Sepsis death risk factor score based on systemic inflammatory response syndrome, quick sequential organ failure assessment, and comorbidities.

OBJECTIVE: In this study, we aimed to evaluate the death risk factors of patients included in the sepsis protocol bundle, using clinical data from qSOFA, SIRS, and comorbidities, as well as development of a mortality risk score. DESIGN: This retrospective cohort study was conducted between 2016 and 2021. SETTING: Two university hospitals in Brazil. PARTICIPANTS: Patients with sepsis. INTERVENTIONS: Several clinical and laboratory data were collected focused on SIRS, qSOFA, and comorbidities. MAIN VARIABLE OF INTEREST: In-hospital mortality was the primary outcome variable. A mortality risk score was developed after logistic regression analysis. RESULTS: A total of 1,808 patients were included with a death rate of 36%. Ten variables remained independent factors related to death in multivariate analysis: temperature ≥38 °C (odds ratio [OR] = 0.65), previous sepsis (OR = 1.42), qSOFA ≥ 2 (OR = 1.43), leukocytes >12,000 or <4,000 cells/mm3 (OR = 1.61), encephalic vascular accident (OR = 1.88), age >60 years (OR = 1.93), cancer (OR = 2.2), length of hospital stay before sepsis >7 days (OR = 2.22,), dialysis (OR = 2.51), and cirrhosis (OR = 3.97). Considering the equation of the binary regression logistic analysis, the score presented an area under curve of 0.668, is not a potential model for death prediction. CONCLUSIONS: Several risk factors are independently associated with mortality, allowing the development of a prediction score based on qSOFA, SIRS, and comorbidities data, however, the performance of this score is low.

COVID-19 in real world: Survival and medical costs of hospitalized patients in Brazil´s first wave.

OBJECTIVE: To evaluate survival and direct medical costs of patients admitted in private hospitals with COVID-19 during the first wave. METHODS: A retrospective, observational study analyzing survival and the economic data retrieved on hospitalized patients with COVID-19. Data from March 2020 to December 2020. The direct cost of hospitalization was estimated using the microcosting method with each individual hospitalization. RESULTS: 342 cases were evaluated. Median age of 61.0 (95% CI 57.0‒65.0). 194 (56.7%) were men. The mortality rate was higher in the female sex (p = 0.0037), ICU (p < 0.001), mechanical ventilation (p<0.001) and elderly groups. 143 (41.8%) patients were admitted to the ICU (95% CI 36.6%-47.1%), of which 60 (41.9%) required MV (95% CI 34.0%-50.0%). Global LOS presented median of 6.7 days (95% CI 6.0-7.2). Mean costs were US$ 7,060,00 (95% CI 5,300.94-8,819,00) for each patient. Mean cost for patients discharged alive and patients deceased was US$ 5,475.53 (95% CI 3,692.91-7,258.14) and US$ 12,955.19 (95% CI 8,106.61-17,803.76), respectively (p < 0.001). CONCLUSIONS: Patients admitted with COVID-19 in these private hospitals point to great economic impact, mainly in the elderly and high-risk patients. It is key to better understand such costs in order to be prepared to make wise decisions during the current and future global health emergencies.

COVID-19 in real world: Survival and medical costs of hospitalized patients in Brazils first wave

ABSTRACT Objective: To evaluate survival and direct medical costs of patients admitted in private hospitals with COVID-19 during the first wave. Methods: A retrospective, observational study analyzing survival and the economic data retrieved on hospitalized patients with COVID-19. Data from March 2020 to December 2020. The direct cost of hospitalization was estimated using the microcosting method with each individual hospitalization. Results: 342 cases were evaluated. Median age of 61.0 (95% CI 57.0-65.0). 194 (56.7%) were men. The mortality rate was higher in the female sex (p = 0.0037), ICU (p < 0.001), mechanical ventilation (p<0.001) and elderly groups. 143 (41.8%) patients were admitted to the ICU (95% CI 36.6%-47.1%), of which 60 (41.9%) required MV (95% CI 34.0%-50.0%). Global LOS presented median of 6.7 days (95% CI 6.0-7.2). Mean costs were US$ 7,060,00 (95% CI 5,300.94-8,819,00) for each patient. Mean cost for patients discharged alive and patients deceased was US$ 5,475.53 (95% CI 3,692.91-7,258.14) and US$ 12,955.19 (95% CI 8,106.61 -17,803.76), respectively (p < 0.001). Conclusions: Patients admitted with COVID-19 in these private hospitals point to great economic impact, mainly in the elderly and high-risk patients. It is key to better understand such costs in order to be prepared to make wise decisions during the current and future global health emergencies.

