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  1. Improving shared decision-making in adolescents through antibiotic education
    Ngadimon IW, Islahudin F, Mohamed Shah N, Md Hatah E, Makmor-Bakry M
    Int J Clin Pharm, 2017 Feb;39(1):120-125.
    PMID: 27905077 DOI: 10.1007/s11096-016-0407-1
    Background Shared decision-making is vital in achieving desired drug therapy goals, especially with antibiotics, in view of the potential long-term reduction in drug resistance. However, shared decision-making is rarely practiced with adolescent patients. Objectives The aim of the study was to identify the effect antibiotic education has on willingness to engage in shared decision-making among adolescents in Malaysia. Setting Participants from secondary schools in Malaysia were enrolled with ethical approval. Method The adolescents answered a validated questionnaire, which included demographics, antibiotic knowledge, attitude towards antibiotic use, and the Control Preference Scale, which measures willingness to engage in shared decision-making. Afterwards, antibiotic education was delivered to participating students. Main outcome measure Knowledge about and attitude toward antibiotics were investigated. Results A total of 510 adolescents participated in the study. Knowledge of antibiotics significantly increased post education (pre 3.2 ± 1.8 vs. post 6.8 ± 2.1, p 
    Matched MeSH terms: Anti-Bacterial Agents/adverse effects; Anti-Bacterial Agents/therapeutic use*
  2. Monitoring of tobramycin in human plasma via mixed matrix membrane extraction prior to capillary electrophoresis with contactless conductivity detection
    Mukhtar NH, Mamat NA, See HH
    J Pharm Biomed Anal, 2018 Sep 05;158:184-188.
    PMID: 29883881 DOI: 10.1016/j.jpba.2018.05.044
    A sample pre-treatment method based on a dynamic mixed matrix membrane tip extraction followed by capillary electrophoresis with contactless conductivity detection (CE-C4D) was evaluated for the determination of tobramycin in human plasma. The extraction tip device consisted of a cellulose triacetate membrane tip wall immobilised with 15% (w/w) of hydrophilic lipophilic balance (HLB) nanoparticles as adsorbent. The extraction was performed dynamically by withdrawing/dispensing the plasma sample through the tip device followed by desorption into 20 μL of acidified aqueous solution at pH 3 prior to the CE-C4D analysis. Under the optimum conditions, the detection limit of the method for tobramycin was 10 ng/mL, with intraday and interday repeatability RSDs of 3.5% and 4.5%, respectively. Relative recoveries in spiked human plasma were 99.6%-99.9%. The developed approach was successfully demonstrated for the quantification of tobramycin in human plasma samples.
    Matched MeSH terms: Anti-Bacterial Agents/blood*; Anti-Bacterial Agents/therapeutic use
  3. Plant-derived Compounds as Potential Source of Novel Anti-Biofilm Agents Against Pseudomonas aeruginosa
    Chung PY
    Curr Drug Targets, 2017;18(4):414-420.
    PMID: 27758704 DOI: 10.2174/1389450117666161019102025
    Pseudomonas aeruginosa is the most common Gram-negative bacterium associated with nosocomial and life-threatening chronic infections in cystic fibrosis patients. This pathogen is wellknown for its ability to attach to surfaces of indwelling medical devices to form biofilms, which consist of a regular array of extracellular polymers. Tenaciously bound to the surface of devices and inherently resilient to antibiotic treatment, P. aeruginosa poses a serious threat in clinical medicine and contributes to the persistence of chronic infections. Studies on microbial biofilms in the past decade involved mainly the understanding of environment signals, genetic elements and molecular mechanisms in biofilm formation, tolerance and dispersal. The knowledge obtained from the studies of these mechanisms is crucial in the establishment of strategies to eradicate or to prevent biofilm formation. Currently, biofilm infections are usually treated with combinations of antibiotics and surgical removal, in addition to frequent replacement of the infected device. More recently, specific natural sources have been identified as antibiofilm agents against this pathogen. This review will highlight the recent progress made by plant-derived compounds against P. aeruginosa biofilm infections in both in vitro or in vivo models.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology*; Anti-Bacterial Agents/therapeutic use
