Prospective Nationwide Surveillance Research Articles

Acute bacterial meningitis without cerebrospinal fluid pleocytosis in children: results from a nationwide prospective surveillance system between 2001 and 2022

ObjectivesWe aimed to describe cases of acute bacterial meningitis (ABM) without cerebrospinal fluid (CSF) pleocytosis and the clinical and biological characteristics of affected children. MethodsWe analyzed results of a nation-wide population-based prospective surveillance study of acute ABM in children aged 3 months to 15 years in France. Absence of CSF pleocytosis was defined as CSF leukocyte count ≤5/mm3. ResultsWe included 4754 cases of acute ABM from 2001 to 2022: 173 patients (3.6%) did not have CSF pleocytosis. ABM cases without CSF pleocytosis were mainly related to meningococcus (70% vs 44% with CSF pleocytosis, P <0.001). When performed in CSF with normal leukocyte count, Gram staining results were positive for 33%, culture for 80%, polymerase chain reaction results for 41%, and antigen detection for 20% of cases. Case fatality rate was higher for cases without than those with CSF pleocytosis (18% vs 6%, P <0.001). On multivariate analysis, absence of CSF pleocytosis was associated only with seizures before hospital arrival (adjusted odds ratio 2.3, 95% confidence interval 1.2-4.6, P <0.01). ConclusionsABM without CSF pleocytosis is infrequent but not exceptional, particularly in children with seizures before hospital arrival. Extended vaccination against meningococcus could prevent this clinical form with a high case fatality rate.

Familial and hereditary pancreatic cancer in Japan.

As in Western countries, familial pancreatic cancer accounts for 5-7% of pancreatic cancer (PC) in Japan. Opportunities for diagnosing hereditary pancreatic cancer (HPC) are increasing owing to the coverage of companion diagnostics and cancer genomic profiling by national health insurance in patients with unresectable or recurrent PC refractory to standard chemotherapies. HPC is recognized in 7% of PCs and 15% of familial pancreatic cancer, including germline variants of BRCA1/2, ATM, PALB2, APC, and mismatch repair genes. Individuals with 5-fold or greater inherited risks of PC are recommended to undergo pancreatic surveillance according to Japanese guidelines. The imaging modalities for this surveillance include endoscopic ultrasound, magnetic resonance cholangiopancreatography, abdominal ultrasound, and enhanced computed tomography. Currently, a nationwide prospective surveillance study is ongoing in Japan. Platinum-based chemotherapy is an effective pancreatic cancer treatment in patients with variants of homologous recombination repair genes (BRCA1/2 and PALB2); however, the use of platinum regimens solely based on familial/personal cancer history remains controversial. The efficacy of olaparib maintenance therapy, as confirmed by the POLO study, has significantly impacted the clinical treatment of advanced PC patients in Japan. Since the initiation of precision cancer medicine in 2019, genetic medicine for PC patients has expanded in Japan.

Clinical and Laboratory Biomarkers as Predictors of Severity in Pediatric Inflammatory Multisystem Syndrome-temporally Associated With SARS-CoV-2: Data From a Prospective Nationwide Surveillance Study in Switzerland.

PIMS-TS (pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2) is a rare but serious condition in children following SARS-CoV-2 infection, characterized by a range of clinical symptoms with varying severity. Understanding risk factors for severe PIMS-TS is crucial for appropriate and timely intervention. To identify factors associated with increased PIMS-TS severity in children. In this nationwide prospective observational study, epidemiological and clinical data was collected from children <18 years of age with suspected or confirmed PIMS-TS from all 29 pediatric hospitals in Switzerland. Children were categorized into 3 groups according to admission to intensive care unit (ICU): non-ICU, ICU-moderate and ICU-severe, defined as requirement of invasive ventilation and/or inotropic support. A total of 204 children were included; 99 (49%) were categorized as non-ICU, 50 (25%) as ICU-moderate and 55 (27%) as ICU-severe. In ICU-severe cases, respiratory and neurological symptoms were more frequent compared with non-ICU cases: 72% versus 47%, P < 0.001 and 66% versus 41%, P = 0.001, respectively. Compared with the non-ICU group, children in the ICU-severe group had lower lymphocyte counts, higher neutrophil-lymphocyte ratios, lower platelet counts, as well as higher C-reactive protein, N-terminal pro-B-type natriuretic peptide, troponin T and creatinine levels at admission. Lymphopenia and elevated troponin T levels at admission were associated with an increased risk of being in the ICU-severe group. The severity of PIMS-TS may be predicted using clinical symptoms and laboratory biomarkers, which help clinicians in decision-making and management of patients.

