Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study.

INTRODUCTION: The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost immune responses. METHODS: RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in São Paulo or Salvador who had received two doses of CoronaVac 6 months previously. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer-BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac. Participants were randomly assigned (5:6:5:5) by a RedCAP computer randomisation system stratified by site, age group (18-60 years or 61 years and over), and day of randomisation, with a block size of 42. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen, using a non-inferiority margin for the geometric mean ratio (heterologous vs homologous) of 0·67. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events. This study was registered with Registro Brasileiro de Ensaios Clínicos, number RBR-9nn3scw. FINDINGS: Between Aug 16, and Sept 1, 2021, 1240 participants were randomly assigned to one of the four groups, of whom 1239 were vaccinated and 1205 were eligible for inclusion in the primary analysis. Antibody concentrations were low before administration of a booster dose with detectable neutralising antibodies of 20·4% (95% CI 12·8-30·1) in adults aged 18-60 years and 8·9% (4·2-16·2) in adults 61 years or older. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was 77 (95% CI 67-88) for Ad26.COV2-S, 152 (134-173) for BNT162b2, 90 (77-104) for ChAdOx1 nCoV-19, and 12 (11-14) for CoronaVac. All heterologous regimens had anti-spike IgG responses at day 28 that were superior to homologous booster responses: geometric mean ratios (heterologous vs homologous) were 6·7 (95% CI 5·8-7·7) for Ad26.COV2-S, 13·4 (11·6-15·3) for BNT162b2, and 7·0 (6·1-8·1) for ChAdOx1 nCoV-19. All heterologous boost regimens induced high concentrations of pseudovirus neutralising antibodies. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were 8·7 (95% CI 5·9-12·9) for Ad26.COV2-S vaccine, 21·5 (14·5-31·9) for BNT162b2, and 10·6 (7·2-15·6) for ChAdOx1 nCoV-19. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529). There were five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home. INTERPRETATION: Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. FUNDING: Ministry of Health, Brazil.

Correlation of Trichosporon asahii Genotypes with Anatomical Sites and Antifungal Susceptibility Profiles: Data Analyses from 284 Isolates Collected in the Last 22 Years across 24 Medical Centers.

Trichosporon asahii is an opportunistic fungal pathogen that can cause severe infections with high mortality rates. Azole derivatives are the best-targeted therapy for T. asahii invasive infections, but azole-resistant isolates have been reported. To investigate peculiarities in the antifungal susceptibility profile (ASP) of T. asahii clinical isolates, we analyzed the genotype distribution, isolation sources, and ASP of 284 strains collected from 1997 to 2019 in different Brazilian medical centers. Species identification and genotype characterization were performed by analysis of the intergenic spacer (IGS1) region of the ribosomal DNA (rDNA). Antifungal susceptibility testing (AST) for amphotericin B and azoles was with the CLSI M27, 4th edition, microdilution broth method. Trends in the ASP of Brazilian T. asahii isolates were investigated using epidemiological cutoff values. Five different genotypes were found among the 284 isolates tested (G1, 76%; G3, 10%; G4, 3%; G5, 7%; and G7, 4%). The isolates were collected mainly from urine (55%) and blood/catheter tip samples (25%) where G1 was the most frequent genotype found (P < 0.05). The G7 isolates exhibited the highest MIC90 values for azoles compared to those for the other genotypes (P < 0.05). Genotype 7 isolates also contributed to the increasing rates of voriconazole non-wild-type isolates found in recent years (P = 0.02). No significant differences were found among the AST results generated by isolates cultured from different anatomical sites. Monitoring T. asahii genotype distributions and antifungal susceptibility profiles is warranted to prevent the spread of azole-resistant isolates.

Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.

OBJECTIVES: To investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients. METHODS: From 1 July to 30 September 2020, cases of T asahii fungemia (TAF) in a Brazilian COVID-19 referral centre were investigated. The epidemiology and clinical courses were detailed, along with a mycological investigation that included molecular species identification, haplotype diversity analysis and antifungal susceptibility testing. RESULTS: Five critically ill COVID-19 patients developed TAF in the period. All five patients had common risk conditions for TAF: central venous catheter at fungemia, previous exposure to broad-spectrum antibiotics, prior echinocandin therapy and previous prolonged corticosteroid therapy. The average time of intensive care unit hospitalisation previous to the TAF episode was 23 days. All but one patient had voriconazole therapy, and TAF 30-day mortality was 80%. The five T asahii strains from the COVID-19 patients belonged to 4 different haplotypes, mitigating the possibility of skin origin and cross-transmission linking the 5 reported episodes. The antifungal susceptibility testing revealed low minimal inhibitory concentrations for azole derivatives. CONCLUSIONS: Judicious prescription of antibiotics, corticosteroids and antifungals needs to be discussed in critically ill COVID-19 patients to prevent infections by hard-to-treat fungi like T asahii.

Differential impact of on-site or telepharmacy in the intensive care unit: a controlled before-after study.

