Evaluation of early de-escalation of empiric antimicrobial therapy in acute leukemia patients with febrile neutropenia at a large academic medical center

Introduction Recent trials have shown early de-escalation of empiric antimicrobial therapy (EAT) in febrile neutropenia has led to less adverse effects with no difference in patient mortality. In 2019, our institution adjusted internal guidelines to de-escalate EAT after 7 days of intravenous anti-pseudomonal therapy in patients with signs of clinical recovery from febrile neutropenia and no evidence of infection. Methods This was a retrospective, single-center, observational, cohort study. Eligible patients were adults with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who received induction chemotherapy and developed febrile neutropenia without documented infection. Patients were separated based on EAT duration: ≤ 9 days and > 9 days. Empiric antimicrobial therapy was defined as the initiation of an anti-pseudomonal beta-lactam. The primary outcome was the difference in number of EAT-free days. Secondary outcomes included fever recurrence, ICU admissions, fever duration, infections post de-escalation, and Clostridioides difficile infection (CDI). Results Forty-four encounters met inclusion. The EAT ≤ 9 days group had 7 more EAT-free days compared to the EAT > 9 days group (p < 0.001). No between-group differences were identified in terms of fever after EAT discontinuation (p = 0.335), ICU admission (p = 0.498), or CDI (p = 0.498). The EAT > 9 days group experienced longer initial fever (p < 0.001) and received addition of resistant Gram-positive coverage (p = 0.014). More patients receiving EAT > 9 days had a diagnosis of AML (p = 0.001). Conclusions Shorter EAT duration did not lead to worse outcomes in patients with AML or ALL who received induction chemotherapy and developed febrile neutropenia without a documented infection source.

Characterization of Antibiotic Use, Documented Infection and Prevalence of Multidrug-Resistant Organisms in Palliative Care Patients Admitted to a Private Hospital in Brazil: A Retrospective, Cohort Study

Objectives: Antibiotic use in palliative care patients is a frequent dilemma. The benefits of their use in terms of quality of end-of-life care or survival improvement are not clear and the potential harm and futility of this practice not well established. Our aim was to characterise the prevalence of antibiotic use, documented infection and multidrug-resistant organisms (MDROs) colonisation among palliative care patients admitted to a private hospital in Brazil. Materials and Methods: Retrospective analysis of all palliative care patients admitted to our hospital during 1 year, including demographic characteristics, diagnosis of infectious disease at admission, antibiotic use during hospital stay, infectious agents isolated in cultures, documented MDRO colonisation and hospital mortality. Results: A total of 114 patients were included in the analysis. Forty-five (39%) were male and the median age was 83 years. About 78% of the patients had an infectious diagnosis at hospital admission and 80% of the patients not admitted with an infectious diagnosis used antibiotics during their stay, out of which a great proportion of large spectrum antibiotics. Previous MDRO colonisation and hospital mortality were similar between patients admitted with or without an infectious diagnosis. Conclusion: Infection is the leading cause of hospital admission in palliative care patients. However, antibiotics prescription is also very prevalent during hospital stay of patients not admitted with an infectious condition. Mortality is very high regardless of the initial reason for hospital admission. Therefore, the impact of multiple large spectrum antibiotics prescription and consequent significant cost burden should be urgently confronted with the real benefit to these patients.

Rapid reinfection with SARS-CoV-2 variant-of-concern Alpha detected in a nurse during an outbreak at a non-covid inpatient ward: lessons learned

We describe the lessons learned during a SARS-CoV-2 variant-of-concern Alpha outbreak investigation at a normal care unit in a university hospital in Amsterdam in December 2020. The outbreak consisted of nine nurses and two roomed-in patient family members. (attack rate 18%). One nurse tested positive with a phylogenetically distinct variant, after a documented infection 83 days prior. Three key points were taken from this investigation. First, it was controlled by adherence to existing guidelines, despite increased transmissibility of the variant. Second, viral sequencing can inform transmission cluster inference, but the epidemiological context is essential to draw appropriate conclusions. Third, reinfections with Alpha variants can occur rapidly after primary infection.

