WHO List Research Articles

Assessing knowledge, attitude, and practices of veterinarians towards antimicrobial use and stewardship as drivers of inappropriate use in Abuja, Nigeria

IntroductionAntimicrobial resistance (AMR) has recently gained worldwide recognition, as the emergence of multi-drug resistant organisms has led to increased mortality and economic burden. This study aimed to assess knowledge, attitudes, and practices of veterinarians towards rational antimicrobial prescribing and identify factors influencing use.MethodsWe interviewed veterinary doctors in Abuja, Nigeria using a 50-point questionnaire distributed via WhatsApp mobile application. The questionnaire inquired about their experiences, knowledge, attitudes, and practices towards AMR and stewardship. We analyzed the data by calculating frequencies and proportions.ResultsOf 220 registered veterinarians, 144 (65.5%) participated in the survey. Most (52.8%) were within the age group 30 - 39 years; males (72.2%), with a Master’s degree (42.4%) and worked in public service (44.4%). Three-quarters (75.7%) had good knowledge of antimicrobials; 47.2% had received training on stewardship while 88.9% reported that they believed that overuse of antimicrobials was the major contributory factor towards AMR. Antimicrobial stewardship regulations are important in veterinary practice. Veterinarians were aware of the occurrence of resistant pathogens and agreed that restricting antimicrobial use in animal health care was necessary to reduce AMR.ConclusionMost respondents referred to the veterinary formulary (VF) when in doubt of the appropriate antimicrobial agent to administer. We recommend that the VF be updated following the WHO list of critically-important-antimicrobials (CIA) and veterinarians educated not to use these CIAs in the treatment of food animals.

Assessment of the availability of snakebite antivenom in health facilities in Ndola District, Zambia: a cross-sectional study.

Despite snakebite antivenom being included on the WHO list of essential medicines, many parts of the world, especially Africa, lack effective and safe antivenoms. A descriptive, field-based, cross-sectional study was undertaken from August to November 2020 in 40 out of 71 health facilities in Ndola district. Interviews and physical inspection were conducted at each facility. The study revealed that only three (8%) of all the private health facilities had antivenom available at the time of the assessment. Factors significantly associated with antivenom supply included lack of central country supply (90%), lack of demand of the antivenom (55%) and no budget allocation for the antivenom (95%). Despite the high number of notified snakebites within Ndola district, there remains poor availability of snakebite antivenom within the district.

The Anti-Leprosy Drug Clofazimine Synergizes with BTK Inhibitors and Proteasome Inhibitors in Drug-Resistant Mantle Cell Lymphoma