BACKGROUND: Clinical pharmacists have an important role in the intensive care unit (ICU) team but are scarce resources. Our aim was to evaluate the impact of on-site pharmacists on medical prescriptions in the ICU. METHODS: This is a retrospective, quasi-experimental, controlled before-after study in two ICUs. Interventions by pharmacists were evaluated in phase 1 (February to November 2016) and phase 2 (February to May 2017) in ICU A (intervention) and ICU B (control). In phase 1, both ICUs had a telepharmacy service in which medical prescriptions were evaluated and interventions were made remotely. In phase 2, an on-site pharmacist was implemented in ICU A, but not in ICU B. We compared the number of interventions that were accepted in phase 1 versus phase 2. RESULTS: During the study period, 8797/9603 (91.6%) prescriptions were evaluated, and 935 (10.6%) needed intervention. In phase 2, there was an increase in the proportion of interventions that were accepted by the physician in comparison to phase 1 (93.9% versus 76.8%, P < 0.001) in ICU A, but there was no change in ICU B (75.2% versus 73.9%, P = 0.845). CONCLUSION: An on-site pharmacist in the ICU was associated with an increase in the proportion of interventions that were accepted by physicians.

Bloodstream infections caused by multidrug-resistant gram-negative bacteria: epidemiological, clinical and microbiological features.

BACKGROUND: Bloodstream infections (BSI) are associated with high morbidity and mortality. This scenario worsens with the emergence of drug-resistant pathogens, resulting in infections which are difficult to treat or even untreatable with conventional antimicrobials. The aim of this study is to describe the epidemiological aspects of BSI caused by multiresistant gram-negative bacilli (MDR-GNB). METHODS: We conducted a laboratory-based surveillance for gram-negative bacteremia over a 1-year period. The bacterial isolates were identified by MALDI-TOF/MS and the antimicrobial susceptibility testing was performed by VITEK®2. Resistance genes were identified through PCR assays. RESULTS: Of the 143 patients, 28.7% had infections caused by MDR-GNB. The risk factors for MDR bacteremia were male sex, age ≥ 60, previous antimicrobial use, liver disease and bacteremia caused by K. pneumoniae. K. pneumoniae was the most frequently observed causative agent and had the highest resistance level. Regarding the resistance determinants, SHV, TEM, OXA-1-like and CTX-M-gp1 were predominant enzymatic variants, whereas CTX-M-gp9, CTX-M-gp2, KPC, VIM, GES, OXA-48-like, NDM and OXA-23-like were considered emerging enzymes. CONCLUSIONS: Here we demonstrate that clinically relevant antibiotic resistance genes are prevalent in this setting. We hope our findings support the development of intervention measures by policy makers and healthcare professionals to face antibiotic resistance.

Assessing the Clinical Impact of the SARS-CoV-2 Gamma Variant on Intensive Care Unit Admissions: Insights from a Reference Hospital in Northeastern Brazil.

The global challenge posed by the prolonged COVID-19 pandemic underscores the critical need for ongoing genomic surveillance to identify emerging variants and formulate effective public health strategies. This retrospective observational study, conducted in a reference hospital in Northeast Brazil and comprising 2116 cases, employed PCR genotyping together with epidemiological data to elucidate the impact of the Gamma variant during its emergence, revealing distinct patterns in hospitalization rates, severity of illness, and outcomes. The study emphasizes the challenges posed by the variant, particularly an increased tendency for ICU admissions and respiratory support, especially among adults aged 18 to 59 without comorbidities. Laboratory analyses further demonstrate elevated inflammatory, coagulation, and hepatic markers in the Gamma variant cohort, suggesting a more severe systemic response. Despite limitations, including a retrospective approach and single-institution data, the study underscores the importance of ongoing genomic surveillance. Overall, this research contributes valuable insights into the impact of the Gamma variant on COVID-19 dynamics, advocating for continued research and surveillance to inform effective public health strategies regarding evolving viral variants.

Effectiveness, Tolerability, and Safety of Different Amphotericin B Formulations in Invasive Fungal Infections: A Multicenter, Retrospective, Observational Study.

