Synergy between amikacin and Protium heptaphyllum essential oil against polymyxin resistance Klebsiella pneumoniae.

AIMS: We investigated the chemical composition and the in vitro and in vivo antibacterial effects of Protium heptaphyllum essential oil (PHEO) alone and in combination with antibiotics against polymyxin-resistant Klebsiella pneumoniae isolates. METHODS AND RESULTS: Hydrodistillation was used to obtain PHEO, and gas chromatography coupled with mass spectrometry revealed α-pinene, δ-3-carene, and ß-pinene as major components present in PHEO. Minimum inhibitory concentration was determined using the broth microdilution technique and ranged from 256 to 512 µg ml-1. The checkerboard method showed synergy with the combination of PHEO and amikacin (AMK) against the polymyxin-resistant K. pneumoniae isolates. In 8 of the 10 isolates tested, the fractional inhibitory concentration indexes (FICIs) ranged from 0.06 to 0.5, while in the remaining two isolates, the combination exerted an additive effect (FICI of 0.6 and 1.0), resulting in AMK dose reduce of range 2- to 16-fold, in the presence of PHEO. Analysis using zero interaction potency revealed high synergy score (63.9). In the in vivo assay, the survival of Caenorhabditis elegans was significantly improved in the presence of PHEO (1 µg ml-1) + AMK (µg ml-1) combination as compared to 32 µg ml-1 AMK alone. Furthermore, PHEO concentrations of 256 and 512 µg ml-1 were found to be non-toxic on the experimental model. CONCLUSION: To our knowledge, this is the first report of such type of synergism demonstrating an antimicrobial effect against polymyxin-resistant K. pneumoniae isolates.

Antimicrobial peptides against polymyxin-resistant Klebsiella pneumoniae: a patent review.

The spread of polymyxin-resistant Klebsiella pneumoniae strains represents an emerging health challenge, limiting treatment options for the patients. Thus, the development of new antimicrobials is an urgent requirement. Antimicrobial peptides (AMPs) are a large class of compounds that are part of innate immune response; these peptides are promising compounds in the field of antimicrobial resistance and are present in all organisms. The present review evaluated patents on antimicrobial peptides tested against polymyxin-resistant K. pneumoniae, available on Espacenet as of September 2022. A total of 1313 patents were examined and 1197 excluded as they were out of focus for this review; 104 patents of peptides tested against K. pneumoniae were included; of which only 14 were tested against polymyxin-resistant K. pneumoniae strains. The results indicated that all AMPs evaluated were in the experimental or pre-clinical phase; the clinical phase is pending. Furthermore, a few peptides were tested effectively against polymyxin-resistant K. pneumoniae. Although, the research and patent filing alone are not enough to develop a suitable antimicrobial therapy, they can represent good starting point upon which to develop new antimicrobials. More investment is required to push these pharmaceuticals through the stages of development to introduce them into the market.

New Technologies to Diagnose and Treat a Multidrug-Resistant Candida auris: A Patent Review.

Candida auris is responsible for hospital outbreaks worldwide. Some C. auris isolates may show concomitant resistance to azoles, echinocandins, and polyenes, thereby possibly leaving clinicians with few therapeutic options. In addition, this multi-drug-resistant yeast is difficult to identify with conventional methods and has the ability to persist on environmental surfaces causing hospital-acquired infections. The development of new treatment options and tools for identification is critical to control, prevent, and establish an early diagnosis of this emerging pathogen. The aim of this study was to perform a critical patent review to explore and identify the latest advances in therapeutic strategies as well as diagnostic methods for C. auris. A total of 19 patents were identified for a preliminary assessment from the Espacenet database. Three patents were excluded as they were out of focus for this review according to their abstract and/or description. The final selection covered 16 patents, which were surveyed by country, year and classified as treatment or diagnostic methods for C. auris. As noted in the patent reading, in recent years, the interest of academic, government and industry sectors have shown an increasing tendency focused on research and development of new therapeutic molecules and diagnostic methods to combat this emerging pathogen.

Development of ELISA Using Recombinant Proteins for the Diagnosis of Mycoplasma hyopneumoniae Infection.

