Ann Lab Med.  2021 May;41(3):293-301. 10.3343/alm.2021.41.3.293.

In Vitro Activity of the Novel Tetracyclines, Tigecycline, Eravacycline, and Omadacycline, Against Moraxella catarrhalis

• Sun X
• Zhang B
• Xu G
• Chen J
• Shang Y
• Lin Z
• Yu Z
• Zheng J
• Bai B

• KMID: 2512687
• DOI: http://doi.org/10.3343/alm.2021.41.3.293

Abstract

Background
Tigecycline, eravacycline, and omadacycline are recently developed tetracyclines. Susceptibility of microbes to these tetracyclines and their molecular mechanisms have not been well elucidated. We investigated the susceptibility of Moraxella catarrhalis to tigecycline, eravacycline, and omadacycline and its resistance mechanisms against these tetracyclines.
Methods
A total of 207 non-duplicate M. catarrhalis isolates were collected from different inpatients. The minimum inhibitory concentrations (MICs) of the tetracyclines were determined by broth microdilution. Tigecycline-, eravacycline-, or omadacycline-resistant isolates were induced under In Vitro pressure. The tet genes and mutations in the 16S rRNA was detected by PCR and sequencing.
Results
Eravacycline had a lower MIC₅₀ (0.06 mg/L) than tigecycline (0.125 mg/L) or omadacycline (0.125 mg/L) against M. catarrhalis isolates. We found that 136 isolates (65.7%) had the tetB gene, and 15 (7.2%) isolates were positive for tetL; however, their presence was not correlated with high tigecycline, eravacycline, or omadacycline ( ≥ 1 mg/L) MICs.Compared with the initial MIC after 160 days of induction, the MICs of tigecycline or eravacycline against three M. catarrhalis isolates increased ≥ eight-fold, while those of omadacycline against two M. catarrhalis isolates increased 64-fold. Mutations in the 16S rRNA genes (C1036T and/or G460A) were observed in omadacycline-induced resistant isolates, and increased RR (the genes encoding 16SrRNA (four copies, RR1-RR4) copy number of 16S rRNA genes with mutations was associated with increased resistance to omadacycline.
Conclusions
Tigecycline, eravacycline, and omadacycline exhibited robust antimicrobial effects against M. catarrhalis. Mutations in the 16S rRNA genes contributed to omadacycline resistance in M. catarrhalis.

Keyword

Moraxella catarrhalis; Tigecycline; Eravacycline; Omadacycline; Susceptibility

Figure

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  Fig. 1 Distribution of tetracycline MICs among the (A) tetB- and (B) tetL-positive M. catarrhalis isolates. Abbreviation: MIC, minimum inhibitory concentration.

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  Fig. 2 Tigecycline-, eravacycline, and omadacycline-resistant isolates were induced under in vitro selection pressure. The arrows in- dicated the time point at which mutations in the 16S rRNA and 30S ribosomal protein S10 genes were detected in the induced isolates. Abbr viations: rRNA, ribosomal RNA; MIC, minimum inhibitory concentration.

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