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Purpose: To report the case of a colchicine overdose to highlight current limitations in the treatment of this toxicologic emergency. Summary: A 23-year-old man was admitted to the intensive care unit (ICU) after attempting suicide via polypharmacy ingestion, which included 80 to 100 colchicine 0.6 mg tablets (approximately 0.9 mg/kg of body weight). He was taken to the emergency department where gastric decontamination was initiated. Because attempts to obtain a colchicine-specific antibody fragment (Fab) were unsuccessful, only supportive therapies were provided throughout his hospitalization. Over the course of several days, the patient experienced the 3 separate evolutionary phases of colchicine toxicity ultimately leading to multiple organ failure and hemodynamic collapse, and death. Conclusion: Acute colchicine intoxication is a rare, but potentially life-threatening event. Although 1 case report demonstrated the successful use of a colchicine-specific Fab fragment in the management of acute colchicine overdose, there is presently no commercially-available antidote for colchicine toxicity. Prompt recognition of the overdose, aggressive gastrointestinal decontamination, and supportive therapies directed at the multi-organ failure remain the standard of care. [ABSTRACT FROM AUTHOR]

Background: The evolution of compliance and driving pressure in ARDS and the effects of time spent on noninvasive respiratory support prior to intubation have not been well studied. We conducted this study to assess the effect of the duration of noninvasive respiratory support prior to intubation (ie, noninvasive ventilation [NIV], high-flow nasal cannula [HFNC], or a combination of NIV and HFNC) on static compliance and driving pressure and retrospectively describe its trajectory over time for COVID-19 and non-COVID-19 ARDS while on mechanical ventilation., Methods: This is a retrospective analysis of prospectively collected data from one university-affiliated academic medical center, one rural magnet hospital, and 3 suburban community facilities. A total of 589 subjects were included: 55 COVID-19 positive, 137 culture positive, and 397 culture-negative subjects. Static compliance and driving pressure were calculated at each 8-h subject-ventilator assessment., Results: Days of pre-intubation noninvasive respiratory support were associated with worse compliance and driving pressure but did not moderate any trajectory. COVID-19-positive subjects showed non-statistically significant worsening compliance by 0.08 units per subject-ventilator assessment ( P = .24), whereas COVID-19-negative subjects who were either culture positive or negative showed statistically significant improvement (0.12 and 0.18, respectively; both P < .05); a statistically similar but inverse pattern was observed for driving pressure., Conclusions: In contrast to non-COVID-19 ARDS, COVID-19 ARDS was associated with a more ominous trajectory with no improvement in static compliance or driving pressures. Though there was no association between days of pre-intubation noninvasive respiratory support and mortality, its use was associated with worse overall compliance and driving pressure., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2023 by Daedalus Enterprises.)

Purpose: This article summarizes the appropriate use and pharmacology of treatments for fibrosing interstitial lung diseases, with a specific focus on the antifibrotic agents nintedanib and pirfenidone., Summary: The interstitial lung diseases are a heterogenous group of parenchymal lung disorders with a common feature-infiltration of the interstitial space with derangement of the normal capillary-alveolar anatomy. Diseases characterized by fibrosis of the interstitial space are referred to as the fibrosing interstitial lung diseases and often show progression over time: idiopathic pulmonary fibrosis is the most common fibrotic interstitial lung disease. Historically, therapies for fibrosing lung diseases have been limited in number, questionable in efficacy, and associated with potential harms. Food and Drug Administration (FDA) approval of the antifibrotic agents nintedanib and pirfenidone for idiopathic pulmonary fibrosis in 2014 heralded an era of reorganization of therapy for the fibrotic interstitial lung diseases. Subsequent investigations have led to FDA approval of nintedanib for systemic sclerosis-associated interstitial lung disease and interstitial lung diseases with a progressive phenotype. Although supportive care and pulmonary rehabilitation should be provided to all patients, the role(s) of immunomodulators and/or immune suppressing agents vary by the underlying disease state. Several agents previously used to treat fibrotic lung diseases (N-acetylcysteine, anticoagulation, and pulmonary vasodilators) lack efficacy or cause harm., Conclusion: With the introduction of effective pharmacotherapy for fibrosing interstitial lung disease, pharmacists have an increasingly important role in the interdisciplinary team managing these patients., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although multiple risk factors for development of pneumonia in patients with trauma sustained in a motor vehicle accident have been studied, the effect of prehospital time on pneumonia incidence post-trauma is unknown., Research Question: Is prolonged prehospital time an independent risk factor for pneumonia?, Study Design and Methods: We retrospectively analyzed prospectively collected clinical data from 806,012 motor vehicle accident trauma incidents from the roughly 750 trauma hospitals contributing data to the National Trauma Data Bank between 2010 and 2016., Results: Prehospital time was independently associated with development of pneumonia post-motor vehicle trauma (P < .001). This association was primarily driven by patients with low Glasgow Coma Scale scores. Post-trauma pneumonia was uncommon (1.5% incidence) but was associated with a significant increase in mortality (P < .001, 4.3% mortality without pneumonia vs 12.1% mortality with pneumonia). Other pneumonia risk factors included age, sex, race, primary payor, trauma center teaching status, bed size, geographic region, intoxication, comorbid lung disease, steroid use, lower Glasgow Coma Scale score, higher Injury Severity Scale score, blood product transfusion, chest trauma, and respiratory burns., Interpretation: Increased prehospital time is an independent risk factor for development of pneumonia and increased mortality in patients with trauma caused by a motor vehicle accident. Although prehospital time is often not modifiable, its recognition as a pneumonia risk factor is important, because prolonged prehospital time may need to be considered in subsequent decision-making., (Published by Elsevier Inc.)