In order to develop a more sensitive and reliable method for detection of serum antibodies against Mycoplasma hyopneumoniae infection in pigs, six recombinant proteins of M. hyopneumoniae (P102, P95, P46, P97 like, Lppt, and hypothetical P987) were used for the standardization of an indirect enzyme-linked immunosorbent assay (ELISA). The proteins were evaluated against 50 sera of the specific pathogen-free and 50 sera of pigs with lesions suggestive of infection. The sensitivity was 88%, 86%, 78%, 74%, 66%, and 60% for the proteins P102, P95, P46, P97 like, Lppt, and hypothetical protein P987, respectively. Moreover, the proteins were used to establish the seroprevalence in two different commercial herds (254 sera pigs from farm considered free of M. hyopneumoniae and 246 from farm with clinical signs of enzootic pneumonia and positive serology for M. hyopneumoniae) and the positive rate was 65.2% for P95, 54.6% for P102, 40.2% for P46, 37.2% for P97 like, 17.4% for the hypothetical P987, and 14% for Lppt protein. In addition, the ELISA with six recombinant proteins was compared to commercial HerdCheck kit using 118 random pig sera samples and the results showed that ELISA with recombinant proteins were more sensitive than the commercial test. These data show that the recombinant proteins P95 and P102 are potential targets to be used in diagnostic tests to detect antibodies against M. hyopneumoniae. Although more studies are necessary, this study provides insights that these recombinant proteins can be useful in epidemiological investigations and as potential biomarkers in differentiating infected animals from those vaccinated.

Tp0684, Tp0750, and Tp0792 Recombinant Proteins as Antigens for the Serodiagnosis of Syphilis.

The incidence of syphilis has increased alarmingly over the years. Its diagnosis continues to be a challenge, leading to the search for new alternative and effective methods. The objective of this study was to select and evaluate three Treponema pallidum recombinant proteins for potential use in syphilis serodiagnosis. Bioinformatics analysis was performed with three T. pallidum antigens (Tp0684, Tp0750, and Tp0792) to assess their physical, antigenic, and structural characteristics. The antigens were chemically synthesized, recombinant plasmids were expressed in Escherichia coli BL21 Star™ (DE3), and the recombinant proteins were purified by nickel affinity chromatography. The antigenicity of the recombinant proteins was evaluated by western blotting and enzyme-linked immunosorbent assay (ELISA), using the sera from patients with primary and latent syphilis. In silico analysis indicated the antigenic potential once the exposed B cell epitopes were detected in the evaluated proteins. Sera from patients with primary and latent syphilis specifically recognized rTp0684, rTp0750, and rTp0792 recombinant antigens. Moreover, the rTp0684-ELISA receiver operating characteristic (ROC) analysis showed an area under the ROC curve of 0.99, indicating high diagnostic efficacy with 97.62% specificity and 95% sensitivity. In conclusion, rTp0684 showed better potential as an antigen for the development of syphilis serodiagnosis. Thus, bioinformatic analysis can be an important tool to guide the selection of antigens for serological diagnosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01017-w.

Molecular and epidemiological surveillance of polymyxin-resistant Klebsiella pneumoniae strains isolated from Brazil with multiple mgrB gene mutations.

The prevalence of polymyxin-resistant Enterobacteriaceae is increasing worldwide. Their emergence is worrisome and limits therapeutic options for severely ill patients. We aimed to investigate the molecular and epidemiological characteristics of polymyxin-resistant Klebsiella pneumoniae circulating in Brazilian hospitals. Polymyxin-resistant K. pneumoniae isolates from two Brazilian healthcare facilities were characterized phenotypically and subjected to whole genome sequencing (WGS). Using the WGS data we determined their sequence type, resistance gene content (resistome), their composition of virulence genes and plasmids. ST11 was the most common (80 %) sequence type among the isolates followed by ST345, ST15 and ST258. A resistome analysis revealed the common presence of blaKPC-2 and less frequently blaSHV-11, blaTEM-1, blaCTX-M-15, and blaOXA-9. Genes conferring resistance to aminoglycosides, fluoroquinolones, phenicols, sulphonamides, tetracyclines, trimethoprim and macrolide-lincosamide-streptogramin were also detected. We observed a clonal spread of polymyxin-resistant K. pneumoniae isolates, with polymyxin-resistance associated with various alterations in the mgrB gene including inactivation by an insertion sequence and nonsense point mutations. We additionally identified a novel 78-bp repeat sequence, encoding a MgrB protein with 26 amino acids duplicated in six isolates. This is the first observation of this type of alteration being associated with polymyxin resistance. Our findings demonstrate that mgrB alterations were the most common source of polymyxin-resistance in Brazilian clinical settings. Interestingly, distinct genetic events were identified among clonally related isolates, including a new amino acid alteration. The clinical implications and investigation of the resistance mechanisms is of great importance to patient safety and control of these infections, particularly in long-term care facilities.

