β-Carboline, a naturally occurring indole alkaloid, holds a momentous spot in the field of medicinal chemistry due to its myriad of pharmacological actions like anticancer, antiviral, antibacterial, antifungal, antileishmanial, antimalarial, neuropharmacological, anti-inflammatory and antithrombotic among others. β-Carbolines exhibit their pharmacological activity via diverse mechanisms. This review provides a recent update (2015-2020) on the anti-infective potential of natural and synthetic β-carboline analogs focusing on its antibacterial, antifungal, antiviral, antimalarial, antileishmanial and antitrypanosomal properties. In cases where enough details are available, a note on its mechanism of action is also added.
Marine microbes provide an important resource to discover new chemical compounds with biological activities beneficial to drug discovery. In our study, two new polyene macrolides, pyranpolyenolides A (1) and B (2), and one new natural cyclic peptide (9), together with two known polyenes (7 and 8) and three known cyclic peptides (10-12), were isolated from a culture of the marine Streptomyces sp. MS110128. In addition, four new polyene macrolides, pyranpolyenolides C-F (3-6), were identified as olefin geometric isomers that were most likely produced by photochemical conversion during the cultivation or isolation procedures. The pyranpolyenolides are 32-membered macrolides endowed with a conjugated tetraene and several pairs of 1,3-dihydroxyl groups. Pyranpolyenolides that contain a hydropyran group have not been previously reported. Four cyclic peptides (9-12) showed significant activities against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant S. aureus with supporting MIC values ranging from 0.025 to 1.25 μg/mL. These cyclic peptides containing piperazic moieties showed moderate activities with MIC values of 12.5 μg/mL against Bacille Calmette Guerin (BCG), an attenuated form of the bovine. Additionally, cyclic peptide 12 showed moderate antifungal activity against Candida albicans with an MIC value of 12.5 μg/mL. KEY POINTS: • Discovery of new polyenes and cyclic peptides from a marine-derived Actinomycete. • Cyclic peptides containing piperazic moieties exhibited good antibacterial activity.
Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a disease of the tropics with high clinical mortality rates. To date, no vaccines are approved for melioidosis and current treatment relies on antibiotics. Conversely, common misdiagnosis and high pathogenicity of Bp hamper efforts to fight melioidosis. This bacterium can be isolated from a wide range of niches such as waterlogged fields, stagnant water bodies, salt water bodies and from human and animal clinical specimens. Although extensive studies have been undertaken to elucidate pathogenesis mechanisms of Bp, little is known about how a harmless soil bacterium adapts to different environmental conditions, in particular, the shift to a human host to become a highly virulent pathogen. The bacterium has a large genome encoding an armory of factors that assist the pathogen in surviving under stressful conditions and assuming its role as a deadly intracellular pathogen. This review presents an overview of what is currently known about how the pathogen adapts to different environments. With in-depth understanding of Bp adaptation and survival, more effective therapies for melioidosis can be developed by targeting related genes or proteins that play a major role in the bacteria's survival.
Pinpointing environmental antibiotic resistance (AR) hot spots in low-and middle-income countries (LMICs) is hindered by a lack of available and comparable AR monitoring data relevant to such settings. Addressing this problem, we performed a comprehensive spatial and seasonal assessment of water quality and AR conditions in a Malaysian river catchment to identify potential "simple" surrogates that mirror elevated AR. We screened for resistant coliforms, 22 antibiotics, 287 AR genes and integrons, and routine water quality parameters, covering absolute concentrations and mass loadings. To understand relationships, we introduced standardized "effect sizes" (Cohen's D) for AR monitoring to improve comparability of field studies. Overall, water quality generally declined and environmental AR levels increased as one moved down the catchment without major seasonal variations, except total antibiotic concentrations that were higher in the dry season (Cohen's D > 0.8, P < 0.05). Among simple surrogates, dissolved oxygen (DO) most strongly correlated (inversely) with total AR gene concentrations (Spearman's ρ 0.81, P < 0.05). We suspect this results from minimally treated sewage inputs, which also contain AR bacteria and genes, depleting DO in the most impacted reaches. Thus, although DO is not a measure of AR, lower DO levels reflect wastewater inputs, flagging possible AR hot spots. DO measurement is inexpensive, already monitored in many catchments, and exists in many numerical water quality models (e.g., oxygen sag curves). Therefore, we propose combining DO data and prospective modeling to guide local interventions, especially in LMIC rivers with limited data.
