Aetiology and use of antibiotics in pregnancy-related infections: results of the WHO Global Maternal Sepsis Study (GLOSS), 1-week inception cohort.

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

Risk factors and mortality of candidemia in a children's public hospital in Sao Paulo, Brazil.

Candida bloodstream infections in children are of special concern in neonatal and pediatric intensive care and patients with comorbidities. This study aimed to estimate the incidence and risk factors associated with mortality in candidemia cases occurring in a public children's hospital in Ribeirao Preto, Brazil. It is a retrospective transversal study. Every patient under the age of 18 admitted to the study facility from January 1, 2013, to December 31, 2019, was considered potentially eligible to be included if they had candidemia. We collected clinical data from medical records. We included 113 blood cultures yielding positive results for Candida. The incidence rate was 2.12 per 1000 admissions. The most common Candida species was Candida parapsilosis. Septic shock during the candidemia episode was the only clinical outcome associated with a relative risk-adjusted (RRa) of 2.77 with an interval >1 (1.12-6.85). Our findings show that the incidence rate and mortality rates of candidemia are in line with those in other children's services in Brazil. We found a global mortality rate of 28.31% (32/113) from candidemia episodes. We highlight the predominance of non-albicans Candida species including C. parapsilosis. Septic shock was the most important factor showing a significant risk of mortality.

Genomic epidemiology of SARS-CoV-2 in large university hospital cohort: the UnCoVER-Brazil project.

This work aimed to study the role of different SARS-CoV-2 lineages in the epidemiology of multiple waves of the COVID-19 pandemic in Ribeirão Preto (São Paulo state), with comparison within Brazil and globally. Viral genomic sequencing was combined with clinical and sociodemographic information of 2,379 subjects at a large Brazilian hospital. On the whole 2,395 complete SARS-CoV-2 genomes were obtained from April 2020 to January 2022. We report variants of concern (VOC) and interest (VOI) dynamics and the role of Brazilian lineages. We identified three World Health Organization VOCs (Gamma, Delta, Omicron) and one VOI (Zeta), which caused distinct waves in this cohort. We also identified 47 distinct Pango lineages. Consistent with the high prevalence of Gamma in Brazil, Pango lineage P.1 dominated infections in this cohort for half of 2021. Each wave of infection largely consisted of a single variant group, with each new group quickly and completely rising to dominance. Despite increasing vaccination in Brazil starting in 2021, this pattern was observed throughout the study and is consistent with the hypothesis that herd immunity tends to be SARS-CoV-2 variant-specific and does not broadly protect against COVID-19.

Long-Term Symptoms among COVID-19 Survivors in Prospective Cohort Study, Brazil.

We conducted a prospective cohort study in a population with diverse ethnic backgrounds from Brazil to assess clinically meaningful symptoms after surviving coronavirus disease. For most of the 175 patients in the study, clinically meaningful symptoms, including fatigue, dyspnea, cough, headache, and muscle weakness, persisted for >120 days after disease onset.

Bacteremia by Leuconostoc mesenteroides in an immunocompetent patient with chronic Chagas disease: a case report.

BACKGROUND: The Leuconostoc mesenteroides are members of the Streptococcae family and currently has been recognized as potential pathogens. This case describes a bacteremia caused by L. mesenteroides in an immunocompetent patient affected by Chagas disease. CASE PRESENTATION: A 67-year-old female patient with chagasic megaesophagus and megacolon was submitted to a Heller myotomy for achalasia in 2000 and endoscopic dilatation in 2015. Patient was admitted to the Nutrology Ward in May 2016 with protein-calorie malnutrition associated with achalasia and receiving enteral nutrition. In July 2016, the patient underwent a Serra-Doria surgery. In the third postoperative day she presented an important abdominal distension. She was submitted to a new surgical intervention, and then a terminal ileum perforation was detected, leading the surgeon to perform an enterectomy with side-to-side anastomosis. The next day after the surgery (4th postoperative day) the patient presented a decreased level of consciousness (Glasgow coma scale = 8), hypotension and hypoxemia. In two samples of blood cultures there was growth of Leuconostoc mesenteroides. Susceptibility pattern was evaluated by the diffusion disk method. The microorganism was susceptible to penicillin, ampicillin, chloramphenicol, erythromycin, and fluoroquinolones, but resistant to rifampin, tetracycline, vancomycin and teicoplanin. CONCLUSION: We concluded that infections caused by L. mesenteroides is serious and should be considered not only in settings of immunosuppression and prolonged antimicrobial use, but also in immunocompetent patients undergoing surgeries involving the gastrointestinal tract.