Antimicrobial activity of plant extracts against carbapenem-producing Klebsiella pneumoniae and in vivo toxicological assessment.

The global spread of multidrug-resistant strains has prompted the scientific community to explore novel sources of chemicals with antimicrobial activity. The aim of the study was to examine the antimicrobial activity in vitro of 28 extracts against carbapenem-producing Klebsiella pneumoniae, individually and in combination with antibiotics and in vivo toxicological assessment of the most active product. The multi-resistant K. pneumoniae strain was submitted for phenotypic and molecular characterization. The antibacterial activity of 28 plant extracts was evaluated alone and in combination with antibiotics against this strain through the agar disk diffusion. Of these, 16 extracts showed synergism against carbapenem-producing K. pneumoniae, being that B. crassifolia extract exhibited synergism with three antibiotics. Based on this assessment, B. crassifolia-extract-induced toxicity on Swiss male mice was evaluated by administering this extract and subsequently determining apoptosis and splenic phagocytosis using the comet and micronucleus assays. The results of this study showed that B. crassifolia extract had synergistic activity promising and groups treated with B. crassifolia exhibited no genotoxic or mutagenic activity, indicating that B. crassifolia extract exerted beneficial effects and appeared safe to use at the studied concentrations.

Impact of mass-screening on tuberculosis incidence in a prospective cohort of Brazilian prisoners.

BACKGROUND: Globally, prison inmates are a high-risk population for tuberculosis (TB), but the specific drivers of disease and impact of mass screening interventions are poorly understood. METHODS: We performed a prospective cohort study to characterize the incidence and risk factors for tuberculosis infection and disease in 12 Brazilian prisons, and to investigate the effect of mass screening on subsequent disease risk. After recruiting a stratified random sample of inmates, we administered a questionnaire to ascertain symptoms and potential risk factors for tuberculosis; performed tuberculin skin testing (TST); collected sera for HIV testing; and obtained two sputum samples for smear microscopy and culture, from participants reporting a cough of any duration. We repeated the questionnaire and all tests for inmates who remained incarcerated after 1 year. TST conversion was defined as TST ≥10 mm and an induration increase of at least 6 mm in an individual with a baseline TST <10 mm. Cox proportional hazard models were performed to identify risk factors associated with active TB. To evaluate the impact of screening on subsequent risk of disease, we compared TB notifications over one year among individuals randomized to screening for active TB with those not randomized to screening. RESULTS: Among 3,771 inmates recruited, 3,380 (89.6 %) were enrolled in the study, and 1,422 remained incarcerated after one year. Among 1,350 inmates (94.9 %) with paired TSTs at baseline and one-year follow-up, 25.7 % (272/1060) converted to positive. Among those incarcerated for the year, 10 (0.7 %) had TB at baseline and 25 (1.8 %) were diagnosed with TB over the subsequent year. Cases identified through active screening were less likely to be smear-positive than passively detected cases (10.0 % vs 50.9 %; p < 0.01), suggesting early case detection. However, there was no reduction in subsequent disease among individuals actively screened versus those not screened (1.3 % vs 1.7 %; p = 0.88). Drug use during the year (AHR 3.22; 95 % CI 1.05-9.89) and knows somebody with TB were (AHR 2.86; 95 % CI 1.01-8.10) associated with active TB during one year of follow up CONCLUSIONS: Mass screening in twelve Brazilian prisons did not reduce risk of subsequent disease in twelve Brazilian prisons, likely due to an extremely high force of infection. New approaches are needed to control TB in this high-transmission setting.

Coproduction of KPC-2 and IMP-10 in Carbapenem-Resistant Serratia marcescens Isolates from an Outbreak in a Brazilian Teaching Hospital.

