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  1. Yashodhara BM, Huat CB, Naik LN, Umakanth S, Hande M, Pappachan JM
    Infect Drug Resist, 2010;3:115-22.
    PMID: 21694900 DOI: 10.2147/IDR.S10743
    Despite intensive efforts to eradicate the disease, tuberculosis continues to be a major threat to Indian society, with an estimated prevalence of 3.45 million cases in 2006. Emergence of multidrug-resistant tuberculosis has complicated eradication attempts in recent years. Incomplete and/inadequate treatment are the main causes for development of drug resistance. Directly observed therapy, short-course (DOTS) is the World Health Organization (WHO) strategy for worldwide eradication of tuberculosis, and our country achieved 100% coverage for DOTS through the Revised National Tuberculosis Control Program in 2006. For patients with multidrug-resistant tuberculosis, the WHO recommends a DOTS-Plus treatment strategy. Early detection and prompt treatment of multidrug-resistant tuberculosis is crucial to avoid spread of the disease and also because of the chances of development of potentially incurable extensively drug-resistant tuberculosis in these cases. This review discusses the epidemiologic, diagnostic, and therapeutic aspects of multidrug-resistant tuberculosis, and also outlines the role of primary care doctors in the management of this dangerous disease.
  2. Amir A, Cheong FW, de Silva JR, Liew JWK, Lau YL
    Infect Drug Resist, 2018;11:1145-1155.
    PMID: 30127631 DOI: 10.2147/IDR.S148664
    Originally known to cause simian malaria, Plasmodium knowlesi is now known as the fifth human malaria species. Since the publishing of a report that largely focused on human knowlesi cases in Sarawak in 2004, many more human cases have been reported in nearly all of the countries in Southeast Asia and in travelers returning from these countries. The zoonotic nature of this infection hinders malaria elimination efforts. In order to grasp the current perspective of knowlesi malaria, this literature review explores the different aspects of the disease including risk factors, diagnosis, treatment, and molecular and functional studies. Current studies do not provide sufficient data for an effective control program. Therefore, future direction for knowlesi research is highlighted here with a final aim of controlling, if not eliminating, the parasite.
  3. Haque M, Sartelli M, McKimm J, Abu Bakar M
    Infect Drug Resist, 2018;11:2321-2333.
    PMID: 30532565 DOI: 10.2147/IDR.S177247
    Health care-associated infections (HCAIs) are infections that occur while receiving health care, developed in a hospital or other health care facility that first appear 48 hours or more after hospital admission, or within 30 days after having received health care. Multiple studies indicate that the common types of adverse events affecting hospitalized patients are adverse drug events, HCAIs, and surgical complications. The US Center for Disease Control and Prevention identifies that nearly 1.7 million hospitalized patients annually acquire HCAIs while being treated for other health issues and that more than 98,000 patients (one in 17) die due to these. Several studies suggest that simple infection-control procedures such as cleaning hands with an alcohol-based hand rub can help prevent HCAIs and save lives, reduce morbidity, and minimize health care costs. Routine educational interventions for health care professionals can help change their hand-washing practices to prevent the spread of infection. In support of this, the WHO has produced guidelines to promote hand-washing practices among member countries.
  4. Haque M, Rahman NAA, McKimm J, Kibria GM, Azim Majumder MA, Haque SZ, et al.
    Infect Drug Resist, 2019;12:1333-1351.
    PMID: 31190922 DOI: 10.2147/IDR.S203364
    Background: Self-medication of drugs to alleviate symptoms is a common global behavior, helping relieve burdens on health services, but many drugs eg, antibiotics are prescription-only. Self-medication of antibiotics (SMA) is an irrational use of drugs, contributing to microbial resistance increasing health care costs and higher mortality and morbidity. This study aimed to assess SMA among university students. Methods: This was a cross-sectional study conducted among medical and non-medical students of the National Defence University of Malaysia. A validated instrument was used to gather data. Ethics approval was obtained. Random and universal sampling was adopted, and SPSS 21 was used for data analysis. Results: A total of 649 students participated in the study: 48.5% male and 51.5% female, 39.3% reported self-medicating with antibiotics. Penicillin, doxycycline, clarithromycin were the antibiotics most used with the majority reporting no adverse drug reactions. Cost savings and convenience were the principal reasons for SMA which were mainly obtained from local retail pharmacies. Despite medical students (particularly the more senior) having better knowledge of antibiotic use than non-medical students, 89% of all research participants responded that practicing SMA was a good/acceptable practice. Conclusion: SMA is common amongst Malaysian students and, despite understanding why SMA is unwise, even medical students self-medicate.
  5. Moussa AA, Md Nordin AF, Hamat RA, Jasni AS
    Infect Drug Resist, 2019;12:3269-3274.
    PMID: 31695445 DOI: 10.2147/IDR.S219544
    Background: Enterococcus faecium and Enterococcus faecalis are among the predominant species causing hospital-acquired infections. Currently, enterococcal infections are treated using combination therapy of an aminoglycoside with cell-wall active agents, which led to high level aminoglycoside resistance (HLAR) and vancomycin resistance (VRE) among enterococci. The aim of this study was to determine the prevalence of HLAR and the distribution of the resistance genes among clinical E. faecalis and E. faecium isolates in Malaysia.

