COVID-19 in hematopoietic stem cell transplant recipients during three years of the pandemic: a multicenter study in Brazil

ABSTRACT Hematopoietic stem cell transplant (HSCT) recipients are at -increased risk for severe COVID-19. The aim of this study was to evaluate the burden of COVID-19 in a cohort of HSCT recipients. This retrospective study evaluated a cohort of adult hospitalized HSCT recipients diagnosed with COVID-19 in two large hospitals in São Paulo, Brazil post-HSCT, from January 2020 to June 2022. The primary outcome was all-cause mortality. Of 49 cases, 63.2% were male with a median age of 47 years. Allogeneic-HSCT (51.2%) and autologous-HSCT (48.9%) patients were included. The median time from HSCT to COVID-19 diagnosis was 398 days (IQR: 1211-134), with 22 (44.8%) cases occurring within 12 months of transplantation. Most cases occurred during the first year of the pandemic, in non-vaccinated patients (n=35; 71.4%). Most patients developed severe (24.4%) or critical (40.8%) disease; 67.3% received some medication for COVID-19, primarily corticosteroids (53.0%). The probable invasive aspergillosis prevalence was 10.2%. All-cause mortality was 40.8%, 51.4% in non-vaccinated patients and 14.2% in patients who received at least one dose of the vaccine. In the multiple regression analyses, the variables mechanical ventilation (OR: 101.01; 95% CI: 8.205 - 1,242.93; p = 0.003) and chest CT involvement at diagnosis ≥50% (OR: 26.61; 95% CI: 1.06 - 664.26; p = 0.04) remained associated with all-cause mortality. Thus, HSCT recipients with COVID-19 experienced high mortality, highlighting the need for full vaccination and infection prevention measures.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation

ABSTRACT Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review

ABSTRACT Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation

ABSTRACT The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

Streptococcus constellatus causing concomitant extra and intracranial abscesses complicated with sagittal sinus thrombosis

ABSTRACT Streptococcus constellatus is a gram-positive coccus member of the Streptococcus anginosus group (SAG). It can be found in the oral flora, and may cause abscess more commonly in the gastrointestinal tract, lungs, and heart. Brain abscesses are severe neurological infections with high mortality rates. Streptococcus species other than S. pneumoniae are rare causes of brain abscesses. This case report highlights a severe case of extra and intracranial abscesses due to S. constellatus in an immunocompetent host

COVID-19 and isolation: Risks and implications in the scenario of new variants

Abstract With the emergence of new variants of SARS-CoV-2, questions about transmissibility, vaccine efficacy, and impact on mortality are important to support decision-making in public health measures. Modifications related to transmissibility combined with the fact that much of the population has already been partially exposed to infection and/or vaccination, have stimulated recommendations to reduce the isolation period for COVID-19. However, these new guidelines have raised questions about their effectiveness in reducing contamination and minimizing impact in work environments. Therefore, a collaborative task force was developed to review the subject in a non-systematic manner, answering questions about SARS-CoV-2 variants, COVID-19 vaccines, isolation/quarantine periods, testing to end the isolation period, and the use of masks as mitigation procedures. Overall, COVID-19 vaccines are effective in preventing severe illness and death but are less effective in preventing infection in the case of the Omicron variant. Any strategy that is adopted to reduce the isolation period should take into consideration the epidemiological situation of the geographical region, individual clinical characteristics, and mask for source control. The use of tests for isolation withdrawal should be evaluated with caution, due to results depending on various conditions and may not be reliable.

Evaluation of eleven immunochromatographic assays for SARS-CoV-2 detection: investigating the dengue cross-reaction

ABSTRACT COVID-19 disease is spread worldwide and diagnostic techniques have been studied in order to contain the pandemic. Immunochromatographic (IC) assays are feasible and a low-cost alternative especially in low and middle-income countries, which lack structure to perform certain diagnostic techniques. Here we evaluate the sensitivity and specificity of eleven different IC tests in 145 serum samples from confirmed cases of COVID-19 using RT-PCR and 100 negative serum samples from blood donors collected in February 2019. We also evaluated the cross-reactivity with dengue using 20 serum samples from patients with confirmed diagnosis for dengue collected in early 2019 through four different tests. We found high sensitivity (92%), specificity (100%) and an almost perfect agreement (Kappa 0.92) of IC assay, especially when we evaluated IgG and IgM combined after 10 days from the onset of symptoms with RT-PCR. However, we detected cross-reactivity between dengue and COVID-19 mainly with IgM antibodies (5 to 20% of cross-reaction) and demonstrated the need for better studies about diagnostic techniques for these diseases.

MRSA outbreak in a Neonatal Intensive Care Unit in a developed country: importance of rapid detection of reservoirs and implementation of intervention measures

ABSTRACT We described a MRSA bloodstream infection outbreak that was rapidly identified and controlled in a Neonatal Intensive Care Unit after implementation of a bundle of measures, including PCR-screening and HCW decolonization. We found 35% of healthcare workers(HCW) colonized with S. aureus by PCR, one of them that presented skin lesion positive for MSSA (same clone and spa type than two patients). Our findings raise the hypothesis that the outbreak could be related to HCW colonization.

