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Pediatr Infect Dis J ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31725552


BACKGROUND: Data on Candida bloodstream infections in pediatric patients in Europe are limited. We performed a retrospective multicenter European study of the epidemiology and outcome of neonatal and pediatric candidemia. MATERIAL AND METHODS: All first positive blood cultures from patients ≤ 18 years of age with candidemia were registered. Patients' demographic and clinical characteristics and causative Candida species were collected and analyzed. Regression analysis was used to identify factors independently associated with mortality. RESULTS: One thousand three hundred ninety-five episodes of candidemia (57.8% male) were reported from 23 hospitals in 10 European countries. Of the 1395 episodes, 36.4% occurred in neonates (≤ 44 weeks postmenstrual age), 13.8% in infants (> 44 weeks postmenstrual age to 1 year) and 49.8% in children and adolescents. Candida albicans (52.5%) and Candida parapsilosis (28%) were the predominant species. A higher proportion of candidemia caused by C. albicans was observed among neonatal patients (60.2%) with highest rates of C. parapsilosis seen among infants (42%). Children admitted to hematology-oncology wards presented the highest rates of non-albicans Candida species. Candidemia because of C. albicans was more frequent than non-albicans Candida in Northern versus Southern Europe (odds ratio, 2.3; 95% confidence interval, 1.8-2.9; P < 0.001). The all-cause mortality at 30 days was 14.4%. All-cause mortality was higher among patients admitted to the neonatal or pediatric intensive care units than other wards. Over time, no significant changes in species distribution were observed. CONCLUSIONS: This first multicenter European study shows unique characteristics of the epidemiology of pediatric candidemia. The insights obtained from this study will be useful to guide clinical management and antifungal stewardship.

Pediatr Infect Dis J ; 38(12): 1219-1223, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31568253


BACKGROUND: Diagnostic challenges combined with the vulnerability of neonates to develop invasive candidiasis (IC) may lead to antifungal administration in the absence of IC. A modified point-prevalence study was performed to obtain an improved insight and understanding of antifungal prescribing in this specific patient population. METHODS: Neonates and infants ≤90 days of age receiving systemic antifungals from 12 centers in England were included. Data were collected prospectively during 26 consecutive weeks and entered into an online REDCap database. RESULTS: Two hundred eighty neonates and infants were included, the majority ≤1 month of age (68.2%). Prematurity was the commonest underlying condition (68.9%). Antifungals were prescribed for prophylactic reason in 79.6%; of those, 64.6% and 76.3% were extreme low birth weight infants and prematurely born neonates, respectively. Additional risk factors were present in almost all patients, but only 44.7% had ≥3 risk factors rendering them more susceptible to develop IC. Nonpremature and non extremely low birth weight premature infants only scored ≥3 risk factors in 32.6% and 15%, respectively. Fluconazole was the most common antifungal used (76.7% of all prescriptions), and commonly underdosed as treatment. The number of microbiologic proven IC was low, 5.4%. CONCLUSIONS: Neonatal antifungal prophylaxis is commonly prescribed outside the recommendations based on known risk profiles. Fluconazole is the main antifungal prescribed in neonates and infants, with underdosing frequently observed when prescribed for treatment. Number of proven IC was very low. These observations should be taken into consideration to develop a national pediatric Antifungal Stewardship program aiming to guide rational prescribing.

Pediatr Infect Dis J ; 38(6S Suppl 1): S2-S6, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31205236


Invasive fungal diseases (IFD) are an important cause of morbidity and mortality in premature neonates and immunocompromised pediatric patients. Their diagnostic and therapeutic management remains a challenge. A nationwide survey was conducted among 13 of the largest pediatric units in the United Kingdom, to obtain insight in the current management of IFD in neonates and children. All responding centers were tertiary teaching centers. The use of fungal diagnostic tools and imaging modalities varied among centers. Antifungal prophylaxis was prescribed in most centers for extreme-low birth weight (LBW) infants and high-risk hemato-oncologic patients, but with a huge variety in antifungals given. An empirical treatment was favored by most centers in case of febrile neutropenia. First line therapy for candidemia consists of either fluconazole or liposomal amphotericin B, with voriconazole being first-line therapy for invasive aspergillosis. Disseminated invasive aspergillosis was most often mentioned as a reason to prescribe combination antifungal therapy. In conclusion, this survey reinforces the fact that there are still important aspects in the management of pediatric IFD which should ideally be addressed in pediatric clinical trials. Attention needs to be given the knowledge gaps as observed in the results of our survey to optimize the management of IFD in children and neonates.

