Antimicrobial Adjuvants Research Articles

In Vitro Antifungal Antibacterial Activity of Partitions from Euphorbia tirucalli L.

We determined the antifungal and antimicrobial sensitivity of Euphorbia tirucalli extracts in vitro. Antifungal and antibacterial activity was determined based on the M38-A and M26-A protocols, respectively. The methanolic and ethanolic partitions demonstrated antidermatophytic activity against Trichophyton rubrum (MIC 125 µg/mL for ethanol and MIC 125 µg/mL for methanol) and T. interdigitalis (MIC 500 µg/mL for ethanol; 125 µg/mL for methanol). These partitions also showed antibacterial activity—the ethanolic partition had an MIC of 1.56 ± 0.02 mg/mL against methicillin-resistant Staphylococcus aureus (clinical isolate), 6.25 ± 0.04 mg/mL against Staphylococcus aureus BAA-44, 3.13 ± 0.13 mg/mL against Pseudomonas aeruginosa 27853, and 3.13 ± 0.15 mg/mL against Escherichia coli ATCC 25922; the methanolic partition showed an MIC of 1.56 ± 0.02 mg/mL against P. aeruginosa 27853 and 1.56 ± 0.043 mg/mL against E. coli ATCC 25922. These partitions show promise as antimicrobial agents or adjuvants in the treatment of infections caused by these microorganisms.

In Vitro Cytotoxicity, Colonisation by Fibroblasts and Antimicrobial Properties of Surgical Meshes Coated with Bacterial Cellulose.

Hernia repairs are the most common abdominal wall elective procedures performed by general surgeons. Hernia-related postoperative infective complications occur with 10% frequency. To counteract the risk of infection emergence, the development of effective, biocompatible and antimicrobial mesh adjuvants is required. Therefore, the aim of our in vitro investigation was to evaluate the suitability of bacterial cellulose (BC) polymer coupled with gentamicin (GM) antibiotic as an absorbent layer of surgical mesh. Our research included the assessment of GM-BC-modified meshes’ cytotoxicity against fibroblasts ATCC CCL-1 and a 60-day duration cell colonisation measurement. The obtained results showed no cytotoxic effect of modified meshes. The quantified fibroblast cells levels resembled a bimodal distribution depending on the time of culturing and the type of mesh applied. The measured GM minimal inhibitory concentration was 0.47 µg/mL. Results obtained in the modified disc-diffusion method showed that GM-BC-modified meshes inhibited bacterial growth more effectively than non-coated meshes. The results of our study indicate that BC-modified hernia meshes, fortified with appropriate antimicrobial, may be applied as effective implants in hernia surgery, preventing risk of infection occurrence and providing a high level of biocompatibility with regard to fibroblast cells.

New diarylpentanoids and chalcones as potential antimicrobial adjuvants

Antimicrobial resistance arises due to several adaptation mechanisms, being the overexpression of efflux pumps (EPs) one of the most worrisome. In bacteria, EPs can also play important roles in virulence, quorum-sensing (QS) and biofilm formation. To identify new potential antimicrobial adjuvants, a library of diarylpentanoids and chalcones was synthesized and tested. These compounds presented encouraging results in potentiating the activity of antimicrobials, being diarylpentanoid 13 the most promising. Compounds 9, 13, 16, 19, 22, and 23 displayed EP inhibitory effect, mainly in Staphylococcus aureus 272123. Compounds 13, 19, 22, and 23 exhibited inhibitory effect on biofilm formation in S. aureus 272,123 while 13 and 22 inhibited QS in the pair Sphingomonas paucimobilis Ezf 10–17 and Chromobacterium violaceum CV026. The overall results, demonstrated that diarylpentanoid 13 and chalcone 22 were active against all the resistance mechanisms tested, suggesting their potential as antimicrobial adjuvants.

Drug Resistance and Epigenetic Modulatory Potential of Epigallocatechin-3-Gallate Against Staphylococcus aureus.

