Universal Definition of the Nonconformal Trace Anomaly.

We show that there exists a generalized, universal notion of the trace anomaly for theories which are not conformally invariant at the classical level. The definition is suitable for any regularization scheme and clearly states to what extent the classical equations of motion should be used, thus resolving existing controversies surrounding previous proposals. Additionally, we exhibit the link between our definition of the anomaly and the functional Jacobian arising from a Weyl transformation.

Collection of cardiac masses. Up-to-date echocardiography and cardiac MRI tools.

Heart masses, including tumors (primary and secondary) and pseudotumor (cysts and thrombus), are rare entities, but of increasing interest in cardiac imaging areas. The clinical manifestations are related to the intracardiac effect of mass, embolization, and systemic symptoms in the case of tumors; however, some of them are detected incidentally. Nowadays, imaging techniques and the advancement of their tools perform the morphological, functional, and tissue characterization of the masses, and additionally know the anatomical relationships, which are crucial factors for the treatment and surgical planning.

NS2B-NS3 protease inhibitors as promising compounds in the development of antivirals against Zika virus: A systematic review.

Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B-NS3 protease (NS2B-NS3 pro), which is essential for viral replication, is a promising molecular target for anti-ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; seven relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B-NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off-label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B-NS3 pro ranged at 0.38-21.6 µM; most compounds exhibited noncompetitive inhibition (66%). All compounds that could inhibit the NS2B-NS3 pro complex showed potent in vitro anti-ZIKV activity with a 50% effective concentration ranging 0.024-50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL-69 cell lines ranged at 0.6-1388.02 µM and the selectivity index was 3.07-1698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases.

Animal venoms as a source of antiviral peptides active against arboviruses: a systematic review.

Arthropod-borne viruses (arboviruses), such as Zika virus (ZIKV), chikungunya virus (CHIKV), dengue virus (DENV), yellow fever virus (YFV), and West Nile virus (WNV), are pathogens of global importance. Therefore, there has been an increasing need for new drugs for the treatment of these viral infections. In this context, antimicrobial peptides (AMPs) obtained from animal venoms stand out as promising compounds because they exhibit strong antiviral activity against emerging arboviral pathogens. Thus, we systematically searched and critically analyzed in vitro and in vivo studies that evaluated the anti-arbovirus effect of peptide derivatives from toxins produced by vertebrates and invertebrates. Thirteen studies that evaluated the antiviral action of 10 peptides against arboviruses were included in this review. The peptides were derived from the venom of scorpions, spiders, wasps, snakes, sea snails, and frogs and were tested against DENV, ZIKV, YFV, WNV, and CHIKV. Despite the high structural variety of the peptides included in this study, their antiviral activity appears to be associated with the presence of positive charges, an excess of basic amino acids (mainly lysine), and a high isoelectric point (above 8). These peptides use different antiviral mechanisms, the most common of which is the inhibition of viral replication, release, entry, or fusion. Moreover, peptides with virucidal and cytoprotective (pre-treatment) effects were also identified. In conclusion, animal-venom-derived peptides stand out as a promising alternative in the search and development of prototype antivirals against arboviruses.

Epilepsy in children with Congenital Zika Syndrome: A systematic review and meta-analysis.

OBJECTIVES: To estimate the overall frequency of epilepsy in children with congenital Zika syndrome (CZS) and describe the profile of seizures and the response rate to anti-epileptic treatment in this group of patients. METHODS: A systematic review and meta-analysis were conducted following the Cochrane Handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed/MEDLINE, Scopus, Cochrane Library, SciELO, and LILACS were searched until June 23, 2020. Observational studies that evaluated the frequency of epilepsy in children diagnosed with CZS according to international criteria were included in the study. RESULTS: Fourteen studies evaluating 903 patients diagnosed with CZS were pooled in a meta-analysis. All studies were conducted in Brazil, with reports published between 2016 and 2020, and included children diagnosed with CSZ from 0 to 40 months of age. The overall rate of epilepsy in children diagnosed with CZS was estimated at 60% (95% confidence interval [CI] 0.51-0.68). The studies included in this review show that the frequency of epilepsy in patients with CSZ varies with age, with higher rates in older children. Epileptic spasms was the primary type of seizure observed in this group, followed by focal and generalized crisis. The response rate to anti-epileptic drugs was considerably low, ranging from 20% of seizure control in the first year and 30% in the second year. SIGNIFICANCE: Children with CZS presented a high cumulative incidence of epilepsy episodes with increased severity and a low response to anti-epileptic therapy, which is associated with the extensive damage caused by the Zika virus on the cortical structures of patients.

