Analysis of two sequential SARS-CoV-2 outbreaks on a haematology-oncology ward and the role of infection prevention.

Two SARS-CoV-2 nosocomial outbreaks occurred on the haematology ward of our hospital. Patients on the ward were at high risk for severe infection because of their immunocompromised status. Whole Genome Sequencing proved transmission of a particular SARS-CoV-2 variant in each outbreak. The first outbreak (20 patients/31 healthcare workers (HCW)) occurred in November 2020 and was caused by a variant belonging to lineage B.1.221. At that time, there were still uncertainties on mode of transmission of SARS-CoV-2, and vaccines nor therapy were available. Despite HCW wearing II-R masks in all patient contacts and FFP-2 masks during aerosol generating procedures (AGP), the outbreak continued. Therefore, extra measures were introduced. Firstly, regular PCR-screening of asymptomatic patients and HCW; positive patients were isolated and positive HCW were excluded from work as a rule and they were only allowed to resume their work if a follow-up PCR CT-value was ≥30 and were asymptomatic or having only mild symptoms. Secondly, the use of FFP-2 masks was expanded to some long-lasting, close-contact, non-AGPs. After implementing these measures, the incidence of new cases declined gradually. Thirty-seven percent of patients died due to COVID-19. The second outbreak (10 patients/2 HCW) was caused by the highly transmissible omicron BA.1 variant and occurred in February 2022, where transmission occurred on shared rooms despite the extra infection control measures. It was controlled much faster, and the clinical impact was low as the majority of patients was vaccinated; no patients died and symptoms were relatively mild in both patients and HCW.

Phenytoin as seizure prophylaxis in hematopoietic stem cell transplantation with busulfan conditioning.

Background: Phenytoin is widely used as primary seizure prophylaxis in hematopoietic stem cell transplantation in patients undergoing myeloablative conditioning with busulfan. Because of the negative side effects of phenytoin, we abandoned phenytoin use in these patients. To assess the effect of this change, we performed a retrospective cohort study on all patients receiving busulfan. Methods: We included 139 patients who underwent conditioning with busulfan for hematopoietic stem cell therapy. We registered the use of phenytoin, as well as the occurrence of seizures, until 7 days after busulfan administration. We compared seizure incidence between patients who received phenytoin and those who did not. Results: Of the 43 patients who received phenytoin prophylaxis, four patients (9.3%) had a seizure during the conditioning regimen, of which two patients had cerebral non-Hodgkin lymphoma. Furthermore, all these 4 patients had very high levels of phenytoin (intoxication). Of the 96 patients that did not receive phenytoin prophylaxis, three patients (3.1%) had a seizure, and one of these patients had an undefined cerebral lesion. Phenytoin did not relate to seizure prevention in a logistic regression analysis. Conclusion: We conclude that phenytoin prophylaxis in patients treated with busulfan is obsolete and possibly harmful, as phenytoin intoxication can occur. We recommend discontinuing the use of phenytoin as primary seizure prophylaxis in these patients.

Controlling a human parainfluenza virus-3 outbreak in a haematology ward in a tertiary hospital: the importance of screening strategy and molecular diagnostics in relation to clinical symptoms.

BACKGROUND: The human parainfluenza virus 3 (HPIV-3) outbreak at the haemato-oncology ward of the Maastricht University Medical Centre in the summer of 2016. AIM: To describe an effective strategy to control the largest reported HPIV-3 outbreak at an adult haematology-oncology ward in the Netherlands by implementing infection control measures and molecular epidemiology investigation. METHODS: Clinical, patient and diagnostic data were both pro- and retrospectively collected. HPIV-3 real-time polymerase chain reaction (HPIV-3 RT-PCR) was validated using oropharyngeal rinse samples. Screening of all new and admitted patients was implemented to identify asymptomatic infection or prolonged shedding of HPIV-3 allowing cohort isolation. FINDINGS: The HPIV-3 outbreak occurred between 9 July and 28 September 2016 and affected 53 patients. HPIV-3 RT-PCR on oropharyngeal rinse samples demonstrated an up to 10-fold higher sensitivity compared with pharyngeal swabs. Monitoring showed that at first positive PCR, 20 patients (38%) were asymptomatic (of which 11 remained asymptomatic) and the average duration of shedding was 14 days (range 1-58). Asymptomatic patients had lower viral load, shorter period of viral shedding (≤14 days) and were mostly immune-competent oncology patients. The outbreak was under control five weeks after implementation of screening of asymptomatic patients. CONCLUSION: Implementation of a sensitive screening method identified both symptomatic and asymptomatic patients which had lower viral loads and allowed early cohort isolation. This is especially important in a ward that combines patients with varying immune status, because both immunocompromised and immune-competent patients are likely to spread the HPIV-3 virus, either through prolonged shedding or through asymptomatic course of disease.

