Cost-effectiveness of linezolid to ventilator-associated pneumonia in Colombia.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a prominent cause of morbidity and mortality in intensive care unit (ICU) patients. Due to the increase in Methicillin resistant Staphylococcus aureus infection, it is important to consider other more effective and safer alternatives compared to vancomycin. This motivates evaluating whether the use of an apparently more expensive drug such as linezolid can be cost-effective in Colombia. METHODS: A decision tree was used to simulate the results in terms of the cost and proportion of cured patients. In the simulation, patients can receive antibiotic treatment with linezolid (LZD 600 mg IV/12 h) or vancomycin (VCM 15 mg/kg iv/12 h) for 7 days, patients they can experience events adverse (renal failure and thrombocytopenia). The model was analyzed probabilistically, and a value of information analysis was conducted to inform the value of conducting further research to reduce current uncertainties in the evidence base. Cost-effectiveness was evaluated at a willingness-to-pay (WTP) value of US$5180. RESULTS: The mean incremental cost of LZD versus VCM is US$-517. This suggests that LZD is less costly. The proportion of patients cured when treated with LZD compared with VCM is 53 vs. 43%, respectively. The mean incremental benefit of LZD versus VCM is 10 This position of absolute dominance (LZD has lower costs and higher proportion of clinical cure than no supplementation) is unnecessary to estimate the incremental cost-effectiveness ratio. There is uncertainty with a 0.999 probability that LZD is more cost-effective than VCM. Our base-case results were robust to variations in all assumptions and parameters. CONCLUSION: LNZ is a cost-effective strategy for patients, ≥ 18 years of age, with VAP in Colombia- Our study provides evidence that can be used by decision-makers to improve clinical practice guidelines.

Methods to appraise available evidence and adequacy of data from a systematic literature review to conduct a robust network meta-analysis of treatment options for patients with hospital-acquired or ventilator-associated bacterial pneumonia.

We aimed to determine if available evidence from a previously conducted systematic literature review was sufficient to conduct a robust network meta-analysis (NMA) using the International Society for Pharmacoeconomics and Outcomes Research Good Practice Task Force NMA study questionnaire to evaluate suitability, relevance, and credibility of available randomized-controlled trials (RCT) of antibacterial therapies for treatment of patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). We assessed feasibility and reliability of an NMA for a connected network of RCTs, and then relevance and credibility of the connected network for informing decision-making. This previously conducted systematic literature review using Cochrane dual-reviewer methodology, Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and PICOTS (population, interventions, comparators, outcomes, timing, and setting) criteria identified 25 citations between 2001 and 2018; 18 were unique RCTs. Trial design characteristics, outcome definitions, assessment time points, and analyses populations varied across studies. Using "clinical response," an efficacy end point to health technology assessment agencies, we assessed potential network credibility, which collapsed from the overall data set to four studies and five interventions. This did not include closed loop(s) needed to assess consistency. Of the studies reporting clinical response, >70% of patients were ventilated at baseline with mean Acute Physiologic Assessment and Chronic Health Evaluation II scores from 14.7 to 17.5. Pseudomonas aeruginosa (range, 18.4-64.1%) and Klebsiella spp. (range, 1.6-49%) were the most common causative pathogens. We identified relevant RCTs for most standard-of-care agents approved for HABP/VABP, which provided a comprehensive evidence base. In summary, our appraisal of available evidence for the clinical response outcome among adult patients with HABP/VABP does not support the conduct of a scientifically robust and clinically meaningful NMA. Although this data is vital to registration, there are significant limitations in these trials for health technology assessments, payor decisions, guidelines, and protocol decisions.

A qualitative assessment of the diagnosis and management of ventilator-associated pneumonia among critical care clinicians exploring opportunities for diagnostic stewardship.

