Fractional Inhibitory Concentration Index Values Research Articles

Promising effects of 1,8 Cineole to control Giardia lamblia infection: Targeting the inflammation, oxidative stress, and infectivity

Reportedly, synthetic drugs such as metronidazole, furazolidone, tinidazole, and quinacrine are used for the treatment of giardiasis but are associated with adverse effects. In this study, we aimed to investigate the in vitro and in vivo effects of eucalyptol (ECT, 1,8 cineole) alone and in combination with metronidazole (MNZ) on Giardia lamblia. The effects of ECT on cell viability, plasma membrane permeability, and gene expression levels of adenylate cyclase (AK) and extracellular signal kinases 1 and 2 (ERK1 and ERK2) in trophozoites of G. lamblia were assessed. In vivo, the effects of ECT alone and in combination with MNZ were assessed on mice infected with G. lamblia. In addition, the gene expression of inflammatory genes (e.g., TNF-α, IL-1β, and IL-10) and antioxidant genes (catalase (CAT), superoxide dismutase 1 (SOD1), glutathione peroxidase 2 (GPX2)) was determined by real-time PCR. The IC50 values of ECT, MNZ, and ECT+MNZ on trophozoites were 30.2 µg/mL, 21.6 µg/mL, and 8.5 µg/mL, respectively. The estimated Fractional inhibitory concentration index (FICI) values for ECT and MNZ were 0.28 and 0.39, respectively. The application of ECT on G. lamblia trophozoites resulted in a dose-dependent increase in plasma membrane permeability, particularly at concentrations of ½ IC50 and IC50 (P < 0.05). The treatment of infected mice with various doses of ECT, mainly in combination with MNZ for 7 days, resulted in a significant decrease (P < 0.001) in the average number and viability of cysts. ECT, especially when combined with MNZ, caused a significant (P < 0.001) reduction in the expression of TNF-α and IL-6 genes, and an increase (P < 0.05) in the expression of IL-10 genes. ECT alone and mainly in combination with MNZ leads to a significant (P < 0.001) increase in the gene expression of CAT, SOD, and GPX genes. These findings demonstrate that the use of ECT in these doses, even for 14 days, does not have any toxic effects on the function of vital liver and kidney tissues. The study findings confirmed the promising effects of ECT against G. lamblia infection both in vitro and in vivo. Considering the possible mechanisms, ECT increases plasma membrane permeability and reduces the expression levels of infectivity-related genes. In addition, ECT suppresses inflammation and oxidative stress, controlling giardiasis in mice. More studies are needed to clarify these findings.

Efficacy of a Novel Antibiotic Drug Combination Toward Multidrug-Resistant Ocular Pathogens.

Antimicrobial resistance is a global health threat, compounded by the reduction in the discovery of new antibiotics. A repurposed drugs-based approach could provide a viable alternative for the treatment of multidrug-resistant (MDR) bacterial infections. In this study, we sought to evaluate the in vitro efficacy of a novel drug combination, polymyxin B/trimethoprim (PT) + rifampin on MDR isolates from patients with bacterial keratitis in India. Forty-three isolates, which included 20 Staphylococcus aureus, 19 Pseudomonas aeruginosa, 3 Pseudomonas stutzeri, and 1 Acinetobacter baumannii, were evaluated for their antibiotic resistance by minimum inhibitory concentration (MIC). Fractional Inhibitory Concentration Index (FICI) testing was performed to measure the antimicrobial impact of PT + rifampin in combination. Among S. aureus isolates, 100% were resistant to at least 1 antibiotic class, 12 (60%) were MDR, and 14 (70%) were classified as methicillin-resistant. Among the gram-negative isolates, >90% were classified as MDR. Fractional Inhibitory Concentration (FIC) testing revealed that PT + rifampin was effective in completely inhibiting growth of all isolates while also displaying additive or synergistic activity in approximately 70% of the strains. Mean FICI values were 0.753 ± 0.311 and 0.791 ± 0.369 for S. aureus and gram-negative isolates, respectively, and a >2-fold reduction in MIC was measured for both PT and rifampin when tested in combination versus alone. Our data demonstrate the ability of PT + rifampin to eliminate all isolates tested, even those conferring MDR, highlighting the promise of this drug combination for the treatment of bacterial keratitis.

