Faculty Bibliography

PURPOSE: Traditionally, sodium chloride 3% has been administered via a central venous line (CVL) because of the perceived risk of infiltration and tissue injury due to its high osmolarity. In clinical practice, sodium chloride 3% is commonly administered through peripheral venous catheters (PVCs) given the necessity of timely administration. However, there is no published data on the safety of administering sodium chloride 3% through PVCs in the adult population. The objective of this study was to evaluate the safety of peripheral venous administration of sodium chloride 3%. MATERIALS AND METHODS: A retrospective review was conducted in patients who received sodium chloride 3% in the intensive care unit (ICU). Patients were excluded if they had a CVL for the entire duration of the infusion or younger than 18 years at the time of administration. Baseline patient and infusion characteristics were collected. Infusion-related adverse events (IRAEs) were recorded, graded, and interventions required were noted. RESULTS: A total of 66 patients were included in the analysis. The most common indication was hyponatremia and majority of the patients were managed in the neurosurgical ICU. The most common risk factor for IRAEs was the presence of altered mental status. Four patients experienced an IRAE at an event rate of 6.1%. Patients who experienced an IRAE ranged from 38 to 82 years old. The IRAEs were grade 1 in severity, managed conservatively with removal of the PVC, and 2 of the 4 patients had their infusions restarted peripherally. The time to initial IRAE ranged from 2 to 94 hours. For the entire cohort, hospital and ICU length of stay were 8 and 4 days, respectively. CONCLUSIONS: The rate of IRAEs related to the infusion of sodium chloride 3% through PVCs appears to be similar to those reported with other hyperosmotic agents and could be considered for patients who need time-sensitive therapy.

Purpose: Leveraging pharmacy personnel resources for the purpose of antimicrobial stewardship program (ASP) operations presents a challenging task. We describe our experience integrating all pharmacists into an ASP, and evaluate the impact on ASP interventions, antimicrobial utilization, rate of selected hospital-onset infections and readmission. Summary: During a study period (January 1 to December 31, 2015), a total of 14 552 ASP-related pharmacy interventions were performed (ASP clinical pharmacotherapy specialists [CPS] n = 4025; non-ASP CPS n = 4888; hospital pharmacists n = 5639). Sixty percent of interventions by ASP CPS were initiated utilizing the dedicated ASP phone, and 40% through prospective audit and feedback. Non-ASP CPS performed interventions during bedside rounds (dose adjustment 23%, initiate new or alternative anti-infective 21%, discontinue antibiotic(s) 12%, therapeutic drug monitoring 11%, de-escalation 4%), whereas hospital pharmacists participated at the point of verification (dose adjustment 75%, restricted antibiotic verification 15%, and reporting major drug-drug interactions 4%). The acceptance rate of interventions by providers and clinicians was >90% for all groups. Annual aggregate antimicrobial use decreased by 6.4 days of therapy/1000 patient-days (DOT/1000 PD; P = 1.0). Ceftriaxone use increased by 8.4 DOT/1000 PD (P = .029) without a significant compensatory increase in the use of antipseudomonal agents. Sustained low rates of hospital-onset Clostridium difficile (CDI) and carbapenem-resistant Enterobacteriaceae (CRE) infections were observed in 2015 compared with the prior year (1.1 and 1.2 cases/1000 PD, 0.2 and 0.1 cases/1000 PD, respectively). Thirty-day readmission rate decreased by 0.6% (P = .019). Conclusions: Integration of all pharmacists into ASP activities based on the level of patient care and responsibilities is an effective strategy to expand clinical services provided by ASP.