Background: Although resuscitation with IV fluids is the cornerstone of sepsis management, consensus regarding their association with improvement in clinical outcomes is lacking., Research Question: Is there a difference in the incidence of respiratory failure in patients with sepsis who received guideline-recommended initial IV fluid bolus of 30 mL/kg or more conservative resuscitation of less than 30 mL/kg?, Study Design and Methods: This was a retrospective analysis of prospectively collected clinical data conducted at an academic medical center in Omaha, Nebraska. We abstracted data from 214 patients with sepsis admitted to a single academic medical center between June 2017 and June 2018. Patients were stratified by receipt of guideline-recommended fluid bolus. The primary outcome was respiratory failure defined as an increase in oxygen flow rate or more intense oxygenation and ventilation support; oxygen requirement and volume were measured at admission, 6 h, 12 h, 24 h, and at discharge. Subgroup analyses were conducted in high-risk patients with congestive heart failure (CHF) as well as those with chronic kidney disease (CKD)., Results: A total of 62 patients (29.0%) received appropriate bolus treatment. The overall rate of respiratory failure was not statistically different between patients who received appropriate bolus or did not (40.3% vs 36.8%; P = .634). Likewise, no differences were observed in time to respiratory failure (P = .645) or risk of respiratory failure (adjusted hazard ratio, 1.1 [95% CI, 0.7-1.7]; P = .774). Results were similar within the high-risk CHF and CKD subgroups., Interpretation: In this single-center retrospective study, we found that by broadly defining respiratory failure as an increase in oxygen requirements, a conservative initial IV fluid resuscitation strategy did not correlate with decreased rates of hypoxemic respiratory failure., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis., Methods: Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation., Results: MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death., Conclusions: In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP < 65 mmHg) and was a significant predictor of mortality. Because HR, lactate, and MAP were associated with mortality, our data support the present strategy of using these measurements to gauge severity of illness upon presentation. Since HR did not moderate or mediate the association between lactate and death, criticisms alleging that lactate caused by sympathetic stimulation is adaptive (i.e., less harmful) do not appear substantiated.

Objectives: Multiple studies have demonstrated an obesity paradox such that obese ICU patients have lower mortality and better outcomes. We conducted this study to determine if the mortality benefit conferred by obesity is affected by baseline serum lactate and mean arterial pressure., Design: Retrospective analysis of prospectively collected clinical data., Setting: Five community-based and one academic medical center in the Omaha, NE., Patients: 7,967 adults hospitalized with sepsis., Interventions: None., Measurements and Main Results: Patients were categorized by body mass index as underweight, normal weight, overweight, or obese. Multivariable logistic regression models were used to estimate the odds of in-hospital death by body mass index category; two-way interactions between body mass index and each covariate were also evaluated. Subgroup and sensitivity analyses were conducted using an ICU cohort and Acute Physiology and Chronic Health Evaluation III scores, respectively. The overall unadjusted mortality rate was 12.1% and was consistently lower in higher body mass index categories (all comparisons, p < 0.007). The adjusted mortality benefit observed in patients with higher body mass index was smaller in patients with higher lactate levels with no mortality benefit in higher body mass index categories observed at lactate greater than 5 mmol/L. By contrast, the association between lower MAP and higher mortality was constant across body mass index categories. Similar results were observed in the ICU cohort. Finally, the obesity paradox was not observed after including Acute Physiology and Chronic Health Evaluation III scores as a covariate., Conclusions: Our retrospective analysis suggests that although patient size (i.e., body mass index) is a predictor of in-hospital death among all-comers with sepsis-providing further evidence to the obesity paradox-it adds that illness severity is critically important whether quantified as higher lactate or by Acute Physiology and Chronic Health Evaluation III score. Our results highlight that the obesity paradox is more than a simple association between body mass index and mortality and reinforces the importance of illness severity.