Synergistic Antibacterial Activity of Curcuma domestica Val. Extract with Tetracycline Against Multidrug-resistant Acinetobacter baumannii

Infections caused by multidrug-resistant (MDR) bacteria are on the rise globally. MDR is facilitated by overexpression of efflux pump and permeability changes of membrane. Acinetobacter baumannii is a pathogenic germ that causes a major problem in infection, also, there has been an increase in the incidence of resistance to various antibiotics. The present study highlights the synergistic of ethanolic extract of Curcuma domestica (EECD) rhizome with tetracycline against multidrug-resistant A. baumannii (MDR-Ab). Assessment of Minimum Inhibitory Concentration (MIC) was determined by microdilution using 96-well plates. The synergistic effect of EECD and tetracycline was determined by checkerboard method. The effect of EECD and tetracycline combination was investigated by bacteriolytic activity and inhibition of efflux pump by Ethidium Bromide (EtBr) accumulation assay. EECD presented the MIC value 250 µg/mL against MDR-Ab. Fractional Inhibitory Concentration Index (FICI) value of EECD and tetracycline combination was 0.4, which showed their synergistic effect. Additionally, the combination of EECD and tetracycline could inhibit the efflux pump in MDR-Ab. This combination can also compromise cell integrity by altering membrane permeability thus lysing the bacteria cells. According to these results, EECD and tetracycline combination has synergistic effects at some sites of action, and thus could be used as a breakthrough to overcome infection problems due to MDR-Ab.&#x0D; &#x0D; Keywords: Acinetobacter baumannii, antibacterial, Curcuma domestica, multidrug-resistant, tetracycline

Differential in vitro susceptibility to ampicillin/ceftriaxone combination therapy among Enterococcus faecalis infective endocarditis clinical isolates.

To investigate the genomic diversity and β-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE). We collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity and employed antibiotic checkerboard assays and a one-compartment pharmacokinetic-pharmacodynamic (PK/PD) model to investigate bacterial susceptibility to ampicillin and ceftriaxone both alone and in combination. Genetically diverse E. faecalis were collected, however, isolates belonging to two STs, ST6 and ST179, were collected from 21/60 (35%) IE patients. All ST6 isolates encoded a previously described mutation upstream of penicillin-binding protein 4 (pbp4) that is associated with pbp4 overexpression. ST6 isolates had higher ceftriaxone MICs and higher fractional inhibitory concentration index values for ampicillin and ceftriaxone (AC) compared to other isolates, suggesting diminished in vitro AC synergy against this lineage. Introduction of the pbp4 upstream mutation found among ST6 isolates caused increased ceftriaxone resistance in a laboratory E. faecalis isolate. PK/PD testing showed that a representative ST6 isolate exhibited attenuated efficacy of AC combination therapy at humanized antibiotic exposures. We find evidence for diminished in vitro AC activity among a subset of E. faecalis IE isolates with increased pbp4 expression. These findings suggest that alternate antibiotic combinations against diverse contemporary E. faecalis IE isolates should be evaluated.

Efficacy of outer membrane permeabilization in promoting aromatic isothiocyanates-mediated eradication of multidrug resistant Gram-negative bacteria and bacterial persisters.

Multidrug resistant (MDR) bacteria are recognized to be one of the most important problems in public health. The outer membrane permeability is a critical intrinsic mechanism of bacterial resistance. In addition, bacteria produce a small number of dormant persister cells causing multidrug tolerance that reduces antimicrobial efficacy. This study aimed to evaluate the inhibitory effects of the combination of aromatic isothiocyanates (ITCs) with membrane-active agents on bacterial persisters and MDR Gram-negative bacteria. Our study demonstrated that membrane-active agents, particularly ethylenediaminetetraacetic acid (EDTA) synergistically enhanced the inhibitory activity of aromatic benzyl ITC and phenethyl ITC against most Gram-negative bacteria strains with fractional inhibitory concentration index values ranging from 0.18 to 0.5 and 0.16 to 0.5, respectively, and contributed to an 8- to 64-fold minimal inhibitory concentration reduction compared with those of aromatic ITCs alone. The EDTA-aromatic ITCs combination effectively reduced the survival rates of tested bacteria and significantly eradicated bacterial persisters (p = 0.033 and 0.037, respectively). The growth kinetics analysis also supported the enhanced inhibitory effect of EDTA-aromatic ITCs combination against tested bacteria. Our results suggested an alternate treatment strategy against Gram-negative bacteria, promoting the entry of aromatic ITCs into bacterial cytoplasm to facilitate bacterial clearance and thus preventing the development of bacterial resistance.

