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. 2021 Mar 18;65(4):e01715-20.
doi: 10.1128/AAC.01715-20. Print 2021 Mar 18.

In Vivo Antibacterial Activity of Acetazolamide

Nader S Abutaleb  1   2 , Ahmed Elkashif  1 , Daniel P Flaherty  3   4   5 , Mohamed N Seleem  6   2
Affiliations

In Vivo Antibacterial Activity of Acetazolamide

Nader S Abutaleb et al. Antimicrob Agents Chemother. .

Abstract

Vancomycin-resistant enterococci (VRE) represent a major public health threat that requires the development of new therapeutics. In the present study, acetazolamide (AZM) was evaluated against enterococci. It inhibited different enterococcal strains tested at clinically achievable concentrations. Moreover, AZM outperformed linezolid, the drug of choice for VRE infections, in two in vivo VRE mouse models-murine colonization-reduction and VRE septicemia. Collectively, these results indicate that AZM warrants consideration as a promising treatment option for VRE infections.

Keywords: VRE bloodstream infections; VRE decolonization; acetazolamide; carbonic anhydrase inhibitors; vancomycin-resistant enterococci (VRE).

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Figures

FIG 1
FIG 1
Burden of VRE (E. faecium HM-952) in the fecal contents of colonized mice. The CFU data were analyzed via a two-way ANOVA with post hoc Dunnett’s test for multiple comparisons. An asterisk (*) indicates a significant difference (P < 0.05) between mice treated with AZM or LZD compared with vehicle. A pound sign (#) indicates a significant difference (P < 0.05) between mice treated with AZM compared to LZD-treated mice.
FIG 2
FIG 2
(A and B) Burden of VRE (E. faecium HM-952) in (A) the cecal contents of colonized mice and (B) the ileal contents of colonized mice (collected at sacrifice on day 8). The CFU data were analyzed via a one-way ANOVA with post hoc Dunnett’s test for multiple comparisons. An asterisk (*) indicates a significant difference (P < 0.05) between mice treated with AZM or LZD compared with untreated mice (vehicle). A pound sign (#) indicates a significant difference (P < 0.05) between mice treated with AZM compared to LZD-treated mice.
FIG 3
FIG 3
In vivo activity of AZM in the murine VRE peritonitis model after infection with E. faecium NR-31909. Kaplan-Meier survival curves were analyzed using a log-rank (Mantel-Cox) test. The asterisk (*) denotes a statistically significant difference (P < 0.05) between mice treated with either AZM or LZD in comparison with the vehicle-treated mice.
FIG 4
FIG 4
(A to C) Burden of VRE (E. faecium NR-31909) in (A) liver, (B) kidneys, and (C) spleen of the infected mice (determined at the time of death for the vehicle-treated animals and at day 5 for all surviving animals). The CFU data were analyzed via a one-way ANOVA with post hoc Dunnett’s test for multiple comparisons. An asterisk (*) indicates a significant difference (P < 0.05) between mice treated with AZM or LZD compared with untreated mice (vehicle). A pound sign (#) indicates a significant difference (P < 0.05) between mice treated with AZM compared to LZD-treated mice.
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