Infection In Neutropenic Children Research Articles

A study on clinical profile of invasive fungal infection in neutropenic children in a tertiary care teaching hospital

Background: Febrile neutropenia is a common complication of anti-cancer chemotherapy. Invasive fungal infections are found mostly after prolonged neutropenia. Early diagnosis and treatment of these infections are of crucial importance. Hence, there is a need to identify the common causative organisms of fungal sepsis in children and our primary objective was to diagnose invasive fungal infections in children of febrile neutropenia and identify the common fungal etiological agents with clinical profile.Methods: This study was done as observational, cross-sectional study for 18 months at the department of microbiology, Lady Hardinge Medical College and department of pediatrics, Kalawati Saran Children’s Hospital. All children less than 18 years of age clinically suspected to have invasive fungal infection with absolute neutrophil count <500 /ml, with fever not responding to antibiotics for more than 3-4 days were included in the study.Results: Hospitalization ≥7 days (100%) was the most common associated risk factor, followed by neutropenia (100%), immunodeficiency (100%), cytotoxic drugs (87.27%) and malignancies (87.27%). Other less commonly associated risk factors were hyperalimentation (23.64%), residence near a construction site (23.64%), presence of urinary catheters (10.91%) and HIV positivity (9.09%). Around 54.54% of sputum samples were positive for fungal culture. A lower positivity was seen in blood culture (14.54%).Conclusions: Candida spp., Aspergillus spp. and Pneumocystis remain the primary fungal pathogens in this patient population. Early clinical suspicion followed by prompt sampling and evaluation for fungal infections may aid in timely diagnosis and reduction of mortality of these patients.

Bloodstream infection in pediatric patients with febrile neutropenia induced by chemotherapy

IntroductionFebrile neutropenia (FN) is a serious complication of cancer chemotherapy. The present study aimed to identify risk factors for documented infection in pediatric patients with FN and cancer. MethodsThis prospective cohort study included patients under 18 years from 2016 to 2018. Infection was defined according to the Centers for Disease Control and Prevention criteria. ResultsA total of 172 febrile neutropenic episodes were evaluated. From univariate analysis, the risk factors were: female gender; monocyte count < 100 cell/mm³, platelets < 50,000, C-reactive protein (CRP) > 90 mg/dl and hemoglobin < 7mg/dl at the onset of an episode; two or more episodes of FN, and; fever onset; positive blood culture at the fever onset. Independent risk factors according to the multivariate analysis were: CRP at the onset of a febrile episode > 90mg/dl, fever onset and first blood culture with a positive result. The lowest probability of infection was related to first episode and to platelets > 50,000 at the onset of fever. ConclusionA CRP > 90 at the onset of a febrile episode, platelets < 50,000, second episode or more, first fever episode during hospitalization and positive first blood culture were found to be associated with a higher risk of infection and they could be useful for the establishment of risk scores for infection in neutropenic children.

Analysis of pathogens and clinical characteristics of bloodstream infection in neutropenic children with hematological malignancies from 2014 to 2018

目的探讨儿童血液病患者在中性粒细胞缺乏（粒缺）期发生血流感染时的病原学分布、耐药情况，为该类患者合理使用抗菌药物提供数据支持。方法回顾性分析2014年1月至2018年12月中国医学科学院血液病医院收治的儿童血液病患者粒缺期发生血流感染时的临床特征、病原菌分布和药物敏感性数据。结果427例儿童血液病患者在粒缺期共发生537次血流感染，30 d全因死亡率为3.7%。其中44.7%例次血流感染的临床特征仅表现为发热，其病原菌以肠杆菌科细菌为主。血流感染常伴口腔黏膜、呼吸道及消化道症状，比例分别为20.7%、20.5%和14.3%。伴不同症状的血流感染病原菌分布不同（χ2=40.561，P=0.001）。共分离出550株病原菌，位于前5位的细菌分别为草绿色链球菌（109株，19.8%）、大肠埃希菌（99株, 18.0%）、表皮葡萄球菌（75株，13.6%）、肺炎克雷伯菌（67株，12.2%）和金黄色葡萄球菌（32株，5.8%）。耐药方面，肠肝菌科细菌及铜绿假单胞菌对于哌拉西林/他唑巴坦、碳青霉烯类药物的耐药率<5%。金黄色葡萄球菌中耐甲氧西林金黄色葡萄球菌（MRSA）的比例为9.7%。结论儿童恶性血液病患者粒缺期发生血流感染病原菌革兰阳性球菌与阴性杆菌比例大致相同，提示经验性抗菌药物使用应具有广谱性，常见分离菌耐药性仍处于较低水平，常用的碳青霉烯类、糖肽类、酶抑制剂复合物类药物如哌拉西林/他唑巴坦等仍具有较好效果。

