Faculty Bibliography

Background. Trimethoprim/Sulfamethoxazole (TMP/SMX) is not routinely employed for urinary tract infections (UTI) with multi-drug-resistant organisms (MDRO) due to paucity of effectiveness data, concerns regarding inadequate urinary penetration, and risk of adverse effects. We describe our experience with TMP/SMX as definitive therapy for MDRO Enterobacteriaceae (MDRO-E). Methods. We carried out a retrospective review of patients hospitalized at a tertiary care center and treated with TMP/SMX as definitive therapy for UTI with MDRO-E (as defined by resistance to third-generation cephalosporins in culture). We evaluated rates of overall cure rate (CR), adverse events (AE), recurrence (RC) and reinfection (RI). Repeat growth of same or different pathogen in urine culture (UC) within 30 days of completion of treatment was defined as RC or RI, respectively. Results. 92 patients had 101 episodes of MDRO-E UTIs treated with TMP/SMX as initial (n = 26, 25.7%) or as step-down therapy (n = 23, 77%) after broad-spectrum empiric antimicrobials (ceftriaxone n = 22, cefepime n = 21, piperacillin/tazobactam n = 12, carbapenems n = 6, ciprofloxacin n = 3). 63 (68.5%) patients were 65 years or older. MDRO-E in 10 (9.9%) episodes were also resistant to carbapenems. Empiric therapy was appropriate in 56 (55.5%) episodes. Median duration of treatment was 8.5 (range 3-24) days for all antimicrobials and 7 (range 2-15) days for TMP-/SMX. Overall CR was 100%. RC/RI was seen in 23/101 (22.8%) episodes (RC n = 9; RI n = 14); UC data were available for 20 of which 8/20 (40%) had a TMP/SMX-resistant organism. 4 (3.9%) patients required readmission for a RC/RI UTI. In terms of AEs: 10 (9.9%) episodes of hyperkalemia (median maximum potassium level 4.5 mmol/L, range 2.7-6.4), 3 (2.9%) episodes of acute kidney injury, 5 episodes of Clostridium difficile infection, and 4 (3.9%) readmissions for a RC/RI UTI within 90 days. Conclusion. Our findings suggest that TMP/SMX can be safe and effective as definitive therapy for ESBL-E UTI. The major AE are hyperkalemia and AKI, the incidence of which is high when TMP/SMX is used in combination with ACEI/ARBs. No clinical factors were found to be predictive of recurrence of reinfection. (Table Presented)

Background: Midline catheters (MCs) have arisen as alternatives to peripherally inserted central catheters (PICCs) for both general intravenous therapy and extended outpatient parenteral therapy. However, there is a lack of data concerning the safety of medication therapy through midline for extended durations. Objective: The purpose of this study is to evaluate the safety of MCs for extended intravenous use. Methods: This was a retrospective cohort study evaluating patients who received intravenous therapy through an MC at a tertiary care academic medical center. The primary end point was the incidence of composite catheter-related adverse events that included local events, catheter dislodgment, infiltration, catheter occlusion, catheter-related venous thromboembolism, extravasation, and line-associated infection. Results: A total of 82 MC placements and 50 PICC placements were included; 50 MCs were for outpatient parenteral antimicrobial therapy, and 32 were for inpatient intravenous use. There were 21 complications per 1000 catheter-days in the outpatient group and 7 complications per 1000 catheter-days in the PICC group (P = 0.91). The median time to complication in both groups was 8 days. The antimicrobial classes commonly associated with complications were cephalosporins, carbapenems, and penicillins. Conclusion and Relevance: Our results suggest that intravenous therapy with MCs is generally safe for prolonged courses that do not exceed 14 days as compared with PICC lines, which can be placed for months. There is still limited evidence for the use of MCs between 14 and 28 days of therapy. This study can help guide our selection of intravenous catheters for the purpose of outpatient antimicrobial therapy.

