Evaluation of clinical and microbiological factors related to mortality in patients with Gram-negative bacterial infections treated with ceftazidime-avibactam: A prospective multicentric cohort study.

OBJECTIVES: This study aimed to evaluate the clinical and microbiological risk factors associated with mortality in patients treated with ceftazidime-avibactam for carbapenem-resistant Gram-negative bacterial infections. METHODS: This multicentric prospective cohort study included hospitalized adult patients with a microbiologically confirmed infection treated with ceftazidime-avibactam for ≥48 hours. The clinical and microbiological risk factors for 30-day mortality were evaluated using a Cox regression model. RESULTS: Of the 193 patients evaluated from the five tertiary hospitals, 127 were included in the study. Thirty-five patients (27.6%) died within 30 days. Infections with AmpC beta-lactamase-carrying bacteria were independently related to 30-day mortality (adjusted hazard ratio [aHR] 2.49, 95% confidence interval [CI] 1.28-4.84, P < 0.01) after adjusting for time from infection to antimicrobial prescription (P = 0.04). Further, these bacterial infections were also related to higher in-hospital mortality (aHR 2.17, 95% CI 1.24-3.78, P < 0.01). Only one patient developed resistance to ceftazidime-avibactam during treatment. CONCLUSIONS: Treatment with ceftazidime-avibactam had worse clinical outcomes in patients with infections with bacteria with chromosomally encoded AmpC beta-lactamase. However, these findings should be confirmed in future studies.

Comparison between Colistin and Polymyxin B in the Treatment of Bloodstream Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii-calcoaceticus Complex.

Polymyxins are still widely used for the treatment of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa bloodstream infections (BSIs). This study seeks to evaluate the impact of polymyxin B versus colistin on mortality and nephrotoxicity in BSI caused by these bacteria. We conducted a retrospective cohort study from 2014 to 2021 in Porto Alegre, Brazil. We included patients aged ≥18 years and excluded patients with polymicrobial infection or treatment for ≤48 h. The 30-day mortality was the primary outcome evaluated through Cox regression. We included 259 patients with BSI episodes: 78.8% caused by A. baumannii and 21.2% caused by P. aeruginosa. Polymyxin B did not impact mortality compared to colistin (adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI), 0.52-1.30; p = 0.40 (when adjusted for COVID-19 comorbidity, p = 0.05), Pitt bacteremia score, p < 0.01; Charlson comorbidity index, p < 0.001; time to start active antimicrobial therapy, p = 0.02). Results were maintained in the subgroups of BSI caused by A. baumannii (aHR, 0.92; 95% CI, 0.55-1.54; p = 0.74), P. aeruginosa (aHR, 0.47; 95% CI, 0.17-1.32; p = 0.15) and critical care patients (aHR, 0.77; 95% CI, 0.47-1.26; p = 0.30). Treatment with polymyxin B or colistin did not impact 30-day mortality in patients with carbapenem-resistant A. baumannii or P. aeruginosa BSI.

Antimicrobial Therapy Duration for Bloodstream Infections Caused by Pseudomonas aeruginosa or Acinetobacter baumannii-calcoaceticus complex: A Retrospective Cohort Study.

BACKGROUND: Ideal therapy duration for Pseudomonas aeruginosa or Acinetobacter baumannii-calcoaceticus complex (ABC) bloodstream infections (BSI) is not defined, especially in the context of carbapenem resistance. In this study, we compared short- (≤7 days) and long-term (>7 days) antimicrobial therapy duration for these infections. METHODS: We performed a retrospective cohort study in two tertiary-care hospitals in Porto Alegre, Brazil, from 2013 to 2019. Eligible patients aged ≥18 years were included and excluded for the following criteria: polymicrobial infections, treatment with non-susceptible antibiotics, complicated infections, or early mortality (<8 days of active antimicrobial therapy). The 30-day mortality risk was evaluated using a Cox regression model. RESULTS: We included 237 BSI episodes, 51.5% caused by ABC and 48.5% by Pseudomonas aeruginosa. Short-term therapy was not associated with 30-day mortality, adjusted hazard ratio 1.01, 95% confidence interval 0.47-2.20, p = 0.98, when adjusted for Pitt score (p = 0.02), Charlson Comorbidity Index score (p < 0.01), and carbapenem resistance (p < 0.01). Among patients who survived, short-term therapy was associated with shorter hospital stay (p < 0.01). Results were maintained in the subgroups of BSI caused by carbapenem-resistant bacteria (p = 0.76), ABC (p = 0.61), and Pseudomonas aeruginosa (p = 0.39). CONCLUSIONS: Long-term therapies for non-complicated Pseudomonas aeruginosa and ABC BSI were not superior to short-term therapy for 30-day mortality.

