Engaging patients in antimicrobial stewardship: co-designed educational tool to improve periprocedural care through de-implementation of guideline-discordant antimicrobial use.

Effective de-implementation models often include replacement of an ineffective practice with an alternative. We co-developed patient education materials as a replacement strategy for inappropriate post-procedural antibiotics in cardiac device procedures. Lessons learned and developed materials may be used to promote infection prevention in other periprocedural settings.

Epidemiology of Gram-Negative Bloodstream Infections in the United States: Results From a Cohort of 24 Hospitals.

Background: To address knowledge gaps in management of Gram-negative bloodstream infection, the Antibiotic Stewardship Implementation Collaborative was established consisting of programs from 24 academic and community hospitals across the United States. Methods: A retrospective cohort study was conducted of unique adult patients with Gram-negative bloodstream infection hospitalized at participating hospitals from January to December 2019. Patient level and microbiologic data were collected via electronic medical record review with a standardized data collection form and data dictionary. Data analysis was largely descriptive. The Pearson χ2 test to compare categorical variables and the Wilcoxon rank sum test for continuous variables were used. Results: In total, 4851 bacterial isolates from 3710 eligible unique patients were included in the cohort. Most common source of infection was the urinary tract (47.9%). Source control was achieved in 84% of cases. Escherichia coli (2471, 51.0%) was the most common Gram-negative organism recovered. Antibiogram combining isolates from all participating centers with species-level susceptibilities and source specific antibiograms for isolates from urinary, respiratory, and intraabdominal source were created. Northeast sites contributed the most extended spectrum beta-lactamase (ESBL) producing organisms (73%), but West sites had the highest percentage of ESBL producers of total isolates (16%). A statistically significant difference in percentage of ESBL-producing organisms in Whites vs. non-Whites (14.6 % and 9.5 %, respectively, P<0.01) was observed. Conclusions: While the present study was conducted pre-pandemic, it highlights the need for stewardship data collaboratives to enhance our understanding of the antimicrobial resistance patterns.

Fluoroquinolone Prescribing for Diabetic Foot Infections following an FDA Drug Safety Communication for Aortic Aneurysm Risk.

In 2018, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication regarding fluoroquinolone-associated aortic aneurysm. This quasi-experimental study assessed antibiotic prescribing for 198 patients hospitalized with diabetic foot infection. Following the warning, median inpatient fluoroquinolone days of therapy (DOT) decreased from 3 to 0 days (P < 0.001), corresponding to increased beta-lactam DOT and outpatient parenteral antimicrobial therapy enrollment. FDA communications may influence antibiotic selection and transitions of care, representing opportunities for antimicrobial stewardship.

Diminishing returns, increasing risks: Impact of antibiotic duration of therapy on respiratory bacterial isolates in hospitalized patients during the coronavirus disease 2019 (COVID-19) pandemic.

In 829 hospital encounters for patients with COVID-19, 73.2% included orders for antibiotics; however, only 1.8% had respiratory cultures during the first 3 hospital days isolating bacteria. Case-control analysis of 30 patients and 96 controls found that each antibiotic day increased the risk of isolating multidrug-resistant gram-negative bacteria (MDR-GNB) in respiratory cultures by 6.5%.

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).

IMPORTANCE: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. OBJECTIVE: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. MAIN OUTCOMES AND MEASURES: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. RESULTS: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. CONCLUSIONS AND RELEVANCE: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

Successful treatment of fulminant Clostridioides difficile infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged, severe neutropenia.

We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high-risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life-saving cure. The patient had subsequent clinical improvement, however, developed multidrug-resistant Pseudomonas aeruginosa bacteremia 2 days post-procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk.

Facility type and surgical specialty are associated with suboptimal surgical antimicrobial prophylaxis practice patterns: a multi-center, retrospective cohort study.