Current practice of intracranial pressure monitoring in children with severe traumatic brain injury-a nationwide prospective surveillance study in Germany.

For management of severe traumatic brain injuries (sTBI) in children, the overall level of evidence to guide diagnostic and therapeutic procedures is low. Since 2016, international guidelines have subsequently suggested invasive intracranial pressure (ICP) monitoring in patients with initial Glasgow Coma Scale (GCS) ≤8. In Germany, ICP monitoring was an individual case decision from 2011 until the 2022 update of the German pediatric TBI guideline. The aim of this study was to evaluate current clinical practice of invasive ICP monitoring in Germany in children <10 years with respect to guideline recommendations. Anonymized clinical data on sTBI cases <10 years of age were collected in a nationwide prospective surveillance study via the German Pediatric Surveillance Unit ESPED from July 2019 until June 2022. Inclusion criteria for the surveillance study were sTBI (initial GCS ≤8) or neurosurgery following TBI. For this analysis, only cases with GCS ≤8 were subject to the present analysis. Descriptive analyses were performed to assess the proportion of ICP monitored patients and describe the cohort. Out of 217 reported cases, 102 cases met the inclusion criteria and thus qualified for ICP monitoring. Of these, 37 (36%) received ICP monitoring. Monitored patients were older, had lower median GCS values at presentation (4 vs. 5), higher mortality (32% vs. 22%), and were more frequently diagnosed with cerebral edema (68% vs. 37%). In children <10 years with sTBI, the present clinical management regarding ICP monitoring deviates from the current German national and international guidelines. The reasons remain unclear, with the low level of evidence in the field of ICP monitoring and the recency of changes in guideline recommendations as potential contributors. Prospective interventional studies should elucidate the benefit of ICP monitoring and ICP directed therapies to provide evidence-based recommendations on ICP monitoring.

Factors influencing the success and complications of intraosseous access in pediatric patients—a prospective nationwide surveillance study in Germany

BackgroundVascular access is essential for the efficient treatment of critically ill children, but it can be difficult to obtain. Our study was conducted to analyze the feasibility and short-term safety of intraosseous access (IO) use as well as factors influencing its success and the incidence of complications in pediatric emergencies and resuscitation. This dataset of systematically documented intraosseous access attempts constitutes one of the largest published in the literature.MethodsTwo-year nationwide prospective surveillance study in Germany from July 2017 to June 2019. Pediatric hospitals anonymously reported the case data of all children aged 28 days to 18 years who arrived with or were treated with an intraosseous access to the German Pediatric Surveillance Unit (GPSU). The main outcomes were the occurrence of complications, overall success and success at the first attempt. The influence of individual factors on outcomes was evaluated using multivariate regression models.ResultsA total of 417 patients underwent 549 intraosseous access attempts. The overall rates of success and success at the first attempt were 98.3% and 81.9%, respectively. Approximately 63.6% of patients were successfully punctured within 3 min from the time of indication. Approximately 47.7% of IO access attempts required patient resuscitation. Dislocation [OR 17.74 (5.32, 59.15)] and other complications [OR 9.29 (2.65, 32.55)] occurred more frequently in the prehospital environment. A total of 22.7% of patients experienced minor complications, while 2.5% of patients experienced potentially severe complications.ConclusionWe conclude that intraosseous access is a commonly used method for establishing emergency vascular access in children, being associated with a low (age-dependent) rate of severe complications and providing mostly reliable vascular access despite a relatively high rate of dislocation.

