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Real-world practice of Helicobacter pylori management: A survey among physicians in Southeast Asia

Quach DT, Vilaichone RK, Luu MN, Lee YY, Ang TL, Miftahussurur M, et al.

Helicobacter, 2023 Dec;28(6):e13018.
PMID: 37634226 DOI: 10.1111/hel.13018

BACKGROUND: Multidrug-resistant Helicobacter pylori strains are emerging in Southeast Asia. This study evaluates the region's real-world practice in H. pylori management.
MATERIALS AND METHODS: Physicians who managed H. pylori eradication in daily practice across 10 Southeast Asian countries were invited to participate in an online questionnaire, which included questions about the local availability of antimicrobial susceptibility tests (ASTs) and their preferred eradication regimens in real-world practice. An empiric regimen was considered inappropriate if it did not follow the local guidelines/consensus, particularly if it contained antibiotics with a high reported resistance rate or was recommended not to be empirically used worldwide.
RESULTS: There were 564 valid responses, including 314 (55.7%) from gastroenterologists (GIs) and 250 (44.3%) from non-GI physicians. ASTs were unavailable in 41.7%. In countries with low and intermediate clarithromycin resistance, the most common first-line regimen was PAC (proton pump inhibitor [PPI], amoxicillin, clarithromycin) (72.7% and 73.2%, respectively). Regarding second-line therapy, the most common regimen was bismuth-based quadruple therapy, PBMT (PPI, bismuth, metronidazole, tetracycline) (50.0% and 59.8%, respectively), if other regimens were used as first-line treatment. Concomitant therapy (PPI, amoxicillin, clarithromycin, metronidazole) (30.5% and 25.9%, respectively) and PAL (PPI, amoxicillin, levofloxacin) (22.7% and 27.7%, respectively) were favored if PBMT had been used as first-line treatment. In countries with high clarithromycin resistance, the most common first-line regimen was PBMT, but the utilization rate was only 57.7%. Alarmingly, PAC was prescribed in 27.8% of patients, ranking as the second most common regimen, and its prescription rate was higher in non-GI physicians than GI physicians (40.1% vs. 16.2%, p

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/therapeutic use
Probiotic containing Lactobacillus reuteri DSM 17648 as an adjunct treatment for Helicobacter pylori infection: A randomized, double-blind, placebo-controlled trial

Ismail NI, Nawawi KNM, Hsin DCC, Hao KW, Mahmood NRKN, Chearn GLC, et al.

Helicobacter, 2023 Dec;28(6):e13017.
PMID: 37614081 DOI: 10.1111/hel.13017

BACKGROUND: Despite multiple therapy regimens, the decline in the Helicobacter pylori eradication rate poses a significant challenge to the medical community. Adding Lactobacillus reuteri probiotic as an adjunct treatment has shown some promising results. This study aims to investigate the efficacy of Lactobacillus reuteri DSM 17648 in H. pylori eradication and its effect in ameliorating gastrointestinal symptoms and adverse treatment effects.
MATERIALS AND METHODS: This randomized, double-blinded, placebo-controlled trial involved treatment-naïve H. pylori-positive patients. Ninety patients received standard triple therapy for 2 weeks before receiving either a probiotic or placebo for 4 weeks. The posttreatment eradication rate was assessed via a 14 C urea breath test in Week 8. The Gastrointestinal Symptom Rating Scale (GSRS) questionnaire and an interview on treatment adverse effects were conducted during this study.
RESULTS: The eradication rate was higher in the probiotic group than in the placebo group, with a 22.2% difference in the intention-to-treat analysis (91.1% vs. 68.9%; p = 0.007) and 24.3% difference in the per-protocol analysis (93.2% vs. 68.9%; p = 0.007). The probiotic group showed significant pre- to post-treatment reductions in indigestion, constipation, abdominal pain, and total GSRS scores. The probiotic group showed significantly greater reductions in GSRS scores than the placebo group: indigestion (4.34 ± 5.00 vs. 1.78 ± 5.64; p = 0.026), abdominal pain (2.64 ± 2.88 vs. 0.89 ± 3.11; p = 0.007), constipation (2.34 ± 3.91 vs. 0.64 ± 2.92; p = 0.023), and total score (12.41 ± 12.19 vs. 4.24 ± 13.72; p = 0.004). The probiotic group reported significantly fewer adverse headache (0% vs. 15.6%; p = 0.012) and abdominal pain (0% vs. 13.3%; p = 0.026) effects.
CONCLUSIONS: There was a significant increase in H. pylori eradication rate and attenuation of symptoms and adverse treatment effects when L. reuteri was given as an adjunct treatment.