Antimicrobial resistance of human pathogens, such as methicillin-resistant Staphylococcus aureus, is described by the World Health Organization as a health global challenge and efforts must be made for the discovery of new effective and safe compounds. This work aims to evaluate epigallocatechin-3-gallate (EGCG) epigenetic and modulatory drug potential against S. aureus in vitro and in vivo. S. aureus strains were isolated from commensal flora of healthy volunteers. Antibiotic susceptibility and synergistic assay were assessed through disk diffusion accordingly to EUCAST guidelines with and without co-exposure to EGCG at final concentrations of 250µg/ml, 100µg/ml, 50µg/ml, and 25µg/ml. Transcriptional expression of orfx, spdC, and WalKR was performed through qRT-PCR. A 90-day interventional study was performed with daily consumption of 225mg of EGCG. Obtained data revealed a high prevalence of S. aureus colonization in healthcare workers and clearly demonstrated the antimicrobial and synergistic potential of EGCG as well as divergent resistant phenotypes associated with altered transcriptional expression of epigenetic and drug response modulators genes. Here, we demonstrate the potential of EGCG for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms and report divergent patterns of epigenetic modulators expression associated with phenotypic resistance profiles.

Antibacterial Activity of Exogenous Glutathione and Its Synergism on Antibiotics in Methicillin-Associated Multidrug Resistant Clinical Isolates of <i>Staphylococcus aureus</i>

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most problematic human pathogens. Antibiotic treatment of MRSA often associated with resistance to multiple classes of antibiotics is extremely challenging and urgently demands action to treat MRSA. Glutathione (GSH) is a biogenic thiol-compound that maintains an optimal intracellular redox-potential required for various normal cellular processes. Antibacterial activity of exogenous GSH has been reported in some bacterial pathogens but is largely unknown in MRSA. Aim: This study aimed to understand antibacterial activity of GSH, its role in antibiotic susceptibility, and a potential antibacterial mechanism in clinical isolates of S. aureus. Materials and Methods: Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), checkerboard, time-killing, and bacterial killing assays were performed for 14 clinical isolates of S. aureus including 10 MRSA and two type strains (ATCC 700699 and 35556). Results: MIC and MBC levels for the clinical and type strains were 15 - 20 mM and 25 - 40 mM of GSH, respectively. Subinhibitory concentrations of GSH synergistically enhanced susceptibility of all tested-antibiotics, resulting in sensitizing all-tested S. aureus. Bacterial-killing produced by GSH-mediated acidity was significantly higher than that by hydrochloric acid-mediated acidity. Conclusion: Overall results concluded that GSH exhibited antibacterial activity on S. aureus regardless of antibiotic susceptibility and synergistically enhanced antibiotic susceptibility. Additionally, GSH-mediated acidity was one of the antibacterial mechanisms. These findings suggest that GSH may be a potential antimicrobial agent or adjuvant for the conventional anti-MRSA regimens.

Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria.

Antimicrobial peptides are one of the lines of defense produced by several hosts in response to bacterial infections. Inspired by them and recent discoveries of xanthones as bacterial efflux pump inhibitors, chiral amides with a xanthone scaffold were planned to be potential antimicrobial adjuvants. The chiral derivatives of xanthones were obtained by peptide coupling reactions between suitable xanthones with enantiomerically pure building blocks, yielding derivatives with high enantiomeric purity. Among 18 compounds investigated for their antimicrobial activity against reference strains of bacteria and fungi, antibacterial activity for the tested strains was not found. Selected compounds were also evaluated for their potential to inhibit bacterial efflux pumps. Compound (R,R)-8 inhibited efflux pumps in the Gram-positive model tested and three compounds, (S,S)-8, (R)-17 and (R,S)-18, displayed the same activity in the Gram-negative strain used. Studies were performed on the inhibition of biofilm formation and quorum-sensing, to which the enantiomeric pair 8 displayed activity for the latter. To gain a better understanding of how the active compounds bind to the efflux pumps, docking studies were performed. Hit compounds were proposed for each activity, and it was shown that enantioselectivity was noticeable and must be considered, as enantiomers displayed differences in activity.

