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Nucleotide sequence of precore region of hepatitis B virus DNA in HBsAg-positive carriers in Malaysia

Ton SH, Iskandar K, Noriah R, Thanaletchimy N

Scand. J. Infect. Dis., 1996;28(6):543-8.
PMID: 9060053

As most published studies on precore mutants have been carried out on isolates from patients with liver diseases, and it is unclear whether HBsAg carriers with viraemia in the absence of HBeAg are also generally infected by such mutants, it was decided to sequence the precore region in some HBV-DNA isolated from HBsAg-positive carriers. Precore sequences of HBV-DNA from 43 HBsAg carriers in Malaysia were studied. Three HBV subtypes were identified according to the nucleotide sequence of the precore region. Most of the carriers were found to be infected by the subtype adr. Mutations were detected in the precore regions. The most common conserved mutation was a silent mutation involving conversion from T to C (CCT to CCC) at position 1858 at codon 15 (proline). It was found that 4/43 (9.3%) had a mutation at the penultimate codon where TGG was changed to TAG. All 4 isolates with the TAG mutation had nt T at position 1858. Of the 4 carriers who were infected by these mutant viruses, 2 were coinfected with the wild type, 1 was infected only by a variant with the mutation at position 1896, while another was infected by a variant with mutations at positions 1896 and 1899. Three of the 4 were anti-HBe positive while 1 was HBeAg positive. Alanine aminotransaminase activities in all 4 carriers were normal. This study therefore demonstrated that variants with stop codons at the penultimate codon could be found in asymptomatic carriers in Malaysia.
Outcomes of children with long-segment and total colon Hirschsprung disease following pull-through

Wardhani AK, Dwiantama K, Iskandar K, Yunus J, Gunadi

Med J Malaysia, 2024 Aug;79(Suppl 4):1-5.
PMID: 39215407

INTRODUCTION: Hirschsprung disease (HSCR) is a congenital disorder caused by the absence of ganglion cells, which leads to a functional obstruction in infants. HSCR is divided into short, long and total colon aganglionosis (TCA). However, post-operative outcome assessment of patients with long-segment and TCA is scarce. We determined the functional outcomes, Hirschsprung-associated enterocolitis (HAEC) and complications of long-segment and TCA HSCR's children following pull-through surgery.
MATERIALS AND METHODS: Descriptive analysis research was done for children with HSCR long-segment and TCA who underwent an operation at our institutionfrom 2013 to 2020. We assessed the functional outcome and HAEC by the Krickenbeck and the HAEC scoring, respectively.
RESULTS: We ascertained 13 HSCR long-segment and six TCA. We performed the following surgical procedures: Duhamel (n=7), Martin (n=4), Kimura (n=1), transabdominal Yancey-Soave (n=3) and transanal endorectal pull-through (n=4). All long-segment patients revealed good functional outcomes, whereas two TCA children suffered soiling and failed to achieve voluntary bowel movement. HAEC was noted in three long-segment and four TCA patients. Furthermore, surgical site infection and diaper rash were noticed in 10 and two patients, respectively.
CONCLUSION: Long-segment patients might have better functional outcomes TCA group, whereas the frequency of HAEC is compatible among arms. Long-term follow-up is important and necessary to identify complications early and define the proper treatment. Our study comprehensively analyzes functional outcomes, HAEC and complications of children with HSCR long-segment and TCA after definitive surgery in a developing country.
Fulltext The Double Burden of the COVID-19 Pandemic and Polypharmacy on Geriatric Population - Public Health Implications

Rahman S, Singh K, Dhingra S, Charan J, Sharma P, Islam S, et al.

Ther Clin Risk Manag, 2020;16:1007-1022.
PMID: 33116550 DOI: 10.2147/TCRM.S272908