  4. Biochemical synthesis of silver nanoprticles using filamentous fungi Penicillium decumbens (MTCC-2494) and its efficacy against A-549 lung cancer cell line
    Majeed S, Abdullah MS, Dash GK, Ansari MT, Nanda A
    Chin J Nat Med, 2016 Aug;14(8):615-20.
    PMID: 27608951 DOI: 10.1016/S1875-5364(16)30072-3
    Biosynthesis of silver and other metallic nanoparticles is one of the emerging research area in the field of science and technology due to their potentiality, especially in the field of nano-biotechnology and biomedical sciences in order to develop nanomedicine. In our present study, Penicillium decumbens (MTCC-2494) was brought from Institute of Microbial Technology (IMTECH) Chandigarh and employed for extracellular biological synthesis of silver nanoparticles. Ag-NPs formation was appeared with a dark brown color inside the conical flask. Characterization of Ag-NPs were done by UV-Spectrophotometric analysis which showed absorption peak at 430 nm determines the presence of nanoparticles, Fourier transform infrared (FT-IR) spectroscopic analysis, showed amines and amides are the possible proteins involved in the stabilization of nanoparticles as capping agent. Atomic force Microscopy (AFM) confirmed the particle are spherical, size was around 30 to 60 nm and also the roughness of nanoparticles. Field emission scanning electron microscopy (FE-SEM) showed the topology of the nanoparticles and were spherical in shape. The biosynthesis process was found fast, ecofriendly and cost effective. Nano-silver particle was found to have a broad antimicrobial activity and also it showed good enhancement of antimicrobial activity of Carbenicillin, Piperacillin, Cefixime, Amoxicillin, Ofloxacin and Sparfloxacin in a synergistic mode. These Ag-NPs showed good anti-cancer activity at 80 μg·mL(-1)upon 24 hours of incubation and toxicity increases upon 48 hours of incubation against A-549 human lung cancer cell line and the synergistic formulation of the antibiotic with the synthesized nanoparticles was found more effective against the pathogenic bacteria studied.
    Matched MeSH terms: Anti-Bacterial Agents/metabolism; Anti-Bacterial Agents/pharmacology
  5. Cellulose nanocomposite films with in situ generated silver nanoparticles using Cassia alata leaf extract as a reducing agent
    Sivaranjana P, Nagarajan ER, Rajini N, Jawaid M, Rajulu AV
    Int J Biol Macromol, 2017 Jun;99:223-232.
    PMID: 28237574 DOI: 10.1016/j.ijbiomac.2017.02.070
    Cotton linters were dissolved in aq. (8% LiOH+15% urea) that was pre-cooled to -12.5°C. Using this solution cellulose gel films were prepared by regeneration method with ethyl alcohol as a coagulant. These wet films were diffused with 10wt% Cassia alata leaf extract that acted as a reducing agent. The leaf extract diffused cellulose wet films were used as the matrix. The wet matrix films were dipped individually in lower concentrated 1-5mM aq.AgNO3 source solutions in the presence of sunlight and allowed the solutions to react with the diffused leaf extract reducing agent which in situ generated the silver nanoparticles (AgNPs) inside the films as well as in the source solution. The AgNPs formed in the source solution were observed by transmission electron microscope (TEM) and scanning electron microscope (SEM) while those formed in situ the films were observed by SEM and the particle size distribution was determined. The cellulose/AgNP composite films showed good antibacterial activity against Escherichia coli bacteria. These nanocomposite films were also characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA) and tensile tests. At temperatures below 300°C, the thermal stability of the nanocomposite films was lower than that of the matrix due to the catalytic effect of AgNPs. The nanocomposite films also possessed good tensile properties. The ecofriendly cellulose/AgNP composite films with good antibacterial activity and tensile properties can be considered for medical applications like dressing materials.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
  6. Synthesis, spectral analysis and antibacterial activity of some novel 5-substituted-2-((6-bromo-3,4-methylenedioxybenzyl)thio)-1,3,4-oxadiazole derivatives
    Rehman A, Siddiqa A, Abbasi MA, Siddiqui SZ, Khan SG, Rasool S, et al.
