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.

Discontinuation of Antibiotics in Patients with Neurological Conditions - A Study on the Impact of an Antimicrobial Stewardship Program (ASP) in a Tertiary Institution.

BACKGROUND: Up to 50% of antibiotics are prescribed either unnecessarily or inappropriately in most hospitals worldwide. In the largest tertiary hospital in Singapore, patients with neurological conditions were often initiated on antibiotics for change in mental state or isolated fevers. We hypothesize that Antimicrobial Stewardship Program (ASP) interventions to discontinue empirical antibiotics in neurological patients with no clinical evidence of bacterial infection are safe. The aim of this study was to compare clinical impact and safety outcomes of ASP interventions between accepted and rejected groups. METHODS: A retrospective review of the ASP database was conducted for all patients admitted to the neurology department in Singapore General Hospital between January 2014 and December 2017. Interventions were followed up and patients were classified into two intervention groups, the accepted and rejected groups. Demographic data, age-adjusted Charlson co-morbidity index, duration of antibiotic therapy, length of hospital stay post-ASP intervention (PLOS), infection-related readmissions and mortality were compared between the two groups. Data were expressed as mean ± standard deviation for continuous variables, and unpaired Student's t-test was performed to determine intergroup differences between mean values. RESULTS: The ASP team recommended 184 interventions, with an overall acceptance rate of 82.6% (152/184). There was no significant difference in demographics and age-adjusted Charlson co-morbidity index between the two groups. The accepted group had a shorter duration of therapy by 1.67 days (4.99±2.50 days vs. 6.66±2.34 days; P<0.01) and a shorter PLOS by 2 days, although this was not statistically significant (22.5±22.2 days vs. 24.5±51.4 days; P=0.83). There were no significant differences between the two groups in 14-day mortality and readmission rates. CONCLUSION: In neurological patients with no clinical evidence of bacterial infections, ASP interventions to discontinue empirical antibiotics were not associated with increased mortality and readmissions but were associated with significant reduction in duration of therapy.

Discontinuation of antibiotic therapy within 24 hours of treatment initiation for patients with no clinical evidence of bacterial infection: a 5-year safety and outcome study from Singapore General Hospital Antimicrobial Stewardship Program.

BACKGROUND: Overprescribing antibiotics for patients with no bacterial infection is of growing global concern. It is important for timely Antimicrobial Stewardship Program (ASP) intervention to discontinue antibiotics for patients whose symptoms can be explained by non-infective causes, and without availability of bacterial cultures and susceptibilities reports. This study aimed to evaluate clinical outcomes and safety of early ASP review in these patients. METHODS: A retrospective review of the ASP database (January 2010 to December 2014) was conducted to identify patients for whom ASP recommended discontinuation of empiric antibiotics within 24 hours of prescribing. Demographics were collected. Clinical outcomes - duration of therapy, length of hospital stay (LOS), infection-related readmissions, and all-cause mortality - were compared between interventions accepted and rejected groups. Continuous data were analysed via unpaired Student's t-test. Categorical data were analysed using χ2 test or Fisher's exact test, as appropriate. RESULTS: The ASP team recommended 794 interventions (overall acceptance rate of 72.9%, 579 of 794). There were no significant between-group differences in underlying demographics, and Charlson comorbidity index score. However, the interventions acceptance group had significantly shorter duration of therapy by 2.61 days (2.72 ± 3.04 vs. 5.33 ± 2.54 days; P < 0.01) and LOS by 7.41 days (7.98 ± 13.14 vs. 15.39 ± 22.62 days; P < 0.01), with estimated cost savings of SGD10 817 per patient. There were no significant between-group differences in 14-day mortality and readmission rates. CONCLUSION: Prompt ASP interventions at Singapore General Hospital were associated with significant reductions in duration of therapy and LOS, with cost savings. It was demonstrated that it is safe to discontinue antibiotics within 24 hours of prescribing for patients with no evidence of bacterial infections.

Impact of Antimicrobial Stewardship Program (ASP) on Outcomes in Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) in an Acute-Tertiary Care Hospital.

INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSSIs) are among the most common infections treated in hospitals, but to date, there has been little information with regards to the implementation of Antimicrobial Stewardship Programs (ASPs) for patients with ABSSSIs. Hence, we aim to evaluate the impact of ASPs on the following outcomes in patients with ABSSSIs: duration of therapy and hospital stay, 14-day reinfection, infection-related readmissions and mortality. METHODS: A retrospective review of the ASP database was conducted, focusing on selected outcomes (as above) among all patients in whom the institution's ASP recommended a change in antibiotic regimen-de-escalation of the antibiotic based on culture results; discontinuation of the antibiotic; narrowing of the empirical coverage; and intravenous-to-oral (i.v.-to-p.o.) switch between September 2009 and December 2012. Data were expressed as mean ± standard deviation for continuous variables, and unpaired Student's t test was performed to determine intergroup differences between mean values. For categorical variables, data were presented as number and percentage and analyzed using the χ (2) test or Fisher's exact test, as appropriate. RESULTS: ASP recommended 407 interventions with an overall acceptance rate of 66.8%. ASP interventions significantly reduced median duration of therapy by 2 [from a median (interquartile range, IQR) of 8 (6-12) days to 6 (4-9) days] and median length of stay by 5 days [from median (IQR) of 12 (5-32) days to 7 (3-18) days]. This led to an estimated total cost avoidance of USD 0.7 million. There were no significant differences in the 14-day reinfection, infection-related readmission and mortality rates between patients whose physicians accepted and those who rejected ASP interventions. CONCLUSION: Interventions recommended by the ASP in Singapore General Hospital were safe and associated with a significant reduction in duration of therapy and hospital stay. The results of our study have affirmed the role of ASP in optimizing the care of patients with ABSSSI.

Microbiology and audit of vascular access-associated bloodstream infections in multi-ethnic Asian hemodialysis patients in a tertiary hospital.

BACKGROUND: In view of high mortality and morbidity rates associated with vascular access-associated bloodstream infection (VAABSI) in hemodialysis patients, clinical practice guidelines recommend empiric antibiotic therapy for suspected vascular access-related infections. We aim to describe the microbiology of confirmed VAABSI and evaluate the choice of empiric antibiotics, and whether they are prescribed in concordance with the in-house antibiotic guidelines. METHODS: This was a single-center, retrospective, observational study conducted in a tertiary hospital. All adult hemodialysis patients aged 21 years and above who had confirmed VAABSI with positive blood culture results dated from January 2011 to June 2012 were recruited. Relevant information was retrieved electronically from the hospital patient online database, SCM 5.5 Sunrise Enterprise Gateway. RESULTS: A total of 144 episodes of VAABSI were recorded from 118 patients. Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) accounted for 64.2% (68/106) of the gram-positive infections. Gram-negative organisms grew in 26.4% (38/144) of blood cultures and Pseudomonas aeruginosa was the most common organism isolated. The recommended in-house guideline was used as empiric therapy in 24 episodes of VAABSI (16.7%). Five patients died due to VAABSI and none were prescribed antibiotics in concordance with in-house guidelines. CONCLUSIONS: Empiric antibiotics against MSSA and MRSA, as well as gram-negative organisms, especially P. aeruginosa, should be used in patients with suspected vascular access-related infections in our institution. Monitoring of microbiological profile is necessary to guide timely administration of appropriate empiric antibiotics. Further studies are necessary to evaluate the relationship between adherence to in-house guidelines and patients' outcomes.