Matched MeSH terms: Anti-Bacterial Agents
Green synthesis, characterisation and antibacterial activities of Strobilanthes crispus-mediated silver nanoparticles (SC-AGNPS) against selected bacteria

Mohamad Hanafiah R, Abd Ghafar SA, Lim V, Musa SNA, Yakop F, Hairil Anuar AH

Artif Cells Nanomed Biotechnol, 2023 Dec;51(1):549-559.
PMID: 37847252 DOI: 10.1080/21691401.2023.2268167

This study aims to characterize and determine the antibacterial activities of synthesized Strobilanthes crispus-mediated AgNPs (SC-AgNPs) against Streptococcus mutans, Escherichia coli and Pseudomonas aeruginosa. S. crispus water extract acts as a reducing and capping agent in the synthesis of AgNPs. The synthesized AgNPs were characterized by using UV-Vis spectrophotometer, dynamic light scattering (DLS), field emission scanning electron microscope (FESEM), X-ray diffractometer (XRD) and Fourier transform infra-red (FTIR). FESEM images showed a rough surface with a spherical shape. The average size distribution of 75.25 nm with a polydispersity index (PDI) of 0.373. XRD analysis matched the face-centred cubic structure of silver. FTIR analysis revealed a shifted peak from 1404.99 to 1345.00 cm-1. MIC and MBC values of SC-AgNPs were 1.25 mg/mL and 2.5 mg/mL against E. coli, P. aeruginosa and S. mutans, respectively. Time-kill assay showed that SC-AgNPs significantly reduced bacterial growth as compared to non-treated bacteria. Morphologies of bacteria treated with SC-AgNPs were shrunk, lysed, irregular and smaller as compared to control. SC-AgNPs significantly disrupted the gene expression of eae A, gtf B and Pel A (p

Matched MeSH terms: Anti-Bacterial Agents/chemistry
Multifunctional and theranostic hydrogels for wound healing acceleration: An emphasis on diabetic-related chronic wounds

Tehrany PM, Rahmanian P, Rezaee A, Ranjbarpazuki G, Sohrabi Fard F, Asadollah Salmanpour Y, et al.

Environ Res, 2023 Dec 01;238(Pt 1):117087.
PMID: 37716390 DOI: 10.1016/j.envres.2023.117087

Hydrogels represent intricate three-dimensional polymeric structures, renowned for their compatibility with living systems and their ability to naturally degrade. These networks stand as promising and viable foundations for a range of biomedical uses. The practical feasibility of employing hydrogels in clinical trials has been well-demonstrated. Among the prevalent biomedical uses of hydrogels, a significant application arises in the context of wound healing. This intricate progression involves distinct phases of inflammation, proliferation, and remodeling, often triggered by trauma, skin injuries, and various diseases. Metabolic conditions like diabetes have the potential to give rise to persistent wounds, leading to delayed healing processes. This current review consolidates a collection of experiments focused on the utilization of hydrogels to expedite the recovery of wounds. Hydrogels have the capacity to improve the inflammatory conditions at the wound site, and they achieve this by diminishing levels of reactive oxygen species (ROS), thereby exhibiting antioxidant effects. Hydrogels have the potential to enhance the growth of fibroblasts and keratinocytes at the wound site. They also possess the capability to inhibit both Gram-positive and Gram-negative bacteria, effectively managing wounds infected by drug-resistant bacteria. Hydrogels can trigger angiogenesis and neovascularization processes, while also promoting the M2 polarization of macrophages, which in turn mitigates inflammation at the wound site. Intelligent and versatile hydrogels, encompassing features such as pH sensitivity, reactivity to reactive oxygen species (ROS), and responsiveness to light and temperature, have proven advantageous in expediting wound healing. Furthermore, hydrogels synthesized using environmentally friendly methods, characterized by high levels of biocompatibility and biodegradability, hold the potential for enhancing the wound healing process. Hydrogels can facilitate the controlled discharge of bioactive substances. More recently, there has been progress in the creation of conductive hydrogels, which, when subjected to electrical stimulation, contribute to the enhancement of wound healing. Diabetes mellitus, a metabolic disorder, leads to a slowdown in the wound healing process, often resulting in the formation of persistent wounds. Hydrogels have the capability to expedite the healing of diabetic wounds, facilitating the transition from the inflammatory phase to the proliferative stage. The current review sheds light on the biological functionalities of hydrogels, encompassing their role in modulating diverse mechanisms and cell types, including inflammation, oxidative stress, macrophages, and bacteriology. Additionally, this review emphasizes the significance of smart hydrogels with responsiveness to external stimuli, as well as conductive hydrogels for promoting wound healing. Lastly, the discussion delves into the advancement of environmentally friendly hydrogels with high biocompatibility, aimed at accelerating the wound healing process.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Green synthesis of chitosan/silver nanocomposite using kaempferol for triple negative breast cancer therapy and antibacterial activity

Bharathi D, Ranjithkumar R, Nandagopal JGT, Djearamane S, Lee J, Wong LS

Environ Res, 2023 Dec 01;238(Pt 1):117109.
PMID: 37696324 DOI: 10.1016/j.envres.2023.117109

