Nicholas M. Fusco

Antibiotic Management of Methicillin-Resistant Staphylococcus aureus–Associated Acute Pulmonary Exacerbations in Cystic Fibrosis

Objective: To review the treatment of methicillin-resistant Staphylococcus aureus (MRSA)–associated acute pulmonary exacerbations (APEs) in cystic fibrosis (CF). Data Sources: A search of PubMed, MEDLINE, Cochrane Library and Clinicaltrials.gov databases through November 2014 was conducted using the search terms Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, pulmonary exacerbations, and cystic fibrosis. Study Selection and Data Extraction: All English-language research articles, case reports, and case series were evaluated. A total of 185 articles were identified related to MRSA and CF; 30 articles that studied treatments of MRSA APE in CF were included. Data Synthesis: The persistent presence of MRSA in the respiratory tract of patients with CF has been associated with higher morbidity and an increased risk of death. Limited clinical data exist supporting the efficacy of any specific antimicrobial currently available for the treatment of APE secondary to MRSA. Conclusions: Data extrapolated from other populations suggest that vancomycin and linezolid are appropriate first-line treatment options for the treatment of APE secondary to MRSA. Second-line options include doxycycline or minocycline and trimethoprim/sulfamethoxazole, each of which may be useful in patients coinfected with other respiratory pathogens, for which they may provide overlapping coverage. Ceftaroline and ceftobiprole are newer antibiotics that appear to have a potential role in the treatment of APE in CF, but the latter is not currently available to the US market. Although potentially useful, clindamycin is limited by high rates of resistance, telavancin is limited by its toxicity profile, and tigecycline is limited by a lack of demonstrated efficacy for infections that are similar to that seen in the CF population. Studies investigating the clinical utility of the above-cited antibiotics for APE in CF secondary to MRSA are desperately needed to broaden the treatment armamentarium for this medical condition.

Effects of Clonidine on Withdrawal From Long-term Dexmedetomidine in the Pediatric Patient.

OBJECTIVE To compare withdrawal symptoms among pediatric intensive care patients receiving clonidine to those not receiving clonidine while being weaned from long-term dexmedetomidine. METHODS This retrospective analysis evaluated Withdrawal Assessment Tool-1 (WAT-1) scores and hemodynamic parameters in pediatric patients on dexmedetomidine for 5 days or longer between January 1, 2009, and December 31, 2012. The primary objective was to compare withdrawal symptoms based on the number of elevated WAT-1 scores among patients on clonidine to those not on clonidine, while being weaned from long-term dexmedetomidine. The secondary objective was to describe withdrawal symptoms associated with long-term dexmedetomidine use. RESULTS Nineteen patients (median age, 1.5 years; interquartile range [IQR], 0.67-3.3) received 20 treatment courses of dexmedetomidine for at least 5 days. Clonidine was received by patients during 12 of the treatment courses. The patients in the clonidine group had an average of 0.8 (range, 0-6) elevated WAT-1 scores 24 hours post wean compared to an average of 3.2 (0-8) elevated WAT-1 scores in the no clonidine group (p = 0.49). There were no significant difierences between prewean and postwean systolic or diastolic blood pressures among the 2 groups. The average heart rate during the postwean period was 112 beats per minute (bpm) (range, 88.5-151.5) in the clonidine group compared to 138.4 bpm (range, 117.8-168.3) in the no clonidine group (p = 0.003). In the clonidine group, the mean change in heart rate postwean compared to prewean was an increase of 3.6 bpm (range, -39.6 to 47.5), compared to a mean increase of 29.9 bpm (range, 5.5-74.7) in the no clonidine group (p = 0.042). CONCLUSIONS There was no difierence in WAT-1 scores between groups, with the clonidine group displaying a trend towards fewer elevated WAT-1 scores during the 24 hours post dexmedetomidine wean. Patients who received clonidine had significantly lower heart rates than the no clonidine group.