Clinicians have traditionally dichotomized bacteria as friendly commensals or harmful pathogens. However, the line separating the two has become blurred with the recognition that the intestinal microbiome is a complex entity in which species can shift sides-from friend to foe and back again-based on crucial factors in their local environment. Significant disruptions in the homeostasis of the microbiome, a phenomenon called dysbiosis, is increasingly associated with a host of untoward effects. Patients in the ICU are at high risk for dysbiosis given the high rate of antibiotic use, acute changes in diet, and the stress of critical illness. Probiotics are living microbes of human origin that when ingested in sufficient quantities, can colonize sites such as the oropharynx and GI tract and provide benefits to the host. In recent years, we have increasingly explored the utility of using probiotics to reverse the intestinal dysbiosis associated with critical illness, thereby reducing select ICU complications associated with increased morbidity and mortality. Although these preliminary efforts have demonstrated varying degrees of success, our present studies suffer from a host of limitations that hinder the strength of their conclusions and the generalizability of their results. Probiotic investigations have been further hobbled by current regulatory requirements, which were designed to serve as the framework for pharmaceutical research. Although such measures are intended to ensure patient safety, they inadvertently impose barriers that stifle innovation regarding nutraceuticals. This review strives to summarize the current evidence regarding the efficacy and safety of probiotics in the ICU as well as to provide an overview of the obstacles probiotic researchers face going forward., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The data evaluating the role of statins in delirium prevention in the intensive care unit are conflicting and limited., Methods: We performed a systematic review and meta-analysis of literature from 1975 to 2015. All English-language adult studies evaluating delirium incidence in statin and statin nonusers were included and studies without a control group were excluded. Mantel-Haenszel model was used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Statistical significance was defined as CI not including unity and P value less than .05., Results: Of a total 57 identified studies, 6 were included. The studies showed high heterogeneity (I 2 = 73%) for all and moderate for cardiac surgery studies (I 2 = 55%). Of 289 773 patients, statins were used in 22 292 (7.7%). Cardiac surgery was performed in 4382 (1.5%) patients and 2321 (53.0%) used statins. Delirium was noted in 710 (3.2%) and 3478 (1.3%) of the patients in the statin and nonstatin groups, respectively, with no difference between groups in the total cohort (RR, 1.05 [95% CI, 0.85-1.29]; P = .56) or in cardiac surgery patients (RR, 1.03 [95% CI, 0.68-1.56]; P = .89)., Conclusions: In critically ill and cardiac surgery patients, this meta-analysis did not show a benefit with statin therapy in the prevention of delirium., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To identify preoperative factors associated with an increased risk of postoperative pneumonia and subsequently develop and validate a risk calculator., Patients and Methods: The American College of Surgeons' National Surgical Quality Improvement Program, a multicenter, prospective data set (2007-2008) was used. Univariate and multivariate logistic regression analyses were performed. The 2007 data set (N=211,410) served as the training set, and the 2008 data set (N=257,385) served as the validation set., Results: In the training set, 3825 patients (1.8%) experienced postoperative pneumonia. Patients who experienced postoperative pneumonia had a significantly higher 30-day mortality (17.0% vs 1.5%; P<.001). On multivariate logistic regression analysis, 7 preoperative predictors of postoperative pneumonia were identified: age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The risk model based on the training data set was subsequently validated on the validation data set, with model performance being very similar (C statistic: 0.860 and 0.855, respectively). The high C statistic indicates excellent predictive performance. The risk model was used to develop an interactive risk calculator., Conclusion: Preoperative variables associated with an increased risk of postoperative pneumonia include age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The validated risk calculator provides a risk estimate for postoperative pneumonia and is anticipated to aid in surgical decision making and informed patient consent., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: There are few data on dose optimization and clinical outcomes of antimicrobial agents based on patients' weight, despite the rising prevalence of obesity. Because there are physiologic, pharmacologic, and dosing differences related to weight, it is important to evaluate the impact of weight on antimicrobial agents to optimize clinical outcomes., Objectives: This study compared effects of weight on efficacy and safety in patients treated with linezolid or vancomycin for complicated skin and skin structure infections (cSSSIs) and nosocomial pneumonia (NP) caused by methicillin-resistant Staphylococcus aureus (MRSA)., Methods: We analyzed data from 2 clinical trials of patients randomized to receive a fixed dose of linezolid or weight-based dosing of vancomycin for the treatment of cSSSIs or NP caused by MRSA. For each study, patients were stratified into quartiles (Q1-4 [lowest to highest weight, respectively]). Clinical success, microbiologic success, and adverse events (AEs) were evaluated., Results: The analysis included 632 patients with cSSSIs (linezolid, n = 316; vancomycin, n = 316) and 447 patients with NP (linezolid, n = 224; vancomycin, n = 223). Among patients with cSSSIs, clinical success rates at the study end with fixed-dose linezolid were similar across all weight quartiles and similar to weight-based dosing of vancomycin for Q1-3. Among Q4 (the highest weight quartile [97-295 kg]), clinical success with vancomycin was significantly lower compared with linezolid (69.5% vs 86.2%; P = 0.03). Among patients with NP, no significant differences in success rates between fixed-dose linezolid and weight-based dosing of vancomycin were observed across all quartiles. Frequencies of AEs were consistent across the quartiles for both indications and by treatment., Conclusions: Except for Q4 within the vancomycin-treated patients for MRSA cSSSI, the efficacy of fixed-dosed linezolid and weight-based dosing of vancomycin was maintained across all weight quartiles and MRSA infection types. The AEs were consistent with the known safety profiles of each drug regardless of weight quartile. ClinicalTrials.gov identifiers: NCT00087490 and NCT00084266., (© 2013 Elsevier HS Journals, Inc. All rights reserved.)