PURPOSE: Data on the real-life use of amphotericin B lipid complex (ABLC) compared with other available formulations are limited. This study aimed to evaluate the effectiveness, tolerability, and safety of different amphotericin B (AMB) intravenously administered in the context of hospital practice for the treatment of invasive fungal infections (IFI) and to provide new insights into the profile of ABLC. METHODS: This is a multicenter, retrospective, observational study conducted at 10 tertiary Brazilian hospitals. Patients first exposed to any formulation of AMB for treating endemic and opportunistic IFI who had received at least 2 intravenous doses were screened. Retrospective data (from January 2014 to December 2019) were extracted from the patients' medical records. Clinical parameters were examined pre- and post-treatment to determine effectiveness; acute infusion-related side effects (IRSE) and drug interruption to determine tolerability; and adverse events, toxicity, and treatment interruption were stated to analyze safety. FINDINGS: Overall, 1879 medical records of patients were identified. The median (interquartile rate) duration of treatment was 14 (7-21) days. The overall success rate (95% confidence interval [CI]) was 65% (95% CI 60-65). ABLC proved to be effective among AMB formulations with 59% (95% CI 55.6-62.5) within complete response. This was significantly higher in patients who received the drug for a longer period, ≥4 weeks compared to <1 week treatment (P < 0.001). IRSE was observed in 446 (23.7%) patients. Eight cases (1.4%) of severe IRSE in pediatrics and 14 (1.1%) in adults resulted in treatment discontinuation. Regarding safety, 637 (33.9%) patients presented some alteration in creatinine levels during AMB exposure, and 89 (4.74%) had to interrupt or discontinue the drug within the first 14 days of therapy because of renal dysfunction. Overall mortality was 34%. IMPLICATIONS: ABLC is an effective formulation for the treatment of invasive fungal infections, with few adverse events leading to drug discontinuation or lethal outcomes. Furthermore, this real-life study confirmed the comparative safety of AMB lipid formulations versus AMB deoxycholate.

Prognostic Trends and Current Challenges in Candidemia: A Comparative Analysis of Two Multicenter Cohorts within the Past Decade.

Candidemia remains a major public health challenge due to its high mortality rates, especially in developing countries. Monitoring epidemiological trends may provide insights for better clinical outcomes. This study aimed to describe trends in the epidemiology, therapeutic practices, and mortality in candidemia through a retrospective comparative analysis between two surveillance cohorts of all candidemic adults at eleven tertiary hospitals in Brazil, from 2010-2011 (Period I) versus 2017-2018 (Period II). A total of 616 cases were diagnosed, with 247 being from Period II. These patients were more likely to have three or more coexisting comorbidities [72 (29.1%) vs. 60 (16.3%), p < 0.001], had a prior history of in-hospital admissions more often [102 (40.3%) vs. 79 (21.4%), p = 0.001], and presented with candidemia earlier after admission, within 15 days (0-328) vs. 19 (0-188), p = 0.01. Echinocandins were more frequently prescribed [102 (41.3%) vs. 50 (13.6%), p = 0.001], but time to antifungal initiation [2 days (0-14) vs. 2 (0-13), p = 0.369] and CVC removal within 48 h [90/185 (48.6%) vs. 148/319 (46.4%), p = 0.644] remained unchanged. Additionally, many patients went untreated in both periods I and II [87 (23.6%) vs. 43 (17.4%), p = 0.07], respectively. Unfortunately, no improvements in mortality rates at 14 days [123 (33.6%) vs. 93 (37.7%), p = 0.343] or at 30 days [188 (51.4%) vs. 120 (48.6%), p = 0.511] were observed. In conclusion, mortality rates remain exceedingly high despite therapeutic advances, probably associated with an increase in patients' complexity and suboptimal therapeutic interventions. Management strategies should be tailored to suit epidemiological changes, expedite diagnosis to reduce the number of untreated eligible patients and guarantee early antifungal initiation and source control.

SARS-CoV-2 Detection via RT-PCR in Matched Saliva and Nasopharyngeal Samples Reveals High Concordance in Different Commercial Assays.

BACKGROUND: Self-collected saliva samples can increase the diagnostic efficiency and benefit healthcare workers, patient care, and infection control. This study evaluated the performance of self-collected saliva samples compared to nasopharyngeal swabs using three commercial kits for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Matched nasopharyngeal and saliva samples were collected from 103 patients with either asymptomatic or symptomatic COVID-19. Both samples were evaluated using three commercial kits (TaqCheck, Allplex, and TaqPath). To evaluate sample stability, viral RNA extraction was performed in the presence or absence of an RNA-stabilizing solution. Storage conditions, including the duration, temperature, and stability after freezing and thawing of the samples, were also evaluated. RESULTS: All the saliva samples showed 100% concordance with the nasopharyngeal swab results using TaqCheck and Allplex kits, and 93% using TaqPath kit. No difference was observed in the samples that used the RNA-stabilizing solution compared to the group without the solution. The Ct values of the freeze-thawed samples after 30 days were higher than those on day 0; however, the results were consistent the fresh samples. CONCLUSION: The high concordance of SARS-CoV-2 detection via reverse transcription-polymerase chain reaction (RT-PCR) in matched saliva and nasopharyngeal samples using different commercial assays reinforces the concept that self-collected saliva samples are non-invasive, rapid, and reliable for diagnosing SARS-CoV-2 infection.

Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial.