Identification of ruthenium (II) complexes with furan-substituted ligands as possible antibacterial agents against Staphylococcus aureus.

The growing burden of antibiotic resistance worldwide calls for developing new classes of antimicrobial strategy. Recently years, the use of adjuvants that rescue antibiotics identified as a promising strategy for overcoming bacterial resistance. In this study, three ruthenium complexes functionalized with furan-substituted ligands([Ru(phen)2 (CAPIP)](ClO4 )2 (Ru(Ⅱ)-1), [Ru(dmp)2 (CAPIP)](ClO4 )2 (Ru(Ⅱ)-2) and [Ru(dmb)2 (CAPIP)](ClO4 )2 (Ru(Ⅱ)-3) (dmb=4,4'-dimethyl-2,2'-bipyridine, phen=1,10-phenanthroline, dmp=2,9-dimethyl-1,10-phenanthroline, CAPIP=(E)-2- (2-(furan-2-yl)vinyl)-1H-imidazo[4,5-f][1,10]phenanthroline)) were designed and synthesized. The antimicrobial activities of all compounds against S. aureus were assessed by growth inhibition assays. The MIC values of three complexes range from 0.015 to 0.050mg/ml. Subsequently, the Ru(II)-2 complexes which exhibited strongest antibacterial activity were further tested against bacteria biofilms formation and toxin secretion. In addition, aimed to test whether ruthenium complexes have potential value as antimicrobial adjuvants, the synergism between Ru(Ⅱ)-2 and some antibiotics against S. aureus were examined through checkerboard method. Interestingly, Ru(Ⅱ)-2 could not only effectively inhibit biofilms formation of S. aureus and inhibit the hemolysin toxin secretion, but also selectivity show synergism with two common antibiotics. More importantly, mouse infection study also verified Ru(Ⅱ)-2 were highly effective against S. aureus in vivo.

Metabolites from Marine-Derived Fungi as Potential Antimicrobial Adjuvants.

Marine-derived fungi constitute an interesting source of bioactive compounds, several of which exhibit antibacterial activity. These acquire special importance, considering that antimicrobial resistance is becoming more widespread. The overexpression of efflux pumps, capable of expelling antimicrobials out of bacterial cells, is one of the most worrisome mechanisms. There has been an ongoing effort to find not only new antimicrobials, but also compounds that can block resistance mechanisms which can be used in combination with approved antimicrobial drugs. In this work, a library of nineteen marine natural products, isolated from marine-derived fungi of the genera Neosartorya and Aspergillus, was evaluated for their potential as bacterial efflux pump inhibitors as well as the antimicrobial-related mechanisms, such as inhibition of biofilm formation and quorum-sensing. Docking studies were performed to predict their efflux pump action. These compounds were also tested for their cytotoxicity in mouse fibroblast cell line NIH/3T3. The results obtained suggest that the marine-derived fungal metabolites are a promising source of compounds with potential to revert antimicrobial resistance and serve as an inspiration for the synthesis of new antimicrobial drugs.

