A novel 2-step process for the management of inpatient beta-lactam allergy labels.

BACKGROUND: Inpatient beta-lactam allergy labels may increase the unnecessary use of aztreonam and non-beta-lactam antibiotics, which can then lead to more adverse events and increased health care costs, OBJECTIVE: To assess the impact of a novel 2-step process (medication history review followed by risk stratification) on rates of beta-lactam delabeling, aztreonam use, and desensitizations on pediatric, adult, and obstetrics inpatients at a tertiary academic center. METHODS: We prospectively collected data on 700 patients who received inpatient consultation from the Beta-Lactam Allergy Evaluation Service between August 2021 and July 2022. Patients were delabeled either by medication review alone, drug challenge alone if with a low-risk history, or penicillin skin test followed by drug challenge if with a high-risk history. Generalized linear regression modeling was used to compare aztreonam days of therapy in the intervention year with the 2 prior years. Drug desensitizations were assessed by electronic chart review. RESULTS: Most of the patients (n = 656 of 700, 94%) had more than or equal to 1 beta-lactam allergy label removed, clarified, or both; 77.9% of these patients (n = 511 of 656) had 587 beta-lactam allergy labels removed. Nearly one-third (n = 149, 27.6%) had 162 allergy labels removed solely by medication history review. All 114 penicillin skin tests performed had negative results, and 98% (8 of 381) of the patients who underwent any drug challenge passed. Only 5.7% of the delabeled patients were relabeled. There was a 27% reduction in aztreonam use (P = .007). Beta-lactam desensitizations were reduced by 80%. CONCLUSION: A full-time inpatient beta-lactam allergy service using medication history review and risk stratification can safely and effectively remove inpatient beta-lactam allergy labels, reduce aztreonam use, and decrease beta-lactam desensitizations.

Monoclonal Antibody Use for Coronavirus Disease 2019 in Pediatric Patients: A Multicenter Retrospective Study.

Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died.

Variation in Clinical Practice and Attitudes on Antibacterial Management of Fever and Neutropenia in Patients With Hematologic Malignancy: A Survey of Cancer Centers Across the United States.

BACKGROUND: Contemporary information regarding fever and neutropenia (FN) management, including approaches to antibacterial prophylaxis, empiric therapy, and de-escalation across US cancer centers, is lacking. METHODS: This was a self-administered, electronic, cross-sectional survey of antimicrobial stewardship physicians and pharmacists at US cancer centers. The survey ascertained institutional practices and individual attitudes on FN management in high-risk cancer patients. A 5-point Likert scale assessed individual attitudes. RESULTS: Providers from 31 of 86 hospitals (36%) responded, and FN management guidelines existed in most (29/31, 94%) hospitals. Antibacterial prophylaxis was recommended in 27/31 (87%) hospitals, with levofloxacin as the preferred agent (23/27, 85%). Cefepime was the most recommended agent for empiric FN treatment (26/29, 90%). Most institutional guidelines (26/29, 90%) recommended against routine addition of empiric gram-positive agents except for specific scenarios. Eighteen of 29 (62%) hospitals explicitly provided guidance on de-escalation of empiric, systemic antibacterial therapy; however, timing of de-escalation was variable according to clinical scenario. Among 34 individual respondents, a majority agreed with use of antibiotic prophylaxis in high-risk patients (25, 74%). Interestingly, only 10 (29%) respondents indicated agreement with the statement that benefits of antibiotic prophylaxis outweigh potential harms. CONCLUSION: Most US cancer centers surveyed had institutional FN management guidelines. Antibiotic de-escalation guidance was lacking in nearly 40% of centers, with heterogeneity in approaches when recommendations existed. Further research is needed to inform FN guidelines on antibacterial prophylaxis and therapy de-escalation.

Early Antibiotic Discontinuation or De-escalation in High-Risk Patients With AML With Febrile Neutropenia and Prolonged Neutropenia.

