Lack of Macrolide Resistance in<i>Chlamydia trachomatis</i>after Mass Azithromycin Distributions for Trachoma

Hong, Kevin C.; Schachter, Julius; Moncada, Jeanne; Zhou, Zhaoxia; House, Jenafir; Lietman, Thomas M.

doi:10.3201/eid1507.081563

Cited by 42 publications

(24 citation statements)

References 11 publications

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“…Azithromycin is probably the most frequently used antibiotic against Chlamydia infections today (31), yet mutations which confer Azm r in these obligate intracellular pathogen do not appear to be selected for in vivo (14,15,36). Of particular interest for this study, tetracycline-resistant isolates of C. suis, a swine strain of Chlamydia, started to appear in pig farms only 50 years after the introduction of chlortetracycline as a growth promoter to poultry, swine, and cattle (18).…”

Section: Discussionmentioning

confidence: 99%

Impact of Azithromycin Resistance Mutations on the Virulence and Fitness of Chlamydia caviae in Guinea Pigs

Binet

Bowlin

Maurelli

et al. 2010

Antimicrob Agents Chemother

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Azithromycin (AZM) is a major drug used in the treatment and prophylaxis of infections caused byChlamydia, yet no significant clinical resistance has been reported for these obligate intracellular bacteria. Nevertheless, spontaneous AZM resistance (Azm r ) arose in vitro at frequencies ranging from 3 ؋ 10 ؊8 to 8 ؋ 10 ؊10 for clonal isolates of Chlamydia caviae, which is a natural pathogen of guinea pigs. Sequencing of the unique 23S rRNA gene copy in 44 independent Azm r isolates identified single mutations at position A 2058 or A 2059 (Escherichia coli numbering system). While SP 6 AZ 1 (A 2058 C) and SP 6 AZ 2 (A 2059 C) Azm r mutants showed growth defects in cell culture and were less pathogenic in the guinea pig ocular infection model than in the parent SP 6 , the three isogenic C. caviae isolates grew equally well in the animal. On the other hand, coinoculation of the C. caviae parent strain with one of the Azm r strains was detrimental for the mutant strain. This apparent lack of association between pathology and bacterial load in vivo showed that virulence of the two Azm r mutants of C. caviae was attenuated. While chlamydial growth in vitro reflects the ability of the bacteria to multiply in permissive cells, survival in the host is a balance between cellular multiplication and clearance by the host immune system. The obligate intracellular nature of Chlamydia may therefore limit emergence of resistance in vivo due to the strength of the immune response induced by the wild-type antibiotic-sensitive bacteria at the time of antibiotic treatment.

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Section: Discussionmentioning

confidence: 99%

Impact of Azithromycin Resistance Mutations on the Virulence and Fitness of Chlamydia caviae in Guinea Pigs

Binet

Bowlin

Maurelli

et al. 2010

Antimicrob Agents Chemother

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“…[5][6][7][8] In such situations, repeated azithromycin MDA may be detrimental if it results in the selection of macrolideresistant pathogens. Although currently there is no evidence that repeated MDA increases the prevalence of azithromycinresistant C. trachomatis, 9 there is epidemiological evidence suggesting that pharyngeal carriage of macrolide-resistant Streptococcus pneumoniae increases following repeated MDA for trachoma control. 10,11 Because S. pneumoniae is a leading cause of childhood mortality, especially in Africa, and because asymptomatic nasopharyngeal carriage is the initial step in the pathogenesis of pneumococcal disease, increased carriage of macrolide-resistant strains is a public health concern.…”

Section: Introductionmentioning

confidence: 99%

Mass administration of azithromycin andStreptococcus pneumoniaecarriage: cross-sectional surveys in the Gambia

Burr

Milne

Jafali

et al. 2014

Bull. World Health Organ.

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“…A single dose of the macrolide antibiotic azithromycin takes less than a week to clear C. trachomatis with an average efficacy of 92–98% and the World Health Organization (WHO) recommended coverage for trachoma control programs is 80% or higher (Lietman et al ., 1999). There is no documented evidence of emerging azithromycin resistance after mass distribution of azithromycin for trachoma (Solomon et al ., 2005; Hong et al ., 2009). …”

Section: Introductionmentioning

confidence: 99%

Mass drug administration: the importance of synchrony

Gao

Lietman

Dong

et al. 2016

Mathematical Medicine and Biology: A Journal of the IMA

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Mass drug administration, a strategy in which all individuals in a population are subject to treatment without individual diagnosis, has been recommended by the World Health Organization for controlling and eliminating several neglected tropical diseases, including trachoma and soil-transmitted helminths. In this article, we derive effective reproduction numbers and average post-treatment disease prevalences of a simple susceptible–infectious–susceptible epidemic model with constant, impulsive synchronized and non-synchronized drug administration strategies. In the non-synchronized model, the individuals in the population are treated at most once per period and their treatment times are uniformly distributed. Mathematically, the set of pulses for the non-synchronized model has the cardinality of the continuum. We show that synchronized and constant strategies are, respectively, the most and least effective treatments in disease control. Elimination through synchronized treatment is always possible when adequate drug efficacy and coverage are fulfilled and sustained. For a strategy with multiple rounds of synchronized treatment per period, the average post-treatment prevalence is irrelevant what the time differences between treatments are, as long as there are the same number of treatments per period.

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Lack of Macrolide Resistance inChlamydia trachomatisafter Mass Azithromycin Distributions for Trachoma

Cited by 42 publications

References 11 publications

Impact of Azithromycin Resistance Mutations on the Virulence and Fitness of Chlamydia caviae in Guinea Pigs

Impact of Azithromycin Resistance Mutations on the Virulence and Fitness of Chlamydia caviae in Guinea Pigs

Mass administration of azithromycin andStreptococcus pneumoniaecarriage: cross-sectional surveys in the Gambia

Mass drug administration: the importance of synchrony

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