SARS-CoV-2 and its different variants caused a "wave and wave" pandemic pattern. During the first wave we demonstrated that standardized Brazilian green propolis extract (EPP-AF®) reduces length of hospital stay in adult patients with COVID-19. Afterwards, we decided to evaluate the impact of EPP-AF in hospitalized patients during the third wave of the pandemic. BeeCovid2 was a randomized, double-blind, placebo-controlled clinical trial in hospitalized COVID-19 adult patients. Patients were allocated to receive an oral dose of 900 mg/day of EPP-AF® or placebo for 10 days. The primary outcome was length of hospital stay. Secondary outcomes included safety, secondary infection rate, duration of oxygen therapy dependency, acute kidney injury and need for intensive care. Patients were followed up for 28 days after admission. We enrolled 188 patients; 98 were assigned to the propolis group and 90 to the placebo group. The post-intervention length of hospital stay was of 6.5 ± 6.0 days in the propolis group versus 7.7 ± 7.1 days in the control group (95% CI - 0.74 [- 1.94 to 0.42]; p = 0.22). Propolis did not have significant impact on the need for oxygen supplementation or frequency of AKI. There was a significant difference in the incidence of secondary infection between groups, with 6.1% in the propolis group versus 18.9% in the control group (95% CI - 0.28 [0.1-0.76], p = 0.01). The use of EPP-AF was considered safe and associated with a decrease in secondary infections. The drug was not associated with a significant reduction in length of hospital stay. ClinicalTrials.gov (NCT04800224).

The use of standardized Brazilian green propolis extract (EPP-AF) as an adjunct treatment for hospitalized COVID-19 patients (BeeCovid2): a structured summary of a study protocol for a randomized controlled trial.

BACKGROUND: The 2019 coronavirus disease (COVID-19) pandemic continues to spread and affects large numbers of people with unprecedented impacts. Experimental evidence has already been obtained for use of the standardized extract of Brazilian green propolis (EPP-AF) against viral targets, and clinical rationality has been demonstrated for testing this extract as an adjunct to treatment in patients affected by COVID-19. The BeeCovid2 study aims to assess whether EPP-AF has an impact on the improvement of patients hospitalized with COVID-19 by reducing the length of hospital stay. METHODS: BeeCovid2 is a randomized, double-blinded, placebo-controlled clinical study being conducted in Brazil to provide further evidence on the effectiveness of standardized green propolis extract as an adjunctive treatment for adults hospitalized with COVID-19. Hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 and up to 14 days of symptoms were included. Patients under mechanical ventilation at randomization, pregnant women, cancer patients, transplanted or using immunosuppression, HIV patients, patients who used propolis in the last 30 days, bacterial or fungal infection at randomization, impossibility of using medication orally or enterally, and advanced chronic diseases (e.g., advanced heart failure, severe liver disease, and end-stage chronic kidney disease). Enrolled patients are randomized at a 1:1 ratio to receive placebo or standardized propolis extract (900 mg/day) for 10 days. The study treatments are administered in a double-blinded manner, and patients are followed for 28 days. The primary outcome is the difference in length of hospital stay in days between groups. Secondary outcomes include the need for mechanical ventilation, the rate of secondary infection, rate of acute kidney injury, the need for renal replacement therapy, the requirement for vasoactive drugs, the use of an intra-aortic balloon pump (IABP), and the use of extracorporeal membrane oxygenation (ECMO). DISCUSSION: This trial is very useful and will provide more data on the effectiveness of using the standardized Brazilian green propolis extract as an adjunctive treatment in association with standard care in adults hospitalized with moderate to severe acute COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04800224 . Registered on March 16, 2021.

SARS-CoV-2 variant of concern P.1 (Gamma) infection in young and middle-aged patients admitted to the intensive care units of a single hospital in Salvador, Northeast Brazil, February 2021.

OBJECTIVES: To evaluate changes in the characteristics of patients with coronavirus disease 2019 (COVID-19) after the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) P.1 (Gamma), by comparing the clinical, demographic, and laboratory profiles of patients hospitalized during the first (May to July 2020) and second (December 2020 to February 2021) pandemic waves. METHODS: Data were collected from the records of COVID-19 patients (n = 4164) admitted to a single hospital in Salvador, Northeast Brazil. SARS-CoV-2 genome sequencing was performed on nasopharyngeal swab samples from 12 patients aged <60 years admitted to the intensive care unit (ICU) in February 2021. RESULTS: Between June 2020 and February 2021, the median age of patients admitted to the ICU decreased from 66 to 58 years (P < 0.05). This was accompanied by an increased proportion of patients without comorbidities (15.32% vs 32.20%, P < 0.0001). A significant reduction in the cycle threshold values of SARS-CoV-2 RT-PCR tests was observed in the second wave (P < 0.0001). Sequencing analysis detected lineage Gamma in all 12 ICU patients sampled in February 2021. CONCLUSIONS: The results of this study demonstrated an increased proportion of younger adults without comorbidities with severe disease during the second COVID-19 wave, shortly after the confirmation of local Gamma circulation.

Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 lineages circulating in Brazil.