Hepatitis B vaccination coverage in patients with diabetes mellitus.

OBJECTIVE: Analyze the factors associated with full hepatitis B vaccination (three doses) in patients with diabetes mellitus. METHOD: Cross-sectional study, conducted in a health unit in a city in the state of São Paulo, with 255 patients on outpatient follow-up, in 2014. Data were obtained from the computerized system of the Municipal Health Department and via a structured questionnaire. A logistic regression model was used for analysis. RESULTS: Full hepatitis B vaccination was noted in 13.7% of the patients and shown to be directly associated with their educational level (OR=1.30; CI: 1.07-1.57) and current or previous work as a health professional (OR=3.21; CI: 1.16-8.89). CONCLUSION: Hepatitis B vaccination coverage was found to be low in patients with diabetes mellitus, indicating their vulnerability to this serious and potentially fatal disease. Higher educational level and working in the field of health were associated with better vaccination coverage. OBJETIVO: Analisar os fatores associados à vacinação completa contra hepatite B (3 doses) em pacientes com diabetes mellitus. MÉTODO: Estudo transversal, realizado em uma Unidade de Saúde, de uma cidade do interior paulista, com 255 pacientes em seguimento ambulatorial, em 2014. Os dados foram obtidos no sistema informatizado da Secretaria Municipal de Saúde e por meio de um questionário estruturado e, para análise, modelo de regressão logística. RESULTADOS: Vacinação completa contra hepatite B foi observada em 13,7% dos pacientes e mostrou-se diretamente associada ao nível de escolaridade (OR=1,30; IC: 1,07-1,57) e ao trabalho atual ou pregresso como profissional da saúde (OR=3,21; IC: 1,16-8,89). CONCLUSÃO: A cobertura vacinal contra hepatite B mostrou-se baixa em pacientes com diabetes mellitus, evidenciando a vulnerabilidade a essa doença grave e potencialmente fatal. Maior escolaridade e o trabalho na área da saúde foram associados a melhor cobertura vacinal.

Expansion and evolution of a virulent, extensively drug-resistant (polymyxin B-resistant), QnrS1-, CTX-M-2-, and KPC-2-producing Klebsiella pneumoniae ST11 international high-risk clone.

In this study, we report the early expansion, evolution, and characterization of a multiresistant Klebsiella pneumoniae clone that was isolated with increasing frequency from inpatients in a tertiary-care university hospital in Brazil. Seven carbapenem- and quinolone-resistant and polymyxin B-susceptible or -resistant K. pneumoniae isolates isolated between December 2012 and February 2013 were investigated. Beta-lactamase- and plasmid-mediated quinolone resistance (PMQR)-encoding genes and the genetic environment were investigated using PCR, sequencing, and restriction fragment length polymorphism (RFLP). Clonal relatedness was established using XbaI-pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and phylogenetic group characterization. Plasmid analyses included PCR-based replicon typing (PBRT) and hybridization of the S1-PFGE product, plasmid MLST, and conjugation experiments. Virulence potential was assessed by PCR by searching for 10 virulence factor-encoding genes (ureA, fimH, kfuBC, uge, wabG, magA, mrkD, allS, rmpA, and cf29a) and by phenotypic tests to analyze the hypermucoviscous phenotype. The genetic context of a multidrug-resistant and extensively drug-resistant K. pneumoniae ST11-KpI clone harboring IncFIIk-Tn4401a-blaKPC-2, qnrS1, and blaCTX-M-2 was found. Moreover, three isolates displayed high resistance to polymyxin B (MICs = 32, 32, and 128 mg/liter) as well as mucous and hypermucoviscous phenotypes. These bacteria also harbored ureA, fimH, uge, wabG, and mrkD, which code for virulence factors associated with binding, biofilm formation, and the ability to colonize and escape from phagocytosis. Our study describes the association of important coresistance and virulence factors in the K. pneumoniae ST11 international high-risk clone, which makes this pathogen successful at infections and points to the quick expansion and evolution of this multiresistant and virulent clone, leading to a pandrug-resistant phenotype and persistent bacteria in a Brazilian hospital.

