Combination Therapies for Biofilm Inhibition and Eradication: A Comparative Review of Laboratory and Preclinical Studies

Abstract

Microbial biofilms are becoming increasingly difficult to treat in the medical setting due to their intrinsic resistance to antibiotics. To combat this, several biofilm dispersal agents are currently being developed as treatments for biofilm infections. Combining biofilm dispersal agents with antibiotics is emerging as a promising strategy to simultaneously disperse and eradicate biofilms or, in some cases, even inhibit biofilm formation. Here we review studies that have investigated the anti-biofilm activity of some well-studied biofilm dispersal agents (e.g., quorum sensing inhibitors, nitric oxide/nitroxides, antimicrobial peptides/amino acids) in combination with antibiotics from various classes. This review aims to directly compare the efficacy of different combination strategies against microbial biofilms and highlight synergistic treatments that warrant further investigation. By comparing across studies that use different measures of efficacy, we can conclude that treating biofilms in vitro and, in some limited cases in vivo, with a combination of an anti-biofilm agent and an antibiotic, appears overall more effective than treating with either compound alone. The review identifies the most promising combination therapies currently under development as biofilm inhibition and eradication therapies.

Bacterial Infections among Patients with Chronic Diseases at a Tertiary Care Hospital in Saudi Arabia

“…The availability of at least two different bacterial species simultaneously could interact with each other to enhance their invasion of the host (pathogenicity) by multiple means, including biofilm formation that is highly resistant to antibiotic drugs. Thus, co-infections and biofilm formation are two linked processes that can be more prevalent in patients with incompetent immunity, which requires an effective combination of antibiotics [ 58 ].…”

The Current Knowledge on the Pathogenesis of Tissue and Medical Device-Related Biofilm Infections

“…New biomaterials based on antibiotics, probiotics, physicochemical coatings, or antibiotic enhancements (ultrasound, bioelectric effect) have been described as effective [ 112 , 113 ]. Some examples of compounds that inhibit biofilm formation are the following: extracellular polymeric substance synthesis inhibitors, adhesion inhibitors, quorum sensing inhibitors, efflux pump inhibitors, cyclic diguanylate inhibitors, nature-derived bioactive scaffolds, antimicrobial peptides, bioactive compounds isolated from fungi, non-proteinogenic amino acids, and antibiotics [ 114 , 115 , 116 , 117 ]. Moreover, leading research has been conducted on the effects of phages and their individual proteins on biofilm [ 118 ].…”

“…Finally, nanotechnology also provides innovative therapeutic approaches to improve the eradication of BRIs [ 119 , 120 , 121 , 122 ]. However, the combination of these anti-biofilm agents with antibiotics appears to be overall more effective than treatment with either compound alone [ 117 ].…”

Strategies to Improve the Potency of Oxazolidinones towards Bacterial Biofilms

“…[51][52][53] The highly antibiotic resistant characteristic of biofilms requires potent antimicrobial agents and novel anti-biofilm strategies. While combination therapies utilizing antibiotics are a viable strategy to treat biofilm related infections, [54][55][56][57][58] one approach to develop new anti-biofilm agents is the structural modification of existing antibiotics.…”