Effectiveness of the BNT162b2 mRNA COVID-19 Vaccine in Pregnancy

Background: As mass vaccination campaigns against COVID-19 accelerate worldwide, there remains only limited evidence regarding vaccine effectiveness (VE) among pregnant women. Pregnant women have been shown to be at risk for severe COVID-19, resulting in adverse obstetrics outcomes, and their immune system is known to undergo alterations during pregnancy. Phase III clinical trials of the approved mRNA COVID-19 vaccines excluded pregnant women, yet current guidelines encourage offering the vaccine to pregnant women. In this study, we examine data from Israel’s largest healthcare organization to evaluate the effectiveness of the BNT162b2 mRNA vaccine among pregnant women. Methods: We conducted an observational cohort study of pregnant women 16 years or older, with no history of SARS-CoV-2, who were vaccinated between December 20, 2020 and June 3, 2021. Vaccinated subjects were matched to unvaccinated controls according to a set of demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. For each outcome, VE was estimated at several periods following vaccination as one minus the risk ratio using the Kaplan–Meier estimator. Results: 10,861 vaccinated women were matched to an identical number of unvaccinated controls. Estimated VE from 7 through 28 days after the second dose was 97% (95% CI 91%-100%) for any documented infection, 96% (86-100%) for infections with documented symptoms, and 85% (32%-100%) for COVID-19-related hospitalization. Only one event of severe illness was observed in the unvaccinated group, and no deaths were observed in either group -- insufficient incidence for estimating VE for these outcomes. Discussion: The BNT162b2 mRNA vaccine was found to have high VE among pregnant women. Since high VE has been reported as one of the strongest predictors of COVID-19 vaccine acceptance among pregnant women, the high VE estimates found in this study have the potential to increase vaccine acceptance in this group. In addition, the present VE estimates are similar to those reported in the general population for the same variants, suggesting that it may be possible to infer the VE for pregnant women from studies in the general population for both current and future variants.

Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: A three-month nationwide experience from Israel

Worldwide shortage of vaccination against SARS-CoV-2 infection while the pandemic is still uncontrolled leads many states to the dilemma whether or not to vaccinate previously infected persons. Understanding the level of protection of previous infection compared to that of vaccination is critical for policy making. We analyze an updated individual-level database of the entire population of Israel to assess the protection efficacy of both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with COVID-19, severe disease, and death due to COVID-19. Vaccination was highly effective with overall estimated efficacy for documented infection of 92·8% (CI:[92·6, 93·0]); hospitalization 94·2% (CI:[93·6, 94·7]); severe illness 94·4% (CI:[93·6, 95·0]); and death 93·7% (CI:[92·5, 94·7]). Similarly, the overall estimated level of protection from prior SARS-CoV-2 infection for documented infection is 94·8% (CI:[94·4, 95·1]); hospitalization 94·1% (CI:[91·9, 95·7]); and severe illness 96·4% (CI:[92·5, 98·3]). Our results question the need to vaccinate previously-infected individuals.

The Pattern of Microorganisms and Drug Susceptibility in Pediatric Oncologic Patients with Febrile Neutropenia

Objective. The study aimed to describe the pattern of causative microorganisms, drug susceptibility, risk factors of antibiotic-resistant bacterial infection, and clinical impact of these organisms on pediatric oncology patients with febrile neutropenia. Methods. A retrospective descriptive study of oncologic patients aged less than 15 years who were diagnosed with febrile neutropenia in King Chulalongkorn Memorial Hospital was conducted between January 2013 to December 2017. Characteristics and clinical outcomes of febrile neutropenia episodes, causative pathogens, and their antibiotic susceptibilities were recorded. Result. This study included 267 patients with 563 febrile neutropenia episodes. The median (range) age was 5.1 years (1 month–15 years). The most common underlying disease was acute lymphoblastic leukemia (42.7%). Of 563 febrile episodes, there were 192 (34.1%) with microbiologically documented infection. Among these 192 episodes of microbiologically documented infection, there were 214 causative pathogens: 154 bacteria (72%), 32 viruses (15%), 27 fungus (12.6%), and 1 Mycobacterium tuberculosis (0.4%). Gram-negative bacteria (48.6%) accounted for most of the causative pathogens. Twenty-three percent of them were multidrug resistant, and 18% were carbapenem resistant. Among Gram-positive bacterial infection which accounted for 23.4% of all specimens, the proportion of MRSA was 20%. The 2-week mortality rate was 3.7%. Drug-resistant Gram-negative bacterial infection caused significant adverse events and mortality compared to nonresistant bacterial infection ( p < 0.05 ). Conclusion. There is high rate of drug-resistant organism infection in pediatric oncology patients in a tertiary-care center in Thailand. Infection with drug-resistant Gram-negative bacterial infection was associated with significant morbidity and mortality. Continuous surveillance for the pattern of drug-resistant infections is crucial.

