In this category, we sorted all the reviews and trials that describe or test active molecules against bacterial cells (able to kill them or inhibit their growth).
Antibiotics seem to be the most represented strategy in basic research (22.0%). However, most of the reviews on antibiotics (71.4%) actually discuss clinical trials or current clinical practices, therefore, in this case, they do not provide an accurate representation of the main trends in basic research.
Antibiotics are also well documented in clinical trials (35.2% of the total), where their use is reported both for prevention and eradication. Intensive antibiotic administration can control and prevent the spreading of infections and is therefore one of the most widely used practices [i] and, unfortunately, at the root of one of the major health threats of the past century: emergence of antimicrobial resistance [ii]. This issue is not only restricted to antibiotic molecules, as even metal ions, such as silver, can incur into resistance [iii,iv,v]. Pharmaceutical companies are therefore exploring innovative antibiotic therapeutics to treat infections generally associated with biofilms.
Specifically, the World Health Organization (WHO) identified eight new antibiotic molecules that reached the market in the last years [vi].
Intensive and prolonged antimicrobial treatments can affect both the intestinal and oral microbiomes and cause other side effects [vii,viii], reducing patient quality of life [ix]. To circumvent the issues related to conventional antibiotic therapy, basic research has been focusing on more specific approaches, including those targeting the biofilm structure, such as quorum sensing inhibitors or EPS production inhibitors [x,xi]. Next-generation antibiofilm strategies need to be as selective as possible against pathogenic microbes, reducing the possibility of adverse events for patients. Healthcare institutions have restricted the use of fluoroquinolones, in spite of these compounds being one of the most effective antibiotic classes against biofilms, due to their side effects, such as dysglycemia, hepatotoxicity, diarrhea, altered mental status, rash, and fever [xii,xiii,xiv].
AlMatar, M., Makky, E.A., Var, I., Koksal, F. The role of nanoparticles in the inhibition of multidrug-resistant bacteria and biofilms. Curr. Drug Deliv. 2018, 15(4), 470-484.
Domalaon, R.; Idowu, T.; Zhanel, G.G.; Schweizer, F. Antibiotic hybrids: the next generation of agents and adjuvants against Gram-negative pathogens? Clin. Microbiol. Rev. 2018, 31(2): e00077-17.
Silver, S. Bacterial silver resistance: molecular biology and uses and misuses of silver compounds. FEMS Microbiol. Rev. 2003, 27(2-3):341-353.
Muller, M. Bacterial silver resistance gained by cooperative interspecies redox behaviour. Antimicrob. Agents Chemother. 2018, 62(8):e00672-18.
Percival, S.L.; Salisbury, A.M.; Chen, R. Silver, biofilms and wounds: resistance revisited. Crit. Rev. Microbiol. 2019, 1-15.
World Health Organization. 2019 antibacterial agents in clinical development: an analysis of the antibacterial clinical development pipeline. 2019.
Fogel, D.B. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: a review. Contemp. Clin. Trials. 2018, 156-164.
Morales, D.; Pacurariu, A.; Slattery, J.; Pinheiro, L.; McGettigan, P.; Kurz, X. Association between peripheral neuropathy and exposure to oral fluoroquinolone or amoxicillin-clavulanate therapy. JAMA Neurol. 2019, 76(7):827-833.
Zhang, Z.; Wagner, V.E. Antimicrobial Coatings and Modifications on Medical Devices. Berlin, Springer. 2017.
Bisht, K.; Wakeman, C. A. Discovery and therapeutic targeting of differentiated biofilm subpopulations. Front. Microbiol. 2019, 10, 1908.
Kuula, L.S.; Viljemaa, K.M.; Backman, J.T.; Blom, M. Fluoroquinolone-related adverse events resulting in health service use and costs: A systematic review. PloS One. 2019, 14(4): e0216029.
Morales, D.; Pacurariu, A.; Slattery, J.; Pinheiro, L.; McGettigan, P.; Kurz, X. Association between peripheral neuropathy and exposure to oral fluoroquinolone or amoxicillin-clavulanate therapy. JAMA Neurol. 2019, 76(7):827-833.
Kuula, L.S.; Viljemaa, K.M.; Backman, J.T.; Blom, M. Fluoroquinolone-related adverse events resulting in health service use and costs: A systematic review. PloS One. 2019, 14(4): e0216029.
WHO – World Health Organization. WHO pharmaceuticals newsletter. 2018, (6):3-35.