Matrix metalloproteinases are associated with severity of disease among COVID-19 patients: A possible pharmacological target.

COVID-19 is a devastating disease and imbalanced matrix metalloproteinase (MMP) activity may contribute to its pathophysiology. This exploratory study examined whether increased circulating concentrations of MMP-2 and MMP-9, and their endogenous inhibitors, the tissue inhibitors of MMP (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4 are persistently found in patients 2 weeks after their recovery from severe or critical COVID-19 as compared with those in healthy controls. Subjects who had severe (n = 26) or critical (n = 25) PCR-confirmed COVID-19 and healthy controls (n = 21) had blood samples drawn 2 weeks after recovery and serum MMP-2, MMP-9, TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were determined using two Human Luminex® Discovery Assays. Circulating MMP activity was also determined by gel zymography. Patients who had severe or critical COVID-19 had increased circulating MMP-9 and MMP-2 concentrations, with increased MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios indicating increased MMP activity, confirmed by gel zymography (all p < 0.05). Higher circulating MMP-9 (but not MMP-2) concentrations were found in critical versus severe COVID-19 (p < 0.05). We found increased circulating MMP-9 and MMP-2 concentrations and activity many days after recovery from the acute disease, with MMP-9 levels associated with disease severity. These biochemical alterations suggest that MMP-2 and MMP-9 may be important pharmacological targets in COVID-19.

Updates and future directions regarding hand hygiene in the healthcare setting: insights from the 3rd ICPIC alcohol-based handrub (ABHR) task force.

Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) pose threats to global health. Effective hand hygiene is essential for preventing HAIs and the spread of AMR in healthcare. We aimed to highlight the recent progress and future directions in hand hygiene and alcohol-based handrub (ABHR) use in the healthcare setting. In September 2023, 42 experts in infection prevention and control (IPC) convened at the 3rd International Conference on Prevention and Infection Control (ICPIC) ABHR Taskforce in Geneva, Switzerland. The purpose of this meeting was to provide a synthesis of recent evidence and formulate a research agenda on four critical areas for the implementation of effective hand hygiene practices: (1) ABHR formulations and hand rubbing techniques, (2) low-resource settings and local production of ABHR, (3) hand hygiene monitoring and technological innovations, and (4) hand hygiene standards and guidelines.

Endemic paracoccidioidomycosis: relationship between clinical presentation and patients' demographic features.

Paracoccidioidomycosis (PCM) is a systemic fungal disease endemic to Latin America and characterized by two clinical presentations, i.e., patients develop either acute/subacute or chronic clinical manifestations. The differences in clinical presentations are mainly dependent on the host immune response, but may also be related to demographic characteristics of some patients. In this retrospective study, 1,219 PCM cases treated between 1970 and 2009 in a university medical center, located in southeastern Brazil, were analyzed according to their clinical and demographic features. The most affected anatomical sites were lungs (63.8%) and oral mucosa (50.0%), with increasing involvement of these sites in accord with the age of the patients. Generalized lymphadenopathy (28.1%) and skin lesions (29.6%) were more frequent on the first decades of life. Involvement of the larynx (16.1%), gut (7.5%), spleen (4.7%), central nervous system (3.4%), bones and joints (2.2%), and adrenal (2.1%) were also variable according to the age of the host. The acute/subacute form of the disease accounted for 26.4% of PCM cases and, on a multivariate analysis, was inversely associated with aging (OR = 0.8 per year, P < 0.001), and directly associated with female sex (OR = 7.2, P < 0.001), mixed black and white racial background (OR = 2.3, P < 0.001) or black skin color (OR = 4.6, P < 0.001). Based on these findings, we have shown that host immune response, as well as age, gender and ethnicity may influence the clinical presentation of PCM.