This case report describes the effect of an envenomation by the Beautiful Pit Viper Trimeresurus venustus (or Cryptelytrops venustus), which is a green pit viper native to Thailand and Malaysia. A previously healthy 60-year-old snake breeder with no relevant medical history was bitten by his adult T. venustus in the third finger of his right hand while taking it out of the feeding box. The bite was painful and swelling progressed to include his whole hand within an hour after the bite. He was treated symptomatically with pre-emptive antibiotics and analgesics, never developed any hematological disorders such as coagulopathy and bleeding or disseminated intravascular coagulation and was discharged 26 hours after the bite. The clinical course in our patient matched two other well-documented cases reported to our Poisons Centre, and one further case presented as a conference-poster. All patients recovered with symptomatic therapy and never required antivenom. Therefore, bites by T. venustus seem to present with less severe symptoms compared to other Trimeresurus species.
Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.
Pseudomonas aeruginosa is considered an opportunistic pathogen, causing a wide variety of infections in compromised hosts, also frequently develops multi-resistance to antibiotics and can colonize various habitats, including water systems. The main aim of this study was to investigate antibiotics susceptibility pattern, genotypic diversity and detection of resistence genes in P. aeruginosa isolates from clinical and aquatic environment sources. Of the 220 P. aeruginosa isolates examined, 48 were clinical isolates and 172 isolates from wastewater and freshwater. Susceptibility to eight antimicrobial agents was carried out by disk diffusion method. Clinical and environmental isolates were screened for the presence of the genes encoding blaKPC-2, blaCTX-M-9, blaPER-1, blaOXA-10, blaIMP-1, blaVIM-2 and blaampC by polymerase chain reaction (PCR). Isolates were examined with PCR-SSCP analysis of partial DNAr 16S sequence. Isolates were mainly resistant to cefoxitin. Multidrug-resistant P. aeruginosa (MDRPA) strains were found in 70% and 90.3% of the clinical and environmental isolates, respectively. The prevalence rates of â-lactamase genes were recorded (blaKPC-2 41.3%, blaVIM-2 36.8%, blaIMP-1 13.6%, blaCTX-M-9 10.9% and blaampC 10.5%,). The PCR-SSCP analysis showed three conformational patterns. All clinical isolates and most environmental isolates were grouped into a single cluster. In this study, we found that P. aeruginosa strains recovered from city water systems must be considered potential reservoir for ESBL genes, especially blaKPC-2 and blaVIM-2.
Major goal of dental treatment is to eradicate the existing diseases of the oral cavity and implement preventive measures to control the spread of the diseases. Various interventions are being used to cure the dental diseases. Due to the nanostructures, high surface volume and biocompatibility, Gold nanoparticles (GNPs) have been experimented in the treatment of gum diseases, dental caries, tissue engineering, dental implantology and diagnosis of cancers. GNPs possess antifungal and antibacterial activity, hence are incorporated in various biomaterials to potentiate the effect. They also enhance the mechanical properties of materials leading to improved outcomes. They are available in different sizes and concentrations to exhibits its beneficial outcomes. These properties of GNPs make these materials as choice of fillers in biomaterials. This review aims to discuss the effect of incorporation of GNPs in several biomaterials used for dental and medical applications.
