Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.
We conducted ...a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.
A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval CI, 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.
Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).
•Booster vaccinations are necessary to protect against emerging SARS-CoV-2 variants.•We tested three vaccine platforms, mRNA, adenovirus-vector and recombinant protein.•Using different vaccine ...platforms did not affect booster safety or immunogenicity.•All three vaccines increased immunity against Omicron BF.7, BQ.1.1.3, and XBB.1.5.6.•Fold-increases were similar for ancestor and Omicron variants within a platform.
The COVID-19 pandemic is over but the highly immunized or naturally exposed global population still requires booster vaccinations against newly emerging SARS-CoV-2 variants. We assessed safety and immunogenicity of booster doses of COVID-19 vaccines based on three different platforms in a setting that mimics the current routine practice in Brazil.
In this phase 3 study from 14 February 2023 to 12 June 2023 we enrolled previously immunized adults to receive an additional booster dose of one of three vaccines. Immunogenicity against ancestor SARS-CoV-2 and Omicron BF.7, BQ.1.1.3, and XBB.1.5.6 sub-lineages was measured as ELISA IgG or virus neutralizing (VNT) antibodies and safety/reactogenicity assessed using diary cards.
Volunteers with a history of full primary COVID-19 immunization striated to three cohorts according to their previous booster vaccination history—0 (n = 26), 1 (n = 140) or 2 (n = 606) booster vaccinations—were randomized 2:1:1 to receive either recombinant protein (SCB-2019, Clover), adenovirus-vector (ChAdOx1-S, AstraZeneca/Fiocruz), or mRNA (BNT162b2, Pfizer/Wyeth). Baseline antibody titers were higher in individuals who had received one or two boosters and titers against both ancestor and Omicron sub-lineages increased in all groups regardless of the number of previous booster doses or the vaccine used. Day 28 geometric mean titers (GMTs) and geometric mean-fold rises (GMFR) against all variants were higher after BNT162b than SCB-2019 or ChAdOx1-S, but BNT162b groups displayed more rapid antibody waning at Day 84. Within cohorts each vaccine elicited similar GMFR against the different SARS-CoV-2 strains. All vaccines were well tolerated with similar solicited reactogenicity profiles.
Protein, adenovirus-vector or mRNA vaccine boosters were equally well tolerated and immunogenic against ancestor SARS-CoV-2 and Omicron sub-lineages in fully primed adults with 0–2 prior boosters. BNT162b induced the highest immune responses but also the most rapid waning of antibodies 3 months after vaccination.
Clinical Trial Registration:ClinicalTrials.gov, identifier NCT05812586.
This study evaluated the influence of the extract of
in adhesion to human buccal epithelial cells (HBEC) biofilm formation and cell surface hydrophobicity (CSH) of
spp. isolated from the oral cavity ...of kidney transplant patients. To evaluate virulence attributes in vitro, nine yeasts were grown in the presence and absence of 1000 μg/mL of the extract. Adhesion was quantified using the number of
cells adhered to 150 HBEC determined by optical microscope. Biofilm formation was evaluated using two methodologies: XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2
-tetrazolium-5-carboxanilide) and crystal violet assay, and further analyzed by electronic scan microscopy. CSH was quantified with the microbial adhesion to hydrocarbons test. We could detect that the extract of
was able to reduce adhesion to HBEC and CSH for both
and non-
species. We also observed a statistically significant reduced ability to form biofilms in biofilm-producing strains using both methods of quantification. However, two highly biofilm-producing strains of
had a very large reduction in biofilm formation. This study reinforces the idea that besides growth inhibition,
may interfere with the expression of some virulence factors of
spp. and may be possibly applied in the future as a novel antifungal agent.
is able to switch from yeast to hyphal growth and this is an essential step for tissue invasion and establishment of infection. Due to the limited drug arsenal used to treat fungal infections and the ...constant emergence of resistant strains, it is important to search for new therapeutic candidates. Therefore, this study aimed to investigate by proteomic analysis the role of a natural product (
) in impairing hypha formation in
. We also tested the potential action of
to prevent and treat oral candidiasis induced in a murine model of oral infection and the ability of polymorphonuclear neutrophils to phagocytize
cells treated with the ethyl acetate fraction of the extract. We found that this fraction greatly reduced hypha formation after morphogenesis induction in the presence of serum. Besides, several proteins were differentially expressed in cells treated with the fraction. Surprisingly, the ethyl acetate fraction significantly reduced phagocytosis in
(Mean 120.36 ± 36.71 yeasts/100 PMNs vs. 44.68 ± 19.84 yeasts/100 PMNs). Oral candidiasis was attenuated when
cells were either pre-incubated in the presence of
or when the fraction was applied to the surface of the oral cavity after infection. These results were consistent with the reduction in CFU counts (2.36 vs. 1.85 Log10 CFU/ml) and attenuation of tissue damage observed with histopathological analysis of animals belonging to treated group. We also observed shorter true hyphae by direct examination and histopathological analysis, when cells were treated with the referred natural product. The
ethyl acetate fraction was non-toxic to human cells.