The synthesis of polymer-encapsulated metal nanoparticles is a growing field of area due to their long-term uses in the development of new technologies. The present study describes the synthesis of chitosan/silver nanocomposite using kaempferol for anticancer and bactericidal activity. The formation of Kf-CS/Ag nanocomposite was confirmed by the development of a brown color and UV-absorbance around 438 nm. The IR study was utilized to determine the existence of Kf and CS in the synthesized nanocomposite. TEM analysis demonstrated that the synthesized nanocomposite have a predominantly uniform spherical shape and size ranges 7-10 nm. EDX spectrum showed the existence of Ag, C, and N elements in the nanocomposite material. Further, Kf-CS/Ag nanocomposite exhibited potential in vitro inhibitory property against triple-negative breast cancer (TNBC) cells and their IC50 values was found to be 53 μg/mL. Moreover, fluorescent assays such as DAPI and AO/EtBr confirmed the apoptosis induction ability of Kf-CS/Ag nanocomposite in MDA-MB-231 cells. The synthesized Kf-CS/Ag nanocomposite showed significant and dose-depended antibacterial property against S. aureus and P. aeruginosa. Thus, the obtained findings demonstrated that the synthesized nanocomposite can be potentially used to improve human health as biocidal nanocomposite in biomedical sectors.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Zingiber officinale Roscoe Essential Oils-Loaded Chitosan Nanoparticles with Enhanced Bactericidal Efficacy against Burkholderia glumae in Rice

Tiran Gunasena M, Hussein MZ, Ali A, Wahab MAA, Bashir Kutawa A, Rafif A, et al.

Chem Biodivers, 2023 Dec;20(12):e202300686.
PMID: 37905394 DOI: 10.1002/cbdv.202300686

Ginger essential oils (GEO) shows exceptional antimicrobial properties against plant pathogens. Due to its high volatility and low stability, it requires encapsulation to retain its effective properties. The GEO-Chitosan (GEO-CS) nanobactericide was developed using the ionic gelation method. The nanobactericides show particle diameters of 465, 28, 35, 48 and 500 nm when sodium tripolyphosphate (TPP) concentrations used in the preparation were 0.0, 0.5, 1.0, 2.0 and 4.0 %, respectively. The X-ray diffraction and the UV-vis studies revealed that the GEO was encapsulated into the chitosan nanoparticles with an encapsulation efficiency of around 46 % and a loading capacity of 27-34 %. The antibacterial activity of GEO-chitosan nanobactericide against Burkholderia glumae (Bg) was found to be 7.5-11.8 mm, with minimum inhibitory concentration and minimum bactericidal concentration values of 15.6 μl/mL and 31.25 μl/mL, respectively. Hence, these findings indicate that the prepared GEO-CS nanobactericides were found to be effective against Bg. This preliminary study is toward the development of new agronanobactericides using a natural product to control Bg.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Comparative taxonomical, biological and pharmacological potential of healthy and geminivirus infected leaves of Hibiscus rosa-sinensis L.: First report

Shaheen S, Khalid S, Siqqique R, Abbas M, Ifikhar T, Ijaz I, et al.

Microb Pathog, 2023 Dec;185:106428.
PMID: 37977480 DOI: 10.1016/j.micpath.2023.106428

In the present research project, the first report on comparative analysis of the taxonomical, biological and pharmacological potential of healthy and geminivirus infected Hibiscus rosa sinensis (L.) leaves of the family Malvaceae was done by using different micro and macroscopic techniques. First of all, leaves were characterized for Cotton leaf curl Multan virus (CLCuMuV) and its associated betasatellite (Cotton leaf curl Multan Betasatellite; CLCuMB). Different morphological parameters like shape and size of stem, leaves, seeds and roots, presence and absence of ligule, distance between nodes and internodes and type of inflorescence etc. were analyzed. CLCuMuV infected H. rosa-sinensis revealed systematic symptoms of infection like chlorosis of leaves, stunted growth, decrease in size of roots, shoots and distortion etc. Anatomical investigation was performed under light ad scanning electron microscope. Different anatomical features like length and shape of guard cells, subsidiary cells, presence or absence of stomata, secretory ducts and trichomes were examined. In both plant samples anomocytic types of stomata and elongated, non-glandular and pointed tip trichomes were present, but the size (especially length and width) of trichomes and other cells like epidermal, subsidiary, and guard cells were highest in virus infected plants likened to healthy one. In the antibacterial activity, the maximum antibacterial potentail was seen in methanolic extract of K. pneumonea while antifungal activity was shown by methanolic extract of A. solani. Plants interact with different biological entities according to environmental conditions continuously and evolved. These types of interactions induce changes positively and negatively on plant metabolism and metabolites production. Many plant viruses also attacked various host plants consequently alter their secondary metabolism. To overcome such virus infected plants produces many important and different types of secondary plant metabolites as a defense response. Subsequent analysis of this n-hexane plant extract using Gas chromatography mass spectroscopy technique revealed that Hibiscus eluted contained 10 main compounds in Healthy sample and 13 compounds in infected one. Presence of essential secondary metabolites were also analyzed by FTIR analysis. The present study provides a comprehensive and novel review on taxonomy (morphology, anatomy) and antimicrobial potential of both healthy and geminivirus infected H. rosa-sinensis.

