Heather Arnold

Hospital resource utilization and costs of inappropriate treatment of candidemia.

Study Objectives. To evaluate the impact of inappropriate therapy—defined as delayed antifungal therapy beyond 24 hours from culture collection, inadequate antifungal dosage, or administration of an antifungal to which an isolate was considered resistant—on postculture hospital length of stay and costs, and to evaluate the relationship between modifiable risk factors, including failure to remove a central venous catheter, antifungal delay, and inadequate dosage, for an additive effect on hospital length of stay and costs.

Use of Adjunctive Aerosolized Antimicrobial Therapy in the Treatment of Pseudomonas aeruginosa and Acinetobacter baumannii Ventilator-Associated Pneumonia

BACKGROUND: Adjunctive aerosolized antibiotics (AAA) have been recommended in the setting of Gram-negative ventilator-associated pneumonia (VAP), but little is known about their influence on clinical outcomes. OBJECTIVE: To assess outcomes associated with AAA for the treatment of Pseudomonas aeruginosa (PA) and Acinetobacter baumannii (AB) VAP. METHODS: A retrospective, single-center cohort study at Barnes-Jewish Hospital in St Louis, Missouri. Consecutive subjects treated for bronchoalveolar lavage-confirmed PA or AB VAP between January 1, 2004 and December 31, 2009 were enrolled. Records of subjects treated with AAA were compared to those who did not receive AAAs (NAAA). RESULTS: Ninety-three patients were evaluated (NAAA n = 74, AAA n = 19, inhaled colistin n =9, inhaled tobramycin n =10). Patients receiving AAA were significantly more likely to be infected with multidrug-resistant bacteria (52.6% vs 14.9%, P < .001) and had greater Acute Physiology and Chronic Health Evaluation II scores (21.4 ± 5.7 vs 17.5 ± 5.3, P = .004) compared to patients receiving NAAA. NAAA subjects experienced a shorter time from VAP onset to appropriate intravenous antibiotic initiation (0.5 ± 0.9 d vs 2.6 ± 5.4 d, P = .038), but length of intravenous therapy was similar between groups (12.8 ± 8.5 d vs 17.8 ± 13.3 d, P = .16). The NAAA group demonstrated significantly shorter mechanical ventilation duration (18.9 ± 15.9 d vs 38.4 ± 32.4 days, P < .001), intensive care unit stay (37.5 ± 42.5 d vs 56.3 ± 31.3 d, P = .001), and hospital stay (39.0 ± 42.5 d vs 58.3 ± 33.4 d, P = .001). However, Kaplan-Meier curves for the probability of 30-day survival from VAP onset demonstrated that patients receiving AAA had statistically greater survival (P = .030 by the log rank test). CONCLUSIONS: Patients with PA and AB VAP may experience favorable survival when treated with AAA, despite greater severity of illness and a greater incidence of multidrug-resistant infection. Large randomized trials are needed to further explore this therapy.

A Comparison of Culture-Positive and Culture-Negative Health-Care-Associated Pneumonia

OBJECTIVE The aim of this study is to describe the initial antibiotic treatment regimens, severity of illness, and in-hospital mortality among culture-negative (CN) and culture-positive (CP) patients with health-care-associated pneumonia (HCAP). METHODS We used a retrospective cohort study, examining adult patients with HCAP from Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. RESULTS Eight hundred seventy patients with HCAP were identified over a 3-year period (January 2003 through December 2005) of whom 431 (49.5%) were CP. Among the non-CP patients, 290 (66.1%) had no respiratory cultures obtained, and 149 (33.9%) had no growth or nonpathogenic oral flora identified and were classified as CN. CN patients were more likely to have received an initial antibiotic regimen (ceftriaxone +/- azithromycin or moxifloxacin) targeting community-acquired pneumonia pathogens compared with CP patients (71.8% vs 25.5%, P < .001). Severity of illness as assessed by ICU admission and mechanical ventilation (MV) was statistically lower in CN compared with CP patients (ICU admittance 12.1% vs 48.7%, P < .001; MV: 6.7% vs 44.5%, P < .001). In-hospital mortality and hospital length of stay were also statistically lower for CN patients (mortality: 7.4% vs 24.6%, P < .001; hospital length of stay: 6.7 +/- 7.4 days vs 12.1 +/- 11.7 days, P < .001). CONCLUSIONS In this analysis, patients with CN HCAP had lower severity of illness, hospital mortality, and hospital length of stay compared with CP patients. These data suggest that patients with CN HCAP differ substantially from patients with HCAP with positive microbiologic cultures.

Comparison of Bivalirudin and Argatroban for the Management of Heparin-Induced Thrombocytopenia

Study Objectives. To compare the effectiveness of bivalirudin and argatroban in achieving anticoagulation goals and to compare clinical outcomes assessing the safety and efficacy in patients with known or suspected heparin‐induced thrombocytopenia (HIT).

Prolonged Infusion Antibiotics for Suspected Gram-Negative Infections in the ICU: A Before-After Study

BACKGROUND: β-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results. OBJECTIVE: To determine whether prolonged infusion of β-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection. METHODS: We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011). RESULTS: A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329). CONCLUSIONS: Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Optimizing sustained use of sedation in mechanically ventilated patients: focus on safety.