PURPOSE: Enteral nutrition (EN) is often held in patients receiving vasopressor support for septic shock. The rationale for this practice is to avoid mesenteric ischemia. The objective of this study is to evaluate the tolerability of EN in patients with septic shock who require vasopressor support and determine factors associated with tolerance of EN. MATERIALS AND METHODS: This was a single-center retrospective review of adult patients admitted to the intensive care unit with a diagnosis of septic shock and an order for EN. The primary outcome was EN tolerance. Secondary outcomes included time to initiation of EN from the start of vasopressor(s), length of stay, and mortality. RESULTS: A total of 120 patients were included. Sixty-two percent of patients tolerated EN. The most common reason for intolerance of EN was gastric residuals > 250 mL (74%). No reports of mesenteric ischemia were observed. A multivariate analysis demonstrated that patients with septic shock initiating EN within 48 hours and receiving norepinephrine-equivalent doses of 0.14 mug/kg/min or less were more likely to tolerate EN. CONCLUSION: Based on our observation, early EN may be tolerated and safely administered in patients with septic shock who are adequately fluid resuscitated and receive doses of < 0.14 mug/kg/min of norepinephrine equivalents.

Background. It is still unclear whether prolonged duration of therapy (DOT) for VAT might be protective against progression to pneumonia. From a stewardship view, shortening DOT may help to contain emergence of multidrug-resistant organisms (MDRO) in PICU. To this effect, we sought to compare clinical characteristics and outcomes in PICU patients with NLFGNR VAT treated with >7 days (prolonged course group, PCG) vs. <=7 days (short course group, SCG). Methods. This retrospective stewardship evaluation between January 2009 and July 2016 was conducted in a 12-bed PICU. Antibiotic choice and DOT were at the physicians' discretion. VAT was defined by signs and symptoms and positive sputum (>=moderate polymorphonuclear cells and >=moderate NLFGNR growth) without radiographic findings. Primary outcomes were rate of microbiologically documented or clinically suspected (CS) pulmonary infection recurrence and emergence of resistance (>=4 increase in minimal inhibitory concentration) or MDRO within 30 days of VAT treatment. Thirty-day readmission and in-hospital mortality were also assessed. Results. Fifty patients were included (PCG n = 27, SCG n = 23). Median age was 1.6 years (0-18.8), PIM2 score was 1 (0.1-82.8), 62% of patients had a tracheostomy at baseline, 70% had P. aeruginosa, and these were comparable between groups. More patients in PCG vs. SCG (44% vs. 13%, P = 0.03) had an admission diagnosis of respiratory failure. Mechanical ventilation (12.5 vs. 5 days, P < 0.01) and PICU stay (16 vs. 6 days, P < 0.01) were longer in PCG vs. SCG. Median DOT was 10 (8-30) in PCG vs. 6 days (3-7) in SCG, with beta-lactams as the common agents and no difference in combination therapy (33% vs. 13%, P = 0.1). Clinical response at the end of treatment was 89% in PCG and 100% in SCG, P = 0.2. Recurrence was 26% in PCG and 9% (all CS) in SCG, P = 0.2 at 17 days (1-29) and 9.5 days (4-15) P = 0.5, respectively. Emergence of resistance or MDRO occurred in 15% in PCG vs. 0% in SCG, P = 0.1. Readmission and in-hospital mortality were 7% vs. 9%, P = 0.9 and 7% vs. 0%, P = 0.5 in PCG and SCG, respectively. Conclusion. In this small cohort of PICU patients with NLFGNR VAT, there was no microbiologically documented recurrence and emergence of resistance or MDRO in SCG compared with PCG. Our findings suggest that short DOT may be considered for children who are less sick including those with a tracheostomy at baseline