Brazilian Public Health System: history and profile of heart failure care and the impacts of COVID-19 / Sistema Público de Saúde Brasileiro: história e perfil dos cuidados com a insuficiência cardíaca e os impactos da COVID-19

Objective: The objective of this study is to describe the general and specific context of hospitalizations for Heart Failure (HF) in the Unified Health System and its main care indicators and economic aspects in the period before and during COVID-19. Methods: The economic indicators were evaluated between January 2011 and June 2022, comparing these indicators before and during the COVID-19 pandemic, using data from the DataSUS Health Information of the Ministry of Health of Brazil. The number of hospitalizations, length of stay, lethality and hospitalization costs were evaluated. The ARIMA method and the general regression model were used to analyze monthly results before and during COVID-19. Results: Hospitalization for HF has decreased in the last 11 years, with the most significant drop in the COVID-19 pandemic. After the pandemic, there was an increase in lethality in patients hospitalized for HF and also an increase in length of stay, despite the decrease in hospitalizations. When analyzing the economic aspects, more than US$ 725 million were spent. The average ticket showed a clear drop in per capita investment, with a real devaluation of 30.46% in the period from 2011 to 2022, which can be related to two main hypotheses: increased effectiveness and effectiveness of the analysis of service costs and/ or chronic underfunding of the Brazilian Public Health System. Conclusion: HF has its lethality worsened over time, especially in the COVID-19 period, also associated with a significant expense with the SUS and a tendency to decrease the allocation of resources.

Objetivo: O objetivo deste estudo é descrever o contexto geral e específico das internações por insuficiência cardíaca (IC) junto ao Sistema Único de Saúde e seus principais indicadores assistenciais e aspectos econômicos no período pré e durante a COVID-19. Métodos: Os indicadores econômicos foram avaliados no período entre janeiro de 2011 e junho de 2022, comparando esses indicadores antes e durante a pandemia por COVID-19, utilizando dados do DataSUS Informações de Saúde do Ministério da Saúde do Brasil. Foram avaliados o número de internações, tempo de internação, etalidade e custos de internação. O método ARIMA e o modelo de regressão geral foram usados para analisar os resultados mensais antes e durante a COVID-19. Resultados: A hospitalização por IC diminuiu nos últimos 11 anos, com queda mais significativa na pandemia da COVID-19. Após a pandemia, houve aumento da letalidade em pacientes internados por IC e também um aumento do tempo de permanência, mesmo diante da diminuição das internações. Ao analisar os aspectos econômicos, foram gastos mais de US$ 725 milhões. O ticket médio apresentou uma clara queda no investimento per capita, com desvalorização real de 30,46% no período de 2011 a 2022, o que pode estar relacionado a duas hipóteses principais: aumento da efetividade e efetividade da análise de custos do atendimento e/ou subfinanciamento crônico do Sistema Público de Saúde Brasileiro. Conclusão: A IC tem sua letalidade agravada ao longo do tempo, principalmente no período da COVID-19, associada também a um gasto relevante com o sistema público brasileiro e a uma tendência de diminuição da alocação de recursos.

Cerebrospinal Fluid Penetration of Vancomycin During Continuous Infusion Therapy in Patients With Nosocomial Ventriculitis.