Meningitis caused by Capnocytophaga canimorsus in a COVID-19 patient: a rare complication of dog bites

ABSTRACT Capnocytophaga canimorsus is a gram-negative rod that is part of the commensal microbiota of dogs' and cats' mouths. In this case, we report an 85-year-old man with COVID-19 who had his right arm bitten by a dog. His symptoms were impaired consciousness, agitation and aggressive behavior. Physical examination revealed neck stiffness and Brudzinski's sign. The cerebrospinal fluid culture was compatible with Capnocytophaga canimorsus. He required intensive care and received a 14-day prescription of meropenem. After 40 days of hospitalization, the patient was fully recovered and was discharged. This case highlights the importance of physician and microbiologist be awareness of this disease, mainly in patients with neurological symptoms after a dog or cat bite.

Polymerase chain reaction targeting 16S ribosomal RNA for the diagnosis of bacterial meningitis after neurosurgery

OBJECTIVES: Bacterial and aseptic meningitis after neurosurgery can present similar clinical signs and symptoms. The aims of this study were to develop and test a molecular method to diagnose bacterial meningitis (BM) after neurosurgery. METHODS: A 16S ribosomal RNA gene PCR-based strategy was developed using artificially inoculated cerebrospinal fluid (CSF) followed by sequencing. The method was tested using CSF samples from 43 patients who had undergone neurosurgery and were suspected to suffer from meningitis, and from 8 patients without neurosurgery or meningitis. Patients were classified into five groups, confirmed BM, probable BM, possible BM, unlikely BM, and no meningitis. RESULTS: Among the samples from the 51 patients, 21 samples (41%) were culture-negative and PCR-positive. Of these, 3 (14%) were probable BM, 4 (19%) were possible BM, 13 (62%) were unlikely BM, and 1 (5%) was meningitis negative. Enterobacterales, non-fermenters (Pseudomonas aeruginosa and Acinetobacter baumannii), Staphylococcus haemolyticus, Granulicatella, Variovorax, and Enterococcus cecorum could be identified. In the group of patients with meningitis, a good agreement (3 of 4) was observed with the results of cultures, including the identification of species. CONCLUSION: Molecular methods may complement the diagnosis, guide treatment, and identify non-cultivable microorganisms. We suggest the association of methods for suspected cases of BM after neurosurgery, especially for instances in which the culture is negative.

A Brazilian university hospital position regarding transplantation criteria for HIV-positive patients according to the current literature

Human immunodeficiency virus (HIV) infection was considered a contraindication for solid organ transplantation (SOT) in the past. However, HIV management has improved since highly active antiretroviral therapy (HAART) became available in 1996, and the long-term survival of patients living with HIV has led many transplant programs to reevaluate their policies regarding the exclusion of patients with HIV infection. Based on the available data in the medical literature and the cumulative experience of transplantation in HIV-positive patients at our hospital, the aim of the present article is to outline the criteria for transplantation in HIV-positive patients as recommended by the Immunocompromised Host Committee of the Hospital das Clínicas of the University of São Paulo.

Cytomegalovirus infection in transplant recipients

Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication) or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease). The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia. .

Management of post-transplant Epstein-Barr virus-related lymphoproliferative disease in solid organ and hematopoietic stem cell recipients

Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) is one of the most serious complications associated with solid organ and hematopoietic stem cell transplantation. PTLD is most frequently seen with primary EBV infection post-transplant, a common scenario for pediatric solid organ recipients. Risk factors for infection or reactivation of EBV following solid organ transplant are stronger immunosuppressive therapy regimens, and being seronegative for receptor. For hematopoietic stem cell transplantation, the risk factors relate to the type of transplant, human leukocyte antigen disparity, the use of stronger immunosuppressants, T-cell depletion, and severe graft-versus-host disease. Mortality is high, and most frequent in patients who develop PTLD in the first six months post-transplant. The primary goal of this article is to provide an overview of the clinical manifestations, diagnosis, accepted therapies, and management of EBV infection in transplant recipients, and to suggest that the adoption of monitoring protocols could contribute to a reduction in related complications.

Smqnr VARIANTS IN CLINICAL ISOLATES OF Stenotrophomonas maltophilia IN BRAZIL / Variantes de Smqnr de isolados clínicos de Stenotrophomonas maltophilia no Brasil

SUMMARY Stenotrophomonas maltophilia contains a novel chromosomally-encoded qnr gene named Smqnr that contributes to low intrinsic resistance to quinolone. We described Smqnr in 13 clinical isolates of S. maltophilia from two Brazilian hospitals, over a 2-year period. The strains were identified by API 20 NE (bioMérieux, France). Susceptibility by microdilution method to trimetroprim/sulfamethoxazole, ciprofloxacin, levofloxacin, minocycline, ceftazidime, chloramphenicol and ticarcillin/clavulanate was performed according to CLSI. PCR detection of Smqnr gene was carried out. The sequence of Smqnr was compared with those deposited in GenBank. Pulsed-field gel electrophoresis (PFGE) of all strains was performed. Thirteen Smqnr positives isolates were sequenced and three novel variants of Smqnr were identified. All 13 Smqnr isolates had distinguishable patterns by PFGE. This is the first report of Smqnr in S. maltophilia isolated in Brazil. .

