WHO List Research Articles

A review of noma cases in a tertiary hospital located in a conflict endemic region in Nigeria

ABSTRACT Noma, a neglected tropical disease (NTD), is a preventable oro-facial gangrenous infection causing destruction of oro-facial tissues if untreated. This descriptive study was conducted in North-Eastern Nigeria which has witnessed armed insurgency increasing risk of noma. Data was obtained from patients’ records at a tertiary hospital after a dental educational outreach using radio and visits to the hospital's ante/postnatal clinics. Data analysis was conducted at 95% confidence interval with p≤ 0.05 considered significant. Records of 49 patients were retrieved but 31 (63.3%) were utilised due to poor documentation. Age ranged from 2–63 years. Children (0–16 years) and Adults (17–59 years) were 67.7% and 25.8% respectively. Males were 13 (41.9%) and females, 18 (58.1%). Poor oral hygiene and malnutrition were common findings. Stage (WHO Staging System) 2 (51.6%) and 4 (22.6%) were the most common presentation. Successfully managed and referred cases were 51.6% and 48.4% respectively. Successful management was associated with early stages of noma (p = <0.001). Children were most vulnerable. Outreaches using radio and education to pregnant women and nursing mothers can boost early presentation and better outcomes. Attention to case documentation and inclusion of noma into the WHO list of NTDs are recommended.

Pharmaceutical nanotechnology: Antimicrobial peptides as potential new drugs against WHO list of critical, high, and medium priority bacteria

Nanobiotechnology is a relatively unexplored area that has, nevertheless, shown relevant results in the fight against some diseases. Antimicrobial peptides (AMPs) are biomacromolecules with potential activity against multi/extensively drug-resistant bacteria, with a lower risk of generating bacterial resistance. They can be considered an excellent biotechnological alternative to conventional drugs. However, the application of several AMPs to biological systems is hampered by their poor stability and lifetime, inactivating them completely. Therefore, nanotechnology plays an important role in the development of new AMP-based drugs, protecting and carrying the bioactive to the target. This is the first review article on the different reported nanosystems using AMPs against bacteria listed on the WHO priority list. The current shortage of information implies a nanobiotechnological potential to obtain new drugs or repurpose drugs based on the AMP-drug synergistic effect.

Loa loa in the Vitreous Cavity of the Eye: A Case Report and State of Art.

ABSTRACT.Loa loa is a filarial nematode responsible for loiasis, endemic to West–Central Africa south of the Sahara and transmitted by flies. This study reports a case of L. loa in the vitreous cavity of the eye of a young patient, along with an in-depth literature review. A 22-year-old woman from Cameroon who migrated from Cameroon to Italy was referred to the Emergency Ophthalmology Department at Policlinico di Bari in July 2021 with the presence of a moving parasite in the subconjunctiva of the left eye. A recent onset of a papular lesion on the dorsal surface of the right wrist and a nodular lesion in the scapular region were detected. L. loa filariasis was diagnosed based on anamnestic data, clinical and paraclinical signs, and a parasitological test confirming the presence of microfilariae in two blood samples collected in the morning of two different days. Because of the unavailability of diethylcarbamazine (DEC), albendazole (ALB) 200 mg twice daily was administered for 21 days. A mild exacerbation of pruritus occurred during treatment, but resolved with the use of an antihistamine. A single dose of 12 mg ivermectin was prescribed at the end of the treatment with albendazole. Unlike other endemic parasite infections, L. loa is not included in the Global Program to Eliminate Lymphatic Filariasis, because it is not mentioned in the WHO and CDC list of neglected tropical diseases. This can result in an overall risk of lack of attention and studies on loiasis, with lack of data on global burden of the disease.