In-vitro Interactions between Fluconazole and Diphenyl Diselenide against Various Candida Species

Background: In the immunocompromised population, Candida species are the most aetiologic agents causing severe nosocomial fungal infections. Candida species, irrespective of being commensals in the human microbiome, are the fourth most prevalent source of potentially fatal yeast infections. Monotherapy is frequently employed to treat invasive fungal infections, but sometimes, patients do not favor the monotherapy treatment regime. It may be because of the reduced susceptibility of the pathogen toward traditional antimycotic drugs. Antimycotic drug combination therapy could be a better choice in such specific circumstances. In our study, we evaluated the interactions of fluconazole with diphenyl diselenide. Methods: The antimycotic susceptibilities of Candida species for fluconazole and diphenyl diselenide were determined by broth microdilution assay, and the in-vitro interactions of fluconazole with diphenyl diselenide were studied by using disc diffusion assay and chequerboard assay. The nature of the interactions was assessed by calculating the fractional inhibitory concentration index (FICI). The interactions were also analyzed by the response surface approach. Results: The minimum inhibitory concentrations (MICs) for fluconazole and diphenyl diselenide as determined by the broth microdilution assay against Candida species were 4 μg/ml-512 μg/ml and 1 μg/ml-32 μg/ml, respectively. The FICI values varied from 0.375 to 2. Conclusion: Our finding demonstrated that there is no antagonism interaction between fluconazole and diphenyl diselenide in Candida species. Thus, this innovative combination should be explored in the future.

Enhancing Antibiotic Efficacy: Exploring Synergistic Interactions between Plant Extracts and Conventional Antibiotics

Medicinal herbs including Senna alata, Ricinus communis, and Lannea barteri have been utilized for centuries to cure a variety of illnesses caused by microbial infections. This study looked at the synergistic effects of these drugs with traditional antibiotics on clinical isolates of Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The test bacteria were chosen based on their minimal potential for monotherapy and susceptibility to at least one antibiotic with a known genetic basis. The interactions of plant extracts with antibiotics against the chosen pathogenic microorganisms were investigated using the agar well diffusion, broth microdilution, and checkerboard methods. Calculated fractional inhibitory concentration index (FICI) values were used to describe how the extracts and antibiotics interacted. All the extracts from the three plants combined with fluconazole exhibited a synergistic interaction against C. albicans (FICI &lt; 0.5). The minimum inhibitory concentration (MIC) of ampicillin against E. coli was demonstrated to be reduced by the combination of the ethanol extract of S. alata with ampicillin, with a FICI value of 0.4 indicating a synergistic effect. With a synergistic action (FICI ˂ 0.5) against P. aeruginosa, the ethanol extract of S. alata and amoxicillin were successful in reducing the MIC of amoxicillin from 0.32 to 0.17 mg/mL. Aqueous L. barteri extract combined with amoxicillin exhibited synergism (FICI &lt; 0.2) against S. aureus with a reduction of MIC from 0.20 to 0.03 mg/mL. The current study is the first to investigate the aforementioned plants in combination with conventional antibiotics for their antimicrobial activities. The findings of this study could be used to create a useful, applicable, feasible, and alternative source of novel antimicrobial agents.

Antibacterial, bacteriolytic, antibiofilm, and synergistic effects of Curcuma species ethanol extracts with antibiotic against multidrug resistant Pseudomonas aeruginosa

Introduction: Curcuma species have shown antibacterial activity against Pseudomonas aeruginosa. The current study was conducted to analyze the antibacterial activity of ethanol extracts of Curcuma species rhizomes, including Curcuma domestica, C. xanthorrhiza, C. mangga, C. zedoaria, and C. aeruginosa against multidrug-resistant Pseudomonas aeruginosa (MDR P. aeruginosa). Furthermore, the mechanism action of Curcuma species in combination with antibiotic against MDR P. aeruginosa and its chemical component were also investigated. Methods: Determination of minimum inhibitory concentration (MIC) was carried out by the microdilution method. The synergistic effects of the extract and tetracycline were determined by the checkerboard method. The effect of the combination of Curcuma species and tetracycline to prevent bacterial resistance was investigated using inhibition of biofilm formation, permeability of bacterial cell membrane, and EtBr accumulation methods. Gas chromatography-mass spectrometry (GC-MS) analysis was also performed. Results: MIC of C. domestica, C. xanthorrhiza, and C. mangga against MDR P. aeruginosa were 125, 250, and 125 µg/mL, respectively. C. xanthorrhiza ethanol extract (7.8 µg/mL) in combination with tetracycline (1.9 µg/mL) revealed a synergistic activity with Fractional Inhibitory Concentration Index (FICI) value of 0.06. The combination of C. xanthorrhiza ethanol extract and tetracycline showed inhibitory effects on biofilm formation and efflux pump of MDR P. aeruginosa. This combination also had bacteriolytic activity. GC-MS analysis led to the identification of ar-turmerone (11.63%) and xanthorrhizol (11.36%) as the major compounds. Conclusion: Combination of C. xanthorrhiza ethanol extract and tetracycline might be developed as an alternative treatment against MDR P. aeruginosa.