Cardiac involvement in children with paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): data from a prospective nationwide surveillance study.

Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) may occur 4 to 8 weeks after SARS-CoV-2 infection. The acute presentation of PIMS-TS has been well described, but data on longer-term outcomes, particularly cardiac, is scarce. This prospective nationwide surveillance study included children and adolescents less than 18 years of age who were hospitalised with PIMS-TS in Switzerland between March 2020 and March 2022. Data was collected from all 29 paediatric hospitals through the Swiss Paediatric Surveillance Unit (SPSU) during hospitalisation and approximately six weeks after discharge. The data was analysed after categorising the participants into three groups based on their admission status to the intensive care unit (ICU) (non-ICU, ICU-moderate) and the requirement for invasive ventilatory and/or inotropic support (ICU-severe). Overall, 204 children were included of whom 194 (95.1%) had follow-up data recorded. Median age was 9.0 years (interquartile range [IQR] 6.0-11.5) and 142 (69.6%) were male. In total, 105/204 (51.5%) required ICU admission, of whom 55/105 (52.4%) received inotropic support and 14/105 (13.3%) mechanical ventilation (ICU-severe group). Echocardiography was performed in 201/204 (98.5%) children; 132 (64.7%) had a cardiac abnormality including left ventricular systolic dysfunction (73 [36.3%]), a coronary artery abnormality (45 [22.4%]), pericardial effusion (50 [24.9%]) and mitral valve regurgitation (60 [29.9%]). Left ventricular systolic dysfunction was present at admission in 62/201 (30.8%) children and appeared during hospitalisation in 11 (5.5%) children. A coronary artery abnormality was detected at admission in 29/201 (14.2%) children and developed during hospitalisation or at follow-up in 13 (6.5%) and 3 (1.5%) children, respectively. None of the children had left ventricular systolic dysfunction at follow-up, but a coronary abnormality and pericardial effusion were found in 12 (6.6%) and 3 (1.7%) children, respectively. School absenteeism at the time of follow-up was more frequent in children who had been admitted to the ICU (2.5% in the non-ICU group compared to 10.4% and 17.6% in the ICU-moderate and ICU-severe group, respectively) (p = 0.011). Cardiac complications in children presenting with PIMS-TS are common and may worsen during the hospitalisation. Irrespective of initial severity, resolution of left ventricular systolic dysfunction is observed, often occurring rapidly during the hospitalisation. Most of the coronary artery abnormalities regress; however, some are still present at follow-up, emphasising the need for prolonged cardiac evaluation after PIMS-TS.

Haemophilus influenzae Type b Vaccine Failure in Portugal: A Nationwide Multicenter Pediatric Survey.

Despite the high effectiveness of the Haemophilus influenzae type b (Hib) vaccine in preventing invasive disease (ID) in children, Hib vaccine failures (VFs) cases may still occur. This study aimed to characterize the Hib-VF cases in Portugal in a 12-year period and trying to identify the possible associated risk factors. Prospective descriptive nationwide surveillance study. Bacteriologic and molecular studies were performed at the same Reference Laboratory. Clinical data were collected by the referring pediatrician. Hib was identified in 41 children with ID and 26 (63%) were considered VF. Nineteen (73%) cases occurred in children less than 5 years old; 12 (46%) occurred before the Hib vaccine booster dose at 18 months of age. Comparing the first and the last 6-year periods of the study, the incidence rate of Hib, VF and total H. influenzae (Hi) ID significantly raised (P < 0.05). VF cases corresponded, respectively, to 13.5% (7/52) and 22% (19/88) of total Hi-ID cases (P = 0.232). Two children died due to epiglottitis and 1 acquired sensorineural hearing loss. Only 1 child had an inborn error of immunity. The immunologic workup performed in 9 children revealed no significant abnormalities. All 25 Hib-VF strains analyzed belonged to the same clonal complex 6. In Portugal, more than 95% of children are vaccinated against Hib, but severe Hib-ID cases still occur. No predisposing factors were clearly identified to justify the increased number of VF in recent years. Along with continued Hi-ID surveillance, Hib colonization and serologic studies should be implemented.