Procalcitonin and C-Reactive Protein/Procalcitonin Ratio as Markers of Infection in Patients With Solid Tumors

Objectives: The roles of procalcitonin (PCT) and C-reactive protein (CRP) in febrile cancer patients is currently unclear. Our aim was to assess these in febrile patients with solid tumors and to identify cut-off values for ruling out infection.Methods: We retrospectively evaluated patients with solid tumors admitted to hospital due to fever. They were divided into those with Fever with microbiologically documented infection (FMDI), Fever with clinically documented infection (FCDI) and Tumor-related fever (TRF). PCT and CRP levels were compared. Receiver-operating curves were plotted to define the best cut-off values for discriminating between infection-related and cancer-related fever.Results: Between January 2015 to November 2018, 131 patients were recorded (mean age 68 years, 67% male, 86% with metastasis). Patients with FMDI or FCDI had significantly higher baseline levels of PCT and lower CRP/PCT than those with TRF. A PCT cut-off value of 0.52 ng/mL for discriminating between infection and cancer-associated fever yielded 75% sensitivity, 55% specificity, 77% positive predictive value (PPV), and 52% negative predictive value (NPV). A CRP/PCT ratio with a cut-off value of 95 showed 56% sensitivity, 70% specificity, 79% NPV, and 44% PPV.Discussion: PCT is a sensitive marker of sepsis or localized infection in patients with solid tumors, but its specificity is poor. The CRP/PCT ratio improves specificity, thus providing a reliable means of ruling out infection for values above 95.

Incidence of infections during the application of high-dose chemotherapy with autologous stem cell transplantation

Introduction: Autologous stem cell transplantation (AHSCT) is a well-established therapy for hematologic malignancies. Changes in transplantation strategies and improvement in supportive care have significantly altered the incidence and pattern of infections in these patients. Aim: Evaluating the frequency of infections in the first 30 days after AHSCT, as well as the possible influence of the number of CD34 + stem cells in the graft and of the engraftment parameters: ALC500_20 (absolute lymphocyte count 0.5x109 / L per day + 20), ANC500_11 (absolute neutrophil count 0.5x109 / L per day + 11), and PLT20_13 (platelets 20x109 / L per day + 13), on the occurrence of infections. Materials and methods: The retrospective cohort study examined 80 patients above the age of 20 years, diagnosed with multiple myeloma (MM), non-Hodgkin's (NHL) or Hodgkin's lymphoma (HL), treated at the Clinic for Hematology of the Clinical Center of Serbia, in the period between July 2006 and December 2017. All episodes of fever and/or documented infection during neutropenia have been reported. Results: The average survival after AHSCT was 34.5 months. A total of 54 patients (67.5%) had a documented infection. Gram-positive infections were five times more common than gram-negative. In gram-positive isolates, coagulase-negative staphylococcus - CoNS was the most common (37.0%) pathogen, followed by Streptococcus a haemolyticus (12.4%). Among gram-negative isolates, Escherichia coli was present in 62.5% of the cases, while Klebsiellaspp. and Ralstonia pickettii were represented with an equal frequency of 12.5%. Fungal infections were rare (Candida spp., 10.0%). Viral infections were verified in 5 (6.3%) patients (Herpes zoster virus 3.8% and H1N1 2.5%). Conclusion: The number of CD34+ stem cells in the graft, as well as the rate of hematopoietic reconstitution, i.e., the achievement of ALC500_20, ANC500_11, and PLT20_13, were not statistically significant for the development of infections in the early phase after AHSCT.