Chemical Profiling, Antibacterial Efficacy, and Synergistic Actions of Ptychotis verticillata Duby Essential Oil in Combination with Conventional Antibiotics

Introduction: The primary aim of the current investigation is to assess the chemical composition and antibacterial efficacy of Ptychotis verticillata essential oil (PVEO) against three Gram-positive bacteria ( Staphylococcus aureus, Micrococcus luteus, and Bacillus subtilis) and three Gram-negative bacteria ( Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae). Furthermore, this research endeavors to investigate the potential synergistic effects of PVEO when combined with established antibiotics (Amoxicillin, Erythromycin, and Ampicillin), with a focus on discerning their interaction dynamics. Methods: The phytochemical profiling of PVEO was performed via the Gas Chromatography-Mass Spectrometry technique. The broth dilution test determined the interaction effect between PVEO and these three antibiotics. Results: Components γ-terpinene (38.96%), p-cymene (19.38%), thymol (18.07%), and carvacrol (6.99%) are the major bioactive moleculs composing this studied essential oil. PVEO demonstrated significant antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.2 against E coli to 2 mg/mL against M luteus. The assessment of the synergistic activity between PVEO and antibiotics was accomplished through the utilization of the Fractional Inhibitory Concentration Index (FICI). The combination of PVEO and amoxicillin against M luteus demonstrated the best synergistic action with a FICI value of 0.43. Conclusion: Significant reductions, ranging from two to sevenfold, in the MIC values of PVEO, and antibiotics were observed. This noteworthy synergistic interaction between highly potent essential oils and synthetic antibiotics holds the potential to open avenues for novel combination therapies aimed at addressing infections caused by multiresistant microorganisms, even at notably reduced concentrations within the pharmaceutical sector.

Effects of chitooligosaccharide on the in vitro antibacterial activity against avian Escherichia coli and the pharmacokinetics of florfenicol in healthy chickens

This study investigates the combined effects of chitooligosaccharide (COS) and florfenicol (FLO) on the inhibition of Escherichia coli in vitro, as well as the pharmacokinetic interactions between these compounds in healthy chickens. The minimum inhibitory concentration (MIC) of COS and FLO alone and the fractional inhibitory concentration index (FICI) after combined treatment were determined using the broth microdilution method and checkerboard method, respectively. Additionally, we evaluated the pharmacokinetic interactions between the 2 types of COS and FLO in healthy chickens. Thirty chickens were randomly divided into 3 groups: Florfenicol group (30 mg/kg), COS J85 group (COS J85 20 mg/kg + florfenicol 30 mg/kg), COS H85 group (COS H85 20 mg/kg + florfenicol 30 mg/kg). Either FLO or COS was orally administered by gavage. The concentrations of FLO in chicken plasma were measured at different time points after the drug withdrawal using high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were calculated by a compartmental method. The results showed that COS J85 and COS H85, when combined with FLO, had FICI values of 0.1875 to 0.75 and 0.3125 to 1, respectively, indicating good synergistic or additive effects against Escherichia coli. The pharmacokinetics of FLO alone and in combination with COS followed a 1-compartment model with first-order absorption and elimination. Furthermore, the pharmacokinetic analysis revealed that the elimination half-life (t1/2ke) of florfenicol was significantly increased in the COS H85 group compared to oral administration of florfenicol alone (P < 0.05). Other pharmacokinetic parameters did not show significant changes (P > 0.05), except between the 2 combined treatment groups, where statistical differences were observed for various parameters, excluding the area under the concentration-time curve from the time of dosing to infinity (AUC) and peak concentration (Cmax).