Rate of exposure to Mayaro virus (MAYV) in Brazil between 1955 and 2018: a systematic review and meta-analysis.

Mayaro fever is an infection caused by Mayaro virus (MAYV) that stands out among the neglected diseases transmitted by arthropods. Brazil is the country with the highest number of confirmed cases of MAYV infection. However, epidemiological surveillance studies conducted in Brazil are decentralized and focus on small outbreaks and unconfirmed cases. Thus, the aim of this review was to determine the general epidemiological profile of MAYV infections in Brazil. Several medical databases (i.e., PUBMED/MEDLINE, Scopus, Cochrane Library, LILACS, SciELO, and Biblioteca Virtual em Saúde) were searched for studies reporting cases of MAYV infections in Brazilian patients. Then, the rate of exposure to MAYV in Brazil was analyzed using RStudio® Software. We identified 37 studies published from 1957 to 2019, containing data of 12,374 patients from 1955 to 2018. The general rate of exposure to MAYV in Brazil was 10% (95% CI; 0.04-0.22), with 1,304 reported cases. The highest incidence of MAYV infection was found in the northern region (13%; 95% CI; 0.05-0.29), with 1,142 cases (88% of all cases). Furthermore, autochthonous MAYV cases have also been reported in the Central West (8%; 95% CI; 0.03-0.18) and Southeast (0.4%; 95% CI; 0.00-0.28). The states with the highest number of cases are Amazonas (490 cases), Pará (276 cases), and Goiás (87 cases). In conclusion, the general rate of exposure to MAYV in Brazil between 1955 and 2018 was considerable, especially in the Legal Amazon, in which 93% of cases were reported.

Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids.

Candida spp. is considered an important cause of healthcare-associated infections worldwide. Currently, the emergence and spread of resistant Candida isolates are being increasingly reported, making the development of new agents urgently needed. In this study, we showed the in vitro anti-Candida activity of seven synthetic 3-alkylpyridine alkaloid analogs. Among them, alkaloid 1 presented a potent antifungal effect, which was independent of its capacity of binding with the fungal membrane ergosterol or cell wall. Analog 1 showed fungistatic and fungicidal effects against C. albicans (MIC 7.8 µg/mL and MFC 62.5 µg/mL), C. glabrata, C. krusei (MIC and MFC 31.2 µg/mL), and C. tropicalis (MIC 31.2 µg/mL and MFC 125 µg/mL). The time kill-curve study showed that compound 1 has a potent fungicidal effect in vitro, eliminating C. albicans cells. Furthermore, an in vitro synergistic effect with ketoconazole was observed for compound 1. This compound also eliminated the yeast-to-hypha transition. However, it showed high cytotoxicity against mammalian cells. Taken together, these findings support the use of compound 1 as a prototype to develop new anti-Candida agents, but molecular modifications should be done to minimize the high cytotoxicity obtained.

Bee products as a source of promising therapeutic and chemoprophylaxis strategies against COVID-19 (SARS-CoV-2).

The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19.

Effectiveness of supplementation with quercetin-type flavonols for treatment of viral lower respiratory tract infections: Systematic review and meta-analysis of preclinical studies.

Viral infections of the lower respiratory tract are considered a public health problem. They affect millions of people worldwide, causing thousands of deaths, and are treated with expensive medicines, such as antivirals or palliative measures. In this study, we conducted a systematic review to describe the use of quercetin-type flavonols against lower respiratory tract viruses and discussed the preclinical impact of this approach on different signs and clinical mechanisms of infection. The systematic review was performed in PubMed/MEDLINE, Scopus, Scielo, and Biblioteca Virtual de Saúde (BVS). After the database search, 11 relevant studies were identified as eligible. The analysis of these studies showed evidence of antiviral activity of quercetin-type flavonols with significantly reduced mortality rate (M-H = 0.19, 95% CI: 0.05 to 0.65, p-value = 0.008) of infected animals and a reduction in the average viral load (IV = -1.93, 95% CI: -3.54 to -0.31, p-value = 0.02). Additionally, quercetin and its derivatives reduced the amount of proinflammatory cytokines, chemokines, reactive oxygen species, mucus production, and airway resistance in animals infected with a respiratory virus. Overall, supplementation with quercetin-type flavonols is a promising strategy for treating viral-induced lower respiratory tract infections.