RESUMO S. maltophilia contem um novo gene qnr cromossômico denominado Smqnr que contribui para baixa resistência intrínseca a quinolonas. Descrevemos Smqnr em 13 isolados clínicos de S. maltophilia de dois hospitais brasileiros, ao longo do período de dois anos. Os isolados foram identificados pela API 20 NE (bioMérieux, França). Susceptibilidade pelo método de microdiluição dos seguintes antibióticos trimetroprim/sulfametoxazol, ciprofloxacina, levofloxacina, minociclina, ceftazidima, cloranfenicol e ticarcilina/clavulanato foi realizada segundo o CLSI. Detecção do gene de Smqnr foi realizada por PCR. A sequência de Smqnr foi comparada com aquelas depositadas no GenBank. Foi realizada eletroforese em gel de campo pulsado (PFGE) de todos os isolados. Treze isolados contendo Smqnr foram sequenciados e identificados três variantes do gene Smqnr. Todos os 13 isolados de Smqnr apresentaram diferentes padrões por PFGE. Este é o primeiro relato de Smqnr em isolados de S. maltophilia no Brasil. .

The minimal inhibitory concentration for sulbactam was not associated with the outcome of infections caused by carbapenem-resistant Acinetobacter sp. treated with ampicillin/sulbactam

OBJECTIVE: The objective of this study was to evaluate whether the outcomes of carbapenem-resistant Acinetobacter infections treated with ampicillin/sulbactam were associated with the in vitro susceptibility profiles. METHODS: Twenty-two infections were treated with ampicillin/sulbactam. The median treatment duration was 14 days (range: 3-19 days), and the median daily dose was 9 g (range: 1.5-12 g). The median time between Acinetobacter isolation and treatment was 4 days (range: 0-11 days). RESULTS: The sulbactam minimal inhibitory concentration (MIC) ranged from 2.0 to 32.0 mg/L, and the MIC was not associated with patient outcome, as 4 of 5 (80%) patients with a resistant infection (MIC≥16), 5 of 10 (50%) patients with intermediate isolates (MIC of 8) and only 1 of 7 (14%) patients with susceptible isolates (MIC ≤4) survived hospitalization. CONCLUSION: These findings highlight the need to improve the correlation between in vitro susceptibility tests and clinical outcome. .

Triagem para o tratamento ambulatorial da neutropenia febril / Screening for the outpatient treatment of febrile neutropenia

A neutropenia febril (NF) é uma complicação frequente e potencialmente fatal nos pacientes em tratamento quimioterápico. Entendemos hoje que a neutropenia febril é considerada uma emergência clínica e que a administração de antibióticos de amplo espectro diminui drasticamente a mortalidade. Estudos sugerem que a neutropenia febril compreende um grupo extremamente heterogêneo e que dados clínicos como febre domiciliar, ausência de hipotensão, ausência de desidratação, ausência de doença pulmonar obstrutiva crônica, ausência de outros sintomas, ausência de infecção fúngica prévia e idade < 60 anos são fatores de proteção para complicações clínicas graves segundo o estudo da Multinational Association for Supportive Care of Cancer (MASCC). Estes dados permitem maior segurança para o tratamento ambulatorial e alta precoce, uma vez que estudos fármaco-econômicos demonstram importante redução de custos no tratamento ambulatorial da neutropenia febril. O objetivo desta revisão é discutir instrumentos de segurança da triagem de um paciente neutropênico febril (principalmente pela utilização do índice MASCC), como também demonstrar as formas descritas na literatura do tratamento ambulatorial e seus resultados.

Febrile neutropenia is a frequent and potentially fatal adverse event of chemotherapy. Nowadays, febrile neutropenia is considered an emergency and it is known that prompt infusion of antibiotics decreases mortality. Several studies demonstrated that febrile neutropenia is a heterogeneous group of diseases and that factors such as outpatient status, no hypotension, no dehydration, no chronic obstructive pulmonary disease, no symptoms, no previous fungal infection and age < 60 years are protective factors against serious complications as demonstrated by the Multinational Association for Supportive Care in Cancer (MASCC). These data show that outpatient treatment and early discharge is safer and much research has shown lower costs for outpatient treatment in low-risk patients with febrile neutropenia. The aim of this work is to review and discuss tools (in particular the MASCC index) for safe screening of febrile neutropenia for outpatient treatment in addition to demonstrate results of research.