Optimizing sustained use of ICU sedation in mechanically ventilated patients requires careful consideration of drug-specific characteristics (E.G. pharmacokinetics), consideration of potential adverse effects in susceptible patients, and utilization of sedation-minimizing strategies. In the era of anxiolytic dosing protocols adjusted to specific patient behaviors as defined by sedation scales in conjunction with daily interruption, midazolam is a reasonable option for long-term sedation. Propofol is an appealing agent for ICU sedation due to its pharmacokinetic profile and a reduced propensity to result in prolonged sedation. However, care should be taken to monitor for potential devastating adverse effects including hypertriglyceridemia and propofol-related infusion syndrome (PRIS). Dexmedetomidine unreliably provides adequate sedation at doses currently approved by the FDA, though upward titration of dexmedetomidine coupled with rescue benzodiazepines and/or fentanyl appears to be safe and comparable to benzodiazepines in the achievement of light to moderate Richmond Agitation Sedation Scale (RASS) goals. Clinicians should closely monitor patients receiving dexmedetomidine for hemodynamic-altering bradycardia. Strategies that promote frequent patient assessment with corresponding sedative dose minimization have demonstrated the benefits of limiting oversedation. Implementation of a sedation protocol requires careful consideration of ICU resources and staffing such that efforts made are sustainable and will be safe and effective for the patient population affected.

Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study

BackgroundThe incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia.MethodsA retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher’s exact test while the student’s t-test or Mann–Whitney U test were used for continuous variables.ResultsNinety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (p = 0.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, p = 0.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, p = 0.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, p = 0.033).ConclusionsAddition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.

Predictors of Outcome in 216 Subjects With ARDS Treated With Inhaled Epoprostenol

BACKGROUND: ARDS is an important cause of respiratory failure and continues to be associated with a high mortality rate. Numerous therapeutic interventions have been employed to improve patient outcomes, including inhaled epoprostenol. METHODS: We examined subjects with ARDS treated with epoprostenol. We compared hospital survivors with nonsurvivors to identify predictors of mortality. RESULTS: Among the cohort (n = 216), there were 80 (37%) hospital survivors and 136 (63%) hospital nonsurvivors. Logistic regression revealed 5 variables associated with hospital mortality: trauma as the etiology for ARDS (adjusted odds ratio [AOR] 0.09, 95% CI 0.04–0.22, P = .006), presence of both pulmonary and nonpulmonary sources of sepsis (AOR 3.06, 95% CI 1.98–4.74, P = .01), an international normalized ratio of > 1.5 (AOR 3.15, 95% CI 2.19–4.54, P = .002), body mass index (1-unit increments, AOR 0.95, 95% CI 0.936–0.965, P = .001), and an incremental change in PaO2/FIO2 during the first 24 h of treatment with epoprostenol (AOR 0.99, 95% CI 0.988–0.994, P = .002). An analysis for 90-d mortality identified the same predictors, with the addition of cumulative fluid balance during treatment with epoprostenol of > 4 L also being an independent predictor (AOR 2.36, 95% CI 1.66–3.37, P = .02). CONCLUSIONS: Although the use of epoprostenol in ARDS remains a therapeutic challenge, we were able to identify predictors of mortality for this important cohort of patients. These predictor variables could be employed in the design of future trials of epoprostenol in ARDS.

Occurrence and predictors of dexmedetomidine infusion intolerance and failure.

Abstract Background: Dexmedetomidine, a selective α2 adrenergic receptor agonist, exhibits sedative, analgesic, anxiolytic, and sympatholytic effects, and may aid in controlling agitation in the intensive care unit (ICU). At our hospital (Barnes-Jewish Hospital, St. Louis, MO), dexmedetomidine is commonly used as a sedative in the medical ICU. Predictors of dexmedetomidine intolerance or failure have not yet been defined. Objective: Describe the rate of dexmedetomidine infusion intolerance/failure and identify patient predictors of intolerance/failure. Methods: This retrospective single-center cohort study evaluated 75 mechanically ventilated adults who received dexmedetomidine infusion. Patients were included in the study if they were aged ≥ 18 years; mechanically ventilated for > 24 hours; received dexmedetomidine infusion for ≥ 1 hour following > 24 hours of continuous infusions of midazolam, fentanyl, or propofol; and were admitted to our medical ICU between August 1, 2009 and August 1, 2010. Multivariate logistic regression analysis was performed to identify independent predictors of intolerance/failure. Results: A total of 85 episodes of dexmedetomidine infusion were analyzed (75 total patients). Eighteen episodes (21%) met the criteria for intolerance/failure and 67 episodes (79%) met the criteria for tolerance/success. The median duration of mechanical ventilation, total dexmedetomidine infusion time, and ICU length of stay did not differ between groups. Nonblack race was the only variable independently associated with treatment failure or intolerance in the logistic regression analysis. Conclusion: Twenty-one percent of dexmedetomidine infusion episodes met the criteria for intolerance/failure. No predictors of intolerance/failure were found to be clinically significant.

Assessment of an alternative meropenem dosing strategy compared with imipenem-cilastatin or traditional meropenem dosing after cefepime failure or intolerance in adults with neutropenic fever.

Study Objective. To compare clinical outcomes of patients receiving an alternative dosage of meropenem with those of patients receiving imipenem‐cilastatin or the traditional dosage of meropenem after failure of or intolerance to cefepime for treatment of febrile neutropenia.