Matched MeSH terms: Anti-Bacterial Agents
Unveiling synergism of polymyxin B with chloramphenicol derivatives against multidrug-resistant (MDR) Klebsiella pneumoniae

Idris N, Leong KH, Wong EH, Abdul Rahim N

J Antibiot (Tokyo), 2023 Dec;76(12):711-719.
PMID: 37821539 DOI: 10.1038/s41429-023-00659-2

Polymyxins are last-line antibiotics against multidrug-resistant Klebsiella pneumoniae but using polymyxins alone may not be effective due to emerging resistance. A previous study found that combining polymyxin B with chloramphenicol effectively kills MDR K. pneumoniae, although the bone marrow toxicity of chloramphenicol is concerning. The aim of this study is to assess the antibacterial efficacy and cytotoxicity of polymyxin B when combined with chloramphenicol and its derivatives, namely thiamphenicol and florfenicol (reported to have lesser toxicity compared to chloramphenicol). The antibacterial activity was evaluated with antimicrobial susceptibility testing using broth microdilution and time-kill assays, while the cytotoxic effect on normal bone marrow cell line, HS-5 was evaluated using the MTT assay. All bacterial isolates tested were found to be susceptible to polymyxin B, but resistant to chloramphenicol, thiamphenicol, and florfenicol when used alone. The use of polymyxin B alone showed bacterial regrowth for all isolates at 24 h. The combination of polymyxin B and florfenicol demonstrated additive and synergistic effects against all isolates (≥ 2 log10 cfu ml-1 reduction) at 4 and 24 h, respectively, while the combination of polymyxin B and thiamphenicol resulted in synergistic killing at 24 h against ATCC BAA-2146. Furthermore, the combination of polymyxin B with florfenicol had the lowest cytotoxic effect on the HS-5 cells compared to polymyxin B combination with chloramphenicol and thiamphenicol. Overall, the combination of polymyxin B with florfenicol enhanced bacterial killing against MDR K. pneumoniae and exerted minimal cytotoxic effect on HS-5 cell line.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Synthesis and Staphylococcus aureus biofilm inhibitory activity of indolenine-substituted pyrazole and pyrimido[1,2-b]indazole derivatives

Yap CH, Ramle AQ, Lim SK, Rames A, Tay ST, Chin SP, et al.

Bioorg Med Chem, 2023 Nov 15;95:117485.
PMID: 37812886 DOI: 10.1016/j.bmc.2023.117485

Staphylococcus aureus is a highly adaptable opportunistic pathogen that can form biofilms and generate persister cells, leading to life-threatening infections that are difficult to treat with antibiotics alone. Therefore, there is a need for an effective S. aureus biofilm inhibitor to combat this public health threat. In this study, a small library of indolenine-substituted pyrazoles and pyrimido[1,2-b]indazole derivatives were synthesised, of which the hit compound exhibited promising antibiofilm activities against methicillin-susceptible S. aureus (MSSA ATCC 29213) and methicillin-resistant S. aureus (MRSA ATCC 33591) at concentrations significantly lower than the planktonic growth inhibition. The hit compound could prevent biofilm formation and eradicate mature biofilms of MSSA and MRSA, with a minimum biofilm inhibitory concentration (MBIC50) value as low as 1.56 µg/mL and a minimum biofilm eradication concentration (MBEC50) value as low as 6.25 µg/mL. The minimum inhibitory concentration (MIC) values of the hit compound against MSSA and MRSA were 50 µg/mL and 25 µg/mL, respectively, while the minimum bactericidal concentration (MBC) values against MSSA and MRSA were > 100 µg/mL. Preliminary structure-activity relationship analysis reveals that the fused benzene ring and COOH group of the hit compound are crucial for the antibiofilm activity. Additionally, the compound was not cytotoxic to human alveolar A549 cells, thus highlighting its potential as a suitable candidate for further development as a S. aureus biofilm inhibitor.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext A survey of Asian Eye Institutions on perioperative antibiotic prophylaxis in cataract surgery

Garg P, Khor WB, Roy A, Tan DT, APAX consortium

Int Ophthalmol, 2023 Nov;43(11):4151-4162.
PMID: 37526782 DOI: 10.1007/s10792-023-02816-w

PURPOSE: To determine current institutional practice patterns for the use of perioperative antibiotics and other measures to prevent infection after cataract surgery in Asia.
METHODS: An online survey-based study of leading eye institutions in China, Hong Kong, India, Indonesia, Japan, Malaysia, Pakistan, Philippines, Singapore, South Korea, Taiwan, Thailand and Vietnam was conducted. The survey was administered to 26 representative key opinion leaders from prominent tertiary eye institutions that are also national academic teaching institutions in Asia. Survey responses were collated and anonymized during analysis.
RESULTS: All surveyed institutions used povidone iodine for the preoperative antiseptic preparation of the eye, with notable variations in the concentration of povidone iodine used for conjunctival sac instillation. Preoperative topical antibiotics were prescribed by 61.5% and 69.2% of institutions in low-risk and high-risk cases, respectively. Regarding the use of intra-operative antibiotics, 60.0% and 66.7% of institutions administered intracameral antibiotics in low-risk and high-risk patients, respectively. Postoperative topical antibiotics use patterns were generally very similar in low-risk and high-risk patients. Over half of the institutions (52.2% and 68.0% in low-risk and high-risk patients, respectively) also indicated prolonged postoperative use of topical antibiotics (> 2 weeks). Not all surveyed institutions had established policies/protocols for perioperative antibiotic use in cataract surgery, endophthalmitis surveillance, and/or a monitoring program for emerging antimicrobial resistance.
CONCLUSION: There are variations in antimicrobial prophylaxis approaches to preoperative, intra-operative and postoperative regimens in cataract surgery in Asia. More evidence-based research is needed to support the development of detailed guidelines for perioperative antibiotic prophylaxis to reduce postoperative infections.

Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
Breaking the Barrier: A Study on Multi-drug Resistance in Breast Abscess at an Academic Malaysian Hospital

Lee CJ, Lai LL, See MH, Velayuthan RD, Doon YK, Lim PE, et al.

World J Surg, 2023 Nov;47(11):2743-2752.
PMID: 37491402 DOI: 10.1007/s00268-023-07108-z

BACKGROUND: In recent years, the increase in antibiotics usage locally has led to a worrying emergence of multi-drug resistant organisms (MDRO), with the Malaysian prevalence rate of methicillin-resistant Staphylococcus aureus (MRSA) ranging from 17.2 to 28.1% between 1999 and 2017. A study has shown that 7% of all non-lactational breast abscesses are caused by MRSA. Although aspiration offers less morbidities compared to surgical drainage, about 20% of women infected by MRSA who initially underwent aspiration subsequently require surgical drainage. This study is conducted to determine the link between aetiology, antimicrobial resistance pattern and treatment modalities of breast abscesses.
METHODS: Retrospective study of reviewing microbiology specimens of breast abscess patients treated at Universiti Malaya Medical Centre from 2015 to 2020. Data collected from microbiology database and electronic medical records were analysed using SPSS V21.
RESULT: A total of 210 specimens from 153 patients were analysed. One-fifth (19.5%) of the specimens isolated were MDRO. Lactational associated infections had the largest proportion of MDR in comparison to non-lactational and secondary infections (38.5%, 21.7%, 25.7%, respectively; p = 0.23). Staphylococcus epidermidis recorded the highest number of MDR (n = 12) followed by S. aureus (n = 8). Adjusted by aetiological groups, the presence of MDRO is linked to failure of single aspirations (p = 0.554) and significantly doubled the risk of undergoing surgical drainage for resolution (p = 0.041).
CONCLUSION: MDR in breast abscess should be recognised as an increasing healthcare burden due to a paradigm shift of MDRO and a rise of resistance cases among lactational associated infection that were vulnerable to undergo surgical incision and drainage for resolution.

Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
Genotypic and phenotypic analysis of Elizabethkingia meningoseptica in bullfrog Rana catesbeiana isolated in Taiwan

Tsai MA, See MS, Chiu CH, Wang PC, Chen SC

J Fish Dis, 2023 Nov;46(11):1239-1248.
PMID: 37519120 DOI: 10.1111/jfd.13842

Elizabethkingia meningoseptica is a hazardous bacterium for agriculture production and human health. The present study identified E. meningoseptica from the bullfrog, human and reference strain BCRC 10677 by API 20NE, 50S ribosome protein L27 sequencing and pulse field gel electrophoresis to differentiate isolates of E. meningoseptica from aquatic animals and humans. All isolates from bullfrogs and humans were identified as E. meningoseptica by DNA sequencing with 98.8%-100% sequence identity. E. meningoseptica displayed significant genetic diversity when analysed using pulsed-field gel electrophoresis (PFGE). There were six distinct pulsotypes, including one pulsotype found in bullfrog isolates and five pulsotypes found in human isolates. However, E. meningoseptica from bullfrog exhibited one genotype only by PFGE. Overall, molecular epidemiological analysis of PFGE results indicated that the frog E. meningoseptica outbreaks in Taiwan were produced by genetically identical clones. The bullfrog isolates were not genetically related to other E. meningoseptica from human and reference isolates. This research provided the first comparisons of biochemical characteristics and genetic differences of E. meningoseptica from human and bullfrog isolates.

Matched MeSH terms: Anti-Bacterial Agents/therapeutic use
Bactericidal role of epidermal mucus of freshwater fish treated with Aeromonas hydrophila