BACKGROUND: There is minimal data evaluating the safety of antibiotic de-escalation in patients with acute myeloid leukemia (AML) with fever and ongoing neutropenia. Therefore, this study evaluated antibiotic prescribing, infection-related outcomes, and patient outcomes of an antibiotic de-escalation initiative. PATIENTS AND METHODS: This pre-post quasiexperimental study included adult patients with AML hospitalized with febrile neutropenia. An antibiotic de-escalation guideline was implemented in January 2017, which promoted de-escalation or discontinuation of intravenous antipseudomonal ß-lactams. The primary outcome assessment was the incidence of bacterial infection in a historical control group before guideline implementation compared with an intervention group after guideline implementation. RESULTS: A total of 93 patients were included. Antibiotic de-escalation occurred more frequently in the intervention group (71.7% vs 7.5%; P<.001), which resulted in fewer days of therapy for intravenous antipseudomonal ß-lactams (14 vs 25 days; P<.001). Thirty-day all-cause mortality and length of hospitalization were not different between groups. However, the intervention group had significantly fewer episodes of Clostridioides difficile colitis (5.7% vs 27.5%; P=.007). CONCLUSIONS: Implementation of an antibiotic de-escalation guideline resulted in decreased use of intravenous antipseudomonal ß-lactams and fewer episodes of C difficile colitis, without adversely impacting patient outcomes. Additional studies are needed, preferably in the form of randomized controlled trials, to confirm these results.

Improving antibiotic use for sinusitis and upper respiratory tract infections: A virtual-visit antibiotic stewardship initiative.

BACKGROUND: Asynchronous virtual patient care is increasingly used; however, the effectiveness of virtually delivering guideline-concordant care in conjunction with antibiotic stewardship initiatives remains uncertain. We developed a bundled stewardship intervention to improve antibiotic use in E-visits for upper respiratory tract infections (URTIs). METHODS: In this before-and-after study, adult patients who completed E-visits for "cough," "flu," or "sinus symptoms" at Michigan Medicine between January 1, 2018, and September 30, 2020, were included. Patient demographics, diagnoses, and antibiotic details were collected. The multifaceted intervention occurred over 6 months. Segmented linear regression was performed to estimate the effect of the intervention on appropriate antibiotic use for URTI diagnoses (defined as no antibiotic prescribed) and sinusitis (defined as guideline-concordant antibiotic selection and duration). Regression lines were fit to data before the bundled intervention (January 2019) and after the bundled intervention (May 2019). RESULTS: In total, 5,151 E-visits were included. The intervention decreased the number of visits for flu, cough, or sinus symptoms prescribed antibiotics from 43.2% to 28.9% (P < .001). Guideline concordance of antibiotic prescriptions improved following the intervention: first-line amoxicillin-clavulanate rose from 37.9% of prescriptions to 66.1% of prescriptions (P < .001), second-line doxycycline rose from 13.8% to 22.7% (P < .001); and median duration of antibiotics decreased from 10 days to 5 days (P < .001). CONCLUSIONS: A multifaceted stewardship bundle for E-visits involving both changes in the EMR and audit and feedback improved guideline-concordant antibiotic use for URTIs. This approach can aid stewardship efforts in the ambulatory care setting with regard to telemedicine.

Antimicrobial Stewardship and the Infection Control Practitioner: A Natural Alliance.

Antibiotic overuse and misuse has contributed to rising rates of multidrug-resistant organisms and Clostridioides difficile. Decreasing antibiotic misuse has become a national public health priority. This review outlines the goals of antimicrobial stewardship, essential members of the program, implementation strategies, approaches to measuring the program's impact, and steps needed to build a program. Highlighted is the alliance between antimicrobial stewardship programs and infection prevention programs in their efforts to improve antibiotic use, improve diagnostic stewardship for C difficile and asymptomatic bacteriuria, and decrease health care-associated infections and the spread of multidrug-resistant organisms.

Monoclonal Antibodies for Early Treatment of COVID-19 in a World of Evolving SARS-CoV-2 Mutations and Variants.

Monoclonal antibodies targeting the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 spike protein are important outpatient treatment options in coronavirus disease 2019 to mitigate progression of disease and prevent hospitalization. The impact of different RBD mutations on the efficacy of the available monoclonal antibodies and processes for incorporating this impact into treatment algorithms are ill defined. Herein, we synthesize the data surrounding the impact of key RBD mutations on the efficacy of US Food and Drug Administration Emergency Use Authorized monoclonal antibodies and describe our approach at Michigan Medicine at monitoring mutation frequency in circulating virus and developing an algorithm that incorporates these data into outpatient treatment pathways.

Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). RESULTS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.