may act on essential proteins mainly related to cellular structure, reducing the capacity of filamentation and attenuating infection in a murine model, without causing any toxic effect on human cells, suggesting that it may be a future therapeutic alternative for the treatment of
infections.
The efficacy and safety of azithromycin in the treatment of COVID-19 remain uncertain. We assessed whether adding azithromycin to standard of care, which included hydroxychloroquine, would improve ...clinical outcomes of patients admitted to the hospital with severe COVID-19.
We did an open-label, randomised clinical trial at 57 centres in Brazil. We enrolled patients admitted to hospital with suspected or confirmed COVID-19 and at least one additional severity criteria as follows: use of oxygen supplementation of more than 4 L/min flow; use of high-flow nasal cannula; use of non-invasive mechanical ventilation; or use of invasive mechanical ventilation. Patients were randomly assigned (1:1) to azithromycin (500 mg via oral, nasogastric, or intravenous administration once daily for 10 days) plus standard of care or to standard of care without macrolides. All patients received hydroxychloroquine (400 mg twice daily for 10 days) because that was part of standard of care treatment in Brazil for patients with severe COVID-19. The primary outcome, assessed by an independent adjudication committee masked to treatment allocation, was clinical status at day 15 after randomisation, assessed by a six-point ordinal scale, with levels ranging from 1 to 6 and higher scores indicating a worse condition (with odds ratio OR greater than 1·00 favouring the control group). The primary outcome was assessed in all patients in the intention-to-treat (ITT) population who had severe acute respiratory syndrome coronavirus 2 infection confirmed by molecular or serological testing before randomisation (ie, modified ITT mITT population). Safety was assessed in all patients according to which treatment they received, regardless of original group assignment. This trial was registered at ClinicalTrials.gov, NCT04321278.
447 patients were enrolled from March 28 to May 19, 2020. COVID-19 was confirmed in 397 patients who constituted the mITT population, of whom 214 were assigned to the azithromycin group and 183 to the control group. In the mITT population, the primary endpoint was not significantly different between the azithromycin and control groups (OR 1·36 95% CI 0·94–1·97, p=0·11). Rates of adverse events, including clinically relevant ventricular arrhythmias, resuscitated cardiac arrest, acute kidney failure, and corrected QT interval prolongation, were not significantly different between groups.
In patients with severe COVID-19, adding azithromycin to standard of care treatment (which included hydroxychloroquine) did not improve clinical outcomes. Our findings do not support the routine use of azithromycin in combination with hydroxychloroquine in patients with severe COVID-19.
COALITION COVID-19 Brazil and EMS.
Candida albicans is a diploid yeast that in some circumstances may cause oral or oropharyngeal infections. This investigation aimed to study the prevalence of Candida spp. and to analyze the ABC ...genotypes of 76 clinical isolates of C. albicans obtained from the oral cavity of kidney transplant patients from two distinct geographic regions of Brazil.
We typed 48 strains with ABC genotyping and Microsatelitte using primer M13 and tested three virulence factors in vitro: phospholipase activity, morphogenesis and the ability to evade from polymorphonuclear neutrophils phagocytosis.
C. albicans was the most prevalent species (86.4%), followed by C. tropicalis (4.5%). C. albicans genotype A was the most prevalent (58 isolates; 76.4%), followed by genotype C (15 isolates; 19.7%) and genotype B (3 isolates; 3.9%). When Microsatellite technique with primer M13 was applied, 80% of the isolates from the South were placed within the same cluster. The majority of Genotype C strains were grouped together within two different clusters. Genotype C was considered more resistant to PMNs attack than genotypes A and B. Strains isolated from the South of Brazil showed also better ability to combat PMNs phagocytosis.
We found a high rate of C. albicans genotype C strains isolated from the oral cavity of this group of patients. This study characterized oral C. albicans strains isolated from kidney transplant recipients and will contribute to a better understanding of the pathogenesis of oral candidiasis.
