The Safety of Aztreonam Versus Ceftazidime in Patients Labeled With Penicillin Allergy: A Cohort Study.

PURPOSE: Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy (PLWPA) in our institutional empirical antibiotic guidelines. Due to a global aztreonam shortage in December 2022, the antimicrobial stewardship unit recommended ceftazidime as a substitute. There is a paucity of real-world data on the safety profile of ceftazidime in PLWPA. Hence, we evaluated tolerability outcomes of ceftazidime use in PLWPA. METHODS: This retrospective cohort study compared PLWPA in Singapore General Hospital who received aztreonam (October 2022-December 2022) or ceftazidime (December 2022-February 2023). Patients were stratified according to their risk of allergic reaction (AR) based on history of penicillin allergy. The severity of AR was based on the Delphi study grading system. The primary outcome was development of AR after initiation of aztreonam or ceftazidime. The secondary tolerability outcomes include hepatotoxicity and neurotoxicity. FINDINGS: There were 168 patients in the study; 69 were men (41.1%) and the median age was 69 years (interquartile range: 59-76 years). Incidence of AR was statistically similar in both arms: 1 of 102 patients (0.98%) in the aztreonam arm vs 2 of 66 patients (3.03%) in the ceftazidime arm (P = 0.33). The patient in the aztreonam arm was deemed at medium risk of having an AR and developed localized rashes (grade 1). Both patients in the ceftazidime arm were deemed at high risk of AR and developed localized skin reaction (grade 1). Hepatotoxicity was observed in 1 patient prescribed aztreonam. No patients in the ceftazidime arm developed adverse events. IMPLICATIONS: Ceftazidime appears to be better tolerated and cheaper compared with aztreonam in PLWPA, and serves as an antimicrobial stewardship strategy to conserve broader-spectrum antibiotics use.

Stemming the Rise of Antibiotic Use for Community-Acquired Acute Respiratory Infections during COVID-19 Pandemic.

At the start of the COVID-19 pandemic, there was an increase in the use of antibiotics for the treatment of community-acquired respiratory tract infection (CA-ARI) in patients admitted for suspected or confirmed COVID-19, raising concerns for misuse. These antibiotics are not under the usual purview of the antimicrobial stewardship unit (ASU). Serum procalcitonin, a biomarker to distinguish viral from bacterial infections, can be used to guide antibiotic recommendations in suspected lower respiratory tract infection. We modified our stewardship approach, and used a procalcitonin-guided strategy to identify "high yield" interventions for audits in patients admitted with CA-ARI. With this approach, there was an increase in the proportion of patients with antibiotics discontinued within 4 days (16.5% vs. 34.9%, p < 0.001), and the overall duration of antibiotic therapy was significantly shorter [7 (6−8) vs. 6 (3−8) days, p < 0.001]. There was a significant decrease in patients with intravenous-to-oral switch of antibiotics to "complete the course" (45.3% vs. 34.4%, p < 0.05). Of the patients who had antibiotics discontinued, none were restarted on antibiotics within 48 h, and there was no-30-day readmission or 30-day mortality attributed to respiratory infection. This study illustrates the importance of the antimicrobial stewardship during the pandemic and the need for ASU to remain attuned to prescriber's practices, and adapt accordingly to address antibiotic misuse to curb antimicrobial resistance.

Clinical and economic evaluation of a surveillance protocol to manage hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

STUDY OBJECTIVE: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab. DESIGN: Prospective, single-arm study. SETTING: National Cancer Centre, Singapore. PATIENTS: Lymphoma patients with resolved HBV infection and scheduled to receive rituximab-based treatment. INTERVENTION: Close monitoring of HBV DNA levels, ie. every 4-6 weeks during rituximab treatment, every 6-8 weeks in the first year post-treatment, and every 3-4 months in the second year post-treatment. MEASUREMENTS: The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation-related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost-minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab. MAIN RESULTS: A total of 66 patients provided analyzable data with a follow-up period of 966.6 months. No hepatitis flare or reactivation-related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis. CONCLUSIONS: The surveillance protocol is an effective, feasible and cost-saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab.

Identifying Potentially Avoidable Readmissions: A Medication-Based 15-Day Readmission Risk Stratification Algorithm.