2041. Impact of Coronavirus Disease 2019 pandemic on healthcare-associated infections at intensive care unit in South Korea: Data from Korean National Healthcare-associated Infections Surveillance System (KONIS)

Abstract Background Coronavirus Disease 2019 (COVID-19) pandemic has influenced hospital infection control practices. We evaluated the impact of the COVID-19 pandemic on healthcare-associated infections (HAIs) in the intensive care unit. Methods We conducted a retrospective analysis using data from the Korean National Healthcare-Associated Infections Surveillance System (KONIS). KONIS has conducted nationwide prospective surveillance of HAIs in intensive care units. Comparisons of incidence rates of bloodstream infection (BSI), central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), and ventilator-associated pneumonia (VAP) before (Jan 2018-Dec 2019) and during the COVID-19 pandemic (Jan 2020-Jun 2021) were performed according to hospital size. The microorganism distributions in BSI, urinary tract infection, and pneumonia were compared between the period before and during the COVID-19 pandemic. Results The incidence rate of BSI significantly decreased during the COVID-19 pandemic than in the pre-COVID-19 period (1.38 vs. 1.19 per 10,000 patient-days; P &amp;lt; 0.001) [Table 1]. Incidence rates of CLABSI (2.30 vs. 2.17 per 1,000 device-days; P = 0.03) and VAP (1.03 vs. 0.81 per 1,000 device-days; P &amp;lt; 0.001) decreased significantly during the COVID-19 pandemic than in the pre-COVID-19 period, whereas that rate of CAUTI was similar between the two periods. The annual trends of incidence rate of CLABSI and VAP also has decreased (Figure 1). According to the hospital size, the incidence rate per 1,000 device-days of CLABSI significantly decreased during the COVID-19 pandemic than in the pre-COVID-19 period in small to medium-sized hospitals (300-699 beds). The incidence rate per 1,000 device-days of VAP significantly decreased only in small-sized hospitals (200-449 beds). The microorganism distributions in HAIs did not change significantly. Conclusion The incidence rates of CLABSI and VAP decreased during the COVID-19 pandemic than in the pre-COVID-19 period, which was attributable to the changes in small to medium-sized hospitals. Disclosures All Authors: No reported disclosures.

Neonatal Pseudohypoaldosteronism Type-1 in Japan.

(1) Background: Pseudohypoaldosteronism type 1 (PHA-1) is a disorder caused by renal tubular resistance to aldosterone and is characterized by problems with sodium regulation. PHA-1 is typically divided into primary PHA-1, which is caused by genetic mutation, and secondary PHA-1, which is associated with urinary tract abnormality. However, data on the clinical features of PHA-1 among newborn infants are limited. (2) Methods: We conducted a nationwide prospective surveillance study of neonatal PHA in Japan from 1 April 2019 to 31 March 2022 as part of a rare disease surveillance project of the Japan Society for Neonatal Health and Development. (3) Results: Fifteen cases (male:female = 7:8), including four primary, four secondary, and seven non-classified cases, were reported during the study period. The median gestational age and birthweight were 34 weeks (28–41) and 1852 g (516–4610), respectively. At the onset, the median serum Na and K levels were 132 mEq/L (117–137) and 6.3 mEq/L (4.7–8.3), respectively. The median plasma renin activity was 45 ng/mL/h (3.1–310, n = 9), active renin concentration was 1017 pg/mL (123–2909, n = 6), and serum aldosterone concentration was 5310 pg/mL (3250–43,700). (4) Conclusions: Neonatal PHA-1 was more common among preterm infants with no male predominance. It developed immediately after birth in cases without genetic or renal complications.

Intraosseous access in neonates is feasible and safe - An analysis of a prospective nationwide surveillance study in Germany.