Ali S, Shah SAUR, Rauf M, Hassan M, Ullah W, Dawar FU

J Fish Dis, 2023 Nov;46(11):1225-1237.
PMID: 37501533 DOI: 10.1111/jfd.13841

This study explored the bactericidal role of the epidermal mucus (EM) of five freshwater Cyprinid fish species namely Ctenopharyngodon idella, Labeo rohita, Catla catla, Hypophthalmichthys molitrix, and Cirrhinus mrigala after treatment with Aeromonas hydrophila. Extracts of EM (crude and acidic) of each species showed bactericidal activity against various Gram -ve (Pseudomonas aeruginosa, Escherichia coli, Aeromonas hydrophila, Edwardsiella tarda, Salmonella enterica, Klebsiella pneumonia, Serratia marcescens, and Enterobacter cloacae) and Gram +ve (Bacillus wiedmannii and Staphylococcus aureus) bacteria compared with standard antibiotics (Fosfomycin). The zone of inhibition (ZOI) was measured in millimetres against antibiotics (Fosfomycin). Variations in bactericidal activity of EM were observed against bacteria from the same and different fish species. The acidic extract was more effective than the crude extract and showed significantly higher ZOI values against various bacteria and Fosfomycin antibiotics. This result shows that fish EM may perform an important role in fish defence against bacteria. Therefore, this study may hint towards the substitution of synthetic antibiotics with fish EM that may be used as a novel 'bactericidal' in aquaculture as well as in humans against bacterial infections.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Antibacterial, bacteriolytic, antibiofilm, and synergistic effects of the peel oils of Citrus microcarpa and Citrus x amblycarpa with tetracycline against foodborne Escherichia coli

Septama AW, Yuandani Y, Khairunnisa NA, Nasution HR, Utami DS, Kristiana R, et al.

Lett Appl Microbiol, 2023 Nov 01;76(11).
PMID: 37898554 DOI: 10.1093/lambio/ovad126

Citrus essential oils (EOs) have shown significant antibacterial activity. The present study was undertaken to evaluate the antibacterial activity of the peel oils of Citrus microcarpa and C. x amblycarpa against Escherichia coli. The minimum inhibition concentration (MIC) was determined by using the broth microdilution assay. The checkerboard method was used to identify synergistic effects of the EOs with tetracycline, while bacteriolysis was assessed by calculating the optical density of the bacterial supernatant, crystal violet assay was used to assess their antibiofilm. Ethidium bromide accumulation test was employed to assess efflux pump inhibition. Electron microscope analysis was performed to observe its morphological changes. The EOs of C. microcarpa and C. x amblycarpa were found to contain D-limonene major compound at 55.78% and 46.7%, respectively. Citrus microcarpa EOs exhibited moderate antibacterial against E. coli with a MIC value of 200 μg/mL. The combination of C. microcarpa oil (7.8 μg/mL) and tetracycline (62.5 μg/mL) exhibited a synergy with FICI of 0.5. This combination inhibited biofilm formation and disrupt bacterial cell membranes. Citrus microcarpa EOs blocked the efflux pumps in E. coli. Citrus microcarpa EOs demonstrated promising antibacterial activity, which can be further explored for the development of drugs to combat E. coli.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Evaluation of potential bacterial protease inhibitor properties of selected hydroxyquinoline derivatives: an in silico docking and molecular dynamics simulation approach

Riaz F, Hossain MS, Roney M, Ali Y, Qureshi S, Muhammad R, et al.

J Biomol Struct Dyn, 2023 Nov;41(19):9756-9769.
PMID: 36399018 DOI: 10.1080/07391102.2022.2146200

Antimicrobial drug resistance (AMR) is a severe global threat to public health. The increasing emergence of drug-resistant bacteria requires the discovery of novel antibacterial agents. Quinoline derivatives have previously been reported to exhibit antimalarial, antiviral, antitumor, antiulcer, antioxidant and, most interestingly, antibacterial properties. In this study, we evaluated the binding affinity of three newly designed hydroxyquinolines derived from sulfanilamide (1), 4-amino benzoic acid (2) and sulfanilic acid (3) towards five bacterial protein targets (PDB ID: 1JIJ, 3VOB, 1ZI0, 6F86, 4CJN). The three derivatives were designed considering the amino acid residues identified at the active site of each protein involved in the binding of each co-crystallized ligand and drug-likeness properties. The ligands displayed binding energy values with the target proteins ranging from -2.17 to -8.45 kcal/mol. Compounds (1) and (3) showed the best binding scores towards 1ZI0/3VOB and 1JIJ/4CJN, respectively, which may serve as new antibiotic scaffolds. Our in silico results suggest that sulfanilamide (1) or sulfanilic acid (3) hydroxyquinoline derivatives have the potential to be developed as bacterial inhibitors, particularly MRSA inhibitors. But before that, it must go through the proper preclinical and clinical trials for further scientific validation. Further experimental studies are warranted to explore the antibacterial potential of these compounds through preclinical and clinical studies.Communicated by Ramaswamy H. Sarma.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Computational modelling of potential Zn-sensitive non-β-lactam inhibitors of imipenemase-1 (IMP-1)

Ayipo YO, Ahmad I, Alananzeh W, Lawal A, Patel H, Mordi MN

J Biomol Struct Dyn, 2023 Nov;41(19):10096-10116.
PMID: 36476097 DOI: 10.1080/07391102.2022.2153168