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.

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.

Double-, single- and none-carbapenem-containing regimens for the treatment of carbapenem-resistant Enterobacterales (CRE) bloodstream infections: a retrospective cohort.

OBJECTIVES: To investigate the effect of double-, single- and none-carbapenem-containing antimicrobial regimens in the treatment of patients with carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs). METHODS: We conducted a retrospective cohort study from 2013 to 2020 in two Brazilian hospitals. Patients ≥18 years old with CRE BSI were included and excluded if death or treatment duration for ≤48 h after BSI or non-Class A-producing carbapenemase isolates. We evaluated the impact of different carbapenem-containing regimens on 30 day mortality through a propensity score adjusted model and a Cox proportional hazards model. RESULTS: Two-hundred and seventy-nine patients were included for analyses: 47 (16.9%), 149 (53.4%) and 83 (29.8%) were treated with double-, single- and none-carbapenem-containing regimens, respectively. One-hundred and seventeen (41.9%) patients died in 30 days. Treatment with a single-carbapenem regimen was associated with a lower risk of death in 30 days compared with therapies containing no carbapenem [adjusted HR (aHR) 0.66, 95% CI 0.44-0.99, P = 0.048], when adjusted for Charlson score and ICU admission at baseline, while double-carbapenem regimens were not associated with a lower risk of death (aHR 0.78, 95% CI 0.46-1.32, P = 0.35). Propensity score adjusted model results went in the same direction. CONCLUSIONS: Double-carbapenem- was not superior to single-carbapenem-containing regimens in patients with CRE BSIs. Single-carbapenem-containing schemes were associated with a lower mortality risk.

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.

Amikacin for the treatment of carbapenem-resistant Klebsiella pneumoniae infections: clinical efficacy and toxicity.

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients > 18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients' 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 µg/mL and did not influence on mortality, regardless of the prescribed dose of this antibiotic (P = 0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profile from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P < 0.01) and combination therapy with colistin (P = 0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P < 0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an effective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not influence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution.

Clinical Use of Polymyxin B.

Polymyxin B is another clinically available polymyxin that has re-emerged in clinical practice to treat infections caused by multi-drug (MDR) or extensively-drug-resistant (XDR) Gram-negative bacteria (GNB). Its chemical structure is very similar to the structure of polymyxin E (colistin). However, since the latter is administered as a prodrug, there are major pharmacokinetic differences between both polymyxins that may potentially determine different clinical and microbiological outcomes. Studies addressing clinical or microbiological outcomes in patients treated with polymyxin B for MDR or XDR GNB are reviewed in this chapter.

A Cohort Study of the Impact of Carbapenem-Resistant Enterobacteriaceae Infections on Mortality of Patients Presenting with Sepsis.

The objective of this study is to evaluate the impact of carbapenem-resistant Enterobacteriaceae (CRE) infection on sepsis 30-day mortality. A retrospective cohort of patients >18 years old with sepsis and organ dysfunction or septic shock was conducted. Univariate analysis was done for variables potentially related to 30-day mortality, and the ones with P values of <0.05 were included in a backward stepwise hierarchic Cox regression model. Variables that remained with P values of <0.05 were retained in the model. A total of 1,190 sepsis episodes were analyzed. Gram-negative bacterial infections occurred in 391 (68.5%) of 571 patients with positive cultures, of which 69 (17.7%) were caused by a CRE organism. Patients with CRE infections had significantly higher 30-day mortality: 63.8% versus 33.4% (P < 0.01). CRE infection was also associated with a lower rate of appropriate empirical therapy (P < 0.01) and with the presence of septic shock (P < 0.01). In the hierarchic multivariate model, CRE remained significant when controlling for demographic variables, comorbidities, and infection site but lost significance when controlling for septic shock and appropriate empirical therapy. Older age (P < 0.01), HIV-positive status (P < 0.01), cirrhosis (P < 0.01), septic shock (P < 0.01), higher quick sepsis-related organ failure assessment (quick-SOFA) (P < 0.01), and appropriate empirical therapy (P = 0.01) remained in the final model. CRE infections were associated with higher crude mortality rates. A lower rate of appropriate empirical therapy and late diagnosis were more frequent in this group, and improvement of stewardship programs is needed.IMPORTANCE The importance of this work relies on exploring the impact of multidrug-resistant bacterial infections such as those with carbapenem-resistant Enterobacteriaceae (CRE) on sepsis mortality. These infections are growing at alarming rates worldwide and are now among the most frequent and difficult-to-treat bacteria due to the very few options for susceptible antimicrobials available. This study examined 1,190 sepsis episodes, and the main findings were as follows: (i) the prevalence of CRE infections significantly increased over time, (ii) CRE infection was associated with higher 30-day mortality than that of patients with other infections (63.8% versus 33.4%), and (iii) the effect of CRE on mortality was probably influenced by the fact that those patients received lower rates of empirical therapy with active antibiotics and were also diagnosed in more advanced stages of sepsis (septic shock). Those findings point to the need for rapid diagnostic methods to identify these bacteria and the need to adjust therapeutic guidelines to this worrisome epidemiological scenario.

Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity.

Polymyxins are valuable antimicrobials for the management of multidrug-resistant Gram-negative bacteria; however, nephrotoxicity associated with these drugs is a very common side effect that occurs during treatment. This article briefly reviews nephrotoxic mechanisms and risk factors for polymyxin-associated acute kidney injury (AKI) and discusses dosing strategies that may mitigate kidney damage without compromising antimicrobial activity. Polymyxins have a very narrow therapeutic window and patients requiring treatment with these drugs are frequently severely ill and have multiple comorbidities, which increases the risk of AKI. Notably, there is a significant overlap between therapeutic and toxic plasma polymyxin concentrations that substantially complicates dose selection. Recent dosing protocols for both colistin and polymyxin B have been developed and may help fine tune dose adjustment of these antibiotics. Minimizing exposure to modifiable risk factors, such as other nephrotoxic agents, is strongly recommended. The dose should be carefully selected, particularly in high-risk patients. The administration of oxidative stress-reducing drugs is a promising strategy to ameliorate polymyxin-associated AKI, but still requires support from clinical studies.

Combination therapy with polymyxin B for carbapenemase-producing Klebsiella pneumoniae bloodstream infection.

Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) bloodstream infections (BSIs) are related to high mortality rates, and combination therapy has been associated with lower mortality in patients treated mostly with colistin. There is a paucity of studies addressing polymyxin B (PMB) treatment for KPC-KP infections. This was a retrospective cohort study of patients with monomicrobial KPC-KP BSIs. The primary outcome was 30-day mortality. Antimicrobial therapy was defined as empirical (started within the first 48 h) or definitive (initiated after >48 h) and was evaluated as follows: monotherapy (only one in vitro active agent or combination therapy of one in vitro active agent plus one or more in vitro non-active agents); and combination therapy with two or more in vitro active agents. A total of 82 KPC-KP BSIs were included; 40 patients (48.8%) died in the first 30 days. Mortality of patients treated with the combination of two in vitro active antimicrobial agents, mostly PMB plus amikacin, was significantly lower (37.5%) compared with monotherapy (64.7%) (P= 0.01). Combination therapy [adjusted hazard ratio (aHR) = 0.40, 95% confidence interval (CI) 0.22-0.83; P = 0.01] was independently associated with lower 30-day survival when controlled for non-surgical admission (aHR = 2.33, 95% CI 1.14-4.80; P = 0.02) and use of vasoactive drugs (aHR = 7.37, 95% CI 3.01-18.02; P < 0.01). In conclusion, combination therapy with two in vitro active agents, mostly PMB plus amikacin, showed a survival benefit compared with other regimens.

Impact of polymyxin-B-associated acute kidney injury in 1-year mortality and renal function recovery.