BackgroundThis was a prospective surveillance study to investigate reports on the safety and frequency of use of intraosseous (IO) access in neonates.MethodsOver a two-year period, paediatric hospitals in Germany were asked to report all cases of IO access to the nationwide Surveillance Unit for Rare Paediatric Diseases (ESPED). Hospitals reporting a case submitted responses via an anonymised electronic questionnaire, providing details on indication, success rate, system used, location, duration to first successful IO access, complications, alternative access attempts and short-term outcome. We present a subset of data for IO use in infants of less than 28 days.ResultsA total of 161 neonates (145 term and 16 preterm born infants) with 206 IO access attempts were reported. In 146 neonates (91%), IO access was successfully established, and success was achieved with the first attempt in 109 neonates (75%). There was no significant impact of gestational age or provider’s educational level on success rates. In 71 infants with successful IO access (79%), the estimated duration of placement was less than 3 min. The proximal tibia was the predominant site used. A semiautomatic battery-driven device was used in 162 attempts (88%). The most often applied medications via IO access were crystalloid fluid and adrenaline. Potentially severe complications occurred in 9 patients (6%).ConclusionWithin this surveillance study, IO access in neonates was feasible and safe. IO access is an important alternative for vascular access in neonates.

Etiological and epidemiological features of acute respiratory infections in China

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children <5 years old and school-age children have the highest viral positivity rate (46.9%) and bacterial positivity rate (30.9%). Influenza virus, respiratory syncytial virus and human rhinovirus are the three leading viral pathogens with proportions of 28.5%, 16.8% and 16.7%, and Streptococcus pneumoniae, Mycoplasma pneumoniae and Klebsiella pneumoniae are the three leading bacterial pathogens (29.9%, 18.6% and 15.8%). Negative interactions between viruses and positive interactions between viral and bacterial pathogens are common. A Join-Point analysis reveals the age-specific positivity rate and how this varied for individual pathogens. These data indicate that differential priorities for diagnosis, prevention and control should be highlighted in terms of acute respiratory tract infection patients’ demography, geographic locations and season of illness in China.

Dynamics of Invasive Pneumococcal Disease in Israel in Children and Adults in the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Era: A Nationwide Prospective Surveillance.

Following 13-valent pneumococcal conjugate vaccine (PCV13) implementation in infants worldwide, overall and vaccine-type invasive pneumococcal disease (IPD) rates declined in children, with variable indirect impact on adults. A population-based, prospective, nationwide active surveillance of IPD in Israel, 2004-2019 (for adults ≥18 years, 2009-2019). The 7-valent PCV (PCV7)/PCV13 were implemented in Israel in July 2009/November 2010, respectively, with >90% uptake in children <2 years. The 23-valent pneumococcal polysaccharide vaccine (PPV-23) uptake among those >65 years was ~75%. For pre-PCV episodes with missing serotype, extrapolations were applied. Overall, PCV13 serotypes (VT13) and non-VT13 (NVT) incidence rate ratios (IRRs) comparing pre-PCV (2004-2008), early-PCV (2009-2011), and late-PCV13 (2016-2019) periods were calculated for different age groups. Overall, 8614 IPD cases were recorded. IPD rates declined by 67% in children <5 and 5-17 years, comparing late-PCV13 versus pre-PCV periods (IRR [95% CI]: .33 [.27-.40] and .33 [.21-.50], respectively). For adults, comparing late-PCV13 with early-PCV periods, rates significantly declined by 53% in those aged 18-44, while rates did not decline significantly in other age groups. VT13 rates significantly declined in all ages, with decline rates ranging between 94% in children <5 years and 60% in adults ≥85 years. NVT rates significantly increased in <5-, 50-64-, and ≥65-year age groups. In the late-PCV13 period, serotypes 3, 14, and 19A remained the predominant VT13, while serotypes 8 and 12F emerged as predominant NVTs. Continuous monitoring of circulating serotypes in all ages demonstrated direct and indirect PCV effects, which are essential for the development of new vaccination strategies.