Mantle Cell Lymphoma (MCL) is a difficult to cure, highly heterogeneous, and aggressive form of non-Hodgkin lymphoma comprising roughly 7% of all cases with a high recurrence rate and poor long-term prognosis. The reported progression-free survival is about 1-2 years, and median overall survival/OS <3 years. Current first-line MCL therapies include combination regimens like R-CHOP, R-DHAP, Hyper-CVAD, VcR-CAP, etc. However, although patients respond well to initial treatment, most eventually progress to relapsed disease state. BTKis (Bruton's tyrosine kinase inhibitors) such as Ibrutinib are standard targeted therapeutic options for refractory or relapsed (R/R) MCL. The proteasome inhibitor (PI) drug Bortezomib/Velcade/Bz is another FDA-approved targeted drug for R/R MCL. However, despite these recent advances in the treatment landscape, R/R MCL still remains incurable with limited therapeutic options and a median OS<10-15 months. Therefore, there is an unmet need to discover novel drugs against R/R MCL.Previously, we have demonstrated that Clofazimine (CLF), an anti-leprosy drug, could potentially be repurposed for the treatment of chronic myeloid leukemia and PI/IMiD resistant multiple myeloma that also targets subclones representing putative stem-like-cells (CSCs). Notably, using single-cell analysis and high dimensional immunophenotyping or CyTOF (Cytometry Time of Flight), we have also identified molecular networks underpinning CLF+PI synergy. We hypothesize that CLF has strong potential to be repurposed as a novel anti-MCL drug, particularly in a relapsed/refractory setting.For this purpose, we used MCL cell lines representing drug-sensitive (JEKO1, MINO), innate PI/BTKi-resistance (Z138; representing refractory patients), and clonally-derived acquired PI/BTKi-resistance (MINO-R; representing relapse patients) as in vitro model systems and showed i) the efficacy of CLF as a single agent (IC 50= 6.9±3.6 uM) and ii) in combination with PIs (Bz) and BTKis (Ibrutinib, Acalabrutinib) against innate and acquired resistant MCL (Fig.1), as well as iii) the unique targeting of putative CSCs by CLF. Remarkably, CLF+BTKi/PI combination lowered the effective BTKi and PI doses required to achieve desired therapeutic response by >10-folds (estimated dose reduction index for BTKi and PI were 12.43 and 10.99, respectively). Further, mRNA-sequencing followed by differential gene expression analysis using DESeq2 and EdgeR revealed that the top significantly upregulated genes following PI+CLF treatment were GSR, DAP3, and DOK1, which have reported anti-tumorigenic activity. The top significantly downregulated genes EHD1, CBX8, DDX17, SOX12, and COMMD3 have reported pro-survival function. Ingenuity pathway analysis revealed protein ubiquitination pathway and cell cycle arrest at the G2/M phase as the top canonical pathways. Causal network analysis showed synergistic drug action significantly elevated the levels of oxidative stress and unfolded protein response. Additionally, PI+CLF combination potentiated AMPK mediated down-regulation of the mTOR signaling pathway, which further led to direct reduction of Cyclin D1 (aberrantly expressed in MCL) and the downregulation of eIF4-p70S6K signaling. The synergistic drug activity also led to the downregulation of oncogenic pathways like p38 MAPK and NF-kB signaling.Recent studies have indicated that intra-tumor heterogeneity due to the presence of stem-like cells in MCL (MCL-CSCs), including CD45+CD19- MCL-initiating cells (MCL-ICs), relatively quiescent-highly clonogenic aldehyde dehydrogenase (ALDH)+ cells and side populations (SP) may drive drug resistance and disease relapse. Notably, we found that several of the differentially regulated genes are critical for the maintenance and functioning of CSCs. For example, PI+CLF combination downregulates Wnt/β catenin signaling, which is found to be frequently overexpressed in MCL-ICs. HIPPO, another signaling pathway involved in the maintenance of cancer stem-ness and emergence of drug resistance, was also down-regulated. Currently, we are validating the specific targeting of putative MCL-CSCs by CLF. Next, we plan to replicate our findings using PDX models of MCL.CLF is an FDA-approved drug as well as on WHO's List of Essential Medicines. Thus, our study introduces CLF as a novel, safe, and inexpensive therapeutic option for the management of R/R MCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pre-Clinical Evaluation of Novel L-Asparaginase Mutants for the Treatment of Acute Lymphoblastic Leukemia