BACKGROUND: Prompt diagnosis and intervention for ventilator-associated pneumonia (VAP) is critical but can lead to overdiagnosis and overtreatment. OBJECTIVES: We investigated healthcare provider (HCP) perceptions and challenges associated with VAP diagnosis, and we sought to identify opportunities for diagnostic stewardship. METHODS: We conducted a qualitative study of 30 HCPs at a tertiary-care hospital. Participants included attending physicians, residents and fellows (trainees), advanced practice providers (APPs), and pharmacists. Interviews were composed of open-ended questions in 4 sections: (1) clinical suspicion and thresholds for respiratory culture ordering, (2) preferences for respiratory sample collection, (3) culture report interpretation, and (4) VAP diagnosis and treatment. Interviews transcripts were analyzed using Nvivo 12 software, and responses were organized into themes. RESULTS: Overall, 10 attending physicians (75%) and 16 trainees (75%) trainees and APPs believed they were overdiagnosing VAP; this response was frequent among HCPs in practice 5-10 years (91%, n = 12). Increased identification of bacteria as a result of frequent respiratory culturing, misinterpretation of culture data, and fear of missing diagnosis were recognized as drivers of overdiagnosis and overtreatment. Although most HCPs rely on clinical and radiographic changes to initiate work-up, the fear of missing a diagnosis leads to sending cultures even in the absence of those changes. CONCLUSIONS: HCPs believe that VAP overdiagnosis and overtreatment are common due to fear of missing diagnosis, overculturing, and difficulty distinguishing colonization from infection. Although we identified opportunities for diagnostic stewardship, interventions influencing the ordering of cultures and starting antimicrobials will need to account for strongly held beliefs and ICU practices.

Assessment of Detectable Serum Tobramycin Concentrations in Patients Receiving Inhaled Tobramycin for Ventilator-Associated Pneumonia.

BACKGROUND: Inhaled tobramycin can be used for empiric or definitive therapy of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. This is believed to minimize systemic exposure and potential adverse drug toxicities including acute kidney injury (AKI). However, detectable serum tobramycin concentrations have been reported after inhaled tobramycin therapy with AKI. METHODS: This retrospective, observational study evaluated mechanically ventilated adult subjects admitted to ICUs at a large, urban academic medical center that received empiric inhaled tobramycin for VAP. Subjects were separated into detectable (ie, ≥ 0.6 mg/L) or undetectable serum tobramycin concentration groups, and characteristics were compared. Independent predictors for detectable serum tobramycin concentration and new onset AKI during or within 48 h of therapy discontinuation were assessed. RESULTS: Fifty-nine inhaled tobramycin courses in 53 subjects were included in the analysis, of which 39 (66.1%) courses administered to 35 (66.0%) subjects had detectable serum tobramycin concentrations. Subjects with detectable serum tobramycin concentrations were older (57.1 y ± 11.4 vs 45.9 ±15.0, P = .004), had higher PEEP (9.2 cm H2O [7.0-11.0] vs 8.0 [5.6-8.9], P = .049), chronic kidney disease stage ≥ 2 (10 [29.4%] vs 0 [0%], P = .009), and higher serum creatinine before inhaled tobramycin therapy (1.26 mg/dL [0.84-2.18] vs 0.76 [0.47-1.28], P = .004). Age (odds ratio 1.09 [95% CI 1.02-1.16], P = .009) and PEEP (odds ratio 1.47 [95% CI 1.08-2.0], P =.01) were independent predictors for detectable serum tobramycin concentration. Thirty-seven subjects had no previous renal disease or injury, of which 9 (24.3%) developed an AKI. Sequential Organ Failure Assessment score (odds ratio 1.72 [95% CI 1.07-2.76], P = .03) was the only independent predictor for AKI. CONCLUSIONS: Detectable serum tobramycin concentrations were frequently observed in critically ill, mechanically ventilated subjects receiving empiric inhaled tobramycin for VAP. Subject age and PEEP were independent predictors for detectable serum tobramycin concentration. Serum monitoring and empiric dose reductions should be considered in older patients and those requiring higher PEEP.

Procalcitonin in the Assessment of Ventilator Associated Pneumonia: A Systematic Review.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common nosocomial infection, associated with considerable mortality and morbidity in critically ill patients; however, its diagnosis and management remain challenging since clinical assessment is often poorly reliable. The aim of this systematic review was to evaluate the role of PCT in the diagnosis and management of critical ill patients affected by VAP. METHODS: We performed a systematic review of the evidence published over the last 10 years and currently available in medical literature search databases (Pubmed, Embase, Web of Knowledge, Cochrane Libraries) and searching clinical trial registries. We regarded as predefined outcomes the role of PCT in diagnosis, therapeutic monitoring, antibiotic discontinuation and prognosis. The Open Science Framework Registration number was doi.org/10.17605/OSF. IO/ZGFKQ RESULTS: 761 articles were retrieved and a total of 18 studies (n° of patients = 1774) were selected and analyzed according to inclusion criteria. In this 2020 update, the systematic review showed that currently, conflicting and inconclusive data are available about the role of PCT in the diagnosis of VAP and in the prediction (i) of the efficacy of antibiotic therapy, and (ii) of the clinical outcome. These studies, instead, seem to agree on the utility of PCT in the management of antibiotic therapy discontinuation. CONCLUSIONS: Currently there is insufficient evidence to support the role of PCT in the routine assessment of patients with VAP. The value of the results published appears to be limited by the deep methodological differences that characterize the various studies available at the present being.