Investigating autonomic nervous system dysfunction among patients with post-COVID condition and prolonged cardiovascular symptoms.

Heart Rate Variability (HRV) and arterial pressure (AP) variability and their responses to head-up tilt test (HUTT) were investigated in Post-COVID-19 syndrome (PCS) patients reporting tachycardia and/or postural hypotension. Besides tachycardia, PCS patients also showed attenuation of the following HRV parameters: RMSSD [square root of the mean of the sum of the squares of differences between adjacent normal-to-normal (NN) intervals] from statistical measures; the power of RR (beat-to-beat interval) spectra at HF (high frequency) from the linear method spectral analysis; occurrence of 2UV (two unlike variation) pattern of RR from the nonlinear method symbolic analysis; and the new family of statistics named sample entropy, when compared to control subjects. Basal AP and LF (low frequency) power of systolic AP were similar between PCS patients and control subjects, while 0 V (zero variation) patterns of AP from the nonlinear method symbolic analysis were exacerbated in PCS patients. Despite tachycardia and a decrease in RMSSD, no parameter of HRV changed during HUTT in PCS patients compared to control subjects. PCS patients reassessed after 6 months showed higher HF power of RR spectra and a higher percentage of 2UV pattern of RR. Moreover, the reassessed PCS patients showed a lower occurrence of 0 V patterns of AP, while the HUTT elicited HR (heart rate) and AP responses identical to control subjects. The HRV and AP variability suggest an autonomic dysfunction with sympathetic predominance in PCS patients. In contrast, the lack of responses of HRV and AP variability indices during HUTT indicates a marked impairment of autonomic control. Of note, the reassessment of PCS patients showed that the noxious effect of COVID-19 on autonomic control tended to fade over time.

Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors).

BACKGROUND: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. METHODS: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. RESULTS: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. CONCLUSIONS: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

Comparing surgeons' skin tolerance and acceptability to alcohol-based surgical hand preparation vs traditional surgical scrub: A matched quasi-experimental study.

BACKGROUND: We aimed to compare the tolerance and acceptability of alcohol-based surgical hand preparation versus handscrubbing with antimicrobial soap and water by surgeons. METHODS: Matched quasi-experimental trial in an academic quaternary care hospital in Ribeirão Preto, Brazil, from April 1 to October, 31, 2017. Participants were cardiac and orthopedics surgeons from the study facility. In the first study phase, they performed handscrubbing with either 2% chlorhexidine (CHG) or 10% iodopovidone (PVP-I) and, in the second phase, they performed handrubbing with alcohol-based handrub (ABHR). Surgeons' skin tolerance and acceptability were evaluated using WHO-validated tools. Data were analyzed using the MacNemar's test within STATA. RESULTS: A total of 33 surgeons participated to the "per protocol" population; the majority were male (94%); mean age of 35 years (SD, 8.5). On product tolerance, there was a minimal variation in redness, scaliness, fissures, and visual evaluation of the skin when handrubbing with ABHR was compared to handscrubbing with either PVP-I or CHX. Regarding acceptability, participants rated better handrubbing with ABHR than handscrubbing with PVP-I when assessing product smell (66.6% vs 0%, p=0.002), color (73.3% vs 0%, p=0.001), product texture (60% vs 0%, p=0.004), skin dryness (60% vs 0%, p=0.004), ease of application (66.6% vs 0%, p=0.002) and overall satisfaction (66.6% vs 6.7% p=0.011). Participants rated similarly handrubbing with ABHR and handscrubbing with CHX, except for product texture, where handrubbing rated better (71,4% vs. 0%, p=0.002). Handrubbing with ABHR was preferred by 73.3%. CONCLUSION: Although handrubbing and handscrubbing were equally well tolerated by surgeons, alcohol-based surgical hand preparation fell into the personal preference for most of them. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (ReBEC), RBR-8ym9yj.

