Is there a direct antimicrobial effect of botulinum neurotoxin type A?

Abstract

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Several studies describe a reduction of symptomatic urinary tract infections in patients with neurogenic detrusor overactivity after intradetrusor injections of botulinum neurotoxin A (BoNT/A). It was, however, unclear if a direct antibacterial effect of BoNT/A plays a role in this clinical observation. This is the first study to investigate a potential antibacterial effect of two frequently used BoNT/A formulations (i.e. Botox® and Dysport®), providing evidence that BoNT/A does not exert an antibacterial effect on lower urinary tract pathogens.

Objective: • To determine a potential direct antimicrobial effect of botulinum neurotoxin type A (BoNT/A).

Materials and methods: • A prospective study was carried out using onabotulinumtoxin A (Botox®) and abobotulinumtoxin A (Dypsort®) in agar diffusion and broth microdilution assays with various clinical urinary tract isolates (Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter baumannii, Citrobacter freundii, Klebsiella oxytoca and Bacillus subtilis). • Inhibition zones (mm) of bacteria around a disc containing 20 µL saline with 4 IU of Botox® were measured in the agar diffusion assay. • Minimal inhibitory concentrations (MICs, IU/mL) of both toxins for all bacteria were determined in the broth microdilution assay after overnight incubation at 35 °C.

Results: • There was no inhibition zone in the agar diffusion assays with any bacterial strain. • The microdilution test using Botox® and Dysport® showed bacterial growth in all dilutions, i.e. MICs > 20 and >100 IU/mL for Botox® and Dysport®, respectively.

Conclusions: • BoNT/A has no direct antimicrobial effect. • The reduced frequency of symptomatic urinary tract infections (sUTIs) in patients with neurogenic detrusor overactivity (NDO) after BoNT/A intradetrusor injections seems to be caused by different indirect mechanisms, which are still not completely understood.