Cyclic and Acyclic Amine Oxide Alkyl Derivatives as Potential Adjuvants in Antimicrobial Chemotherapy against Methicillin-Resistant Staphylococcus aureus with an MDR Profile

The dramatic intensification of antimicrobial resistance occurrence in pathogenic bacteria concerns the global community. The revitalisation of inactive antibiotics is, at present, the only way to go through this health system crisis and the use of antimicrobial adjuvants is turning out the most promising approach. Due to their low toxicity, eco-friendly characteristics and antimicrobial activity, amphoteric surfactants are good candidates. This study investigated the adjuvant potentialities of commercial acyclic and newly cyclic N-oxide surfactants combined with therapeutically available antibiotics against MDR methicillin-resistant Staphylococcus aureus (MRSA). The safety profile of the new cyclic compounds, compared to commercial surfactants, was preliminarily assessed, evaluating the cytotoxicity on human peripheral mononuclear blood cells and the haemolysis in human red blood cells. The compounds show an efficacious antimicrobial activity strongly related to the length of the carbon atom chain. In drug–drug interaction assays, all surfactants act synergistically, restoring sensitivity to oxacillin in MRSA, with dodecyl acyclic and cyclic derivatives being the most effective. After evaluating the cytotoxicity and considering the antimicrobial action, the most promising compound is the L-prolinol amine-oxide C12NOX. These findings suggest that the combination of antibiotics with amphoteric surfactants is a valuable therapeutic option for topical infections sustained by multidrug-resistant S. aureus.

Acidic amino acids as counterions of ciprofloxacin: Effect on growth and pigment production in Staphylococcus aureus NCTC 8325 and Pseudomonas aeruginosa PAO1.

Antimicrobial resistance (AMR) is emerging as a global threat to public health. One of the strategies employed to combat AMR is the use of adjuvants which act to enhance or reinstate antimicrobial activity by inhibiting resistance mechanisms. However, these adjuvants are themselves not immune to selecting resistant phenotypes. Thus, there is a need to utilise mechanisms which are either less likely to or unable to trigger resistance. One commonly employed mechanism of resistance by microorganisms is to prevent antimicrobial uptake or efflux the antibiotic which manages to permeate its membrane. Here we propose amino acids as antimicrobial adjuvants that may be utilizing alternate mechanisms to fight AMR. We used a modified ethidium bromide (EtBr) efflux assay to determine its efflux in the presence of ciprofloxacin within Staphylococcus aureus (NCTC 8325) and Pseudomonas aeruginosa (PAO1). In this study, aspartic acid and glutamic acid were found to inhibit growth of both bacterial species. Moreover, a reduced production of toxic pigments, pyocyanin and pyoverdine by P. aeruginosa was also observed. As evident from similar findings with tetracycline, these adjuvants, may be a way forward towards tackling antimicrobial resistance.

Human glucose-dependent insulinotropic polypeptide (GIP) is an antimicrobial adjuvant re-sensitising multidrug-resistant Gram-negative bacteria.

Increasing antibiotic resistance in Gram-negative bacteria has mandated the development of both novel antibiotics and alternative therapeutic strategies. Evidence of interplay between several gastrointestinal peptides and the gut microbiota led us to investigate potential and broad-spectrum roles for the incretin hormone, human glucose-dependent insulinotropic polypeptide (GIP) against the Enterobacteriaceae bacteria, Escherichia coli and Erwinia amylovora. GIP had a potent disruptive action on drug efflux pumps of the multidrug resistant bacteria E. coli TG1 and E. amylovora 1189 strains. The effect was comparable to bacterial mutants lacking the inner and outer membrane efflux pump factor proteins AcrB and TolC. While GIP was devoid of direct antimicrobial activity, it has a potent membrane depolarizing effect, and at low concentrations, it significantly potentiated the activity of eight antibiotics and bile salt by reducing MICs by 4-8-fold in E. coli TG1 and 4-20-fold in E. amylovora 1189. GIP can thus be regarded as an antimicrobial adjuvant with potential for augmenting the available antibiotic arsenal.