Background: Postoperative pneumonia (PP) and respiratory failure (PRF) are known to be the most common nonwound complications after bariatric surgery. Our objective was to identify their current prevalence after bariatric surgery and to study the preoperative factors associated with them using data from the American College of Surgeons' National Surgical Quality Improvement Program., Methods: Patients undergoing bariatric surgery were identified from the National Surgical Quality Improvement Program (2006-2008), a multicenter, prospective database. Univariate analysis and multivariate logistic regression analysis were performed., Results: Of 32,889 patients, PP was diagnosed in 187 patients (.6%) and PRF in 204 patients (.6%). The overall 30-day morbidity rate was 6.4%, with PP and PRF accounting for 18.7%. The 30-day mortality rate was greater for the patients with PP and PRF than those without (4.3% versus .16% and 13.7% versus .10%, P < .0001). The hospital length of stay was also longer in patients with PP/PRF (P < .0001). On multivariate analysis, congestive heart failure (odds ratio 5.3, 95% confidence interval 1.20-23.26) and stroke (odds ratio 4.1, 95% confidence interval 1.42-11.49) were the greatest preoperative risk factors for PP. Previous percutaneous coronary intervention (odds ratio 2.8, 95% confidence interval 1.64-4.74) and dyspnea at rest (odds ratio 2.64, 95% confidence interval 1.13-6.13) were the factors most strongly associated with PRF. Bleeding disorder, age, chronic obstructive pulmonary disease, and type of surgery were risk factors for both (P < .05). Smoking also predisposed to PP, and diabetes mellitus, anesthesia time, and increasing weight also predisposed to PRF (P < .05 for all)., Conclusion: Although PP and PRF are infrequent, they account for one fifth of the postoperative morbidity and are associated with significantly increased 30-day mortality. They can be predicted by various risk factors, emphasizing the importance of patient optimization and careful selection before bariatric surgery., (Copyright © 2012 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Probiotics are living microorganisms that, when ingested in adequate amounts, provide benefits to the host. The benefits include either a shortened duration of infections or decreased susceptibility to pathogens. Proposed mechanisms of beneficial effects include improving gastrointestinal barrier function, modification of the gut flora by inducing host cell antimicrobial peptides and/or local release of probiotic antimicrobial factors, competition for epithelial adherence, and immunomodulation. With increasing intensive care unit (ICU) antibacterial resistance rates and fewer new antibiotics in the research pipeline, focus has been shifted to non-antibiotic approaches for the prevention and treatment of nosocomial infections. Probiotics offer promise to ICU patients for the prevention of antibiotic-associated diarrhea, Clostridium difficile infections, multiple organ dysfunction syndrome, and ventilator-associated pneumonia. Our current understanding of probiotics is confounded by inconsistency in probiotic strains studied, optimal dosages, study durations, and suboptimal sample sizes. Although probiotics are generally safe in the critically ill, adverse event monitoring must be rigorous in these vulnerable patients. Delineation of clinical differences of various effective probiotic strains, their mechanisms of action, and optimal dosing regimens will better establish the role of probiotics in various disorders. However, probiotic research will likely be hindered in the future given a recent ruling by the U.S. Food and Drug Administration.