Nocardia infection is rare in bone marrow transplant (BMT) recipients with less than 30 cases reported in the literature [1-4]. The majority of the cases occurred late in the post-transplant period. Common clinical presentations included formation of widespread and multiple abscesses. Bone marrow hypoplasia is an uncommon finding. We describe the first case of nocardiosis, diagnosed at day 100 after non-myeloablative allogeneic peripheral blood stem cell transplantation, presenting as pancytopenia and hypocellular marrow. Eradication of the infection with antibiotics resulted in complete hematological recovery.
There is a major concern about the increased use of antibiotics in dental practice and the emergence of resistant bacterial strains. In recent years, dentists have reported a shift from narrow-spectrum to broad-spectrum antibiotic prescriptions due to increasing antibiotic resistance. The aims of this study are to investigate the prescribing patterns of the therapeutic and prophylactic use for antibiotics in various dental situations by dental practitioners. The study also specifically investigates the prescribing habits of dental practitioners regarding certain cardiac conditions and related dental procedures in patients predisposed to infective endocarditis. This study utilized a questionnaire which was designed to investigate the antibiotic prescribing patterns by dental practitioners in the Klang Valley region. The returned questionnaires were analyzed using SPSS, to identify compliance to antibiotic guidelines by Malaysia National Clinical Guidelines (MNCG) (2003) and American Heart Association Guidelines (AHAG) (2008). 217 dentists responded to the questionnaire and the responses show that there is a wide variety of antibiotic prescriptions among dentists and there is also misuse of antibiotics in some clinical dental conditions. The results also show that there is a large variation in the antibiotic prescriptions patterns for prophylaxis against infective endocarditis. Furthermore, there is uncertainty as to which cardiac conditions required prophylaxis and for which particular dental procedures. This study concludes that there is a clear need for the development of prescribing guidelines, regular monitoring of antibiotic prescriptions by dental practitioners and educational initiatives to encourage the rational and appropriate use of the antibiotics.
Food-borne diseases have always been a major concern to the consumers, food safety authorities and food industries. Hylocereus spp or Pitaya peels are normally treated as wastes and will be discarded during processing. In this study, the antibacterial activity of ethanol, chloroform and hexane extracts from Hylocereus polyrhizus (red flesh pitaya) and Hylocereus undatus (white flesh pitaya) peels against nine pathogens was evaluated using disc diffusion method and broth micro-dilution method. Result from disc diffusion method showed that chloroform extracts from H. polyrhizus and H. undatus peel were found to exhibit good antibacterial activity where almost all the pathogens studied were successfully inhibited. Result of the minimum inhibitory concentration (MIC) showed that all extracts inhibit the growth of bacteria in the range of 1.25-10.00 mg/mL for all bacteria while their minimum bacteriacidal concentrations (MBC) indicated double of the MICs concentration except for B. cereus, L. monocytogenes and C. jejuni. Even though there is no clear trend indicating which bacteria were sensitive most to the extract, it can be concluded that chloroform extract of both H. polyrhizusand H. undatus peel showed the most potent antibacterial activity. Thus, these findings could be used further to understand the antibacterial property of the peel of pitaya fruits.
Backgrounds & Objective: Antimicrobial resistance is an alarming public health threat that requires urgent global solution. Implementation of antimicrobial stewardship program (ASP) is an essential practice element for healthcare institutions in gate-keeping judicious antimicrobial use. This study highlighted the development, first year experience, and result of the implementation of ASP utilizing persuasive and restrictive approaches in a Malaysian district hospital.
Methods: An observational study was conducted between January 2015 to December 2015 on implementation of ASP among hospitalized inpatients age 12 years old and above.
Results: Recommendations were provided for 60% of cases (110 patients) with the average acceptance rate of 83.33%. Majority of the interventions were to stop the antimicrobial therapy (30.3%), and the most common audited antimicrobials was Piperacillin/Tazobactam (25.5%), followed by Meropenem (11.82%), Amoxicillin/Clavulanate and Vancomycin (8.18%) respectively. The concordance rate towards authorization policy was increased in 2015 (71.59% of cases) as compared before the implementation of ASP in 2014 (60.6% of cases). Restrictive enforcement under ASP had been shown to improve significantly adherence rate towards antimicrobials authorization policy (p-value: 0.004).
