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Fulltext Decoding Antioxidant and Antibacterial Potentials of Malaysian Green Seaweeds: Caulerpa racemosa and Caulerpa lentillifera

Yap WF, Tay V, Tan SH, Yow YY, Chew J

Antibiotics (Basel), 2019 Sep 17;8(3).
PMID: 31533237 DOI: 10.3390/antibiotics8030152

Seaweeds are gaining a considerable amount of attention for their antioxidant and antibacterial properties. Caulerpa racemosa and Caulerpa lentillifera, also known as 'sea grapes', are green seaweeds commonly found in different parts of the world, but the antioxidant and antibacterial potentials of Malaysian C. racemosa and C. lentillifera have not been thoroughly explored. In this study, crude extracts of the seaweeds were prepared using chloroform, methanol, and water. Total phenolic content (TPC) and total flavonoid content (TFC) were measured, followed by in vitro antioxidant activity determination using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Antibacterial activities of these extracts were tested against Methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Liquid chromatography-mass spectrometry (LCMS) analysis was then used to determine the possible compounds present in the extract with the most potent antioxidant and antibacterial activity. Results showed that C. racemosa chloroform extract had the highest TPC (13.41 ± 0.86 mg GAE/g), antioxidant effect (EC50 at 0.65 ± 0.03 mg/mL), and the strongest antibacterial effect (97.7 ± 0.30%) against MRSA. LCMS analysis proposed that the chloroform extracts of C. racemosa are mainly polyunsaturated and monounsaturated fatty acids, terpenes, and alkaloids. In conclusion, C. racemosa can be a great source of novel antioxidant and antibacterial agents, but isolation and purification of the bioactive compounds are needed to study their mechanism of action.
Fulltext WGS-Based Analysis of Carbapenem-Resistant Acinetobacter baumannii in Vietnam and Molecular Characterization of Antimicrobial Determinants and MLST in Southeast Asia

Wareth G, Linde J, Nguyen NH, Nguyen TNM, Sprague LD, Pletz MW, et al.

Antibiotics (Basel), 2021 May 11;10(5).
PMID: 34064958 DOI: 10.3390/antibiotics10050563

Carbapenem-resistant Acinetobacter baumannii (A. baumannii, CRAb) is an emerging global threat for healthcare systems, particularly in Southeast Asia. Next-generation sequencing (NGS) technology was employed to map genes associated with antimicrobial resistance (AMR) and to identify multilocus sequence types (MLST). Eleven strains isolated from humans in Vietnam were sequenced, and their AMR genes and MLST were compared to published genomes of strains originating from Southeast Asia, i.e., Thailand (n = 49), Myanmar (n = 38), Malaysia (n = 11), Singapore (n = 4) and Taiwan (n = 1). Ten out of eleven Vietnamese strains were CRAb and were susceptible only to colistin. All strains harbored ant(3")-IIa, armA, aph(6)-Id and aph(3") genes conferring resistance to aminoglycosides, and blaOXA-51 variants and blaADC-25 conferring resistance to ß-lactams. More than half of the strains harbored genes that confer resistance to tetracyclines, sulfonamides and macrolides. The strains showed high diversity, where six were assigned to sequence type (ST)/2, and two were allocated to two new STs (ST/1411-1412). MLST analyses of 108 strains from Southeast Asia identified 19 sequence types (ST), and ST/2 was the most prevalent found in 62 strains. A broad range of AMR genes was identified mediating resistance to ß-lactams, including cephalosporins and carbapenems (e.g., blaOXA-51-like, blaOXA-23, blaADC-25, blaADC-73, blaTEM-1, blaNDM-1), aminoglycosides (e.g., ant(3")-IIa, aph(3")-Ib, aph(6)-Id, armA and aph(3')-Ia), phenicoles (e.g., catB8), tetracyclines (e.g., tet.B and tet.39), sulfonamides (e.g., sul.1 and sul.2), macrolides and lincosamide (e.g., mph.E, msr.E and abaF). MLST and core genome MLST (cgMLST) showed an extreme diversity among the strains. Several strains isolated from different countries clustered together by cgMLST; however, different clusters shared the same ST. Developing an action plan on AMR, increasing awareness and prohibiting the selling of antibiotics without prescription must be mandatory for this region. Such efforts are critical for enforcing targeted policies on the rational use of carbapenem compounds and controlling AMR dissemination and emergence in general.
Fulltext Prevalence of Vancomycin-Resistant Enterococcus (VRE) in Companion Animals: The First Meta-Analysis and Systematic Review

Wada Y, Irekeola AA, E A R ENS, Yusof W, Lih Huey L, Ladan Muhammad S, et al.