Characteristics of neonatal herpes simplex virus infections in Germany: results of a 2-year prospective nationwide surveillance study

ObjectiveTo assess incidence and burden of neonatal herpes simplex virus (HSV) infections and to explore possible transmission routes.MethodsA 2-year prospective nationwide surveillance study performed in 2017 and 2018. All German...

Prevalence of Capsular Serotype, Pilus Island Distribution, and Antibiotic Resistance in Pediatric and Adult Invasive Group B Streptococcus Isolates: Data From a Nationwide Prospective Surveillance Study in Germany.

For neonates, group B Streptococcus is life threatening. Current prevention strategies remain insufficient, especially for cases of late-onset sepsis, where intrapartum antibiotic prophylaxis has demonstrated no benefit. One promising approach is the vaccination of pregnant women, which offers protective immunity via transplacental transmission of neutralizing antibodies. Our nationwide, prospective surveillance study aimed to characterize the prevalence of pilus antigen, capsular polysaccharide serotypes, and antibiotic resistance from invasive GBS infections in neonates and compare these results with those from children and adults in Germany. Our study includes 173 neonatal isolates of a total of 450 reported cases during the study period (incidence: 0.34/1000 live births), in addition to 2 pediatric and 803 adult isolates. The comparison between neonatal and adult isolates reveals age-dependent differences in capsular serotype and pilus type distribution and differences in antibiotic resistance patterns.

Incidence of and Mortality Due to Human Prion Diseases in Taiwan: A Prospective 20-Year Nationwide Surveillance Study from 1998 to 2017.

IntroductionEpidemiologic studies of Creutzfeldt-Jakob disease (CJD) have been undertaken worldwide since the new variant CJD outbreak in 1996 in the United Kingdom. A nationwide report system, the Creutzfeldt-Jakob Disease Surveillance Unit (CJDSU), directed by the Centers for Disease Control of Taiwan, was established in 1997 to identify human prion diseases.MethodsFrom 1998 to 2017, 647 cases were referred to the committee for confirmation. The report to CJDSU included a structured questionnaire recording the clinical, demographic data, and potential iatrogenic exposure, and the results of the clinical and laboratory examination, including tests of blood and cerebrospinal fluid, electroencephalography, and brain magnetic resonance imaging.ResultsIn total, 356 cases (women, n=178) were ascertained to be human prion diseases, and 97.4% (n=347) were sporadic CJD, including three definite, 314 probable, and 30 possible cases; one probable variant CJD and 8 cases of the genetic form human prion diseases. The age- and gender-specific average annual incidence were also significantly higher in the second decade (0.95/1,000,000) than in the first decade (0.63/1,000,000), with an incidence rate ratio of 1.51. The incidences increased with increasing age, reaching a peak at the age of 70–79 years. The 10-year survival curve for sCJD patients showed that the 1-, 5-, and 10-year cumulative survival rate were 52%, 5%, and 1%, respectively. PRNP polymorphisms in 170 patients showed that 98.8% were M129M and 97.6% E219E.DiscussionThe significant increase in incidence after 2008 suggests the increase in the awareness of this rare disease among physicians. The longer disease duration in patients with sCJD in Taiwan than in other countries indicates that the comprehensive support of the health care system, as well as the end-of-life care culture in Taiwan, may prolong survival time in patients with such a progressive and fatal disease.