IntroductionAcute Lymphoblastic Leukemia (ALL) accounts for 20% of all hematological malignancies. L-Asparaginase has been a mainstay of ALL for the last 6 decades and is also included in the WHO list of essential medicines for ALL. Escherichia coli L-asparaginase (EcA) was the first asparaginase to be approved for clinical use. However being isolated from bacteria, EcA has many side-effects which in turn affects the tolerability and efficacy of the drug. EcA administration may cause strong immunogenic and hypersensitive reactions in the patients, necessitating withdrawal of the drug. Sensitive individuals react to repeated EcA administration with formation of anti-drug antibodies (ADAs) that bind to and inactivate the enzyme leading to inadequate plasma levels of EcA. Another serious drawback of EcA is the glutaminase activity which leads to neurotoxicity. Other side effects include hepatotoxicity, thromboembolism and pancreatitis. Although a number of attempts have been made to alleviate these problems by rational protein engineering, the optimization of therapy with EcA for ALL patients still remains a challenge. In an attempt to deal with these problems, we created several EcA mutants. On the basis of their activity, stability and antigenicity we short-listed four EcA mutants (Mutant A, B, C and D) having favourable properties for further development.MethodsWe identified and mutated several B-cell epitopes and amino acid residues at the EcA interface that are responsible for activity, stability and antigenicity. Enzyme activity was measured at 37 oC (optimum temperature for EcA). Glutaminase activity of the mutants was measured and compared to the wild type EcA. The cytotoxicity of the EcA variants was verified in ALL sensitive REH cell lines by performing MTT assay after 24 h incubation. Further the antigenicity of the mutants was assessed by performing indirect ELISA where the binding of the mutants to the commercially available l-asparaginase antibody was analysed. Further, in vivo immunogenicity was evaluated by immunizing Balc C mice with primary and booster doses of EcA mutants over 66 days followed by the measurement of IgG and IgM titers. In addition, the binding of wild-type EcA and mutants to pre-existing anti-asparaginase antibodies in serum isolated from primary and relapsed ALL patients receiving asparaginase therapy was studied by indirect ELISA. Pharmacokinetics of the mutants was evaluated in female Balb C mice by plotting the asparaginase activity-time curve till 24 h following administration of a single i.v. dose of 50 IU/kg and compared with the wildtype. Finally the safety of the EcA mutants was determined by performing single-dose acute toxicity study at 3 dose levels in Balb C mice.ResultsAt 37 oC, we did not find any significant difference in asparaginase activity of any EcA variant with the wild-type. All four variants showed markedly reduced glutaminase activity as compared to wild-type EcA (P<0.05). In MTT assay Mutant D showed 34.02%, Mutant B (32.4%), Mutant C (31.4%), Mutant A (24.22%), and wild type EcA (24.37%) reduction in REH cell viability in comparison to untreated cells. Binding to commercially available anti-asparaginase antibody was 49.09%, 32.63%, 27.43% less for Mutant D, Mutant B and Mutant C respectively compared to wild type EcA. Mice immunized with Mutant D showed 5-fold lower titres of IgG and 4-fold lower titres of IgM in comparison to wild type. Similarly, when compared to wild type, mice immunized with Mutant C showed 2.5-fold lower titres of IgG and 3.5-fold lower titres of IgM. At the same time Mutants B, C and D showed 2-3 fold less binding to pre-existing anti-asparaginase antibodies in samples collected from primary ALL patients undergoing asparaginase therapy. Similarly mutants B, C and D showed approximately 2-fold less binding to pre-existing anti-asparaginase antibodies in samples collected from relapsed ALL patients. Pharmacokinetic profiling showed that half life of Mutant A (267.28 ± 9.74), Mutant B (213.29 ± 6.53) and Mutant D (273.83 ± 35.45) was significantly longer than the wild type (102.17 ± 7.7). In acute toxicity study, we did not observe any significant toxicity of the mutants over the wildtype EcA. The findings are summarized in the figure.ConclusionConsidering the immunogenicity, antigenicity and pharmacokinetics, mutant D emerged as a potent drug candidate for further development in the treatment of ALL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A closer look on the variety and abundance of the faecal resistome of wild boar

Antimicrobial resistance (AMR) is a serious problem for public and animal health, and also for the environment. Monitoring and reporting the occurrence of AMR determinants and bacteria with the potential to disseminate is a priority for health surveillance programs around the world and critical to the One Health concept. Wildlife is a reservoir of AMR, and human activities can strongly influence their resistome.The main goal of this work was to study the resistome of wild boar faecal microbiome, one of the most important game species in Europe using metagenomic and culturing approaches. The most abundant genes identified by the high-throughput qPCR array encode mobile genetic elements, including integrons, which can promote the dissemination of AMR determinants. A diverse set of genes (n = 62) conferring resistance to several classes of antibiotics (ARGs), some of them included in the WHO list of critically important antimicrobials were also detected. The most abundant ARGs confer resistance to tetracyclines and aminoglycosides. The phenotypic resistance of E. coli and Enterococcus spp. were also investigated, and together supported the metagenomic results.As the wild boar is an omnivorous animal, it can be a disseminator of AMR bacteria and ARGs to livestock, humans, and the environment. This study supports that wild boar can be a key sentinel species in ecosystems surveillance and should be included in National Action Plans to fight AMR, adopting a One Health approach.