Antibiotics (Basel), 2021 Jan 31;10(2).
PMID: 33572528 DOI: 10.3390/antibiotics10020138

Antimicrobial resistance in companion animals is a major public health concern worldwide due to the animals' zoonotic potential and ability to act as a reservoir for resistant genes. We report on the first use of meta-analysis and a systematic review to analyze the prevalence of vancomycin-resistant Enterococcus (VRE) in companion animals. Databases such as MedLib, PubMed, Web of Science, Scopus, and Google Scholar were searched. The information was extracted by two independent reviewers and the results were reviewed by a third. Two reviewers independently assessed the study protocol using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist and the study quality using the Joanna Briggs Institute (JBI) critical appraisal checklist for prevalence data. OpenMeta analyst and comprehensive meta-analysis (CMA) were used for the meta-analysis. The random effect model was used, and publication bias was assessed using the Eggers test and funnel plot. Between-study heterogeneity was assessed, and the sources were analyzed using the leave-one-out meta-analysis, subgroup analysis and meta-regression. Twenty-two studies met the eligibility criteria, but because some studies reported the prevalence of VRE in more than one companion animal, they were considered as individual studies, and 35 studies were therefore added to the final meta-analysis. Sampling period of the included studies was from 1995-2018. Of the 4288 isolates tested in the included studies, 1241 were VRE. The pooled prevalence of VRE in companion animals was estimated at 14.6% (95% CI; 8.7-23.5%; I2 = 97.10%; p < 0.001). Between-study variability was high (t2 = 2.859; heterogeneity I2 = 97.10% with heterogeneity chi-square (Q) = 1173.346, degrees of freedom (df) = 34, and p < 0.001). The funnel plot showed bias, which was confirmed by Eggers test (t-value = 3.97165; p = 0.00036), and estimates from the leave-one-out forest plot did not affect the pooled prevalence. Pooled prevalence of VRE in dogs and cats were 18.2% (CI = 9.4-32.5%) and 12.3%, CI = 3.8-33.1%), respectively. More studies were reported in Europe than in any other continent, with most studies using feces as the sample type and disc diffusion as the detection method. With the emergence of resistant strains, new antimicrobials are required in veterinary medicine.
Fulltext Transformation of Biowaste for Medical Applications: Incorporation of Biologically Derived Silver Nanoparticles as Antimicrobial Coating

Vigneswari S, Amelia TSM, Hazwan MH, Mouriya GK, Bhubalan K, Amirul AA, et al.

Antibiotics (Basel), 2021 Feb 24;10(3).
PMID: 33668352 DOI: 10.3390/antibiotics10030229

Nanobiotechnology has undoubtedly influenced major breakthroughs in medical sciences. Application of nanosized materials has made it possible for researchers to investigate a broad spectrum of treatments for diseases with minimally invasive procedures. Silver nanoparticles (AgNPs) have been a subject of investigation for numerous applications in agriculture, water treatment, biosensors, textiles, and the food industry as well as in the medical field, mainly due to their antimicrobial properties and nanoparticle nature. In general, AgNPs are known for their superior physical, chemical, and biological properties. The properties of AgNPs differ based on their methods of synthesis and to date, the biological method has been preferred because it is rapid, nontoxic, and can produce well-defined size and morphology under optimized conditions. Nevertheless, the common issue concerning biological or biobased production is its sustainability. Researchers have employed various strategies in addressing this shortcoming, such as recently testing agricultural biowastes such as fruit peels for the synthesis of AgNPs. The use of biowastes is definitely cost-effective and eco-friendly; moreover, it has been reported that the reduction process is simple and rapid with reasonably high yield. This review aims to address the developments in using fruit- and vegetable-based biowastes for biologically producing AgNPs to be applied as antimicrobial coatings in biomedical applications.
Fulltext Potential of Nanoparticles Integrated with Antibacterial Properties in Preventing Biofilm and Antibiotic Resistance

Thambirajoo M, Maarof M, Lokanathan Y, Katas H, Ghazalli NF, Tabata Y, et al.

Antibiotics (Basel), 2021 Nov 02;10(11).
PMID: 34827276 DOI: 10.3390/antibiotics10111338

Nanotechnology has become an emerging technology in the medical field and is widely applicable for various clinical applications. The potential use of nanoparticles as antimicrobial agents is greatly explored and taken into consideration as alternative methods to overcome the challenges faced by healthcare workers and patients in preventing infections caused by pathogenic microorganisms. Among microorganisms, bacterial infections remain a major hurdle and are responsible for high morbidity and mortality globally, especially involving those with medical conditions and elderly populations. Over time, these groups are more vulnerable to developing resistance to antibiotics, as bacterial biofilms are difficult to destroy or eliminate via antibiotics; thus, treatment becomes unsuccessful or ineffective. Mostly, bacterial biofilms and other microbes can be found on medical devices and wounds where they disperse their contents which cause infections. To inhibit biofilm formations and overcome antibiotic resistance, antimicrobial-loaded nanoparticles alone or combined with other substances could enhance the bactericidal activity of nanomaterials. This includes killing the pathogens effectively without harming other cells or causing any adverse effects to living cells. This review summarises the mechanisms of actions employed by the different types of nanoparticles which counteract infectious agents in reducing biofilm formation and improve antibiotic therapy for clinical usage.
Fulltext Bioactive Compounds from the Bornean Endemic Plant Goniothalamus longistipetes