We describe an outbreak caused by KPC-2- and IMP-10-producing Serratia marcescens isolates in a Brazilian teaching hospital. Tigecycline was the only active antimicrobial agent tested. The blaIMP-10 gene was located in a new class 1 integron, named In990, carried by a nonconjugative plasmid, in contrast to blaKPC-2.

Active and latent tuberculosis in Brazilian correctional facilities: a cross-sectional study.

BACKGROUND: Tuberculosis (TB) rates among prisoners are more than 20 times that of the general population in Brazil, yet there are limited data available to facilitate the development of effective interventions in this high-transmission setting. We aimed to assess risk factors for TB infection and evaluate the yield of mass screening for active disease among inmates. METHODS: We administered a questionnaire and tuberculin skin test (TST) to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV testing and two sputum samples for smear microscopy and culture from participants reporting a cough of any duration. Hierarchical Poisson regression models were used to evaluate factors associated with latent tuberculosis infection (LTBI). RESULTS: We recruited 3,380 inmates, of which 2,861 (84.6%) were males from 8 prisons, and 519 (15.4%) were females from 4 prisons. Among the 1,020 (30%) subjects who reported a cough, we obtained sputum from 691 (68%) and identified 31 cases of active TB for a point prevalence of 917 (95% CI, 623-1302) per 100,000 prisoners. Evaluation of the two sputum smear samples failed to identify 74% of the TB cases, and 29% of the cases reported less than 2 weeks of symptoms. Obtaining a second culture identified an additional 7 (24%) cases. The prevalences of LTBI were 22.5% and 11.7% for male and female prisoners, respectively and duration of incarceration (in years) was associated with LTBI in male and female in the multivariable model (1.04, 95% CI, 1.01-1.07 and 1.34, 95% CI, 1.06-1.70, respectively). The prevalence of LTBI is 8.6% among newly incarcerated inmates, among whom LTBI prevalence significantly increased by 5% with each year of incarceration. CONCLUSIONS: Although the overall LTBI prevalence among inmates in Central-West Brazil is low, tuberculosis incidence is high (>1,800/100,00), likely due to the high force of infection among a largely susceptible inmate population. Efforts to reduce transmission in prisons may require mass screening for active TB, utilizing sputum culture in case-detection protocols.

Impact of COVID-19 pandemic in the Brazilian maternal mortality ratio: A comparative analysis of Neural Networks Autoregression, Holt-Winters exponential smoothing, and Autoregressive Integrated Moving Average models.

BACKGROUND AND OBJECTIVES: The acute respiratory infection caused by severe acute respiratory syndrome coronavirus disease (COVID-19) has resulted in increased mortality among pregnant, puerperal, and neonates. Brazil has the highest number of maternal deaths and a distressing fatality rate of 7.2%, more than double the country's current mortality rate of 2.8%. This study investigates the impact of the COVID-19 pandemic on the Brazilian Maternal Mortality Ratio (BMMR) and forecasts the BMMR up to 2025. METHODS: To assess the impact of the COVID-19 pandemic on the BMMR, we employed Holt-Winters, Autoregressive Integrated Moving Average (ARIMA), and Neural Networks Autoregression (NNA). We utilized a retrospective time series spanning twenty-five years (1996-2021) to forecast the BMMR under both a COVID-19 pandemic scenario and a controlled COVID-19 scenario. RESULTS: Brazil consistently exhibited high maternal mortality values (mean BMMR [1996-2019] = 57.99 ±6.34/100,000 live births) according to World Health Organization criteria. The country experienced its highest mortality peak in the historical BMMR series in the second quarter of 2021 (197.75/100,000 live births), representing a more than 200% increase compared to the previous period. Holt-Winter and ARIMA models demonstrated better agreement with prediction results beyond the sample data, although NNA provided a better fit to previous data. CONCLUSIONS: Our study revealed an increase in BMMR and its temporal correlation with COVID-19 incidence. Additionally, it showed that Holt-Winter and ARIMA models can be employed for BMMR forecasting with lower errors. This information can assist governments and public health agencies in making timely and informed decisions.

Antifungal activity of Caryocar brasiliense camb. Alone or along with antifungal agents against multidrug-resistant Candida auris.