Pseudomonas aeruginosa as a priority group representative of bacteria with multiple antibiotic resistance

The aim: the aim of the research is an analytical review of the scientific literature on Рseudomonas aeruginosa as a priority group representative of bacteria with multiple antibiotics resistance.&#x0D; Materials and methods. The research was conducted by the method of scientific literature open source analysis: PubMed, Elsevier, electronic resources of the National Library named after V. I. Vernadsky and others.&#x0D; Results. The problem of antibiotic resistance is rightly called the “apocalypse of the XXI century”.&#x0D; P. aeruginosa bacteria are characterized by a very high natural ability to form resistant forms to antimicrobial drugs due to the formation of specific resistance genes, the ability to resist the entry of antibiotics into the cell or remove antibiotics from the cell, and form biofilms.&#x0D; A characteristic feature of the epidemic and epizootic processes of P. aeruginosa, as an opportunistic ubiquitous microorganism is host-pathogenic interaction - the interaction of the pathogen with the host organism. The peculiarity of this bacterium is opportunism and long-term persistence in the body of the host and in the environment.&#x0D; The global trend towards the spread of antibiotic-resistant gram-negative bacteria, including P. aeruginosa, underscores the need to develop comprehensive response strategies targeting all sectors of health.&#x0D; Conclusions. Bacteria P. aeruginosa is classified in 1th Critical Group of the WHO list of resistant to antibiotics "priority pathogens". Among the main reasons that contribute to the emergence of resistance are irrational antibiotic therapy in both humans and animals, and the use of antibiotics as growth stimulants in animal husbandry.&#x0D; While more R&amp;D is vital, alone, it cannot solve the problem. To address resistance, there must also be better prevention of infections and appropriate use of existing antibiotics in humans and animals, as well as rational use of any new antibiotics that are developed in future.&#x0D; New methods of combating antibiotic resistance and antibacterial substances, alternatives to antibiotics (biofilm-destroying drugs, antimicrobial peptides (AMP), bacteriophages, nanopreparations, etc.) can make a positive contribution to overcoming the multiple drug resistance of gram-negatives

Structure and lipid dynamics in the maintenance of lipid asymmetry inner membrane complex of A. baumannii

Multi-resistant bacteria are a major threat in modern medicine. The gram-negative coccobacillus Acinetobacter baumannii currently leads the WHO list of pathogens in critical need for new therapeutic development. The maintenance of lipid asymmetry (MLA) protein complex is one of the core machineries that transport lipids from/to the outer membrane in gram-negative bacteria. It also contributes to broad-range antibiotic resistance in several pathogens, most prominently in A. baumannii. Nonetheless, the molecular details of its role in lipid transport has remained largely elusive. Here, we report the cryo-EM maps of the core MLA complex, MlaBDEF, from the pathogen A. baumannii, in the apo-, ATP- and ADP-bound states, revealing multiple lipid binding sites in the cytosolic and periplasmic side of the complex. Molecular dynamics simulations suggest their potential trajectory across the membrane. Collectively with the recently-reported structures of the E. coli orthologue, this data also allows us to propose a molecular mechanism of lipid transport by the MLA system.

Assessment of Essential Newborn Care Practices in the Squatter Settlements of Islamabad Capital Territory in Pakistan

