Evaluating eravacycline’s efficacy against pediatric carbapenem-resistant <i>Klebsiella pneumoniae</i> in China: a 6-year study

Eravacycline (ERV) has demonstrated promising <i>in vitro</i> antibacterial activity against carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP). Nonetheless, its clinical application in pediatric cases remains underexplored. Therefore, we assessed the <i>in vitro</i> activities of ERV and tigecycline (TGC) against CRKP isolates obtained from pediatric patients in China between 2019 and 2024. The susceptibility rates of the 74 CRKP strains to TGC and ERV were 100% and 87.8%, respectively. Both TGC and ERV had MIC ranges of 0.125-2 μg/mL, with MIC<sub>50</sub> at 0.25 µg/mL and MIC<sub>90</sub> at 1 µg/mL. Statistically significant differences in ERV susceptibility were observed across different carbapenemases, sequence types (STs), and age groups, with the type of carbapenemase emerging as the primary determinant. The lowest susceptibility was noted for <i>bla<sub>KPC-2</sub></i> (64.3%) and ST11 (54.6%), while <i>bla<sub>NDM-1</sub></i> (97.4%), ST25, and ST17 (100%) exhibited the highest. The lowest susceptibility was observed in CRKP strains isolated from >3-year group (46.7%), whereas strains from both neonates and toddlers exhibited 100% susceptibility. When the MIC was below 0.5 µg/mL, ERV exhibited higher inhibition rates against CRKP compared to TGC. However, at MIC values of 0.5, 0.75, 1.5, and 2 µg/mL, the inhibition rates of both drugs were comparable. Among CRKP strains carrying <i>bla<sub>KPC-2</sub></i>, <i>bla<sub>NDM-1</sub></i>, and <i>bla<sub>NDM-5</sub></i>, both the MIC<sub>50</sub> and MIC<sub>90</sub> values of ERV were less than or equal to TGC's. ERV consistently had lower or equal MIC<sub>90</sub> values compared to TGC for common STs, except for ST11, where ERV's MIC<sub>50</sub> was also lower or equal. ERV demonstrated significant <i>in vitro</i> activity against pediatric CRKP isolates collected over a 6-year period, supporting its potential benefits in treating pediatric CRKP infections, although further <i>in vivo</i> validation is necessary.IMPORTANCEEravacycline (ERV) has demonstrated promising <i>in vitro</i> antibacterial activity against carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP). Current research predominantly addresses adult populations, leaving its clinical application in pediatric cases insufficiently explored. Given that the resistance mechanisms of CRKP in pediatric patients differ from those in adults, primarily due to the production of metallo-β-lactamases, and considering that ERV, like tigecycline, may be used off-label in pediatric populations, this study was conducted. The results demonstrate that ERV exhibited significant <i>in vitro</i> efficacy against pediatric CRKP isolates. However, unlike previous studies, the susceptibility rates of ERV vary considerably across different carbapenemases, sequence types, and age groups of CRKP, with the type of carbapenemase emerging as the primary determinant. These findings suggest that ERV has promising <i>in vitro</i> activity against CRKP isolates from pediatric patients, indicating potential clinical applicability for this demographic.

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Journal
Microbiology Spectrum
Published
2025-11-21
DOI
https://doi.org/10.1128/spectrum.02482-25
Primary Topic
Antibiotic Resistance in Bacteria
Type
article
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article

Evaluating eravacycline’s efficacy against pediatric carbapenem-resistant Klebsiella pneumoniae in China: a 6-year study

Mingming Zhou, Shixing Liu, Xiucai Zhang, Chao Fang et al.
Microbiology Spectrum
Antibiotic Resistance in Bacteria
article

Evaluating eravacycline’s efficacy against pediatric carbapenem-resistant Klebsiella pneumoniae in China: a 6-year study

Mingming Zhou, Shixing Liu, Xiucai Zhang, Chao Fang, Hongqiang Shen, Yuhan Zhao, Jun Xia
article en

Abstract

Eravacycline (ERV) has demonstrated promising <i>in vitro</i> antibacterial activity against carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP). Nonetheless, its clinical application in pediatric cases remains underexplored. Therefore, we assessed the <i>in vitro</i> activities of ERV and tigecycline (TGC) against CRKP isolates obtained from pediatric patients in China between 2019 and 2024. The susceptibility rates of the 74 CRKP strains to TGC and ERV were 100% and 87.8%, respectively. Both TGC and ERV had MIC ranges of 0.125-2 μg/mL, with MIC<sub>50</sub> at 0.25 µg/mL and MIC<sub>90</sub> at 1 µg/mL. Statistically significant differences in ERV susceptibility were observed across different carbapenemases, sequence types (STs), and age groups, with the type of carbapenemase emerging as the primary determinant. The lowest susceptibility was noted for <i>bla<sub>KPC-2</sub></i> (64.3%) and ST11 (54.6%), while <i>bla<sub>NDM-1</sub></i> (97.4%), ST25, and ST17 (100%) exhibited the highest. The lowest susceptibility was observed in CRKP strains isolated from >3-year group (46.7%), whereas strains from both neonates and toddlers exhibited 100% susceptibility. When the MIC was below 0.5 µg/mL, ERV exhibited higher inhibition rates against CRKP compared to TGC. However, at MIC values of 0.5, 0.75, 1.5, and 2 µg/mL, the inhibition rates of both drugs were comparable. Among CRKP strains carrying <i>bla<sub>KPC-2</sub></i>, <i>bla<sub>NDM-1</sub></i>, and <i>bla<sub>NDM-5</sub></i>, both the MIC<sub>50</sub> and MIC<sub>90</sub> values of ERV were less than or equal to TGC's. ERV consistently had lower or equal MIC<sub>90</sub> values compared to TGC for common STs, except for ST11, where ERV's MIC<sub>50</sub> was also lower or equal. ERV demonstrated significant <i>in vitro</i> activity against pediatric CRKP isolates collected over a 6-year period, supporting its potential benefits in treating pediatric CRKP infections, although further <i>in vivo</i> validation is necessary.IMPORTANCEEravacycline (ERV) has demonstrated promising <i>in vitro</i> antibacterial activity against carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP). Current research predominantly addresses adult populations, leaving its clinical application in pediatric cases insufficiently explored. Given that the resistance mechanisms of CRKP in pediatric patients differ from those in adults, primarily due to the production of metallo-β-lactamases, and considering that ERV, like tigecycline, may be used off-label in pediatric populations, this study was conducted. The results demonstrate that ERV exhibited significant <i>in vitro</i> efficacy against pediatric CRKP isolates. However, unlike previous studies, the susceptibility rates of ERV vary considerably across different carbapenemases, sequence types, and age groups of CRKP, with the type of carbapenemase emerging as the primary determinant. These findings suggest that ERV has promising <i>in vitro</i> activity against CRKP isolates from pediatric patients, indicating potential clinical applicability for this demographic.

Microbiology SpectrumVol. 14(1)
Children's Hospital of Zhejiang University (CN)
Openalex Percentile: Top 69%
Antibiotic Resistance in Bacteria
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