    Pak J Pharm Sci, 2018 Sep;31(5):1783-1790.
    PMID: 30150171
    A number of novel 5-substituted-2-((6-bromo-3,4-methylenedioxybenzyl)thio)-1,3,4-Oxadiazole derivatives (6a-l) have been synthesized to evaluate their antibacterial activity. Using aryl/aralkyl carboxylic acids (1a-l) as precursors, 5-substituted-1,3,4-Oxadiazol-2-thiols (4a-l) were yielded in good amounts. The derivatives, 4a-l, were subjected to electrophilic substitution reaction on stirring with 6-bromo-3,4-methylenedioxybenzyl chloride (5) in DMF to synthesize the required compounds. All the synthesized molecules were well characterized by IR, 1H-NMR, 13C-NMR and EIMS spectral data and evaluated for antibacterial activity against some bacterial strains of Gram-bacteria. The molecule, 6d, demonstrated the best activity among all the synthesized molecules exhibiting weak to moderate inhibition potential.
    Matched MeSH terms: Anti-Bacterial Agents/analysis*; Anti-Bacterial Agents/chemical synthesis*
  7. Fulltext Wound Healing Properties of Selected Natural Products
    Ibrahim N', Wong SK, Mohamed IN, Mohamed N, Chin KY, Ima-Nirwana S, et al.
    Int J Environ Res Public Health, 2018 10 25;15(11).
    PMID: 30366427 DOI: 10.3390/ijerph15112360
    Wound healing is a complex process of recovering the forms and functions of injured tissues. The process is tightly regulated by multiple growth factors and cytokines released at the wound site. Any alterations that disrupt the healing processes would worsen the tissue damage and prolong repair process. Various conditions may contribute to impaired wound healing, including infections, underlying diseases and medications. Numerous studies on the potential of natural products with anti-inflammatory, antioxidant, antibacterial and pro-collagen synthesis properties as wound healing agents have been performed. Their medicinal properties can be contributed by the content of bioactive phytochemical constituents such as alkaloids, essential oils, flavonoids, tannins, saponins, and phenolic compounds in the natural products. This review highlights the in vitro, in vivo and clinical studies on wound healing promotions by the selected natural products and the mechanisms involved.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use
  8. Thiol-functionalized magnetic carbon nanotubes for magnetic micro-solid phase extraction of sulfonamide antibiotics from milks and commercial chicken meat products
    Nasir ANM, Yahaya N, Zain NNM, Lim V, Kamaruzaman S, Saad B, et al.
    Food Chem, 2019 Mar 15;276:458-466.
    PMID: 30409620 DOI: 10.1016/j.foodchem.2018.10.044
    Thiol-functionalized magnetic carbon nanotubes (TMCNTs) were employed as the sorbent in the magnetic micro-solid phase extraction (M-µ-SPE) of sulfonamide antibiotics (SAs) in water, milks and chicken meat products prior to high performance liquid chromatography-diode array detector (HPLC-DAD) analysis. The synthesized sorbent was characterized by several spectroscopic techniques. Optimum conditions were: 20 mg of TMCNTs at pH 4, 2 min extraction time, 10% addition of salt and 30 mL of sample volume. Under the optimized TMCNTs-M-µ-SPE and HPLC-DAD conditions, the method showed good linearity in the range of 0.1-500 µg L-1 (r2 ≥ 0.9950), low limits of detection (0.02-1.5 µg L-1), good analytes recovery (80.7-116.2%) and acceptable RSDs (0.3-7.7%, n = 15). The method was applied to tap water (1), milks (15) and commercial chicken meat products (35), SAs were detected in five chicken meat samples (3.0-25.7 µg L-1). The method is critically compared to those reported in the literature.
    Matched MeSH terms: Anti-Bacterial Agents/analysis*; Anti-Bacterial Agents/isolation & purification
  9. Antimicrobial Exploration Between Counterpart Endosymbiont and Host Plant (Tamarindus indica Linn.)
    Chigurupati S, Vijayabalan S, Selvarajan KK, Aldubayan M, Alhowail A, Mani V, et al.
    Curr Pharm Biotechnol, 2020;21(5):384-389.
    PMID: 31657678 DOI: 10.2174/1389201020666191028105325
    BACKGROUND: Endophytic bacteria produce various bioactive secondary metabolites, which benefit human health. Tamarindus indica L. is well known for its medicinal value in human health care. Several studies have reported on its biological effects from various parts of T. indica, but only a few studies have been devoted to examining the biological activity of endophytes of T. indica.

