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1.
Pediatr Infect Dis J ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31725552

RESUMO

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.

2.
Curr HIV Res ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31644409

RESUMO

BACKGROUND: In resource-rich settings the rate of mother-to-child transmission of human immunodeficiency virus (HIV) has dramatically decreased by virtue of a combination of preventive strategies during the last two decades. CASE PRESENTATION: We present a case of progressive developmental milestone loss in a toddler with previously unknown congenitally acquired human immunodeficiency virus (HIV) infection, complicated by an Epstein-Barr virus (EBV) coinfection. CONCLUSION: Our report underscores the differential diagnosis between HIV encephalopathy and EBV encephalitis and the vertical transmission of the HIV infection, which constitutes an alarming issue in terms of public health.

3.
Microb Drug Resist ; 25(9): 1347-1356, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31364923

RESUMO

We evaluated the effects of enhanced infection control measures (ICMs) on carriage and infections of carbapenem-resistant Gram-negative bacteria (CRGNB) in a pediatric intensive care unit. We conducted a quasi-experimental study, including patients with infections of CRGNB retrospectively for 13 months and those participating in an active surveillance program prospectively for 22 months. Active surveillance (weekly rectal swabs) was implemented during a 63-week subperiod with standard ICMs and a subsequent 27-week subperiod with enhanced ICMs (intensified ICMs supplemented with audits and feedback). Prevalence, colonization pressure, incidence, and infections of CRGNB and compliance with ICMs and enhanced ICMs were recorded. Evaluation of results was performed using time series (TS) and interrupted TS. Compliance with hand hygiene improved during the second subperiod of active surveillance compared with the first; prevalence, colonization pressure, and incidence of CRGNB decreased significantly. The linear trend of centered moving average for carbapenem-resistant Klebsiella pneumoniae (CRKP) decreased from 1.2 to 0.1 infections/1,000 bed-days (IBD) (p = 0.046), while it remained unchanged for carbapenem-resistant Acinetobacter baumannii (CRAB) and increased for carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 0.0 to 2.1 IBD (p < 0.001). Enhanced ICMs can reduce CRKP infections in endemic units, in contrast to CRPA and CRAB infections, which are more difficult to eradicate.

4.
Arch Dis Child ; 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31446393

RESUMO

OBJECTIVE: To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). DESIGN: A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. SETTING: 39 NNUs from 12 countries. PATIENTS: Any neonate admitted to one of the participating NNUs. INTERVENTIONS: This was an observational cohort study. RESULTS: The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. CONCLUSION: AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31265930

RESUMO

OBJECTIVES: To forecast the monthly incidence rates of infections (infections/1000 bed-days, IBD) due to carbapenem-resistant Klebsiella pneumoniae (CRKP), Pseudomonas aeruginosa (CRPA), Acinetobacter baumannii (CRAB) and total Gram-negative bacteria (CRGNB) in an endemic intensive care unit (ICU) during the subsequent year (December 2016-December 2017). METHODS: An observational 52-month period (August 2012-November 2016) was used. Two forecasting models, simple seasonal model for CRGNB, CRKP and CRPA, and Winters' additive model for CRAB infections, were applied. RESULTS: They predicted highest infection rates for CRKP, CRAB and CRGNB in January and September 2017 (23.8/23.4, 24.6/28.5 and 46.8/46.7 IBD, respectively) and for CRPA in February (8.3) and March 2017 (7.9). The highest observed rates for CRKP, CRAB, and CRGNB were indeed in January and September 2017 (25.6/19.04, 34.2/23.8 and 59.8/42.8 IBD, respectively); and for CRPA in February (15.2) and March of the same year (12.7). The increased rates may be associated with personnel's annual work program and behavioral factors. CONCLUSIONS: Forecasting models in endemic ICU's may assist in the implementation strategies of infection control measures.