Role of the environment in transmission of Gram-negative bacteria in two consecutive outbreaks in a haematology-oncology department.

In 2019-2020, two subsequent outbreaks caused by phenotypically identical ESBL-producing Enterobacter cloacae and multi-drug-resistant (MDR) Pseudomonas putida were detected in respectively 15 and 9 patients of the haematology-oncology department. Both bacterial species were resistant to piperacillin-tazobactam, used empirically in (neutropenic) sepsis in our hospital, and ciprofloxacin, used prophylactically in selective digestive decontamination for haematology patients. The E. cloacae outbreak was identified in clinical cultures of blood and urine. Despite intensified infection control measures, new cases were found in weekly point-prevalence screening cultures. Environmental samples of sinks and shower drains appeared positive in 18.1%. To diminish the environmental contamination burden, all siphons of sinks were replaced, and disinfection of sinks and shower drains was intensified using chlorine and soda on a daily basis. Replacement of shower drains was not possible. The outbreak of P. putida remained limited to rectal cultures only, and disappeared spontaneously without interventions. During both outbreaks, multiple strains of the incriminated bacterium were found simultaneously (demonstrated by Amplified-Fragment Length Polymorphism and/or Whole-Genome Multi-locus Sequencing Typing) in patients as well as the environment. It was experimentally shown that a biofilm on the toilet edge may act as a source for nosocomial transmission of Gram-negative bacteria. In conclusion, the drainage system of the hospital is an important reservoir of MDR bacteria, threatening the admitted patients. In existing hospitals, biofilms in the drainage systems cannot be removed. Therefore, it is important that in (re)building plans for hospitals a plan for prevention of nosocomial transmission from environment to patients is incorporated.

Predictors of short-term and long-term mortality in critically ill patients admitted to the intensive care unit following allogeneic stem cell transplantation.

Historically, the mortality of patients admitted to the ICU after allogeneic stem cell transplantation (alloSCT) is high. Advancements in transplantation procedures, infectious monitoring and supportive care may have improved the outcome. This study aimed to determine short-term and long-term mortality after ICU admission of patients after alloSCT and to identify prognostic clinical and transplantation-related determinants present at ICU admission for long-term outcome. A multicenter cohort study was performed to determine 30-day and 1-year mortality within 2 years following alloSCT. A total of 251 patients were included. The 30-day and 1-year mortality was 55% and 80%, respectively. Platelet count <25 × 109/L (OR: 2.26, CI: 1.02-5.01) and serum bilirubin >19 µmol/L (OR: 2.47 CI: 1.08-5.65) at admission, other donor than a HLA-matched-related or HLA-matched-unrelated donor (OR: 4.59, CI: 1.49-14.1) and vasoactive medication within 24 h (OR: 2.35, CI: 1.28-4.31) were associated with increased 30-day mortality. Other donor than a HLA-matched-related or HLA-matched-unrelated donor (OR: 1.9, CI: 1.13-3.19), serum bilirubin >77 (OR: 2.05, CI: 1.28-3.30) and vasoactive medication within 24 h (OR: 1.65, CI: 1.12-2.43) were associated with increased 1-year mortality. Neutropenia was associated with decreased 30-day and 1-year mortality (OR: 0.29, CI: 0.14-0.59 and OR: 0.70, CI: 0.48-0.98). Myeloablative conditioning and T cell-depleted transplantation were not associated with increased mortality.

Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of four treatment regimens.

Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.