Several COVID-19 vaccines have shown good efficacy in clinical trials, but there remains uncertainty about the efficacy of vaccines against different variants. Here, we investigate the efficacy of ChAdOx1 nCoV-19 (AZD1222) against symptomatic COVID-19 in a post-hoc exploratory analysis of a Phase 3 randomised trial in Brazil (trial registration ISRCTN89951424). Nose and throat swabs were tested by PCR in symptomatic participants. Sequencing and genotyping of swabs were performed to determine the lineages of SARS-CoV-2 circulating during the study. Protection against any symptomatic COVID-19 caused by the Zeta (P.2) variant was assessed in 153 cases with vaccine efficacy (VE) of 69% (95% CI 55, 78). 49 cases of B.1.1.28 occurred and VE was 73% (46, 86). The Gamma (P.1) variant arose later in the trial and fewer cases (N = 18) were available for analysis. VE was 64% (-2, 87). ChAdOx1 nCoV-19 provided 95% protection (95% CI 61%, 99%) against hospitalisation due to COVID-19. In summary, we report that ChAdOx1 nCoV-19 protects against emerging variants in Brazil despite the presence of the spike protein mutation E484K.

Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes challenging immune and inflammatory phenomena. Though various therapeutic possibilities have been tested against coronavirus disease 2019 (COVID-19), the most adequate treatment has not yet been established. Propolis is a natural product with considerable evidence of immunoregulatory and anti-inflammatory activities, and experimental data point to potential against viral targets. We hypothesized that propolis can reduce the negative effects of COVID-19. METHODS: In a randomized, controlled, open-label, single-center trial, hospitalized adult COVID-19 patients were treated with a standardized green propolis extract (EPP-AF®ï¸) as an adjunct therapy. Patients were allocated to receive standard care plus an oral dose of 400 mg or 800 mg/day of green propolis for seven days, or standard care alone. Standard care included all necessary interventions, as determined by the attending physician. The primary end point was the time to clinical improvement, defined as the length of hospital stay or oxygen therapy dependency duration. Secondary outcomes included acute kidney injury and need for intensive care or vasoactive drugs. Patients were followed for 28 days after admission. RESULTS: We enrolled 124 patients; 40 were assigned to EPP-AF®ï¸ 400 mg/day, 42 to EPP-AF®ï¸ 800 mg/day, and 42 to the control group. The length of hospital stay post-intervention was shorter in both propolis groups than in the control group; lower dose, median 7 days versus 12 days (95% confidence interval [CI] -6.23 to -0.07; p = 0.049) and higher dose, median 6 days versus 12 days (95% CI -7.00 to -1.09; p = 0.009). Propolis did not significantly affect the need for oxygen supplementation. In the high dose propolis group, there was a lower rate of acute kidney injury than in the controls (4.8 vs 23.8%), (odds ratio [OR] 0.18; 95% CI 0.03-0.84; p = 0.048). No patient had propolis treatment discontinued due to adverse events. CONCLUSIONS: Addition of propolis to the standard care procedures resulted in clinical benefits for the hospitalized COVID-19 patients, especially evidenced by a reduction in the length of hospital stay. Consequently, we conclude that propolis can reduce the impact of COVID-19.

Effect of a palliative care program on trends in intensive care unit utilization and do-not-resuscitate orders during terminal hospitalizations. An interrupted time series analysis. / Efeitos de um programa de cuidados paliativos nas tendências de utilização da unidade de terapia intensiva e ordens de não reanimar durante hospitalizações terminais. Análise de séries temporais interrompidas.

OBJECTIVE: To assess the effect of the implementation of a palliative care program on do-not-resuscitate orders and intensive care unit utilization during terminal hospitalizations. METHODS: Data were retrospectively collected for all patients who died in a tertiary hospital in Brazil from May 2014 to September 2016. We analyzed the frequency of do-not-resuscitate orders and intensive care unit admissions among in-hospital deaths. Interrupted time series analyses were used to evaluate differences in trends of do-not-resuscitate orders and intensive care unit admissions before (17 months) and after (12 months) the implementation of a palliative care program. RESULTS: We analyzed 48,372 hospital admissions and 1,071 in-hospital deaths. Deaths were preceded by do-not-resuscitate orders in 276 (25.8%) cases and admissions to the intensive care unit occurred in 814 (76%) cases. Do-not-resuscitate orders increased from 125 (20.4%) to 151 (33%) cases in the pre-implementation and post-implementation periods, respectively (p < 0.001). Intensive care unit admissions occurred in 469 (76.5%) and 345 (75.3%) cases in the pre-implementation and post-implementation periods, respectively (p = 0.654). Interrupted time series analyses confirmed a trend of increased do-not-resuscitate order registrations, from an increase of 0.5% per month pre-implementation to an increase of 2.9% per month post-implementation (p < 0.001), and demonstrated a trend of decreased intensive care unit utilization, from an increase of 0.6% per month pre-implementation to a decrease of -0.9% per month in the post-implementation period (p = 0.001). CONCLUSION: The implementation of a palliative care program was associated with a trend of increased registration of do-not-resuscitate orders and a trend of decreased intensive care unit utilization during terminal hospitalizations.