Assessment of the Clinical Pulmonary Infection Scores for prediction of ventilator associated pneumonia in patients with out of hospital cardiac arrest.

BACKGROUND: Patients suffering out-of-hospital cardiac arrest (OHCA) are at an increased risk of aspiration pneumonitis and development of subsequent aspiration pneumonia. The diagnostic uncertainty in this context can lead to a large proportion receiving broad spectrum antibiotics. METHODS: This was a three-year, retrospective cohort study of consecutive patients admitted with OHCA. Data were collected in an Australian tertiary centre intensive care unit (ICU) between December 2016-December 2019. We assessed the incidence of Ventilator associated pneumonia (VAP), admission Clinical Pulmonary Infection Scores (CPIS) in patients with OHCA and its' association with VAP at day 3 [1]. We also assessed antibiotics prescribing (timing of initiation and drug choice) and intensive care mortality relative to the day 1 CPIS. RESULTS: Over the three years, 100 patients were admitted with OHCA. The incidence of VAP was 6%. The CPIS on admission was not associated with development of VAP at day 3 (p = 0.75) and no significant association was found between choice of antibiotic regimens and VAP incidence. Timing of initiation of antibiotics was associated with VAP (12hrs vs 48hrs, p = 0.035) but not the choice of antibiotic (penicillin and cephalosporins vs antipseudomonal antibiotics). CPIS score at day 1 was not associated with ICU mortality in a multivariate analysis. CONCLUSION: We demonstrated a very low incidence of VAP in OHCA patients in comparison to published studies. In this context, there was no evidence for an association between CPIS score and VAP at day 3. The CPIS may have utility as a decision support tool for targeted antibiotic prescribing in this cohort.

A Minority of Patients on Mechanical Ventilation Consume Disproportionate Resources: A Retrospective Cohort Study.

BACKGROUND: The Pareto principle states that the majority of any effect comes from a minority of the causes. This property is widely used in quality improvement science. RESEARCH QUESTION: Among patients requiring mechanical ventilation (MV), are there subgroups according to MV duration that may serve as potential nodes for high-value interventions aimed at reducing costs without compromising quality? STUDY DESIGN AND METHODS: This multicenter retrospective cohort study included approximately 780 hospitals in the Premier Research Database (2014-2018). Patients receiving MV were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification, and International Classification of Diseases, Tenth Revision, codes. They were then divided into quintiles according to MV duration; their hospital costs, post-MV onset length of stay (LOS), ICU LOS, and cumulative post-MV onset hospital days per quintile were compared. RESULTS: A total of 691,961 patients were included in the analysis. Median [interquartile range] duration of MV in days by quintile was as follows: quintile 1 (Q1), 1 [1, 1]; Q2, 2 [2, 2]; Q3, 3 [3, 3]; Q4, 6 [6, 7]; and Q5, 13 [10, 19]. Median [interquartile range] post-MV onset LOS (Q1, 2 [0, 5]; Q5, 17 [12, 26]) and hospital costs (Q1, $15,671 [$9,180, $27,901]; Q5, $70,133 [$47,136, $108,032]) rose from Q1 through Q5. Patients in Q5 consumed 47.7% of all post-MV initiation hospital days among all patients requiring MV, and the mean per-patient hospital costs in Q5 exceeded the sum of costs incurred by Q1 to Q3. Adjusted marginal mean (95% CI) hospital costs rose exponentially from Q1 through Q5: Q2 vs Q1, $3,976 ($3,354, $4,598); Q3 vs Q2, $5,532 ($5,103, $5,961); Q4 vs Q3, $11,705 ($11,071, $12,339); and Q5 vs Q4, $26,416 ($25,215, $27,616). INTERPRETATION: Patients undergoing MV in the highest quintiles according to duration of MV consume a disproportionate amount of resources, as evidenced by MV duration, hospital LOS, and costs, making them a potential target for streamlining MV care.