Background. Due to altered pharmacokinetics/pharmacodynamics in critically ill patients, administration of beta-lactams as EI provides better target attainment in therapeutic drug monitoring studies. To optimize meropenem (MER) dosing in patients with severe sepsis or septic shock, our antimicrobial stewardship program implemented a MER EI protocol in an 18-bed medical intensive care unit (MICU) in March 2014. Methods. We conducted a retrospective evaluation to compare outcomes in MICU patients with severe sepsis and septic shock who received MER for >=72h administered as EI 1 g over 3 h Q8H with a total daily dose (TDD) 3g (1/2015-1/2017) vs. SI 500 mg over 30 minutes Q6H with TDD 2 g (1/2012-1/2014). ICU mortality and clinical response (CR) were evaluated as endpoints. CR was defined by improvement in signs and symptoms of infection. Results. Of 667 patients who received MER, 148 were included (EI n = 52, SI n = 96). Age, weight, comorbidities (malignancy 31 vs. 33%, P = 0.8; chronic liver disease [CLD] 15 vs. 23%, P = 0.4), severity of illness (median mAPACHE II 18 vs. 19, P = 0.6; SOFA 5 vs. 6, P = 0.5) and vasopressors' use (75 vs. 79%, P = 0.5) were comparable between EI and SI groups. Serum creatinine (SCr) was lower in EI group (median 1.1 vs. 1.4 SI, P = 0.05). Gram-negative (GN) pathogens (MIC<=0.25 mg/mL, 94%) were identified in 44% of patients in EI vs. 38% in SI group, P = 0.5. MER TDD was higher in EI group (3 vs. 1.5g SI, P < 0.01) with no difference in use of combination therapy (64 vs. 46%, P = 0.06). ICU mortality (median time to death 9 days) was lower (19 vs. 37%, P = 0.047) and CR was higher (83 vs. 46%, P = 0.038) in EI vs. SI group. Total pressor days on MER were shorter (2 vs. 3 days, P < 0.01) and white blood cell normalization rate was higher (87% vs. 51%, P < 0.01) in EI vs. SI group, whereas there was no difference in days of mechanical ventilation, duration of MER therapy and ICU stay. After adjusting for SCr, severity of illness scores, combination therapy and SI group in a multivariate model, CLD (OR 3.3, 95% CI 1.36-7.77, P = 0.008) and lower MER TDD (OR 1.8, 95% CI 1.09-2.98, P = 0.02) were independent predictors of ICU mortality. Conclusion. In this cohort of MICU patients with severe sepsis or septic shock and low MIC of GN pathogens, there was improved mortality and CR in MER EI group. Our finding of potential benefit of higher MER TDD in these patients warrants further exploration in a prospective study

PURPOSE: The integration of pharmacy residents into an antimicrobial stewardship program (ASP) is described, and data on the residents' ASP interventions and outcomes are reported. SUMMARY: ASP coverage of nighttime, holiday, and weekend shifts is often provided by infectious diseases (ID) medical fellows and staff pharmacists, potentially leading to inconsistent stewardship practices. As part of an initiative by a large urban hospital to provide around-the-clock, comprehensive ASP services 7 days a week, postgraduate year 2 (PGY2) pharmacy residents in ID or critical care were assigned to provide ASP coverage on weekends. Over a 12-month period, residents providing ASP weekend coverage documented a total of 1,443 interventions, of which 1,000 (69%) were pursuant to 72-hour prospective audit and feedback review and 443 (31%) occurred during ASP phone coverage. A comparison of overall antimicrobial utilization (mean +/- S.D. days of therapy [DOT] per 1,000 patient-days [PD]) before and after implementation of resident ASP coverage on weekends showed a decrease in aggregate antimicrobial use from 799.3 +/- 46.8 to 740.7 +/- 17.3 DOT/1,000 PD (a difference of 58.6 DOT/1,000 PD, p = 0.08), with a corresponding decline in the incidence of hospital-onset Clostridium difficile infection (from 1.18 cases to 0.9 case per 1,000 PD). CONCLUSION: By expanding the hospital's ASP services by assigning PGY2 pharmacy residents to weekend coverage, the institution was able to provide high-level clinical care 7 days per week, which benefited both patients and PGY2 pharmacy residents while meeting national ASP regulatory requirements.