ETHNOPHARMACOLOGICAL RELEVANCE: Candida auris poses a severe global health threat, with many strains resistant to antifungal treatments, complicating therapy. Exploring natural compounds alongside conventional drugs offers promising therapeutic avenues. The antifungal potential of the ethanolic extract from Caryocar brasiliense (Cb-EE), a plant native to the Brazilian cerrado and renowned for its medicinal properties, was investigated against C. auris. AIM OF THE STUDY: The study examined the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of Cb-EE. MATERIALS AND METHODS: Leaves of C. brasiliense were processed to extract ethanolic extract, which was evaluated for phenolic compounds, flavonoids, and tannins. The antifungal capacity was determined through broth microdilution and checkerboard methods, assessing interaction with conventional antifungals. RESULTS: Cb-EE demonstrated fungistatic activity against various Candida species and Cryptococcus neoformans. Synergy with fluconazole and additive effects with other drugs were observed. Cb-EE inhibited C. auris growth, with the combination of fluconazole extending inhibition. Mechanistic studies revealed interference with fungal membranes, confirmed by sorbitol protection assays, cellular permeability tests, and scanning electron microscopy (SEM). Hemocompatibility and in vivo toxicity tests on Tenebrio molitor showed safety. CONCLUSION: Cb-EE, alone or in combination with fluconazole, effectively treated C. auris infections in vitro and in vivo, suggesting its prospective role as an antifungal agent against this emerging pathogen.

Synergistic interaction of polymyxin B with carvacrol: antimicrobial strategy against polymyxin-resistant Klebsiella pneumoniae.

Objective: The antimicrobial activities of the synergistic combination of carvacrol and polymyxin B against polymyxin-resistant Klebsiella pneumoniae were evaluated. Methods: The methods employed checkerboard assays to investigate synergism, biofilm inhibition assessment and membrane integrity assay. In addition, the study included in vivo evaluation using a mouse infection model. Results: The checkerboard method evaluated 48 combinations, with 23 indicating synergistic action. Among these, carvacrol 10 mg/kg plus polymyxin B 2 mg/kg exhibited in vivo antimicrobial activity in a mouse model of infection, resulting in increased survival and a significant decrease in bacterial load in the blood. Conclusion: Polymyxin in synergy with carvacrol represents a promising alternative to be explored in the development of new antimicrobials.

In this study, we wanted to find a new way to fight a bacteria called Klebsiella pneumoniae, which is not easily killed by medication. We mixed two drugs, carvacrol and polymyxin B, to see if they would work together to fight the bacteria. We found that the mixed treatment helped to kill the bacteria. We also tried this mixed treatment in sick mice, and they got better. Our study shows that this mixed treatment might be a new way to fight bacteria that are hard to kill with regular drugs. Next, we hope to learn more about how it works.

Molecular characterization of Treponema pallidum isolates from Brazil.

Syphilis remains a public health concern in Brazil, and the data on the characterization and resistance of Treponema pallidum in Brazil is limited. The present study aimed to detect Treponema DNA in the lesions and blood samples obtained from individuals diagnosed with syphilis. The Brazilian isolates were submitted to the Enhanced Centers for Disease Control and Prevention (ECDC) scheme and also analyzed for resistance gene. Treponemal DNA from 18 lesions and 18 blood specimens were submitted for amplification using Polymerase Chain Reaction (PCR) and Polymerase Chain Reaction in Real Time (RT-PCR). Eight samples from lesions and eight from blood were positive in the RT-PCR analysis. Eight lesions and three blood samples were positive using PCR. Two samples exhibited azithromycin resistance. The Brazilian isolate types 14d/g, 14 d/c, 15d/c, and 15d/e were identified using the ECDC scheme. The three subtypes 14d/c, 15d/c, and 15d/e have been identified in Brazil for the first time.

Seroprevalence of Treponema pallidum infection among high-risk populations from Brazil.