OBJETIVO: Avaliar os efeitos da implantação de um programa de cuidados paliativos no estabelecimento de ordens de não reanimar e na utilização da unidade de terapia intensiva em hospitalizações terminais. MÉTODO: Os dados de todos os pacientes que faleceram em um hospital terciário brasileiro, entre maio de 2014 e setembro de 2016, foram coletados de forma retrospectiva. Analisamos a frequência do estabelecimento de ordens de não reanimar e de admissões à unidade de terapia intensiva entre os casos de óbito hospitalar. Utilizou-se análise de séries temporais interrompidas para avaliar as diferenças, em termos de tendências de estabelecimento de ordens de não reanimar e de admissões à unidade de terapia intensiva antes (15 meses) e após (12 meses) a implantação do programa de cuidados paliativos. RESULTADOS: Analisamos um total de 48.372 admissões ao hospital, dentre as quais 1.071 óbitos no hospital. Os óbitos foram precedidos de ordens de não reanimar em 276 (25,8%) casos e ocorreram admissões à unidade de terapia intensiva em 814 (76%) casos. O estabelecimento de ordens de não reanimar aumentou de 125 (20,4%) para 151 (33%) casos, na comparação entre os períodos antes e após a implantação do programa de cuidados paliativos (p < 0,001). Ocorreram admissões à unidade de terapia intensiva em 469 (76,5%) e 345 (75,3%) dos casos, respectivamente, nos períodos pré e após a implantação do programa de cuidados paliativos (p = 0,654). A análise de séries temporais confirmou tendência ao aumento do estabelecimento de ordens de não reanimar de 0,5% por mês antes da implantação para 2,9% ao mês após a implantação (p < 0,001), demonstrando-se tendência à diminuição de utilização da unidade de terapia intensiva, de uma tendência a aumento de 0,6% ao mês, antes da implantação do programa, para diminuição de -0,9% ao mês no período, após a implantação (p = 0,001). CONCLUSÃO: A implantação de um programa de cuidados paliativos se associou com tendência ao aumento no estabelecimento de ordens de não reanimar e à diminuição do uso da unidade de terapia intensiva durante hospitalizações terminais.

New guidelines for the clinical management of febrile neutropenia and sepsis in pediatric oncology patients.

OBJECTIVES: To provide a foundation for the diagnostic, prophylactic and therapeutic management of febrile neutropenia and sepsis in children with oncological diseases, with special attention to new protocols and guidelines. SOURCES: A review of the scientific literature utilizing an electronic bibliographic search on MEDLINE, Medscape, SciELO, Google, Cochrane and PubMED using the keywords febrile, neutropenic, cancer, children, sepsis, intensive, care. Articles published between 1987 and 2007 were selected, with preference given to review articles, protocols, systematic reviews, epidemiological studies, task force recommendations and phase III clinical trials. Consensus documents published by the Infectious Diseases Society of America, the Center for Diseases Control and the Infectious Diseases Working Party of the German Society of Hematology and Oncology, in addition to the recommendations of the World Federation of Pediatric Intensive and Critical Care Societies and Society of Critical Care Medicine, were also reviewed. SUMMARY OF THE FINDINGS: The use of aggressive chemotherapy regimens, bone marrow transplantation and intensive care resources have increased the survival rates of children with cancer and also their infectious morbidity, with septic complications as the principal cause of mortality. Several risk factors have been identified, such as neutropenia, oncology type, clinical signs and inflammatory response markers (polymerase chain reaction, procalcitonin) and also increased resistance to antimicrobials and antifungal agents. Protocols for risk classification, diagnosis and treatment should be established at each service, taking into account the microbiological flora of each population. Pediatric intensive care has increased the short and long-term survival of these patients. CONCLUSIONS: Oncology patients are particularly vulnerable to infectious complications. Early identification and treatment are fundamental to improving survival rates.

Direct identification from positive blood broth culture by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Bloodstream infections (BSIs) are among the most concerning bacterial infections. They are one of the leading causes of morbidity and mortality, and occur in 30-70% of critical care patients. The prompt identification of the causative microorganism can help choosing the appropriate antimicrobial therapy that will lead to better clinical outcomes. Blood culture is one of the most relevant tests for microbiological diagnosis of bacterial infections. The introduction of the MALDI-TOF microbiological diagnosis significantly decreased the time of identifying microorganisms. However, it depends on the growth on solid culture medium. In this study, 538 bottles of positive blood cultures were evaluated to test the accuracy of an in house modified protocol. The study sample consisted of 198 Gram-negative and 350 Gram-positive bacteria. In all, 460 (83.94%) species were identified based on the direct plate findings. The protocol allowed the identification of 185/198 (93.43%) of the Gram-negative bacteria, including aerobes, anaerobes, and non-fermenters, and 275/350 (78.85%) of the Gram-positive bacteria. The proposed method has the potential to provide accurate results in comparison to the traditional method with the potential to reduce the turnaround time for the results and optimize antimicrobial therapy in BSI.

