Dataset Information

In vitro activity of a novel aminomethylcycline antibacterial (KBP-7072), a third-generation tetracycline, against clinical isolates with molecularly characterized tetracycline resistance mechanisms.

ABSTRACT:

Objectives

This study evaluated the in vitro activity of KBP-7072 against 413 contemporary surveillance isolates, including subsets with known tetracycline resistance genes.

Materials

In total, 105 Klebsiella pneumoniae (51 tetracycline resistant), 103 Escherichia coli (52 tetracycline resistant), 103 Staphylococcus aureus (51 tetracycline resistant) and 102 Streptococcus pneumoniae (51 tetracycline resistant) isolates were included. These isolates were tested by broth microdilution using fresh media. CLSI/EUCAST breakpoints were applied, except for tigecycline and omadacycline, which used FDA criteria.

Results

KBP-7072 (MIC₅₀, 0.06 mg/L), tigecycline (MIC₅₀, 0.12 and 0.25 mg/L) and omadacycline (MIC₅₀, 0.12 and 0.5 mg/L) showed similar MIC₅₀s for tetracycline-susceptible and -resistant S. aureus. Other tetracycline comparators had their MIC₅₀ increased 64- to 256-fold by tet. For S. pneumoniae, KBP-7072 (MIC_50/90, ≤0.015/0.03 mg/L) showed the lowest MICs, which remained unchanged for tetracycline-susceptible or -resistant isolates [mostly tet(M)]. Similar MICs were observed for omadacycline (MIC_50/90, 0.03-0.06/0.06 mg/L) and tigecycline (MIC_50/90, 0.03/0.03 mg/L) in the S. pneumoniae population. Tetracycline-susceptible and -resistant E. coli [94.2% tet(A)/tet(B)], KBP-7072 (MIC₉₀, 0.25 and 1 mg/L, respectively) and tigecycline (MIC₉₀, 0.25 and 0.5 mg/L) showed similar MIC₉₀s. KBP-7072 (MIC_50/90, 0.25/0.5 mg/L) and tigecycline (MIC_50/90, 0.5/0.5 mg/L) had the lowest MIC for tetracycline-susceptible K. pneumoniae. The MIC for KBP-7072 (MIC_50/90, 1/4 mg/L) and tigecycline (MIC_50/90, 1/2 mg/L) increased 2- to 8-fold for tetracycline-resistant K. pneumoniae, which mostly produced Tet(A).

Conclusions

KBP-7072 activity was minimally affected by the presence of acquired tetracycline genes.

SUBMITTER: Pfaller MA

PROVIDER: S-EPMC8669227 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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<i>In vitro</i> activity of a novel aminomethylcycline antibacterial (KBP-7072), a third-generation tetracycline, against clinical isolates with molecularly characterized tetracycline resistance mechanisms.

Pfaller Michael A MA Li Li L Liu Qingmei Q Zhang Jay J Huband Michael D MD Lindley Jill M JM Mendes Rodrigo E RE

JAC-antimicrobial resistance 20211214 4

<h4>Objectives</h4>This study evaluated the <i>in vitro</i> activity of KBP-7072 against 413 contemporary surveillance isolates, including subsets with known tetracycline resistance genes.<h4>Materials</h4>In total, 105 <i>Klebsiella pneumoniae</i> (51 tetracycline resistant), 103 <i>Escherichia coli</i> (52 tetracycline resistant), 103 <i>Staphylococcus aureus</i> (51 tetracycline resistant) and 102 <i>Streptococcus pneumoniae</i> (51 tetracycline resistant) isolates were included. These isolat ...[more]

PMID: 34917942

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