Background: Guidelines recommend discontinuation of antimicrobial prophylaxis within 24 h after incision closure in uninfected patients. However, how facility and surgical specialty factors affect the implementation of these evidence-based surgical prophylaxis guidelines in outpatient surgery is unknown. Thus, we sought to measure how facility complexity, including ambulatory surgical center (ASC) status and availability of ancillary services, impact adherence to guidelines for timely discontinuation of antimicrobial prophylaxis after outpatient surgery. A secondary aim was to measure the association between surgical specialty and guideline compliance. Methods: A multi-center, national Veterans Health Administration retrospective cohort from 10/1/2015-9/30/2017 including any Veteran undergoing an outpatient surgical procedure in any of five specialties (general surgery, urology, ophthalmology, ENT, orthopedics) was created. The primary outcome was the association between facility complexity and proportion of surgeries not compliant with discontinuation of antimicrobials within 24 h of incision closure. Data were analyzed using logistic regression with adjustments for patient and procedural factors. Results: Among 153,097 outpatient surgeries, 7712 (5.0%) received antimicrobial prophylaxis lasting > 24 h after surgery; rates ranged from 0.4% (eye surgeries) to 13.7% (genitourinary surgeries). Cystoscopies and cystoureteroscopy with lithotripsy procedures had the highest rates (16 and 20%), while hernia repair, cataract surgeries, and laparoscopic cholecystectomies had the lowest (0.2-0.3%). In an adjusted logistic regression model, lower complexity ASC and hospital outpatient departments had higher odds of prolonged antimicrobial prophylaxis compared to complex hospitals (OR ASC, 1.3, 95% CI: 1.2-1.5). Patient factors associated with higher odds of noncompliance with antimicrobial discontinuation included younger age, female sex, and white race. Genitourinary and ear/nose/throat surgeries were associated with the highest odds of prolonged antimicrobial prophylaxis. Conclusions: Facility complexity appears to play a role in adherence to surgical infection prevention guidelines. Lower complexity facilities with limited infection prevention and antimicrobial stewardship resources may be important targets for quality improvement. Such interventions may be especially useful for genitourinary and ear/nose/throat surgical subspecialties. Increasing pharmacy, antimicrobial stewardship and/or infection prevention resources to promote more evidence-based care may support surgical providers in lower complexity ambulatory surgery centers and hospital outpatient departments in their efforts to improve this facet of patient safety.

Clinical characteristics and treatment outcomes among respiratory syncytial virus (RSV)-infected hematologic malignancy and hematopoietic stem cell transplant recipients receiving palivizumab.

Palivizumab has been used to treat respiratory syncytial virus (RSV)-infected hematologic malignancy patients at our institution based on limited published data. We conducted this retrospective study to evaluate clinical outcomes and mortality rates of RSV-infected hematologic malignancy patients from 2007 to 2016. A total of 67 patients (19 received palivizumab and 47 received supportive care) were identified. Palivizumab-treated patients had a significantly higher proportion of underlying ischemic heart disease, graft-versus-host-disease, hypogammaglobulinemia, and concomitant pulmonary infections. There were no significant differences in mortality rates or readmission rates between the two groups. The estimated odds ratio for death in patients receiving palivizumab after adjusting for propensity scores and covariates were 0.12 ([0.01, 1.32], p = .08) and 0.09 ([0.01, 1.03], p = .05) respectively. After adjustment for factors associated with severity of illness, there was no difference in mortality among patients treated with palivizumab.

Prolonged antimicrobial prophylaxis following cardiac device procedures increases preventable harm: insights from the VA CART program.

