Quinn A. Czosnowski

Adjunctive aerosolized antibiotics for treatment of ventilator-associated pneumonia.

Study Objective. To determine clinical and microbiologic success in patients receiving adjunctive aerosolized antibiotics for the treatment of ventilator‐associated pneumonia (VAP).

Fidaxomicin for the Treatment of Clostridium difficile Infections

Objective: To evaluate the pharmacology, microbiology, safety, and efficacy of fidaxomicin for treatment of Clostridium difficile infections (CDI). Data Sources: Literature was identified through Ovid MEDLINE (1940-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) using the search terms fidaxomicin, OPT-80, PAR-101, OP-118, difimicin, tiacumicin, lipiarmycin, Clostridium difficile, Clostridium difficile infection, Clostridium difficile-associated diarrhea, and cost. Drug monographs were retrieved from manufacturers’ Web pages, and the Red Book component of Micromedex was used for cost Information. Study Selection and Data Extraction: All pertinent Phase 1,2, and 3 studies published in English were included. Data Synthesis: Fidaxomicin is a macrocyclic compound bactericidal against C. difficile and inhibits toxin and spore production. It has poor oral absorption with high fecal concentrations. Available Phase 2 and 3 data with fidaxomicin 200 mg orally every 12 hours demonstrate similar effectiveness in treating CDI compared to oral vancomycin. Fidaxomicin was shown to have less frequency of recurrent infections. Adverse effects are uncommon and occur at similar rates as with oral vancomycin. The most frequently reported adverse effects are gastrointestinal, hematologic, and electrolyte disorders. Available data are lacking in several areas, including the efficacy and safety of fidaxomicin compared to established regimens for mild-to-moderate, life-threatening, and recurrent CDIs. The cost of a 10-day course of fidaxomicin is significantly more than that of metronidazole and vancomycin for treatment of mild-to-moderate CDI. Conclusions: Fidaxomicin appears to be an effective and safe alternative to oral vancomycin for treatment of mild-to-moderate and severe CDI. Data on its use compared to guideline-recommended therapies for mild-to-moderate and life-threatening CDI are needed. Further data assessing the cost-effectiveness of fidaxomicin are needed. Currently, it cannot be recommended over vancomycin for treatment of CDI. However, it may be considered for treatment of recurrent infections.

Evaluation of glycemic control following discontinuation of an intensive insulin protocol

BACKGROUND Intensive insulin protocols (IIPs) have been demonstrated to reduce morbidity and mortality in critically ill patients. Currently, there are no published studies evaluating glycemic control after discontinuation of an IIP. OBJECTIVE The purpose of this study was to compare blood glucose (BG) control during an IIP and for 5 days following its discontinuation (follow-up period). METHODS The study was a retrospective review of intensive care unit patients who received an IIP for >or=24 hours. Data were collected during the last 12 hours of the IIP and subsequent follow-up period. RESULTS For all 65 included patients, the mean +/- standard deviation for BG on the IIP was 123 +/- 26 mg/dL versus 168 +/- 50 mg/dL following discontinuation of the IIP (P < 0.001). The median (interquartile range) insulin that was administered decreased from 40 (22-65) units on the IIP to 8 (0-18) units after the IIP was stopped (P < 0.001). The mean daily BG during the follow-up period was significantly higher than that during the IIP (P < 0.001). Additionally, an insulin requirement of >20 units during the last 12 hours of the IIP was identified as a risk factor for poor glycemic control during the follow-up period (odds ratio: 4.62; 95% confidence interval: 1.17-18.17). CONCLUSIONS This study demonstrates a significant increase in BG following discontinuation of an IIP. Higher insulin requirements during the last 12 hours of an IIP were identified as an independent risk factor for poor glycemic control following the IIP. A standardized insulin transition protocol may help better control BG after discontinuation of an IIP.

Bivalirudin for Patients with Heparin-Induced Thrombocytopenia Undergoing Cardiovascular Surgery:

Objective To evaluate the uso of bivalirudin in patients with heparin-induced thrombocytopenia (HIT) undergoing cardiovascular surgery. Data Sources: Relevant information was identified through a search of MEDLINE (1966–April 2008), international Pharmaceutical Abstracts (1960–April 2008), and Cochrane Databases (publications archived until April 2008) using the terms bivalirudin, heparin-induced thrombocytopenia, and cardiovascular surgery. Study Selection And Data Extraction: Prospective and retrospective studies, case reports, and case series in adults were eligible for inclusion if bivalirudin had been used in a patient with known HIT undergoing any cardiovascular surgical procedure other than percutaneous coronary intervention. Data Synthesis: Two small, open-label, multicenter clinical trials were identified that evaluated treatment with bivalirudin in patients with HIT undergoing coronary artery bypass graft surgery. Ono looked at on-pump cardiopulmonary bypass (CPB), while the other looked at off-pump CPB. Procedural success was achieved at day 7 in 94% (n = 46) of patients in the on-pump CPB study and in 92% (n = 47) of patients in the off-pump CPB study. Dosing strategies varied between the 2 trials, with the on-pump study using a 1-mg/kg bivalirudin bolus followed by a 2.5-mg/kg/h infusion; the off-pump study used a 0.75-mg/kg bolus followed by a 1.75-mg/kg/h infusion. In addition, 10 case reports met the criteria to be included in the review and are summarized. In these cases, procedural success was reported using various bivalirudin doses in valve repair and replacement, right ventricular assist device implantation, and heart transplantation. Conclusions: Growing data demonstrate procedural success with bivalirudin in patients with HIT undergoing cardiovascular surgery. However, bivalirudin dosing and goal-activated clotting times varied between the studies and case reports. Bivalirudin represents a viable alternative to heparin in patients with HIT undergoing cardiovascular surgery; however, further trials are warranted to identify optimal dosing and monitoring parameters.