Development of milk drink with whey fermented and acceptability by children and adolescents.

Malnutrition is one of the main trouble relationship children development, it is linking of infectious disease, affect brain development, learning delay and others. The school feeding is an important action to mitigate this, but the acceptability of new and healthy products still a challenge. The goal of this article was to develop a fermented drink, replacing milk to whey, added of mangaba pulp and iron, to improve the nutritional quality of products. Two formulations were developed with a difference in ratio milk and whey. The pH, acidity, nutritional label, microbiology and sensorial assay with target public (children and adolescents) of formulations were evaluated. Highlights the contribution of protein, calcium and iron to daily value of intake recommended of formulations, 8.4%, 15.2% and 44.3%, respectively. The microbiological parameters founded shows that the formulations were developed according to good manufacture practice. The formulation and age showed significant effect in acceptability of judges, but gender did not effect. The increase of whey concentration in formulation improved the acceptability, ranking to 91.5% to children and 73.6% to adolescents. The developed formulations are a great option to novel food products, given the high acceptance of the fermented milk drink by potential consumers and nutritional aport.

Rate of polymyxin resistance among Acinetobacter baumannii recovered from hospitalized patients: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to determine the rate of polymyxin resistance among Acinetobacter baumannii isolates causing infection in hospitalized patients around the world during the period of 2010-2019. The systematic review was performed on September 1, 2019, using PubMed/MEDLINE, Scopus, and Web of Science; studies published after January 1, 2010, were selected. The data were summarized in tables, critically analyzed, and treated statistically using the RStudio® Software with Meta package and Metaprop Command. After applying exclusion factors, 41 relevant studies were selected from 969 articles identified on literature search. The overall rate of polymyxin-resistant A. baumannii (PRAB) related to hospitalized patients was estimated to be 13% (95% CI, 0.06-0.27), where a higher rate was observed in America (29%; 95% CI, 0.12-0.55), followed by Europe (13%; 95% CI, 0.02-0.52), and Asia (10%; 95% CI, 0.02-0.32). The extensive use of polymyxins on veterinary to control bacterial infection and growth promotion, as well as the resurgence in prescription and use of polymyxins in the clinics against carbapenem-resistant gram-negative bacteria, may have contributed to the increased incidence of PRAB. The findings of this meta-analysis revealed that the rate of PRAB recovered from hospitalized patients is distinctively high. Thus, action needs to be taken to develop strategies to combat the clinical incidence of PRAB-induced hospital infections.

The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review.

The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Saúde (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus.

Identification of Zika Virus NS2B-NS3 Protease Inhibitors by Structure-Based Virtual Screening and Drug Repurposing Approaches.

The NS2B-NS3 protease has been identified as an attractive target for drug development against Zika virus (ZIKV) and combined drug repurposing and structure-based virtual screening has improved the development of antiviral drugs. In this study, we performed a structure-based virtual screening of 1861 Food and Administration (FDA) approved drugs available in DrugBank by the selection and docking validation of crystal structure of ZIKV NS2B-NS3 protease (PDB ID 5H4I ) using Glide and DOCK 6 software. The antihistaminic chlorcyclizine (Grid score -24.8 kcal/mol) exhibited the most promising interaction with NS2B-NS3 protease in comparison to crystallography ligand (Grid score -15.6 kcal/mol) by interaction to Tyr161 by hydrophobic interactions in the binding site of NS2B-NS3 which is recognized as an important amino acid in substrate molecular recognition. Cytotoxicity and global antiviral activity assay in Vero cells by MTT method showed that chlorcyclizine reduced the ZIKV induced cytopathic effect (EC50 of 69.0 ± 7.3 µM and SI = 1.9), and explicit molecular dynamics simulations implemented on a NAMD program indicated great stability of chlorcyclizine in protease binding site, suggesting the repurposing of chlorcyclizine as a promising finding in anti-ZIKV drug development.

Identification of a Potential Zika Virus Inhibitor Targeting NS5 Methyltransferase Using Virtual Screening and Molecular Dynamics Simulations.

The NS5 methyltransferase (MTase) has been reported as an attractive molecular target for antivirals discovery against the Zika virus (ZIKV). Here, we report structure-based virtual screening of 42 390 structures from the Development Therapeutics Program (DTP) AIDS Antiviral Screen Database. Among the docked compounds, ZINC1652386 stood out due to its high affinity for MTase in comparison to the cocrystallized ligand MS2042, which interacts with the Asp146 residue in the MTase binding site by hydrogen bonding. Subsequent molecular dynamics simulations predicted that this compound forms a stable complex with MTase within 50 ns. Thus, ZINC1652386 may represent a promising ZIKV methyltransferase inhibitor.