COVID-19 pandemic is inducing acute respiratory distress syndrome, multi-organ failure, and eventual death. Respiratory failure is the leading cause of mortality in the elderly population with pre-existing medical conditions. This group is particularly vulnerable to infections due to a declined immune system, comorbidities, geriatric syndrome, and potentially inappropriate polypharmacy. These conditions make the elderly population more susceptible to the harmful effects of medications and the deleterious consequences of infections, including MERS-CoV, SARS-CoV, and SARS-CoV-2. Chronic diseases among elderlies, including respiratory diseases, hypertension, diabetes, and coronary heart diseases, present a significant challenge for healthcare professionals. To comply with the clinical guidelines, the practitioner may prescribe a complex medication regimen that adds up to the burden of pre-existing treatment, potentially inducing adverse drug reactions and leading to harmful side-effects. Consequently, the geriatric population is at increased risk of falls, frailty, and dependence that enhances their susceptibility to morbidity and mortality due to SARS-CoV-2 respiratory syndrome, particularly interstitial pneumonia. The major challenge resides in the detection of infection that may present as atypical manifestations in this age group. Healthy aging can be possible with adequate preventive measures and appropriate medication regimen and follow-up. Adherence to the guidelines and recommendations of WHO, CDC, and other national/regional/international agencies can reduce the risks of SARS-CoV-2 infection. Better training programs are needed to enhance the skill of health care professionals and patient's caregivers. This review explains the public health implications associated with polypharmacy on the geriatric population with pre-existing co-morbidities during the COVID-19 pandemic.
Quorum sensing: a new prospect for the management of antimicrobial-resistant infectious diseases

Haque M, Islam S, Sheikh MA, Dhingra S, Uwambaye P, Labricciosa FM, et al.

Expert Rev Anti Infect Ther, 2021 05;19(5):571-586.
PMID: 33131352 DOI: 10.1080/14787210.2021.1843427

INTRODUCTION: Quorum-sensing (QS) is a microbial cell-to-cell communication system that utilizes small signaling molecules to mediates interactions between cross-kingdom microorganisms, including Gram-positive and -negative microbes. QS molecules include N-acyl-homoserine-lactones (AHLs), furanosyl borate, hydroxyl-palmitic acid methylester, and methyl-dodecanoic acid. These signaling molecules maintain the symbiotic relationship between a host and the healthy microbial flora and also control various microbial virulence factors. This manuscript has been developed based on published scientific papers.
AREAS COVERED: Furanones, glycosylated chemicals, heavy metals, and nanomaterials are considered QS inhibitors (QSIs) and are therefore capable of inhibiting the microbial QS system. QSIs are currently being considered as antimicrobial therapeutic options. Currently, the low speed at which new antimicrobial agents are being developed impairs the treatment of drug-resistant infections. Therefore, QSIs are currently being studied as potential interventions targeting QS-signaling molecules and quorum quenching (QQ) enzymes to reduce microbial virulence.
EXPERT OPINION: QSIs represent a novel opportunity to combat antimicrobial resistance (AMR). However, no clinical trials have been conducted thus far assessing their efficacy. With the recent advancements in technology and the development of well-designed clinical trials aimed at targeting various components of the, QS system, these agents will undoubtedly provide a useful alternative to treat infectious diseases.
Fulltext Menace of antimicrobial resistance in LMICs: Current surveillance practices and control measures to tackle hostility

Sharma A, Singh A, Dar MA, Kaur RJ, Charan J, Iskandar K, et al.

J Infect Public Health, 2022 Feb;15(2):172-181.
PMID: 34972026 DOI: 10.1016/j.jiph.2021.12.008

Antimicrobial Resistance (AMR) is significant challenge humanity faces today, with many patients losing their lives every year due to AMR. It is more widespread and has shown a higher prevalence in low- and middle-income countries (LMICs) due to lack of awareness and other associated reasons. WHO has suggested some crucial guidelines and specific strategies such as antimicrobial stewardship programs taken at the institutional level to combat AMR. Creating awareness at the grassroots level can help to reduce the AMR and promote safe and effective use of antimicrobials. Control strategies in curbing AMR also comprise hygiene and sanitation as microbes travel from contaminated surroundings to the human body surface. As resistance to multiple drugs increases, vaccines can play a significant role in curbing the menace of AMR. This article summarizes the current surveillance practices and applied control measures to tackle the hostility in these countries with particular reference to the role of antimicrobial stewardship programs and the responsibilities of regulatory authorities in managing the situation.
Is it time to reconsider prophylactic antimicrobial use for hematopoietic stem cell transplantation? a narrative review of antimicrobials in stem cell transplantation

Jahan D, Peile E, Sheikh MA, Islam S, Parasnath S, Sharma P, et al.

