“Ukatamanga weka utamangisa, tikatamanga awili, tifikapatali - When you run alone, you run fast. When you run together, you run far Zambian Proverb

UNZA-UCLMS

Research and Training Programme

K21 -  Quaternary ammonium silanes for controlling hospital acquired infections

Background

Despite broad availability of broad-spectrum antibiotics, anti-TB, anti-malarial and anti-fungal drugs, and anti-retroviral therapy (ART) at large hospitals across sub-Saharan Africa, mortality rates remain high. Inaccurate diagnosis and treatment of common infections and complex co-morbidities, and rampant nosocomial infections of multi-drug resistant bacteria are prime candidates which might explain these high mortality rates. There is an urgent need for innovative new approaches to infection control, incorporating novel technologies and compounds, which when combined with strong leadership and infection control stewardship, have the potential to dramatically reduce infection rates, significantly reducing morbidity and mortality.


Due to its low toxicity, 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride (SiQAC), an organofunctional trialkosilane has been used in antimicrobial coatings of medical devices [1-3]. The antimicrobial activity of this compound is attributed to the long, cationic, lipophilic-C18H37 alkyl chain that penetrates bacterial cell membranes to produce leakage, autolysis and cell death [4]. When the SiQAC is reacted with tetraethylorthosilicate, the resulting molecule becomes more hydrophobic and is designated as K21. Methacrylate derivatives of the same molecule have been evaluated for the material properties, antimicrobial activities and cytotoxicity [5] and are designated as K18. This molecule has been incorporated into an antimicrobial hand disinfectant ointment (fiteBac hand sanitizer) that has antiviral activity against noroviruses [6]. Antiviral activity of these compounds has been demonstrated against HSV-1 and HHV-6 (Bhupesh Prusty, personal communication), as well as potent antimicrobial effects (Dharam Ablahis, personal communication).

Studies in Zambia

We are undertaking a range of in vitro experiments at the University Teaching Hospital, Lusaka, Zambia, to evaluate these compounds as follows:


  • Evaluation of the bactericidal activity of K21 against a panel of clinical isolates, including multi-drug resistant Klebsiella and E-coli, and Staphylococcus aureus
  • Evaluating the capacity of K21, K18 and fiteBac hand sanitizer to prevent biofilm formation on hard surfaces
  • Evaluation of K21 to inhibit growth of Tuberculosis (TB) and Multiple-Drug resistant Tuberculosis (MRD-TB) clinical isolates.

K21-E structure and molecular formula

fiteBac germicidal hand sanitizer

References

1. Gottenbos B, van der Mei HC, Klatter F, Nieuwenhuis P, Busscher HJ. In vitro and in vivo antimicrobial activity of covalently coupled quaternary ammonium silane coatings on silicone rubber. Biomaterials 2002; 23(6): 1417-23.

2. Isquith AJ, Abbott EA, Walters PA. Surface-bonded antimicrobial activity of an organosilicon quaternary ammonium chloride. Applied microbiology 1972; 24(6): 859-63.

3. Oosterhof JJ, Buijssen KJ, Busscher HJ, van der Laan BF, van der Mei HC. Effects of quaternary ammonium silane coatings on mixed fungal and bacterial biofilms on tracheoesophageal shunt prostheses. Applied and environmental microbiology 2006; 72(5): 3673-7.

4. Ahlstrom B, Thompson RA, Edebo L. Loss of bactericidal capacity of long-chain quaternary ammonium compounds with protein at lowered temperature. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 1999; 107(6): 606-14.

5. Gong SQ, Niu LN, Kemp LK, et al. Quaternary ammonium silane-functionalized, methacrylate resin composition with antimicrobial activities and self-repair potential. Acta biomaterialia 2012; 8(9): 3270-82.

6. Baban B, Liu JY, Tay FR, Pashley DH. Use of a new, simple, laboratory method for screening the antimicrobial and antiviral properties of hand sanitizers. American journal of dentistry 2012; 25(6): 327-31.