Assessment of preauthorization and 24-hour expert consultation as a restrictive antimicrobial stewardship bundle in a Brazilian tertiary-care hospital: an interrupted time series analysis.

BACKGROUND: Worldwide, healthcare facilities face high and often inappropriate consumption of antimicrobials. However, there are limited antimicrobial stewardship (ASP) studies from low- and middle-income countries that include restrictive measures and their impacts on antimicrobial consumption. AIM: This study aims to assess the impact of a restrictive bundle (preauthorization requirements and offering consultation with an infectious diseases physician 24 hours a day) on antimicrobial consumption, in a tertiary hospital in Brazil. METHODS: We conducted an interrupted time series analysis (ITS) with pharmacy-based data from January 2010 to December 2018 to evaluate changes of level and slope in antimicrobial consumption (expressed in DDD/1,000 patient-days) after the implementation of the restrictive bundle in September 2014. Fourteen restricted antimicrobials (amphotericin B deoxycholate, liposomal amphotericin B, micafungin, voriconazole, ganciclovir, amikacin, ampicillin/sulbactam, daptomycin, ertapenem, levofloxacin, linezolid, piperacillin/tazobactam, polymyxin B, and tigecycline) and eight unrestricted were analysed. FINDINGS: Among the 14 restricted antimicrobials, four presented a significant negative level change: micafungin (-2,14, p=.027), voriconazole (-14.72, p<.001), ertapenem (-1.89, p=.007) and amikacin (-13.98, p<.001). The only negative slope change was observed for the liposomal amphotericin B, -0.532 (p=.009). The restricted antibiotics group presented an increased consumption trend (1.068, p=.002) compared to the pre-intervention period, a similar change was observed for the unrestricted antibiotics group (1.360, p<.001). CONCLUSION: Preauthorization and 24 hour expert consultation were partially effective as a restrictive antimicrobial stewardship bundle in a Brazilian tertiary-care hospital. Increased consumption of unrestricted antimicrobials was observed as a side effect of the intervention.

Impact of a dental care intervention on the hospital mortality of critically ill patients admitted to intensive care units: A quasi-experimental study.

BACKGROUND: We aimed to evaluate the impact of providing dental care to critically ill patients on their risk of death and ventilator-associated pneumonia (VAP). METHODS: A quasi-experimental study was conducted in 2 intensive care units (ICU) from 2016 to 2019. The intervention consisted of implementing routine dental care, focusing on oral hygiene and periodontal treatment, at least 3 times a week, for patients admitted to the study units. In the pre-intervention period, routine oral hygiene was provided by the ICU nursing staff. The primary and secondary study outcomes were mortality, evaluated at the end of the ICU stay, and VAP incidence density, respectively. Data were analyzed using the ARIMA (autoregressive integrated moving average) time series model in R software. RESULTS: During the intervention period, 5,147 dental procedures were performed among 355 patients. The time series showed that ICU mortality was 36.11%, 32.71%, and 32.30% within the 3 years before the intervention, and 28.71% during the intervention period (P = .015). VAP incidence density did not significantly change during the study period (P = .716). CONCLUSION: A dental care intervention focused on oral hygiene and periodontal treatment regularly provided by dentists to critically ill patients may decrease their risk of dying in the ICU. Randomized clinical trials should be performed to confirm these findings. TRIAL REGISTRATION: WHO-affiliated Brazilian Clinical Trials Registry. RBR-4jmz36. Registered 7 October 2018, before first patient enrollment.

Potential cannabidiol (CBD) repurposing as antibacterial and promising therapy of CBD plus polymyxin B (PB) against PB-resistant gram-negative bacilli.

