Immunogenicity of heterologous prime/boost inactivated and mRNA COVID-19 vaccine

Introduction: In August 2021, Thailand imported the BNT162b2 mRNA COVID-19 vaccine. The prioritised group to receive the BNT162b2 vaccine were health professionals. The BNT162b2 vaccine scheduled for healthcare workers were two-dose regimen administered three weeks apart, the third dose booster in two-dose inactivated CoronaVac vaccine recipients or as a second dose in health professionals who had received the CoronaVac or adenoviral-vectored (ChAdOx1-S) vaccine as the first dose regardless of the interval between the first and second dose. Methods: This study aims to evaluate the immunogenicity of the heterologous prime boost CoronaVac followed by BNT162b2 in health professionals. Results: The CoronaVac/BNT162b2 vaccine recipients elicited higher neutralizing activity against the original Wuhan and all variants of concern than in the recipients of the two-dose CoronaVac. Conclusions: The heterologous CoronaVac/BNT162b2 could be used as an alternative regimen in countries experiencing the vaccine shortages and in individuals experiencing the adverse events following CoronaVac.

Complete Remissions to PD-1 Blockade in Combination with Reduced-Dose ICE Chemotherapy in Two Cases of Relapsed or Refractory Classical Hodgkin Lymphoma with Bulky Lung Involvement after Failed PD-1 Blockade

Objective: To report 2 cases of relapsed or refractory classical Hodgkin lymphoma with bulky lung involvement who failed PD-1 blockade, obtained long-term complete remission after treatment with PD-1 blockade in combination with ICE chemotherapy, and provide an alternative regimen for this kind of patient. Methods: The clinical data of 2 patients suffering refractory or relapsed Hodgkin's lymphoma with bulky lung involvement who were resistant to PD-1 monoclonal antibody were collected, the treatment processes, efficacy and toxic side effects of the patients were summarized. Results: Both HL patients relapsed after multi-line chemotherapies and radiotherapy. One patient relapsed after autologous hematopoietic stem cell transplantation. The main manifestations were cough and dyspnea caused by large lung masses. Both patients received 3 kinds of PD-1 blockade. One progressed after stopping Nivolumab and enrolled the clinical trial of decitabine and Camrelizumab for 6 courses and got stable disease（SD）, then changed to Camrelizumab combined with ICE for 4 cycles and obtain complete metabolic remission（CMR）. The other patient progressed with Nivolumab or Camrelizumab combined with A (B) VD regimen, and 2 courses of BV. She was then treated with Sintilimab combined with ICE for 4 cycles and obtain CMR. Both patients' cough and dyspnea were significantly improved, and lung lesions were significantly reduced after receiving 1 cycle of PD-1 blockade with ICE regimen and the quality of life was greatly improved. After 4 courses of treatment, the PET/CT assessment achieved CMR. The main side effect was a second-degree bone marrow suppression and can be tolerable for the patient. Conclusion: PD-1 blockade combined with ICE regimen chemotherapy has significant curative effect and mild adverse reactions, can be used to treat cases of relapsed or refractory classic HL with bulky lung involvement resistant to PD-1 blockade. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

1125. Decreasing Concomitant Vancomycin and Piperacillin-Tazobactam Use in Children to Reduce Incidence of Acute Kidney Injury

Background Concomitant use of vancomycin (V) and piperacillin-tazobactam (PT) is associated with increased incidence of acute kidney injury (AKI). AKI develops 3 times faster on this combination compared to alternative vancomycin combinations. We sought to reduce AKI in our patients by reducing concomitant use of V/PT using a QI framework. Methods We implemented several PDSA cycles to reduce concomitant V/PT use at a 415-bed quaternary children’s hospital in Boston, MA. Interventions included substitution of PT with other agents in surgical prophylaxis guidelines and order sets starting in February 2020 and in the hospital-wide sepsis order set in March 2021. The Antimicrobial Stewardship Program reinforced these changes during daily audit-and-feedback reviews. In November 2020, we implemented an electronic alert that apprises clinicians of the AKI risk when V/PT are ordered and recommends an alternative regimen. We measured the monthly number of patients on combination V/PT, new exposures to nephrotoxic medications, AKI events, and the percentage of days with serum creatinine monitoring for patients on ≥2 nephrotoxic medications. Results From 02/01/20 to 05/31/21, the number of patients exposed to combination V/PT decreased from 23 to 6 per month (Figure 1). New nephrotoxic medication exposures declined from 17.1 to 7.7 per 1,000 patient days, and AKI events dropped from 2.8 to 0.6 per 1,000 patient days (Figures 2 and 3). The percentage of days with serum creatinine monitoring increased from 60% to 66%. Rate of New Exposures to Nephrotoxic Medications per 1000 Patient Days Conclusion Revising guidelines and electronic order sets and implementing an order alert led to marked decreases in exposures to V/PT and nephrotoxic medications overall and was associated with reduced AKI events. Use of electronic health record tools is an effective way to drive safer antimicrobial use. Disclosures Gabriella S. Lamb, MD, MPH, Nothing to disclose