Antibiotic resistance (AR) remains one of the leading global health challenges, mostly implicated in disease-related deaths. The Enterobacteriaceae-producing metallo-β-lactamases (MBLs) are critically involved in AR pathogenesis through Zn-dependent catalytic destruction of β-lactam antibiotics, yet with limited successful clinical inhibitors. The efficacy of relevant broad-spectrum β-lactams including imipenem and meropenem are seriously challenged by their susceptibility to the Zn-dependent carbapenemase hydrolysis, as such, searching for alternatives remains imperative. In this study, computational molecular modelling and virtual screening methods were extensively applied to identify new putative Zn-sensitive broad-spectrum inhibitors of MBLs, specifically imipenemase-1 (IMP-1) from the IBScreen database. Three ligands, STOCK3S-30154, STOCK3S-30418 and STOCK3S-30514 selectively displayed stronger binding interactions with the enzymes compared to reference inhibitors, imipenem and meropenem. For instance, the ligands showed molecular docking scores of -9.450, -8.005 and -10.159 kcal/mol, and MM-GBSA values of -40.404, -31.902 and -33.680 kcal/mol respectively against the IMP-1. Whereas, imipenem and meropenem showed docking scores of -9.038 and -10.875 kcal/mol, and MM-GBSA of -31.184 and -32.330 kcal/mol respectively against the enzyme. The ligands demonstrated good thermodynamic stability and compactness in complexes with IMP-1 throughout the 100 ns molecular dynamics (MD) trajectories. Interestingly, their binding affinities and stabilities were significantly affected in contacts with the remodelled Zn-deficient IMP-1, indicating sensitivity to the carbapenemase active Zn site, however, with non-β-lactam scaffolds, tenable to resist catalytic hydrolysis. They displayed ideal drug-like ADMET properties, thus, representing putative Zn-sensitive non-β-lactam inhibitors of IMP-1 amenable for further experimental studies.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
The phenotypes and genotypes associated with biofilm formation among methicillin-susceptible Staphylococcus aureus (MSSA) isolates collected from a tertiary hospital in Terengganu, Malaysia

Jones SU, Chew CH, Yeo CC, Abdullah FH, Othman N, Kee BP, et al.

Int Microbiol, 2023 Nov;26(4):841-849.
PMID: 36805382 DOI: 10.1007/s10123-023-00335-3

Methicillin-susceptible Staphylococcus aureus (MSSA) is an important nosocomial pathogen worldwide. This study aims to investigate the in vitro biofilm-forming ability of clinical MSSA isolated from various sources in the main public tertiary referral hospital in Terengganu, Malaysia and to detect the presence of biofilm-associated and regulatory genes among these isolates. A total of 104 MSSA isolates [pus (n = 75), blood (n = 24), respiratory secretions (n = 2), eye (n = 2), and urine (n = 1)] were investigated for slime production and biofilm formation using Congo red agar and crystal violet microtitre plate, respectively. Fifteen MSSA isolates with varying degrees of biofilm formation were selected for validation via a real-time cell analyser. All isolates were screened for microbial surface components recognising adhesive matrix molecules (MSCRAMM) and accessory gene regulator (agr) using polymerase chain reaction assay. A total of 76.0% (79/104) isolates produced slime layer, while all isolates developed biofilm as follows: 52.8% (55/104) strong biofilm producers, 40.4% (42/104) intermediate biofilm producers, and 6.7% (7/104) weak biofilm producers. A total of 98.1% (102/104) isolates carried at least one of the screened MSCRAMM gene(s) with the eno gene detected at the highest rate (87.5%, 91/104), while the sasG gene was significantly associated with strong biofilm production (p = 0.015). Three agr groups, 1, 2, and 3, were detected among the MSSA isolates with a predominance of agr-3 (32.7%, 34/104). In conclusion, biofilm formation varied greatly among clinical MSSA isolates, and the presence of sasG gene and agr-1 may play important role in initiating MSSA infections via biofilm formation.

Matched MeSH terms: Anti-Bacterial Agents
Fulltext Unveiling the volatile compounds and antibacterial mechanisms of action of Cupressus sempervirens L., against Bacillus subtilis and Pseudomonas aeruginosa

Al-Mijalli SH, El Hachlafi N, Jeddi M, Abdallah EM, Assaggaf H, Qasem A, et al.

Biomed Pharmacother, 2023 Nov;167:115609.
PMID: 37801906 DOI: 10.1016/j.biopha.2023.115609