Impact of a Best Practice Advisory for Pediatric Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: Infectious diseases (ID) consultation and optimal antibiotic therapy improve outcomes in Staphylococcus aureus bacteremia (SAB). Data on strategies to improve adherence to these practices in children are limited. METHODS: This was a quasi-experimental study evaluating the impact of an electronic medical record (EMR)-based best practice advisory (BPA) for SAB, recommending ID consult and optimal antibiotic therapy based on rapid mecA gene detection. Inpatients < 21 years old with SAB before (January 2015-July 2017) and after (August 2017-December 2018) BPA implementation were included. Primary outcome was receipt of ID consult. Secondary outcomes included receipt of optimal therapy, time to ID consult and optimal therapy, recurrent SAB, and 30-day all-cause mortality. ID consultation rates pre- and postimplementation were compared using interrupted time series (ITS) analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for time to optimal therapy were calculated using Cox regression. RESULTS: We included 99 SAB episodes (70 preintervention, 29 postintervention). Preintervention, 48 (68.6%) patients received an ID consult compared to 27 (93.1%) postintervention, but this was not statistically significant on ITS analysis due to a preexisting trend of increasing consultation. Median hours to optimal therapy decreased from 26.1 to 5.5 (P = .03), most notably in patients with methicillin-sensitive S. aureus (MSSA) (42.2 to 10.8; P < .01). On Cox regression, BPA implementation was associated with faster time to optimal therapy (HR, 3.22 [95% CI, 1.04-10.01]). CONCLUSIONS: Implementation of an EMR-based BPA for SAB resulted in faster time to optimal antibiotic therapy, particularly for patients with MSSA. ID consultation increased throughout the study period and was not significantly impacted by the BPA.

Tocilizumab for treatment of mechanically ventilated patients with COVID-19.

BACKGROUND: Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). FINDINGS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. INTERPRETATION: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings.

Incorporating preauthorization into antimicrobial stewardship pharmacist workflow reduces Clostridioides difficile and gastrointestinal panel testing.

OBJECTIVE: To evaluate whether incorporating mandatory prior authorization for Clostridioides difficile testing into antimicrobial stewardship pharmacist workflow could reduce testing in patients with alternative etiologies for diarrhea. DESIGN: Single center, quasi-experimental before-and-after study. SETTING: Tertiary-care, academic medical center in Ann Arbor, Michigan. PATIENTS: Adult and pediatric patients admitted between September 11, 2019 and December 10, 2019 were included if they had an order placed for 1 of the following: (1) C. difficile enzyme immunoassay (EIA) in patients hospitalized >72 hours and received laxatives, oral contrast, or initiated tube feeds within the prior 48 hours, (2) repeat molecular multiplex gastrointestinal pathogen panel (GIPAN) testing, or (3) GIPAN testing in patients hospitalized >72 hours. INTERVENTION: A best-practice alert prompting prior authorization by the antimicrobial stewardship program (ASP) for EIA or GIPAN testing was implemented. Approval required the provider to page the ASP pharmacist and discuss rationale for testing. The provider could not proceed with the order if ASP approval was not obtained. RESULTS: An average of 2.5 requests per day were received over the 3-month intervention period. The weekly rate of EIA and GIPAN orders per 1,000 patient days decreased significantly from 6.05 ± 0.94 to 4.87 ± 0.78 (IRR, 0.72; 95% CI, 0.56-0.93; P = .010) and from 1.72 ± 0.37 to 0.89 ± 0.29 (IRR, 0.53; 95% CI, 0.37-0.77; P = .001), respectively. CONCLUSIONS: We identified an efficient, effective C. difficile and GIPAN diagnostic stewardship approval model.

Stewardship-Hospitalist Collaboration.

Hospitalists represent a rapidly emerging specialty group that treats a large proportion of hospitalized patients with infections. Antimicrobial stewardship programs and hospitalist groups that focus on building a collaborative approach have been extremely successful in optimizing antimicrobial prescribing and improving patient outcomes. We discuss the tools needed to build collaborative relationships, summarize published examples of successful stewardship-hospitalist collaboration, and provide guidance on developing collaborative interventions.

A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections.