Antimicrobial Susceptibility Pattern of Bacteria Isolated from Blood Urine and Wound Swab in Febrile Neutropenic Children in a Tertiary Level Hospital, Bangladesh.

Fever is the commonest symptom of infection in neutropenic children with malignancy, under chemotherapy. To avoid bacterial complications, it is necessary to diagnose infection early and to administer empirical antibiotic. The aim of this study was to find out the causative bacteria and their antimicrobial susceptibility pattern in febrile neutropenic children who were under chemotherapy. The study was conductedin a tertiarylevel hospital,Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Blood, urine and wound swab were collected for culture from 30 febrile neutropenic children, age 1-15 years. Out of 70 samples total 26(37.14%)yielded growth of bacteria among which 6(20%), 12(40%), and 8 (80%) were isolated from blood, urine and wound swab respectively. Among thebacteria Pseudomonas spp, Esche coli and Staph aureus weremost frequently isolated. Meropenem, imipenem and netilmicin were the most sensitive against gram negative bacteria and the entire isolated gram positive bacteria were 100% sensitive to vancomycin and linezolid.&#x0D; Bangladesh J Med Microbiol 2017; 11 (2): 5-8

Significant Morbidity and Mortality Attributable to Rothia Mucilaginosa Infections in Children with Hematological Malignancies or Following Hematopoietic Stem Cell Transplantation

Rothia mucilaginosa is a gram-positive coccus that poses a diagnostic challenge and often requires DNA pyrosequencing for diagnosis as it can be easily mistaken for coagulase-negative staphylococci on initial culture results. While it is often times normal human oral and upper respiratory tract microbiota, it can be a virulent pathogen in immunocompromised patients. Most commonly, it causes bacteremia (catheter and non-catheter related) and meningitis in these patients. Our objective was to report the incidence of R. mucilaginosa infections in neutropenic children with hematological malignancies or following hematopoietic stem cell transplantation at a major children's hospital. We report 11 patients in this cohort who developed clinically significant R. mucilaginosa infections, including three deaths directly attributable to this microorganism. Three patients developed significant neurological involvement, accounting for two of the deaths, and one patient died of disseminated infection. Except for one, all patients had severe neutropenia, central line catheters, and mucosal breakdown at the time of infection. Patients who succumbed never achieved neutrophil recovery. In conclusion, R. mucilaginosa can lead to life-threatening infections in immunocompromised hosts, especially in profoundly neutropenic patients.

Procalcitonin as an early marker of bacterial infection in neutropenic febrile children with acute lymphoblastic leukemia

The aim of this study was to assess the value of procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-a), interleukin (IL)-1b, IL-8, and soluble TNF receptor II (sTNFRII) in early and rapid diagnosis of infection in neutropenic children with acute lymphoblastic leukemia (ALL) and to distinguish bacterial from viral infections. The study included five groups (A, B, C, D, and E) of children with ALL undergoing intensive chemotherapy. Groups A and B consisted of neutropenic children with bacterial and viral infection, respectively. Groups C and D consisted of nonneutropenic children with bacterial and viral infection, respectively. Group E consisted of children without neutropenia and without fever. In all groups, blood samples were collected upon admission and then for 7 days on a daily basis. Levels of CRP, PCT, TNF-a, IL-1b, IL-8, and sTNFRII were determined in all blood samples. We found a highly significant difference in PCT levels between bacterial and nonbacterial episodes. Sensitivity and specificity of PCT were 94 and 96.5%, respectively. Serial measurement of PCT levels on a daily basis seems to be helpful for early prediction of severe bacterial infections, monitoring febrile episodes regarding response to antibiotic therapy, and early detection of complications in the infectious process.

