Azithromycin and Septic Shock Outcomes.

Introduction: Although there is evidence describing the immunomodulatory effects of macrolide antibiotics, there is little literature exploring the clinical effects these properties may have and their impact on measurable outcomes. Objective: The purpose of this study was to determine if empiric antimicrobial regimens containing azithromycin shorten time to shock resolution. Methods: A retrospective study was performed in adults with septic shock admitted to intensive care units (ICUs) of 3 university-affiliated, urban teaching hospitals between June 2012 and June 2016. Eligible patients with septic shock required treatment with norepinephrine as the first-line vasopressor for a minimum of 4 hours and received at least 48 hours of antimicrobial treatment from the time of shock onset. Propensity scores were utilized to match patients who received azithromycin to those who did not. Results: A total of 3116 patients met initial inclusion criteria. After propensity score matching, 258 patients were included, with 124 and 134 patients in the azithromycin and control groups, respectively. Median shock duration was similar in patients treated with or without azithromycin (45.6 hr vs 59.7 hr, P = .44). In-hospital mortality was also similar (37.9% vs 38.1%, P = .979). There were no significant differences in mechanical ventilation duration, ICU length of stay (LOS), or hospital LOS. Conclusions: In patients admitted to the ICU with septic shock, empiric azithromycin did not have a significant effect on shock duration, mechanical ventilation duration, ICU LOS, hospital LOS, or in-hospital mortality.

Increased Enoxaparin Dosing Requirements for Treatment of Deep Vein Thrombosis in a Severely Burned Patient: Case Report and Literature Review.

Dosing of enoxaparin for deep vein thrombosis (DVT) prophylaxis in acutely burned patients has been shown to result in anti-Xa levels below target range. We describe the first case report, to our knowledge, of a severely burned patient who, despite prophylactic dosing of enoxaparin 30 mg subcutaneously twice daily, developed an acute DVT that required high-dose enoxaparin (100 mg [1.5 mg/kg] subcutaneously every 8 hours) to maintain anti-Xa levels within the therapeutic range (0.6-1 IU/ml). Pharmacokinetic evaluations were performed using anti-Xa levels measured throughout the patient's hospital stay to validate the appropriateness of this high-dose regimen based on established therapeutic anti-Xa level ranges. These results suggest that routine anti-Xa level monitoring, regardless of enoxaparin dosing, is necessary for burn patients who are receiving enoxaparin given their hypermetabolic state following injury.

The Retrospective Cohort of Extended-Infusion Piperacillin-Tazobactam (RECEIPT) study: a multicenter study.

STUDY OBJECTIVE: To compare the effectiveness of extended-infusion piperacillin-tazobactam with that of similar-spectrum, nonextended-infusion [H9252]-lactam antibiotics in the treatment of gram-negative infections. DESIGN: Multicenter, retrospective medical record review. SETTING: Fourteen hospitals throughout the United States. PATIENTS: A total of 359 adults treated for gram-negative infections between January 1, 2007, and February 28, 2010, with either 4-hour extended-infusion piperacillin-tazobactam (186 patients) or nonextended-infusion comparator antibiotics (173 patients), which consisted of cefepime, ceftazidime, imipenem-cilastatin, meropenem, doripenem, or piperacillin-tazobactam. MEASUREMENTS AND MAIN RESULTS: Deidentified data were collected on demographics, renal function, Acute Physiology and Chronic Health Evaluation II score, chronic health conditions, source of infection and type of organism, intensive care unit (ICU) length of stay, total length of stay, type and duration of antimicrobial therapy, and in-hospital mortality. The primary outcome was mortality rate of the patients receiving extended-infusion piperacillin-tazobactam versus those receiving nonextended-infusion comparator antibiotics. Secondary outcomes were hospital length of stay, ICU length of stay, and total duration of antibiotic therapy. Baseline characteristics were similar between groups, except a significantly lower proportion of patients in the extended-infusion group were treated with a concomitant intravenous aminoglycoside (5.9% vs 16.2%, p<0.01), were infected with Pseudomonas species (22.6% vs 39.9%, p<0.01), or had positive respiratory cultures (30.7% vs 43.4%, p=0.01). Antibiotic duration, hospital length of stay, and ICU length of stay were similar between groups. In-hospital mortality was significantly decreased in the extended-infusion piperacillin-tazobactam group versus those receiving comparator antibiotics (9.7% vs 17.9%, p=0.02). Multivariate analysis confirmed that extended-infusion piperacillin-tazobactam prolonged survival by 2.77 days (p<0.01) and reduced the risk of mortality (odds ratio 0.43, p=0.05). CONCLUSION: Pharmacodynamic dosing using extended-infusion piperacillintazobactam demonstrated favorable outcomes, including mortality, when compared with nonextended-infusion, similar-spectrum [H9252]-lactams in the treatment of patients with documented gram-negative infections. Prospective, randomized trials are needed to further corroborate these findings.

Infectious diseases in the critically ill patients.

Infection is common in the critically ill and often results due to the severity of the patient's illness. Recent data suggest 51% of intensive care unit (ICU) patients are infected, and 71% receive antimicrobial therapy. Bacterial infection is the primary concern, although some fungal infections are opportunistic. Infection more than doubles the ICU mortality rate, and the costs associated with infection may be as high as 40% of total ICU expenditures. There are many contemporary antimicrobial resistance concerns that the critical care clinician must consider in managing the pharmacotherapy of infection. Methicillin resistance in Staphylococcus aureus, vancomycin resistance in Enterococci, beta-lactamase resistance in Enterobacteriaceae, multidrug resistance in Pseudomonas aeruginosa and Acinetobacter species, fluoroquinolone resistance in Escherichia coli, and fungal resistance are among the most common issues ICU clinician's must face in managing infection. Critical illness causes changes in pharmacokinetics that influence drug and dosing considerations. Absorption, distribution, metabolism, and excretion may all be affected by the various disease states that define critical illness. Several specific diseases are discussed, including ventilator-associated pneumonia, various fungal infections, gastrointestinal infections due to Clostridium difficile, urinary tract infections, and bloodstream infections. Within each disease section, discussion includes causes and prevention strategies, microbiology, evidence-based guidelines, and important caveats.