Serum lipid profile as a predictor of dengue severity: A systematic review and meta-analysis.

Dengue virus is known to modulate host cell lipid metabolism in order to promote efficient viral replication. Recent studies have focused on circulating lipids as potential biomarkers of dengue severity; however, the results obtained so far lack the consistency to establish a definite relationship between the two. Therefore, in the present study, we investigated serum lipids as potential biomarkers of dengue severity by conducting a meta-analysis of the currently available clinical data. Nine studies that evaluated 1,953 patients were included in the review, many of which were cross-sectional (44.4%) and conducted in Asian countries (55.5%). These studies observed the presence of lipids in serum samples (77%) of patients in the acute phase of the disease (88.8%). Circulating total-cholesterol (P = .001) and LDL (P = .001) levels, but not HDL (P = .07), VLDL (P = .9) and triglyceride (P = .57) levels, were inversely and significantly correlated with dengue severity. Total cholesterol (P ≤ .001) and LDL (P = .001) were also useful in determining the risk of hypovolemic shock in patients with severe dengue. Subgroup analysis showed that factors, such as design (cross-sectional vs cohort), racial-ethnic differences (Asian vs Latin Americans), and age range (children vs adult) influenced the correlation and also contributed to the high level of heterogeneity in the studies. Our meta-analysis demonstrates that total-cholesterol and LDL-cholesterol levels should be explored as routine laboratory markers for dengue severity, as they will help in employing an appropriate patient therapy, and thus optimize the use of available resources.

Plasmid-mediated quinolone resistance (PMQR) among Enterobacteriales in Latin America: a systematic review.

The plasmid-mediated quinolone resistance (PMQR) genes have changed the resistance pattern to quinolones, especially among Enterobacteriales. The dissemination of these genes in Latin American countries, where the prescription of fluoroquinolones is high, has been described in several studies; however, no review of the impact of PMQR in this continent has been conducted. This review summarized current knowledge about the circulation of PMQR among Enterobacteriales in Latin American. After the search and selection, 61 articles were included in the study. Most of studies reported PMQR genes among Enterobacteriales from human (47/61, 77%) and animal (18/61, 29.5%) samples, recovered mainly in Brazil (23/61, 37.7%), Mexico (11/61, 18%), and Uruguay (7/61, 11.5%). Nine different PMQR genes (qnrA, qnrB, qnrS, qnrD, qnrE, aac-(6')-Ib-cr, oqxA, oqxB, and qepA) were found in Latin America, with aac (6')-Ib-cr (37/61, 60.6%) and qnrB (26/61, 42.6%) being the most frequently reported. Escherichia coli (40/61, 65.6%) was the species most frequently reported to carry a PMQR gene, followed by Klebsiella pneumoniae (24/61, 39.3%), Enterobacter cloacae (15/61, 24.6%), and Salmonella spp. (14/61, 22.9%). Thus, this review provides important information which might help in designing measures to control the spread of quinolone resistance determinants on this continent.

Cardiac sympathetic drive is increased in cafeteria diet-fed rats independent of impairment in peripheral baroreflex and chemoreflex functions.

BACKGROUND AND AIMS: Consumption of a high caloric diet induces autonomic imbalance, which can lead to cardiovascular disease. Impaired arterial baroreflex control is suggested to play an important role in cardiovascular autonomic imbalance, often seen in obesity. We previously demonstrated that cafeteria diets increase the sympathetic drive to white and brown adipose tissue. METHODS AND RESULTS: After feeding a cafeteria diet to rats for 26 days, we evaluated: (i)heart rate (HR) and arterial pressure (AP); (ii)baroreflex and chemoreflex function; and (iii) autonomic modulation of the heart and vessels, measured through pulse interval (PI) and systolic arterial pressure (SAP) variability analyses and following administration of autonomic blockers. The cafeteria diet increased body fat mass and serum insulin, leptin, triacylglycerol and cholesterol levels. Baseline HR (15%) was also increased, accompanied by increased power in the low frequency band (60%) and in the low frequency/high frequency ratio (104%) in the PI spectra. Nonlinear analysis revealed an increased occurrence of 0V (39%) and decreased occurrence of 2UV (18%) patterns. Following administration of autonomic blockers, we observed an increase in cardiac sympathetic tone (425%) in cafeteria diet-fed rats. The cafeteria diet had no effect on AP, SAP variability, baroreflex and chemoreflex control. CONCLUSION: Our findings suggest that consumption of a cafeteria diet increases sympathetic drive to the heart but not to the blood vessels, independent of impairment in baroreflex and chemoreflex functions. Other mechanisms may be involved in the increased cardiac sympathetic drive, and compensatory vascular mechanisms may prevent the development of hypertension in this model of obesity.