    OBJECTIVES: In the present study, an endophyte was isolated from the leaves of T. indica and screened for its antimicrobial potential.

    METHODS: The selected endophyte was identified by 16s rRNA partial genome sequencing and investigated for their antimicrobial potency. The preliminary phytochemical tests were conducted for the affirmation of phytoconstituents in the endophytic crude ethyl acetate extract of T. indica (TIM) and total phenolic content was performed. The antimicrobial potential of TIM was evaluated against human pathogenic ATCC gram-positive and gram-negative bacterial strains.

    RESULTS: TIM exhibited an appreciable amount of gallic acid equivalent phenolic content (21.6 ± 0.04 mg GAE/g of crude extract). TIM showed the Minimum Inhibitory Concentration (MIC) at 250 μg/mL and Minimum Bactericidal Concentration (MBC) at 500 μg/mL among the selected human pathogenic ATCC strains. At MIC of 500 μg/mL, TIM displayed a significant zone of inhibition against P. aeruginosa and N. gonorrhoeae.

    CONCLUSION: The results from our study highlighted for the first time the antimicrobial potential of endophytic bacterial strain Bacillus velezensis in T. indica leaves and it could be further explored as a source of natural antimicrobial agents.

    Matched MeSH terms: Anti-Bacterial Agents/isolation & purification; Anti-Bacterial Agents/pharmacology*
  10. BSA Binding, molecular docking and in vitro biological screening of some new 1, 2, 4-triazole heterocycles bearing azinane nucleus
    Iqbal J, Rehman A, Abbasi MA, Siddiqui SZ, Khalid H, Laulloo SJ, et al.
    Pak J Pharm Sci, 2020 Jan;33(1):149-160.
    PMID: 32122843
    A series of new compounds (5a-q), derived from 5-(1-(4-nitrophenylsulfonyl) piperidin-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol (3) were proficiently synthesized to evaluate their biological activities. 1-(4-Nitrophenylsulfonyl) piperidine-4-carbohydrazide (2) was refluxed with phenylisothiocyanate to yield an adduct which was cyclized to compound 3 by reflux reaction with 10 % potassium hydroxide. The targeted compounds 5a-q, were synthesized by stirring alkyl/aralkyl halides (4a-q) and compound 3 in a polar aprotic solvent. 1H-NMR, 13C-NMR, EI-MS and IR spectral techniques were employed to confirm the structures of all the synthesized compounds. The compounds were biologically evaluated for BSA binding studies followed by anti-bacterial, anti-inflammatory and acetylcholinesterase (AChE) activities. The active sites responsible for the best AChE inhibition were identified through molecular docking studies. Compound 5e bearing 4-chlorobenzyl moiety found most active antibacterial and anti-inflammatory agent among the synthesized compounds. The whole library of synthesized compounds except compounds 5d and 5f was found highly active for AChE inhibition and recommended for in vivo studies so that their therapeutic applications may come in utilization.
    Matched MeSH terms: Anti-Bacterial Agents/chemical synthesis; Anti-Bacterial Agents/pharmacology*
  11. Profiling of gene expression in methicillin-resistant Staphylococcus aureus in response to cyclo-(L-Val-L-Pro) and chloramphenicol isolated from Streptomyces sp., SUK 25 reveals gene downregulation in multiple biological targets
    Zin NM, Al-Shaibani MM, Jalil J, Sukri A, Al-Maleki AR, Sidik NM
    Arch Microbiol, 2020 Oct;202(8):2083-2092.
    PMID: 32494868 DOI: 10.1007/s00203-020-01896-x
    Chloramphenicol (CAP) and cyclo-(L-Val-L-Pro) were previously isolated from Streptomyces sp., SUK 25 which exhibited a high potency against methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to profile gene expression of MRSA treated with CAP and cyclo-(L-Val-L-Pro) compounds using DNA microarray. Treatment of MRSA with CAP resulted in upregulation of genes involved in protein synthesis, suggesting the coping mechanism of MRSA due to the inhibition of protein synthesis effect from CAP. Most upregulated genes in cyclo-(L-Val-L-Pro) were putative genes with unknown functions. Interestingly, genes encoding ribosomal proteins, cell membrane synthesis, DNA metabolism, citric acid cycle and virulence were downregulated in MRSA treated with cyclo-(L-Val-L-Pro) compound, suggesting the efficacy of this compound in targeting multiple biological pathways. Contrary to CAP, with only a single target, cyclo-(L-Val-L-Pro) isolated from this study had multiple antimicrobial targets that can delay antibiotic resistance and hence is a potential antimicrobial agent of MRSA.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use
  12. Quorum sensing: a new prospect for the management of antimicrobial-resistant infectious diseases
    Haque M, Islam S, Sheikh MA, Dhingra S, Uwambaye P, Labricciosa FM, et al.
    Expert Rev Anti Infect Ther, 2021 05;19(5):571-586.
    PMID: 33131352 DOI: 10.1080/14787210.2021.1843427
    INTRODUCTION: Quorum-sensing (QS) is a microbial cell-to-cell communication system that utilizes small signaling molecules to mediates interactions between cross-kingdom microorganisms, including Gram-positive and -negative microbes. QS molecules include N-acyl-homoserine-lactones (AHLs), furanosyl borate, hydroxyl-palmitic acid methylester, and methyl-dodecanoic acid. These signaling molecules maintain the symbiotic relationship between a host and the healthy microbial flora and also control various microbial virulence factors. This manuscript has been developed based on published scientific papers.

