agents occurred in the early 1990s (14)(15)(16). Due to syndromic management, no new data on antimicrobial susceptibility have been available for nearly 20 years.…”

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confidence: 99%

A (p)ppGpp-Null Mutant of Haemophilus ducreyi Is Partially Attenuated in Humans Due to Multiple Conflicting Phenotypes

Holley

Gangaiah

et al. 2014

Infect Immun

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f (p)ppGpp responds to nutrient limitation through a global change in gene regulation patterns to increase survival. The stringent response has been implicated in the virulence of several pathogenic bacterial species. Haemophilus ducreyi, the causative agent of chancroid, has homologs of both relA and spoT, which primarily synthesize and hydrolyze (p)ppGpp in Escherichia coli. We constructed relA and relA spoT deletion mutants to assess the contribution of (p)ppGpp to H. ducreyi pathogenesis. Both the relA single mutant and the relA spoT double mutant failed to synthesize (p)ppGpp, suggesting that relA is the primary synthetase of (p)ppGpp in H. ducreyi. Compared to the parent strain, the double mutant was partially attenuated for pustule formation in human volunteers. The double mutant had several phenotypes that favored attenuation, including increased sensitivity to oxidative stress. The increased sensitivity to oxidative stress could be complemented in trans. However, the double mutant also exhibited phenotypes that favored virulence. When grown to the mid-log phase, the double mutant was significantly more resistant than its parent to being taken up by human macrophages and exhibited increased transcription of lspB, which is involved in resistance to phagocytosis. Additionally, compared to the parent, the double mutant also exhibited prolonged survival in the stationary phase. In E. coli, overexpression of DksA compensates for the loss of (p)ppGpp; the H. ducreyi double mutant expressed higher transcript levels of dksA than the parent strain. These data suggest that the partial attenuation of the double mutant is likely the net result of multiple conflicting phenotypes.

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confidence: 99%

A (p)ppGpp-Null Mutant of Haemophilus ducreyi Is Partially Attenuated in Humans Due to Multiple Conflicting Phenotypes

Holley

Gangaiah

et al. 2014

Infect Immun

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“…Except as indicated below, the isolates were routinely grown on chocolate agar supplemented with 1% IsoVitaleX at 35°C in a 5% CO 2 atmosphere. For ribotyping and determination of MICs, the chocolate agar was supplemented with 5% fetal bovine serum (FBS) as described previously (6).…”

Section: Methodsmentioning

confidence: 99%

Haemophilus ducreyi Is Susceptible to Protegrin

Fortney¹,

Totten

Lehrer

et al. 1998

Antimicrob Agents Chemother

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Protegrins, potent antimicrobial peptides found in porcine leukocytes, have activity against the sexually transmitted pathogens Neisseria gonorrhoeae,Chlamydia trachomatis, and human immunodeficiency virus type 1. We tested synthetic protegrin 1 (PG-1) for activity against nine isolates of Haemophilus ducreyi, the etiologic agent of chancroid. The test organisms included CIP 542 (the type strain), 35000HP (a human-passaged variant of 35000), 35000HP-RSM2 (an isogenicd-glycero-d-manno-heptosyltransferase mutant of 35000HP), and six clinical isolates. The isolates were epidemiologically unrelated, represented three HindIII ribotypes, and had varying antimicrobial resistance patterns. In bactericidal assays, five isolates were rapidly killed by synthetic PG-1. In radial diffusion assays, all nine isolates were exquisitely sensitive to PG-1. These data highlight the potential of protegrins for development as topical agents to prevent many sexually transmitted diseases, including chancroid.

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“…However, in patients where concomitant infection of H. ducreyi and HIV is diagnosed, a longer course of therapy and close monitoring are mandatory 78-80 · A number of antibiotics have since been tried in the preceding eventful decade, with capricious success. [79][80][81][82][83][84][85][86][87][88][89] Prominent amongst them are flexoxacin, which is useful both in HIV-1 sero-positive and sero-negative individuals with chancroid, 83 with a recorded 35% failure of ceftriaxone in HIV-1 positive patients; 84 a single i.m. 2-g dose of spectinomycin is also safe and effective, 85 as is three doses of enoxacin 400 mg at 12-h intervals.…”

Section: Treatment and Follow Upmentioning

confidence: 99%