Prevalence of bloodstream infection pathogens in hemato-oncological patients and predictors of carbapenem-resistant gram-negative bacterial infections during febrile neutropenia.

BACKGROUND: Carbapenem-Resistant Gram-Negative (CRGN) Bloodstream Infections (BSI) represent a therapeutic challenge, especially in the context of Febrile Neutropenia (FN) in cancer patients. METHODS: We characterized pathogens causing BSI in patients aged ≥18 years who had undergone systemic chemotherapy for solid or hematological cancers between 2012 and 2021 in Porto Alegre, Brazil. Predictors of CRGN were evaluated through a case-control analysis. Each case was matched to two controls from whom CRGN were not isolated and had the same sex and year of inclusion in the study. RESULTS: From 6094 blood cultures evaluated, 1512 (24.8%) showed positive results. Gram-negative bacteria accounted for 537 (35.5%) of the isolated bacteria, of which 93 (17.3%) were carbapenem-resistant. From 105 patients included in the case-control analysis, all cases had baseline hematological malignancies (60% acute myeloid leukemia). Variables related to CRGN BSI in Cox regression analysis were the first chemotherapy session (p<0.01), chemotherapy performed in the hospital setting (p = 0.03), intensive care unit admission (p<0.01), and CRGN isolation in the previous year (p<0.01). Patients with CRGN BSI received 75% less empirical active antibiotics and had 27.2% higher 30-day mortality rates than controls. CONCLUSIONS: A CRGN risk-guided approach should be considered for empirical antibiotic therapy in patients with FN.

Melatonin for prevention of acute kidney injury in patients treated with intravenous polymyxin B: a double-blind, placebo-controlled randomized clinical trial.

OBJECTIVES: To evaluate the effect of melatonin versus placebo on the incidence of acute kidney injury (AKI) in patients treated with polymyxin B. METHODS: We performed a single-centre, double-blind, randomized clinical trial (NCT03725267) of 30-mg oral melatonin versus placebo for patients treated with intravenous polymyxin B. Patients aged ≥18 years receiving polymyxin B for ≤48 hours were eligible. Melatonin or placebo pills were administered until the end of polymyxin B treatment or for a maximum of 14 days. The main outcome was any level of AKI. RESULTS: Eighty-eight patients were randomized: 44 in the melatonin group and 44 in the placebo group. The study ended prematurely because of polymyxin B shortage during the COVID-19 pandemic. The patients' mean age was 63.6 ± 17.3 years, and 60.2% of the patients were men. Forty-six (52.3%, 23 in each group) patients developed AKI during the follow-up period. The incidence rate of AKI was 81.9/1000 and 77.4/1000 patients per day in melatonin and placebo groups, respectively (hazard ratio, 1.09; 95% CI, 0.61-1.94; p 0.78). Renal failure and 30-day mortality were similar between the groups. Moreover, the incidence of AKI was not different in pre-specified sub-groups. DISCUSSION: Melatonin initiated in the first 48 hours of therapy did not reduce the incidence of AKI in patients treated with polymyxin B.

Prevalence of bloodstream infection pathogens in hemato-oncological patients and predictors of carbapenem-resistant gram-negative bacterial infections during febrile neutropenia

ABSTRACT Background: Carbapenem-Resistant Gram-Negative (CRGN) Bloodstream Infections (BSI) represent a therapeutic challenge, especially in the context of Febrile Neutropenia (FN) in cancer patients. Methods: We characterized pathogens causing BSI in patients aged ≥18 years who had undergone systemic chemotherapy for solid or hematological cancers between 2012 and 2021 in Porto Alegre, Brazil. Predictors of CRGN were evaluated through a case-control analysis. Each case was matched to two controls from whom CRGN were not isolated and had the same sex and year of inclusion in the study. Results: From 6094 blood cultures evaluated, 1512 (24.8%) showed positive results. Gram-negative bacteria accounted for 537 (35.5%) of the isolated bacteria, of which 93 (17.3%) were carbapenem-resistant. From 105 patients included in the case-control analysis, all cases had baseline hematological malignancies (60% acute myeloid leukemia). Variables related to CRGN BSI in Cox regression analysis were the first chemotherapy session (p<0.01), chemotherapy performed in the hospital setting (p = 0.03), intensive care unit admission (p<0.01), and CRGN isolation in the previous year (p<0.01). Patients with CRGN BSI received 75% less empirical active antibiotics and had 27.2% higher 30-day mortality rates than controls. Conclusions: A CRGN risk-guided approach should be considered for empirical antibiotic therapy in patients with FN.

Antimicrobial stewardship programme associated with earlier prescription of in vitro susceptible therapy and lower 14-day mortality in patients with carbapenem-resistant Enterobacterales bacteraemia: a cohort study.