7.
Pediatr Infect Dis J ; 38(9): 920-928, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31335570

RESUMO

BACKGROUND: Ceftazidime-avibactam is effective and well tolerated in adults with complicated urinary tract infection (cUTI), but has not been evaluated in children with cUTI. METHODS: This single-blind, multicenter, active-controlled, phase 2 study (NCT02497781) randomized children ≥3 months to <18 years with cUTI (3:1) to receive intravenous (IV) ceftazidime-avibactam or cefepime for ≥72 hours, with subsequent optional oral switch. Total treatment duration was 7-14 days. Primary objective was assessment of safety. Secondary objectives included descriptive efficacy and pharmacokinetics. A blinded observer determined adverse event (AE) causality and clinical outcomes up to the late follow-up visit (20-36 days after the last dose of IV/oral therapy). RESULTS: In total, 95 children received ≥1 dose of IV study drug (ceftazidime-avibactam, n = 67; cefepime, n = 28). The predominant baseline Gram-negative uropathogen was Escherichia coli (92.2%). AEs occurred in 53.7% and 53.6% patients in the ceftazidime-avibactam and cefepime groups, respectively. Serious AEs occurred in 11.9% (ceftazidime-avibactam) and 7.1% (cefepime) patients. One serious AE (ceftazidime-avibactam group) was considered drug related. In the microbiologic intent-to-treat analysis set, favorable clinical response rates >95% were observed for both groups at end-of-IV and remained 88.9% (ceftazidime-avibactam) and 82.6% (cefepime) at test-of-cure. Favorable per-patient microbiologic response at test-of-cure was 79.6% (ceftazidime-avibactam) and 60.9% (cefepime). CONCLUSIONS: Ceftazidime-avibactam was well tolerated in children with cUTI, with a safety profile consistent with that of adults with cUTI and of ceftazidime alone, and appeared effective in children with cUTI due to Gram-negative pathogens.

8.
Mycoses ; 62(10): 920-927, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271702

RESUMO

BACKGROUND: Recent outbreaks of Candida auris further exemplify that invasive Candida infections are a substantial threat to patients and healthcare systems. Even short treatment delays are associated with higher mortality rates. Epidemiological shifts towards more resistant Candida spp. require careful surveillance. OBJECTIVES: Triggered by the emergence of C auris and by increasing antifungal resistance rates the European Confederation of Medical Mycology developed an international Candida Registry (FungiScope™ CandiReg) to allow contemporary multinational surveillance. METHODS: CandiReg serves as platform for international cooperation to enhance research regarding invasive Candida infections. CandiReg uses the General Data Protection Regulation compliant data platform ClinicalSurveys.net that holds the electronic case report forms (eCRF). Data entry is supported via an interactive macro created by the software that can be accessed via any Internet browser. RESULTS: CandiReg provides an eCRF for invasive Candida infections that can be used for a variety of studies from cohort studies on attributable mortality to evaluations of guideline adherence, offering to the investigators of the 28 ECMM member countries the opportunity to document their cases of invasive Candida infection. CandiReg allows the monitoring of epidemiology of invasive Candida infections, including monitoring of multinational outbreaks. Here, we describe the structure and management of the CandiReg platform. CONCLUSION: CandiReg supports the collection of clinical information and isolates to improve the knowledge on epidemiology and eventually to improve management of invasive Candida infections. CandiReg promotes international collaboration, improving the availability and quality of evidence on invasive Candida infection and contributes to improved patient management.

9.
Pediatr Infect Dis J ; 38(8): 812-815, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31135647

RESUMO

BACKGROUND: Emergence of extensively drug-resistant (XDR) or pan drug-resistant (PDR) Enterobacteriaceae is a major public threat especially for young patients. Treatment options for these bacteria are extremely limited with no safety data existing for neonates and children. Ceftazidime-avibactam has activity against Gram-negative bacteria producing Klebsiella pneumoniae carbapenemase, but virtually no data exist on its use in neonatal and pediatric patients. METHODS: We present a single-center case series of neonates and children <5 years treated with ceftazidime-avibactam for XDR or PDR K. pneumoniae infections until August 2018. Medical records of patients who received ceftazidime-avibactam for at least 2 days (6 doses) were reviewed. Clinical, laboratory and microbiologic data were collected using a prestructured form. Adverse events and clinical/microbiologic responses and 15- and 30-day outcome were assessed. RESULTS: In our case series, 8 patients (median age 53 days, range from 13 days to 4.5 years) received 9 courses of ceftazidime-avibactam at a dose of 62.5 mg/kg q8h for suspected or proven XDR/PDR K. pneumoniae infections including bloodstream infections (8 courses), central nervous system infections (2 courses) and urinary tract infection (1 course). All patients were critically ill and received other antibiotics prior and concomitantly with the administration of ceftazidime-avibactam. There was no treatment discontinuation due to adverse events. Clinical and microbiologic responses occurred in all patients, and no patient died by day 30. CONCLUSIONS: Administration of ceftazidime-avibactam appears to be well tolerated and efficacious against in vitro susceptible XDR or PDR Enterobacteriaceae without being associated with significant adverse events.