    Materials and methods: Seventy-five enterococci isolates recovered from different clinical sources were re-identified by subculturing on selective medium, Gram staining, biochemical profiling (API 20 Strep), and 16s rRNA sequencing. Antimicrobial susceptibility testing (AST) was performed using Kirby-Bauer disc diffusion, E-test, and broth microdilution methods. PCR amplification was used to detect the presence of aminoglycoside modifying enzyme (AME) genes [aac(6')-Ie-aph(2")-Ia, aph(2")-Ib, aph(2")-Ic, aph(2")-Id, aph(3')-IIIa]. Descriptive data analysis was used to analyze the antibiotic susceptibility profiles and the distribution of HLAR genes.

    Results: The majority of the isolates recovered from the clinical samples are E. faecalis (66.7%), with the highest recovery from the pus. The prevalence of HLGR (51%) is higher when compared to HLSR (45-49%). Analysis of the resistance genes showed that bifunctional genes aac(6')-Ie-aph(2")-Ia and aph(3')-IIIa contributed to the HLAR E. faecalis and E. faecium. The other AME genes [aph(2")-Ib, aph(2")-Ic, aph(2")-Id] were not detected in this study.

    Conclusion: This study provides the first prevalence data on HLAR and the distribution of the AME genes among E. faecalis and E. faecium isolates from Malaysia. These highlight the need for continued antibiotic surveillance to minimize its emergence and further dissemination.

  6. Hanafiah A, Binmaeil H, Raja Ali RA, Mohamed Rose I, Lopes BS
    Infect Drug Resist, 2019;12:3051-3061.
    PMID: 31632095 DOI: 10.2147/IDR.S219069
    Aims and objectives: Helicobacter pylori has been classified as high priority pathogen by the WHO in 2017. The emergence of antibiotic-resistant strains is one of the main causes of treatment failure in H. pylori infection. This study determined and characterized primary and secondary resistances in H. pylori in Malaysia.

    Materials and methods: Gastric biopsies from antrum (n=288) and corpus (n=283) were obtained from 288 patients who underwent endoscopy at Universiti Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur, Malaysia. Antibiotic susceptibility to six classes of antibiotics was determined by the E-test. Mutations conferring in resistance in functional genes were identified by PCR and sequencing.

    Results: Overall resistance rates to metronidazole, clarithromycin and levofloxacin were 59.3% (35/59), 35.6% (21/59) and 25.4% (15/59), respectively. Secondary isolates showed significantly higher resistance rates to clarithromycin compared to the primary isolates. Mixed infection with susceptible and resistant isolates was observed in 16.2% (6/37) of cases, of which 83.3% (n=5) had infection with the same strain. 41% (18/44) of isolates were resistant to more than one class of antibiotics of which 50% (9/18) were multidrug-resistant, two being primary and seven being secondary isolates. Mutations in rdxA, 23S rRNA and gyrA genes were associated with resistance to metronidazole, clarithromycin and levofloxacin, respectively.

    Conclusion: The high level of resistance to metronidazole, clarithromycin and levofloxacin seen in H. pylori isolates in our setting warrants the need for continuous surveillance and highlights caution in use of antibiotics generally used as first-line therapy in H. pylori eradication regimen.

  7. Rayanakorn A, Katip W, Goh BH, Oberdorfer P, Lee LH
    Infect Drug Resist, 2019;12:3955-3965.
    PMID: 32021313 DOI: 10.2147/IDR.S233326
    Purpose: Streptococcus suis (S. suis) is an emerging zoonotic disease mainly in pigs, causing serious infections in humans with high prevalence in Southeast Asia. Despite a relatively high mortality rate, there are limited data regarding the risk factors of this life-threatening infection. Therefore, a 13-year retrospective cohort study in Chiang Mai, Thailand during 2005-2018 was conducted to explore risk factors associated with S. suis mortality and to update the outcomes of the disease.