Conclusion: ASP was successfully implemented in a district hospital. Future studies on its clinical outcomes are important to evaluate its effectiveness as well as focus on the improvement to the pre-existing strategies and measures.
KEY WORDS: Antimicrobial stewardship, Anti-Infective agents, Drug resistance, Malaysia, Rural hospital
A facile stereoselective synthesis of novel dispiro indeno pyrrolidine/pyrrolothiazole-thiochroman hybrids has been achieved by 1,3-dipolar cycloaddition of azomethine ylides, generated in situ from ninhydrin and sarcosine/thiaproline, on a series of 3-benzylidenethiochroman-4-ones. The synthesised compounds were screened for their antimycobacterial, anticancer and AchE inhibition activities. Compound 4l (IC50 1.07μM) has been found to exhibit the most potent antimycobacterial activity compared to cycloserine (12 times), pyrimethamine (37 times) and ethambutol (IC50 <1.56μM) and 6l (IC50=2.87μM) is more active than both cycloserine (4 times) and pyrimethamine (12 times). Three compounds, 4a, 6b and 6i, display good anticancer activity against CCRF-CEM cell lines. Compounds 6g and 4g display maximum AchE inhibitory activity with IC50 values of 1.10 and 1.16μmol/L respectively.
Acute mastoid abscess is common in daily practice. In children, it is usually caused by unsuccessful treatment or partially treated acute otitis media (AOM). Some authors had reported that chronic suppurative otitis media (CSOM) can be the source of infection but it is usually associated with the presence of cholesteatoma. A case of an acute mastoid abscess in a 7 year old girl is presented. She had a history of severe otalgia with left post auricular swelling for 3 days. Clinically she was febrile, the left otoscopy showed diffuse post auricular swelling and sagging of the posterior wall of the external canal. She underwent an emergency cortical mastoidectomy for the left mastoid abscess and had an uneventful recovery. In conclusion, this patient was partially treated with antibiotics which increased the risk for ‘masked mastoiditis’, and she later developed a mastoid abscess. Therefore we advocate that all AOM patients should be treated with antibiotics at least for a duration of one week.
Ophthalmia neonatorum remains a significant cause of ocular morbidity, blindness and even death in underdeveloped countries. The organisms causing ophthalmia neonatorum are acquired mainly from the mother's birth canal during delivery and a small percentage of cases are acquired by other ways. Chlamydia and Neisseria are the most common pathogens responsible for the perinatal infection. Fortunately in most cases, laboratory studies can identify the causative organism and unlike other form of conjunctivitis, this perinatal ocular infection has to be treated with systemic antibiotics to prevent systemic colonization of the organism. Routine prophylaxis with 1% silver nitrate solution (credes method) has been discontinued in many developed nations for the fear of development of chemical conjunctivitis.
Clostridium difficile can cause severe diseases with significant morbidity and mortality in infected patients.
The rate of Clostridium difficile infection is high in North America and European countries. Metronidazole
and vancomycin have been recommended as the treatments of choice since 1990s. Recurrent infection
due to Clostridium difficile is common after several days of antibiotic administration. Probiotics have
been used in these patients as an adjunct treatment with some successful findings. However, a detailed
investigation on the use of probiotic for infected patients is still needed, particularly for its real efficacy.
CONTEXT: To investigate the antibiotic prescribing training received by dental students, clinical experience in treating child patients, awareness of antibiotic prescribing guidelines, preparedness in antibiotic prescribing, and compliance with antibiotic prescribing guidelines for the management of dental infections in children.