Syphilis is a significant public health concern worldwide. According to the 2020 estimates, nearly 7.1 million new cases of syphilis have been reported globally, with over 30 % of these cases reported from American nations, particularly Brazil. Concerns have been raised regarding the susceptibility of specific groups to syphilis due to challenges and vulnerabilities that place these groups at a higher risk of infections or complications in the treatment outcomes. The present study aimed to compare the seroprevalence and the factors associated with syphilis among such high-risk groups. The study was designed as a cross-sectional one and was conducted with pregnant women, people living with HIV (PLHIV), people living with tuberculosis (PLTB), indigenous and healthy populations in Mato Grosso do Sul, Brazil. The study was conducted between June 2019 and August 2022, during which the included patients were subjected to treponemal and non-treponemal serological assays. The study also included a survey conducted through a self-reported questionnaire to collect information regarding the participants' demographics and sexual behaviors. A total of 550 samples were collected, with 110 participants in each of the five groups. The results of the study revealed that the seroprevalence of Treponema pallidum infection in pregnant women, PLHIV, PLTB, indigenous and healthy populations of the study region was 10 % (n = 11/110), 41.81 % (n = 46/110), 17.27 % (n = 19/110), 5.45 % (n = 6/110), and 8.18 % (n = 9/110), respectively. Homosexual orientation (p = 0.04) and a history of sexually transmitted infection (STI) (p = 0.01) were associated with the seroprevalence of T. pallidum infection in PLHIV. However, no such associations were noted in the remaining four groups. The seroprevalence of T. pallidum infection was observed to vary significantly among the different high-risk groups, which highlighted the persistent concern of syphilis, particularly among vulnerable populations. These findings underscore the significance of focused interventions and public health strategies customized to the specific requirements of each of the groups evaluated in the present study to decrease the number of cases of syphilis and thereby prevent future complications in patients with other serious infections.

Seroprevalence of Treponema pallidum infection in Brazilian indigenous people: a cross-sectional study.

Indigenous communities in Brazil have a complex epidemiological profile, which increases their chances of contracting sexually transmitted diseases. However, limited data is available on Treponema pallidum infections in this population. We investigated the seroprevalence and risk factors associated with T. pallidum infection in an indigenous population of Dourados, Mato Grosso do Sul. Blood samples were collected from September 2017 to March 2020, and the participants were interviewed to obtain comprehensive data on demography and sexual behavior. Serological tests were performed to detect T. pallidum infection. Besides conducting descriptive analysis, we performed Chi-squared tests and determined the bivariate odds ratio. The data were also analyzed using logistic regression. Among the 2190 invited individuals, 1927 (88%) were included in this study. The seroprevalence of T. pallidum infection was 2.91%. The results of a multivariate analysis showed that individuals who were 30-39 years old, with up to 4 years of school education, living in households without piped water, with a history of genital lesions, multiple sexual partners, and having a history of STIs had the highest seroprevalence of T. pallidum. This study showed that behavioral, social, and economic factors play an important role in the transmission of T. pallidum within the indigenous population. Thus, targeted intervention, including imparting education in the native language, mass testing initiatives, and implementing public policies to improve socioeconomic indicators, is needed to reduce the cases of syphilis in this community.

Typing of Treponema pallidum in a Brazilian sample and follow-up of treatment using molecular assays.

Syphilis remains a significant public health concern, with serological assays being the primary method for diagnosis. However, molecular techniques have proven to be reliable tools for the diagnosis and understanding of the transmission dynamics of Treponema pallidum infection. This study aimed to evaluate the efficacy of syphilis treatment using molecular assays, perform Enhanced Centers for Disease Control and Prevention (ECDC) typing, and analyze resistance (macrolide and doxycycline) in the T. pallidum isolate. PCR assay amplified treponemal DNA only from the lesion sample, whereas qPCR was able to amplify DNA in both lesion and blood samples before treatment. Throughout the treatment follow-up, qPCR effectively did not identify treponemal DNA in the blood for up to one to two weeks after treatment. ECDC typing revealed the genotype 14 e/g in the Brazilian T. pallidum isolate, and the presence of the A2058G mutation in 23 S rRNA gene, indicating macrolide resistance. Although, the G1058C mutation in 16 S rRNA gene was not detected. Notably, qPCR demonstrated its potential for diagnosing T. pallidum in blood samples, even when the treponemal DNA levels were low, enabling more accurate and sensitive diagnosis and guiding better syphilis therapy. In addition, to the best of our knowledge, this study represents the first identification of subtype 14 e/g and azithromycin resistance in a Brazilian T. pallidum isolate.