Review of health economic models exploring and evaluating treatment and management of hospital-acquired pneumonia and ventilator-associated pneumonia.

BACKGROUND: Hospital-acquired pneumonia (HAP) is pneumonia that occurs ≥48 h after hospital admission; it is the most common hospital-acquired infection contributing to death. Ventilator-associated pneumonia (VAP) arises ≥48-72 h after intubation. Opinions differ on whether VAP is a subset of HAP; the same pathogens predominate in both. Compared with VAP-free controls, patients developing VAP are twice as likely to die and have significantly longer stays in intensive care units. Guidelines recommend that microbiological cultures should guide antibiotic treatment, but these lack sensitivity and take 48-72 h to process, meaning that initial therapy must be empiric, generally with broad-spectrum agents. Given increasing pressure to improve both antibiotic stewardship and patient outcomes, the National Institute for Health and Care Excellence and the Infectious Diseases Society of America recommend research into rapid molecular diagnostic tests to identify causative organisms and their antibiotic resistances. Ideally, these would supersede culture, being quicker and more sensitive. In the UK, the INHALE research programme, funded by the National Institute for Health Research, is exploring rapid molecular diagnostics to inform treatment of HAP/VAP and, given resource implications, incorporates a health economic component. AIM: To identify previous economic modelling of HAP/VAP costs to inform this component. METHODS: Literature review of HAP/VAP studies with economic modelling identified from three databases. FINDINGS: Twenty studies were identified. Only one study specifically evaluated strategies to improve diagnosis; the remaining 19 studies omitted this important aspect. CONCLUSION: HAP/VAP modelling would be improved by better awareness of long-term outcomes and treatment complexity. To the authors' knowledge, no similar literature reviews of economic modelling for HAP/VAP have been published.

Cost-drivers of medical expenses in burn care management.

BACKGROUND: Profound differences exist in the cost of burn care globally, thus we aim to investigate the affected factors and to delineate a strategy to improve the cost-effectiveness of burn management. METHODS: A retrospective analysis of 66 patients suffering from acute burns was conducted from 2013 to 2015. The average age was 26.7 years old and TBSA was 42.1% (±25.9%). We compared the relationship between cost and clinical characteristics. RESULTS: The estimated cost of acute burn care with the following formula (10,000 TWD) = -19.80 + (2.67 × percentage of TBSA) + (124.29 × status of inhalation injury) + (147.63 × status of bacteremia) + (130.32 × status of respiratory tract infection). CONCLUSION: The majority of the cost were associated with the use of antibiotics and burns care. Consequently, it is crucial to prevent nosocomial infection in order to promote healthcare quality and reduce in-hospital costs.

Population pharmacokinetics and Monte Carlo simulations of sulbactam to optimize dosage regimens in patients with ventilator-associated pneumonia caused by Acinetobacter baumannii.

BACKGROUND: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Acinetobacter baumannii remains one of the leading causes of the high mortality rate in critically ill patients. Sulbactam has been considered as an alternative concomitant medication with other effective antimicrobial agents for the treatment of these MDR microorganisms. The aims of this study were (i) to characterize the population pharmacokinetics (PK) and (ii) to assess the efficacy of various dosage regimens of sulbactam in terms of probability of target attainment (PTA). METHODS: The PK studies were carried out following administration of 2 g of sulbactam every 12 h on the 7th dose of drug administration in 16 patients with VAP, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% and 60% the exposure time during which the total plasma drug concentration remained above the MIC (T>MIC). RESULTS: The volume of distribution and total clearance of sulbactam were 22.17 ±â€¯1.60 L and 6.76 ±â€¯2.37 L/h, respectively. For pathogens with a MIC of 8 µg/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4 g/dL and CLCR 90-120 mL/min following administration of sulbactam as a 4-h infusion of 1 g every 6 h, 2 g every 12 h, and 2 g every 8 h were 98.65%, 78.07% and 98.23%, respectively. For pathogens with a MIC of 16 µg/mL, the high PTAs of achieving (≥90%) 60% T>MIC in patients with serum albumin 1.7-2.4 g/dL and CLCR 90-120 mL/min following administration of sulbactam as a 4-h infusion of 2 g every 6 h, and 3 g every 8 h were 98.83% and 95.59%, respectively. CONCLUSION: These findings indicate that high dosage combination regimens are required for the treatment of life-threatening infections in critically ill patients with VAP.