Avaliação da colonização por bactérias multirresistentes em pacientes admitidos via central de regulação do estado em um hospital filantrópico em Salvador, Bahia / Evaluation of colonization by multiresistant bacteria in patients admitted via central regulation of the state in a philanthropic hospital in Salvador, Bahia / Evaluación de la colonización por bacterias multirresistentes en pacientes admitidos vía central de regulación del estado en un hospital filantrópico en Salvador, Bahia

Justificativa e Objetivos: Infecções Relacionadas à Assistência à Saúde (IRAS) são consideradas um problema de saúde pública cujo controle pode minimizar a morbimortalidade dos pacientes. A instituição precoce de isolamento de contato para pacientes possivelmente colonizados por microrganismos multirresistentes (MR), pode reduzir sua disseminação os casos de IRAS e custos hospitalares. O objetivo deste estudo foi avaliar a frequência e impacto de culturas de vigilância positivas com microrganismos multirresistentes (MR) após um surto de Enterococcus spp. resistentes à vancomicina (VRE). Métodos: Foram implementadas rotinas de coleta de culturas de vigilância a partir de abril de 2014 para pacientes procedentes de outras unidades de saúde via Central de Regulação do Estado e Município em um hospital filantrópico em Salvador­BA. Resultados: Foram avaliados 663 pacientes no período de dezembro de 2014 a dezembro de 2015, sendo que 42 destes apresentaram cultura de vigilância positiva para microrganismos gram positivos e negativos MR. Após a implementação da rotina de realização de culturas de vigilância, não foram mais detectados surtos na nossa unidade. Conclusão: A rotina de culturas de vigilância pode funcionar como um importante instrumento na prevenção da disseminação de MR.(AU)

Background and Objectives: Health Care Related Infections (IRAS) are considered a public health problem whose control can minimize patients' morbidity and mortality. The early institution of contact isolation for patients possibly colonized by multiresistant (MR) microorganisms can reduce their spread in cases of IRAS and hospital costs. This study aimed to evaluate the frequency and impact of positive surveillance cultures with multiresistant (MR) microorganisms following an outbreak of vancomycin resistant Enterococcus spp. (VRE). Methods: Surveillance cultures collection routines were implemented since April / 14 for patients referred from other health to a philanthropic hospital in Salvador ­ Bahia via state and municipal referral center. Results: A total of 663 patients were evaluated in the period from December / 14 to December / 15, and 42 of them had a positive surveillance culture for gram positive and negative MR microorganisms. After the routine implementation of surveillance cultures, no outbreaks were detected in our unit. Conclusion: Despite the high cost, the study showed that routine surveillance cultures are an important tool in preventing MR dissemination.(AU)

Justificación y objetivos: Infecciones Relacionadas a la Asistencia sanitaria (IRAS) se consideran un problema de salud pública cuyo control puede minimizar la morbimortalidad de los pacientes. La institución precoz de aislamiento de contacto para pacientes posiblemente colonizados por microrganismos multirresistentes (MR), puede reducir su diseminación de los casos de IRAS y costos hospitalarios. El objetivo del estudio fue evaluar la frecuencia e impacto de cultivos de vigilancia positivos con microrganismos multirresistentes (MR) después de un brote de Enterococcus spp. resistentes a la vancomicina (VRE). Métodos: Se implementaron rutinas de recolección de cultivos de vigilancia a partir de abril / 14 para pacientes procedentes de otras unidades de salud vía Central de Regulación del Estado y Municipio en un hospital filantrópico en Salvador - BA. Resultados: Se evaluaron 663 pacientes en el período de diciembre / 14 a diciembre / 15, siendo que 42 de ellos presentaron un cultivo de vigilancia positiva para microrganismos gram positivos y negativos MR. Después de la implementación de la rutina de realización de cultivos de vigilancia, ya no se detectaron brotes en nuestra unidad. Conclusión: La rutina de cultivos de vigilancia puede ser un importante instrumento en la prevención de la diseminación de MR.(AU)

Colistin induced neurotoxity: a case report and review of literature / Neurotoxicidade induzida pela colistina: relato de caso e revisão de literatura

OBJECTIVE: To describe a case of neurotoxity associated to Colistin. CASE DESCRIPTION: A 29-year-old black male under treatment for urinary tract infection with identification of Klebsiella pneumoniae in urine culture resistant to all carbapenem antibiotics, presented visual turbidity, paresthesia on the face and upper left limb, slowed and discordant speech in the fourth day of Colistin use. Symptoms improved after reduction of the dose of colistin with adjustment for renal function, with complete reversion after discontinuation of the drug. CONCLUSIONS: Colistin-mediated neurotoxicity must be suspected in patients with altered mental status of unknown etiology and therapy promptly interrupted.