BACKGROUND: We sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI). METHODS: Retrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (≥ 72 h) for ABSSSI and ≥ one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on renal replacement therapy or AKI at baseline, were excluded. The primary outcome was V-AKI by the vancomycin guidelines criteria. RESULTS: In total, 415 patients were included. V-AKI occurred in 39 (9.4%) patients. Independent risk factors for V-AKI were: chronic alcohol abuse (aOR 4.710, 95% CI 1.929-11.499), no medical insurance (aOR 3.451, 95% CI 1.310-9.090), ICU residence (aOR 4.398, 95% CI 1.676-11.541), Gram-negative coverage (aOR 2.926, 95% CI 1.158-7.392) and vancomycin duration (aOR 1.143, 95% CI 1.037-1.260). Based on infection severity and comorbidities, 34.7% of patients were candidates for oral antibiotics at baseline and 39.3% had non-purulent cellulitis which could have been more appropriately treated with a beta-lactam. Patients with V-AKI had significantly longer hospital lengths of stay (9 vs. 6 days, p = 0.001), higher 30-day readmission rates (30.8 vs. 9.0%, p < 0.001) and increased all-cause 30-day mortality (5.1 vs. 0.3%, p = 0.024) CONCLUSIONS: V-AKI occurred in approximately one in ten ABSSSI patients and may be largely prevented by preferential use of oral antibiotics whenever possible, using beta-lactams for non-purulent cellulitis and limiting durations of vancomycin therapy.

Long-term risk of hepatocellular carcinoma mortality in 23220 hospitalized patients treated with micafungin or other parenteral antifungals.

BACKGROUND: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up. METHODS: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs. RESULTS: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04-2.24). CONCLUSIONS: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study.

ß-Lactam vs Non-ß-Lactam Antibiotics and Surgical Site Infection in Colectomy Patients.

BACKGROUND: Surgical site infections (SSIs) represent a significant preventable source of morbidity, mortality, and cost. Prophylactic antibiotics have been shown to decrease SSI rates, and ß-lactam antibiotics are recommended by national guidelines. It is currently unclear whether recommended ß-lactam and recommended non-ß-lactam antibiotic regimens are equivalent with respect to SSI risk reduction in colectomy patients. STUDY DESIGN: We conducted a retrospective cohort study of SSI rates between prophylactic intravenously administered recommended ß-lactam and non-ß-lactam in colectomy patients (25 CPT codes) collected by the Michigan Surgical Quality Collaborative from January 2013 to February 2018. Surgical site infection rates were compared as a dichotomous variable (no SSI vs SSI). Mixed-effects regression was used to compare the association between receiving a ß-lactam or non-ß-lactam antibiotic and likelihood of having an SSI. RESULTS: Of 9,949 patients, 9,411 (94.6%) received ß-lactam antibiotics and 538 (5.4%) received non-ß-lactam antibiotics. Overall, there were 622 (6.3%) patients with SSIs. Of the patients receiving ß-lactam antibiotics, SSIs developed in 571 (6.1%) compared with 51 (9.5%) patients in the non-ß-lactam group. After applying mixed-effects logistic regression, prophylactic treatment with a non-ß-lactam regimen was associated with significantly higher odds of surgical site infection (odds ratio 1.65; 95% CI 1.20 to 2.26; p < 0.01). CONCLUSIONS: Colectomy patients receiving ß-lactam antibiotics had a lower likelihood of SSI compared with those receiving non-ß-lactam antibiotics, even when antibiotics were compliant with national recommendations. Our findings suggest that surgeons should prescribe ß-lactam antibiotics for prophylaxis whenever possible, reserving alternatives for those rare patients with true allergies or clinical indications for non-ß-lactam antibiotic prophylaxis.

Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study.

Background: Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration. Objective: To examine predictors and outcomes associated with excess duration of antibiotic treatment. Design: Retrospective cohort study. Setting: 43 hospitals in the Michigan Hospital Medicine Safety Consortium. Patients: 6481 general care medical patients with pneumonia. Measurements: The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care-associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment. Results: Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge. Limitation: Retrospective design; not all patients could be contacted to report 30-day outcomes. Conclusion: Patients hospitalized with pneumonia often receive excess antibiotic therapy. Excess antibiotic treatment was associated with patient-reported adverse events. Future interventions should focus on whether reducing excess treatment and improving documentation at discharge improves outcomes. Primary Funding Source: Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program.