Mechanistic insight into the synergistic antimicrobial potential of Fagonia indica Burm.f. extracts with cefixime

Fagonia indica Burm.f. is known for its anti-infective character and has been studied in the present work as a synergistic remedy against resistant bacterial strains. Initially, phytochemicals were quantified in n-Hexane (n-Hex), ethyl acetate (E.A), methanol (MeOH), and aqueous (Aq.) extracts by Total Phenolic Content (TPC), Total Flavonoid Content (TFC) and Reverse Phase High Performance Liquid Chromatography (RP-HPLC) analysis. Later, after establishing an antibacterial resistance profile for extracts and antibiotics against gram-positive and gram-negative strains, synergism was evaluated in combination with cefixime through time-kill kinetics and bacterial protein estimation studies. Topographic images depicting synergism were obtained by scanning electron microscopy for Methicilin-resistant Staphylococcus aureus (MRSA) and Resistant Escherichia coli (R.E. coli). Results showed the presence of maximum phenolic (28.4 ± 0.67 μg GAE/mg extract) and flavonoid (11 ± 0.42 μg QE/mg extract) contents in MeOH extract. RP-HPLC results also displayed maximum polyphenols in MeOH extract followed by E.A extract. Clinical strains were resistant to cefixime whereas these were moderately inhibited by all extracts (MIC 150–300 µg/ml) except Aq. extract. E.A and n-Hex extracts demonstrated maximum synergism (Fractional inhibitory concentration index (FICI) 0.31) against R.E. coli. The n-Hex extract displayed total synergism against R.P. a with a 4-fold reduction in cefixime dose. Time-kill kinetics showed maximum inhibition of gram-negative bacterial growth from 3 to 12 h when treated at FICI and 2FICI values with > 10-fold reduction of the extracts’ dose. All combinations demonstrate > 70 % protein content inhibition with bacterial cell wall disruption in SEM images. Fortunately, FICI concentrations have low hemolytic potential (<5%). Conclusively, F. indica extracts can mitigate antimicrobial resistance against cefixime and can be investigated in detail by in vivo and mechanistic studies.

Improving antimicrobial activity of brown propolis with incorporation of Arthrospira platensis

Propolis exhibits a high content of flavonoids and phenolic acids, hence demonstrating significant antioxidant properties, which have received considerable attention as antimicrobial agents. This study aimed to assess the total phenolic and flavonoid contents of Turkish brown propolis from Gaziantep and Adana provinces, as well as their in-vitro antioxidant, antibacterial, and antifungal activities alone and in combination with Arthrospira platensis. The purification and extraction of propolis were done using 80% ethyl alcohol. The results showed that there was no significant difference in total flavonoid content and antimicrobial activity between the two different propolis samples, but significant differences in their antioxidant activity and total phenolic content were observed (p < 0.05). Both propolis and A. platensis showed good antimicrobial activity against the tested microorganisms alone and in combination. The fractional inhibitory concentration index values demonstrated a synergistic effect between propolis and A. platensis against Staphylococcus aureus, Escherichia coli, and Candida albicans. The results of this study provide empirical evidence that endorses the conventional use of propolis and A. platensis as agents with antibacterial properties. Furthermore, these findings propose that the combination of propolis and A. platensis has promise as a prospective approach for the development of natural antibiotics in forthcoming research endeavors.

Synergistic Effect of Thymol-Ciprofloxacin Combination on Planktonic Cells and Biofilm of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic bacteria causing severe and life-threatening infections in individuals with weakened immune systems. P. aeruginosa forms antibiotic-resistant biofilms, rendering it challenging to treat; hence, alternate therapies are required to eliminate it. Treatment of infections using a combination of drugs is gaining momentum to combat drug-resistant pathogens, including P.aeruginosa. This study explores the synergistic effects of Thymol in combination with Ciprofloxacin, Amikacin and Colistin against planktonic cells and biofilm of P.aeruginosa. Thymol in combination with Ciprofloxacin yields the fractional inhibitory concentration index values 0.156 and 0.375 in P.aeruginosa strains, GC14 and ATCC 9027, respectively, highlighting a robust synergistic effect on both the planktonic and biofilm of P.aeruginosa. The results showed that Thymol (512μg/mL) and Ciprofloxacin (0.125μg/mL) were the most effective combination with 95 and 93.5% total biofilm inhibition in GC14 and PA27, respectively, compared to the Thymol (512μg/mL) and Ciprofloxacin (0.125μg/mL) alone. Our findings suggest that the combinations of Thymol and Ciprofloxacin may be a potential therapeuticstrategy to address the issue of infections caused by P.aeruginosa biofilms.