Network meta-analysis and pharmacoeconomic evaluation of antibiotics for the treatment of patients infected with complicated skin and soft structure infection and hospital-acquired or ventilator-associated penumonia.

Background: Infections due to methicillin-resistant Staphylococcus aureus (MRSA) cause serious health risks and significant economic burdens and the preferred drugs are still controversial. Methods: We performed a network meta-analysis (NMA) to compare the efficacy and safety of antibiotics used to treat inpatients with complicated skin and soft structure infections (cSSSI) or hospital-acquired or ventilator-associated pneumonia (HAP/VAP). We also developed a decision tree model to assess the cost-effectiveness of antibiotics. Results: Forty-nine randomized controlled trials met the inclusion criteria (34 for cSSSI, 15 for HAP/VAP) and compared the efficacy and safety of 16 antibiotics. For cSSSI, NMA indicated that for clinical cure, linezolid was superior than vancomycin (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.19-2.02), while tedizolid (OR 1.39, CI 0.70-2.76) was similar to vancomycin. In terms of safety, there were no significant differences between any two interventions on total adverse events. Based on drug and hospital costs in America, the incremental cost-effectiveness ratios (ICERs) per life-year saved for linezolid and tedizolid compared with vancomycin were US$2833 and US$5523. For HAP/VAP, there were no significant effects either for clinical cure or for safety endpoints between linezolid and vancomycin in NMA. ICERs per life-year saved for linezolid compared with vancomycin were US$2185. Conclusion: In these clinical trials, considering efficacy, safety, and cost-effectivenes, linezolid and tedizolid showed their superiority in MRSA cSSSI; while linezolid might be recommended to treat MRSA pneumonia. Although vancomycin was not cost-effective in pharmacoeconomic evaluation, it is still the first-line treatment for MRSA infection in the clinical practice. This study might provide new insights of therapeutic choices for patients with MRSA infections whilst awaiting the arrival of higher quality evidence.

A sequential density-based empirical likelihood ratio test for treatment effects.

In health-related experiments, treatment effects can be identified using paired data that consist of pre- and posttreatment measurements. In this framework, sequential testing strategies are widely accepted statistical tools in practice. Since performances of parametric sequential testing procedures vitally depend on the validity of the parametric assumptions regarding underlying data distributions, we focus on distribution-free mechanisms for sequentially evaluating treatment effects. In fixed sample size designs, the density-based empirical likelihood (DBEL) methods provide powerful nonparametric approximations to optimal Neyman-Pearson-type statistics. In this article, we extend the DBEL methodology to develop a novel sequential DBEL testing procedure for detecting treatment effects based on paired data. The asymptotic consistency of the proposed test is shown. An extensive Monte Carlo study confirms that the proposed test outperforms the conventional sequential Wilcoxon signed-rank test across a variety of alternatives. The excellent applicability of the proposed method is exemplified using the ventilator-associated pneumonia study that evaluates the effect of Chlorhexidine Gluconate treatment in reducing oral colonization by pathogens in ventilated patients.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.

BACKGROUND: Carbapenem resistance is a growing concern. Applying a novel algorithm, we examined epidemiology and outcomes of carbapenem resistance among gram-negative pathogens in hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). METHODS: In a retrospective cohort design within the Premier Research database (2009-2016), all hospitalized adult patients with a gram-negative organism in a respiratory or blood culture specimen who fit criteria for HAP/VAP based on International Classification of Diseases, Ninth Revision, Clinical Modification, codes were included in the study. RESULTS: Among 8,969 patients with HAP/VAP, 1,059 isolates (11.8%) were carbapenem-resistant (CR) organisms. Patients with CR organisms were more likely female (41.4% vs 33.2%; P < .001) and medical admissions (33.8% vs 27.4%, P < .001) than those with carbapenem-susceptible (CS) organisms. Patients with carbapenem resistance had higher comorbidity burden than those with carbapenem susceptibility (median [interquartile range] Charlson Comorbidity Index score, 3 [1-4] vs 2 [1-4]; P < .001). Pseudomonas aeruginosa was the most common gram-negative pathogen overall (24.9%) and among CS organisms (23.5%), and was second to Stenotrophomonas maltophilia (44.0%) among CR organisms (35.3%). Acinetobacter baumannii accounted for 11.8% of CR organisms and 2.5% of CS organisms (P < .001). Patients with carbapenem resistance were more likely than those with carbapenem susceptibility to receive inappropriate empiric therapy (25.8% vs 10.0%; P < .001). Carbapenem resistance did not affect adjusted mortality (22.9% CR vs 21.6% CS) or postinfection length of stay (except among survivors of VAP), but it was associated with excess costs ($8,921; 95% CI, 3,864-13,977). CONCLUSIONS: Using administrative data, our novel algorithm identified patients with pneumonia at high risk for death, consistent with HAP/VAP. Among them, carbapenem resistance occurred in 12% of all cases and was associated with substantial excess in hospital costs.