BACKGROUND: Stratifying patients according to 15-day readmission risk would be useful in identifying those who may benefit from targeted interventions during and/or following hospital discharge that are designed to reduce the likelihood of readmission. METHODS: A prediction model was derived via a case-control analysis of patients discharged from a tertiary hospital in Singapore using multivariate logistic regression. The model was validated in two independent external cohorts separated temporally and geographically. Model discrimination was assessed using the C-statistic, while calibration was assessed using the Hosmer-Lemeshow χ2 and the Brier score statistics. RESULTS: A total of 1291 patients were included with 670, 101, and 520 patients in the derivation, temporal, and geographical validation cohorts, respectively. Age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.03, p=0.008), anemia (OR 2.08, 95% CI 1.15-8.05, p=0.015), malignancy (OR 3.37, 95% CI 1.16-9.80, p=0.026), peptic ulcer disease (OR 3.05, 95% CI 1.12-8.26, p=0.029), chronic obstructive pulmonary disease (OR 3.16, 95% CI 1.24-8.05, p=0.016), number of discharge medications (OR 1.06, 95% CI 1.01-1.12, p=0.026), discharge to nursing homes (OR 3.57, 95% CI 1.57-8.34, p=0.003), and premature discharge against medical advice (OR 5.05, 95% CI 1.20-21.23, p=0.027) were independent predictors of 15-day readmission risk. The model demonstrated reasonable discrimination on the temporal and geographical validation cohorts with a C-statistic of 0.65 and 0.64, respectively. Model miscalibration was observed in both validation cohorts. CONCLUSION: A 15-day readmission risk prediction model is proposed and externally validated. The model facilitates the targeting of interventions for patients who are at high risk of an early readmission.

Real-World Impact of Setting a Narrow International Normalized Ratio Target Range in the Management of Older Adult Patients on Warfarin.

INTRODUCTION: Elderly patients intrinsically have higher bleeding risks, deterring clinicians from prescribing them oral anticoagulants. Setting a narrow international normalized ratio (INR) target range might potentially mitigate some of these risks. This study sought to compare the outcomes of elderly patients who were assigned to either a narrow INR target range or the conventional INR target range in a real-world environment. METHODS: This was a retrospective cohort study with the primary and secondary outcomes being the mean percentage time above INR 3.0 and the mean percentage time below INR 2.0 and the incidents of bleeding and thromboembolism associated with oral anticoagulant therapy, respectively. Patients and health care workers managing them had no prior knowledge of this study. RESULTS: Data of 150 patients with a narrow INR target range (2.0-2.5) and 164 patients with a conventional INR target range (2.0-3.0) were collected and analyzed. The narrow INR group had significantly higher underlying risks of bleeding than the conventional INR group. Patients in the narrow INR group had a significantly lower percentage time above INR 3.0 but no significant difference in the percentage time below INR 2.0. Adjusted incidence rate ratio (IRR) for bleeding events was significantly lower for the narrow INR group, while the adjusted IRR for thromboembolic events between both groups was similar. CONCLUSION: Patients assigned to a narrow INR target range in real-world practice spent a significantly lower amount of time below an INR of 3.0 compared to conventional INR target range with lower incidents of bleeding complications and no increase in subtherapeutic INRs.

Clinical impact of drug-drug interaction between aspirin and prednisolone at a cancer center.

BACKGROUND: Adverse gastrointestinal (GI) events are complications in aspirin and prednisolone cotherapy. The prevalence of adverse GI events would be expected to be increased with cotherapy due to the overlapping toxicities of the 2 drugs. However, there is a dearth of literature investigating how often this interaction causes clinically important adverse GI events. OBJECTIVES: This retrospective study aimed to determine the prevalence of adverse GI events associated with the coadministration of aspirin and prednisolone. The use of gastroprotectant agents was also studied. METHODS: The medical records of patients with cancer prescribed aspirin and prednisolone therapy between January 2007 and June 2011 were analyzed. The duration of aspirin-prednisolone overlap, prevalence of adverse GI events, and details on the concurrent use of other medications were evaluated. RESULTS: The study included data from 142 patients (male, 64.8%; mean [SD] age, 67.4 [11.0] years). A total of 78.9% of the patients were on some form of gastroprotectant, the most common class of which was proton pump inhibitors. The prevalence of adverse GI events was 4.2% (6 patients). Four patients had presented with GI symptoms (abdominal pain, diarrhea, dysphagia, and vomiting); 3 patients had signs of GI injury (duodenal ulcers, iron deficiency anemia, and a Mallory-Weiss tear). The Naranjo algorithm classified 5 patients experienced possible adverse drug reactions (ADRs), and 1 as a probable ADR. CONCLUSION: Our study found that the prevalence of adverse GI events was low and managed to establish a weak association between the occurrence of events and the coadministration of aspirin and prednisolone. This finding, together with the concurrent prescription of gastroprotectants, suggests that the clinical impact of the aspirin and prednisolone DDI is minimal.