METHODS: This was a cross-sectional study involving final year dental students from Malaysian and Asian dental schools. A self-administered questionnaire consisting of five clinical case scenarios was e-mailed to all final year students at selected dental schools. Students' responses were compared for each clinical case scenario with the prescribing guidelines of the American Academy of Pediatric Dentistry and the American Dental Association. Compliance in each scenario was tested for association with their preparedness in antibiotic prescribing, previous training on antibiotic prescribing and awareness of antibiotic prescribing guidelines using Chi-square test. Data collected were analyzed using SPSS statistics version 20.
RESULTS: A total of 108 completed responses were received. About 74 (69%) students were from Malaysian dental schools. The compliance rate with prescribing guidelines ranged from 15.7% to 43.5%. Those attending Malaysian dental schools (47.3%) and those who had treated child patient more often (46.3%) were more likely (P < 0.05) to be aware of the guidelines. Those who had received antibiotic prescribing training (21.3%) were more likely to think they were well prepared in antibiotic prescribing (P < 0.05).
CONCLUSIONS: Final year dental students had low awareness and compliance with antibiotic prescribing guidelines. Further research is needed to investigate how compliance with the guidelines may be enhanced.
A total of 49 isolates of V. parahaemolyticus and 8 isolates of V. cholerae isolated from freshwater fish of patin (Pangasius hypopthalmus) and red tilapia (Oreochromis sp.) were purchased from different retail level in Selangor, Malaysia. All of the isolates showed a multiple resistances towards all 15 antibiotics tested. Some of the isolates show a high resistance to different antibiotics including bacitracin, vancomycin, tetracycline, furazididone, cephalothin and erythromycin. However, both species was susceptible towards imipenem. Overall antibiotics resistance patterns of all isolates were resistant from 2 to 14 resistance patterns with multiple antibiotic resistance (MAR) index ranging from 0.13 to 0.93 respectively. As the results obtained in the dendrogram produced from both species had indicates that these antibiotics were intensively used whether in the aquaculture farm through feeds during culture or at the hatchery production of seed. Thus, this study will provides an essential information of the MAR index and also the clustering analysis in order to determine the biosafety of Vibrio spp. in freshwater aquaculture fish sold at different retail level in Malaysia.
Bioactive compounds from Quercus Infectoria (manjakani) were extracted with six different types of solvents: 100% methanol, ethanol, acetone, aqueous and 70% methanol and ethanol. High Performance liquid chromatography (HPLC) was used to identify and quantify the active compounds, namely gallic acid and tannic acid. Total phenolics content were determined by Folin-Ciocalteu while antioxidant and antibacterial activity were tested using DPPH free radicals scavenging and disc diffusion assay. The result revealed that aqueous extract contained the highest concentration of bioactive compounds compared to other types of solvents which are 51.14 mg/g sample and 1332.88 mg/g sample of gallic acid and tannic acid respectively.. The highest level of phenolic compound was found in 100% acetone extract (121 mg GAE/g). The results demonstrated that aqueous extract gives the highest antioxidant activity approximately 94.55% while acetone extract gives the largest inhibition zone for disc diffusion assay which is 19.00 mm respectively. The results revealed rich sources of gallic acid and tannic acid in Q. infectoria which might provide a novel source of these natural antioxidant and antibacterial activity.
This study was undertaken to characterize the antibiotic resistance and randomly amplified polymorphic DNA (RAPD) profiles of Vibrio parahaemolyticus isolates from raw vegetable samples. A total of 46 isolates of V. parahaemolyticus recovered from raw vegetables samples and were confirmed by PCR were analyzed in this study. Most of the isolates were resistant to nalidixic acid (93.48%) and were the least resistant towards imipinem (4.35%). The MAR index results also demonstrated high individual and multiple resistances to antibiotics among the isolates. From the RAPD analysis, the size for RAPD fragments generated ranged from 250 bp to 1,500 bp, with most of the strains contained three major gene fragments of 350, 1,000 and 1,350 bp. The RAPD profiles revealed a high level of DNA sequence diversity within the isolates. Antibiotic resistance and RAPD proved to be effective tools in characterizing and differentiating the V. parahaemolyticus strains.