BACKGROUND:Although dalbavancin's (DBV's) long half-life and one-time dosing strategy confer ideal administration in the ambulatory setting, the optimal role of DBV in the management of acute bacterial skin and skin structure infections (ABSSSIs) remains to be elucidated. OBJECTIVES/OBJECTIVE:The primary objective of this study was to compare treatment outcomes of ABSSSI between patients who received DBV in the emergency department (ED) as part of standard care versus patients who received DBV as part of a telehealth program. METHODS:This was a retrospective cohort study evaluating patients who received DBV at 3 urban EDs. The primary end point was the incidence of ABSSSI recurrence. Secondary outcomes included need for hospital admission and ED length of stay (LOS; in hours). RESULTS:A total of 65 ABSSSI treatment courses were included; 42 were included in the telehealth criteria (TC) cohort and 23 in the initial criteria (IC) cohort. There were 14% (6/42) infection recurrences in the TC cohort and 22% (5/23) in the IC cohort, with median time to recurrence being 4 and 14 days, respectively. Median ED LOS was significantly shorter in the TC (5 vs 25 hours, P < 0.05). Numerically fewer individuals in the TC cohort required inpatient admission (0 vs n = 2, 9%). Conclusion and Relevance: Our results suggest that patients may be safely administered DBV in an ED setting, with telehealth follow-up. Providing structured patient selection criteria is an effective method of assisting ED providers in selecting appropriate DBV candidates to limit potential recurrences and readmissions.

Background. Oral treatment strategies for Enterobacteriaceae bacteremia (EB) are controversial, with both beta-lactams (BL) and fluoroquinolones (FQ) used in clinical practice. FQ may be preferred for their high bioavailability, but other oral antibiotics are needed due to concerns of resistance and adverse effects. As an effort to facilitate antibiotic stewardship, BL should be explored as an additional oral option for EB treatment. Methods. This retrospective study compared clinical characteristics and outcomes in patients with EB treated with BL vs. FQ as definitive oral therapy between January 2013 and July 2017. Adult patients diagnosed with their first incidence of EB and transitioned from IV antibiotics to either study antibiotic class were included. Primary and secondary outcomes assessed recurrence, collateral damage, readmission, and all-cause mortality. Results. A total of 173 patients were included (BL n = 59, FQ n = 114). Median age was 70 years, Pitt bacteremia score was 2 (range 0-7), and Charlson Comorbidity Index was 5 (0-12); all were comparable between groups. Urinary source of infection was most common (57%). The majority of oral BL courses used cefpodoxime (63%). More patients in FQ vs. BL had a prior transplant (9% vs. 0%, P = 0.05), presence of abscess (11% vs. 0%, P = 0.01), and Infectious Diseases consultation (63% vs. 34%, P = 0.0001). Onset of EB in an intensive care unit was more common in BL vs. FQ (24% vs. 10%, P = 0.01). Median duration of IV and oral therapy was 5 vs. 4 days, P = 0.22 and 11 vs. 12 days, P = 0.17 in BL and FQ, respectively. Recurrence within 90 days was 7% in BL and 4% in FQ, P = 0.49 (adjusted OR 1.44, 95% CI 0.31-6.66; P = 0.64). Multivariate analysis identified liver cirrhosis (OR 16.89, 95% CI 1.06-268.32; P = 0.05) as an independent predictor of recurrence within 90 days. All secondary outcomes were similar between BL vs. FQ: superinfection within 90 days (10% vs. 9%, P = 0.76), C. difficile infection within 90 days (3% vs. 1%, P = 0.27), 30-day readmission (15% vs. 20%, P = 0.43), all-cause 30-day mortality (0% vs. 3%, P = 0.55). Conclusion. In our cohort of patients with EB, clinical outcomes were similar between those treated with oral BL compared with FQ. Oral BL may be considered for definitive treatment of EB, although further investigation in larger studies is needed

BACKGROUND:Parameters within reconstitution, storage, stability, and administration may be optimized according to the unique pharmacokinetics of each antibiotic to ensure a successful desensitization. OBJECTIVE:The study aims to evaluate the successfulness and safety of antibiotic desensitization protocols developed by the pharmacy department at our institution. METHODS:A retrospective study was conducted at an 800-bed, urban, tertiary care, academic medical center. A total of 36 patients 18 years of age or older, admitted to our intensive care units between March 2013 and July 2017, who underwent antibiotic desensitization utilizing our pharmacy developed protocols were included. RESULTS:In 36 patients, 61 desensitization cases were identified and included; 17 (47%) were male, 27 (75%) were Caucasian, and the median age was 55 years (range 19-94). In all, 15 different antibiotics were administered for desensitization, with meropenem (n = 12, 20%), ampicillin (n = 7, 11%), piperacillin/tazobactam (n = 7, 11%), and penicillin (n = 7, 11%) being the most common; 59 (97%) of 61 desensitizations were completed successfully with or without experiencing reactions, and 53 (89%) of the successful desensitization cases were completed without reactions. Two cases were categorized as anaphylaxis, which was severe enough to terminate the desensitization process. Of the 59 cases successfully completed, the 6 (10%) cases that experienced reactions were managed successfully during desensitization with completion of the process. Conclusion and Relevance: The findings suggest that our pharmacy-developed antibiotic desensitization protocols are successful and safe and may be adapted by other institutions.