PROCALCITONIN AND C-REACTIVE PROTEIN SERUM LEVELS AS MARKERS OF INFECTION IN A PEDIATRIC POPULATION WITH FEBRILE NEUTROPENIA AND CANCER

Background: Procalcitonin and C-reactive-protein are inflammatory markers for sepsis. The authors evaluated their sensitivity and specificity in pediatric patients with cancer and febrile neutropenia. Procedure: Serum procalcitonin and C-reactive-protein were evaluated. Patients (n = 54) were divided into 2 groups, with severe infection (n = 18) or without documented infection (n = 36). Results: Procalcitonin and C-reactive protein were significantly higher in the high-risk group. Procalcitonin displayed 72.2% sensitivity and 80.5% specificity. C-reactive-protein had a sensitivity of 77.7% and specificity of 77.2%. Conclusions: Procalcitonin is an accurate predictor of bacterial infection in neutropenic children, while C-reactive-protein may be a better screening test in emergency settings.

Malnutrition and neutropenia in children treated for Burkitt lymphoma in Malawi

Infection in neutropenic children is a major cause of morbidity and mortality in children treated for cancer. In developing countries, children with cancer are often malnourished at diagnosis. In Blantyre, Malawi, children with Burkitt lymphoma are treated with a local protocol with limited toxicity. The aim of this study was to evaluate the incidence and outcome of febrile neutropenia during this treatment and the association with malnutrition at diagnosis. We documented nutritional status, febrile and/or neutropenic episodes, antibiotic therapy and short term outcome of all children with Burkitt lymphoma treated according to the local protocol and admitted from January 2007 to March 2008. Fifty eight (69%) of 84 patients were acutely malnourished at diagnosis with an arm muscle area (AMA) below the 5(th) percentile. Malnutrition at diagnosis was associated with a significantly higher rate of profound neutropenia. This association remained significant (OR 12; 95% C.I. 1.5 - infinitely; P = 0.012) after control for clinical stage of disease, bone marrow involvement and HIV infection which are possible confounders. All patients with profound neutropenia, prolonged neutropenia and treatment related deaths were malnourished at diagnosis. Four (4.9%) of 81 patients died of treatment related causes; three of them due to a Gram negative septicaemia. Acute malnutrition at diagnosis is associated with significantly more treatment related profound neutropenia. The intensity of chemotherapeutic regimens has to be adapted to the level of available supportive care and patients' nutritional status and tolerance to avoid unacceptable morbidity and mortality. This local treatment protocol for Burkitt lymphoma has a treatment related mortality of 5% in patients in Malawi.

PROCALCITONIN AND C-REACTIVE PROTEIN SERUM LEVELS AS MARKERS OF INFECTION IN A PEDIATRIC POPULATION WITH FEBRILE NEUTROPENIA AND CANCER

Background: Procalcitonin and C-reactive-protein are inflammatory markers for sepsis. The authors evaluated their sensitivity and specificity in pediatric patients with cancer and febrile neutropenia. Procedure: Serum procalcitonin and C-reactive-protein were evaluated. Patients (n = 54) were divided into 2 groups, with severe infection (n = 18) or without documented infection (n = 36). Results: Procalcitonin and C-reactive protein were significantly higher in the high-risk group. Procalcitonin displayed 72.2% sensitivity and 80.5% specificity. C-reactive-protein had a sensitivity of 77.7% and specificity of 77.2%. Conclusions: Procalcitonin is an accurate predictor of bacterial infection in neutropenic children, while C-reactive-protein may be a better screening test in emergency settings.