The purpose of the present study was to evaluate the identification of 19 Brazilian C. dubliniensis based on the biochemical profile exhibited when tested by the commercial identification kit ID 32C ...(bioMerieux). Thirteen of the isolates were rigorously identified as C. dubliniensis and the remaining isolates (six) were considered as having a doubtful profile but the software also suggested that there was 83.6% of chances for them to be C. dubliniensis. As well as pointed by the literature the identification obtained by phenotypic tests should be considered presumptive for C. dubliniensis due to variability of this new species.
This study was designed to investigate the oral yeast colonization rate of household contacts of AIDS patients. Sixty‐four AIDS household contacts were sequentially enrolled along with 103 ...HIV‐negative blood bank donors (control group). Samples were obtained by swabbing the oral mucosa. Yeast isolates were identified by classical methods and antifungal susceptibility testing was performed according to NCCLS microbroth assay. Candida spp. was recovered from the oral cavity of 33% of the AIDS household contacts, in contrast with 14% of the control group (P = 0.003 or P = 0.04 after adjusting for oral prosthesis use). Candida albicans was the most frequently isolated species in both groups. All of the isolates were susceptible to fluconazole, itraconazole and ketoconazole. In conclusion, we were able to demonstrate a higher colonization rate in the AIDS household contacts group compared with the control group. No resistant isolates to antifungal drugs was observed. We suggest that the contact with AIDS patients may play a role as a risk factor for developing oral colonization by Candida spp.
Zusammenfassung. In dieser Studie wurde die Rate der oralen Hefebesiedlung bei Kontaktpersonen in AIDS‐Haushalten untersucht. Die AIDS‐Haushalt‐Kontaktgruppe umfaßte 64 Personen, die Kontrollgruppe 103 HIV‐negative Blutspender. Mundschleimhaut‐Abstriche bildeten das Untersuchungsmaterial. Die Hefeisolate wurden nach herkömmlichen Methoden identifiziert und ihre Antimykotikaresistenz im NCCLS‐Mikrodilutionstest bestimmt. Candida‐Arten wurden bei 33% der AIDS‐Kontaktgruppe gefunden und bei 14% der Kontrollgruppe (P = 0.003 bzw. 0.04 bei Berücksichtigung der Prothesenträger). Candida albicans war die am häufigsten isolierte Art in beiden Gruppen. Alle Isolate waren empfindlich für Fluconazol, Itraconazol und Ketoconazol. Damit wurde aufgezeigt, dass AIDS‐Kontaktpersonen häufiger als die Kontrollgruppe Candida‐besiedelt sind. Resistenzphänomene wurden nicht beobachtet. Es steht zu vermuten, dass der Kontakt mit AIDS‐Patienten einen Risikofaktor zur Candida‐Besiedlung darstellt.
This study was designed to investigate the oral yeast colonization rate of household contacts of AIDS patients. Sixty-four AIDS household contacts were sequentially enrolled along with 103 ...HIV-negative blood bank donors (control group). Samples were obtained by swabbing the oral mucosa. Yeast isolates were identified by classical methods and antifungal susceptibility testing was performed according to NCCLS microbroth assay. Candida spp. was recovered from the oral cavity of 33% of the AIDS household contacts, in contrast with 14% of the control group (P = 0.003 or P = 0.04 after adjusting for oral prosthesis use). Candida albicans was the most frequently isolated species in both groups. All of the isolates were susceptible to fluconazole, itraconazole and ketoconazole. In conclusion, we were able to demonstrate a higher colonization rate in the AIDS household contacts group compared with the control group. No resistant isolates to antifungal drugs was observed. We suggest that the contact with AIDS patients may play a role as a risk factor for developing oral colonization by Candida spp.
The purpose of the present study was to evaluate the identification of 19 Brazilian C. dubliniensis based on the biochemical profile exhibited when tested by the commercial identification kit ID 32C ...(bioMerieux). Thirteen of the isolates were rigorously identified as C. dubliniensis and the remaining isolates (six) were considered as having a doubtful profile but the software also suggested that there was 83.6% of chances for them to be C. dubliniensis. As well as pointed by the literature the identification obtained by phenotypic tests should be considered presumptive for C. dubliniensis due to variability of this new species.Dezenove culturas de C. dubliniensis isoladas no Brasil, previamente identificadas através de métodos genotípicos, foram avaliadas pelo kit comercial ID 32C (bioMerieux). Treze culturas foram identificadas como C. dubliniensis, mas as demais (seis) evidenciaram perfil duvidoso, embora o software do sistema sugerisse 83,6% de chances das mesmas pertencerem à espécie C. dubliniensis. A literatura tem registrado grande variabilidade fenotípica com esta espécie e, por isto, as identificações obtidas com este sistema deverão ser consideradas como presuntivas.
PDF