Microbial Transformation of Hesperidin and Biological Evaluation.

The main aim of the study was the biotransformation evaluation of hesperidin for functionalization by 25 different nonhuman pathogenic microorganisms. As a result, four metabolites were identified and characterized. The structure of pinocembrin and naringenin from the microbial transformation of hesperidin was determined initially with LC/MS-MS. The metabolites eriodictyol and hesperetin were isolated, and their molecular structure was determined by NMR and MS. Pinocembrin, eriodictyol, and naringenin were characterized as new hesperidin microbial transformation metabolites, to the best of our knowledge. In order to evaluate the bioactivity, in vitro 5-lipoxygenase (5-LOX) enzyme inhibition, antioxidant, antimicrobial, and acute toxicity evaluations using the brine shrimp assay of hesperidin and its metabolites were performed comparatively. According to antioxidant and anti-inflammatory activity results, hesperetin metabolite was more active than naringenin and hesperidin. The antimicrobial activity of hesperetin and naringenin against the human pathogenic Staphylococcus aureus strain was relatively higher when compared with the substrate hesperidin. In line with this result, biofilm activity of hesperetin and naringenin against S. aureus with combination studies using biofilm formation methods was carried out. The checkerboard combination method was utilized for biofilm layering, also for the first time in the present study. As an initial result, it was observed that hesperidin and naringenin exerted a synergistic activity with a fractional inhibitory concentration index (FICI) value of 1.063. Considering the bioactivity of hesperidin, hesperetin, and naringenin used as substrates are relatively nontoxic. The microbial and enzymatic biotransformation of natural products such as hesperetin and its new bioactive metabolites still have pharmacological potential, which needs further experimentation at the molecular level..

Menthol- and thymol-based ciprofloxacin derivatives against Mycobacterium tuberculosis: in vitro activity, lipophilicity, and computational studies

In this work, we investigated the antitubercular properties of Ciprofloxacin derivatives conjugated with menthol and thymol moieties. For the sixteen derivatives, we established minimal inhibitory concentrations (MIC) using isolates of Mycobacterium tuberculosis that were resistant or susceptible to other antibiotics. For the most potent compound 1‐cyclopropyl‐6‐fluoro‐7‐{4‐[6‐((1R,2S,5R)‐2‐isopropyl‐5‐methylcyclohexyloxy)‐6‐oxohexyl]piperazin‐1‐yl}‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylic acid (6), we determined fractional inhibitory concentration index (FICI) values to confirm antibacterial susceptibility and synergistic effects with other reference drugs. In addition, chromatographic studies of all the derivatives demonstrated a significant three to four-fold increase in lipophilicity and affinity to phospholipids compared to Ciprofloxacin. Finally, we conducted structure-based studies of the investigated compounds using molecular docking and taking into account protein target mutations associated with fluoroquinolone resistance. In summary, our findings indicate that the investigated compounds possess tuberculostatic properties, with some showing similar or even better activity against resistant strains compared to reference drugs. Increased lipophilicity and affinity to phospholipids of the new derivatives can offer several advantages for new drug candidates, beyond just improved cell membrane penetration. However, further studies are needed to fully understand their safety, efficacy, and mechanism of action.

Antibacterial Effect of Cinnamon and Citronella Oils Combination Against Acne-Related Bacteria

Acne vulgaris is a dermatological disease whose pathogenesis is due to high sebum secretion, hyperkeratinization, hormonal changes, or bacterial infections. Staphylococcus epidermidis and Staphylococcus aureus are bacteria that can induce inflammation in acne. Cinnamomum burmannii and Cymbopogon nardus essential oils have been reported to have antibacterial activity against S. epidermidis and S. aureus. This study aimed to obtain the type of interaction of a combination of C. burmannii and C. nardus oils in inhibiting bacteria associated with acne. Essential oil components were identified using gas chromatography-mass spectrometry (GCMS). Optimize the combination of C. burmannii and C. nardus oils using the checkerboard method. Furthermore, the Fractional Inhibitory Concentration Index (FICI) value is calculated to determine the effect of a combination that is synergistic, additive, not different or antagonistic. The main components of C. burmannii oil identified are cinnamaldehyde, eucalyptol, cinnamyl acetate, α-limonene, and α-terpineol. While C. nardus oil contains the five largest components: geraniol, citronellal, citronellol, citral, and geranyl acetate. Cinnamomum burmannii oil yielded 0.28%, with a refractive index of 1.5237. Meanwhile, the yield of C. nardus oil was 0.26%, with a refractive index of 1.4667. The combination of both oils yielded a FICI value of 1.5. The conclusion of this study shows that the combination of the two essential oils produces an indifferent effect against both S. epidermidis and S. aureus.