Assessment of in vivo versus in vitro biofilm formation of clinical methicillin-resistant Staphylococcus aureus isolates from endotracheal tubes.

Our aim was to demonstrate that biofilm formation in a clinical strain of methicillin-resistant Staphylococcus aureus (MRSA) can be enhanced by environment exposure in an endotracheal tube (ETT) and to determine how it is affected by systemic treatment and atmospheric conditions. Second, we aimed to assess biofilm production dynamics after extubation. We prospectively analyzed 70 ETT samples obtained from pigs randomized to be untreated (controls, n = 20), or treated with vancomycin (n = 32) or linezolid (n = 18). A clinical MRSA strain (MRSA-in) was inoculated in pigs to create a pneumonia model, before treating with antibiotics. Tracheally intubated pigs with MRSA severe pneumonia, were mechanically ventilated for 69 ± 16 hours. All MRSA isolates retrieved from ETTs (ETT-MRSA) were tested for their in vitro biofilm production by microtiter plate assay. In vitro biofilm production of MRSA isolates was sequentially studied over the next 8 days post-extubation to assess biofilm capability dynamics over time. All experiments were performed under ambient air (O2) or ambient air supplemented with 5% CO2. We collected 52 ETT-MRSA isolates (placebo N = 19, linezolid N = 11, and vancomycin N = 22) that were clonally identical to the MRSA-in. Among the ETT-MRSA isolates, biofilm production more than doubled after extubation in 40% and 50% under 5% CO2 and O2, respectively. Systemic antibiotic treatment during intubation did not affect this outcome. Under both atmospheric conditions, biofilm production for MRSA-in was at least doubled for 9 ETT-MRSA isolates, and assessment of these showed that biofilm production decreased progressively over a 4-day period after extubation. In conclusion, a weak biofilm producer MRSA strain significantly enhances its biofilm production within an ETT, but it is influenced by the ETT environment rather than by the systemic treatment used during intubation or by the atmospheric conditions used for bacterial growth.

Costo de las neumonías asociadas a la ventilación mecánica en pacientes adultos en un hospital general en Chile / Cost evaluation of ventilator-associated pneumonia in adult patients in a general hospital in Chile

Resumen Introducción: La neumonía asociada a la ventilación mecánica (NAVM) es un evento adverso que aumenta la morbi-mortalidad y costos. Genera días adicionales de hospitalización y de procedimientos diagnósticos y terapéuticos para su tratamiento. No existen datos actualizados nacionales respecto al exceso de costos por NAVM. Objetivo: Dimensionar el costo de las NAVM en un hospital general de la Región Metropolitana. Pacientes y Métodos: Aplicación del protocolo caso-control de costos de infecciones intrahospitalarias de la Organización Panamericana de la Salud (OPS) y cálculo directo de gasto en exceso por evento de NAVM. Se comparó el exceso de días de hospitalización, de antimicrobianos en dosis diaria definida (DDD) y de cultivos. Resultados: Se recolectaron 18 casos de NAVM entre los años 2012 y 2015 en pacientes adultos. Se seleccionaron 18 controles pareados por edad y género. Se observó una mayor estadía promedio de 6,1 días en los casos (p < 0,05), una mayor prescripción de antimicrobianos (diferencia promedio de 11,7 DDD, sin significancia estadística) y un exceso de solicitud de cultivos con una diferencia promedio de 3,2 (p < 0,05). El costo unitario por NAVM fue de 4.475 USD. Conclusiones: Los eventos de NAVM generan una mayor estadía hospitalaria, consumo de recursos diagnósticos y terapéuticos.