Teo SP, Bhakta S, Stapleton P, Gibbons S

Antibiotics (Basel), 2020 Dec 16;9(12).
PMID: 33339285 DOI: 10.3390/antibiotics9120913

The present study aimed to screen plants for bioactive compounds with potential antibacterial activities. In our efforts to evaluate plants from Borneo, we isolated and elucidated the structures of four natural products from the bioactive fraction of a chloroform extract of Goniothalamus longistipetes using various chromatographic and spectroscopic techniques. The bioactive compounds were identified as a known styryllactone, (+)-altholactone ((2S,3R,3aS,7aS)-3-hydroxy-2-phenyl-2,3,3a,7a-tetrahydrobenzo-5(4H)-5-one) (1), a new styryllactone, (2S,3R,3aS,7aS)-3-hydroxy-2-phenyl-2,3,3a,7a-tetrahydrobenzo-5(4H)-5-one) (2) as well as a new alkaloid, 2,6-dimethoxyisonicotinaldehyde (3) and a new alkenyl-5-hydroxyl-phenyl benzoic acid (4). 1 and 4 showed broad-spectrum anti-bacterial activities against Gram-positive and Gram-negative bacteria as well as acid-fast model selected for this study. Compound 2 only demonstrated activities against Gram-positive bacteria whilst 3 displayed selective inhibitory activities against Gram-positive bacterial strains. Additionally, their mechanisms of anti-bacterial action were also investigated. Using Mycobacterium smegmatis as a fast-growing model of tubercle bacilli, compounds 1, 2 and 4 demonstrated inhibitory activities against whole-cell drug efflux and biofilm formation; two key intrinsic mechanisms of antibiotic resistance. Interestingly, the amphiphilic compound 4 exhibited inhibitory activity against the conjugation of plasmid pKM101 in Escherichia coli using a plate conjugation assay. Plasmid conjugation is a mechanism by which Gram-positive and Gram-negative-bacteria acquire drug resistance and virulence. These results indicated that bioactive compounds isolated from Goniothalamus longistipetes can be potential candidates as 'hits' for further optimisation.
Fulltext Impact of Extended and Restricted Antibiotic Deescalation on Mortality

Teh HL, Abdullah S, Ghazali AK, Khan RA, Ramadas A, Leong CL

Antibiotics (Basel), 2021 Dec 27;11(1).
PMID: 35052899 DOI: 10.3390/antibiotics11010022

BACKGROUND: More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. This study aims to compare the survival curve of patient de-escalated (early or late) against those not de-escalated on antibiotics, to determine the association of patient related, clinical related, and pressure sore/device related characteristics on all-cause 30-day mortality and determine the impact of early and late antibiotic de-escalation on 30-day all-cause mortality.
METHODS: This is a retrospective cohort study on patients in medical ward Hospital Kuala Lumpur, admitted between January 2016 and June 2019. A Kaplan-Meier survival curve and Fleming-Harrington test were used to compare the overall survival rates between early, late, and those not de-escalated on antibiotics while multivariable Cox proportional hazards regression was used to determine prognostic factors associated with mortality and the impact of de-escalation on 30-day all-cause mortality.
RESULTS: Overall mortality rates were not significantly different when patients were not de-escalated on extended or restricted antibiotics, compared to those de-escalated early or later (p = 0.760). Variables associated with 30-day all-cause mortality were a Sequential Organ Function Assessment (SOFA) score on the day of antimicrobial stewardship (AMS) intervention and Charlson's comorbidity score (CCS). After controlling for confounders, early and late antibiotics were not associated with an increased risk of mortality.
CONCLUSION: The results of this study reinforce that restricted or extended antibiotic de-escalation in patients does not significantly affect 30-day all-cause mortality compared to continuation with extended and restricted antibiotics.
Fulltext Clinical Efficacy of Repeated Applications of Local Drug Delivery and Adjunctive Agents in Nonsurgical Periodontal Therapy: A Systematic Review

Tan OL, Safii SH, Razali M

Antibiotics (Basel), 2021 Sep 28;10(10).
PMID: 34680759 DOI: 10.3390/antibiotics10101178