The objective of this study was to evaluate the impact of polymyxin B (PMB) -associated acute kidney injury (AKI) in 1-year mortality and renal function recovery. Patients >18 years old who survived the first 30 days after PMB therapy were followed for 1 year. The impact of AKI and renal failure (using RIFLE score) in 1-year mortality was analysed, along with other confounding variables. Variables with a P-value ≤0.2 were included in a forward stepwise Cox regression model. In the subgroup of patients who developed AKI, we evaluated renal function recovery. A total of 234 patients were included for analyses. Of these, 108 (46.1%) died, in a median time of 63 (38.3-102.5) days. The use of other nephrotoxic drugs along with PMB (P = 0.05), renal failure (P = 0.03), dialysis (P < 0.01) and re-exposure to PMB (P<0.01), were all significantly related to 1-year mortality, while male gender had a protective effect (P = 0.01). Independent factors related to death were age (adjusted hazard ratio (aHR) 1.02, 95% confidence interval (CI) 1.00-1.03, P = 0.02), re-exposure to PMB (aHR 2.69, 95% CI 1.82-3.95, P<0.01), and male gender (aHR0.6, 95% CI 0.41-0.87, P = 0.01), when controlled for renal failure (aHR 1.28, 95% CI 0.78-2.10, P = 0.34).Thirty one of 94 (33%) patients who developed AKI had renal function recovery within 1 year. Mortality rates were high in the first year after PMB use and only one-third of patients who developed AKI returned to baseline renal function. Strategies to reduce renal toxicity are urgently needed in these patients.

Severe Infusion-Related Adverse Events and Renal Failure in Patients Receiving High-Dose Intravenous Polymyxin B.

The use of very high doses of polymyxin B (PMB) against carbapenem-resistant Gram-negative bacilli has been addressed in in vitro experiments as a strategy to improve bacterial killing and suppress resistance emergence. However, the toxicities of very high doses in patients are unknown. We conducted a retrospective cohort study assessing patients receiving PMB at >3 mg/kg of body weight/day or a total dose of ≥250 mg/day. The main outcomes were severe infusion-related adverse events according to the Common Terminology Criteria for Adverse Events and the renal failure category of RIFLE criteria for acute kidney injury (AKI) during treatment. A total of 222 patients were included for analysis of infusion-related events. The mean PMB dose was 3.61 ± 0.97 mg/kg/day (median total dose/day = 268 mg). Severe infusion-related adverse events occurred in two patients, resulting in an incidence of 0.9% (95% confidence interval, 0.2 to 3.2%); one was classified as a life-threatening adverse event, and one was classified as a severe adverse event. Renal failure was analyzed in 115 patients, and 25 (21.7%) patients presented renal failure (54 [47.0%] developed any degree of AKI, categorized as risk [27.8%], injury [25.9%], and failure [46.3%]). Treatment with a vasoactive drug, concomitant treatment with nephrotoxic drugs, and baseline creatinine clearance were independent risk factors for renal failure. Neither the PMB daily dose scaled by body weight nor the total daily dose was associated with renal failure. The in-hospital mortality rate was 60% (134 patients): 26% of deaths (57 patients) occurred during treatment, and none occurred during infusion. Our data suggest that high-dose schemes have an acceptable safety profile and could be further tested in clinical trials assessing strategies to improve patient outcomes and minimize the emergence of PMB resistance.

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.

Neoplasias mais prevalentes em pessoas vivendo com HIV / Most prevalent cancers in people living with HIV

Introdução: Com o advento da Terapia Antirretroviral (TARV), importantes mudanças na epidemiologia das principais doenças associadas à morbimortalidade em pessoas vivendo com HIV (PVHIV) ocorreram. Desde então, verifica-se, especialmente em países desenvolvidos, uma diminuição do número de mortes por doenças infecciosas e um aumento de casos de neoplasia nesta população, fato relacionado com o aumento da sobrevida propiciado após a introdução da TARV. Diante disso, faz-se necessário compreender o novo cenário no qual esses pacientes estão inseridos, a fim de criar estratégias no manejo das patologias. Métodos: Revisão de literatura referente a neoplasias prevalentes em pessoas vivendo com HIV por meio de pesquisa no PubMed ­ artigos publicados durante período de 2014 a 2018 ­ e dados brasileiros de fontes governamentais. Resultados: No contexto do HIV, as neoplasias podem ser classificadas como Definidoras de AIDS, ou não. Além disso, podem estar relacionadas a infecções virais crônicas sobrepostas, como é o caso do Papiloma Vírus Humano, Vírus Epstein Barr e Herpes Vírus. Existem rastreamentos bem estabelecidos a fim de diminuir a morbimortalidade por causas neoplásicas em PVHIV. Conclusão: O conhecimento geral de neoplasias em PVHIV apresenta importância crescente, dada prevalência da doença em nosso meio. Estratégias de screening e atualizações sobre novas linhas terapêuticas surgiram nos últimos anos. Sabendo empregá-las corretamente, podemos aumentar a expectativa de vida e melhoramos desfechos nessa população.

