David M. Hill

Linezolid Bladder Irrigation as Adjunctive Treatment for a Vancomycin-Resistant Enterococcus faecium Catheter-Associated Urinary Tract Infection

Objective: To describe the first reported successful use of adjunctive linezolid bladder irrigation. Case Summary: An 89-year-old woman with 10% TBSA burns developed septic shock and anuric acute kidney insufficiency. She acquired a urinary tract infection caused by vancomycin-resistant Enterococcus faecium (VREfm). Based on clinical status, a linezolid bladder irrigation was initiated in addition to high-dose intravenous linezolid and demonstrated microbiological cure with 7 days of treatment. Discussion: Linezolid is primarily hepatically cleared and has no labeled indication for urinary tract infections. Anuria adds an additional complication of potentially reduced urinary drug concentrations. Bladder irrigation offers the benefit of achieving high local drug concentrations, but there are no data regarding such a route for linezolid. This case report is the first demonstrating the use, stability, safety, and efficacy of linezolid as a continuous bladder irrigation. Conclusions: Linezolid use as a bladder irrigation may be a feasible route of administration in anuric, critically ill patients with VREfm and few antimicrobial options. Further studies are warranted.

Rational Selection and Use of Antimicrobials in Patients with Burn Injuries

Caring for patients with burn injuries is challenging secondary to the acute disease process, chronic comorbidities, and underrepresentation in evidence-based literature. Much current practice relies on extrapolation of guidance from different patient populations and wide variations in universal practices. Identifying infections or sepsis in this hypermetabolic population is imperfect and often leads to overprescribing of antimicrobials, suboptimal dosing, and multidrug resistance. An understanding of pharmacokinetics and pharmacodynamics may aid optimization of dosing regimens to better attain treatment targets. This article provides an overview of the current status of burn infection and attempts recommendations for consideration to improve universally accepted care.

Outcome analysis of colistin-treated burn center patients

OBJECTIVES Intravenous colistimethate sodium (CMS) use in burn center patients is increasing due to the emergence of multidrug-resistant gram-negative bacteria. However, optimal dosing strategies and factors that may contribute to treatment failure are limited. The purpose of this study was to determine factors that may contribute to treatment failure in colistin-treated burn center patients. METHODS This retrospective, observational study included burn center patients that received ≥48h of intravenous CMS between June 1, 2009 and June 30, 2014. Data was collected utilizing the institutions electronic medical record system. Statistical analysis included demographic, univariable, and multivariable analysis to determine factors that may predict clinical failure of burn center patients requiring intravenous CMS. RESULTS Eighty-one patients were included in this study, with 55 patients (68%) achieving clinical success. A total daily dose (TDD) of >5mg/kg ideal body weight (IBW) was associated with significantly less clinical failure (odds ratio=0.21; 95% CI, 0.05, 0.91). Additionally, clinical failure was significantly higher in patients with wounds as the primary source of infection, creatinine clearances of 91-120mL/min, and those receiving renal replacement therapy. No difference was observed in nephrotoxicity when comparing TDD >5mg/kg IBW and TDD ≤5mg/kg IBW. CONCLUSIONS Clinical success was significantly higher with larger intravenous CMS doses in burn center patients. Higher CMS doses were not found to be associated with increased nephrotoxicity within this patient group.

Renal Replacement Therapy in Severe Burns: A Multicenter Observational Study

Abstract Acute kidney injury (AKI) after severe burns is historically associated with a high mortality. Over the past two decades, various modes of renal replacement therapy (RRT) have been used in this population. The purpose of this multicenter study was to evaluate demographic, treatment, and outcomes data among severe burn patients treated with RRT collectively at various burn centers around the United States. After institutional review board approval, a multicenter observational study was conducted. All adult patients aged 18 or older, admitted with severe burns who were placed on RRT for acute indications but not randomized into a concurrently enrolling interventional trial, were included. Across eight participating burn centers, 171 subjects were enrolled during a 4-year period. Complete data were available in 170 subjects with a mean age of 51 ± 17, percent total body surface area burn of 38 ± 26% and injury severity score of 27 ± 21. Eighty percent of subjects were male and 34% were diagnosed with smoke inhalation injury. The preferred mode of therapy was continuous venovenous hemofiltration at a mean delivered dose of 37 ± 19 (ml/kg/hour) and a treatment duration of 13 ± 24 days. Overall, in hospital, mortality was 50%. Among survivors, 21% required RRT on discharge from the hospital while 9% continued to require RRT 6 months after discharge. This is the first multicenter cohort of burn patients who underwent RRT reported to date. Overall mortality is comparable to other critically ill populations who undergo RRT. Most patients who survive to discharge eventually recover renal function.