Evaluation of the treatment of diabetic ketoacidosis in the medical intensive care unit

OBJECTIVE To determine if treatment of DKA in a sample of adult medical intensive care unit (MICU) patients was consistent with the 2006 ADA Hyperglycemic Crises in Adult Patients with Diabetes Clinical Guidelines. METHODS Medical records were reviewed for all adult patients admitted to a MICU with a diagnosis of DKA between July 1, 2007 and June 30, 2010. The primary composite endpoint assessed fluid resuscitation (total mL/kg) at 24 hours, insulin bolus dose, and continuous insulin infusion (units/kg or units/kg/hour) to determine whether the 2006 ADA clinical guidelines for Hyperglycemic Crises in Adult Patients with Diabetes were followed. Secondary outcome measures were DKA resolution, ICU length of stay, frequency of rebound DKA within 48 hours, frequency of hypoglycemia, and time to transition to subcutaneous insulin. RESULTS A total of 60 patients met inclusion criteria. For patients treated in compliance with the clinical guidelines compared to those that were not, total volume IV fluid infused during the first 24 hours (4.88 ± 0.77 mL/kg/hour and 2.74 ± 1.08 mL/kg/hour), mean dose of the insulin bolus (0.13 ± 0.04 units/kg and 0.06 ± 0.06 units/kg) and initial rate of the insulin infusions (0.11 ± 0.02 units/kg/hour and 0.08 ± 0.03 units/kg/hour) were significantly different (p <0.001). Treatment of 12 patients (20%) followed the 2006 ADA clinical guidelines, and mean time to resolution of DKA and MICU length of stay trended toward a shorter duration in these patients. CONCLUSION Compliance with the 2006 ADA Hyperglycemic Crises in Adult Patients with Diabetes clinical guidelines was low for treatment of DKA in a sample of adult patients admitted to a MICU. Institutional guidelines for the management of diabetic ketoacidosis should be investigated as a strategy to improve compliance with national guidelines.

Association of Vancomycin Trough Concentration With Response to Treatment for Acute Pulmonary Exacerbation of Cystic Fibrosis

Background Our goal was to determine the relationship between serum vancomycin trough concentrations (VTCs) and changes in pulmonary function among individuals with an acute pulmonary exacerbation (APE) of cystic fibrosis (CF). Methods We included subjects who were ≥6 years of age, were hospitalized for an APE of CF between May 1, 2012, and April 30, 2014, were administered vancomycin for ≥48 hours, and had a history of airway infection with methicillin-resistant Staphylococcus aureus. Pearson correlations were performed to characterize the relationship between VTC and pulmonary function. Results The mean final VTC (± standard deviation) was 12.6 ± 3.3 µg/mL; 40 (81.6%) of 49 final VTCs were in the range of 10 to <15 µg/mL. The mean change in forced expiratory volume in 1 second (FEV1) between admission and discharge was 24.5% ± 24.4% (P < .001) of predicted values. Forty-two (85.7%) patients returned to their baseline FEV1. No correlation between the change in FEV1 and VTC (Pearson r = -0.10; P = .49) was identified. Similarly, VTC, daily weight-adjusted vancomycin dose, and vancomycin area under the concentration-time curve normalized to the minimum inhibitory concentration (AUC/MIC) were not significant predictors of change in FEV1 or return to baseline FEV1 on multivariate analysis. One (2%) subject experienced acute kidney injury. Conclusions The majority of patients experienced improvement in pulmonary function and a return to their baseline FEV1 while achieving a VTC in the range of 10 to <15 µg/mL. We were unable to identify a correlation between markers of vancomycin exposure and change in pulmonary function test results. Additional studies are needed to reinforce the efficacy of VTCs of 10 to 15 µg/mL for treating APEs of CF.

Time to First Antimicrobial Administration After Onset of Sepsis in Critically Ill Children