BACKGROUND: This study aimed to evaluate the utility of a commercial kit used to measure serum vancomycin concentrations to determine vancomycin concentrations in cerebrospinal fluid (CSF) samples and evaluate CSF penetration when administered as a continuous high-dose infusion in patients with nosocomial ventriculitis. METHODS: This study included patients with external ventricular drain infection who were admitted to the intensive care unit between January 2018 and September 2020. After validation, CSF samples from 33 patients were collected. All patients received 30 mg/kg of vancomycin as a loading dose followed by 60 mg/kg as a maintenance dose in continuous infusion; all CSF samples were collected at least 48 hours after the first dose. RESULTS: Thirty-three patients were enrolled in this study. The median serum creatinine level was 0.66 mg/dL (0.5-0.92; n = 30), and median creatinine clearance was 119.2 mL/min (64.6-138.4; n = 13). The median serum vancomycin 24-hour area under the curve (AUC24h) was 838 mg*h/L (515-1010). The median CSF vancomycin concentration was 5.20 mg/L (1.95-12.4). Median serum vancomycin concentration was 34.9 mg/L (21.47-42.1), and median CSF/serum ratio was 18.6% (8.4-41.5). Acute renal injury occurred in 21% (n = 7) of the patients by the end of the therapy. In addition, the vancomycin CSF/serum ratio was positively correlated with the median serum creatinine level (r = 0.670; P = 0.004). CONCLUSIONS: Commercial vancomycin kits used to measure serum samples may be used to evaluate vancomycin concentrations in the CSF. Vancomycin penetration into CSF was 18.6%.

Clinical Outcomes and Costs of Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Inpatients: A Cross-Sectional Study.

INTRODUCTION:  Venous thromboembolism (VTE) is the primary cause of preventable death in hospitalized patients in the United States. This is a cross-sectional study with a brief cost analysis of thromboprophylaxis with rivaroxaban and enoxaparin in acutely ill medical inpatients. METHODS:  The study included a total of 122 patients admitted to a public teaching hospital from December 2019 to January 2021. The sample was equally divided into two groups according to the thromboprophylactic agent prescribed: rivaroxaban or enoxaparin. The primary outcomes included bleeding and symptomatic, ultrasonography-confirmed arterial or venous thrombotic events during or within 90 days after hospitalization. Our secondary outcome was the direct costs of each anticoagulant in US dollars over the 14 months. RESULTS:  During hospitalization, two events were detected in the enoxaparin group: minor bleeding with minimum intervention required (1.6%) and a deep vein thrombosis (DVT) case (1.6%) confirmed by ultrasonography. Within 90 days after discharge, two patients, one of each sample (1.6% vs. 1.6%), were readmitted due to confirmed acute arterial occlusion. Concerning financial assessment, the mean unit cost of enoxaparin during the 14 months assessed was 102.14% more expensive than rivaroxaban. CONCLUSIONS:  Both rivaroxaban and enoxaparin showed equivalence in effectiveness and safety in thromboprophylaxis in medical inpatients, aside from possible financial benefit with the first-mentioned drug.

Cost minimization analysis of outpatient parenteral/oral antibiotic therapy at a trauma hospital: Public health system.

OBJECTIVE: To evaluate the impact of outpatient parenteral antimicrobial therapy (OPAT) on a public hospital in a middle-income country. DESIGN: A retrospective, observational study analyzing the economic data retrieved on the dehospitalization of patients on antibiotic therapy. SETTING: Public university trauma hospital. PATIENTS: Data were collected from June 2017 to May 2020. Antibiotic cost, hospital length of stay, and risk of multidrug-resistant (MDR) infection or colonization were reviewed, along with the break-even point at which a balance occurs between OPAT antimicrobial costs and all in-hospital costs. A cumulative risk curve was constructed showing the incidence of MDR during the review period. RESULTS: In total, 225 patients were studied. The implementation of OPAT resulted in a reduction of $156,681 (49.6%), which is equivalent to an average of $696 per patient, as well as a shortened length of stay, from 33.5 to 15.7 days. OPAT reduces the risk of acquiring infection by MDR bacteria by having the final treatments administered outside of the hospital environment. The breakeven curves, comparing the duration of the OPAT to daily medication costs, allowed for the prediction of the time and dollar costs of antibiotic therapy. CONCLUSIONS: OPAT presented a significant cost savings, shortened length of stay, and reduced risk of contamination of patients by MDR.