The aim of this systematic review is to compare the clinical efficacy of repeated applications of local drug delivery and adjunctive agents (LDAs) in nonsurgical periodontal therapy (NSPT) compared to subgingival mechanical debridement (SMD) alone. The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, EMBASE, Web of Science, hand-searched literature and grey literature databases were searched for randomized controlled clinical trials (RCTs) with a minimum of 6-month follow-up. The outcomes of interest were changes in probing pocket depth and clinical attachment level as well as patient-centred outcomes. Of 1094 studies identified, 16 RCTs were included in the qualitative analysis. Across 11 different adjuncts analysed, only two studies utilizing minocycline gel/ointment and antimicrobial photodynamic therapy (aPDT) with indocyanine green photosensitizer had statistically significant differences in primary outcomes when compared to their control groups. Only one study on aPDT methylene blue 0.005% had compared single versus multiple applications against its control group. A mean range of 0.27-3.82 mm PD reduction and -0.09-2.82 mm CAL gain were observed with repeated LDA application. Considerable clinical heterogeneity and methodological flaws in the included studies preclude any definitive conclusions regarding the clinical efficacy of repeated LDA applications. Future RCTs with a direct comparison between single and repeated applications should be conducted to confirm or refute the clinical advantages of repeated LDA application in the nonsurgical management of periodontitis.
Fulltext Adherence to National Antimicrobial Guidelines in Hospitalized Geriatric Patients with Community-Acquired Pneumonia: A Prospective Observational study in a Malaysian Hospital

Shakeel S, Muneswarao J, Abdul Aziz A, Yeong Le H, Abd Halim FS, Rehman AU, et al.

Antibiotics (Basel), 2021 Dec 04;10(12).
PMID: 34943702 DOI: 10.3390/antibiotics10121490

The evaluation of disease progression and onsite therapeutic care choices for community-acquired pneumonia (CAP) patients is vital for their well-being and the optimum utilization of healthcare resources. The current study was conducted to assess physicians' adherence to clinical practice standards and antibiotic prescribing behavior for the treatment of CAP in older people. A prospective study that included 121 consecutive patients admitted for CAP was conducted at Kulim Hospital, Kedah, from March 2020 to August 2020. Medical records including demographic data, comorbidity, physical examination, laboratory or radiologic findings, and drugs used for the treatment of CAP were accessed from bed head tickets (BHT). The mean age for patients was 73.5 ± 6.2 years, 73 (60.3%) and 48 (39.6%) were males and females, respectively. Amoxicillin/clavulanate (19.8%) was the most prescribed antibiotic for non-severe pneumonia followed by ampicillin sodium/sulbactam sodium (6.6%), while in patients with severe CAP beta-lactam + beta lactamase inhibitors (BLIs) with a combination of macrolide were the most common antibiotics prescribed either in patients with (21.4%) or without co-morbidities (8.2%). The average length of stay in the hospital with severe pneumonia was 6-7 days for 23.9% of patients and < 5 days for 21.4% of patients. The duration of intravenous antibiotics in patients with severe pneumonia was 6-7 days for 32.2% of patients. The present findings revealed the adherence of antibiotic prescribing practices to the Malaysian National Antimicrobial Guideline 2019 for CAP therapy among geriatric patients and adherence to the CAP criteria for hospital admissions.
Fulltext The Efficacy of Moina micrura Enriched with Probiotic Bacillus pocheonensis in Enhancing Survival and Disease Resistance of Red Hybrid Tilapia (Oreochromis spp.) Larvae

Samat NA, Yusoff FM, Rasdi NW, Karim M

Antibiotics (Basel), 2021 Aug 16;10(8).
PMID: 34439039 DOI: 10.3390/antibiotics10080989