Expert Rev Anti Infect Ther, 2021 10;19(10):1259-1280.
PMID: 33711240 DOI: 10.1080/14787210.2021.1902304

INTRODUCTION: Hematopoietic Stem Cell Transplantation (HSCT) is a life-saving procedure for multiple types of hematological cancer, autoimmune diseases, and genetic-linked metabolic diseases in humans. Recipients of HSCT transplant are at high risk of microbial infections that significantly correlate with the presence of graft-versus-host disease (GVHD) and the degree of immunosuppression. Infection in HSCT patients is a leading cause of life-threatening complications and mortality.
AREAS COVERED: This review covers issues pertinent to infection in the HSCT patient, including bacterial and viral infection; strategies to reduce GVHD; infection patterns; resistance and treatment options; adverse drug reactions to antimicrobials, problems of antimicrobial resistance; perturbation of the microbiome; the role of prebiotics, probiotics, and antimicrobial peptides. We highlight potential strategies to minimize the use of antimicrobials.
EXPERT OPINION: Measures to control infection and its transmission remain significant HSCT management policy and planning issues. Transplant centers need to consider carefully prophylactic use of antimicrobials for neutropenic patients. The judicious use of appropriate antimicrobials remains a crucial part of the treatment protocol. However, antimicrobials' adverse effects cause microbiome diversity and dysbiosis and have been shown to increase morbidity and mortality.
Fulltext Convalescent Plasma Therapy for Management of COVID-19: Perspectives and Deployment in the Current Global Pandemic

Samad N, Sodunke TE, Banna HA, Sapkota A, Fatema AN, Iskandar K, et al.

Risk Manag Healthc Policy, 2020;13:2707-2728.
PMID: 33262668 DOI: 10.2147/RMHP.S281388

The world is striving against the severe crisis of the COVID-19 pandemic. Healthcare professionals are struggling to treat their patients based on nonspecific therapies. Amidst this uncertainty, convalescent plasma therapy (CPT) has appeared to be an interim adjuvant therapy for severely ill patients of COVID-19 until long-term clinical trial treatment options are available. Considering the transfusion-related hazards, especially lung injuries and microbial transmission, where sensitivity is not ensured, rigorous trials should be conducted to determine this therapy's efficacy. Moreover, the ratio of recovered cases to plasma donors is not satisfying, which questioning this therapy's availability and accessibility. Although some countries are making the treatment free, the attributable cost mandates a justification for its suitability and sustainability. Our article aimed to review the published facts and findings of CPT's effectiveness in lowering the mortality rate of COVID-19. This pandemic showed that healthcare systems worldwide need core reform. A unified global collaboration must align and coordinate to face the current pandemic and enhance world readiness for future outbreaks based on health equity and equality.
Fulltext Strategies to Prevent Healthcare-Associated Infections: A Narrative Overview

Haque M, McKimm J, Sartelli M, Dhingra S, Labricciosa FM, Islam S, et al.

Risk Manag Healthc Policy, 2020;13:1765-1780.
PMID: 33061710 DOI: 10.2147/RMHP.S269315

Healthcare-associated infections (HCAIs) are a major source of morbidity and mortality and are the second most prevalent cause of death. Furthermore, it has been reported that for every one-hundred patients admitted to hospital, seven patients in high-income economies and ten in emerging and low-income economies acquire at least one type of HCAI. Currently, almost all pathogenic microorganisms have developed antimicrobial resistance, and few new antimicrobials are being developed and brought to market. The literature search for this narrative review was performed by searching bibliographic databases (including Google Scholar and PubMed) using the search terms: "Strategies," "Prevention," and "Healthcare-Associated Infections," followed by snowballing references cited by critical articles. We found that although hand hygiene is a centuries-old concept, it is still the primary strategy used around the world to prevent HCAIs. It forms one of a bundle of approaches used to clean and maintain a safe hospital environment and to stop the transmission of contagious and infectious microorganisms, including multidrug-resistant microbes. Finally, antibiotic stewardship also has a crucial role in reducing the impact of HCAIs through conserving currently available antimicrobials.
Fulltext Highlighting the gaps in quantifying the economic burden of surgical site infections associated with antimicrobial-resistant bacteria

Iskandar K, Sartelli M, Tabbal M, Ansaloni L, Baiocchi GL, Catena F, et al.