Carbapenem stewardship with ertapenem and antimicrobial resistance-a scoping review.

Consumption of carbapenem has increased due to extended-spectrum beta-lactamase-producing bacteria spreading. Ertapenem has been suggested as a not carbapenem-resistance inducer. We performed a scoping review of carbapenem-sparing stewardship with ertapenem and its impact on the antibiotic resistance of Gram-negative bacilli. We searched PubMed for studies that used ertapenem as a strategy to reduce resistance to carbapenems and included epidemiologic studies with this strategy to evaluate susceptibility patterns to cephalosporins, quinolones, and carbapenems in Gram-negative-bacilli. The search period included only studies in English, up to February 2018. From 1294 articles, 12 studies were included, mostly from the Americas. Enterobacteriaceae resistance to quinolones and cephalosporins was evaluated in 6 studies and carbapenem resistance in 4 studies. Group 2 carbapenem (imipenem/meropenem/doripenem) resistance on A. baumannii was evaluated in 6 studies. All studies evaluated P. aeruginosa resistance to Group 2 carbapenem. Resistance profiles of Enterobacteriaceae and P. aeruginosa to Group 2 carbapenems were not associated with ertapenem consumption. The resistance rate of A. baumannii to Group 2 carbapenems after ertapenem introduction was not clear due to a lack of studies without bias. In summary, ertapenem as a strategy to spare use of Group 2 carbapenems may be an option to stewardship programs without increasing resistance of Enterobacteriaceae and P. aeruginosa. More studies are needed to evaluate the influence of ertapenem on A. baumannii.

Comparison of intermittent versus continuous-infusion vancomycin for treating severe patients in intensive care units.

PURPOSE: The aim of this study was to compare pharmacokinetic characteristics between intermittent infusion and continuous infusion of vancomycin for critically ill patients admitted to intensive care units. METHODS: Intermittent therapy was administered for 60minutes and prescribed as a loading dose of 30mg/kg and continued with 15mg/kg q12h. Continuous infusion was prescribed as a loading dose of 30mg/kg followed by 30mg/kg on constant infusion pump. Blood samples from vancomycin intermittent infusion group were collected 1h before third dose, 1h, 8h and 24h after third dose infusion. Blood samples from vancomycin continuous infusion group were collected 1h after loading dose, 12h, 24h, 36h, and 48h after continuous infusion initiation. RESULTS: Median serum concentration of continuous infusion group at 24-hour was 23.59µg/mL [14.52-28.97], while of intermittent infusion group at 23-hour was 12.30µg/mL [7.27-18.12] and on 25-hour was 17.58µg/mL [12.5-22.5]. Medians AUC24-48h were 357.2mg.h/L and 530.2mg.h/L for intermittent infusion and continuous infusion groups, respectively (p=0.559). CONCLUSION: Vancomycin CI reached steady state earlier, which guaranteed therapeutic levels from the first day and made it possible to manage therapeutic drug monitoring faster.

Comparison of intermittent versus continuous-infusion vancomycin for treating severe patients in intensive care units

Abstract Purpose The aim of this study was to compare pharmacokinetic characteristics between intermittent infusion and continuous infusion of vancomycin for critically ill patients admitted to intensive care units. Methods Intermittent therapy was administered for 60 minutes and prescribed as a loading dose of 30 mg/kg and continued with 15 mg/kg q12 h. Continuous infusion was prescribed as a loading dose of 30 mg/kg followed by 30 mg/kg on constant infusion pump. Blood samples from vancomycin intermittent infusion group were collected 1 h before third dose, 1 h, 8 h and 24 h after third dose infusion. Blood samples from vancomycin continuous infusion group were collected 1 h after loading dose, 12 h, 24 h, 36 h, and 48 h after continuous infusion initiation. Results Median serum concentration of continuous infusion group at 24-hour was 23.59 µg/mL [14.52-28.97], while of intermittent infusion group at 23-hour was 12.30 µg/mL [7.27-18.12] and on 25-hour was 17.58 µg/mL [12.5-22.5]. Medians AUC24-48h were 357.2 mg.h/L and 530.2 mg.h/L for intermittent infusion and continuous infusion groups, respectively (p = 0.559). Conclusion Vancomycin CI reached steady state earlier, which guaranteed therapeutic levels from the first day and made it possible to manage therapeutic drug monitoring faster.