Pediatr Infect Dis J ; 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30199483


BACKGROUND: Detection of cytomegalovirus (CMV) DNA by real-time polymerase chain reaction (rt-PCR) in dried blood spots (DBS) collected for newborn screening has been assessed for retrospective diagnosis of congenital CMV (cCMV) infection, with variable results (sensitivities ranging from 34% to 100%). We aimed to assess the accuracy of this technique in Spain in a large patient series. METHODS: Ambispective, multicenter study including patients with confirmed cCMV from the Spanish Registry of cCMV patients (REDICCMV). cCMV was established on the presence of CMV DNA in any body fluid, by positive culture findings, or by molecular techniques during the first 2 weeks of life. Children in whom cCMV had been excluded were used as negative controls. Neonatal DBS samples were collected from both groups. The presence of CMV DNA was assessed by rt-PCR (RealStar CMV, Altona, Hamburg, Germany) in a central laboratory. RESULTS: One-hundred and three patients and 81 controls from 10 hospitals were included. The performance of CMV DNA determination in DBS for the diagnosis of cCMV was as follows (95% CI): sensitivity 0.56 (0.47-0.65), specificity 0.98 (0.91-0.99), positive likelihood ratio 22.81 (5.74-90.58), negative likelihood ratio 0.45 (0.36-0.56). Sensitivity increased with the birth viral load (bVL) log category. In cCMV patients, lower bVL was the single variable associated with a negative DBS rt-PCR result (p=0.017). CONCLUSION: The sensitivity of CMV rt-PCR in DBS in our series was low and correlated with the bVL. Thus, a negative DBS result would not rule out cCMV infection, especially in patients with a low viremia level at birth.

Arch Dis Child ; 103(11): 1061-1066, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29871901


BACKGROUND: Human parechovirus (HPeV), like enteroviruses, usually causes mild self-limiting respiratory and gastrointestinal symptoms. In infants, HPeV can occasionally cause serious illnesses, including sepsis-like syndrome and encephalitis. In summer 2016, Public Health England (PHE) received increasing reports of severe HPeV infections nationally. We, therefore, reviewed all infants with confirmed HPeV across England during 2016. METHODS: HPeV cases in infants aged <12 months reported to PHE during 2016 were followed up using a clinical questionnaire. Additional cases identified by clinicians completing the questionnaire were also included. RESULTS: We identified 106 infants with confirmed HPeV infection during 2016. The disease peaked during early summer. Most infants (98/106, 92%) were aged <90 days, and 43% (46/106) were neonates. Fever was the most commonly reported symptom (92%) and signs of circulatory shock were present in 53%. Eighteen infants (18%) required paediatric intensive care admission. Most infants had normal or low C reactive protein concentrations (<10 mg/dL in 75%, <50 mg/dL in 98%). A lumbar puncture was performed in 98% of cases; 92% (33/36) of neonates and 93% (53/57) of older infants had normal white cell count in the cerebrospinal fluid (CSF). Nearly all reported cases (98%) were confirmed by CSF PCR. All infants survived, but five had ongoing seizures after hospital discharge. CONCLUSIONS: HPeV is an important cause of febrile illness in infants and can have severe clinical presentations. Early diagnosis may help reduce antimicrobial use, unnecessary investigations and prolonged hospitalisation. While prognosis remains favourable, some infants will develop long-term complications-paediatricians should ensure appropriate follow-up after discharge.

Pediatr Infect Dis J ; 37(3): e81-e83, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29189657


Perinatal tuberculosis is an uncommon condition but with a high mortality and a challenging diagnosis. We present 4 cases of perinatal tuberculosis managed between 1991 and 2014 in a Spanish Tertiary Hospital. The infection should be considered in patients with progressive respiratory symptoms and with a poor response to conventional antibiotic therapy, especially in those with positive epidemiologic risk. Bronchoscopy can be a useful tool for diagnosis.