Antibiotic synergy as a strategy for combating multidrug-resistant bacteria: a review of mechanisms and clinical implications
DOI:
https://doi.org/10.18203/2394-6040.ijcmph20232868Keywords:
MDRB, Antibiotic synergy, Treatment efficacy, Resistance mechanisms, Biofilm-associated infectionsAbstract
Multidrug-resistant bacteria (MDRB) are a global concern due to their resistance to multiple antibiotics. The rise of MDRB is attributed to factors like antibiotic misuse and horizontal gene transfer. Limited treatment options led to increased morbidity, mortality, and healthcare costs. MDRB spreads within healthcare and community settings, posing risks to vulnerable populations. Urgent efforts are needed to combat MDRB, including antibiotic synergy, which enhances therapeutic efficacy. Synergy disrupts bacterial processes, improves penetration and intracellular accumulation, and inhibits resistance mechanisms. It is crucial in treating biofilm-associated infections. Methods like checkerboard assays and time-kill assays assess synergistic effects, while high-throughput screening enables rapid identification. The rise of multidrug resistance has prompted urgent calls for concerted efforts to address this global health crisis. Antibiotic synergy broadens treatment options, allows dose reduction, and addresses biofilm infections. Careful implementation is necessary to minimize resistance and drug interactions. Successful case studies highlight the potential of antibiotic synergy against MDRB.
Metrics
References
Alanis AJ. Resistance to antibiotics: are we in the post-antibiotic era? Arch Med Research. 2005;36(6):697-705.
Serwecińska L. Antimicrobials and antibiotic-resistant bacteria: a risk to the environment and to public health. Water. 2020;12(12):3313.
Colomb-Cotinat M, Lacoste J, Brun-Buisson C, Jarlier V, Coignard B, Vaux S. Estimating the morbidity and mortality associated with infections due to multidrug-resistant bacteria (MDRB), France, 2012. Antimicrobial Resistance Infect Control. 2016;5(1):1-11.
AMR NGHRUoGSo. Whole-genome sequencing as part of national and international surveillance programmes for antimicrobial resistance: A roadmap. BMJ Global Heal. 2020;5(11):e002244.
Suk JE, Semenza JC. Future infectious disease threats to Europe. Am J Publ Heal. 2011;101(11):2068-79.
Pérez J, Contreras-Moreno FJ, Marcos-Torres FJ, Moraleda-Muñoz A, Muñoz-Dorado J. The antibiotic crisis: How bacterial predators can help. Computational Structural Biotechnol J. 2020;18:2547-55.
Zilahi G, Artigas A, Martin-Loeches I. What’s new in multidrug-resistant pathogens in the ICU? Anna Intensive Care. 2016;6(1):1-11.
Sun W, Weingarten RA, Xu M, Southall N, Dai S, Shinn P et al. Rapid antimicrobial susceptibility test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria. Emerging Microbes Infect. 2016;5(1):1-11.
Worthington RJ, Melander C. Combination approaches to combat multidrug-resistant bacteria. Trends in biotechnology. 2013;31(3):177-184.
Bolla J-M, Alibert-Franco S, Handzlik J, Chevalier J, Mahamoud A, Boyer G et al. Strategies for bypassing the membrane barrier in multidrug resistant Gram-negative bacteria. FEBS letters. 2011;585(11):1682-90.
Shang D, Liu Y, Jiang F, Ji F, Wang H, Han X. Synergistic antibacterial activity of designed Trp-containing antibacterial peptides in combination with antibiotics against multidrug-resistant Staphylococcus epidermidis. Frontiers in Microbiol. 2019;10:2719.
Chawla M, Verma J, Gupta R, Das B. Antibiotic potentiators against multidrug-resistant bacteria: discovery, development, and clinical relevance. Frontiers in Microbiol. 2022;13.
Pervin Z, Hassan MM. Synergistic therapeutic actions of antimicrobial peptides to treat multidrug-resistant bacterial infection. Rev Res Med Microbiol. 2021;32(2):83-89.
Gupta A, Saleh NM, Das R, Landis RF, Bigdeli A, Motamedchaboki K et al. Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection. Nano Futures. 2017;1(1):015004.
Kohanski MA, Dwyer DJ, Collins JJ. How antibiotics kill bacteria: from targets to networks. Nature Rev Microbiol. 2010;8(6):423-35.
Mc Dermott PF, Walker RD, White DG. Antimicrobials: modes of action and mechanisms of resistance. Int J Toxicol. 2003;22(2):135-43.
