A consensus document for the clinical management of invasive fungal diseases in pediatric patients with hematologic cancer and/or undergoing hematopoietic stem cell transplantation in Brazilian medical centers

ABSTRACT In the present paper we summarize the suggestions of a multidisciplinary group including experts in pediatric oncology and infectious diseases who reviewed the medical literature to elaborate a consensus document (CD) for the diagnosis and clinical management of invasive fungal diseases (IFDs) in children with hematologic cancer and those who underwent hematopoietic stem-cell transplantation. All major multicenter studies designed to characterize the epidemiology of IFDs in children with cancer, as well as all randomized clinical trials addressing empirical and targeted antifungal therapy were reviewed. In the absence of randomized clinical trials, the best evidence available to support the recommendations were selected. Algorithms for early diagnosis and best clinical management of IFDs are also presented. This document summarizes practical recommendations that will certainly help pediatricians to best treat their patients suffering of invasive fungal diseases.

Central venous catheter-related infections caused by Corynebacterium amycolatum and other multiresistant non-diphtherial corynebacteria in paediatric oncology patients

ABSTRACT Bloodstream and venous catheter-related corynebacterial infections in paediatric patients with haematological cancer were investigated from January 2003 to December 2014 at the Brazilian National Cancer Institute in Rio de Janeiro, Brazil. We observed that during cancer treatment, invasive corynebacterial infections occurred independent of certain factors, such as age and gender, underlying diseases and neutropenia. These infections were ssscaused by Corynebacterium amycolatum and other non-diphtherial corynebacteria. All cases presented a variable profile of susceptibility to antimicrobial agents, except to vancomycin. Targeted antibiotic therapy may contribute to catheters maintenance and support quality of treatment. Non-diphtherial corynebacteria must be recognized as agents associated with venous access infections. Our data highlight the need for the accurate identification of corynebacteria species, as well as antimicrobial susceptibility testing.

Cepas E-ESKAPE multidrogorresistentes aisladas en hemocultivos de pacientes con cáncer / Multidrug resistance E-ESKAPE strains isolated from blood cultures in patients with cancer

Resumen: Objetivo: Describir la tendencia de cepas multidrogorresistentes (MDR) aisladas en hemocultivos de pacientes con cáncer durante el periodo de 2005 a 2015. Material y métodos: Análisis retrospectivo en el que se procesaron 33 127 hemocultivos. La identificación y la sensibilidad antimicrobianas se realizaron a través de métodos automatizados WaLK away (Siemens Laboratory Diagnostics) y BD Phoenix (Becton, Dickinson and Company). Se determinaron cepas resistentes de acuerdo con la concentración mínima inhibitoria, según los parámetros del Clinical and Laboratory Standards Institute (CLSI). Resultados: 5604 (16.9%) aislamientos fueron positivos, con 6397 aislamientos, 3732 (58.4%) bacilos gramnegativos, 2355 (36.9%) cocos grampositivos, 179 (2.7%) levaduras y 126 (1.9%) bacilos grampositivos. Escherichia coli (n=1 591, 24.5%) fue la bacteria más frecuente, 652 (41%) productoras de beta-lactamasas de espectro-extendido (BLEE); Enterococcus faecium 143 (2.1%), 45 (31.5%) resistente a vancomicina; Staphylococcus aureus 571 (8.7%), 121 (21.2%) resistentes a meticilina (SARM); Klebsiella pneumoniae 367 (5.6%), 41 (11.2%) BLEE, Acinetobacter baumannii 96 (1.4%), 23 (24%) MDR; Pseudomonas aeruginosa 384 (5.6%), 43 (11.2%) MDR. Las cepas MDR se aislaron más frecuentemente en pacientes con neoplasias hematológicas en comparación con tumores sólidos; SARM (RM=4.48, IC95% 2.9-6.8); E. coli BLEE (RM=1.3, IC95% 1.10-1.65) y A. baumannii-MDR (RM=3.2, IC95% 1.2-8.3). Conclusiones. Se observó un aislamiento significativamente mayor de cepas E-ESKAPE MDR en pacientes con neoplasias hematológicas.