A broad-spectrum beta-lactam-sparing stewardship program in a middle-income country public hospital: antibiotic use and expenditure outcomes and antimicrobial susceptibility profiles.

BACKGROUND: Antimicrobial stewardship programs are an efficient way to reduce inappropriate use of antimicrobials and costs; however, supporting data are scarce in middle-income countries. The aim of this study was to evaluate antibiotic use, bacterial susceptibility profiles, and the economic impact following implementation of a broad-spectrum beta-lactam-sparing antimicrobial stewardship program. METHODS: An interrupted time-series analysis was performed to evaluate antibiotic use and expenditure over a 24-month period (12 months before the antimicrobial stewardship program and in the 12 months after implementation of the antimicrobial stewardship program). Antibiotics were classified into one of two groups: beta-lactam antibiotics and beta-lactam-sparing antibiotics. We also compared the antimicrobial susceptibility profiles of key pathogens in each period. RESULTS: Beta-lactam antibiotics use decreased by 43.04 days of therapy/1000 patient-days (p=0.04) immediately following antimicrobial stewardship program implementation, whereas beta-lacta-sparing antibiotics use increased during the intervention period (slope change 6.17 days of therapy/1000 patient-days, p<0.001). Expenditure decreased by $2089.99 (p<0.001) immediately after intervention and was maintained at this level over the intervention period ($-38.45; p=0.24). We also observed that a greater proportion of pathogens were susceptible to cephalosporins and aminoglycosides after the antimicrobial stewardship program. CONCLUSIONS: The antimicrobial stewardship program significantly reduced the use of broad-spectrum beta-lactam-antibiotics associated with a decrease in expenditure and maintenance of the susceptibility profile in Gram-negative bacteria.

A broad-spectrum beta-lactam-sparing stewardship program in a middle-income country public hospital: antibiotic use and expenditure outcomes and antimicrobial susceptibility profiles

ABSTRACT Background: Antimicrobial stewardship programs are an efficient way to reduce inappropriate use of antimicrobials and costs; however, supporting data are scarce in middle-income countries. The aim of this study was to evaluate antibiotic use, bacterial susceptibility profiles, and the economic impact following implementation of a broad-spectrum beta-lactam-sparing antimicrobial stewardship program. Methods: An interrupted time-series analysis was performed to evaluate antibiotic use and expenditure over a 24-month period (12 months before the antimicrobial stewardship program and in the 12 months after implementation of the antimicrobial stewardship program). Antibiotics were classified into one of two groups: beta-lactam antibiotics and beta-lactam-sparing antibiotics. We also compared the antimicrobial susceptibility profiles of key pathogens in each period. Results: Beta-lactam antibiotics use decreased by 43.04 days of therapy/1000 patient-days (p = 0.04) immediately following antimicrobial stewardship program implementation, whereas beta-lacta-sparing antibiotics use increased during the intervention period (slope change 6.17 days of therapy/1000 patient-days, p < 0.001). Expenditure decreased by $2089.99 (p < 0.001) immediately after intervention and was maintained at this level over the intervention period ($−38.45; p = 0.24). We also observed that a greater proportion of pathogens were susceptible to cephalosporins and aminoglycosides after the antimicrobial stewardship program. Conclusions: The antimicrobial stewardship program significantly reduced the use of broad-spectrum beta-lactam-antibiotics associated with a decrease in expenditure and maintenance of the susceptibility profile in Gram-negative bacteria.

Depression and anxiety in hospitalized patients on contact precautions for multidrug-resistant microorganisms.