Background: While Pakistan has shown progress in reducing child mortality, significant challenges exist in reducing neonatal mortality rate. WHO recommends a package of “essential newborn care” practices based on effective coverage to improve newborn survival. Aim: To assess the coverage of Essential Newborn Care (ENC) as defined by WHO guidelines, in the squatter settlements of Islamabad Capital Territory (ICT). Methods: This cross-sectional survey gathered community-based data on newborn care practices from 416 eligible mothers within randomly selected squatter settlements of ICT. Three composite outcomes (safe cord care, optimal thermal care and good neonatal feeding) were generated by combining individual practices from a list of WHO recommended ENC practices. ENC was considered when all practices within each domain of safe cord care, ideal thermal care and good neonatal feeding were fulfilled. Results: Only 2.9% of newborns received all components of WHO recommended ENC. Seventeen percent newborns received safe cord care, 40.4% received optimal thermal care and 28.8% followed WHO recommended neonatal feeding practice. Various cultural and societal misconceptions were reported which translate into harmful practices for newborn care. Conclusion: The study highlighted an extremely low coverage level of effective essential newborn care. Pakistan needs to address issues of quality care for newborns through policy and programs which focus on Maternal, Newborn, and Child Health (MNCH) continuum of care. It needs a concerted effort at the grass root level, especially training front line workers to educate mothers on various cultural and societal misconceptions that translate into harmful practices for newborns.

Antibiotic Prescription in Veterinary Consultations in Bhutan: A Retrospective Cross-Sectional Study.

The veterinary prescription of antibiotics in low- and middle-income countries (LMIC) remains largely undocumented. In Bhutan, however, the national veterinary service keeps records of their activities and prescriptions, which offer an opportunity to establish a benchmark to assess the use of these agents in this and other LMIC. A cross-sectional retrospective study was designed and 2,266 handwritten veterinary records from 2017 were sampled from 23 animal health premises (AHPs) to estimate individual and an overall proportion of consultations that resulted in an antibiotic prescription. The frequency of antibiotic prescription per species, type of AHP, and according to WHO's AWaRe index and OIE list of priority antimicrobials were also explored. It was estimated that 31% (95% confidence interval: 29–33%; intracluster correlation: 0.03) of the veterinary consultations resulted in an antibiotic prescription. The incidence of antibiotic prescription was highest in consultations of poultry across AHP. Across species, diarrhea and wounds were frequently treated with broad-spectrum antibiotics including sulfonamides, tetracyclines, trimethoprim + sulfa, and penicillin. Between 45% and 70% antibiotics prescribed correspond to AWaRe's access group and up to 25% to AWaRe's watch group. Over 70% of antibiotics dispensed in veterinary consultations for any species correspond to the OIE's veterinary critically important antimicrobial agents. Overall, the study demonstrated positive features of veterinary antimicrobial stewardship in Bhutan, given the conservative proportion of consultation that results in this type of prescription and the type of antibiotic prescribed. Although the veterinary service closely follows the Bhutanese Standard Treatment Guidelines, the prescription of antibiotics to key species should be closely monitored. Our study suggests that further improvements of antibiotic stewardship can be achieved through standardisation of antibiotic prescription to some species, a revision of the guidelines toward reducing the prescription of antibiotics of high relevance for human medicine, and by including details of clinical investigation, use of tests, and treatment outcomes in veterinary consultation records.

Challenge in the Discovery of New Drugs: Antimicrobial Peptides against WHO-List of Critical and High-Priority Bacteria.

Bacterial resistance has intensified in recent years due to the uncontrolled use of conventional drugs, and new bacterial strains with multiple resistance have been reported. This problem may be solved by using antimicrobial peptides (AMPs), which fulfill their bactericidal activity without developing much bacterial resistance. The rapid interaction between AMPs and the bacterial cell membrane means that the bacteria cannot easily develop resistance mechanisms. In addition, various drugs for clinical use have lost their effect as a conventional treatment; however, the synergistic effect of AMPs with these drugs would help to reactivate and enhance antimicrobial activity. Their efficiency against multi-resistant and extensively resistant bacteria has positioned them as promising molecules to replace or improve conventional drugs. In this review, we examined the importance of antimicrobial peptides and their successful activity against critical and high-priority bacteria published in the WHO list.