    AREAS COVERED: Furanones, glycosylated chemicals, heavy metals, and nanomaterials are considered QS inhibitors (QSIs) and are therefore capable of inhibiting the microbial QS system. QSIs are currently being considered as antimicrobial therapeutic options. Currently, the low speed at which new antimicrobial agents are being developed impairs the treatment of drug-resistant infections. Therefore, QSIs are currently being studied as potential interventions targeting QS-signaling molecules and quorum quenching (QQ) enzymes to reduce microbial virulence.

    EXPERT OPINION: QSIs represent a novel opportunity to combat antimicrobial resistance (AMR). However, no clinical trials have been conducted thus far assessing their efficacy. With the recent advancements in technology and the development of well-designed clinical trials aimed at targeting various components of the, QS system, these agents will undoubtedly provide a useful alternative to treat infectious diseases.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage; Anti-Bacterial Agents/pharmacology*
  13. Pharmacodynamic Analysis of Meropenem and Fosfomycin Combination Against Carbapenem-Resistant Acinetobacter baumannii in Patients with Normal Renal Clearance: Can It Be a Treatment Option?
    Mohd Sazlly Lim S, Heffernan AJ, Roberts JA, Sime FB
    Microb Drug Resist, 2021 Apr;27(4):546-552.
    PMID: 32898467 DOI: 10.1089/mdr.2020.0197
    Background and Objective: Combination therapy may be a treatment option against carbapenem-resistant Acinetobacter baumannii (CR-AB) infections. In this study, we explored the utility of fosfomycin in combination with meropenem (FOS/MEM) against CR-AB isolates. Materials and Methods: Screening of synergistic activity of FOS/MEM was performed using the checkerboard assay. A pharmacokinetic/pharmacodynamic analysis was performed for various FOS/MEM regimens using Monte Carlo simulations. Results: The minimum inhibitory concentration (MIC) required to inhibit the growth of 50% of the isolates (MIC50) and MIC required to inhibit the growth of 90% of the isolates (MIC90) of FOS and MEM were reduced fourfold and twofold, respectively. The combination was synergistic against 14/50 isolates. No antagonism was observed. Sixteen out of fifty isolates had MEM MICs of ≤8 mg/L when subjected to combination therapy, compared to none with monotherapy. Forty-one out of 50 isolates had FOS MICs of ≤128 mg/L when subjected to combination therapy, compared to 17/50 isolates with monotherapy. The cumulative fraction response for MEM and FOS improved from 0% to 40% and 40% to 80%, with combination therapy, respectively. Conclusions: Addition of MEM improved the in vitro activity of FOS against the CR-AB isolates. FOS/MEM could be a plausible option to treat CR-AB for a small fraction of isolates.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage; Anti-Bacterial Agents/pharmacology*
  14. Fulltext Synergistic antibacterial activity of Curcumin with antibiotics against Staphylococcus aureus
    Teow SY, Ali SA
    Pak J Pharm Sci, 2015 Nov;28(6):2109-14.
    PMID: 26639480
    This study evaluated the synergistic antibacterial activity of Curcumin with 8 different antibiotic groups. Two reference, one clinical and ten environmental strains of Staphylococcus aureus (S. aureus) were tested. Disc diffusion assay with 25 μg/mL Curcumin demonstrated synergism in combination with a majority of tested antibiotics against S. aureus. However, checkerboard micro dilution assay only showed synergism, fractional inhibitory concentration index (FICI) <0.5 in three antibiotics i.e. Gentamicin, Amikacin, and Ciprofloxacin. Other antibiotics showed indifferent interactions but no antagonism was observed. In time-kill curve, appreciable reduction of bacterial cells was also observed in combination therapy (Curcumin + antibiotics) compared to monotherapy (Curcumin or antibiotic(s) alone). The antibiotics with higher synergistic interaction with Curcumin are arranged in a decreasing order: Amikacin > Gentamicin > Ciprofloxacin.
    Matched MeSH terms: Anti-Bacterial Agents/isolation & purification; Anti-Bacterial Agents/pharmacology*
  15. Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes
    Ling SS, Magosso E, Khan NA, Yuen KH, Barker SA
    Drug Dev Ind Pharm, 2006 Mar;32(3):335-45.
    PMID: 16556538
    A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage; Anti-Bacterial Agents/pharmacokinetics*
  16. Semi-mechanistic PK/PD modelling of meropenem and sulbactam combination against carbapenem-resistant strains of Acinetobacter baumannii
    Mohd Sazlly Lim S, Heffernan AJ, Zowawi HM, Roberts JA, Sime FB
    Eur J Clin Microbiol Infect Dis, 2021 Sep;40(9):1943-1952.