Fatal granulomatous amoebic encephalitis due to free-living amoebae in two boys in two different hospitals in Lima, Perú.

Granulomatous amoebic encephalitis caused by free-living amoebae is a rare condition that is difficult to diagnose and hard to treat, generally being fatal. Anti-amoebic treatment is often delayed because clinical signs and symptoms may hide the probable causing agent misleading the appropriate diagnostic test. There are four genera of free-living amoeba associated with human infection, Naegleria, Acanthamoeba sp., Balamuthia and Sappinia. Two boys were admitted with diagnosis of acute encephalitis. The history of having been in contact with swimming pools and rivers, supports the suspicion of an infection due to free-living amoebae. In both cases a brain biopsy was done, the histology confirmed granulomatous amoebic encephalitis with the presence of amoebic trophozoites.

Epidemiological Impact and Hospitalization costs applied to dengue in the Midwest region of Minas Gerais state, Brazil, from SUS perspective.

BACKGROUND & OBJECTIVES: Dengue is considered one of the greatest public health challenges in the world, especially, for tropical and subtropical countries. Brazil highlights with considerable number of registers associated with this arbovirus, with emphasis on the state of Minas Gerais and its municipalities in regions such as the midwest. We aimed to evaluate the economic and epidemiological impact of dengue in the midwest region of minas Gerais, from SUS perspective. METHODS: Our study evaluated the epidemiological impact of dengue fever in the midwest region of Minas Gerais using data applied to Divinópolis city from SUS perspective between 2000 to 2015 considering SIH/SUS database (hospitalization registers) and 2007 to 2017 using the SINAN database (notification cases). We analyzed the number of notification registers and hospital services, as well as their costs, from a SUS perspective associated with this infection. RESULTS: There were 26,516 notifications associated with dengue, with 21,953 cases being confirmed by SEMUSA, with a median incidence of 211 cases/100,000 inhabitants of dengue notifications between 2007 and 2017. The southeast and southwest regions in the municipality are highlighted with high number of cases. Additionally, 160 hospitalizations were recorded with 33.79% in individuals between 15 and 34 years old and expenses of USD 53,737.21 for SUS between 2000 and 2015. INTERPRETATION & CONCLUSION: Divinópolis is the reference (social and economic) municipality of the midwest region in Minas Gerais state. Our study is the first conducted involving a long period of follow up applied to dengue context in this locality, especially, including the costs associated with hospitalization services. We hope to contribute to the discussions regarding the coping strategies of the disease, considering the impact in its different regions, highlighting the need for continued efforts and initiatives aimed at combating the vector of this and other arboviruses such as Zika and chikungunya.

Chromosomally encoded and plasmid-mediated polymyxins resistance in Acinetobacter baumannii: a huge public health threat.

Acinetobacter baumannii is an opportunistic pathogen associated with nosocomial and community infections of great clinical relevance. Its ability to rapidly develop resistance to antimicrobials, especially carbapenems, has re-boosted the prescription and use of polymyxins. However, the emergence of strains resistant to these antimicrobials is becoming a critical issue in several regions of the world because very few of currently available antibiotics are effective in these cases. This review summarizes the most up-to-date knowledge about chromosomally encoded and plasmid-mediated polymyxins resistance in A. baumannii. Different mechanisms are employed by A. baumannii to overcome the antibacterial effects of polymyxins. Modification of the outer membrane through phosphoethanolamine addition, loss of lipopolysaccharide, symmetric rupture, metabolic changes affecting osmoprotective amino acids, and overexpression of efflux pumps are involved in this process. Several genetic elements modulate these mechanisms, but only three of them have been described so far in A. baumannii clinical isolates such as mutations in pmrCAB, lpxACD, and lpsB. Elucidation of genotypic profiles and resistance mechanisms are necessary for control and fight against resistance to polymyxins in A. baumannii, thereby protecting this class for future treatment.