Where old is gold again: antidepressants in Nepal, 1961–2021

The so-called psychopharmaceutical revolution began in the 1950s, with apparently ever better drugs coming to market. Amitriptyline (Elavil), introduced in 1961, was one of the first ‘antidepressants’. Over the next decades, many other antidepressants came out, including fluoxetine (Prozac). In the 2000s, critiques that antidepressants were no better than placebos could not slow down a massive global rise of prescriptions. In 2018, a large meta-analysis of clinical trials argued that antidepressants were indeed better than placebos, but that none of the new drugs was as effective as the old amitriptyline. 1961 is also the birth year of psychiatry in the Himalayan country of Nepal. Since the 1960s, Nepali psychiatrists have been using amitriptyline as their first-line drug. The inclusion of amitriptyline in the first WHO list of Essential Drugs (1977) cemented its status. All the ‘new’ psychopharmaceuticals came to Nepal, but they never displaced the ‘old’ amitriptyline. No other drug could beat amitriptyline's affordability, availability, and efficacy for the typical Nepali depression patient: a ‘somatizer’ who suffers from multiple bodily aches, insomnia, and anxiety. Fieldwork with Nepali psychiatrists reveals the tenacity of local affordances over global changes in evidence and health policy.

Antimicrobial drug usage pattern in poultry farms in Nigeria: implications for food safety, public health and poultry disease management.

Good antimicrobial drug stewardship in food‑producing animals boosts productivity and limits transmission of zoonotic pathogens, but the imprudent usage is counterproductive. A nation‑wide survey to determine the pattern of antimicrobial drug usage in poultry was therefore conducted across 12 of the 36 States in Nigeria. The survey was conducted using structured questionnaire designed to elicit information on socio‑demographics, pattern of antimicrobial drug usage and awareness of the consequences of imprudent use of antimicrobials in food‑producing animals, among 2,402 randomly selected poultry farmers. Critically important antimicrobials, belonging to the WHO's lists of 'Highest' and 'High' priority antibiotics, were administered sub‑therapeutically for prophylaxis and growth enhancement purposes. Many diseases that warranted the antimicrobial administration were of viral etiology. Only 64.2% of the farmers administered the drug based on veterinary doctors' prescription. Majority (62.3%) of the farmers did not observe recommended withdrawal period after the drug administration. Awareness of the respondents on consequences of non‑prudent agricultural use of antimicrobials was generally poor. There is need for enlightenment of the farmers on the benefits of prudent agricultural use of antimicrobials. Immediate discontinuation of sale of essential antimicrobials as over‑the‑counter drugs is imperative to safeguard their therapeutic efficacy and curtail spread of antimicrobial‑resistance organisms.

#95: Clinical Profile and Outcome of Pediatric Acute Lymphoblastic Leukemia Patients with Tuberculosis at the Philippine General Hospital

Abstract Background The Philippines remains one of the countries on the WHO list of high-burden countries for tuberculosis (TB), and malignancy has long been recognized as a risk factor for this disease. This report describes the clinical profile and outcomes of pediatric patients with acute lymphoblastic leukemia (ALL) diagnosed with tuberculosis. Methods Medical records of pediatric patients with ALL consulting at the University of the Philippines – Philippines General Hospital diagnosed from January 2015 to December 2017 (excluding those with concomitant HIV infection) were reviewed. Those diagnosed with tuberculosis infection were further analyzed, obtaining demographic data, results of diagnostics, and treatment. Results Out of 102 patients, 5 were found to have tuberculosis, all of them being male, with an average age of 7.2 years old. All cases were pulmonary, with one patient having multi-drug-resistant TB. PPD was positive in 4 cases, with indurations measuring &amp;gt;10mm, while chest radiographs showed nonspecific findings for 3 patients. Of 3 patients who underwent sputum AFB testing, one had a positive result. While 1 patient was diagnosed with TB and ALL concurrently, majority of patients were diagnosed after entering remission. Three patients completed 6 months of TB treatment, while 1 patient is still on medication for multi-drug-resistant tuberculosis. One patient abandoned treatment. Conclusion In this group of ALL patients, malnutrition and corticosteroid use were not found to be independent risk factors for TB. As TB disease may be due to reactivation of latent TB infection (LTBI) during immunosuppression, screening for LTBI may be a worthwhile strategy to decrease morbidity. Transmission precautions are emphasized to reduce acquired TB infection in immunocompromised populations.