SURVEY ON THE USE OF CARBAPENEM ANTIBIOTICS AT CAN THO CHILDREN’S HOSPITAL

Objective: To survey the use of carbapenem antibiotics at Can Tho Children’s Hospital. Objects and methods: Retrospective-descriptive study on 140 medical records of patients being treated at departments of Can Tho Children’s Hospital during the period from June 1st, 2020 to December 31st, 2020. Results: 26.43% of carbapenems were indicated empirically initiate, 73.57% of carbapenem was indicated in alternative regimens as the presence of microbiological results or worsened or impaired patient status. Carbapenem was mainly used in combination regimens. The proportion of the combination in the initiation regimen was 100%. In which, the proportion of combination regimen between carbapenem and an antibiotic (or vancomycin or gentamicin) was mainly. The rate of combination of three antibiotics was 18.9%. In the replacement regimen, the proportion of combination regimen was 79.6%. Of these, 57.3% of the carbapenem was combined with another antibiotic, most of which was combined with vancomycin. Combination regimen of three or four antibiotics accounted for a low percentage. Conclusion: 26.43% of carbapenem was indicated empirically initiate, 73.57% of carbapenem was indicated in an alternative regimen in the presence of microbiological results or worsened or impaired patient status. Carbapenem was mainly used in combination regimens.

The efficacy and safety of intravenous lincosamide therapy in methicillin-resistant Staphylococcus aureus bacteremia

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia has a high case-fatality rate, but currently recommended antimicrobial therapies have many shortcomings. The efficacy and safety of lincosamide therapy for MRSA bacteraemia is incompletely defined. Materials and methods: A retrospective audit of the management of all adults with MRSA bacteraemia at an Australian tertiary-referral hospital between 1 January 2007 and 31 December 2020. Results: 176 patients were included. The case-fatality rate declined from 14/57 (25%) in the first half of the study to 12/119 (10%) in the second half (p=0.01). Of the 172 patients receiving antibiotics, 62 (36%) received a lincosamide-predominant regimen (lincosamide monotherapy for >50% of the intravenous course). The patients receiving lincosamide-predominant intravenous therapy had lower in-hospital mortality (odds ratio (OR): 0.07 (95% confidence interval (CI): 0.01-0.53), p=0.01) and a lower incidence of renal complications (OR (95% CI): 0.34 (0.15-0.75), p=0.008) than patients receiving an alternative regimen. In multivariate analysis that also considered age, disease severity, comorbidity, infectious diseases consultation, source control and the year of admission, patients receiving a lincosamide-predominant regimen were still less likely to die in hospital than those receiving an alternative regimen (OR (95% CI): 0.05 (0.00-0.65), p=0.02). Conclusions: Lincosamides appear to have utility - at least as stepdown therapy - in the treatment of MRSA bacteremia, particularly in young, clinically stable patients with few comorbidities in whom endocarditis has been excluded. Prospective studies will help define their optimal role.

CASE SERIES OF PATIENTS UNDER BIWEEKLY TREATMENT WITH LARONIDASE: A REPORT OF A SINGLE CENTER EXPERIENCE

ABSTRACT Objective: To report the stabilization of urinary glycosaminoglicans (GAG) excretion and clinical improvements in patients with mucopolysaccharidosis type I (MPS I) under an alternative dose regimen of laronidase of 1.2 mg/kg every other week. Methods: We participated in a dose-optimization trial for laronidase in MPS-I patients using four alternative regimens: 0.58 mg/kg every week, 1.2 mg/kg every two weeks, 1.2 mg/kg every week and 1.8 mg/kg every other week (EOW). After the trial ended, the patients resumed the recommended dose and regimen of 0.58 mg/kg every week. Under this regimen, some patients presented difficulties in venous access and were unable to commute weekly to the treatment center. Therefore, we used an alternative regimen that consisted of 1.2 mg/kg EOW in eight patients. A retrospective study of medical records of MPS-I patients who underwent both enzyme replacement therapy (ERT) regimens, of 0.58 mg/kg every week and 1.2 mg/kg EOW, was done. Results: Patients remained clinically stable under the alternative regimen, did not present elevation of urinary GAG nor any adverse event. Conclusions: The switch of dose regimen to 1.2 mg/kg EOW of laronidase was safe, and did not cause any clinical worsening in patients who had been previously under standard dose ERT.