Landscape of Invasive Fusariosis in Pediatric Cancer Patients: Results of a Multicenter Observational Study From Latin America.

Invasive fusariosis (IF) is a life-threatening opportunistic infection that affects vulnerable hosts. We conducted a multicenter and multinational retrospective study to characterize the natural history and clinical management of IF in pediatric cancer patients. We selected patients <18 years old who were sequentially hospitalized in 10 Latin American medical centers with a diagnosis of IF between 2002 and 2021. Data were collected using an electronic case report form complemented by a dictionary of terms. We assessed mortality rates at 30, 60, and 90 days. We collected data from 60 episodes of IF (median age, 9.8 years) that were mostly documented in patients with hematologic cancer (70%). Other risk conditions found were lymphopenia (80%), neutropenia (76.7%), and corticosteroid exposure (63.3%). IF was disseminated in 55.6% of patients. Skin lesions was present in 58.3% of our patients, followed by pulmonary involvement in 55%, sinusitis in 21.7%, bone/joint involvement in 6.7% and 1 case each of endocarditis and brain abscess. Positive blood and skin biopsy cultures were detected in 60% and 48.3% of cases, respectively. Fusarium solani complex was the most commonly identified agent (66.6%). The majority of patients received monotherapy within the first 72 hours (71.6%), either with voriconazole or amphotericin B formulation. The mortality rates at 30, 60, and 90 days were 35%, 41.6%, and 45%, respectively. An important factor affecting mortality rates appears to be disseminated disease. The high percentage of patients with fungal involvement in multiple organs and systems highlights the need for extensive workup for additional sites of infection in severely immunocompromised children.

Impact of Anti-CMV IgG Titers and CD34 Count Prior to Hematopoietic Stem Cell Transplantation from Alternative Donors on CMV reactivation.

Cytomegalovirus (CMV) reactivation remains one of the main infectious complications following hematopoietic stem cell transplantation (HSCT). In this study, we explored the role of anti-CMV antibody titers in HSCT from alternative donors and to compare the risk of CMV reactivation between posttransplant cyclophosphamide-based haploidentical HSCT and antithymocyte globulin-based unrelated donor (URD) HSCT. We included 98 CMV-positive patients, 30 undergoing haploidentical HSCT and 68 undergoing URD HSCT. The majority of patients had a malignant disease (84%), received a myeloablative conditioning regimen (78%), and received a bone marrow graft (90%). The median pretransplantation anti-CMV IgG level was 109 U/mL. With median follow-up of 2.2 years, a total of 72 CMV reactivations occurred in 50 patients. There was no difference in CMV reactivation pattern between haploidentical HSCT recipients and URD HSCT recipients. In multivariable analysis until the first event, the incidence of CMV reactivation was higher in patients with anti-CMV IgG levels >100 U/mL (hazard ratio [HR], 2.38; P = .005) and in patients diagnosed with grade II-IV acute graft-versus-host disease (GVHD) (HR, 10.8; P = .003) after day +50 and lower in patients who received higher doses of CD34 cells (HR, .44; P = .006). In multivariable analysis for recurring events, the incidence of CMV reactivation was higher in patients receiving reduced-intensity conditioning (HR, 1.69: P = .04) and in patients with acute GVHD (HR, 1.88; P = .02), and lower in those who received higher doses of CD34 cells (HR, .55; P = .01). In summary, we have shown that pretransplantation anti-CMV IgG titers are correlated with CMV reactivation risk. More studies are needed to assess how this information can be incorporated in HSCT. The use of high-dose cellular grafts, a modifiable risk factor, also protects against CMV reactivation.

Fluorine-18-fluorodeoxyglucose PET/CT in hematopoietic stem cell transplant patients with fusariosis: initial findings of a case series review.

BACKGROUND: Fusariosis is an opportunistic fungal infection that affects mostly leukemic and hematopoietic stem cell transplant patients. Locally invasive and disseminated infection may occur. Treatment is challenging, and besides evaluation of immune status, one also needs to take into account organ involvement to predict the duration and prognosis. OBJECTIVE: The aim of this study was to present the findings and clinical follow-up from a series of cases of Fusarium spp. infections in patients subjected to hematopoietic stem cell transplant evaluated with one or more fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT scans, according to the source of clinical culture sample (blood or wound secretion). RESULTS: Ten patients were included. In this series, 18F-FDG PET/CT was able to detect osteomyelitis in three patients. CONCLUSION: Although having a small number of patients and lack of standard approach, 18F-FDG PET/CT seemed useful to discriminate uncomplicated cases of primary bloodstream infections and detect occult foci of metastatic infection in patients with positive cutaneous lesions cultures.