BACKGROUND: The rate of cardiovascular implantable electronic device (CIED) infection is increasing coincident with an increase in the number of device procedures. Preprocedural antimicrobial prophylaxis reduces CIED infections; however, there is no evidence that prolonged postprocedural antimicrobials additionally reduce risk. Thus, we sought to quantify the harms associated with this approach. OBJECTIVE: To measure the association between Clostridium difficile infection (CDI), acute kidney injury (AKI) and receipt of prolonged postprocedural antimicrobials. METHODS: CIED procedures entered into the VA Clinical Assessment Reporting and Tracking Electrophysiology (CART-EP) database during fiscal years 2008-2016 were included. The primary outcome was 90-day incidence of CDI and the secondary outcome was the 7-day incidence of AKI. The primary exposure measure was duration of postprocedural antimicrobial therapy. Associations were measured using Cox-proportional hazards and binomial regression. RESULTS: Prolonged postprocedural antimicrobial therapy was identified following 3,331 of 6,497 CIED procedures (51.3%), and the median duration of prophylaxis was 5 days. Prolonged postprocedural antimicrobial use was associated with increased risk of CDI (hazard ratio [HR], 2.90; 95% confidence interval [CI], 1.54-5.46). Of the 27 patients who developed CDI, 11 subsequently died. Postprocedural antimicrobial use with ≥2 antimicrobials was associated with an increased risk of AKI (OR, 4.16; 95% CI, 2.50-6.90). The impact was particularly significant when one of the dual agents prescribed was vancomycin (adjusted OR, 8.41; 95% CI, 5.53-12.79). CONCLUSIONS: Prolonged antimicrobial prophylaxis following CIED procedures increases preventable harm; this practice should be discouraged in procedural settings such as the cardiac electrophysiology laboratory.

Perioperative antimicrobial prophylaxis and prevention of hepatobiliary surgical site infections.

OBJECTIVE: To characterize the microbiology of hepatobiliary surgical site infections (SSIs) and to explore the relationship between specific antimicrobial prophylaxis regimens and the development of SSIs. DESIGN: Retrospective matched case-control study comparing patient, procedure, and antimicrobial prophylaxis characteristics among patients undergoing a hepatobiliary surgical procedure with and without an SSI. SETTING: A tertiary referral acute-care facility. METHODS: Patients undergoing procedures defined as "BILI" (bile duct, liver, or pancreas surgery) using National Healthcare Safety Network (NHSN) definitions, excluding those undergoing concomitant liver transplantation, from January 2013 through June 2016 were included in the study population. The SSIs were identified through routine infection control surveillance using NHSN definitions. All patients who developed an SSI were considered cases. Controls were selected randomly matched 2:1 with cases based on fiscal quarter of the procedure. Logistic regression modeling was performed to explore variables associated with SSI, including antimicrobial prophylaxis received. RESULTS: Among 975 procedures, 80 (8.2%) resulted in an SSI. Most cases involved an organism nonsusceptible to standard prophylaxis regimens, including cefazolin (68.8%), cefazolin plus metronidazole (61.3%), and ampicillin-sulbactam (52.5%). In a multivariate model, antimicrobial coverage against Enterococcus spp (aOR, 0.58; 95% confidence interval [CI], 0.17-2.04; P=.40) and against Pseudomonas spp (aOR, 2.40; 95% CI, 0.56-10.29; P=.24) were not protective against the development of an SSI. The presence of a documented ß-lactam allergy was significantly associated with the development of an SSI (aOR, 3.54; 95% CI, 1.36-9.19; P=.009). CONCLUSIONS: Although SSIs at the study institution were associated with pathogens nonsusceptible to the most commonly used prophylaxis regimens, broader-spectrum coverage was not associated with a reduction in SSIs.

Does the Beta-Lactam Matter? Nafcillin versus Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bloodstream Infections.

BACKGROUND: Antistaphylococcal penicillins have historically been regarded as the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). However, recent outcomes data compared to cefazolin treatment are conflicting. OBJECTIVE: This study compared treatment failure and adverse effects associated with nafcillin and cefazolin for MSSA BSI. METHODS: Adult inpatients with MSSA BSI between January 1, 2009 and August 31, 2015 were included in this retrospective cohort study if they received ≥72 h of nafcillin or cefazolin as directed therapy after no more than 72 h of any empiric therapy. The primary composite endpoint was treatment failure defined by clinician documentation, 30-day recurrence of infection, all-cause 30-day in-hospital mortality, or loss to follow-up. Secondary outcomes included antibiotic-related acute kidney injury (AKI), acute interstitial nephritis (AIN), hepatotoxicity, and rash. RESULTS: Among 157 patients, 116 (73.9%) received nafcillin and 41 (26.1%) received cefazolin. The baseline characteristics were similar except cefazolin-treated patients had higher APACHE II scores and more frequent renal dysfunction. No difference in the composite treatment failure outcome (28.4 vs. 31.7%; p = 0.69) was detected between the nafcillin and cefazolin groups, respectively. In a sensitivity analysis excluding patients without known follow-up, there was no significant difference of treatment failure. AKI, AIN, hepatotoxicity, and rash were all numerically more frequent among nafcillin-treated patients. CONCLUSIONS: Among nafcillin- or cefazolin-treated patients with MSSA BSI, there was no significant difference in treatment failure. Observing more frequent presumptive adverse effects associated with nafcillin receipt, future prospective studies evaluating cefazolin appear warranted.