World J Emerg Surg, 2019;14:50.
PMID: 31832084 DOI: 10.1186/s13017-019-0266-x

Antibiotics are the pillar of surgery from prophylaxis to treatment; any failure is potentially a leading cause for increased morbidity and mortality. Robust data on the burden of SSI especially those due to antimicrobial resistance (AMR) show variable rates between countries and geographical regions but accurate estimates of the incidence of surgical site infections (SSI) due to AMR and its related global economic impact are yet to be determined. Quantifying the burden of SSI treatment is an incentive to sensitize governments, healthcare systems, and the society to invest in quality improvement and sustainable development. However in the absence of a unified epidemiologically sound infection definition of SSI and a well-designed global surveillance system, the end result is a lack of accurate and reliable data that limits the comparability of estimates between countries and the possibility of tracking changes to inform healthcare professionals about the appropriateness of implemented infection prevention and control strategies. This review aims to highlight the reported gaps in surveillance methods, epidemiologic data, and evidence-based SSI prevention practices and in the methodologies undertaken for the evaluation of the economic burden of SSI associated with AMR bacteria. If efforts to tackle this problem are taken in isolation without a global alliance and data is still lacking generalizability and comparability, we may see the future as a race between the global research efforts for the advancement in surgery and the global alarming reports of the increased incidence of antimicrobial-resistant pathogens threatening to undermine any achievement.
Fulltext Surveillance of antimicrobial resistance in low- and middle-income countries: a scattered picture

Iskandar K, Molinier L, Hallit S, Sartelli M, Hardcastle TC, Haque M, et al.

Antimicrob Resist Infect Control, 2021 03 31;10(1):63.
PMID: 33789754 DOI: 10.1186/s13756-021-00931-w

Data on comprehensive population-based surveillance of antimicrobial resistance is lacking. In low- and middle-income countries, the challenges are high due to weak laboratory capacity, poor health systems governance, lack of health information systems, and limited resources. Developing countries struggle with political and social dilemma, and bear a high health and economic burden of communicable diseases. Available data are fragmented and lack representativeness which limits their use to advice health policy makers and orientate the efficient allocation of funding and financial resources on programs to mitigate resistance. Low-quality data means soaring rates of antimicrobial resistance and the inability to track and map the spread of resistance, detect early outbreaks, and set national health policy to tackle resistance. Here, we review the barriers and limitations of conducting effective antimicrobial resistance surveillance, and we highlight multiple incremental approaches that may offer opportunities to strengthen population-based surveillance if tailored to the context of each country.
Fulltext WSES/GAIS/SIS-E/WSIS/AAST global clinical pathways for patients with intra-abdominal infections

Sartelli M, Coccolini F, Kluger Y, Agastra E, Abu-Zidan FM, Abbas AES, et al.

World J Emerg Surg, 2021 09 25;16(1):49.
PMID: 34563232 DOI: 10.1186/s13017-021-00387-8

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in hospitals worldwide. The cornerstones of effective treatment of IAIs include early recognition, adequate source control, appropriate antimicrobial therapy, and prompt physiologic stabilization using a critical care environment, combined with an optimal surgical approach. Together, the World Society of Emergency Surgery (WSES), the Global Alliance for Infections in Surgery (GAIS), the Surgical Infection Society-Europe (SIS-E), the World Surgical Infection Society (WSIS), and the American Association for the Surgery of Trauma (AAST) have jointly completed an international multi-society document in order to facilitate clinical management of patients with IAIs worldwide building evidence-based clinical pathways for the most common IAIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting information was shared by an international task force from 46 countries with different clinical backgrounds. The aim of the document is to promote global standards of care in IAIs providing guidance to clinicians by describing reasonable approaches to the management of IAIs.
Fulltext Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Sartelli M, Weber DG, Ruppé E, Bassetti M, Wright BJ, Ansaloni L, et al.

World J Emerg Surg, 2017;12:35.
PMID: 28785301 DOI: 10.1186/s13017-017-0147-0

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].
Fulltext Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA)

Sartelli M, Weber DG, Ruppé E, Bassetti M, Wright BJ, Ansaloni L, et al.

World J Emerg Surg, 2016;11:33.
PMID: 27429642 DOI: 10.1186/s13017-016-0089-y

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

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