103 Bacterial blood-stream infections in neutropenic children with hematologic/oncologic disorders at a Tertiary Care Centre in Saudi Arabia

103 Bacterial blood-stream infections in neutropenic children with hematologic/oncologic disorders at a Tertiary Care Centre in Saudi Arabia

Serum adenosine deaminase and procalcitonin concentrations in neutropenic febrile children with acute lymphoblastic leukaemia

Neutropenia as a state of immunosuppression is probably the major problem in patients suffering from acute lymphoblastic leukaemia undergoing intensive chemotherapy. Fever is frequent in neutropenic patients and often related to infection. Clinically, the presence of infection in patients with neutropenia may be difficult to establish, because there are usually few signs of infection. The aim of this work was to study sensitive markers for early diagnosis of microbial infection in neutropenic children undergoing intensive chemotherapy as a treatment for acute lymphoblastic leukaemia. The study included three groups (A, B and C) of children with acute lymphoblastic leukaemia and neutropenia. Group A consisted of 29 children with febrile neutropenia and microbial infection, aged 1-14 years (5.8+/-2.9), 11 boys and 18 girls; Group B of 38 children with febrile neutropenia without microbial infection, aged 2-14 years (6.8+/-3.1), 14 boys and 24 girls; and Group C of 53 children with neutropenia without fever and without infection, aged 1-14 years (5.9+/-2.1), 21 boys and 32 girls. Blood samples were collected upon admission and before the start of any antimicrobial treatment. The samples were used for blood culture, serological tests, leukocyte count and analysis of levels of C-reactive protein, procalcitonin, total adenosine deaminase (ADA) activity and its isoenzymes, ADA-1 and ADA-2. According to our results the procalcitonin levels and total ADA activity discriminated best between neutropenic febrile (Groups A and B) and neutropenic afebrile episodes (Group C). In conclusion, this study suggests procalcitonin and total ADA activity as two easily measurable and cost effective markers for the assessment of immune response in febrile neutropenic patients with acute lymphoblastic leukaemia.

Treatment of fungal infections in neutropenic children.

Fungal infections have emerged as one of the most significant complications of antineoplastic therapy and marrow transplantation in children. Morbidity and mortality associated with fungal infections are high. Recent trends indicate that the incidence and spectrum of fungal infections are increasing, partly because of the increase in the number of children receiving intensive chemotherapy and marrow transplantation, but also because of the successful management of bacterial and viral infections. Though many factors may contribute to risk for developing a fungal infection, prolonged neutropenia is the most important. Until recently, options for antifungal therapy were limited. Advances include less toxic formulations of amphotericin B and an expanding armamentarium of azoles as well as new antifungal compounds. This review addresses the therapeutic options available for treatment of fungal infections in immunocompromised children.

The effects of antifungal chemoprophylaxis and empiric therapy on invasive fungal infection in neutropenic children with malignant neoplasms.

Since January 1987, chemoprophylaxis and empiric therapy with antifungal drugs have been used routinely in neutropenic children with neoplasms. The incidence of terminal invasive fungal infection (IFI) diagnosed by autopsy findings is compared in two groups: group A, consisting of 25 patients autopsied between January 1982 and December 1986, and group B, consisting of 14 patients autopsied between January 1987 and December 1991. There was no difference in the incidence of IFI between the two groups, but the characteristics of IFI appeared to differ. With the recent intensification of chemotherapy, the patients in group B had more risk factors for IFI. It might therefore have been anticipated that group B patients may have shown an increase in IFI. No such increase was observed, suggesting that the prophylaxis was effective. Autopsy findings also showed that the target organs of IFI were localized and that systemic candidiasis was decreased in group B. It is thus concluded that the present antifungal countermeasures are effective, although some problems still remain.

Carumonam as prophylaxis against bacterial infection in neutropenic children with malignancy

Carumonam as prophylaxis against bacterial infection in neutropenic children with malignancy

A Randomised Comparison of Ceftazidime and Piperacillin, Both in Combination with Flucloxacillin for Treatment of Febrile Episodes in Neutropenic Children