The administration of probiotics via live feeds, such as Artemia and rotifers, has gained significant attention. Moreover, indiscriminate use of antibiotics in conventional aquaculture practices in order to prevent or control disease outbreaks has resulted in the occurrence of residues and antimicrobial resistance. Thus, the application of eco-friendly feed additives, such as probiotics, as a safer alternative has received increasing attention in recent years. However, only minimal information on the administration of probiotics via freshwater cladoceran Moina micrura is available despite being commonly used for larval and post-larval feeding of freshwater crustaceans and fish. Thus, this study aimed to evaluate the application of Bacillus pocheonensis strain S2 administered via M. micrura to red hybrid tilapia (Oreochromis spp.) larvae. Bacillus pocheonensis that has been previously isolated from Spirulina sp. was subjected to preliminary in vitro evaluation of antagonistic properties. The agar well-diffusion assay revealed that this probiont could inhibit the growth of Streptococcus agalactiae and Aeromonas hydrophila. The size of inhibition zones ranged from 8.8 ± 0.2 to 18.2 ± 0.4 mm. Moina micrura was later used as a biological model in preliminary in vivo bacterial challenge assays to evaluate the efficacy of B. pocheonensis in protecting the host from diseases. Moina micrura was pre-enriched with B. pocheonensis at 104 and 106 CFU mL-1 before S. agalactiae and A. hydrophila were introduced into the culture. The study revealed that B. pocheonensis at 104 CFU mL-1 was able to significantly enhance the survival of M. micrura after being challenged with both pathogens (63 ± 3%) in comparison to the control group. The relative percentage survival (RPS) of M. micrura was highest (p < 0.05) when treated with B. pocheonensis at both concentrations 104 and 106 CFU mL-1 (38.33) after being challenged against S. agalactiae. To assess the efficacy of B. pocheonensis in protecting red hybrid tilapia against streptococcosis, the larvae were fed with either unenriched (control) Moina or probiont-enriched Moina daily for 10 days. A significantly (p < 0.05) higher survival rate (77 ± 3%) was observed in larvae fed with probiont-enriched M. micrura compared to other treatments, and the RPS was recorded at 62.90. In addition, the S. agalactiae load was suppressed in larvae fed probiont-enriched M. micrura (6.84±0.39 CFU mL-1) in comparison to the control group (7.78±0.09 CFU mL-1), indicating that the probiont might have contributed to the improvement of tilapia health and survival. This study illustrated that M. micrura was suitable to be used as a vector for probiotics in freshwater fish larvae as an alternative to hazardous antibiotics for disease control.
Fulltext Prevalence of Multidrug-Resistant and Extended-Spectrum Beta-Lactamase-Producing Shigella Species in Asia: A Systematic Review and Meta-Analysis

Salleh MZ, Nik Zuraina NMN, Hajissa K, Ilias MI, Banga Singh KK, Deris ZZ

Antibiotics (Basel), 2022 Nov 18;11(11).
PMID: 36421297 DOI: 10.3390/antibiotics11111653

Shigellosis remains one of the leading causes of morbidity and mortality worldwide and is the second leading cause of diarrheal mortality among all age groups. However, the global emergence of antimicrobial-resistant Shigella strains, limiting the choice of effective drugs for shigellosis, has become the major challenge in the treatment of Shigella infections. The aim of this systematic review and meta-analysis was to provide an updated picture of the prevalence of antimicrobial-resistant Shigella species in Asia. A comprehensive and systematic search was performed on three electronic databases (PubMed, ScienceDirect and Scopus), in which 63 eligible studies published between 2010 and 2022 were identified. From our meta-analysis of proportions using a random-effects model, the overall prevalence of Shigella spp. in Asian patients was estimated to be 8.0% (95% CI: 5.5-10.5). The pooled prevalence rates of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing Shigella strains were 68.7% (95% CI: 59.9-77.5) and 23.9% (95% CI: 12.9-34.8), respectively. Concerning recommended antimicrobial drugs for Shigella, the prevalence of resistance was highest for ciprofloxacin (29.8%) and azithromycin (29.2%), followed by ceftriaxone (23.8%), in spite of their importance as first- and second-line treatments for shigellosis. In contrast, resistance to carbapenems, such as ertapenem (0.0%), imipenem (0.1%) and meropenem (0.0%), was almost non-existent among the 49 tested antibiotics. The significantly high prevalence estimation suggests that the multidrug-resistant Shigella is a pressing threat to public health worthy of careful and justified interventions. Effective antibiotic treatment strategies, which may lead to better outcomes for the control and treatment of shigellosis in Asia, are essential.
Fulltext Synergistic Antimicrobial Activity of Ceftriaxone and Polyalthia longifolia Methanol (MEPL) Leaf Extract against Methicillin-Resistant Staphylococcus aureus and Modulation of mecA Gene Presence

Ranjutha V, Chen Y, Al-Keridis LA, Patel M, Alshammari N, Adnan M, et al.

Antibiotics (Basel), 2023 Feb 27;12(3).
PMID: 36978344 DOI: 10.3390/antibiotics12030477

Medicinal plants are an essential source of traditional curatives for numerous skin diseases. Polyalthia longifolia (Sonn.) Thwaites (Annonaceae family) is a medicinal plant used to cure skin illnesses. P. longifolia is usually applied in folkloric therapeutical systems to treat skin diseases. The methicillin-resistant Staphylococcus aureus (MRSA) bacteria is among the essential bacteria contributing to skin diseases. Hence, to verify the traditional medicinal claim of P. longifolia usage in skin disease treatment, the current research was performed to study the synergistic antibacterial activity of standardized Polyalthia longifolia methanol leaf extract (MEPL) against MRSA bacteria. The synergistic antimicrobial activity result of ceftriaxone, when mixed with MEPL, against MRSA was investigated by the disc diffusion method, broth microdilution method, checkerboard dilution test, and modulation of mecA gene expression by multiplex polymerase chain reaction (multiplex PCR). The MEPL extract exhibited good synergistic antimicrobial activity against MRSA. Using the checkerboard method, we confirmed the synergistic effect of MEPL from P. longifolia and ceftriaxone (2:1) for MRSA with a marked reduction of the MIC value of the ceftriaxone from 8000 µg/mL to 1000 µg/mL. Moreover, the combination of MEPL with ceftriaxone significantly (p < 0.05) inhibited the presence of the resistant mecA gene in the tested strain. The LC-ESI-MS/MS analysis identified compounds that were reported to exhibit antimicrobial activity. Conclusively, the MEPL extract, an important etiological agent for skin diseases, showed worthy synergistic antimicrobial action against MRSA bacteria, thus supporting the traditional use of P. longifolia.
Fulltext Colonization of Methicillin-Resistant Staphylococcus aureus (MRSA) among Medical Students in Tertiary Institution in Central Malaysia