    PMID: 33884516 DOI: 10.1007/s10096-021-04252-z
    Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are commonly used. In this study, we explored the potential efficacy of meropenem-sulbactam combination (MEM/SUL) against CR-AB. The checkerboard method was used to screen for synergistic activity of MEM/SUL against 50 clinical CR-AB isolates. Subsequently, time-kill studies against two CR-AB isolates were performed. Time-kill data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Subsequently, Monte Carlo simulations were performed to estimate the probability of 2-log kill, 1-log kill or stasis at 24-h following combination therapy. The MEM/SUL demonstrated synergy against 28/50 isolates. No antagonism was observed. The MIC50 and MIC90 of MEM/SUL were decreased fourfold, compared to the monotherapy MIC. In the time-kill studies, the combination displayed synergistic killing against both isolates at the highest clinically achievable concentrations. At concentrations equal to the fractional inhibitory concentration, synergism was observed against one isolate. The PK/PD model adequately delineated the data and the interaction between meropenem and sulbactam. The effect of the combination was driven by sulbactam, with meropenem acting as a potentiator. The simulations of various dosing regimens revealed no activity for the monotherapies. At best, the MEM/SUL regimen of 2 g/4 g every 8 h demonstrated a probability of target attainment of 2-log10 kill at 24 h of 34%. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log10 reduction in bacterial burden demonstrated that MEM/SUL may potentially be effective against some CR-AB infections.
    Matched MeSH terms: Anti-Bacterial Agents/pharmacokinetics*; Anti-Bacterial Agents/pharmacology
  17. Fulltext Bacterial Cellulose: Production, Characterization, and Application as Antimicrobial Agent
    Lahiri D, Nag M, Dutta B, Dey A, Sarkar T, Pati S, et al.
    Int J Mol Sci, 2021 Nov 30;22(23).
    PMID: 34884787 DOI: 10.3390/ijms222312984
    Bacterial cellulose (BC) is recognized as a multifaceted, versatile biomaterial with abundant applications. Groups of microorganisms such as bacteria are accountable for BC synthesis through static or agitated fermentation processes in the presence of competent media. In comparison to static cultivation, agitated cultivation provides the maximum yield of the BC. A pure cellulose BC can positively interact with hydrophilic or hydrophobic biopolymers while being used in the biomedical domain. From the last two decades, the reinforcement of biopolymer-based biocomposites and its applicability with BC have increased in the research field. The harmony of hydrophobic biopolymers can be reduced due to the high moisture content of BC in comparison to hydrophilic biopolymers. Mechanical properties are the important parameters not only in producing green composite but also in dealing with tissue engineering, medical implants, and biofilm. The wide requisition of BC in medical as well as industrial fields has warranted the scaling up of the production of BC with added economy. This review provides a detailed overview of the production and properties of BC and several parameters affecting the production of BC and its biocomposites, elucidating their antimicrobial and antibiofilm efficacy with an insight to highlight their therapeutic potential.
    Matched MeSH terms: Anti-Bacterial Agents/metabolism; Anti-Bacterial Agents/pharmacology*
  18. Fulltext Development of Antibacterial, Degradable and pH-Responsive Chitosan/Guar Gum/Polyvinyl Alcohol Blended Hydrogels for Wound Dressing
    Khan MUA, Iqbal I, Ansari MNM, Razak SIA, Raza MA, Sajjad A, et al.
    Molecules, 2021 Sep 30;26(19).
    PMID: 34641480 DOI: 10.3390/molecules26195937
    The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels' crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker-Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R2 = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications.
    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*; Anti-Bacterial Agents/chemistry
  19. Bacterial biofilms associated skin disorders: Pathogenesis, advanced pharmacotherapy and nanotechnology-based drug delivery systems as a treatment approach
    Vyas T, Rapalli VK, Chellappan DK, Dua K, Dubey SK, Singhvi G
    Life Sci, 2021 Dec 15;287:120148.
    PMID: 34785190 DOI: 10.1016/j.lfs.2021.120148
    BACKGROUND: Biofilms are microcolonies of microbes that form communities with a variety of microbes, exhibit the same gene composition but differ in gene expression. Biofilm-associated infections have been in existence for a long, however, biofilm-associated skin disorders have not been investigated much.