Polymyxin B is used as a last treatment resort for multidrug-resistant Gram-negative bacterial infections. The objectives of this study were to examine the population pharmacokinetics of polymyxin B and investigate factor(s) influencing pharmacokinetic variability. Four serial blood samples each were collected from 35 adult patients at steady state. The concentrations of individual polymyxin B components were analyzed using a validated liquid chromatography / tandem mass spectrometry assay and combined to derive total concentrations. A maximum likelihood expectation maximization approach was used to fit the data. Various demographic variables were investigated as potential covariates for clearance and volume of distribution (V_d ) using linear regression analysis. A one-compartment model fit to the data satisfactorily (r²  = 0.96). The best-fit mean ± SD for clearance and V_d were 2.5 ± 1.1 L/h and 34.3 ± 16.4 L, respectively. Creatinine clearance was found to be a statistically significant covariate of clearance, but the magnitude was deemed clinically insignificant.

Nephrotoxicity is a known adverse effect of polymyxin B (PMB). Animal data suggests that once daily dosing may reduce the rate and delay the onset of acute kidney injury (AKI).In a multicenter, retrospective study, we evaluated adult patients with a creatinine clearance (CrCl) ≥30 mL/min who received ≥48h of PMB therapy. The primary endpoint was the difference in rate of AKI comparing once and twice daily PMB dosing. Secondary endpoints included time to AKI and recovery of renal function.Of 273 eligible patients, 100 from each group were matched based on propensity scores. In the matched groups, nephrotoxicity, defined according to RIFLE criteria, was more frequent with once versus twice daily dosing (47% vs. 17% P=0.0005). After adjusting for residual differences by multivariate conditional logistic regression, once daily dosing was more likely to result in nephrotoxicity (adjusted odds ratio 2.5, 95% CI 1.413-4.541, P=0.002). Among 64 patients who developed AKI, the median onset was similar between groups (7 days with once vs. 6 days with twice daily dosing, P=0.095). Of 37 patients who had their serum creatinine evaluated subsequently, 29/37 (78%) had recovery of renal function. No patient required renal replacement therapy.Our findings suggest that AKI is significantly more common with PMB once daily as compared to twice daily dosing with no difference in time to AKI. Prospective randomized study is warranted to validate these results.

Extended infusion (EI) administration of β-lactams can improve target attainment in critically ill patients with altered pharmacokinetics/pharmacodynamics. To optimize meropenem dosing in patients with severe sepsis/septic shock, our Antimicrobial Stewardship Program implemented a EI meropenem (EIM) protocol in an 18-bed Medical Intensive Care Unit in March 2014. In this retrospective study, we compared intensive care unit (ICU) mortality and clinical response in patients who received meropenem for ≥72 hours administered per EIM protocol of 1 g over 3 hours every 8 hours versus intermittent infusion (IIM) protocol of 500 mg over 30 minutes every 6 hours. Age, weight, comorbidities, severity of illness, and vasopressor use were comparable between groups (EIM protocol n = 52, IIM protocol n = 96). The IIM protocol group had higher rates of renal dose adjustment at meropenem initiation. Among 56 identified gram-negative (GN) pathogens, 94% had meropenem minimal inhibitory concentration ≤0.25 mg/L. The ICU mortality was lower (19 vs 37%; P = .032) and clinical response was higher (83% vs 46%; P < .01) in the EIM protocol versus IIM protocol group. Total vasopressor days were shorter (2 vs 3 days; P = .038), and white blood cell normalization rate was higher (87% vs 51%; P < .01) in the EIM protocol versus IIM protocol group. There was no difference in days of mechanical ventilation, duration of therapy, and ICU stay. The IIM protocol was also identified as an independent risk factor associated with ICU mortality (hazard ratio: 3.653, 95% confidence interval: 1.689-7.981; P = .001) after adjusting for Sequential Organ Failure Assessment score. In this cohort of patients with severe sepsis/septic shock and highly susceptible GN pathogens, there was improved mortality and clinical response in the EIM protocol group.

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.