Rampal S, Zainuddin NH, Elias NA, Tengku Jamaluddin TZM, Maniam S, Teh SW, et al.

Antibiotics (Basel), 2020 Jul 06;9(7).
PMID: 32640588 DOI: 10.3390/antibiotics9070382

Methicillin-resistant Staphylococcus aureus or MRSA infection is virulent and presents with a broad spectrum of severity. Limited regional reports that specifically outlined the potential risk of medical students being part of the dissemination of MRSA in healthcare settings were noted. This study aims to assess the prevalence and contributory factors of colonization of MRSA on neckties, headscarves, and ID badges among medical students in a local medical university in Malaysia. A cross-sectional study was conducted involving 256 medical students. A validated questionnaire was used to collect the data, and sample swabs were collected between July and August 2013 by swabbing neckties, headscarves, or identification badges. The swabs were then streaked onto mannitol salt agar (MSA) and incubated at 37 °C overnight. Out of 433 samples taken, 40 swabs (9.24%) were positive for Staphylococcus aureus. Out of the 40 swabs, five (12.5%) isolates were MRSA (one culture was isolated from the headscarf of a preclinical student, one culture was isolated from the necktie of clinical students, while the remaining three were isolated from identification badges of clinical students. There was no significant association between age, gender, ethnicity, and phase of medical students with the colonization of MRSA (p > 0.05). There was a significant association between knowledge score on hand hygiene practice and phase of medical students. MRSA colonies were present on neckties, headscarves, and identification badges of medical students of all phases. The findings from this study suggest the need for improvement of hand hygiene knowledge and discontinuity of mandatory use of physical ID badges and neckties among medical students.
Fulltext Local Trends of Antibiotic Prescriptions for Necrotizing Fasciitis Patients in Two Tertiary Care Hospitals in Central Malaysia

Rampal S, Ganesan T, Sisubalasingam N, Neela VK, Tokgöz MA, Arunasalam A, et al.

Antibiotics (Basel), 2021 Sep 17;10(9).
PMID: 34572702 DOI: 10.3390/antibiotics10091120

BACKGROUND: Necrotizing fasciitis (NF) is a rapidly progressive inflammatory infection of the soft tissue (also known as the fascia) with a secondary necrosis of the subcutaneous tissues, leading to a systemic inflammatory response syndrome (SIRS), shock and eventually death despite the availability of current medical interventions. The clinical management of this condition is associated with a significant amount of morbidity with a high rate of mortality. The prognosis of the disease is affected by multiple factors, which include the virulence of the causative pathogen, local host immunity, local wound factors and empirical antibiotics used. The local trends in the prescription of empirical antibiotics are often based on clinical practice guidelines (CPG), the distribution of the causative microorganism and the cost-effectiveness of the drug. However, there appears to be a paucity of literature on the empirical antibiotic of choice when dealing with necrotizing fasciitis in the clinical setting. This paper will outline common causative microorganisms and current trends of prescription in two tertiary centres in Central Malaysia.
METHODS: This was a cross-sectional study using retrospective data of patients treated for NF collected from two tertiary care hospitals (Hospital Seremban and Hospital Ampang) in Central Malaysia. A total of 420 NF patients were identified from the five years of retrospective data obtained from the two hospitals.
RESULTS: The top three empirical antibiotics prescribed are ampicillin + sulbactam (n = 258; 61.4%), clindamycin (n = 55; 13.1%) and ceftazidime (n = 41; 9.8%). The selection of the antibiotic significantly impacts the outcome of NF. The top three causative pathogens for NF are Streptococcus spp. (n = 79; 18.8%), Pseudomonas aeruginosa (n = 61; 14.5%) and Staphylococcus spp. (n = 49; 11.7%). The patients who received antibiotics had 0.779 times lower chances of being amputated. Patients with a lower laboratory risk indicator for necrotizing fasciitis (LRINEC) score had 0.934 times lower chances of being amputated.
CONCLUSIONS: In this study, the most common empirical antibiotic prescribed was ampicillin + sulbactam followed by clindamycin and ceftazidime. The antibiotics prescribed lower the risk of having an amputation and, hence, a better prognosis of the disease. Broad-spectrum empirical antibiotics following surgical debridement reduce the mortality rate of NF.
Fulltext Deploying a Novel Approach to Prepare Silver Nanoparticle Bellamya bengalensis Extract Conjugate Coating on Orthopedic Implant Biomaterial Discs to Prevent Potential Biofilm Formation