Antimicrobial Adjuvants - A Novel Approach to Manage Antimicrobial Resistance

Antibiotic resistance is one of the most prevalent, complex and serious global health issues, and needs to be monitored and controlled with medicine. Many approaches have been used to reduce the emergence and impact of resistance to antibiotics. The antimicrobial adjuvant approach is considered as novel, more effective and less expensive. The said approach not only suppresses the emergence of resistance but also conserves the activity of existing antibiotics by offering a promising strategy that is also complementary to the discovery of new antibiotics. This review contains an outline of the basic types of antibiotic adjuvant, their structure, the basis of their operation, their substrate antibiotics and the challenges in this field, as well as the role of potential compounds, namely β-lactamase inhibitors, efflux pump inhibitors and permeability enhancers in antibiotic resistance and their possible solutions.

Mechanisms of Antimicrobial Resistance (AMR) and Alternative Approaches to Overcome AMR.

Antimicrobials are useful compounds intended to eradicate or stop the growth of harmful microorganisms. The sustained increase in the rates of antimicrobial resistance (AMR) worldwide is worrying and poses a major public health threat. The development of new antimicrobial agents is one of the critical approaches to overcome AMR. However, in the race towards developing alternative approaches to combat AMR, it appears that the scientific community is falling behind when pitched against the evolutionary capacity of multi-drug resistant (MDR) bacteria. Although the "pioneering strategy" of discovering completely new drugs is a rational approach, the time and effort taken are considerable, the process of drug development could instead be expedited if efforts were concentrated on enhancing the efficacy of existing antimicrobials through: combination therapies; bacteriophage therapy; antimicrobial adjuvants therapy or the application of nanotechnology. This review will briefly detail the causes and mechanisms of AMR as background, and then provide insights into a novel, future emerging or evolving strategies that are currently being evaluated and which may be developed in the future to tackle the progression of AMR.

Hit Identification of New Potent PqsR Antagonists as Inhibitors of Quorum Sensing in Planktonic and Biofilm Grown Pseudomonas aeruginosa.

Current treatments for Pseudomonas aeruginosa infections are becoming less effective because of the increasing rates of multi-antibiotic resistance. Pharmacological targeting of virulence through inhibition of quorum sensing (QS) dependent virulence gene regulation has considerable therapeutic potential. In P. aeruginosa, the pqs QS system regulates the production of multiple virulence factors as well as biofilm maturation and is a promising approach for developing antimicrobial adjuvants for combatting drug resistance. In this work, we report the hit optimisation for a series of potent novel inhibitors of PqsR, a key regulator of the pqs system, bearing a 2-((5-methyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)thio) acetamide scaffold. The initial hit compound 7 (PAO1-L IC50 0.98 ± 0.02 μM, PA14 inactive at 10 μM) was obtained through a virtual screening campaign performed on the PqsR ligand binding domain using the University of Nottingham Managed Chemical Compound Collection. Hit optimisation gave compounds with enhanced potency against strains PAO1-L and PA14, evaluated using P. aeruginosa pqs-based QS bioreporter assays. Compound 40 (PAO1-L IC50 0.25 ± 0.12 μM, PA14 IC50 0.34 ± 0.03 μM) is one of the most potent PqsR antagonists reported showing significant inhibition of P. aeruginosa pyocyanin production and pqs system signaling in both planktonic cultures and biofilms. The co-crystal structure of 40 with the PqsR ligand binding domain revealed the specific binding interactions occurring between inhibitor and this key regulatory protein.

Modified Nanoparticles as Potential Agents in Bone Diseases: Cancer and Implant-Related Complications.

Materials sized 1–100 nm are the nanotechnology’s field of interest. Because of the unique properties such as the ability to penetrate biological barriers and a high surface to volume ratio, nanoparticles (NPs) are a powerful tool to be used in medicine and industry. This review discusses the role of nanotechnology in bone-related issues: osteosarcoma (bone cancer), the biocompatibility of the implants and implant-related infections. In cancer therapy, NPs can be used as (I) cytotoxic agents, (II) drug delivery platforms and (III) in thermotherapy. In implant-related issues, NPs can be used as (I) antimicrobial agents and (II) adjuvants to increase the biocompatibility of implant surface. Properties of NPs depend on (I) the type of NPs, (II) their size, (III) shape, (IV) concentration, (V) incubation time, (VI) functionalization and (VII) capping agent type.