BACKGROUND: Contact precautions for patients with multidrug-resistant organisms (MDROs) have been associated with adverse effects. The aim of this study was, therefore, to evaluate the level of anxiety and depression through different standardized scales in patients isolated by MDROs. METHODS: This is a case-control study with hospitalized patients on contact precautions for MDROs. A questionnaire survey was conducted to analyse the presence and level of depression and anxiety. A multivariable analysis was performed to define independent questions for anxiety/depression scores to create a short questionnaire facilitating a practical approach to the care of hospitalized patients with MDROs. A receiver operating characteristic (ROC) curve was plotted to determine the diagnostic ability of the simplified score. RESULTS: A total of 141 patients were included in the study, among whom 68 were isolated because of MDRO colonization while 73 were not isolated (control-group). Forty-five (31.9%) patients had some degree of anxiety. Patients in MDRO contact isolation had a higher level of anxiety than those who were not isolated (55.9% vs. 9.6%, p < 0.001). The equation obtained by multivariated analysis allowed for the construction of a score with ROC area of 0.949 and a sensitivity of 91.1%. CONCLUSION: Contact isolation for MDROs is associated with increased depression and anxiety. A simple anxiety score was developed and should be validated for screening.

Antimicrobial therapy with aminoglycoside or meropenem in the intensive care unit for hospital associated infections and risk factors for acute kidney injury.

There have historically been concerns of acute kidney injury (AKI) with the use of aminoglycosides. The present study aimed to compare the AKI incidence and mortality rate between critically ill patients treated with aminoglycoside or meropenem in the intensive care unit setting using a propensity score matching approach. This cross-sectional study was conducted at two university hospitals from January 2011 to October 2017. Clinical and laboratorial data were evaluated to exclude potential confounders and to calculate the Charlson index. AKI was classified according to the Acute Kidney Injury Network criteria. All tests were two-tailed, and a p value ≤ 0.05 was considered significant in the univariate and multivariate analyses. We included 494 patients, 95 and 399 of whom used meropenem and aminoglycoside, respectively. Patients in the subgroup that used meropenem were matched with controls (aminoglycoside). Among the 494 patients, 120 developed any grade of AKI (24.2%). After propensity score matching, there were no significant differences in AKI incidence and mortality rate between the aminoglycoside and meropenem groups (p = 0.324 and 0.464, respectively). Patients on the aminoglycoside regimen neither presented a higher AKI incidence nor mortality rate when compared with those on the meropenem regimen. Aminoglycosides may be a safe option for the treatment of critically ill patients on carbapenem sparing antimicrobial stewardship programs.

Carbapenem stewardship with ertapenem and antimicrobial resistance-a scoping review

Abstract Consumption of carbapenem has increased due to extended-spectrum beta-lactamase-producing bacteria spreading. Ertapenem has been suggested as a not carbapenem-resistance inducer. We performed a scoping review of carbapenem-sparing stewardship with ertapenem and its impact on the antibiotic resistance of Gram-negative bacilli. We searched PubMed for studies that used ertapenem as a strategy to reduce resistance to carbapenems and included epidemiologic studies with this strategy to evaluate susceptibility patterns to cephalosporins, quinolones, and carbapenems in Gram-negative-bacilli. The search period included only studies in English, up to February 2018. From 1294 articles, 12 studies were included, mostly from the Americas. Enterobacteriaceae resistance to quinolones and cephalosporins was evaluated in 6 studies and carbapenem resistance in 4 studies. Group 2 carbapenem (imipenem/meropenem/doripenem) resistance on A. baumannii was evaluated in 6 studies. All studies evaluated P. aeruginosa resistance to Group 2 carbapenem. Resistance profiles of Enterobacteriaceae and P. aeruginosa to Group 2 carbapenems were not associated with ertapenem consumption. The resistance rate of A. baumannii to Group 2 carbapenems after ertapenem introduction was not clear due to a lack of studies without bias. In summary, ertapenem as a strategy to spare use of Group 2 carbapenems may be an option to stewardship programs without increasing resistance of Enterobacteriaceae and P. aeruginosa. More studies are needed to evaluate the influence of ertapenem on A. baumannii.