Incidence of Hypoglycemia in Burn Patients: A Focus for Process Improvement:

Background: Glycemic control in burn patients is critical for reducing infection and mortality. Objective: This study was conducted to assess the incidence and outcomes of hypoglycemia during continuous insulin infusions (CII). Methods: This institutional review board–approved study was a retrospective, single burn center, electronic chart review. Patients admitted between January 1, 2013, and October 31, 2014, who received a CII were included. Patients with incomplete data or who received <24 hours of CII were excluded. Results: Thirty-eight patients met inclusion criteria; 6 were excluded. The average patient was a 52-year-old Caucasian male with a 33% total body surface area burn and an acute physiology and chronic health evaluation (APACHE) II score of 20.Hypoglycemia was present for 87 of 6540 hours of CII therapy (1.1%). Two-thirds experienced a serum glucose <70 mg/dL and half <60 mg/dL. The most commonly assessed reasons for the hypoglycemic episodes were protocol violations (47%) and glucose variability (30%). After multivariable logistic regression, only history of diabetes remained a statistically significant risk factor with an odds ratio of 15.4 (95% confidence interval: 2.5-95.1). Four different CII protocols were prescribed. All protocols had a high glucose variability, as assessed by hours / day within goal range (13.1 ± 2.5, 14.1 ± 3.1, 14.3 ± 2.4, 9.8; P = .282). Conclusion: The amount of different protocols likely contributed to protocol violations and glucose variability. Our data demonstrate the need to create and consolidate usage to a single protocol in attempts to improve glycemic control.

Characterization of variables for potential impact on vancomycin pharmacokinetics in thermal or inhalation injury

OBJECTIVE To characterize the pharmacokinetics of vancomycin dosing in thermal or inhalation injury as they relate to percent total body surface area burn (TBSA) and days since injury (DSI). METHODS This retrospective 3-year study included patients with thermal or inhalation injury receiving vancomycin. Patient demographics and course data were collected using the institutions electronic medical record. RESULTS Six hundred and fifty-four patients were included in the study; 124 remained after exclusion. Clearance (CL) was augmented in patients closer to their date of injury. CL and total daily dose requirements significantly increased with larger percent TBSA injured that was independent of volume of distribution (Vd). Larger percent TBSA also predicted increased occurrence of renal injury prior to vancomycin initiation. A modified sample set was also analyzed to control for renal dysfunction. Creatinine clearance (CrCl) estimated via the Cockcroft-Gault equation significantly impacted CL and total daily dose. To obtain a goal trough of 15-20mg/L, the average patient in the modified sample with ≥10% TBSA required 64.7mg/kg/day (or 16.2mg/kg every 6hours). CONCLUSIONS DSI, percent TBSA, and CrCl can be used to predict faster vancomycin CL and need for higher total daily doses. Augmented pharmacokinetics can occur as early as two days after injury and decrease with time. Acceptable target trough attainment is still lacking and this data should assist in performance improvements for initial vancomycin dosing.

Pharmacokinetics of Imipenem/Cilastatin Burn Intensive Care Unit Patients Undergoing High-Dose Continuous Venovenous Hemofiltration

High‐dose continuous venovenous hemofiltration (CVVH) is a continuous renal replacement therapy (CRRT) used frequently in patients with burns. However, antibiotic dosing is based on inference from studies assessing substantially different methods of CRRT. To address this knowledge gap for imipenem/cilastatin (I/C), we evaluated the systemic and extracorporeal clearances (CLs) of I/C in patients with burns undergoing high‐dose CVVH.

In vitro stability of polyurethane and silicone feeding tubes exposed to fish oil

Fish oil supplements rich in the ω-3 polyunsaturated fatty acids, eicosa-pentaenoic acid and docosahexaenoic acid have been used as treatment for a variety diseases. The most common dosage form of pharmaceutical-grade fish oil is a large liquid-filled capsule that is difficult for some patients to