Randomized Comparison of 3 High-Level Disinfection and Sterilization Procedures for Duodenoscopes.

BACKGROUND AND AIMS: Duodenoscopes have been implicated in the transmission of multidrug-resistant organisms (MDRO). We compared the frequency of duodenoscope contamination with MDRO or any other bacteria after disinfection or sterilization by 3 different methods. METHODS: We performed a single-center prospective randomized study in which duodenoscopes were randomly reprocessed by standard high-level disinfection (sHLD), double high-level disinfection (dHLD), or standard high-level disinfection followed by ethylene oxide gas sterilization (HLD/ETO). Samples were collected from the elevator mechanism and working channel of each duodenoscope and cultured before use. The primary outcome was the proportion of duodenoscopes with an elevator mechanism or working channel culture showing 1 or more MDRO; secondary outcomes included the frequency of duodenoscope contamination with more than 0 and 10 or more colony-forming units (CFU) of aerobic bacterial growth on either sampling location. RESULTS: After 3 months of enrollment, the study was closed because of the futility; we did not observe sufficient events to evaluate the primary outcome. Among 541 duodenoscope culture events, 516 were included in the final analysis. No duodenoscope culture in any group was positive for MDRO. Bacterial growth of more than 0 CFU was noted in 16.1% duodenoscopes in the sHLD group, 16.0% in the dHLD group, and 22.5% in the HLD/ETO group (P = .21). Bacterial growth or 10 or more CFU was noted in 2.3% of duodenoscopes in the sHLD group, 4.1% in the dHLD group, and 4.2% in the HLD/ETO group (P = .36). MRDOs were cultured from 3.2% of pre-procedure rectal swabs and 2.5% of duodenal aspirates. CONCLUSIONS: In a comparison of duodenoscopes reprocessed by sHLD, dHLD, or HLD/ETO, we found no significant differences between groups for MDRO or bacteria contamination. Enhanced disinfection methods (dHLD or HLD/ETO) did not provide additional protection against contamination. However, insufficient events occurred to assess our primary study end-point. ClinicalTrials.gov no: NCT02611648.

Does Adjunctive Tigecycline Improve Outcomes in Severe-Complicated, Nonoperative Clostridium difficile Infection?

Severe Clostridium difficile infection is associated with a high rate of mortality; however, the optimal treatment for severe- complicated infection remains uncertain for patients who are not candidates for surgical intervention. Thus, we sought to evaluate the benefit of adjunctive tigecycline in this patient population using a retrospective cohort adjusted for propensity to receive tigecycline. We found that patients who received tigecycline had similar outcomes to those who did not, although the small sample size limited power to adjust for comorbidities and severity of illness.

Should We Prescribe Antibiotics to This Patient With Persistent Upper Respiratory Symptoms?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

The American College of Physicians (ACP) and the Centers for Disease Control and Prevention (CDC) recently published advice for high-value care on the appropriate use of antibiotics for acute respiratory tract infections. They conducted a narrative literature review of evidence for antibiotic use in this setting that included recent clinical guidelines from professional societies supplemented by randomized, controlled trials; meta-analyses; and systematic reviews. They concluded that clinicians should reserve antibiotic treatment for acute rhinosinusitis in patients with persistent symptoms for more than 10 days, high fever and purulent nasal discharge or facial pain lasting for at least 3 consecutive days, or worsening symptoms after a typical viral illness that lasted 5 days and had initially improved ("double-sickening"). In this Grand Rounds, 2 prominent clinicians debate whether to initiate antibiotic treatment in a 62-year-old man with a history of recurrent sinusitis who presents with persistent upper respiratory symptoms. They review the data on which the ACP/CDC recommendations are based and discuss the potential benefits and risks, as well as the challenges and controversies, of prescribing antibiotic therapy in this setting.