    Patients and methods: S. suis positive cases were derived from those with positive S. suis isolates from microbiological culture results and Matrix-Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF). Potential risk factors of mortality were identified using univariate and multivariate logistic regression.

    Results: Of 133 patients with culture-proven S. suis infection identified, there were 92 males and 41 females. The mean age was 56.47 years. Septicemia (55.64%) was the most common clinical manifestation followed by meningitis (37.59%) and infective endocarditis (25.56%). Alcohol drinking and raw pork consumption were documented in 66 (49.62%) and 49 (36.84%) cases respectively. The overall mortality rate was 12.03% (n=16). According to the multivariate analysis, the independent risk factors for mortality were prolonged bacteremia ≥ 6 days (OR = 43.57, 95% CI = 2.46-772.80, P =0.010), septic shock (OR = 13.34, 95% CI = 1.63-109.03, P =0.016), and direct bilirubin > 1.5 mg/dL (OR = 12.86, 95% CI = 1.91-86.59, P =0.009).

    Conclusion: S. suis is not infrequent in Northern Thailand, where the cultural food habit of raw pork eating is still practiced. To the best of our knowledge, this is the largest series focusing on risk factors of S. suis mortality which has been conducted in Thailand. Prolonged bacteremia ≥ 6 days, septic shock, and direct bilirubin > 1.5 mg/dL were strong predictors associated with S. suis mortality. The mortality risk factors identified may be further utilized in clinical practice and future research to improve patient outcomes.

  8. Obande GA, Banga Singh KK
    Infect Drug Resist, 2020;13:455-483.
    PMID: 32104017 DOI: 10.2147/IDR.S217571
    Nucleic acid amplification technology (NAAT) has assumed a critical position in disease diagnosis in recent times and contributed significantly to healthcare. Application of these methods has resulted in a more sensitive, accurate and rapid diagnosis of infectious diseases than older traditional methods like culture-based identification. NAAT such as the polymerase chain reaction (PCR) is widely applied but seldom available to resource-limited settings. Isothermal amplification (IA) methods provide a rapid, sensitive, specific, simpler and less expensive procedure for detecting nucleic acid from samples. However, not all of these IA techniques find regular applications in infectious diseases diagnosis. Disease diagnosis and treatment could be improved, and the rapidly increasing problem of antimicrobial resistance reduced, with improvement, adaptation, and application of isothermal amplification methods in clinical settings, especially in developing countries. This review centres on some isothermal techniques that have found documented applications in infectious diseases diagnosis, highlighting their principles, development, strengths, setbacks and imminent potentials for use at points of care.
  9. Ali M, Naureen H, Tariq MH, Farrukh MJ, Usman A, Khattak S, et al.
    Infect Drug Resist, 2019;12:493-499.
    PMID: 30881054 DOI: 10.2147/IDR.S187836
    Background: Intensive care units (ICUs) are specialized units where patients with critical conditions are admitted for getting specialized and individualized medical treatment. High mortality rates have been observed in ICUs, but the exact reason and factors affecting the mortality rates have not yet been studied in the local population in Pakistan.

    Aim: This study was aimed to determine rational use of antibiotic therapy in ICU patients and its impact on clinical outcomes and mortality rate.

    Methods: This was a retrospective, longitudinal (cohort) study including 100 patients in the ICU of the largest tertiary care hospital of the capital city of Pakistan.

    Results: It was observed that empiric antibiotic therapy was initiated in 68% of patients, while culture sensitivity test was conducted for only 19% of patients. Thirty-percent of patients developed nosocomial infections and empiric antibiotic therapy was not initiated for those patients (P<0.05). Irrational antibiotic prescribing was observed in 86% of patients, and among them, 96.5% mortality was observed (P<0.05). The overall mortality rate was 83%; even higher mortality rates were observed in patients on a ventilator, patients with serious drug-drug interactions, and patients prescribed with irrational antibiotics or nephrotoxic drugs. Adverse clinical outcomes leading to death were observed to be significantly associated (P<0.05) with irrational antibiotic prescribing, nonadjustment of doses of nephrotoxic drugs, use of steroids, and major drug-drug interactions.

    Conclusion: It was concluded that empiric antibiotic therapy is beneficial in patients and leads to a reduction in the mortality rate. Factors including irrational antibiotic selection, prescribing contraindicated drug combinations, and use of nephrotoxic drugs were associated with high mortality rate and poor clinical outcomes.