Synergistic antibacterial evaluation of Coriandri aetheroleum and linalool with standard antibiotics

Within this work, it was aimed to investigate the in vitro antibacterial properties of the Pharma grade coriander (Coriandrum sativum L.) essential oil, and its combinations. The chemical composition of the essential oil was confirmed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analyses, simultaneously. Furthermore, the potential antibacterial activity of both the essential oil, and (+)-linalool with standard compounds chloramphenicol, and ciprofloxacin were evaluated using an in vitro microdilution assay against a panel of selected pathogens, namely Acinetobacter baumannii, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Initially, the minimum inhibitory concentrations (MIC) were determined, the essential oil as well as (+)-linalool and the standard antibiotics were combined for the synergistic antibacterial activity potential, where the combination activities were expressed as fractional inhibitory concentration index values (Σ FIC). The Coriander oil was relatively more effective against B. cereus, P. aeruginosa, E. coli, A. baumannii (2500 µg/mL) compared to S. aureus (5000 µg/mL), respectively. (+)- Linalool was found as effective as the essential oil (2500-5000 µg/mL). Coriander oil and antibiotic combinations showed synergistic effects against B. cereus (∑FIC= 0.375), E. coli (∑FIC= 0.078) and S. aureus (∑FIC= 0.375). Combination with (+)-linalool, and antibiotics showed synergistic effects against B. cereus (∑FIC= 0.375), E. coli (∑FIC= 0.093), as well as against S. aureus (∑FIC= 0.375), respectively. To the best of our knowledge, this is the first time of the antimicrobial combination study of linalool, coriander oil, chloramphenicol, and ciprofloxacin. The initial findings of this work suggest further natural product and drug combination evaluations.

Synergistic Effect of Combined Antibiotic and Methanolic Extracts of Withania somnifera and Catharanthus roseus against MDR Salmonella enterica Serovar Typhi

Typhoid has become the most neglected and majorly affecting disease of tropical and subtropical countries, including India, and is among the most important global health problems, as the emergence of multidrug resistance has shut down the effect of antimicrobial agents and makes it difficult to control the bacteria inside the host. Hence, there is a great need to develop some natural-based drugs, which will be new promising natural therapeutic interventions with high efficacy and lesser side effects in comparison to synthetic drugs already available for typhoid treatment. The present study completely focused on the synergistic effect of bioactive constituents of medicinal plants in combination to synthetic drugs for enhancing the bacterial eradication mechanism. The methanolic extracts of 25 medicinal plants were screened for their antisalmonella effect and out of which only 2 plants were studied further on the basis of their high effectiveness against 17 MDR isolates using well diffusion assay and MIC/MBC determination. The synergistic activity was assessed with two nonantibiotics (ibuprofen and paracetamol) and 3 antibiotics (ceftazidime chloramphenicol, and trimethoprim) using methods of growth inhibitory indices (GIIs) and fractional inhibitory concentration index (FICI). The highly effective methanolic extracts were of W. somnifera and C. roseus, and the synergism was obtained in terms of GIIs and FICI values of 0.9 and 0.3 and 0.9 and 0.5, respectively, fulfilling the criteria for both extracts, respectively. The results for combinations of plant extracts and antibiotics ceftazidime, trimethoprim, and chloramphenicol and nonantibiotics (analgesic drugs) ibuprofen and paracetamol showed good synergistic activity (100%, 88%, 50%, 45%, and 35%, respectively) against the MDR isolates of S. Typhi. The present study also suggests that in the future, combined treatment with the antibiotics and the bioactive compounds can enhance the immune system to perform better action against the external pathogens as well as in the treatment of internal pathogens, and the combinations will be the successful immune modulators.