Clinical and Microbiologic Outcomes in Trauma Patients Treated for Stenotrophomonas maltophilia Ventilator-Associated Pneumonia

Study Objectives. To determine clinical and microbiologic plus clinical success rates in critically ill trauma patients who received treatment for Stenotrophomonas maltophilia ventilator‐associated pneumonia (VAP). Design. Retrospective medical record review.

Methylprednisolone Sodium Succinate–Associated Macroglossia in a Critically Ill Patient

Allergic hypersensitivity reactions are a rare adverse effect of corticosteroids. Previous reports have identified patients who developed symptoms of urticaria, dyspnea, hypotension, bronchospasm, and angioedema occurring within minutes to an hour after corticosteroid administration. A 35‐year‐old woman is described who developed an atypical reaction of isolated macroglossia after receiving intravenous methylprednisolone sodium succinate for myasthenic crisis. Macroglossia was identified on day 2 of therapy and worsened through day 5. On day 5, she was transitioned to prednisone 50 mg daily administered by feeding tube. Tongue swelling improved by day 7 and on day 10, the patient was extubated. The patient required reintubation due to stridor, but received a tracheostomy and was weaned off mechanical ventilation by day 15. The reaction was not confirmed with skin‐prick tests, intradermal tests, or a drug rechallenge; however, she had previously received and tolerated all other drugs administered during this time. Due to the timing of administration and onset of symptoms, we feel this adverse drug reaction was likely due to administration of methylprednisolone. Applying the Naranjo adverse drug reaction probability scale to this case, a score of six was obtained, indicating a probable association between the administration of methylprednisolone and the development of macroglossia. As intravenous corticosteroids are often used in the treatment of allergic reactions, they may be overlooked as a cause of macroglossia and other allergic reactions; therefore, practitioners need to be aware of the possibility of this adverse effect secondary to corticosteroid administration. In the event of methylprednisolone sodium succinate–induced macroglossia, alternative nonesterified corticosteroids, such as dexamethasone or prednisone, should be considered if continuation of therapy is required.

905: DIGOXIN DOSING IN PATIENTS UNDERGOING CONTINUOUS RENAL REPLACEMENT THERAPY

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Digoxin is frequently used in hemodynamically unstable patients with heart failure or atrial fibrillation in the ICU. Data are limited to guide dosing in patients who also require continuous venovenous hemofiltration (CVVH). Common drug references recommend doses of 62.5 mCg every 48 hours, however this recommendation arises from a study conducted when CVVH ultrafiltration rates were primarily less than 1,800mL/hr. The purpose of this study was describe digoxin dosing requirements for patients on contemporary rates of CVVH UF. Methods: This study was a retrospective observational cohort conducted in intensive care units at a large academic medical center. Thirty-two patients were identified via electronic medical record database query as having received digoxin therapy while also on CVVH between June 1, 2011 and May 31, 2016. Patients had to be on digoxin and have a measured level while on CVVH to be included in this study. The primary endpoint was to investigate the dose of digoxin required to achieve serum concentrations between 0.5–1.9mcg/mL. Patients were evaluated utilizing descriptive statistics. Results: The median UF rate was 2,791mL/hr, with 30/32 (94%) of patients having a UF rate greater than 1800 ml/hour. 14/32 patients had a non-steady state (NSS) level obtained, with a median NSS level of 1.14mcg/mL on a median digoxin dose of 125mcg daily. Of the 9 patients with a steady state level, the median steady state level was 0.75mcg/mL on a median dose of 125mcg daily. No patients had a serum concentration greater than 2mcg/mL or documented digoxin toxicity. Conclusions: Most patients receiving CVVH with commonly used UF rates require daily dosing of digoxin. In the absence of further data, therapeutic drug monitoring should still be instituted in patients on CVVH who require digoxin.

1023: Impact of patient location on time to antimicrobial administration in severe sepsis and septic shock

Introduction: No study has examined the differences in time to antimicrobials between patient locations at the time of severe sepsis and septic shock onset and its impact on outcomes. This study aimed to compare the time from onset of severe sepsis or septic shock to antimicrobial administration bet