Allahverdiyev AM, Kon KV, Abamor ES, Bagirova M, Rafailovich M. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents. Expert review of anti-infective therapy. 2011;9(11):1035-52.
Liu Y, Tong Z, Shi J, Li R, Upton M, Wang Z. Drug repurposing for next-generation combination therapies against multidrug-resistant bacteria. Theranostics. 2021;11(10):4910.
Pagès J-M, Amaral L. Mechanisms of drug efflux and strategies to combat them: challenging the efflux pump of Gram-negative bacteria. Biochimica et Biophysica Acta (BBA)-Proteins Proteomics. 2009;1794(5):826-33.
Wright GD. Antibiotic adjuvants: rescuing antibiotics from resistance. Trends Microbiol. 2016;24(11):862-71.
Uruén C, Chopo-Escuin G, Tommassen J, Mainar-Jaime RC, Arenas J. Biofilms as promoters of bacterial antibiotic resistance and tolerance. Antibiotics. 2020;10(1):3.
Hemmati F, Rezaee MA, Ebrahimzadeh S, Yousefi L, Nouri R, Kafil HS et al. Novel strategies to combat bacterial biofilms. Molecular Biotechnol. 2021;63(7):569-86.
Ozseven AG, Ozseven L. Do different interpretative methods used for evaluation of checkerboard synergy test affect the results? Mikrobiyoloji Bulteni. 2012;46(3):410-20.
Saiman L. Clinical utility of synergy testing for multidrug-resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis:‘the motion for’. Paediatric respiratory reviews. 2007;8(3):249-55.
White RL, Burgess DS, Manduru M, Bosso JA. Comparison of three different in vitro methods of detecting synergy: time-kill, checkerboard, and E test. Antimicrobial agents and chemotherapy. 1996;40(8):1914-8.
Jenkins SG, Schuetz AN. Current concepts in laboratory testing to guide antimicrobial therapy. Paper presented at: Mayo Clinic Proceedings. 2012.
Zhu M, Tse MW, Weller J, Chen J, Blainey PC. The future of antibiotics begins with discovering new combinations. Ann N York Academy Sci. 2021;1496(1):82-96.
Cheng Y-S, Williamson PR, Zheng W. Improving therapy of severe infections through drug repurposing of synergistic combinations. Curr Opinion Pharmacol. 2019;48:92-8.
Bueno J. Antimicrobial adjuvants drug discovery, the challenge of avoid the resistance and recover the susceptibility of multidrug-resistant strains. J Microb Biochem Technol. 2016;8(3):169-76.
ilancioglu K, Unlu O. Multidrug resistance stimulated antagonistic antibiotic interactions. Rom J Leg Med. 2017;25(4):331-6.
Gajdács M. The continuing threat of methicillin-resistant Staphylococcus aureus. Antibiotics. 2019;8(2):52.
Bao M, Zhang L, Liu B, Li L, Zhang Y, Zhao H et al. Synergistic effects of anti-MRSA herbal extracts combined with antibiotics. Future Microbiol. 2020;15(13):1265-76.
Foster TJ. Can β-lactam antibiotics be resurrected to combat MRSA? Trends Microbiol. 2019;27(1):26-38.
Sakagami Y, Mimura M, Kajimura K, Yokoyama H, Linuma M, Tanaka T et al. Anti‐MRSA activity of sophoraflavanone G and synergism with other antibacterial agents. Letters Applied Microbiol. 1998;27(2):98-100.
Zuo G-Y, Li Y, Wang T, Gen-Chun W, Yun-Ling Z, Wei-Dong P. Synergistic antibacterial and antibiotic effects of bisbenzylisoquinoline alkaloids on clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). Molecules. 2011;16(12):9819-26.
Fatima H, Goel N, Sinha R, Khare SK. Recent strategies for inhibiting multidrug-resistant and β-lactamase producing bacteria: A review. Colloids and Surfaces B: Biointerfaces. 2021;205:111901.
Bassetti M, Righi E, Viscoli C. Novel β-lactam antibiotics and inhibitor combinations. Expert Opinion Investigational Drugs. 2008;17(3):285-96.
Sawa T, Kooguchi K, Moriyama K. Molecular diversity of extended-spectrum β-lactamases and carbapenemases, and antimicrobial resistance. J Intensive Care. 2020;8:1-13.
Van Duin D, Bonomo RA. Ceftazidime/avibactam and ceftolozane/tazobactam: second-generation β-lactam/β-lactamase inhibitor combinations. Clin Infectious Diseases. 2016;63(2):234-41.