An intervention to reduce stigma and improve management of depression, risk of suicide/self-harm and other significant emotional or medically unexplained complaints among adolescents living in urban slums: protocol for the ARTEMIS project

BackgroundThere are around 250 million adolescents in India. Adolescents are vulnerable to common mental disorders with depression and self-harm accounting for a major share of the burden of death and disability in this age group. Around 20% of children and adolescents are diagnosed with/ or live with a disabling mental illness. A national survey has found that suicide is the third leading cause of death among adolescents in India. The authors hypothesise that an intervention involving an anti-stigma campaign co-created by adolescents themselves, and a mobile technology-based electronic decision support system will help reduce stigma, depression, and suicide risk and improve mental health for high-risk adolescents living in urban slums in India.MethodsThe intervention will be implemented as a cluster randomised control trial in 30 slum clusters in each of the cities of Vijayawada and New Delhi in India. Adolescents aged 10 to 19 years will be screened for depression and suicide ideation using the Patient Health Questionnaire (PHQ-9). Two evaluation cohorts will be derived—a high-risk cohort with an elevated PHQ-9 score ≥ 10 and/or a positive response (score ≥ 2) to the suicide risk question on the PHQ-9, and a non-high-risk cohort comprising an equal number of adolescents not at elevated risk based on these scores.DiscussionThe key elements that ARTEMIS will focus on are increasing awareness among adolescents and the slum community on these mental health conditions as well as strengthening the skills of existing primary healthcare workers and promoting task sharing. The findings from this study will provide evidence to governments about strategies with potential for addressing the gaps in providing care for adolescents living in urban slums and experiencing depression, other significant emotional or medically unexplained complaints or increased suicide risk/self-harm and should have relevance not only for India but also for other low- and middle-income countries.Trial statusProtocol version – V7, 20 Dec 2021Recruitment start date: tentatively after 15th July 2022Recruitment end date: tentatively 14th July 2023 (1 year after the trial start date)Trial registrationThe trial has been registered in the Clinical Trial Registry India, which is included in the WHO list of Registries (https://www.who.int/clinical-trials-registry-platform/network/primary-registries) Reference No. CTRI/2022/02/040307. Registered on 18 February 2022.The tentative start date of participant recruitment for the trial will begin after 15th July 2022.

Use of cefepime/sulbactam in the treatment of infections caused by carbapenem-resistant bacteria

Cefepime/sulbactam is a combined antibiotic with a wide spectrum of antimicrobial activity, including cefepime, the fourth-generation cephalosporin, and sulbactam, the beta-lactamase inhibitor, in a 1:1 ratio. Cefepime/sulbactam has a bactericidal effect: it causes a disorder in cell wall synthesis due to blockade of transpeptidase and a disorder in the formation of cross-links in peptidoglycan [1]. Today, the problem of antibiotic resistance is growing rapidly. In the WHO list, a critically high level of priority for the development of new antibiotics is occupied by infections caused by ESBL-producing gram-negative bacteria that are resistant to cephalosporins, as well as carbapenem-resistant Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa [2]. Infections caused by multiresistant bacteria are characterized by a longer course, require prolonged hospitalization, are very difficult to treat with modern antibacterial drugs, and increase the risk of death [3]. In this regard, a deeper study of the action of individual antibacterial drugs and their combination with β-lactamase inhibitors in the treatment of diseases caused by multiresistant microorganisms is crucial.

Simple and Scalable Cathodic Synthesis of 1H-1-Hydroxyquninolin-4-ons and 4H-4-Hydroxy-1,2,4-benzothiadiazine-1,1-dioxides