In vitro effectiveness of ceftazidime-avibactam in combination with aztreonam on carbapenemase-producing Enterobacterales

ObjectiveThis work aimed to describe the in vitro performance of the combined activity of ceftazidime-avibactam (CZA) plus aztreonam (ATM) against carbapenemase-producing Enterobacterales (CPE). MethodsWe studied 44 CPE clinical isolates: NDM-1 (31), KPC-2 (5), KPC-3 (3), VIM-2 (2), NDM-1+KPC-2 (2), and OXA-48 (1). The efficacy of CZA in combination with were determined by two methods: (i) Kirby-Bauer's double disk synergy test and; (ii) Determination of the minimum inhibitory concentration to CZA by E-test, in either Mueller-Hinton agar alone or, supplemented with ATM 4 mg/L. Additionally, the Fractional inhibitory concentration index (FICI) was determined; values of ≤ 0.5 were interpreted as synergistic, while FICI > 0.5 were considered indifferent. ResultsAll isolates were carbapenem-resistant, 14 were resistant to CZA and ATM, 15 were only CZA resistant, 12 were only ATM resistant, and three were susceptible to both. 34/44 isolates presented positive double disk synergy tests between CZA and ATM regardless of their susceptibility profile, the isolates with negative synergy tests were susceptible to at least one of the agents. On the other hand, the 21 isolates selected to compare the MIC to CZA alone and CZA plus 4 mg/L ATM of exhibited FICI values between 0.016 and 0.125, indicating a synergistic effect. ConclusionsThis method is available to clinical laboratories and would provide valuable information to guide the treatment of infections with CZA and ATM. In this sense, the use of CZA together with ATM is a potentially suitable combination for the treatment of carbapenemase-producing microorganisms.

Evaluation of In vitro Efficacy of Meropenem/Colistin and Meropenem/Fosfomycin Combinations on Multidrug Resistant Gram-Negative Bacilli

The rate of extensively drug-resistant and pan-resistant gram-negative rods isolated as infectious agents is increasing around the world and in Türkiye. One of the important options in the treatment of these infections is the combined use of antibiotics. Therefore, the aim of this study was to investigate the in vitro effect of meropenem/colistin and meropenem/fosfomycin combinations on carbapenem-resistant gram-negative bacilli isolated as infectious agents. Escherichia coli (n= 6), Klebsiella pneumoniae (n= 10), Pseudomonas aeruginosa (n= 5), and Acinetobacter baumannii (n= 6) isolates were recovered from blood and tracheal aspirate samples of patients hospitalized in our hospital's intensive care unit were included in the study. In the first stage of the combination study, minimal inhibitory concentrations (MIC) were investigated by broth microdilution for meropenem and colistin, and agar dilution methods for fosfomycin. In the second stage of the study, synergy, partial synergy, indifference, and antagonistic effects were investigated with the checkerboard method for the meropenem/colistin combination and the agar dilution method for the meropenem/fosfomycin combination. The checkerboard results were interpreted as follows: fractional inhibitory concentration index (FICI) values ≤ 0.5 synergy, < 0.5-≤ 1 partial synergy, > 1-≤ 4 indifference and FIC values of > 4 antagonism. MIC values obtained in the study were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Of the 27 isolates studied with the broth microdilution method, 63% were found to be colistin-resistant and 37% susceptible. The MIC values of fosfomycin against Enterobacterales group bacteria were found to be in the range of 2-2048 mg/L. Two of the six E.coli isolates and nine of the 10 K.pneumoniae isolates were found to be resistant to fosfomycin (IV). The MIC values of ≥ 128 mg/L were found in all 11 non-fermentative gram-negative rods with intrinsic resistance to fosfomycin. In the combination of meropenem/ colistin, synergy and partial synergy were observed in 11 (40.7%) of 27 isolates, an indifference effect was observed in 13 (48.2%), and antagonistic effects were observed in three (11.1%) of the isolates. The synergy and partial synergy effects of this combination were 37.5% for Enterobacterales group bacteria, 50% for E.coli, and 30% for K.pneumoniae. Regarding the 11 non-fermentative gram-negative rods included in the study, 83.3% synergy and partial synergy was found in A.baumannii for the meropenem/colistin combination, while no synergy and partial synergistic effect was found in P.aeruginosa. Meropenem/fosfomycin synergy and partial synergy effects were 83.3% (5/6) for E.coli, 100% (8/8) for K.pneumoniae, 100% (6/6) for A.baumannii, and 25% (1/4) for P.aeruginosa. In all of the isolates studied, meropenem/fosfomycin combination was found to be more effective than the meropenem/colistin combination. It would be meaningful to support these data obtained in vitro with clinical efficacy results to be obtained as a result of the application of antibiotics in vivo, taking into account the pharmacokinetic and pharmacodynamic properties of the antibiotics used in this study.