Is There a Resistance Threshold for Macrolide Consumption? Positive Evidence from an Ecological Analysis of Resistance Data from Streptococcus pneumoniae, Treponema pallidum, and Mycoplasma genitalium

Kenyon, Chris; Manoharan-Basil, Sheeba Santhini; Dijck, Christophe Van

doi:10.1089/mdr.2020.0490

Cited by 23 publications

(13 citation statements)

References 43 publications

(87 reference statements)

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“…Macrolides are primarily effective against Gram-positive bacteria (e.g. Streptococcus pneumoniae or Mycoplasma genitalium [5]) since the molecular structure of the drugs in combination with the decreased permeability of the cell wall makes them less potent against Gram-negative bacteria. However, semi-synthetic macrolides, notably azithromycin, show greater activity towards Gram-negative bacteria, which has led to macrolides also being considered as a first-line treatment for many proteobacterial pathogens (e.g.…”

Section: Introductionmentioning

confidence: 99%

Large-scale characterization of the macrolide resistome reveals high diversity and several new pathogen-associated genes

et al. 2022

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Macrolides are broad-spectrum antibiotics used to treat a range of infections. Resistance to macrolides is often conferred by mobile resistance genes encoding Erm methyltransferases or Mph phosphotransferases. New erm and mph genes keep being discovered in clinical settings but their origins remain unknown, as is the type of macrolide resistance genes that will appear in the future. In this study, we used optimized hidden Markov models to characterize the macrolide resistome. Over 16 terabases of genomic and metagenomic data, representing a large taxonomic diversity (11 030 species) and diverse environments (1944 metagenomic samples), were searched for the presence of erm and mph genes. From this data, we predicted 28 340 macrolide resistance genes encoding 2892 unique protein sequences, which were clustered into 663 gene families (<70 % amino acid identity), of which 619 (94 %) were previously uncharacterized. This included six new resistance gene families, which were located on mobile genetic elements in pathogens. The function of ten predicted new resistance genes were experimentally validated in Escherichia coli using a growth assay. Among the ten tested genes, seven conferred increased resistance to erythromycin, with five genes additionally conferring increased resistance to azithromycin, showing that our models can be used to predict new functional resistance genes. Our analysis also showed that macrolide resistance genes have diverse origins and have transferred horizontally over large phylogenetic distances into human pathogens. This study expands the known macrolide resistome more than ten-fold, provides insights into its evolution, and demonstrates how computational screening can identify new resistance genes before they become a significant clinical problem.

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Section: Introductionmentioning

confidence: 99%

Large-scale characterization of the macrolide resistome reveals high diversity and several new pathogen-associated genes

et al. 2022

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“…Besides transmission of resistant strains, acquired resistance after drug exposure is important for the spread of unsusceptible types ( Pineiro et al, 2019 ). As discussed for M. pneumoniae , acquisition of resistance can be expected for any genotype of M. genitalium , and regional differences in prescriptions and consumption of macrolides and quinolones might play an important role in the resistance rate among circulating strains ( Kenyon et al, 2021 ). This is especially the case in risk groups for sexually transmitted infections, who often receive antibiotic therapy against infections with pathogens other than M. genitalium .…”

Section: Association Of Typing Results With Epidemiological and Clini...mentioning

confidence: 99%

Molecular Tools for Typing Mycoplasma pneumoniae and Mycoplasma genitalium

Dumke

2022

Front. Microbiol.

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Mycoplasma pneumoniae and Mycoplasma genitalium are cell wall-less bacteria with strongly reduced genome content and close phylogenetic relatedness. In humans, the only known natural host, the microorganisms colonize the respiratory or genitourinary mucosa and may cause a broad range of clinical presentations. Besides fundamental differences in their tissue specificity, transmission route, and ability to cause prevalence peaks, both species share similarities such as the occurrence of asymptomatic carriers, preferred populations for infection, and problems with high rates of antimicrobial resistance. To further understand the epidemiology of these practically challenging bacteria, typing of strains is necessary. Since the cultivation of both pathogens is difficult and not performed outside of specialized laboratories, molecular typing methods with adequate discriminatory power, stability, and reproducibility have been developed. These include the characterization of genes containing repetitive sequences, of variable genome regions without the presence of repetitive sequences, determination of single and multi-locus variable-number tandem repeats, and detection of single nucleotide polymorphisms in different genes, respectively. The current repertoire of procedures allows reliable differentiation of strains circulating in different populations and in different time periods as well as comparison of strains occurring subsequently in individual patients. In this review, the methods for typing M. pneumoniae and M. genitalium, including the results of their application in different studies, are summarized and current knowledge regarding the association of typing data with the clinical characteristics of infections is presented.

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“…This finding has important consequences. It suggests that reducing fluoroquinolone consumption to below certain thresholds could reduce the probability of resistance sprreading in all of these bacterial species [15,16]. This may be particularlry important for N. gonorrhoeae.…”

Section: Discussionmentioning

confidence: 99%

Syndemics of Fluoroquinolone Resistance in N. gonorrhoeae, E. coli and K. pneumoniae: A Global Ecological Analysis

Kenyon¹

2021

Preprint

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It is unclear how important it is to reduce fluoroquinolone consumption in the general population to prevent the spread of fluoroquinolone resistance in Neisseria gonorrhoeae (bystander selection). Methods We assessed bystander selection by using Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in N. gonorrhoeae was correlated with the prevalence of fluoroquinolone resistance in four other gram-negative species - Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Results Fluoroquinolone resistance in N. gonorrhoeae was positively associated with homologous resistance in all 4 species - A. baumanii. (ρ=0.61, P=0.0003, E. coli (ρ=0.67, P<0.0001), K. pneumoniae (ρ=0.52, P=0.0004) and P. aeruginosa (ρ=0.40, P=0.0206). Positive associations were also found between the national prevalence of fluoroquinolone resistance and fluoroquinolone consumption in the general population in the preceding year for 4 of the 5 species. Conclusions Gonococcal fluoroquinolone resistance can be productively viewed as being part of a syndemic of fluoroquinolone resistance. Strengthening antimicrobial stewardship programs may help retard the spread of fluoroquinolone resistance in N. gonorrhoeae.

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Is There a Resistance Threshold for Macrolide Consumption? Positive Evidence from an Ecological Analysis of Resistance Data from Streptococcus pneumoniae, Treponema pallidum, and Mycoplasma genitalium

Cited by 23 publications

References 43 publications

Large-scale characterization of the macrolide resistome reveals high diversity and several new pathogen-associated genes

Large-scale characterization of the macrolide resistome reveals high diversity and several new pathogen-associated genes

Molecular Tools for Typing Mycoplasma pneumoniae and Mycoplasma genitalium

Syndemics of Fluoroquinolone Resistance in <em>N. gonorrhoeae</em>, <em>E. coli</em> and <em>K. pneumoniae</em>: A Global Ecological Analysis

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