Susceptibility of Brazilian influenza A(H1N1)pdm09 viruses to neuraminidase inhibitors in the 2014-2016 seasons: Identification of strains bearing mutations associated with reduced inhibition profile.

Neuraminidase inhibitors (NAIs) are the main class of antivirals currently used for the treatment of influenza infections. As influenza viruses are constantly evolving, drug-resistance can emerge resulting in reduced effectiveness of treatment. This study evaluated the presence of molecular markers associated with NAI susceptibility in 724 influenza A(H1N1)pdm09 positive samples from Brazilian surveillance system from the 2014-2016 seasons, including 76 isolates tested for oseltamivir (OST) susceptibility and 23 isolates also tested for zanamivir, peramivir and laninamivir susceptibility. We identified the H275Y (n = 3) and I223K (n = 1) NA substitutions, associated with reduced inhibition (RI) by the NAIs. Noteworthy, no epidemiological links were identified among the patients infected with the mutant viruses. Phylogenetic analysis from NA and hemagglutinin genes showed that mutant viruses were not clustered. All mutant virus strains carried the permissive substitutions V241I and N369K, in addition to the N386K, which has been shown to destabilize the NA structure. Functional NA analysis of one virus containing the H275Y mutation confirmed its highly RI profile to OST and peramivir and demonstrated that it had decreased viral replication and NA thermostability compared to the wild type virus. The remaining tested isolates presented normal inhibition profile to the NAIs tested. In conclusion, the overall frequency of influenza A(H1N1)pdm09 viruses bearing mutations associated with NAI RI was 0.6%, similar to what has been observed in recent global studies.

Immunoproteome of Aspergillus fumigatus using sera of patients with invasive aspergillosis.

Invasive aspergillosis is a life-threatening lung or systemic infection caused by the opportunistic mold Aspergillus fumigatus. The disease affects mainly immunocompromised hosts, and patients with hematological malignances or who have been submitted to stem cell transplantation are at high risk. Despite the current use of Platelia™ Aspergillus as a diagnostic test, the early diagnosis of invasive aspergillosis remains a major challenge in improving the prognosis of the disease. In this study, we used an immunoproteomic approach to identify proteins that could be putative candidates for the early diagnosis of invasive aspergillosis. Antigenic proteins expressed in the first steps of A. fumigatus germination occurring in a human host were revealed using 2-D Western immunoblots with the serum of patients who had previously been classified as probable and proven for invasive aspergillosis. Forty antigenic proteins were identified using mass spectrometry (MS/MS). A BLAST analysis revealed that two of these proteins showed low homology with proteins of either the human host or etiological agents of other invasive fungal infections. To our knowledge, this is the first report describing specific antigenic proteins of A. fumigatus germlings that are recognized by sera of patients with confirmed invasive aspergillosis who were from two separate hospital units.

Detection of the influenza A(H1N1)pdm09 virus carrying the K-15E, P83S and Q293H mutations in patients who have undergone bone marrow transplant.

The 2009 pandemic influenza A(H1N1)pdm09 virus emerged and caused considerable morbidity and mortality in the third world, especially in Brazil. Although circulating strains of A(H1N1)pdm09 are A/California/04/2009-like (CA-04-like) viruses, various studies have suggested that some mutations in the viral hemagglutinin (HA) may be associated with enhanced severity and fatality. This phenomenon is particularly challenging for immunocompromised individuals, such as those who have undergone bone marrow transplant (BMT), because they are more likely to display worse clinical outcomes to influenza infection than non-immunocompromised individuals. We studied the clinical and viral aspects of post-BMT patients with confirmed A(H1N1)pdm09 diagnosis in the largest cancer hospital in Brazil. We found a viral strain with K-15E, P83S and Q293H polymorphisms in the HA, which is presumably more virulent, in these individuals. Despite that, these patients showed only mild symptoms of infection. Our findings complement the discovery of mild cases of infection with the A(H1N1)pdm09 virus with the K-15E, P83S and Q293H mutations in Brazil and oppose other studies that have linked these changes with increased disease severity. These results could be important for a better comprehension of the impact of the pandemic influenza in the context of BMT.

Different outcomes between cyclophosphamide plus horse or rabbit antithymocyte globulin for HLA-identical sibling bone marrow transplant in severe aplastic anemia.