STUDY OBJECTIVE: Despite recent reports of relatively high rates (16-37%) of acute kidney injury (AKI) in patients receiving the combination of intravenous piperacillin-tazobactam (PTZ) and vancomycin, data are limited evaluating the impact of PTZ infusion strategy on the occurrence of nephrotoxicity. The objective of this study was to compare the rates of nephrotoxicity in patients receiving vancomycin in combination with PTZ administered as an extended infusion (EI) versus a standard infusion (SI). DESIGN: Single-center, retrospective, matched-cohort study. SETTING: Large academic tertiary care hospital. PATIENTS: Two hundred eighty adults with a creatinine clearance (CrCl) of 40 ml/minute or higher who received at least 96 hours of vancomycin plus PTZ EI (140 patients) or vancomycin plus PTZ SI (140 patients) between January 1, 2009, and December 31, 2011, and between January 1, 2013, and December 31, 2014 (year 2012 was skipped due the closure of inpatient units following Superstorm Sandy); 48 patients in each group were admitted to the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The median age of all patients was 67 (interquartile range [IQR] 54-77) years, and CrCl was 75 (IQR 55-107) ml/minute. Nephrotoxicity was assessed by the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) criteria. Rates of AKI, according to these criteria, were similar between groups: 17.9% versus 17.1% (p=1) and 32.9% versus 29.3% (p=0.596) for the PTZ EI and PTZ SI groups, respectively. When controlling for residual differences between groups in a conditional logistic regression analysis, no association was observed between receipt of PTZ EI and RIFLE-defined AKI (odds ratio 0.522, 95% confidence interval 0.043-6.295, p=0.609). Time to onset of nephrotoxicity was 4 (IQR 3-6) days, with no significant difference noted between groups (p=0.887). CONCLUSION: Our findings suggest a similar rate of nephrotoxicity between patients who received vancomycin in combination with PTZ EI versus PTZ SI. These results need to be further validated in a prospective randomized controlled study.

BACKGROUND: Opioid-induced constipation (OIC) is common in critically ill patients; it leads to complications that can increase hospital stay and, rarely, bowel perforation. Opioid antagonists are considered a logical approach to treat OIC; however, the agent of choice has yet to be determined. OBJECTIVE: To assess the effectiveness and safety of enteral naloxone (NTX) versus subcutaneous methylnaltrexone (MNTX) for the treatment of OIC in the medical intensive care unit. METHODS: This retrospective review evaluated patients who received fentanyl continuous infusions for at least 72 hours and were initiated on NTX or MNTX. Active colitis, mechanical gastrointestinal obstruction, and inability to receive NTX orally were exclusion criteria. The primary outcome was time to first bowel movement (BM). Secondary outcomes included total number of BMs within 48 hours, opioid requirements after NTX or MNTX, and change in any of the following after the opioid antagonist: heart rates, mean arterial pressures, and level of sedation. A post hoc subgroup analysis of patients on vasopressors was conducted. RESULTS: Baseline characteristics were similar between patients receiving NTX (n = 52) and MNTX (n = 48), except the MNTX group required a higher median norepinephrine dose (0.22 vs 0.1 microg/kg/min, P = 0.001). The median times to first BM for NTX and MNTX were 30 and 24 hours ( P = 0.165). There was no difference in the primary outcomes for patients on vasopressors. Both groups did not require additional fentanyl equivalents, as evidenced by stable vitals and opioid requirements during treatment. CONCLUSIONS: Both agents appear to be effective and safe for the treatment of OIC; however, future controlled prospective trials are warranted.

BACKGROUND: Cefepime and meropenem are used frequently in hospitalized patients for broad-spectrum empiric coverage, however, practitioners are often reluctant to prescribe these antibiotics for patients with a self-reported nonsevere, nontype I allergic reaction to penicillin. METHODS: Retrospective review of electronic medical records of adults with a self-reported allergy to penicillin who received at least 1 dose of cefepime, ceftriaxone, cefoxitin, cephalexin, or meropenem to assess incidence and type of allergic reactions. RESULTS: Of 175 patients included, 10 (6%) patients experienced an allergic reaction. The incidence for individual study drugs were cefepime 6% (6 of 96), meropenem 5% (3 of 56), cefoxitin 8% (1 of 13), ceftriaxone 0% (0 of 69), and cephalexin 0% (0 of 8). The majority of patients experienced a rash with or without pruritus and fever. Patients with a concomitant "sulfa" allergy (odds ratio [OR] 5.4, 95% confidence interval [CI] 1.4-21, P = .02) or >/=3 other drug allergies (OR 6.4, 95% CI 1.3-32, P = .025) were more likely to have an allergic reaction. CONCLUSIONS: In one of the largest retrospective reviews of hospitalized patients who received full dose therapy with cefepime, ceftriaxone, and meropenem, the incidence of allergic reactions was low and reactions were mild. Cefepime, ceftriaxone, and meropenem can be considered for use in patients with a self-reported nontype I penicillin allergy.