In vitro antimicrobial activity of narasin and monensin in combination with adjuvants against pathogens associated with canine otitis externa.

The emergence of antimicrobial resistance represents a serious human and animal health risk. Good antimicrobial stewardship is essential to prolong the lifespan of existing antibiotics, and new strategies are required to combat infections in man and animals. To determine the in vitro interaction of ionophores (narasin or monensin) with antimicrobial adjuvants (N-acetylcysteine (NAC), Tris-EDTA or disodium EDTA) against bacterial strains representing pathogens associated with canine otitis externa (OE). American Type Culture Collection (ATCC) strains Staphylococcus aureus 29213, Pseudomonas aeruginosa 27853 and P.aeruginosa biofilm producer PAO1, and a clinical isolate of Proteus mirabilis from a case of canine OE were tested. A 2D microdilution checkerboard method was used, allowing calculation of fractional inhibitory concentration index (FICI), dose reduction index (DRI) and plotting of isobolograms. The combination of narasin with either Tris-EDTA or disodium EDTA produced additive effects (FICI=0.75) against P.aeruginosa ATCC 27853 and P.aeruginosa biofilm producer ATCC PAO1. An additive effect (FICI=0.53-0.75) was found against S.aureus ATCC 29213 when narasin or monensin were combined with NAC. The highest DRI (32-fold) was found with monensin/NAC where the MIC of monensinwas reduced from 4 to 0.125μg/mL. The combination of narasin with Tris-EDTA or disodium EDTA is a promising strategy to inhibit the intrinsic resistance elements of Gram-negative bacteria. These novel combinations potentially could be useful as a multimodal approach to treat mixed infections in canine OE.

Sensitization of avian pathogenic Escherichia coli to amoxicillin in vitro and in vivo in the presence of surfactin.

The purpose of this study is to assess the antibiotics adjuvant effect of surfactin for boosting the treatment effect of amoxicillin. Surfactin is used as a surfactant to mediate flux of mono-and divalent cations, such as calcium, across lipid bilayer membranes. In this study, we demonstrated that surfactin can increase the activity of amoxicillin against avian pathogenic Escherichia coli (APEC) in vitro with antimicrobial assays such as minimum inhibitory concentrations (MIC) and fractional inhibitory concentration (FIC). Additionally in the model of chick infection, surfactin exerted adjuvant effects with amoxicillin against APEC by lowering the numerical value of mortality and liver bacterial loads, and regulating the expression of inflammatory cytokines et al. We concluded that surfactin can act as a novel antimicrobial adjuvant with amoxicillin against AEPC infection in chicken.

Biofilm production by pathogens associated with canine otitis externa, and the antibiofilm activity of ionophores and antimicrobial adjuvants.

Otitis externa (OE) is a frequently reported disorder in dogs associated with secondary infections by Staphylococcus, Pseudomonas and yeast pathogens. The presence of biofilms may play an important role in the resistance of otic pathogens to antimicrobial agents. Biofilm production of twenty Staphylococcus pseudintermedius and twenty Pseudomonas aeruginosa canine otic isolates was determined quantitatively using a microtiter plate assay, and each isolate was classified as a strong, moderate, weak or nonbiofilm producer. Minimum biofilm eradication concentration (MBEC) of two ionophores (narasin and monensin) and three adjuvants (N-acetylcysteine (NAC), Tris-EDTA and disodium EDTA) were investigated spectrophotometrically (OD570nm ) and quantitatively (CFU/ml) against selected Staphylococcus and Pseudomonas biofilm cultures. Concurrently, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of planktonic cultures were assessed. 16/20 of the S.pseudintermedius clinical isolates were weak biofilm producers. 19/20 P.aeruginosa clinical isolates produced biofilms and were distributed almost equally as weak, moderate and strong biofilm producers. While significant antibiofilm activity was observed, no MBEC was achieved with narasin or monensin. The MBEC for NAC ranged from 5,000-10,000µg/ml and from 20,000-80,000µg/ml against S.pseudintermedius and P.aeruginosa, respectively. Tris-EDTA eradicated P.aeruginosa biofilms at concentrations ranging from 6,000/1,900 to 12,000/3,800µg/ml. The MBEC was up to 16-fold and eightfold higher than the MIC/MBC of NAC and Tris-EDTA, respectively. Disodium EDTA reduced biofilm growth of both strains at concentrations of 470µg/ml and higher. It can be concluded that biofilm production is common in pathogens associated with canine OE. NAC and Tris-EDTA are effective antibiofilm agents in vitro that could be considered for the treatment of biofilm-associated OE in dogs.