The standard regimen for HLA-identical sibling bone marrow transplant (BMT) in severe aplastic anemia (SAA) is cyclophosphamide (Cy) and horse antithymocyte globulin (ATG). Horse ATG has been replaced by rabbit ATG in many countries due to the unavailability of the former product. This study was designed to assess if these ATG preparations are interchangeable in the preparative regimen for matched related BMT in SAA. Forty consecutive BMTs were retrospectively analyzed: 20 received Cy plus horse ATG and 20 received Cy plus rabbit ATG as the preparative regimen. Conditioning with rabbit ATG was protective against acute graft-versus-host disease (aGVHD) grades II-IV and moderate-severe chronic GVHD (cGVHD), with incidence rates of 0% versus 35.2% (P = .009) and 0% versus 34.0% (P = .04), respectively. On day +100, the probability of proven/probable invasive fungal disease (IFD) was higher in patients conditioned with rabbit ATG, 31.2% versus 5.5%, respectively (P = .04). Earlier cytomegalovirus (CMV) reactivation (40 versus 50 days; P = .02) was observed with rabbit ATG. An inferior lymphocyte count on days +30 (0.360 versus 0.814 × 10(9)/L; P = .01) and +90 (0.744 versus 1.330 × 10(9)/L; P = .006) was noticed in recipients of rabbit ATG. The incidence of stable mixed chimerism was higher in recipients of rabbit ATG (18.2% versus 80%, respectively; P = .004). These results suggest that horse and rabbit ATG preparations have different biological and clinical properties and should not be used interchangeably in the preparative regimen for related BMT in SAA.

Streptococcal bacteremia in patients submitted to hematopoietic stem celltransplantation: The role of tooth brushing and use of chlorhexidine

A retrospective evaluation of 73 consecutive recipients of hematopoietic stem cell transplantation (HSCT) wasconducted to investigated the role of oral care and incidence of streptococcal bacteremia in patients submittedto hematopoietic stem cell transplantation. Patients were retrospectively evaluated and divided into group A(GA=38) and group B (GB=35). During hospitalization patients from GA performed oral hygiene daily with extrasoft toothbrush and toothpaste besides performing mouth cleaning with an ethanol-free 0.12% chlorhexidine solutiontree times a day. In contrast GB patients performed mouth cleaning with extra soft toothbrush and toothpaste,but no chlorhexidine was used. Using the Chi square test it was observed that all patients from GA presentednegative blood culture for alpha-hemolytic Streptococcus viridans and Candida albicans and only 1 patient withoutoral mucositis from GB presented positive blood cultures for Streptococcus intermedius (p=0.48). The resultsindicate that methodology used for oral care before the HSCT and the practice of tooth brushing during the periodwere effective in preventing streptococcal bacteremia. Moreover, our data suggest that the mouth cleaning withchlorhexidine during HSCT may be not mandatory (AU)

Streptococcal bacteraemia in patients submitted to hematopoietic stem cell transplantation: the role of tooth brushing and use of chlorhexidine.

A retrospective evaluation of 73 consecutive recipients of hematopoietic stem cell transplantation (HSCT) was conducted to investigated the role of oral care and incidence of streptococcal bacteremia in patients submitted to hematopoietic stem cell transplantation. Patients were retrospectively evaluated and divided into group A (GA=38) and group B (GB=35). During hospitalization patients from GA performed oral hygiene daily with extra soft toothbrush and toothpaste besides performing mouth cleaning with an ethanol-free 0.12% chlorhexidine solution tree times a day. In contrast GB patients performed mouth cleaning with extra soft toothbrush and toothpaste, but no chlorhexidine was used. Using the Chi square test it was observed that all patients from GA presented negative blood culture for alpha-hemolytic Streptococcus viridans and Candida albicans and only 1 patient without oral mucositis from GB presented positive blood cultures for Streptococcus intermedius (p=0.48). The results indicate that methodology used for oral care before the HSCT and the practice of tooth brushing during the period were effective in preventing streptococcal bacteremia. Moreover, our data suggest that the mouth cleaning with chlorhexidine during HSCT may be not mandatory.

Ralstonia pickettii bloodstream infections at a Brazilian cancer institution.

We describe a series of Ralstonia pickettii bloodstream infections (BSI) that occurred in 19 oncohematologic patients admitted to a hospital for patients with cancer, in the city of Rio de Janeiro, from July 1999 to February 2006. Fifty-four R. pickettii isolates were recovered from blood and catheter-tip specimens (1-5 isolates per patient). Two patients eventually died of causes unrelated to R. pickettii BSI. Eight pulsed-field gel electrophoresis genotypes were resolved (A-H), with two detected in more than 1 patient: genotype B, in 2 patients (1.5%), and E, in 12 patients (63.2%). R. pickettii emerged as a new pathogen at our institution, causing at least one outbreak. Cross-transmission of the pathogen, infusion of a putative contaminated intravenous solution, and persistent colonization of medical devices were the likely sources of R. pickettii BSI.