111 febrile episodes in 98 neutropenic children were randomly treated with either ceftazidime (CAZ) 150 mg/kg/day or with piperacillin (PIP) 200 mg/kg/day, both combined with flucloxacillin (FLUC) 50 mg/kg/day. A total of 37/47 (79%) eligible episodes in the CAZ group and 41/53 (77%) in the PIP group were cured without needing to stop the initial therapy. The success without modification of the treatment in the verified septicaemias in the CAZ group was 8/18 (44%) and in the PIP group 5/18 (28%). Of the bacteriologically documented infections, 13/24 (54%) in the CAZ group and 11/24 (46%) in the PIP group were cured without modification of the therapy. Similarly, 17/31 (55%) of all the isolated bacteria in the CAZ group and 14/33 (42%) in the PIP group were eradicated with the initial therapy. Overall there were 13 deaths of which 4 in the CAZ group and 5 in the PIP group occurred during the infection. An increasing granulocyte count exceeding 0.25 x 10(9)/l at the end of the therapy was a good prognostic sign for the outcome of the infection. This study indicates that CAZ is as effective as PIP in the treatment of infections in neutropenic children.

Itraconazole Versus Ketoconazole for the Prophylaxis of Fungal Infection in Neutropenic Children: Results of Two Consecutive Nonrandomized Studies

Two consecutive nonrandomized studies were conducted in children with prolonged granulocytopenia to evaluate the prophylactic antifungal activity of ketoconazole and the new triazole itraconazole. The conditions were equivalent in both studies. The incidence of colonization was 10% in the ketoconazole group and 19% in the itraconazole group (this difference is not significant). For suspected and proven infections, the incidence was 5% for ketoconazole and 10% for itraconazole, but the incidences were too low for statistical comparison. Although the colonization rate was higher for itraconazole, there was no sign of Aspergillus, whereas in the ketoconazole group an autopsy, proven aspergillosis has been reported.

Ketoconazole Prevents Fungal Infections in Neutropenic Children

Ketoconazole Prevents Fungal Infections in Neutropenic Children

Severe Gram-negative infections in neutropenic children cured by imipenem/cilastatin in combination with an aminoglycoside

Nine severe Gram-negative septicaemias in neutropenic (less than 500 neutrophils/mm3) children with neoplastic diseases were treated with imipenem/cilastatin (75 mg/kg/day) in combination with an aminoglycoside. The bacterial strains (Pseudomonas aeruginosa 7, P. putida 1, Enterobacter cloacae 1) were resistant to penicillins and cephalosporins, or were isolated during treatment with a broad-spectrum penicillin to which the bacterial strain was sensitive in vitro. The mean duration of neutropenia was 18.5 (3-51) days and duration of treatment 20 (8-51) days. Pyrexia was controlled in 2.8 (1-10) days and eradication of the pathogen from blood in one day. No clinical and biological adverse reaction was observed. These results show imipenem/cilastatin to be an effective treatment of infections in severely immunocompromised patients.

Granulocyte transfusions in children using filter-collected cells.

Twenty-three children with various stages and morphologic types of leukemia were treated with multiple granulocyte transfusions obtained by filtration leukapheresis when neutropenia-associated infection appeared unresponsive to antibiotics. All children meeting the above qualifications were given granulocyte transfusions during this time period. Twenty-one of 23 became afebrile during or shortly after the transfusions; one died with disseminated Herpes simplex; and one became well enough to be discharged, although he was never free of fever. Frequent mild to moderate fever and chills were noted. One child developed a severe pulmonary reaction followed by resolution of pneumonia. Filtration leukapheresis is a useful adjunct in controlling severe infections in neutropenic children.

Granulocyte transfusion in treatment of infected neutropenic children.

Thirty episodes of infection in severely neutropenic children with acute leukaemia and aplastic anaemia resistant to antibiotics were treated with total of 51 granulocyte transfusions collected from normal donors by means of an Aminco continuous flow cell separator. The mean granulocyte increment in the recipients was 820/mm3 at 1 hour and 307/mm3 at 15 hours post-transfusion and it showed a correlation with the number of cells transfused, the size of the child, and his pretransfusion granulocyte count. Fifteen (50%) episodes responded clinically by 24 hours and 23 (77%) by 5 days post-transfusion. Two more children recovered more slowly and 5 died. Poor response was associated with multiple-site infections and with a prolonged period of infection before granulocyte transfusion, but the primary diagnosis did not influence the outcome. We conclude that granulocyte transfusion significantly reduces the mortality and morbidity from infection in neutropenic children with acute leukaemia.