Immune Response to an Inactivated Vaccine of SARS-CoV-2 (CoronaVac) in an Indigenous Brazilian Population: A Cohort Study.

INTRODUCTION: Although the adaptive immune responses to the CoronaVac vaccine are known, their dynamics in indigenous communities remain unclear. In this study, we assessed the humoral and cellular immune responses to CoronaVac (Sinovac Biotech Life Sciences, 2021 NCT05225285, Beijing, China), in immunized Brazilian indigenous individuals. METHODS: We conducted a prospective cohort study on indigenous Brazilian people between February 2021 and June 2021. Analyses of immune responses were carried out before (T1) and after a vaccination schedule was completed (T2). Demographic data were collected using a questionnaire. RESULTS: We initially included 328 patients; among them, 120 (36.6%) had no SARS-CoV-2 antibodies. Peripheral blood mononuclear cells (PBMCs) were collected from 106 patients during follow-up visits, of which 91 samples were analyzed by immunophenotyping assay to detect SARS-CoV-2-specific memory T-cell response. Post-vaccination, the levels of memory B-cells and Natural Killer T-lymphocytes increased. Bororó village residents, females, and Terena ethnic group members had higher levels of anti-spike IgG antibodies post-vaccination, whereas alcohol and tobacco users had lower concentrations. CONCLUSIONS: To our best knowledge, this was the first comprehensive assessment of antibody and T-cell responses against CoronaVac vaccination in indigenous patients. Our findings showed that antibody response and T-cell immunity against SARS-CoV-2 were present in most patients following the vaccination schedule.

Antimicrobial and antibiofilm activities of desloratadine against multidrug-resistant Acinetobacter baumannii.

Aim: The antimicrobial and antibiofilm activities of the antihistamine desloratadine against multidrug-resistant (MDR) Acinetobacter baumannii were evaluated. Results: Desloratadine inhibited 90% bacterial growth at a concentration of 64 µg/ml. The combination of desloratadine with meropenem reduced the MIC by twofold in the planktonic state and increased the antibiofilm activity by eightfold. Survival curves showed that combinations of these drugs were successful in eradicating all bacterial cells within 16 h. Scanning electron microscopy also confirmed a synergistic effect in imparting a harmful effect on the cellular structure of MDR A. baumannii. An in vivo model showed significant protection of up to 83% of Caenorhabditis elegans infected with MDR A. baumannii. Conclusion: Our results indicate that repositioning of desloratadine may be a safe and low-cost alternative as an antimicrobial and antibiofilm agent for the treatment of MDR A. baumannii infections.

Multidrug-resistant gram-negative bacteria in patients with COVID-19: An epidemiological and clinical study.

Epidemiological data regarding the incidence of secondary multidrug-resistant (MDR) Gram-negative infection in patients with coronavirus disease (COVID-19) in Brazil are still ambiguous. Thus, a case-control study was designed to determine factors associated with the acquisition of MDR Gram-negative bacteria (GNB) in patients with and without COVID-19 and describe the mortality rates and clinical features associated with unfavorable outcomes. In total, we assessed 280 patients admitted to Brazilian intensive care units from March/2020 to December/2021. During the study, 926 GNB were isolated. Out of those, 504 were MDR-GNB, representing 54.4% of the resistance rate. In addition, out of 871 patients positive for COVID-19, 73 had secondary MDR-GNB infection, which represented 8.38% of documented community-acquired GNB-MDR infections. The factors associated with patients COVID-19-MDR-GNB infections were obesity, heart failure, use of mechanical ventilation, urinary catheter, and previous use of ß-lactams. Several factors associated with mortality were identified among patients with COVID-19 infected with MDR-GNB, including the use of a urinary catheter; renal failure; and the origin of bacterial cultures such as tracheal secretion, exposure to carbapenem antibiotics, and polymyxin. Mortality was significantly higher in patients with COVID-19-MDR-GNB (68.6%) compared to control groups, where COVID-19 was 35.7%, MDR-GNB was 50%, and GNB was 21.4%. Our findings demonstrate that MDR-GNB infection associated with COVID-19 has an expressive impact on increasing the case fatality rate, reinforcing the importance of minimizing the use of invasive devices and prior exposure to antimicrobials to control the bacterial spread in healthcare environments to improve the prognosis among critical patients.