OBJECTIVES Delay of antimicrobial administration in adult patients with severe sepsis and septic shock has been associated with a decrease in survival to hospital discharge. The primary objective of this investigation was to determine the time to first antimicrobial administration after the onset of sepsis in critically ill children. Secondary objectives included appropriateness of empiric antimicrobials and microbiological testing, fluid resuscitation during the first 24 hours after onset of sepsis, intensive care unit and hospital length of stay, and mortality. METHODS Retrospective, chart review of all subjects less than or equal to 18 years of age admitted to the pediatric intensive care unit (PICU) with a diagnosis of sepsis between January 1, 2011, and December 31, 2012. RESULTS A total of 72 subjects met the inclusion criteria during the study period. Median time to first antimicrobial administration by a nurse after the onset of sepsis was 2.7 (0.5-5.1) hours. Cultures were drawn prior to administration of antimicrobials in 91.7% of subjects and were repeated within 48 hours in 72.2% of subjects. Empiric antimicrobial regimens were appropriate in 91.7% of cases. The most common empiric antimicrobial regimens included piperacillin/tazobactam plus vancomycin in 19 subjects (26.4%) and ceftriaxone plus vancomycin in 15 subjects (20.8%). Median PICU length of stay was 129 (64.6-370.9) hours, approximately 5 days, and median hospital length of stay was 289 (162.5-597.1) hours, approximately 12 days. There were 4 deaths during the study period. CONCLUSIONS Time to first antimicrobial administration after onset of sepsis was not optimal and exceeded the recommendations set forth in international guidelines. At our institution, the process for treating pediatric patients with severe sepsis and septic shock should be modified to increase compliance with national guidelines.

Vancomycin Versus Vancomycin Plus Rifampin for the Treatment of Acute Pulmonary Exacerbations of Cystic Fibrosis.

OBJECTIVES This study aimed to compare the change in pulmonary function in children and adolescents with cystic fibrosis (CF) who were infected with methicillin-resistant Staphylococcus aureus (MRSA) treated with either vancomycin (VAN) alone or vancomycin plus rifampin (VAN-RIF). METHODS Included patients were ages 6 to 20 years; hospitalized for an acute pulmonary exacerbation (APE) of CF from May 1, 2012, to April 30, 2014; had a respiratory tract culture positive for MRSA within 1 month of index hospital admission; received at least 48 consecutive hours of VAN or VAN-RIF; and had admission and discharge pulmonary function tests. The primary end point was change in percent predicted forced expiratory volume in 1 second (FEV1). RESULTS A total of 39 encounters met inclusion criteria: 24 in the VAN group (mean age 15.1 years) and 15 in the VAN-RIF group (mean age 13.7 years). There were no between-group differences in mean percent change in FEV1 (32.6% ± 28.8% vs. 21.1% ± 12.1%; p = 0.091), mean percent change in forced vital capacity (22.6% ± 25.8% vs. 14% ± 9.4%; p = 0.127), or return to baseline FEV1 (20 [83.3%] vs. 14 [93.3%] patients; p = 0.631). Median (IQR) length of stay (13 days [11-14 days] vs. 13 days [9-14 days]; p = 0.6) and median (IQR) time to readmission (82 days [43-129 days] vs. 147 days [78-219 days]; p = 0.2) were similar between the VAN and VAN-RIF groups, respectively. CONCLUSIONS Vancomycin monotherapy appears to be adequate when treating APEs of CF in children and adolescents with moderate lung disease and high MRSA VAN minimum inhibitory concentrations. Therefore, the addition of RIF may be unnecessary; however, larger studies are needed to confirm these findings.

Characterization of Vaccination Policies for Attendance and Employment at Day/Summer Camps in New York State:

Introduction: New York state requires day/summer camps to keep immunization records for all enrolled campers and strongly recommends requiring vaccination for all campers and staff. The objective of this study was to characterize immunization requirements/recommendations for children/adolescents enrolled in and staff employed at day/summer camps in New York state. Methods: An electronic hyperlink to a 9-question survey instrument was distributed via e-mail to 178 day/summer camps located in New York state cities with a population size greater than 100 000 people. A follow-up telephone survey was offered to nonresponders. The survey instrument included questions pertaining to vaccination documentation policies for campers/staff and the specific vaccines that the camp required/recommended. Fisher’s exact and Chi-square tests were used to analyze categorical data. Results: Sixty-five day/summer camps responded to the survey (36.5% response rate): 48 (73.8%) and 23 (41.8%) camps indicated having a policy/procedure for documenting vaccinations for campers and staff, respectively. Camps that had a policy/procedure for campers were more likely to have a policy/procedure for staff (P = .0007). Age-appropriate vaccinations that were required/recommended for campers by at least 80% of camps included: measles, mumps, and rubella (MMR), diphtheria, tetanus, and pertussis (DTaP), hepatitis B, inactivated/oral poliovirus (IPV/OPV), Haemophilus influenzae type b (Hib), and varicella. Age-appropriate vaccinations that were required/recommended for staff by at least 80% of camps included: DTaP, hepatitis B, IPV/OPV, MMR, meningococcus, varicella, Hib, and tetanus, diphtheria, and pertussis (Tdap). Conclusion: Vaccination policies at day/summer camps in New York state appear to be suboptimal. Educational outreach may encourage camps to strengthen their immunization policies, which may reduce the transmission of vaccine-preventable diseases.