OBJECTIVES: This study analysed the impact of antimicrobial stewardship team (AST) evaluation on time to susceptible in vitro therapy and mortality of patients with carbapenem-resistant Enterobacterales (CRE) bacteraemia. METHODS: We performed a retrospective cohort study (February 2018 to July 2020) to evaluate the impact of AST evaluation, along with other clinical and microbiological variables, on time to appropriate antibiotics, 14-day mortality and in-hospital mortality in patients aged >18 years with CRE bacteraemia. A Cox regression model was used for multivariate analysis. RESULTS: A total of 142 patients were included. The proportion of patients who received appropriate antibiotics in the first 5 days after bacteraemia was 82/92 (89.1%) versus 29/50 (58.0%) evaluated and not evaluated by the AST, respectively (P < 0.01). AST evaluation reduced the median time to appropriate therapy (49.8 h vs. 71.1 h; P = 0.01). AST intervention was independently associated with earlier prescription of appropriate therapy (P = 0.02) when controlled for septic shock (P < 0.01) and CRE isolation in the previous 90 days (P = 0.04). Regarding mortality, 51 patients (35.9%) died within 14 days (25.8% vs. 44.7% with and without AST intervention, respectively; P = 0.02) and 82 patients (57.7%) in hospital (52.2% vs. 68.0% evaluated and not evaluated by the AST, respectively; P = 0.08). AST intervention was independently protective for 14-day mortality (P = 0.03) when controlled for septic shock status (P < 0.01). CONCLUSION: AST guidance improves the quality of antibiotic prescriptions and clinical outcomes in patients with CRE bacteraemia.

Profilaxia pré-exposição no controle do HIV: uma revisão de efetividade e potenciais complicações / Preexposure prophylaxis for HIV control: a review of effectiveness and potential complications

INTRODUÇÃO. A infecção por HIV permanece sendo um problema de saúde mundial. Dessa forma, a Profilaxia Pré-Exposição (PrEP) surgiu como um método complementar de prevenção. Este trabalho tem como objetivo avaliar a eficácia da PrEP contra a infecção por HIV, o contexto de resistência viral e incidência de infecções sexualmente transmissíveis. MÉTODOS. Revisão narrativa, com busca de artigos na plataforma PubMed, utilizando os descritores HIV AND PrEP, filtrando para artigos do tipo ensaio clínico ou coorte prospectiva, realizados em humanos, publicados há, no máximo, 10 anos e em língua inglesa. RESULTADOS. A eficácia da PrEP contra infecção por HIV foi avaliada por 8 estudos. Elevados níveis de proteção contra o HIV foram demonstrados, com taxas de efetividade variando entre 73% e 85% considerando aderência adequada ao tratamento profilático. A resistência viral foi reportada em 7 estudos que avaliaram pacientes infectados por HIV durante o uso da PrEP, 6 deles identificaram casos de resistência viral, variando conforme os níveis de aderência obtidos e o perfil de uso dos pacientes. Um estudo feito em Montreal, Canadá, verificou maior incidência de infecções sexualmente transmissíveis em indivíduos usuários de PrEP, com um aumento generalizado de 72%. CONCLUSÃO. A PrEP é uma medida eficaz na proteção contra o HIV, sendo uma importante ferramenta de saúde pública no controle da doença. Apesar de sua efetividade, a PrEP não é isenta de limitações, repercutindo em riscos elevados de infecções sexualmente transmissíveis associadas e resistência viral. O papel do profissional de saúde é fundamental na indicação adequada e acompanhamento de pessoas que podem se beneficiar do uso da PrEP.

AIMS. HIV infection is a worldwide health issue, in that scenario PrEP has emerged as a complementary method of prevention. This review aims to evaluate the effectiveness of Pre-exposure prophylaxis (PrEP) against HIV infection, the viral resistance context, and the incidence of associated sexually transmitted infections. METHODS. It was conducted a narrative review on the PubMed platform using the descriptors HIV AND PrEP. Included studies were clinical trials or prospective cohorts, performed in humans, published in a maximum of 10 years and in English language. RESULTS. The effectiveness of PrEP against HIV infection was evaluated by 8 studies. High levels of protection against HIV have been demonstrated, with effectiveness rates varying between 73% and 85% in studies with proper adherence to the prophylactic treatment. Viral resistance was reported in 7 studies evaluating HIV-infected patients during the use of PrEP, 6 of which have identified cases of viral resistance, varying according to adherence levels achieved and patient profile. A study in Montréal, Canada, found a higher incidence of sexually transmitted infections in individuals using PrEP, with a generalized increase of 72%. CONCLUSION. PrEP is an effective way of prevention and an important public health tool for disease control. Despite its effectiveness, PrEP has limitations: it reflects higher risks of sexually transmitted diseases and viral resistance. Health professionals play a central role indicating PrEP and following-up people who can benefit from its use.