Intravenous-to-oral antibiotic switch therapy: a cross-sectional study in critical care units.

BACKGROUND: This study aimed to evaluate the oral switch (OS) stewardship intervention in the intensive care unit (ICU). METHODS: This was a retrospective study with a convenience sample in two Brazilian ICUs from different hospitals in patients with sepsis receiving antibiotic therapy. The stewardship intervention included OS in patients diagnosed with sepsis when clinical stability was achieved. The primary outcome was overall mortality. Other variables evaluated were as follows: cost of antimicrobial treatment, daily costs of intensive care, acute kidney injury, and length of stay. RESULTS: There was no difference in mortality between the OS and non-OS groups (p = 0.06). Length of stay in the ICU (p = 0.029) was shorter and acute kidney injury incidence (p = 0.032) and costs of antimicrobial therapy (p < 0.001) were lower in the OS group. CONCLUSION: OS stewardship programs in the ICU may be considered a safe strategy. Switch therapy reduced the cost and shortened the length of stay in ICUs.

Efficacy of Ceftriaxone 1 g daily Versus 2 g daily for The Treatment of Community-Acquired Pneumonia: A Systematic Review with Meta-Analysis.

Introduction: Ceftriaxone has been recommended as a first-line treatment for various infections; however, the doses for pneumonia have not been a consensus in randomized clinical trials. To compare ceftriaxone 1 g daily efficacy to other ceftriaxone dosing regimens in community-acquired pneumonia. Area covered: We performed a systematic review and meta-analysis on PubMed, Web of Science, Scopus, and LILACS. Randomized controlled trials of ceftriaxone in community-acquired pneumonia were included. Outcomes included clinical cure in modified intention-to-treatment, clinically and microbiologically evaluable patients. Expert opinion: Ceftriaxone dosages of 1 g daily are as safe and effective as other antibiotic regimens for community-acquired pneumonia. Twenty-four articles fulfilled the inclusion criteria. Twelve studies evaluated ceftriaxone regimens at a dosage of 2 g daily and 12 studies evaluated ceftriaxone at a dosage of 1 g daily. The odds-ratio of clinical cure in the modified intention-to-treatment patients administered either ceftriaxone (4666 patients) or a comparator (4411 patients) was 0.98 (95% CI [0.82-1.17]). Comparator regimens showed similar efficacy to ceftriaxone regimens of 1 g daily, with an odds ratio of 1.03 (95% CI [0.88-1.20]). Dosages higher than ceftriaxone 1 g daily did not result in improved clinical outcomes for community-acquired pneumonia patients (OR 1.02, 95% CI [0.91-1.14]).

Polymyxin B and colistin-the economic burden of nephrotoxicity against multidrug resistant bacteria.

BACKGROUND: Polymyxin B and colistin are nephrotoxic drugs used in the treatment of carbapenem-resistant Enterobacteriaceae. The aim of this study is to evaluate the burden of costs due to polymyxin associated AKI and propose a simulated break-even price for new therapies. METHODS: The pharmacoeconomic model is based on two large cross-sectional studies of polymyxin nephrotoxicity. Total direct costs in patients with and without renal failure were compared. The direct cost of each hemodialysis section (USD82.94) and daily hospital charges (USD934.85) were based on the values used in a major public hospital in the city where the clinical study was performed. The break-even price of new drugs was simulated considering eventual new drugs as effective as polymyxins, but less nephrotoxic in different percentages. Outcomes of patients after hospital discharge were not evaluated. RESULTS: Total direct cost of the group of patients who survived without AKI was significantly lower than total direct cost of the groups either with AKI or the group who died without AKI. There was a tendency of even higher costs in those who died with AKI and dialysis. Direct cost of hemodialysis was not as important as the longer hospitalization after sepsis. Considering daily cost of polymyxin is USD60, drugs with 50% less AKI could be considered cost-beneficial if the daily cost is lower than USD160. CONCLUSIONS: AKI in patients with carbapenem-resistant Enterobacteriaceae treated with polymyxin increases both length of stay in hospital and total costs.