Measuring changes in pharmacy and nursing students’ perceptions following an interprofessional high-fidelity simulation experience

ABSTRACT The purpose of this study was to evaluate the effects of interprofessional high-fidelity simulation-based learning (SBL) on third-year pharmacy and senior nursing students’ perceptions of interprofessional care. Students participated in an interprofessional high-fidelity SBL experience consisting of two hospital-based scenarios followed by a debriefing. The “Student Perceptions of Interprofessional Clinical Education–Revised” (SPICE-R) instrument was administered pre- and post-SBL. The “Student Satisfaction and Self-Confidence in Learning” (SSSCL) instrument, which uses a 5-point Likert scale, was administered post-SBL. A total of 104 (78%) pharmacy and 93 (77%) nursing students completed both the pre- and post-survey instruments. Baseline differences between pharmacy and nursing students included number of clinical hours completed [200 (190–240) vs. 210 (209–210); p < 0.001] and previous/current experiencing working directly with other healthcare professionals [71 (53%) vs. 88 (73%); p < 0.001]. Median score increases were observed for all SPICE-R items (p < 0.01) for pharmacy students and nine of ten SPICE-R items (p < 0.01) for nursing students. All students rated both the experience and their confidence highly on the SSSCL; however, nursing scores were higher than pharmacy scores for 7 of 13 items (p < 0.05). An interprofessional high-fidelity SBL experience increased pharmacy and nursing students’ perceptions of interprofessional care.

Procalcitonin to Detect Bacterial Infections in Critically Ill Pediatric Patients

The diagnostic power of procalcitonin (PCT) in the pediatric intensive care unit (PICU) is uncertain. This study aimed to determine the diagnostic ability of PCT to detect serious bacterial infections (SBI) in a heterogeneous PICU population. This was a retrospective cohort study of patients on whom a PCT level was obtained within 48 hours of admission to a PICU from 2013 to 2015. Discriminatory ability of PCT to predict SBI was examined by test and receiver operating characteristics (AUC [area under the curve]-ROC). Seventy-five patients were included and 28 (37%) had an SBI (median PCT = 6.48 ng/mL) compared with 47 (63%) in the noninfection group (median PCT = 0.23 ng/mL, P < .0001). PCT was able to adequately predict SBI (AUC-ROC = 0.83, 95% CI 0.74-0.93; P < .0001), and a PCT ≥1.28 ng/mL was the optimal threshold to detect SBI with a positive predictive value of 76.7% and negative predictive value of 88.9%. PCT adequately predicted SBI in a heterogeneous PICU population and may be useful for minimizing antibiotic consumption.

677: DESCRIPTION OF CRITICALLY ILL CHILDREN WITH VERY ELEVATED PROCALCITONIN LEVELS

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) discharge. There were no differences between survivors and non-survivors in age, sex, race, comorbidities, recent hospitalization, history of penicillin allergy, source of infection, or MDR gram-negative organism. History of solid organ transplant was more common in the survivor group, while vasopressor and ventilator use prior to index culture were more common in the non-survivors. ICU and hospital LOS prior to index culture was longer in the non-survivor group vs. survivor group (7 vs. 4 days, p<0.001; and 14 vs. 7 days, p=0.006). Patients who were documented as being treated for active infection were included in a multiple logistic regression. In this analysis, achievement of source control was the only variable independently associated with an increase in survival to hospital discharge. Conclusions: A higher than expected percentage of critically ill surgical patients with MDR gram-negative infections survived to hospital discharge. Achievement of source control was predictive of increased survival.