Cathodic synthesis is a highly attractive technique for N,O bond reduction.[1] Especially, electro-reductions of nitro arenes enable the access to high-valuable products like nitrones and N-heterocycles.[2] These substances are in general unique structural motifs in natural products or in compounds with significant biological properties, such as antibiotic, antiplasmodial, antimycotic, antihypertensive, hyperglycemic and cytotoxic activities.[3] Commonly used synthesis methods require large amounts of metallic reducing agents, expensive transition metal catalysts, or hazardous oxidizers in case the corresponding heterocycles are accessible otherwise.[4] Several examples have been described with constant potential conditions using mercury or sacrificial lead electrodes.[5] Due to cathodic corrosion of heavy metals, this proves to be a critical aspect and mercury is banned in the most countries for technical applications.[6] Therefore, the urge for more sustainable processes is of high focus.We describe an access to 1H-1-hydroxyquninolin-4-ons by cathodic reaction of nitrobenzoyl acetones synthesized from broad available nitrobenzoic acids. Using metal-free BDD cathodes (boron-doped diamond), sulfuric acid as a simple supporting electrolyte, in addition to an aqueous electrolyte system with an environmentally benign co-solvent agree with sustainable and green aspects. The scalability under constant current conditions in an undivided cell has been shown in a twentyfold scale. The electrochemical synthesis protocol was applied to 18 examples including the antibiotic substance HQNO (1H-2-heptyl-1-hydroxy quinolin-4-ons) and various precursors for enzymatic aurachine synthesis.[7] Furthermore, we developed a method to a novel substance class of 4H-4-hydroxy-1,2,4-benzothiadiazine-1,1-dioxides. Reduction of the nitro precursors applying BDD cathodes result in hydroxylamines using divided cells with glass frits as separators. The applicability of this electro-reductive cyclisation is demonstrated by the synthesis of a broad product scope with activated, deactivated, labile and sterically demanding substitution patterns for potential further modification towards pharmaceutical applications.[8] Particularly, we described the synthesis of the N-Hydroxy analogues of diazoxide, a medication on the WHO list of essential medicines.[8,9] Studies on the biological activities of these new compounds are currently performed.

The polyamino-isoprenyl potentiator NV716 revives disused antibiotics against Gram-negative bacteria in broth, infected monocytes, or biofilms, by disturbing the barrier effect of their outer membrane

Potentiators can improve antibiotic activity against difficult-to-treat Gram-negative bacteria like Escherichia coli, Klebsiella pneumoniae or Acinetobacter baumannii. They represent an appealing strategy in view of the paucity of therapeutic alternatives in case of multidrug resistance. Here, we examine the ability of the polyamino-isoprenyl compound NV716 to restore the activity of a series of disused antibiotics (rifampicin, azithromycin, linezolid, fusidic acid, novobiocin, chloramphenicol, and doxycycline, plus ciprofloxacin as an active drug) against these three species in planktonic cultures, but also in infected human monocytes and biofilms and we study its underlying mechanism of action. NV716 considerably reduced the MICs of these antibiotics (2–11 doubling dilutions), the highest synergy being observed with the more lipophilic drugs. This potentiation was related to a strong interaction of NV716 with LPS, ensuing permeabilization of the outer membrane, and leading to an increased accumulation of the antibiotics inside bacteria. Moreover, NV716 increased the relative potency of all drugs against intracellular infection by the same bacteria as well as their maximal efficacy, probably related to an improvement of antibiotic activity against persisters. Lastly, NV716 also enhanced rifampicin activity against biofilms from these three species. All these effects were observed at sub-MIC concentrations of NV716 (and thus unrelated to a bactericidal effect), and in conditions for which no toxicity was evidenced towards eukaryotic cells. Altogether, these data highlight for the first time the potential interest of NV716 as an adjuvant against these Gram-negative pathogens placed in the priority list of WHO for search of new therapies.

The state of tuberculosis in South Africa: what does the first national tuberculosis prevalence survey teach us?

South Africa is among WHO's list of 30 high-burden tuberculosis countries and has one of the highest incidence rates of notified tuberculosis in the world.1 In The Lancet Infectious Diseases, Sizulu Moyo and colleagues2 report their findings from the first national tuberculosis prevalence survey in South Africa, which is a very important study that provides improved understanding of the true extent of tuberculosis and helps to identify groups who might be underserved by health services and where tuberculosis might be undiagnosed.

Is noma a neglected/overlooked tropical disease?