Abstract: Objective: To describe the trend of multidrug resistant (MDR) strains isolated from blood in patients with cancer from 2005 to 2015. Materials and methods: 33 127 blood cultures were processed by retrospective analysis. Identification and antimicrobial sensitivity were performed through automated methods: WaLK away (Siemens Laboratory Diagnostics) and BD Phoenix (Becton, Dickinson and Company). Resistant strains were determined according to the minimum inhibitory concentration, following the parameters of the Clinical and Laboratory Standards Institute (CLSI). Results: Of 6 397 isolates, 5 604 (16.9%) were positive; 3 732 (58.4%) Gram- bacilli; 2 355 (36.9%) Gram+ cocci; 179 (2.7%) yeasts, and 126 (1.9%) Gram+ bacilli. Escherichia coli (n=1 591, 24.5%) was the most frequent bacteria, with 652 (41%) strains being extended-spectrum beta-lactamases producers (ESBL); of Enterococcus faecium (n=143, 2.1%), 45 (31.5%) were vancomycin resistant; of Staphylococcus aureus (n=571, 8.7%), 121 (21.2%) methicillin resistant (MRSA); of Klebsiella pneumoniae (n=367, 5.6%), 41 (11.2%) ESBL; of Acinetobacter baumanii (n=96, 1.4%), 23 (24%) MDR, and of Pseudomonas aeruginosa (n=384, 5.6%), 43 (11.2%) MDR. MDR strains were significantly more frequent in patients with hematological malignancies, compared to those with solid tumors: MRSA (OR=4.48, 95%CI 2.9-6.8), ESBL E. coli (OR=1.3, 95%CI 1.10-1.65) and MDR Acinetobacter baumanii (OR=3.2, 95%CI 1.2-8.3). Conclusions: We observed significantly higher isolations of E-ESPAKE MDR strains in patients with hematological malignancies.

Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes / Infecção por bactérias gram-negativas multirresistentes em uma unidade de terapia intensiva pediátrica oncológica: fatores de risco e resultados

ABSTRACT OBJECTIVE: This study aimed at evaluating the predictors and outcomes associated with multidrug-resistant gram-negative bacterial (MDR-GNB) infections in an oncology pediatric intensive care unit (PICU). METHODS: Data were collected relating to all episodes of GNB infection that occurred in a PICU between January of 2009 and December of 2012. GNB infections were divided into two groups for comparison: (1) infections attributed to MDR-GNB and (2) infections attributed to non-MDR-GNB. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, healthcare-associated infection, neutropenia in the preceding 7 days, duration of neutropenia, length of hospital stay before ICU admission, length of ICU stay, and the use of any of the following in the previous 30 days: antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy. Other variables included initial appropriate antimicrobial treatment, definitive inadequate antimicrobial treatment, duration of appropriate antibiotic use, time to initiate adequate antibiotic therapy, and the 7- and 30-day mortality. RESULTS: Multivariate logistic regression analyses showed significant relationships between MDR-GNB and hematologic diseases (odds ratio [OR] 5.262; 95% confidence interval [95% CI] 1.282-21.594; p = 0.021) and healthcare-associated infection (OR 18.360; 95% CI 1.778-189.560; p = 0.015). There were significant differences between MDR-GNB and non-MDR-GNB patients for the following variables: inadequate initial empirical antibiotic therapy, time to initiate adequate antibiotic treatment, and inappropriate antibiotic therapy. CONCLUSIONS: Hematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients.

RESUMO OBJETIVO: Este estudo visou a avaliar os preditores e resultados associados às infecções por bactérias gram-negativas multirresistentes (BGN-MR) em uma unidade de terapia intensiva pediátrica oncológica (UTIP). MÉTODOS: Foram coletados dados com relação a todos os episódios de infecção por BGN que ocorreram em uma UTIP entre janeiro de 2009 e dezembro de 2012. As infecções por BGN foram divididas em dois grupos para comparação: 1) infecções atribuídas a BGN-MR e 2) infecções atribuídas a BGN não multirresistente. As variáveis de interesse incluíram idade, sexo, presença de tumor sólido ou malignidade hematológica, câncer, uso de cateter venoso central, infecção anterior por Pseudomonas aeruginosa, infecção hospitalar, neutropenia nos sete dias anteriores, duração da neutropenia, tempo de internação antes da UTI, duração da internação na UTI e uso de quaisquer dos seguintes nos 30 dias anteriores: agentes antimicrobianos, corticosteroides, quimioterapia ou radioterapia. Outras variáveis incluíram: tratamento antimicrobiano inicial adequado, tratamento antimicrobiano definitivo inadequado, duração do uso de antibióticos adequados, tempo de início da terapia antibiótica adequada, mortalidade em sete dias e mortalidade em 30 dias. RESULTADOS: As análises de regressão logística multivariada mostraram relações significativas entre as BGN-MR e as doenças hematológicas (razão de chance (RC) 5,262; intervalo de confiança de 95% (IC de 95%) 1,282-21,594; p = 0,021) e infecções hospitalares (RC 18,360; IC de 95% 1,778-189,560; p = 0,015). Houve diferenças significativas entre os pacientes com BGN-MR e BGN não MR com relação às seguintes variáveis: recebimento de terapia antibiótica empírica inicial inadequada, tempo para início do tratamento antibiótico adequado e recebimento de terapia antibiótica inadequada. CONCLUSÕES: A malignidade hematológica e a infecção hospitalar foram significativamente associadas à infecção por BGN-MR nessa amostra de pacientes pediátricos oncológicos.