Rationale: Enteral administration of probiotics may modify the gastrointestinal environment in a manner that preferentially favors the growth of minimally virulent species. It is unknown whether probiotic modification of the upper aerodigestive flora can reduce nosocomial infections., Objectives: To determine whether oropharyngeal and gastric administration of Lactobacillus rhamnosus GG can reduce the incidence of ventilator-associated pneumonia (VAP)., Methods: We performed a prospective, randomized, double-blind, placebo-controlled trial of 146 mechanically ventilated patients at high risk of developing VAP. Patients were randomly assigned to receive enteral probiotics (n = 68) or an inert inulin-based placebo (n = 70) twice a day in addition to routine care., Measurements and Main Results: Patients treated with Lactobacillus were significantly less likely to develop microbiologically confirmed VAP compared with patients treated with placebo (40.0 vs. 19.1%; P = 0.007). Although patients treated with probiotics had significantly less Clostridium difficile-associated diarrhea than patients treated with placebo (18.6 vs. 5.8%; P = 0.02), the duration of diarrhea per episode was not different between groups (13.2 ± 7.4 vs. 9.8 ± 4.9 d; P = 0.39). Patients treated with probiotics had fewer days of antibiotics prescribed for VAP (8.6 ± 10.3 vs. 5.6 ± 7.8 d; P = 0.05) and for C. difficile-associated diarrhea (2.1 ± 4.8 SD d vs. 0.5 ± 2.3 d; P = 0.02). No adverse events related to probiotic administration were identified., Conclusions: These pilot data suggest that L. rhamnosus GG is safe and efficacious in preventing VAP in a select, high-risk ICU population. Clinical trial registered with www.clinicaltrials.gov (NCT00613795).

Healthcare-associated pneumonia (HCAP) represents one of the largest subsets of patients with pneumonia. Based on epidemiological projections for the aging U.S. population, the number of hospitalizations for HCAP is expected to increase exponentially for the next several decades. The unique risk factors for colonization with resistant pathogens in these patients provide multiple opportunities for HCAP prevention. However, our current understanding of the most effective prevention measures is woefully inadequate and constitutes an extrapolation from studies done in community-acquired and hospital-acquired pneumonia patients. This review explores common prevention strategies that may be applicable to HCAP, highlights areas of controversy that require further study, and describes several areas of ongoing novel investigation.

Increasingly, patients are receiving treatment at facilities other than hospitals, including long-term-health care facilities, assisted-living environments, rehabilitation facilities, and dialysis centers. As with hospital environments, nonhospital settings present their own unique risks of pneumonia. Traditionally, pneumonia in these facilities has been categorized as community-acquired pneumonia (CAP). However, the new designation for pneumonias acquired in these settings is health care-associated pneumonia (HCAP), which covers pneumonias acquired in health care environments outside of the traditional hospital setting and excludes hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and CAP. Although HCAP is currently treated with the same protocols as CAP, recent evidence indicates that HCAP differs from CAP with respect to pathogens and prognosis and, in fact, more closely resembles HAP and VAP. The HCAP Summit convened national infectious disease opinion leaders for the purpose of analyzing current literature, clinical trial data, diagnostic considerations, therapeutic options, and treatment guidelines related to HCAP. After an in-depth analysis of these areas, the infectious disease investigators participating in the summit were surveyed with regard to 10 clinical practice statements. The results were then compared with results of the same survey as completed by 744 Infectious Diseases Society of America members. The similarities and differences between those survey results are the basis of this publication.