10.
Mol Biol Rep ; 46(3): 3497-3500, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989561

RESUMO

We report a predominance (64.7%) of polyclonal carbapenem-resistant Acinetobacter baumannii (CRAB) strains concurrently producing OXA-23 and OXA-58 carbapenemases in a pediatric intensive care unit in an endemic area. This is the first report of emergence of such double-OXA CRAB strains in a single unit worldwide.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30642942

RESUMO

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) can cause biofilm-related bloodstream infections associated with significant morbidity and mortality worldwide. We investigated the bactericidal activities of colistin (CST), rifampin (RIF), meropenem (MEM), gentamicin (GEN), and tigecycline (TGC) alone and that of CST in combination with RIF, MEM, GEN, or TGC against CR-Kp mature biofilms. Twenty CR-Kp blood isolates were derived from an equal number of bloodstream infections in adult patients. Biofilm formation was assessed by staining with 0.4% crystal violet and measuring the optical density spectrophotometrically at 545 nm. Biofilm damage was measured as the percent reduction of metabolic activity by an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] assay. The MIC50 for biofilms was determined as the minimum concentration that caused ≥50% bacterial damage compared to that for untreated controls. Antibacterial drug interactions were analyzed by the Bliss independence model. Four of the 20 CR-Kp isolates were biofilm producers. Biofilm MIC50s of CST, RIF, MEM, GEN, and TGC for these isolates were 64, 8, >256, 128, and 8 mg/liter, respectively. Synergistic interactions were observed at 32 to 64 mg/liter of CST combined with 0.25 to 4 mg/liter of RIF, at 32 mg/liter of CST combined with 0.007 to 0.25 mg/liter of MEM, and at 16 to 32 mg/liter of CST combined with 16 to 64 mg/liter of TGC. The synergy was highest for CST plus RIF, with a mean ΔE ± standard error (SE) of 49.87% ± 9.22%, compared to 29.52% ± 4.97% for CST plus MEM (P < 0.001) and 32.44% ± 6.49% for CST plus TGC (P < 0.001). Indifferent results were exhibited by CST plus GEN. None of the combinations exhibited antagonism. These drug interaction findings, especially those for CST with RIF, may be of importance in the treatment of biofilm-related CR-Kp infections.

13.
Microb Drug Resist ; 25(5): 712-716, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30589601

RESUMO

The molecular epidemiology of endemic carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB) in an intensive care unit located in an endemic area with high rates of resistance was investigated. A CRPA strain producing VIM and KPC concurrently was detected for the first time in an endemic area. CRKP strains producing K. pneumoniae carbapenemase predominated and were mainly assigned to the "hyperepidemic Greek clone." Predominant OXA-23-like producing CRAB strains were assigned to multiple pulsotypes.

14.
Pediatr Infect Dis J ; 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30418357

RESUMO

BACKGROUND: Treatment with an echinocandin is recommended as first-line therapy for patients with invasive candidiasis including candidemia (ICC). Little is known about the efficacy and safety of anidulafungin in children with ICC. METHODS: Eligible patients with ICC aged 2-<18 years were enrolled into this prospective, open-label, non-comparative, international study (NCT00761267), and received anidulafungin for 10-35 days (3 mg/kg on Day 1, 1.5 mg/kg daily thereafter). Safety was assessed through Week 6 follow-up. Efficacy, measured by global response (based on clinical and microbiologic responses), was assessed at: end of intravenous treatment (EOIVT); end of treatment; Weeks 2 and 6 follow-up. RESULTS: Forty-nine patients (n=19, 2-<5 years; n=30, 5-<18 years) received ≥1 dose of anidulafungin (median 11 days; range 1-35 days) and were assessed for safety. Among 48 patients with a Candida spp. isolated, C. albicans (37.5%), C. parapsilosis (25.0%), C. tropicalis (14.6%), and C. lusitaniae (10.4%) were the most frequent Candida spp. All patients reported ≥1 treatment-emergent adverse event (AE), with diarrhea (22.4%), vomiting (24.5%), and pyrexia (18.4%) being most frequent. Five patients discontinued treatment due to AEs, of which 4 discontinuations were considered related to anidulafungin. All-cause mortality was 8.2% (4/49) by EOIVT and 14.3% (7/49) by Week 6 follow-up. None of 7 deaths during the study period were considered treatment-related. Global response success rate was 70.8% at EOIVT. CONCLUSIONS: These data support the use of anidulafungin as a treatment option for ICC in children aged 2-<18 years at the studied dose.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