Cupressus sempervirens is a known traditional plant used to manage various ailments, including cancer, inflammatory and infectious diseases. In this investigation, we aimed to explore the chemical profile of Cupressus sempervirens essential oil (CSEO) as well as their antibacterial mode of action. The volatile components were characterized using gas chromatography coupled to a mass spectrometer (GC-MS). The results revealed remarkable antibacterial properties of EO derived from C. sempervirens. GC-MS analysis indicated that C. sempervirens EO characterized by δ-3-carene (47.72%), D-limonene (5.44%), β-pinene (4.36%), β-myrcene (4.02%). The oil exhibited significant inhibitory effects against a range of bacteria, including Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 13048, Bacillus cereus (Clinical isolate), Pseudomonas aeruginosa ATCC 27853, and Escherichia coli ATCC 25922. These inhibitory effects surpassed those of conventional antibiotics. Furthermore, the EO demonstrated low minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs), indicating its bactericidal nature (MBC/MIC < 4.0). Time-kill kinetics analysis showed that CSEO was particularly effective at 2 × MIC doses, rapidly reduced viable count of B. subtilis and P. aeruginosa within 8 h. This suggests that the oil acts quickly and efficiently. The cell membrane permeability test further demonstrated the impact of CSEO on the relative conductivity of B. subtilis and P. aeruginosa, both at 2 × MIC concentrations. These observations suggest that EO disrupts the bacterial membrane, thereby influencing their growth and viability. Additionally, the cell membrane integrity test indicated that the addition of CSEO to bacterial cultures resulted in the significant release of proteins from the bacterial cells. This suggests that EO affects the structural integrity of the bacterial cells. Furthermore, the anti-biofilm assay confirmed the efficacy of CSEO as a potent anti-biofilm agent. It demonstrated the oil's ability to inhibit quorum sensing, a crucial mechanism for biofilm formation, and its competitive performance compared to the tested antibiotics.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology; Anti-Bacterial Agents/chemistry
Synthesis and evaluation of antibacterial activity of transition metal-oleoyl amide complexes

Farhan N, Al-Maleki AR, Sarih NM, Yahya R

Bioorg Chem, 2023 Nov;140:106786.
PMID: 37586131 DOI: 10.1016/j.bioorg.2023.106786

Recent studies show that some metal ions, injure microbial cells in various ways due to membrane breakdown, protein malfunction, and oxidative stress. Metal complexes are suited for creating novel antibacterial medications due to their distinct mechanisms of action and the variety of three-dimensional geometries they can acquire. In this Perspective, the present study focused on new antibacterial strategies based on metal oleoyl amide complexes. Thus, oleoyl amides ligand (fatty hydroxamic acid and fatty hydrazide hydrate) with the transition metal ions named Ag (I), Co (II), Cu (II), Ni (II) and Sn (II) complexes were successfully synthesized in this study. The metals- oleoyl amide were characterized using elemental analysis, and fourier transforms infrared (FTIR) spectroscopy. The antibacterial effect of metals- oleoyl amide complexes was investigated for Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) by analysing minimum inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and scanning electron microscopy (SEM). The results showed that metal-oleoyl amide complexes have high antibacterial activity at low concentrations. This study inferred that metal oleoyl amide complexes could be utilised as a promising therapeutic antibacterial agent.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology
Fulltext Virulence gene profiles and antimicrobial susceptibility of Salmonella Brancaster from chicken

Khoo E, Roslee R, Zakaria Z, Ahmad NI

J Vet Sci, 2023 Nov;24(6):e82.
PMID: 38031519 DOI: 10.4142/jvs.23053

BACKGROUND: The current conventional serotyping based on antigen-antisera agglutination could not provide a better understanding of the potential pathogenicity of Salmonella enterica subsp. enterica serovar Brancaster. Surveillance data from Malaysian poultry farms indicated an increase in its presence over the years.
OBJECTIVE: This study aims to investigate the virulence determinants and antimicrobial resistance in S. Brancaster isolated from chickens in Malaysia.
METHODS: One hundred strains of archived S. Brancaster isolated from chicken cloacal swabs and raw chicken meat from 2017 to 2022 were studied. Two sets of multiplex polymerase chain reaction (PCR) were conducted to identify eight virulence genes associated with pathogenicity in Salmonella (invasion protein gene [invA], Salmonella invasion protein gene [sipB], Salmonella-induced filament gene [sifA], cytolethal-distending toxin B gene [cdtB], Salmonella iron transporter gene [sitC], Salmonella pathogenicity islands gene [spiA], Salmonella plasmid virulence gene [spvB], and inositol phosphate phosphatase gene [sopB]). Antimicrobial susceptibility assessment was conducted by disc diffusion method on nine selected antibiotics for the S. Brancaster isolates. S. Brancaster, with the phenotypic ACSSuT-resistance pattern (ampicillin, chloramphenicol, streptomycin, sulphonamides, and tetracycline), was subjected to PCR to detect the corresponding resistance gene(s).
RESULTS: Virulence genes detected in S. Brancaster in this study were invA, sitC, spiA, sipB, sopB, sifA, cdtB, and spvB. A total of 36 antibiogram patterns of S. Brancaster with a high level of multidrug resistance were observed, with ampicillin exhibiting the highest resistance. Over a third of the isolates displayed ACSSuT-resistance, and seven resistance genes (β-lactamase temoneira [blaTEM], florfenicol/chloramphenicol resistance gene [floR], streptomycin resistance gene [strA], aminoglycoside nucleotidyltransferase gene [ant(3″)-Ia], sulfonamides resistance gene [sul-1, sul-2], and tetracycline resistance gene [tetA]) were detected.
CONCLUSION: Multidrug-resistant S. Brancaster from chickens harbored an array of virulence-associated genes similar to other clinically significant and invasive non-typhoidal Salmonella serovars, placing it as another significant foodborne zoonosis.

Matched MeSH terms: Anti-Bacterial Agents/pharmacology

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