Investigation of a Candida guilliermondii Pseudo-outbreak Reveals a Novel Source of Laboratory Contamination.

Candida guilliermondii was isolated from sterile specimens with increasing frequency over a several-month period despite a paucity of clinical evidence suggesting true Candida infections. However, a health care-associated outbreak was strongly considered due to growth patterns in the microbiology laboratory that were more consistent with true infection than environmental contamination. Therefore, an extensive investigation was performed to identify its cause. With the exception of one case, patient clinical courses were not consistent with true invasive fungal infections. Furthermore, no epidemiologic link between patients was identified. Rather, extensive environmental sampling revealed C. guilliermondii in an anaerobic holding jar in the clinical microbiology laboratory, where anaerobic plates were prereduced and held before inoculating specimens. C. guilliermondii grows poorly under anaerobic conditions. Thus, we postulate that anaerobic plates became intermittently contaminated. Passaging from intermittently contaminated anaerobic plates to primary quadrants of aerobic media during specimen planting yielded a colonial growth pattern typical for true specimen infection, thus obscuring laboratory contamination. A molecular evaluation of the C. guilliermondii isolates confirmed a common source for pseudo-outbreak cases but not for the one true infection. In line with Reason's model of organizational accidents, active and latent errors coincided to contribute to the pseudo-outbreak. These included organism factors (lack of growth in anaerobic conditions obscuring plate contamination), human factors (lack of strict adherence to plating order, leading to only intermittent observation of aerobic plate positivity), and laboratory factors (novel equipment). All of these variables should be considered when evaluating possible laboratory-based pseudo-outbreaks.

Cardiac Electrophysiology Laboratories: A Potential Target for Antimicrobial Stewardship and Quality Improvement?

BACKGROUND Infections following cardiovascular implantable electronic device (CIED) procedures, including pacemaker and implantable cardioverter-defibrillators, are devastating and costly. Preimplantation prophylactic antimicrobials are effective for reducing postprocedural infections. However, routine postprocedural antimicrobials are not associated with improved outcomes, and they may be harmful. Thus, we sought to characterize antimicrobial use patterns following CIED procedures. DESIGN All patients who underwent CIED procedures from October 1, 2007 to September 30, 2013 and had procedural information entered into the VA Clinical Assessment Reporting and Tracking (CART) software program were included in this study. All antibiotic prescriptions lasting more than 24 hours following device implantation or revision were identified using pharmacy databases, and postprocedural antibiotic use lasting more than 24 hours was characterized. RESULTS In total, 3,712 CIED procedures were performed at 34 VA facilities on 3,570 patients with a mean age of 71.7 years (standard deviation [SD], 11.1 years), 98.4% of whom were male. Postprocedural antibiotics >24 hours were prescribed following 1,579 of 3,712 CIED procedures (42.5%). The median duration of therapy was 5 days (interquartile range [IQR], 3-7 days). The most commonly prescribed antibiotic was cephalexin (1,152 of 1,579; 72.9%), followed by doxycycline (118 of 1,579; 7.47%) and ciprofloxacin (93 of 1,579; 5.9%). Vancomycin was used in 73 of 1,579 prescriptions (4.62%). Among the highest quartile of procedural volume, prescribing practices varied considerably, ranging from 3.2% to 77.6%. CONCLUSIONS Nearly 1 in 2 patients received prolonged postprocedural antimicrobial therapy following CIED procedures, and the rate of postprocedural antimicrobial therapy use varied considerably by facility. Given the lack of demonstrated benefit of routine prolonged antimicrobial therapy following CIED procedures, antimicrobial use following cardiac device interventions may be a potential target for quality improvement programs and antimicrobial stewardship. Infect Control Hosp Epidemiol 2016;37:1005-1011.