Background: Ventilator-associated pneumonia (VAP) is an adverse event that increases morbidity, mortality and costs due to a prolonged stay and requirement of microbiological studies and antimicrobial therapy. There is not recent data of VAP costs in Chile. Aim: To evaluate additional costs in adult patients with VAP compared to controls in a general hospital in the Metropolitan Area. Patients and Methods: Use of the PAHO paired casecontrol protocol for cost evaluation associated to nosocomial infections and estimation of cost in excess per VAP event. Length of stay (LOS) in excess, antimicrobial consumption in daily-defined doses (DDD), and number of microbiological studies were compared between both groups. Results: From 2012 to 2015, 18 patients with VAP events were identified with their respective controls. LOS exceeded 6.1 days on average among patients with VAP respect to controls (p < 0.05). DDD was higher among patients with VAP (difference 11.7 DDD) as well as number of cultures (3.2 higher on average, p < 0.05). Cost in excess per VAP event reached 4,475 USD. Conclusions: In our Centre, VAP events are associated to a higher LOS, antimicrobial consumption and microbiological studies.

Biomarkers kinetics in the assessment of ventilator-associated pneumonia response to antibiotics - results from the BioVAP study.

PURPOSE: Our aim was to evaluate the role of biomarker kinetics in the assessment of ventilator-associated pneumonia (VAP) response to antibiotics. MATERIALS AND METHODS: We performed a prospective, multicenter, observational study to evaluate in 37 microbiologically documented VAP, the kinetics of C-reactive protein (CRP), procalcitonin (PCT), mid-region fragment of pro-adrenomedullin (MR-proADM). The kinetics of each variable, from day 1 to 6 of therapy, was assessed with a time dependent analysis comparing survivors and non-survivors. RESULTS: During the study period kinetics of CRP as well as its relative changes, CRP-ratio, was significantly different between survivors and non-survivors (p=0.026 and p=0.005, respectively). On day 4 of antibiotic therapy, CRP of survivors was 47% of the initial value while it was 96% in non-survivors. The kinetics of other studied variables did not distinguish between survivors and non-survivors. In survivors the bacterial load also decreased markedly. Adequate initial antibiotic therapy was associated with lower mortality (p=0.025) and faster CRP decrease (p=0.029). CONCLUSIONS: C-reactive protein kinetics can be used to identify VAP patients with poor outcome as soon as four days after the initiation of treatment. (Trial registration - NCT02078999; registered 3 August 2012).

Management of ventilator associated pneumonia with a new antibiotic adjuvant entity (ceftriaxone+sulbactam+disodium edetate) - A novel approach to spare carbapenems.

BACKGROUND: Ventilator associated pneumonia (VAP) is one of the most serious nosocomial infections in Intensive Care Unit (ICU). The aim of this study was to evaluate a new approach to spare the carbapenems for the management of patients diagnosed with VAP due to Acinetobacter baumannii (A. baumannii). METHOD: This retrospective study was conducted on VAP patients presenting for treatment at tertiary care centre between May 2014 and March 2016. The case sheets of patients who have been treated for VAP with meropenem, antibiotic adjuvant entity (AAE) and colistin were analysed. RESULTS: Out of 113 patients analysed, 24 (21.3%) patients were having VAP due to MDR A. baumannii. Microbial sensitivity has shown that 87.5% of patients were sensitive to AAE and colistin whereas all of them were resistant to meropenem, imipenem and gentamycin. The mean treatment durations were 12.4±2.1, 13.2±2.4 and 14.3±2.1days for AAE, meropenem+colistin and AAE+colistin treatment groups. In AAE susceptible patients, the mean treatment duration and cost could be reduced by 23-24% and 43-53% if AAE is used empirically. In AAE-resistant patients, the mean treatment duration and cost could be reduced by 21% and 26% if AAE+colistin regime is used empirically instead of meropenem followed by AAE+colistin. CONCLUSIONS: Clinical assessment with microbial eradication and pharmaco-economic evaluation clearly shows benefits in using AAE empirically in the management of A. baumannii infected VAP cases.

Aggressive versus conservative antibiotic use to prevent and treat ventilator-associated pneumonia in patients with severe traumatic brain injury: comparison of two case series.