Noma is a debilitating orofacial necrotizing bacterial disease that disproportionately affects impoverished malnourished persons, particularly young children, the vast majority of whom live in tropical and subtropical areas in sub-Saharan Africa. It has a very high mortality rate; causes significant physical and psychological morbidity, stigmatization and social discrimination; could be prevented, controlled and indeed eliminated by common public health interventions; and is overlooked with regard to public health awareness, in-depth scientific research activities and allocation of funding for prevention, treatment and research.According to the WHO, noma comprises five sequential ‘stages’: (1) necrotizing gingivitis, (2) edema, (3) gangrene, (4) scarring and (5) sequelae. This WHO staging of noma is contentious, leading to diagnostic confusion with misestimation of the number of noma cases reported in epidemiological studies. We therefore suggest a simpler, more practical and scientifically valid two-stage classification comprising only (1) acute noma and (2) arrested noma.Noma meets all the WHO criteria for classification as a neglected tropical disease (NTD). Most survivors of noma live with gross physical disfigurement and disability, and with impaired psychosocial functioning, so they are very often stigmatized and unjustifiably discriminated against. Owing to the paucity of evidence-based epidemiological data on noma, the relatively low number of people affected worldwide, and its apparently limited geographic distribution, noma does not yet feature on the WHO's list of NTDs, or on any global health agenda, and thus has not become a health priority for global action. We strongly support the inclusion of noma within the WHO list of NTDs. Without doubt this will increase the awareness of noma among healthcare providers and promote the systematic international accumulation and recording of data about noma.

Evaluation and treatment of acute migraine in the emergency department

Headache is one of the most common neurological complaints admitted to emergency deprtment (ED). In different studies, the proportion of patients admitted to the emergency room due to nontraumatic headache is around 0.5-4.5%. Most of the patients with headache (22-55%) are benign primary headaches. Among primary headaches, migraine is the most common reason for admission to the emergency department. As can be seen in all ages, it usually occurs at a young age. The male to female ratio is 3: 1 and its prevalence is estimated to be 5% in men and 15-17% in women. According to WHO's list of common diseases, loss of functionality and disability, migraine attacks are in the fifth place in women and among the first twenty diseases in men. Therefore, it is very important to manage migraine attacks in the emergency room. When we look at the previous reviews on this subject, we can deduce that they are not always appropriate for emergency physicians, since most of the articles are quite long and detailed. Our aim in this review is to give enough information in the light of current information about migraine headache that emergency physicians will need.

Enterococcal biofilm-A nidus for antibiotic resistance transfer?

Enterococci, which are on the WHO list of priority pathogens, are commonly encountered in hospital acquired infection and are becoming increasing significant due to the development of strains resistant to multiple antibiotics. Enterococci are also important microorganisms in the environment, and their presence is frequently used as an indicator of faecal pollution. Their success is related to their ability to survive within a broad range of habitats and the ease by which they acquire mobile genetic elements, including plasmids, from other bacteria. The enterococci are frequently present within a bacterial biofilm, which provides stability and protection to the bacterial population along with an opportunity for a variety of bacterial interactions. Enterococci can accept extrachromosomal DNA both from within its own species and from other bacterial species, and this is enhanced by the proximity of the donor and recipient strains. It is this exchange of genetic material that makes the role of biofilms such an important aspect of the success of enterococci. There remain many questions regarding the most suitable model systems to study enterococci in biofilms and regarding the transfer of genetic material including antibiotic resistance in these biofilms. This review focuses on some important aspects of biofilm in the context of horizontal gene transfer (HGT) in enterococci.

Tuberculosis contact investigation in African Portuguese-speaking countries at End TB Strategy era: a scoping review

ObjectivesThe contact investigation of tuberculosis (TB) index case is one of the critical elements pointed by the WHO to reach the end of the TB epidemic. The scoping review aimed...