Qamer S, Che-Hamzah F, Misni N, Joseph NMS, Al-Haj NA, Amin-Nordin S

Antibiotics (Basel), 2023 Sep 03;12(9).
PMID: 37760700 DOI: 10.3390/antibiotics12091403

This study is based on the premise of investigating antibacterial activity through a novel conjugate of silver nanoparticles (AgNPs) and antimicrobial peptides (AMPs) in line with a green synthesis approach by developing antimicrobial-coated implants to prevent bacterial resistance. The AMPs were obtained from Bellamya Bengalensis (BB), a freshwater snail, to prepare the nanocomposite conjugate, e.g., AgNPs@BB extract, by making use of UV-Visible spectroscopy. The antimicrobial assessment of AgNPs@BB extract conjugate was performed using the Resazurin Microtiter Assay Method (REMA), followed by the use of three biocompatible implant materials (titanium alloys, Ti 6AL-4V stainless steel 316L, and polyethylene). Finally, the coating was analyzed under confocal microscopy. The results revealed a significant reduction of biofilm formation on the surfaces of implants coated with conjugate (AgNPs@BB extract) in comparison to uncoated implants. For the MTT assay, no significant changes were recorded for the cells grown on the AgNPs/AMP++ sample in high concentrations. Staphylococcus epidermidis, however, showed more prominent growth on all implants in comparison to Staphylococcus aureus. It is evident from the results that Staphylococcus epidermidis is more susceptible to AgNPs@BB extract, while the minimum inhibitory concentration (MIC) value of AgNPs@BB extract conjugates and biosynthesized AgNPs was also on the higher side. This study indicates that AgNPs@BB extract carries antibacterial activity, and concludes that an excessive concentration of AgNPs@BB extract may affect the improved biocompatibility. This study recommends using robust, retentive, and antimicrobial coatings of AgNPs@BB extract for implantable biocompatible materials in accordance with the novel strategy of biomaterial applications.
Fulltext Biosynthesised Silver Nanoparticles Loading onto Biphasic Calcium Phosphate for Antibacterial and Bone Tissue Engineering Applications

Padmanabhan VP, Sivashanmugam P, Kulandaivelu R, Sagadevan S, Sridevi B, Govindasamy R, et al.

Antibiotics (Basel), 2022 Dec 08;11(12).
PMID: 36551437 DOI: 10.3390/antibiotics11121780

Biphasic calcium phosphate (BCP) serves as one of the substitutes for bone as it consists of an intimate mixture of beta-tricalcium phosphate (β-TCP) and hydroxyapatite (HAP) in different ratios. BCP, because of its inbuilt properties such as osteoconductivity, biocompatibility, and biostability in several clinical models serves as a bone substituent for orthopedic applications. Therefore, the present study aimed to assess the effectiveness of silver (Ag) nanoparticles (NPs) combined with BCP composites for the orthopedic sector of bone tissue regeneration and growth. In this regard, we first synthesized Ag-BCP microclusters by the double-emulsion method and then characterized the composite for various physicochemical properties, including the crystallinity and crystal structure, bonding and functionality, porosity, morphology, surface charges, topography, and thermal stability. In addition, the antibacterial activity of Ag-BCP was tested against gram-positive and gram-negative microorganisms such as Staphylococcus aureus, Candida albicans, and Escherichia coli. Finally, the cytocompatibility of Ag-BCP was confirmed against the fibroblast cells in vitro.
Fulltext Targeting PirAvp and PirBvp Toxins of Vibrio parahaemolyticus with Oilseed Peptides: An In Silico Approach

Ong JH, Wong WL, Wong FC, Chai TT

Antibiotics (Basel), 2021 Oct 05;10(10).
PMID: 34680792 DOI: 10.3390/antibiotics10101211