    OBJECTIVES: Biofilms, which are made mostly of the matrix can be thought of as communities of microbes that are more virulent and more difficult to eradicate as compared to their planktonic counterparts. Currently, several formulations are available in the market which have the potential to treat biofilm-assisted skin disorders. However, the existing pharmacotherapies are not competent enough to cure them effectively and entirely, in several cases.

    KEY FINDINGS: Especially with the rising resistance towards antibiotics, it has become particularly challenging to ameliorate these disorders completely. The new approaches are being used to combat biofilm-associated skin disorders, some of them being photodynamic therapy, nanotherapies, and the use of novel drug delivery systems. The focus of attention, however, is nanotherapy. Micelles, solid lipid nanoparticles, quatsomes, and many others are being considered to find a better solution for the biofilm-associated skin disorders.

    SIGNIFICANCE: This review is an attempt to give a perspective on these new approaches for treating bacterial biofilms associated with skin disorders.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage*; Anti-Bacterial Agents/metabolism
  20. Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of Pseudomonas aeruginosa Induced Keratitis in Rabbits
    Singh S, Agarwal R, Razak ZA, Ngu R, Nyein LL, Vasudevan S, et al.
    J Ocul Pharmacol Ther, 2018 01 17;34(1-2):214-223.
    PMID: 29341837 DOI: 10.1089/jop.2017.0098
    PURPOSE: Pseudomonas aeruginosa is the most common causative organism for contact lens-associated corneal ulcer and is commonly treated with fluoroquinolones. With the emergence of resistant strains, it is important to investigate alternative therapies. Despite well-established efficacy of tazocin against systemic Pseudomonas infections, its topical use for the treatment of Pseudomonas keratitis has not been described, hence this study was aimed to find the ocular permeation of Tazocin and its efficacy in treating keratitis in rabbit eyes.

    METHODS: We investigated the ocular permeation of topical tazocin after single drop application in normal rabbit eyes by estimating piperacillin and tazobactam concentrations in cornea, aqueous, and vitreous using a validated LC-MS/MS method. Furthermore, we determined the efficacy of repeated dose administration of tazocin against experimentally induced P. aeruginosa keratitis in rabbits in comparison to moxifloxacin. To determine the efficacy, clinical examination, histopathological examination, and estimation of bacterial load and inflammatory cytokines in cornea were done.

    RESULTS: Significant corneal concentration of piperacillin and tazobactam was detected in normal rabbit corneas after single dose treatment with tazocin. In rabbits with Pseudomonas-induced keratitis, topical tazocin caused significant clinical and histopathological improvement. This improvement was associated with reduction in corneal bacterial load and inflammatory cytokines. Compared to moxifloxacin 0.5%, tazocin treated group showed greater clinical response which was associated with higher interleukin (IL)-1β, lower tumor necrosis factor (TNF)-α, a comparable level of IL-8, greater reduction in corneal bacterial load, and lesser inflammatory cell infiltration.

    CONCLUSION: Tazocin showed good ocular penetration and was effective in treatment of Pseudomonas induced keratitis in rabbits.

    Matched MeSH terms: Anti-Bacterial Agents/administration & dosage; Anti-Bacterial Agents/pharmacology*
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