Optimising tuberculosis care for refugees affected by armed conflicts

Globally, tuberculosis remains a leading cause of death from an infectious disease. 1 WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021https://www.who.int/publications/i/item/9789240037021Date accessed: March 9, 2022 Google Scholar 2022's theme for World TB Day, on March 24, is “Invest to End TB. Save Lives”. Tuberculosis control requires a pragmatic, tailored, multipronged approach to diagnose and treat all people with tuberculosis disease (drug-susceptible, drug-resistant, multidrug-resistant, and extensively drug-resistant tuberculosis) and latent tuberculosis infection, to prevent transmission, and to mitigate the risk of drug resistance. The COVID-19 pandemic has disrupted health services and derailed already overburdened tuberculosis control programmes worldwide, including in eastern Europe, substantially setting back progress 1 WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021https://www.who.int/publications/i/item/9789240037021Date accessed: March 9, 2022 Google Scholar towards achieving the UN Sustainable Development Goal (SDG) and End TB targets. 2 Migliori GB Thong PM Alffenaar JW et al. Gauging the impact of the COVID-19 pandemic on tuberculosis services: a global study. Eur Respir J. 2021; 582101786 Crossref PubMed Scopus (41) Google Scholar The invasion of Ukraine by Russia, and the ongoing armed conflict, is having hugely damaging effects on health services, health infrastructure, and personnel, and further diminishes hope of achieving End TB targets for eastern Europe—now a seemingly insurmountable task. Although incidence rates of tuberculosis in Ukraine have gradually decreased over the past decade, Ukraine features in the WHO list of 20 countries with the highest estimated number of people with incident drug-resistant tuberculosis and it has one of the highest rates of HIV–tuberculosis co-infection and latent multidrug-resistant tuberculosis infection in Europe. 1 WHOGlobal tuberculosis report 2021. World Health Organization, Geneva2021https://www.who.int/publications/i/item/9789240037021Date accessed: March 9, 2022 Google Scholar Drug-resistant tuberculosis is difficult to diagnose, expensive to treat, requires long-term treatment, has high mortality, and requires careful follow-up to monitor adverse drug side-effects and ensure a cure.

Study of controlled migration of cadmium and lead into foods from plastic utensils for children.

Lead (Pb) is a highly neurotoxic chemical element known for reducing intelligence quotient (IQ) and promoting antisocial behavior in children and adolescents, while cadmium (Cd) is a carcinogenic bioaccumulative element. Both these metals are included in the priority pollutant list of the United States Environmental Protection Agency and in the WHO List of Chemicals of Major Public Health Concern, where contaminated foods and beverages are the most common pathways of exposure. The objective of this study was to determine total Cd and Pb levels in colored plastic utensils (cups, mugs, bowls, feeding bottles, and plates) for use by children and to measure the specific migration of these elements into beverages and foods. Total contaminant levels were determined using a handheld X-ray fluorescence analyzer. Specific migration tests were conducted using the simulant solutions acetic acid 3% (m/v) and water. Migration levels were determined by ICP-MS. Specific migration tests for Pb were also performed on commercially available samples (cola soft drink, orange juice, vinegar, and milk), with levels determined by graphite-furnace atomic absorption spectrometry (GF-AAS). A total of 674 utensils were analyzed in loco at major commercial centers in Greater São Paulo, of which 87 were purchased for containing Cd and Pb concentrations above permitted limits. Mean concentrations of the metals detected in the purchased utensils were 1110ppm for Pb and 338ppm for Cd. For specific migration assays, Pb levels were 187, 13, and 380 times above the permitted limit (0.01mg.kg -1) for acetic acid, water, and orange juice, respectively. Cd levels were 50 and 2.4 times above the maximum permitted limit (0.005mg.kg -1) for acetic acid and water, respectively. The districts where the utensils were purchased were grouped according to their social vulnerability index and compared using ANOVA. Pb levels were different between low and medium/high social vulnerability groups (p = 0.006). The findings corroborate the initial hypothesis that these utensils constitute a major source of exposure to PTEs such as Cd and Pb, pointing to the need for stricter regulation and inspection by the Brazilian regulatory agencies.