Predictors of 7- and 30-day mortality in pediatric intensive care unit patients with cancer and hematologic malignancy infected with Gram-negative bacteria

Background: Infection with Gram-negative bacteria is associated with increased morbidity and mortality. The aim of this study was to evaluate the predictors of 7- and 30-day mortality in pediatric patients in an intensive care unit with cancer and/or hematologic diseases and Gram-negative bacteria infection. Methods: Data were collected relating to all episodes of Gram-negative bacteria infection that occurred in a pediatric intensive care unit between January 2009 and December 2012, and these cases were divided into two groups: those who were deceased seven and 30 days after the date of a positive culture and those who survived the same time frames. Variables of interest included age, gender, presence of solid tumor or hematologic disease, cancer status, central venous catheter use, previous Pseudomonas aeruginosa infection, infection by multidrug resistant-Gram-negative bacteria, colonization by multidrug resistant-Gram- negative bacteria, neutropenia in the preceding seven days, neutropenia duration ≥3 days, healthcare-associated infection, length of stay before intensive care unit admission, length of intensive care unit stay >3 days, appropriate empirical antimicrobial treatment, definitive inadequate antimicrobial treatment, time to initiate adequate antibiotic therapy, appropriate antibiotic duration ≤3 days, and shock. In addition, use of antimicrobial agents, corticosteroids, chemotherapy, or radiation therapy in the previous 30 days was noted. Results: Multivariate logistic regression analysis resulted in significant relationship between shock and both 7-day mortality (odds ratio 12.397; 95% confidence interval 1.291–119.016 p = 0.029) and 30-day mortality (odds ratio 6.174; 95% confidence interval 1.760–21.664 p = 0.004), between antibiotic duration ≤3 days and 7-day mortality (odds ratio 21.328 95% confidence interval 2.834-160.536; p = 0.003), and between colonization by multidrug re...

Factors influencing the early mortality in haematological malignancy patients with nosocomial Gram negative bacilli bacteraemia: a retrospective analysis of 154 cases

BACKGROUND: The aim of this study is to assess the factors influencing the early mortality (7- day after index blood culture) in haematological malignancy patients with Gram negative bacilli (GNB) bacteraemia. METHODS: Infection control committee records were reviewed to identify the cases between March 2006 and June 2011. Only one bacteraemic episode per patient was included in the study. RESULTS: A total of 154 patients with GNB bacteraemia were identified. The early mortality rate was 19.5% (30 out of 154). Blood cultures revealed Enterobacteriacea in 120 patients (Escherichia coli; 86, Klebsiella spp.; 28, Enterobacter cloacea; 6) and glucose non-fermenting GNB in 34 patients (Pseudomonas aeruginosa; 15, Acinetobacter baumannii; 11, Stenotrophomonas maltophilia; 7, Burkholderia cepacia; 1). Forty (33.3%) out of 120 Enterobacteriaceae were extended spectrum beta-lactamase (ESBL) producers and 18 (52.9%) out of 34 glucose non-fermenting GNB were multidrug resistant. Carbapenems were administered as first line therapy in 139 out of 154 patients. In univariate analysis Pitt's bacteraemia score, presence of aplastic anaemia, bacteraemia caused by glucose non-fermentating GNB, inappropriate empirical antibacterial treatment, presence of severe sepsis or septic shock, unable to achieve microbiological cure, and intensive care unit (ICU) acquired bacteraemia were associated with mortality. Multivariate analysis showed ICU acquired bacteraemia (OR, 12.55; 95% CI, 2.34-67.38, p = 0.003) as an independent factor associated with early mortality. CONCLUSION: Haematological malignancy patients who require ICU care are at high risk for early mortality related to GNB bacteraemia. Based on the local findings pointing out high rate of multidrug resistance, carbapenems combined with colistin seems to be a reasonable approach as empirical treatment of these patients. However, increasing carbapenem resistance rate is of concern.