Improving the Inhibitory Effect of Phages against Pseudomonas aeruginosa Isolated from a Burn Patient Using a Combination of Phages and Antibiotics.

Antibiotic resistance causes around 700,000 deaths a year worldwide. Without immediate action, we are fast approaching a post-antibiotic era in which common infections can result in death. Pseudomonas aeruginosa is the leading cause of nosocomial infection and is also one of the three bacterial pathogens in the WHO list of priority bacteria for developing new antibiotics against. A viable alternative to antibiotics is to use phages, which are bacterial viruses. Yet, the isolation of phages that efficiently kill their target bacteria has proven difficult. Using a combination of phages and antibiotics might increase treatment efficacy and prevent the development of resistance against phages and/or antibiotics, as evidenced by previous studies. Here, in vitro populations of a Pseudomonas aeruginosa strain isolated from a burn patient were treated with a single phage, a mixture of two phages (used simultaneously and sequentially), and the combination of phages and antibiotics (at sub-minimum inhibitory concentration (MIC) and MIC levels). In addition, we tested the stability of these phages at different temperatures, pH values, and in two burn ointments. Our results show that the two-phages-one-antibiotic combination had the highest killing efficiency against the P. aeruginosa strain. The phages tested showed low stability at high temperatures, acidic pH values, and in the two ointments. This work provides additional support for the potential of using combinations of phage–antibiotic cocktails at sub-MIC levels for the treatment of multidrug-resistant P. aeruginosa infections.

List of People Who Reviewed for JMS in 2020

List of People Who Reviewed for JMS in 2020

Human Immunodeficiency Virus type 1 Drug Resistance Mutations in Patients Failing Antiretroviral Therapy in Lebanon from 2009 to 2013

Background: Antiretroviral drug resistance remains a significant problem in the clinical management of patients infected with the Human Immunodeficiency Virus type-1. Aim: This study investigates and reports data on the molecular characterization of HIV-1 isolates from patients who are in a state of therapy failure. Methods: This is a retrospective study conducted on 65 patients in therapy failure. Inclusion criteria included patients diagnosed as being in therapy failure between the years 2009 and 2013. We defined ART failure as either a failure to achieve viral suppression or a failure to detect viral loads below 500 copies/mL after virological suppression in at least two plasma samples. We used the published WHO list for surveillance of transmitted resistance and the Stanford HIV Drug Resistance Database to identify drug resistance mutations. Results: 65% of the participants had at least one drug resistance mutation (DRM). 12% of the population sampled had resistance to only one ART class, 32% presented with resistance to two classes of antiretroviral drugs, and 20% had resistance to all three classes of drugs. The prevalence of nucleoside transcriptase inhibitor (NRTI) mutations was 55%, the most common DRM being M184V. The prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations was 58%, with the most common mutation being the K103N mutation. The prevalence of protease inhibitors drug resistance mutations was 23%, with mutations V82A and I47V being present in 10% of the study population. Conclusion: Our study is the first molecular characterization of DRM emergence in HIV-1 strains from patients failing antiretroviral therapy in Lebanon. Continuous monitoring of resistance patterns for HIV in the country is necessary to tackle the emergent drug resistance.

RANGE OF DIRECT-ACTING ANTI-VIRAL DRUGS FOR TREATMENT OF CHRONIC HEPATITIS C LISTED BY THE WORLD HEALTH ORGANIZATION, THE RUSSIAN FEDERATION AND THE VOLGOGRAD REGION

Viral hepatitis is an international public health threat. With the adoption of the UN Assembly Resolution in 2016, the problem of hepatitis no longer remains in the shadows. An important step towards eradicating chronic hepatitis C (CHC) is the introduction of direct-acting antiviral drugs into treatment standards. They appeared in the WHO List of Essential Medicines for the first time since 2014. On the territory of the Russian Federation, the number of registered international nonproprietary names increased in 2014-2020 by 3.5 times and at the time of 2020 it was 10. Direct-acting antiviral drugs were included in the Vital and most Essential Drugs List since 2017 (10 %), and by 2020 this indicator had increased by 7 times. In general, in the Russian Federation since 2017, there has been progress in solving a global problem through the use of more effective drugs, which cannot be said about the regions of our country. So, in the Volgograd region, not a single Direct-acting antiviral drugs of preferential leave for the treatment of CHC on an outpatient basis has been registered.