This study aimed to assess the ultrapure cannabidiol (CBD) antibacterial activity and to investigate the antibacterial activity of the combination CBD + polymyxin B (PB) against Gram-negative (GN) bacteria, including PB-resistant Gram-negative bacilli (GNB). We used the standard broth microdilution method, checkerboard assay, and time-kill assay. CBD exhibited antibacterial activity against Gram-positive bacteria, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, Moraxella catarrhalis), and Mycobacterium tuberculosis, but not against GNB. For most of the GNB studied, our results showed that low concentrations of PB (≤ 2 µg/mL) allow CBD (≤ 4 µg/mL) to exert antibacterial activity against GNB (e.g., Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii), including PB-resistant GNB. CBD + PB also showed additive and/or synergistic effect against LOS-expressing GND. Time-kill assays results showed that the combination CBD + PB leads to a greater reduction in the number of colony forming units per milliliter compared to CBD and PB alone, at the same concentration used in combination, and the combination CBD + PB was synergistic for all four PB-resistant K. pneumoniae isolates evaluated. Our results show that CBD has translational potential and should be further explored as a repurposed antibacterial agent in clinical trials. The antibacterial efficacy of the combination CBD + PB against multidrug-resistant and extensively drug-resistant GNB, especially PB-resistant K. pneumoniae, is particularly promising.

Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Importance: Owing to its anti-inflammatory properties and antiviral "in vitro" effect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cannabidiol (CBD) has been proposed as a potential treatment for coronavirus disease 2019 (COVID-19). Objective: To investigate the safety and efficacy of CBD for treating patients with mild to moderate COVID-19. Design: Randomized, parallel-group, double-blind, placebo-controlled clinical trial conducted between July 7 and October 16, 2020, in two sites in Brazil. Setting: Patients were recruited in an emergency room. Participants: Block randomized patients (1:1 allocation ratio-by a researcher not directly involved in data collection) with mild and moderate COVID-19 living in Ribeirão Preto, Brazil, seeking medical consultation, and those who voluntarily agreed to participate in the study. Interventions: Patients received 300 mg of CBD or placebo added to standard symptomatic care during 14 days. Main Outcome and Measure: The primary outcome was reduction or prevention of the deterioration in clinical status from mild/moderate to severe/critical measured with the COVID-19 Scale or the natural course of the resolution of typical clinical symptoms. Primary study outcome was assessed on days 14, 21, and 28 after enrollment. Results: A total of 321 patients were recruited and assessed for eligibility, and 105 were randomly allocated either in CBD (n=49) or in placebo (n=42) group. Ninety-one participants were included in the analysis of efficacy. There were no baseline between-group differences regarding disease severity (χ2=0.025, p=0.988) and median time to symptom resolution (12 days [95% confidence interval, CI, 6.5-17.5] in the CBD group, 9 days [95% CI, 4.8-13.2] in the placebo group [χ2=1.6, p=0.205 by log-rank test]). By day 28, 83.3% in the CBD group and 90.2% in the placebo group had resolved symptoms. There were no between-group differences on secondary measures. CBD was well tolerated, producing mostly mild and transient side effects (e.g., somnolence, fatigue, changes in appetite, lethargy, nausea, diarrhea, and fever), with no significant differences between CBD and placebo treatment groups. Conclusions and Relevance: Daily administration of 300 mg CBD for 14 days failed to alter the clinical evolution of COVID-19. Further trials should explore the therapeutic effect of CBD in patients with severe COVID-19, possibly trying higher doses than the used in our study. Trial Registration: ClinicalTrials.gov identifier NCT04467918 (date of registration: July 13, 2020).

Dissemination of blaKPC-2 by the spread of Klebsiella pneumoniae clonal complex 258 clones (ST258, ST11, ST437) and plasmids (IncFII, IncN, IncL/M) among Enterobacteriaceae species in Brazil.

This article reports the spread of bla(KPC-2) in the Sao Paulo and Rio de Janeiro states, facilitated by globally spread K. pneumoniae clonal complex 258 (CC258) clones (ST258, ST11, and ST437) and a diversity of plasmids (IncFII, IncN, and IncL/M, two untypeable plasmids carrying Tn4401a or Tn4401b) successfully disseminated among species of the Enterobacteriaceae (Enterobacter cloacae, Serratia marcescens, and Citrobacter freundii). It also constitutes the first description of sequence type 258 (ST258) in Brazil, which was associated with a nosocomial hospital outbreak in Ribeirao Preto city.