BACKGROUND: In patients with traumatic brain injury (TBI), ventilator-associated pneumonia (VAP) is considered a dangerous complication, prompting early aggressive antibiotic treatment and prophylaxis. While this approach increases the selection of multidrug-resistant bacteria (MDR), its clinical benefit has not been demonstrated. METHODS: One-year incidence of VAP in severe TBI patients (ICU stay >48 hours, with either Glasgow Coma Scale ≤8 or receiving intracranial pressure monitoring, or having undergone emergency surgery) and the prevalence of MDR among those who eventually developed it, were compared in two Italian intensive care units (ICUs) adopting different antibiotic approaches. Antibiotic use was guideline-driven and aggressive in the Pisa-based unit (165 eligible patients), and very conservative and coupled with non-pharmacological prevention measures in Cesena (262 patients). Data were also compared with those of 208 Italian ICUs participating in the same infection surveillance program. RESULTS: Patient case mix and general care were similar in the two units. Overall antibiotic pressure was higher in Pisa (58.9% vs. 26.1% of beds occupied by patients receiving antibiotics, P<0.0001), as was antibiotic prophylaxis in eligible patients (87.3% vs. 7.6%, P<0.0001; Italian ICUs, 69.2%) and empirical therapy in those who developed VAP (60.8% vs. 25.2%, P<0.0001; Italian ICUs, 51.6%). The incidence rate of VAP did not significantly differ (39.8 per 1000 days of mechanical ventilation in Pisa, 49.3 in Cesena, P=0.16), although it occurred earlier in Cesena (23.0% early VAP in Pisa vs. 61.2% in Cesena, P<0.0001). Mortality was higher in Pisa but Cesena transferred more patients to other hospitals, precluding comparison of the two rates. The prevalence of MDR was higher in Pisa (38.2% vs. 9.9%, P<0.0001; Italian ICUs, 30.2%). CONCLUSIONS: Although not conclusive, these results call into question the prevalent aggressive use of antibiotics in TBI patients and urge the scientific community to produce better evidence for clinical recommendations.

[Cost evaluation of ventilator-associated pneumonia in adult patients in a general hospital in Chile]. / Costo de las neumonías asociadas a la ventilación mecánica en pacientes adultos en un hospital general en Chile.

BACKGROUND: Ventilator-associated pneumonia (VAP) is an adverse event that increases morbidity, mortality and costs due to a prolonged stay and requirement of microbiological studies and antimicrobial therapy. There is not recent data of VAP costs in Chile. AIM: To evaluate additional costs in adult patients with VAP compared to controls in a general hospital in the Metropolitan Area. PATIENTS AND METHODS: Use of the PAHO paired casecontrol protocol for cost evaluation associated to nosocomial infections and estimation of cost in excess per VAP event. Length of stay (LOS) in excess, antimicrobial consumption in daily-defined doses (DDD), and number of microbiological studies were compared between both groups. RESULTS: From 2012 to 2015, 18 patients with VAP events were identified with their respective controls. LOS exceeded 6.1 days on average among patients with VAP respect to controls (p < 0.05). DDD was higher among patients with VAP (difference 11.7 DDD) as well as number of cultures (3.2 higher on average, p < 0.05). Cost in excess per VAP event reached 4,475 USD. CONCLUSIONS: In our Centre, VAP events are associated to a higher LOS, antimicrobial consumption and microbiological studies.

Bacteriological Assessment of Pneumonia Caused by Gram-Negative Bacteria in Patients Hospitalized in Intensive Care Unit.

The article presents the results of 11-year study (2005-2015) of Gram-negative bacteria responsible for pneumonia in 2033 mechanically ventilated patients hospitalized in Intensive Care Unit. Of 8796 biological samples, consisting mainly of bronchial aspirate (97.9 %), 2056 bacterial strains were isolated and subjected to identification. VITEK 2 was used to determine drug susceptibility (classified according to the EUCAST criteria). ESBL, MBL and KPC-producing strains were identified by means of phenotypic methods using appropriate discs. The findings were that the predominant bacteria responsible for infections consisted of Enterobacteriaceae (42.0 %), Acinetobacter baumannii (37.2 %), Pseudomonas aeruginosa (16.1 %), and Stenotrophomonas maltophila (4.7 %). We observed a rise in the number of bacteria causing pneumonia throughout the study period, especially in S. maltophila and Enterobacteriaceae ESBL (+). Gram-negative bacilli were 100 % susceptible to colistin, apart from naturally resistant strains such as Proteus mirabilis, Serratia marcescens, whereas Enterobacteriaceae ESBL (+) were susceptible to imipenem and meropenem. Acinetobacter baumannii strains exhibited the lowest drug susceptibility. In conclusion, we report an increase in the prevalence of pneumonia associated with Gram-negative bacteria in mechanically ventilated intensive care patients. Colistin remains the most effective drug against the majority of Gram-negative bacteria. Therapeutic problems are common in the course of treatment of Acinetobacter baumannii infections.