Ameliorative role of Syzygium aromaticum aqueous extract on synaptosomal tyrosine hydroxylase activity, oxidative stress parameters, and behavioral changes in lead-induced neurotoxicity in mice.

This study reports the protective role of the aqueous extract of Syzygium aromaticum (ESA) against lead (Pb)-induced neurotoxicity in mice. Thirty male mice weighing between 18g and 25g were randomly divided into five groups. (1) Group 1 (control group), (2) group 2 (Pb-test group): was administered with a solution containing 0.1% (w/v) of lead acetate (PbAc), (3) group 3 (ESA+Pb100 group): was administered with 0.1% (w/v) of PbAc followed by 100mg/kg of S. aromaticum extract by gavage, (4) group 4 (ESA+Pb200): was administered with 0.1% (w/v) of PbAc followed by 200mg/kg of S. aromaticum extract, and (5) group 5 (ESA-group): was administered with 100mg/kg of S. aromaticum. Level of lead was determined by atomic absorption spectroscopy. Cerebral cortex synaptosomes prepared from mice administered orally with lead-acetate shown a significantly increased (p<.05) in tyrosine hydroxylase and protein carbonyl level and significantly decreased (p<.05) superoxide dismutase, glutathione reductase, and glutathione transferase activities. Also, there was a significant increase in brain lead concentration level, however, it was observed that S. aromaticum significantly reduced (p<.05) the level of lead at all tested doses. S. aromaticum rescued cerebral cortex synaptosomes from lead-induced neurotoxicity by relieving oxidative stress and abating elevated tyrosine hydroxylase activity. Moreover, S. aromaticum at the different dose grade (100mg and 200mg) abrogated the loss of motor performance in mice groups induced with lead. Altogether, our findings showed that S. aromaticum possesses antioxidant and neuro-modulatory potential against lead-induced neuronal damage. PRACTICAL APPLICATIONS: Environmental pollution with heavy metals is a known public health concern and their incremental concentrations in soil and water have risen to an unprecedented degree. Lead is one of the top 10 contaminants on the WHO's list of substances of greatest public health concern that impact the brain. However, exogenous natural bioactive supplements molecules could be one of the remedies to reduce Pb-induced toxicity. Our findings indicate therefore that, S. aromaticum could be a good fit for lowering Pb neurotoxicity and could be suggested as a neuroprotective molecule against neurodegenerative diseases involving catecholaminergic dysfunction induced by metallic elements.

List of People Who Reviewed for JMS in 2021

List of People Who Reviewed for JMS in 2021

Addition of direct oral anticoagulants to the World Health Organization model list of essential medicines for the treatment of atrial fibrillation: An African perspective.

Atrial fibrillation (AF) is a major cause of adverse cardiovascular outcomes, and its prevalence is fast rising in Africa. The advent of direct oral anticoagulants (DOACs) has been a major revolution for the prevention of AF-related stroke and systemic embolism given the significant advantage over vitamin K antagonists in terms of both efficacy, safety, and adherence. However, due to their high cost, equitable access to DOACs has been a challenge, especially in low- and middle-income countries. Therefore, the recent addition of DOACs to the 21st WHO list of essential medicines comes as good news. African governments should take this opportunity to scale up the accessibility to DOACs for African patients with AF. This could be achieved through advocacy, appropriate training of health professionals, task shifting, patient education, strategic partnership to increase availability and quality of low-cost generic drugs, and appropriate medico-economic studies.

Tertiary hospital sewage as reservoir of bacteria expressing MDR phenotype in Brazil.

