title: 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).
  
  
  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.
authors.affiliation: Neuro-Urology, Spinal Cord Injury Center & Research, University of Zurich, Balgrist University Hospital, Zurich, Switzerland.
authors.forename: Jens
authors.initials: J
authors.lastname: Wöllner
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schmidig
authors.forename: Flavia
authors.initials: F
authors.lastname: Gregorini
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kessler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Zbinden
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mehnert
mesh_terms: D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage*; D015169:Colony Count, Microbial; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007267:Injections; D009498:Neurotoxins / Q000008:administration & dosage; D011446:Prospective Studies; D001743:Urinary Bladder / Q000187:drug effects / Q000382:microbiology*; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000188:drug therapy*; D014552:Urinary Tract Infections / Q000209:etiology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D009498:Neurotoxins; D019274:Botulinum Toxins, Type A