  10. Marzan M, Islam DZ, Lugova H, Krishnapillai A, Haque M, Islam S
    Infect Drug Resist, 2021;14:519-533.
    PMID: 33603416 DOI: 10.2147/IDR.S289964
    Background: Antibiotics are lifesaving drugs, and inappropriate uses lead to the resistance that renders them ineffective. This study aims to understand knowledge, attitude, and practice (KAP) concerning antibiotic use and resistance among university students in Bangladesh.

    Methods: A cross-sectional study was performed from January to April 2020 among students at Jahangirnagar University (JU), Bangladesh. Purposive sampling was conducted through an in-person interview using a structured questionnaire. Students from the faculties of biological sciences and non-biology background were included. The univariate ordinal regression technique was used to analyze the relationship between predictors and good knowledge about the antibiotics. A two-tailed p-value was calculated to determine statistical association.

    Results: Out of 205 study participants, 92 and 113 responders were from biological science faculty and non-biology disciplines, respectively. Less than half of the students (42.4%) showed a good knowledge level (scores higher than 80%). Biology-background students possess better knowledge than non-biology students [odds ratio (OR) = 4.44, 95% confidence level (CL) (2.56, 7.70), p < 0.001]. A better attitude was noticed among all students. The self-medication rate was quite low, and more than 90% of students were found to consume antibiotics according to the physician's prescription. Lack of treatment adherence was recorded, and students admitted to stop-taking antibiotics when symptoms disappeared (48.67% biology and 36.26% non-biology). Multivariate regression analysis was unable to detect any significant association between self-medication and gender, student category or the level of knowledge about antibiotics.

    Conclusion: Students of biological science background possessed better knowledge indicating the importance of appropriate curriculum imparted in knowledge buildup. Introducing a short course about the risk and development of antibiotic resistance will grow the students' awareness to avoid the resistance phenomenon.

  11. Kaur RJ, Charan J, Dutta S, Sharma P, Bhardwaj P, Sharma P, et al.
    Infect Drug Resist, 2020;13:4427-4438.
    PMID: 33364790 DOI: 10.2147/IDR.S287934
    Background: COVID-19 caused by SARS-CoV-2 virus emerged as an unprecedented challenge to discover effective drugs for its prevention and cure. Hyperinflammation-induced lung damage is one of the poor prognostic indicators causing a higher rate of morbidity and mortality of COVID-19 patients. Favipiravir, an antiviral drug, is being used for COVID-19 treatment, and we currently have limited information regarding its efficacy and safety. Thus, the present study was undertaken to evaluate the adverse drug events (ADEs) reported in the WHO pharmacovigilance database.

    Methods: This study analyzed all suspected ADEs related to favipiravir reported from 2015. The reports were analyzed based on age, gender, and seriousness of ADEs at the System Organ Classification (SOC) level and the individual Preferred Term (PT) level.

    Results: This study is based on 194 ADEs reported from 93 patients. Most frequent ADEs suspected to be caused by the favipiravir included increased hepatic enzymes, nausea and vomiting, tachycardia, and diarrhea. Severe and fatal ADEs occurred more frequently in men and those over the age of 64 years. Blood and lymphatic disorders, cardiac disorders, hepatobiliary disorders, injury poisoning, and procedural complications were more common manifestations of severe ADEs.

    Conclusion: This study revealed that favipiravir appears to be a relatively safe drug. An undiscovered anti-inflammatory activity of favipiravir may explain the improvement in critically ill patients and reduce inflammatory markers. Currently, the data is based on very few patients. A more detailed assessment of the uncommon ADEs needs to be analyzed when more information will be available.

  12. Urmi UL, Nahar S, Rana M, Sultana F, Jahan N, Hossain B, et al.
    Infect Drug Resist, 2020;13:2863-2875.
    PMID: 32903880 DOI: 10.2147/IDR.S262493
    Introduction: Klebsiella pneumoniae carbapenemase (KPC) belongs to the Group-A β-lactamases that incorporate serine at their active site and hydrolyze various penicillins, cephalosporins, and carbapenems. Metallo-beta-lactamases (MBLs) are group-B enzymes that contain one or two essential zinc ions in the active sites and hydrolyze almost all clinically available β-lactam antibiotics. Klebsiella pneumoniae remains the pathogen with the most antimicrobial resistance to KPC and MBLs.

    Methods: This research investigated the blaKPC, and MBL genes, namely, blaIMP, blaVIM, and blaNDM-1 and their phenotypic resistance to K. pneumoniae isolated from urinary tract infections (UTI) in Bangladesh. Isolated UTI K. pneumoniae were identified by API-20E and 16s rDNA gene analysis. Their phenotypic antimicrobial resistance was examined by the Kirby-Bauer disc diffusion method, followed by minimal inhibitory concentration (MIC) determination. blaKPC, blaIMP, blaNDM-1, and blaVIM genes were evaluated by polymerase chain reactions (PCR) and confirmed by sequencing.