High doses of antibiotics used in hospitals can affect the microbial composition of sewers, selecting resistant bacteria. In this sense, we evaluated the antibiotic resistance profile and the multiresistant phenotype of bacteria isolated in sewage from a tertiary hospital in the interior São Paulo state, Brazil. For bacteria isolation, 10 µL of sewage samples were sown in selective culture media and the isolates were identified using VITEK-2 automatized system. The antibiotic sensitivity test was performed by disk diffusion. High percentages of resistance were found for amoxicillin, ampicillin, ceftazidime, clindamycin, vancomycin and the multidrug-resistant phenotype (MDR) was attributed to 60.7% of the isolates. Our results show bacteria classified as critical/high priority by WHO List of Priority Pathogens (Enterococcus and Staphylococcus aureus resistant to vancomycin and Enterobacteriaceae resistant to carbapenems) in hospital sewage. Therefore, the implementation of disinfection technologies for hospital sewage would reduce the bacterial load in the sewage that will reach urban wastewater treatment plants, minimizing superficial water contamination and bacterial resistance spread in the environment.

Seasonal and Technological Shifts of the WHO Priority Multi-Resistant Pathogens in Municipal Wastewater Treatment Plant and Its Receiving Surface Water: A Case Study.

The present study was focused on the identification of multi-resistant bacteria from the WHO priority pathogens list in the samples taken from different stages of the full-scale municipal wastewater treatment plant and receiving water. Additionally, the seasonal variations of the selected multi-resistant pathogens were analyzed in the samples. In order to the aim of the study, the metagenomic DNA from the collected samples was isolated and sequenced. The samples were collected in three campaigns (spring, summer, autumn). Metagenomic DNA was isolated by the commercial kits, according to the manufacturer’s instruction. Illumina sequencing system was employed, and the R program was used to metagenomic analysis. It was found that the wastewater samples and receiving water contained the multi-resistant bacteria from the WHO priority pathogens list. The seasonal and technological variations affected the distribution of the pathogens in the wastewater. No effect of the effluent on the pathogens in the receiving water was observed. The results indicated that antibiotic-resistant “priority pathogens” from the WHO list are there in the waste- and receiving water. Technological process and seasons effected their distribution in the environment. Metagenomic analysis can be used as sufficient tool in microbiological and human health risk assessment.

Investigating the OXA Variants of ESKAPE Pathogens.

ESKAPE pathogens are the leading cause of nosocomial infections. The Global Priority List of WHO has categorized ESKAPE as priority 1 and 2 pathogens. Even though several mechanisms contribute to antimicrobial resistance, OXA β-lactamase has emerged as a new threat in combating nosocomial infections. In the present study we have investigated the presence of OXA and their variants, copy number, distribution on chromosomes/plasmids, subfamilies, phylogenetic relationships, amino acid identities and variabilities in ESKAPE pathogens. Our results revealed that a total of 929 OXA were present in 2258 completely assembled genomes, which could be further subdivided into 16 sub-families. Among all the ESKAPE pathogens, OXA were highly prevalent in A. baumannii, followed by P. aeruginosa and K. pneumoniae but completely absent in E. faecium and S. aureus while, only a few copies were found in Enterobacter spp. Most of the OXA variants belonged to the OXA-51-like subfamily (200 proteins), followed by OXA-50-like subfamily (189 proteins), OXA-23-like subfamily (156 proteins) and OXA-1-like subfamily (154 proteins). OXA-51-like, OXA-213-like, OXA-134-like, OXA-58-like, OXA-24-like and OXA-20-like subfamilies were present exclusively in A. baumannii. Phylogenetic tree of the subfamilies revealed that OXA-1-like and OXA-33-like, OXA-51-like and OXA-213-like and, OXA-5-like and OXA-10-like belonged to the same branches with amino acid identities as 100%, 97.10% and 80.90% respectively. This indicates that the members of these subfamily-pairs might have evolved from the same ancestor or have recently diverged. Thus, a judicious use of carbapenems is warranted to curtail the rise of new OXA enzymes and preserve them. This is the first detailed report about the OXA of ESKAPE pathogens.