Faculty Bibliography

OBJECTIVE:The data regarding the effectiveness of chemical prophylaxis against recurrent C. difficile infection (CDI) remain conflicting. DESIGN/METHODS:Retrospective cohort study on the effectiveness of oral vancomycin for prevention of recurrent CDI. SETTING/METHODS:Two academic centers in New York. METHODS:Two participating hospitals implemented an automated alert recommending oral vancomycin 125 mg twice daily in patients with CDI history scheduled to receive systemic antimicrobials. Measured outcomes included breakthrough and recurrent CDI rates, defined as CDI during and 1 month after initiation of prophylaxis, respectively. A self-controlled, before-and-after study design was employed to examine the effect of vancomycin prophylaxis on the prevalence of vancomycin-resistant Enterococcus spp (VRE) colonization and infection. RESULTS:We included 264 patients in the analysis. Breakthrough CDI was identified in 17 patients (6.4%; 95% confidence interval [CI], 3.8%-10.1%) and recurrent in 22 patients (8.3%; 95% CI, 5.3%-12.3%). Among the 102 patients with a history of CDI within the 3 months preceding prophylaxis, 4 patients (3.9%; 95% CIs, 1.1%-9.7%) had breakthrough CDI and 9 had recurrent disease (8.8%; 95% CIs, 4.1%-16.1%). In the 3-month period following vancomycin prophylaxis, we detected a statistically significant increase in both the absolute number of VRE (χ2, 0.003) and the ratio of VRE to VSE isolates (χ2, 0.003) compared to the combined period of 1.5 months preceding and the 3-4.5 months following prophylaxis. This effect persisted 6 months following prophylaxis. CONCLUSIONS:Prophylactic vancomycin is an effective strategy to prevent CDI recurrence, but it increases the risk of VRE colonization. Thus, a careful selection of patients with high benefit-to-risk ratio is needed for the implementation of this preventive policy.

PURPOSE:A critical shortage of small-volume parenteral solutions in late 2017 led hospitals to develop strategies to ensure availability for critical patients, including administration of antibiotics as intravenous push (IVP). Minimal literature has been published to date that assesses the safety of administration of beta-lactams via this route. Therefore, the purpose of this study was to evaluate the safety of IVP administration of select beta-lactam antibiotics. METHODS:We performed a retrospective review of IVP administrations of aztreonam, ceftriaxone, cefepime, and meropenem at two campuses of the New York University Langone Health system after October 2017. Patients receiving surgical prophylaxis or more than one IVP antibiotic simultaneously were excluded. The primary endpoint was adverse events (ADE) following IVP administration of antibiotics. RESULTS:We evaluated 1000 patients who received IVP aztreonam (n = 43), ceftriaxone (n = 544), cefepime (n = 368) or meropenem (n = 45). There were 10 (1%) ADE observed, 5 of which were allergic reactions. Four ADE were neurotoxicity related to IVP cefepime. Based on the Naranjo score, 1 adverse event was "probably" and 3 were "possibly" related to cefepime IVP administration. Lastly, only 1 report of phlebitis was observed with the use of IVP ceftriaxone. CONCLUSIONS:The use of IVP as an alternative to intravenous piggyback (IVPB) during times of drug shortage for select beta-lactam antibiotics appears to be safe, and ADE are similar to those previously described for IVPB administration. Future studies evaluating clinical outcomes between IVP and IVPB administration may be of benefit.

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.