Acute hepatopancreatic necrosis disease (AHPND), caused by PirAvp- and PirBvp-releasing Vibrio parahaemolyticus strains, has resulted in massive mortality in shrimp aquaculture. Excessive use of antibiotics for AHPND management has led to antibiotic resistance, highlighting the urgency to search for alternatives. Using an in silico approach, we aimed to discover PirAvp/PirBvp-binding peptides from oilseed meals as alternatives to antibiotics. To search for peptides that remain intact in the shrimp digestive tract, and therefore would be available for toxin binding, we focused on peptides released from tryptic hydrolysis of 37 major proteins from seeds of hemp, pumpkin, rape, sesame, and sunflower. This yielded 809 peptides. Further screening led to 24 peptides predicted as being non-toxic to shrimp, fish, and humans, with thermal stability and low water solubility. Molecular docking on the 24 peptides revealed six dual-target peptides capable of binding to key regions responsible for complex formation on both PirAvp and PirBvp. The peptides (ISYVVQGMGISGR, LTFVVHGHALMGK, QSLGVPPQLGNACNLDNLDVLQPTETIK, ISTINSQTLPILSQLR, PQFLVGASSILR, and VQVVNHMGQK) are 1139-2977 Da in mass and 10-28 residues in length. Such peptides are potential candidates for the future development of peptide-based anti-AHPND agents which potentially mitigate V. parahaemolyticus pathogenesis by intercepting PirAvp/PirBvp complex formation.
Fulltext Prevalence of Antibiotic-Resistant Seafood-Borne Pathogens in Retail Seafood Sold in Malaysia: A Systematic Review and Meta-Analysis

Odeyemi OA, Amin M, Dewi FR, Kasan NA, Onyeaka H, Stratev D, et al.

Antibiotics (Basel), 2023 Apr 28;12(5).
PMID: 37237733 DOI: 10.3390/antibiotics12050829

The objective of this study was to examine the frequency and extent of antibiotic-resistant pathogens in seafood sold in Malaysia, using a systematic review and meta-analysis approach to analyze primary research studies. Four bibliographic databases were systematically searched for primary studies on occurrence. Meta-analysis using a random-effect model was used to understand the prevalence of antibiotic-resistant bacteria in retail seafood sold in Malaysia. A total of 1938 primary studies were initially identified, among which 13 met the inclusion criteria. In the included primary studies, a total of 2281 seafoods were analyzed for the presence of antibiotic-resistant seafood-borne pathogens. It was observed that 51% (1168/2281) of the seafood was contaminated with pathogens. Overall, the prevalence of antibiotic-resistant seafood-borne pathogens in retail seafood was 55.7% (95% CI: 0.46-0.65). Antibiotic-resistant Salmonella species had an overall prevalence of 59.9% (95% CI: 0.32-0.82) in fish, Vibrio species had an overall prevalence of 67.2% (95% CI: 0.22-0.94) in cephalopods, and MRSA had an overall prevalence of 70.9% (95% CI: 0.36-0.92) in mollusks. It could be concluded that there is a high prevalence of antibiotic-resistant seafood-borne pathogens in the retail seafood sold in Malaysia, which could be of public health importance. Therefore, there is a need for proactive steps to be taken by all stakeholders to reduce the widespread transmission of antibiotic-resistant pathogens from seafood to humans.
Fulltext Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013-2022: Data from the European Registry on H. pylori Management (Hp-EuReg)

Nyssen OP, Pratesi P, Spínola MA, Jonaitis L, Pérez-Aísa Á, Vaira D, et al.

Antibiotics (Basel), 2023 Sep 10;12(9).
PMID: 37760723 DOI: 10.3390/antibiotics12091427

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.
Fulltext In Vitro Efficacy of Flomoxef against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Associated with Urinary Tract Infections in Malaysia

Ngoi ST, Teh CSJ, Chong CW, Abdul Jabar K, Tan SC, Yu LH, et al.

Antibiotics (Basel), 2021 Feb 11;10(2).
PMID: 33670224 DOI: 10.3390/antibiotics10020181

The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has greatly affected the clinical efficacy of β-lactam antibiotics in the management of urinary tract infections (UTIs). The limited treatment options have resulted in the increased use of carbapenem. However, flomoxef could be a potential carbapenem-sparing strategy for UTIs caused by ESBL-producers. Here, we compared the in vitro susceptibility of UTI-associated ESBL-producers to flomoxef and established β-lactam antibiotics. Fifty Escherichia coli and Klebsiella pneumoniae strains isolated from urine samples were subjected to broth microdilution assay, and the presence of ESBL genes was detected by polymerase chain reactions. High rates of resistance to amoxicillin-clavulanate (76-80%), ticarcillin-clavulanate (58-76%), and piperacillin-tazobactam (48-50%) were observed, indicated by high minimum inhibitory concentration (MIC) values (32 µg/mL to 128 µg/mL) for both species. The ESBL genes blaCTX-M and blaTEM were detected in both E. coli (58% and 54%, respectively) and K. pneumoniae (88% and 74%, respectively), whereas blaSHV was found only in K. pneumoniae (94%). Carbapenems remained as the most effective antibiotics against ESBL-producing E. coli and K. pneumoniae associated with UTIs, followed by flomoxef and cephamycins. In conclusion, flomoxef may be a potential alternative to carbapenem for UTIs caused by ESBL-producers in Malaysia.

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