Introduction: With the advent of antiretroviral therapy (ART), some important changes in the epidemiology of the major diseases associated with morbidity and mortality in people living with HIV (PLHIV) have occurred. Then, especially in developed countries, there has been a decrease in the number of deaths due to infectious diseases and an increase in cases of neoplasia in this population, a fact related to the increase in survival after the introduction of HAART. It is necessary to understand the new scenario in which these patients are inserted, in order to create new strategies in the management of these pathologies. Methods: Literature review of prevalent neoplasms in people living with HIV using PubMed research - articles published during the period from 2014 to 2018 - and Brazilian data from governmental sources. Results: In the context of HIV, cancer can be classified as AIDSdefining or not. Furthermore, they may be related to overlapping chronic viral infections, such as Human Papilloma Virus, Epstein-Barr Virus and Herpes Virus. There are well-established screenings to reduce neoplastic morbidity and mortality in PLHIV. Conclusion: General knowledge of malignancies in PLHIV has increased importance, given the prevalence of the disease in our country. Screening strategies and updates on new therapeutic approaches have emerged in recent years. Once we know how to use them correctly, we may increase life expectancy and improve outcomes in this population.

Neutropenia febril: abordagem diagnóstica e terapêutica / Febrile neutropenia: diagnostic and therapeutic approach

Introdução: A neutropenia febril (NF) é uma das mais graves complicações em pacientes com câncer submetidos a quimioterapia. Estes casos exigem pronta avaliação diagnóstica e instituição de terapêutica adequada. A conduta frente a tal emergência ainda é muito discutida apesar dos avanços no tratamento. O objetivo do estudo foi revisar na literatura as medidas mais eficazes de manejo sindrômico da NF. Métodos: Este artigo é uma revisão bibliográfica realizada entre abril e maio de 2018 sobre neutropenia febril. Foi realizada pesquisa de artigos científicos de revisão, guidelines e artigos originais, dos últimos 15 anos. Resultados: O reconhecimento imediato do paciente com NF e seu adequado tratamento com início imediato de terapia empírica, conforme o risco do paciente, são definidores de qualidade do manejo desta síndrome. Conclusão: A avaliação inicial de todos os pacientes com NF deve ser ágil para que terapia empírica seja imediatamente iniciada.

Introduction: Febrile neutropenia (NF) is one of the most serious complications in cancer patients undergoing chemotherapy. These cases require prompt diagnostic evaluation and management. The objective of the study was to review the most effective aspects of NF syndromic management in the literature. Methods: This article is a bibliographical review performed between April and May of 2018 on febrile neutropenia. Research was done on review articles, seminars and original articles of the last 15 years. Results: The immediate recognition of the patient with NF and its appropriate treatment with immediate onset of empirical therapy, according to the risk of the patient, are critical and impact clinical outcomes. Conclusion: The initial assessment of all NF patients should be agile for empirical therapy to be initiated immediately.

Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B.

Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P< 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48;P< 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations.

Clinical features and mortality of patients on renal replacement therapy receiving polymyxin B.

There are no clinical data for polymyxin B (PMB) in patients on renal replacement therapy (RRT). The aim of this study was to evaluate the characteristics of patients on RRT receiving PMB and to identify predictors of 30-day mortality, with special focus on dosage. A multicentre prospective cohort study including patients aged ≥18 years treated with PMB for ≥48h while on any type of RRT was performed. In total, 88 patients were evaluated, including 34 (38.6%) on continuous venovenous haemodialysis (CVVH) and 54 (61.4%) on intermittent haemodialysis. Most patients (81.8%) received recommended doses between 1.5mg/kg/day and 3.0mg/kg/day. The 30-day mortality was 51.1% (45/88 patients). There was no significant association of dose (in mg/kg) with mortality. A PMB average daily dose ≥200mg was predictive of decreased 30-day mortality in the multivariate model (hazard ratio=0.35, 95% confidence interval 0.14-0.90; P=0.03), whilst CVVH (P=0.04), higher Charlson co-morbidity index (P=0.02) and Acute Physiology and Chronic Health Evaluation (APACHE) II score (P=0.04), and Pseudomonas aeruginosa infection (P=0.001) were independent risk factors for mortality. The results were not changed by the inclusion of patient weight or dose (in mg/kg) in the model, although the latter was significantly correlated with total daily dose. This is the first clinical study to show that higher doses of PMB are associated with lower mortality in patients on RRT.