OBJETIVO: Descrever um caso de neurotoxidade associada à Colistina. DESCRIÇÃO DO CASO (desnecessário repetição): Um homem negro de 29 anos sob tratamento para infecção do trato urinário com identificação de Klebsiella pneumoniae (escrever corretamente) em cultura de urina resistente a carbapenêmicos, apresentou turvação visual, parestesia em face e membro superior esquerdo, discurso lento e discordante na quarto dia de uso da Colistina. Os sintomas melhoraram após a redução da dose de colistina com ajuste para a função renal, com reversão completa após a descontinuação do fármaco. CONCLUSÕES: A neurotoxicidade mediada por colistina deve ser suspeitada em pacientes com estado mental alterado de etiologia desconhecida e a terapia prontamente interrompida.

Efeitos de um programa de cuidados paliativos nas tendências de utilização da unidade de terapia intensiva e ordens de não reanimar durante hospitalizações terminais. Análise de séries temporais interrompidas / Effect of a palliative care program on trends in intensive care unit utilization and do-not-resuscitate orders during terminal hospitalizations. An interrupted time series analysis

RESUMO Objetivo: Avaliar os efeitos da implantação de um programa de cuidados paliativos no estabelecimento de ordens de não reanimar e na utilização da unidade de terapia intensiva em hospitalizações terminais. Método: Os dados de todos os pacientes que faleceram em um hospital terciário brasileiro, entre maio de 2014 e setembro de 2016, foram coletados de forma retrospectiva. Analisamos a frequência do estabelecimento de ordens de não reanimar e de admissões à unidade de terapia intensiva entre os casos de óbito hospitalar. Utilizou-se análise de séries temporais interrompidas para avaliar as diferenças, em termos de tendências de estabelecimento de ordens de não reanimar e de admissões à unidade de terapia intensiva antes (15 meses) e após (12 meses) a implantação do programa de cuidados paliativos. Resultados: Analisamos um total de 48.372 admissões ao hospital, dentre as quais 1.071 óbitos no hospital. Os óbitos foram precedidos de ordens de não reanimar em 276 (25,8%) casos e ocorreram admissões à unidade de terapia intensiva em 814 (76%) casos. O estabelecimento de ordens de não reanimar aumentou de 125 (20,4%) para 151 (33%) casos, na comparação entre os períodos antes e após a implantação do programa de cuidados paliativos (p < 0,001). Ocorreram admissões à unidade de terapia intensiva em 469 (76,5%) e 345 (75,3%) dos casos, respectivamente, nos períodos pré e após a implantação do programa de cuidados paliativos (p = 0,654). A análise de séries temporais confirmou tendência ao aumento do estabelecimento de ordens de não reanimar de 0,5% por mês antes da implantação para 2,9% ao mês após a implantação (p < 0,001), demonstrando-se tendência à diminuição de utilização da unidade de terapia intensiva, de uma tendência a aumento de 0,6% ao mês, antes da implantação do programa, para diminuição de -0,9% ao mês no período, após a implantação (p = 0,001). Conclusão: A implantação de um programa de cuidados paliativos se associou com tendência ao aumento no estabelecimento de ordens de não reanimar e à diminuição do uso da unidade de terapia intensiva durante hospitalizações terminais.

ABSTRACT Objective: To assess the effect of the implementation of a palliative care program on do-not-resuscitate orders and intensive care unit utilization during terminal hospitalizations. Methods: Data were retrospectively collected for all patients who died in a tertiary hospital in Brazil from May 2014 to September 2016. We analyzed the frequency of do-not-resuscitate orders and intensive care unit admissions among in-hospital deaths. Interrupted time series analyses were used to evaluate differences in trends of do-not-resuscitate orders and intensive care unit admissions before (17 months) and after (12 months) the implementation of a palliative care program. Results: We analyzed 48,372 hospital admissions and 1,071 in-hospital deaths. Deaths were preceded by do-not-resuscitate orders in 276 (25.8%) cases and admissions to the intensive care unit occurred in 814 (76%) cases. Do-not-resuscitate orders increased from 125 (20.4%) to 151 (33%) cases in the pre-implementation and post-implementation periods, respectively (p < 0.001). Intensive care unit admissions occurred in 469 (76.5%) and 345 (75.3%) cases in the pre-implementation and post-implementation periods, respectively (p = 0.654). Interrupted time series analyses confirmed a trend of increased do-not-resuscitate order registrations, from an increase of 0.5% per month pre-implementation to an increase of 2.9% per month post-implementation (p < 0.001), and demonstrated a trend of decreased intensive care unit utilization, from an increase of 0.6% per month pre-implementation to a decrease of -0.9% per month in the post-implementation period (p = 0.001). Conclusion: The implementation of a palliative care program was associated with a trend of increased registration of do-not-resuscitate orders and a trend of decreased intensive care unit utilization during terminal hospitalizations.