    Results: Fifty-eight K. pneumoniae were identified from 142 acute UTI cases. Their phenotypic resistance to amoxycillin-clavulanic acid, cephalexin, cefuroxime, ceftriaxone, and imipenem were 98.3%, 100%, 96.5%, 91.4%, 75.1%, respectively. Over half (31/58) of the isolates contained either blaKPC or one of the MBL genes. Individual prevalence of blaKPC, blaIMP, blaNDM-1, and blaVIM were 15.5% (9), 10.3% (6), 22.4% (13), and 19% (11), respectively. Of these, eight isolates (25.8%, 8/31) were found to have two genes in four different combinations. The co-existence of the ESBL genes generated more resistance than each one individually. Some isolates appeared phenotypically susceptible to imipenem in the presence of blaKPC, blaIMP, blaVIM, and blaNDM-1 genes, singly or in combination.

    Conclusion: The discrepancy of genotype and phenotype resistance has significant consequences for clinical bacteriology, precision in diagnosis, the prudent selection of antimicrobials, and rational prescribing. Heterogeneous phenotypes of antimicrobial susceptibility testing should be taken seriously to avoid inappropriate diagnostic and therapeutic decisions.

  13. Abubakar AR, Sani IH, Godman B, Kumar S, Islam S, Jahan I, et al.
    Infect Drug Resist, 2020;13:4673-4695.
    PMID: 33402839 DOI: 10.2147/IDR.S289037
    A novel coronavirus-2 (SARS-CoV-2) was first identified in Wuhan, China, and quickly spread globally. Several treatments have been proposed, many of which have proven ineffective. Consequently, there is a need to review the published evidence of drug clinical trials to guide future prescribing. A systematic review of published clinical trials and retrospective observational studies was carried out. The search was made using PubMed, Embase, MEDLINE, and China National Knowledge Infrastructure (CNKI) databases. Articles published between January 2020 and October 2020 and written in the English language were retrieved and included in the study. Researches that used traditional medicine, in-vitro and in-vivo animal studies, as well as reviews were excluded. Seventy-three relevant articles that fulfilled the inclusion criteria were finally selected and reviewed. Hydroxychloroquine, chloroquine, and azithromycin produced no clinical evidence of efficacy in randomized controlled clinical trials (RCT). However, retrospective observational studies reported the efficacy of remdesivir and lopinavir/ritonavir in reducing viral load, although there have been concerns with lopinavir/ritonavir and, more recently, remdesivir. Recently, tocilizumab, dexamethasone, and methylprednisolone significantly relieved lung inflammation and decreased mortality in patients with severe COVID-19. In addition, convalescent plasma was effective in boosting strong immunity among patients with mild COVID-19. There is currently no single worldwide approved therapeutic option for patients with COVID-19 despite the initial hype with medicines, including hydroxychloroquine. Nonetheless, dexamethasone has shown promise in symptomatic treatment and convalescent plasma in boosting immunity. New treatments are currently being researched, and the findings will be reported accordingly to provide evidence-based guidance for prescribers and policymakers.
  14. Majumder MAA, Rahman S, Cohall D, Bharatha A, Singh K, Haque M, et al.
    Infect Drug Resist, 2020;13:4713-4738.
    PMID: 33402841 DOI: 10.2147/IDR.S290835
    Antimicrobial resistance (AMR) is a serious threat to global public health. It increases morbidity and mortality, and is associated with high economic costs due to its health care burden. Infections with multidrug-resistant (MDR) bacteria also have substantial implications on clinical and economic outcomes. Moreover, increased indiscriminate use of antibiotics during the COVID-19 pandemic will heighten bacterial resistance and ultimately lead to more deaths. This review highlights AMR's scale and consequences, the importance, and implications of an antimicrobial stewardship program (ASP) to fight resistance and protect global health. Antimicrobial stewardship (AMS), an organizational or system-wide health-care strategy, is designed to promote, improve, monitor, and evaluate the rational use of antimicrobials to preserve their future effectiveness, along with the promotion and protection of public health. ASP has been very successful in promoting antimicrobials' appropriate use by implementing evidence-based interventions. The "One Health" approach, a holistic and multisectoral approach, is also needed to address AMR's rising threat. AMS practices, principles, and interventions are critical steps towards containing and mitigating AMR. Evidence-based policies must guide the "One Health" approach, vaccination protocols, health professionals' education, and the public's awareness about AMR.
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