16.
J Fungi (Basel) ; 4(4)2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30314389

RESUMO

The main indications for antifungal drug administration in pediatrics are reviewed as well as an update of the data of antifungal agents and antifungal policies performed. Specifically, antifungal therapy in three main areas is updated as follows: a) Prophylaxis of premature neonates against invasive candidiasis; b) management of candidemia and meningoencephalitis in neonates; and c) prophylaxis, empiric therapy, and targeted antifungal therapy in children with primary or secondary immunodeficiencies. Fluconazole remains the most frequent antifungal prophylactic agent given to high-risk neonates and children. However, the emergence of fluconazole resistance, particularly in non-albicans Candida species, should be considered during preventive or empiric therapy. In very-low birth-weight neonates, although fluconazole is used as antifungal prophylaxis in neonatal intensive care units (NICU's) with relatively high incidence of invasive candidiasis (IC), its role is under continuous debate. Amphotericin B, primarily in its liposomal formulation, remains the mainstay of therapy for treating neonatal and pediatric yeast and mold infections. Voriconazole is indicated for mold infections except for mucormycosis in children >2 years. Newer triazoles-such as posaconazole and isavuconazole-as well as echinocandins, are either licensed or under study for first-line or salvage therapy, whereas combination therapy is kept for refractory cases.

17.
Future Microbiol ; 13: 1431-1446, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30256161

RESUMO

AIM: While ventilator-associated pneumonia (VAP) remains frequent in Pediatric ICU, there is no gold standard for diagnosis. METHODOLOGY: We conducted a systematic PUBMED analysis (January 1990-January 2017) searching original, full-length studies addressing only pediatric patients; for VAP diagnosis, only those comparing different diagnostic methods and for VAP prevention those implementing preventive measures. RESULTS: Among 367 articles, 17 and 16 were analyzed for diagnosis and prevention, respectively. For diagnosis, 13 studies used CDC criteria; whereas, 14 assessed algorithms: clinical pulmonary index score, ventilator-associated events and biomarkers. Among five randomized trials assessing preventive strategies one found a role of probiotics. Ventilator-care bundles reduced VAP rates. CONCLUSION: Absence of diagnostic gold standard impedes comparison of current approaches and preventive strategies.

20.
Mycoses ; 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30091261

RESUMO

BACKGROUND: Accurate diagnosis of mucormycosis, a life-threatening fungal infection, remains a challenge for physicians. OBJECTIVES: To identify the causative Mucorales in fresh clinical samples and formalin-fixed paraffin-embedded (FFPE) samples of patients with proven mucormycosis by molecular method. PATIENTS/METHODS: Fresh clinical samples of patients with proven mucormycosis according to the EORTC/MSG criteria admitted between 2015 and 2017 and histopathologically proven FFPE archives collected during 2004-2007 and 2015-2017 from Mazandaran University-affiliated hospitals of northern Iran were included. Seminested PCR targeting the 18S rDNA of Mucorales and ITS region was performed, and PCR products were then sequenced. RESULTS: While culture was positive only in 5 of 9 (56%) of fresh specimen cases, PCR was positive in all 9 (100%) histologically proven mucormycosis. Ten of 18 (56%) FFPE samples were PCR-positive. Overall, Mucorales PCR was positive in 19 of 27 (70%) samples. Mucorales species were Rhizopus arrhizus in 16 (84%) cases, R. arrhizus/Amylomyces rouxii in 2 (10.5%) cases and Rhizopus stolonifer in one case (5.5%). Among 27 mucormycosis cases, 25 (93%) cases were rhinocerebral, and 2 (7%) cases were disseminated. Diabetes mellitus (74%) and neutropaenia (63%) were the main risk factors. CONCLUSIONS: Seminested PCR targeting 18S rDNA region of Mucorales is useful for identification of the causative agents of mucormycosis.

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