List of People Who Reviewed for this Special Issue

List of People Who Reviewed for this Special Issue

Trends in antimicrobial use in livestock animals in Pakistan

Background: For decades, antimicrobials has been used in livestock for treatment and as growth promotor. It has been suggested that overall burden of antimicrobial resistance has increased due to contribution of antimicrobial use (AMU) from animals. Surveillance of AMU in animal production system is one of the key objectives of Pakistan National Action Plan on AMR. Therefore, aims of this study was to monitor AMU in commercial dairy and poultry farms in Pakistan. Methods and materials: Two large corporate commercial dairy farms and two commercial broilers farms in Pakistan were selected for monitoring AMU for a period of one year. For chicken, the amount of antimicrobial administered by the farmer to produce 1 kg of live chicken was estimated by dividing the total amount of antimicrobial used (milligrams) by the estimated body weight (kg) of the bird. In case of dairy, we used Antimicrobial Treatment Incidence (ATI) metrics, where, total amount of active-ingredient used in terms of the number of treatments as per the labelled daily dose animal (LDDA) over 1000 cows per day is evaluated as ATI. Results: In poultry, the most commonly used antimicrobials for therapeutic purposes were colistin (65 mg/kg), doxycycline (51.81 mg/kg) and tylosin (44.7 mg/kg). Colistin was used most frequently in all the 12 flocks on two poultry farms. In dairy cow, aminoglycosides (11.05 cow-days), penicillins (8.29 cow-days), and tetracyclines (8.1 cow-days) were the most frequently used antimicrobial-classes. A total of 6/11 (54.5%) antimicrobials belonged to WHO list of critically important for human use with highest priority. Conclusion: Intensive livestock farming in Pakistan is consuming alarmingly high amount of antimicrobials critical for human healthcare. These data provide a reference for further surveillance and research initiatives aiming to reduce AMU in food animals.

Antibiotic use prior to seeking medical care in patients with persistent fever: a cross-sectional study in four low- and middle-income countries

ObjectivesCommunity-level antibiotic use contributes to antimicrobial resistance, but is rarely monitored as part of efforts to optimize antibiotic use in low- and middle-income countries (LMICs). We investigated antibiotic use in the 4 weeks before study inclusion for persistent fever. MethodsThe NIDIAG-Fever (Neglected Infectious diseases DIAGnosis-Fever) study investigated aetiologies of infections in patients ≥5 years old with fever ≥1 week in six healthcare facilities in Cambodia, the Democratic Republic of the Congo (DRC), Nepal, and Sudan. In the present nested cross-sectional study, we describe prevalence and choice of antibiotics before and at study inclusion, applying the Access/Watch/Reserve (AWaRe) classification of the WHO List of Essential Medicines. Factors associated with prior antibiotic use were analysed. ResultsOf 1939 participants, 428 (22.1%) reported the prior use of one or more antibiotics, ranging from 6.3% (24/382, Cambodia) to 35.5% (207/583, Nepal). Of 545 reported antibiotics, the most frequent were Watch group antibiotics (351/545, 64.4%), ranging from 23.6% (DRC) to 82.1% (Nepal). Parenteral administration ranged from 5.9% to 69.6% between study sites. Antibiotic use was most frequent among young patients (5–17 years of age; risk ratio 1.42, 95%CI 1.19–1.71) and men (RR 1.29; 95%CI 1.09–1.53). No association was found with specific symptoms. Of 555 antibiotics started before study inclusion, 275 (49.5%) were discontinued at study inclusion. ConclusionsWatch antibiotics were frequently used, and discontinued upon study inclusion. The antibiotic use frequency and choice varied importantly between LMICs. Data on local antibiotic use are essential to guide efforts to optimize antibiotic use in LMICs, should not be restricted to hospitals, and need to take local healthcare utilization into account.