In vitro antimicrobial activity of seven adjuvants against common pathogens associated with canine otitis externa.

An antibiotic adjuvant is a chemical substance used to modify or augment the effectiveness of primary antimicrobial agents against drug-resistant micro-organisms. Its use provides an alternative approach to address the global issue of antimicrobial resistance and enhance antimicrobial stewardship. To determine the antimicrobial activity of a panel of potential antimicrobial adjuvants against common pathogens associated with canine otitis externa (OE). A number of type strains and clinical isolates (n=110) from canine OE were tested including Staphylococcus pseudintermedius, β-haemolytic Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis and Malassezia pachydermatis. Antimicrobial activities of monolaurin, monocaprin, N-acetylcysteine (NAC), polymyxin B nonapeptide, Tris-EDTA, Tris-HCL and disodium EDTA were tested using microdilution methodology according to CLSI guidelines. N-acetylcysteine, Tris-EDTA and disodium EDTA had antimicrobial activity against both type strains and otic pathogens. The other adjuvants tested had limited to no efficacy. NAC had a minimal inhibitory concentration (MIC) range of 2,500-10,000μg/mL for the various organisms. Pseudomonas aeruginosa isolates were eight times more susceptible to disodium EDTA in the presence of Tris-HCL in comparison to disodium EDTA alone. Malassezia pachydermatis isolates were most susceptible to Tris-EDTA (MIC90 =190/60μg/mL) and disodium EDTA (MIC90 =120μg/mL). N-acetylcysteine, Tris-EDTA and disodium EDTA have intrinsic antimicrobial activity and represent promising adjuvants that could be used to enhance the efficacy of existing antibiotics against Gram-negative and multidrug-resistant bacterial infections. These agents could be combined with other antimicrobial agents in a multimodal approach for mixed ear infections in dogs.

Antimicrobial Adjuvants- An Innovative Strategy for Handling Antimicrobial Resistance Displayed by Microbes

Human and animal health care workers around the world are sounding the alarm for the development of new antibiotics to counter the ever growing menace of multidrug resistant pathogenic bacteria However there are increasing numbers of reports regarding extremely drug resistant bacteria for which there are limited or no therapeutic options So far the drug discovery has failed to keep pace with the rapidly evolving microbes which has resultantly lead to innovation gap related to development and marketing of new antibiotics Moreover microbial resistance towards antimicrobials is a way complex and multifaceted mechanism Nevertheless many strategies may be employed to minimize the impact and emergence of resistance Use of antimicrobial adjuvants are one of such effective strategies These adjuvants are chemically active moieties that have slight to no antibiotic action but may block antimicrobial resistance or boost action of antimicrobial They are therefore administered along with antimicrobials and may be divided broadly into two important groups The Class I agents having direct action on microbe whereas Class II agents having direct action on host defense mechanisms to potentiate antimicrobial action Antimicrobial adjuvants are a mean to suppress the emergence of bacterial resistance as well as rescue the antimicrobial activity of present drugs in a cost effective manner presenting an orthogonal approach to new antibiotic discovery