Objective: To review the available clinical data supporting the use of probiotics in preventing and treating serious nosocomial infections., Data Source: A Medline database from 1996 to July 2006 and references from identified articles were used to perform a literature search relating to the clinical applications of probiotics in preventing and treating Clostridium difficile-associated diarrhea (CDD) and prevention of hospital-associated pneumonia (HAP)., Conclusion: Nosocomial infections like HAP and CDD contribute significantly to health-care costs in the United States. These clinical problems are associated with prolonged hospital stays and increased mortality in critically ill patients. The emergence of multidrug-resistant pathogens in cases of HAP and the recent description of an epidemic, toxin gene-variant strain of C difficile, combined with the anticipated lack of new antimicrobial agents in the near future emphasize the need for new, innovative strategies to prevent and treat these diseases. Probiotics normally function as colonizers and contribute to the overall health of their hosts by multiple mechanisms including immune and antibacterial effects. There is no current clinical evidence to support the use of probiotics to restore the normal human flora in critically ill patients and reduce HAP rates. Probiotics can prevent episodes of antibiotic-associated diarrhea, but their utility in treating and preventing CDD requires demonstration of benefit in multicenter clinical trials, preferably sponsored by the National Institutes of Health.

A 25-year-old, 54-kg Hispanic man who had recently started multidrug therapy for pulmonary tuberculosis presented in status epilepticus after ingesting 9 g of isoniazid in a suicide attempt. Successful management of this patient required collaboration between several institutions to provide the large amount of necessary intravenous pyridoxine. Ultimately, this single overdose depleted the supply of intravenous pyridoxine for a significant region of the state of Nebraska. Isoniazid is commonly used to treat tuberculosis, but it is encountered relatively infrequently as the cause of an acute overdose. Severe isoniazid overdoses may present as seizure activity that is refractory to conventional antiepileptic therapy. Although intravenous pyridoxine is an effective antidote for isoniazid overdoses in patients presenting with status epilepticus, this agent has few indications and is typically stocked in limited quantities. In regions with large populations of patients who receive antituberculosis therapy, collaborative networks must be created to ensure that adequate supplies of intravenous pyridoxine (> or = 20 g) are available for effective treatment of isoniazid poisonings.

Study Objectives: To evaluate clinical characteristics and treatment patterns among patients with ventilator-associated pneumonia (VAP), including the implementation of and outcomes associated with deescalation therapy., Design: Prospective, observational, cohort study., Setting: Twenty ICUs throughout the United States., Patients: A total of 398 ICU patients meeting predefined criteria for suspected VAP., Interventions: Prospective, handheld, computer-based data collection regarding routine VAP management according to local institutional practices, including clinical and microbiological characteristics, treatment patterns, and outcomes., Measurements and Results: The most frequent ICU admission diagnoses in patients with VAP were postoperative care (15.6%), neurologic conditions (13.3%), sepsis (13.1%), and cardiac complications (10.8%). The mean (+/- SD) duration of mechanical ventilation prior to VAP diagnosis was 7.3 +/- 6.9 days. Major pathogens were identified in 197 patients (49.5%) through either tracheal aspirate or BAL fluid and included primarily methicillin-resistant Staphylococcus aureus (14.8%), Pseudomonas aeruginosa (14.3%), and other Staphylococcus species (8.8%). More than 100 different antibiotic regimens were prescribed as initial VAP treatment, the majority of which included cefepime (30.4%) or a ureidopenicillin/monobactam combination (27.9%). The mean duration of therapy was 11.8 +/- 5.9 days. In the majority of cases (61.6%), therapy was neither escalated nor deescalated. Escalation of therapy occurred in 15.3% of cases, and deescalation occurred in 22.1%. The overall mortality rate was 25.1%, with a mean time to death of 16.2 days (range, 0 to 49 days). The mortality rate was significantly lower among patients in whom therapy was deescalated (17.0%), compared with those experiencing therapy escalation (42.6%) and those in whom therapy was neither escalated nor deescalated (23.7%; chi2= 13.25; p = 0.001)., Conclusions: Treatment patterns for VAP vary widely from institution to institution, and the overall mortality rate remains unacceptably high. The deescalation of therapy in VAP patients appears to be associated with a reduction in mortality, which is an association that warrants further clinical study.