Characterizing non-linear effects of hospitalisation duration on antimicrobial resistance in respiratory isolates: an analysis of a prospective nationwide surveillance system

ObjectivesOur objective was to systematically study the influence of length of hospital stay on bacterial resistance in relevant respiratory tract isolates. MethodsUsing prospective epidemiological data from the National Swiss Antibiotic Resistance Surveillance System, susceptibility testing results for respiratory isolates retrospectively retrieved from patients hospitalised between 2008 and 2014 were compiled. Generalized additive models were used to illustrate resistance rates relative to hospitalisation duration and to adjust for co-variables. ResultsIn all, 19 622 isolates of six relevant and predominant species were included. Resistance patterns for the predominant species showed a species-specific and antibiotic-resistance-specific profile in function of hospitalisation duration. The oxacillin resistance profile in Staphylococcus aureus isolates was constantly increasing (monophasic). The pattern of resistance to cefepime in Pseudomonas aeruginosa was biphasic with a decreasing resistance rate for the first 5 days of hospitalisation and an increase for days 6–30. A different biphasic pattern occurred in Escherichia coli regarding amoxicillin-clavulanic acid resistance: odds/day increased for the first 7 days of hospitalisation and then remained stable for days 8–30. In the adjusted models epidemiological characteristics such as age, ward type, hospital type and linguistic region were identified as relevant co-variables for the resistance rates. The contribution of these confounders was specific to the individual species/antibiotic resistance models. ConclusionsResistance rates do not follow a dichotomic pattern (early versus late nosocomial) as suggested by current hospital-acquired pneumonia treatment guidelines. Duration of hospitalisation rather appears to have a more complex and non-linear relationship with bacterial resistance in hospital-acquired pneumonia, also depending on host and environmental factors.

Cerebral Venous Thrombosis in Neonates, Children and Adolescents; Results from the German Pediatric Surveillance Unit for Rare Pediatric Diseases (ESPED)

INTRODUCTIONCerebral sinovenous thrombosis (CSVT) is a serious disease, that leads to longterm neurological sequaelae in the majority of survivors. There is uncertainty with regard to age specific individual risk factors, the impact of hereditary thrombophilia or underlying diseases on development of thrombosis or outcome. Previously published cohort studies have described epidemiology, treatment practices and outcomes, but those studies are limited due to small sample size or diversity of the populations included. Neonatal CSVT is seen as a disease entity different from cerebral thrombosis in older children with regard to etiology and outcome, evidence is lacking. OBJECTIVESTo evaluate the influence of transient risk factors and hereditary thrombophilia on clinical course, treatment practices and early outcome in a population based national cohort of children with CSVT. To study the influence of age (neonatal versus pediatric) on risk factors and outcome in CSVT. METHODSWe conducted a prospective nationwide surveillance study in pediatric patients <18 years through the hospital-based German Pediatric Surveillance Unit (ESPED). We included consecutive patients from 0-18 years of age admitted to hospitals in Germany with diagnosis of a first CSVT with an enrolment period between 2001-2010. Diagnosis was confirmed using MRI or CT imaging. Laboratory analysis of coagulation parameters have either been analyzed according to standardized thrombophilia screening protocols in the local hospitals or centrally in study center at the University of Muenster. We followed the course of disease over a period of 36 months. Follow up investigation included repetitive MRI or CT imaging and questionnaires on clinical outcome and recurrence. RESULTSA total of 599 patients, from birth to 18 years with a diagnosis of CSVT were enrolled in the study. We have observed a male predominance with 61%. 138 (23%) CSVT cases were diagnosed during the neonatal period, 461 (77%) patients were older than one month at time of diagnosis. In our cohort 40% of neonates and 20% of older infants/children developed thrombosis without identified underlying predisposing diseases. The majority of transient triggers associated with the development of thrombosis were local (mastoiditis, 18%) or systemic (sepsis, meningitis, 13%) infections or asparaginase administration during treatment for leukemia or lymphoma (12%). Outcome, dependent both on age at onset and existence of transient triggers was worse in children with spontaneous CSVT compared to triggered CSVT with regard to mortality rate (11 vs. 3%), patency of the veins and neurological impairment. Moreover, presenting symptoms as well as the clinical course differed between neonates and older infants/children. CONCLUSIONIn the pediatric population studied most of CSVT events were associated with infections as transient trigger. CSVT in neonates and children older than 1 months of age differed both with regard to underlying risk factors, treatment and outcome. Age specific, randomized controlled trials comparing treatment strategies are needed to optimize care in these patients. DisclosuresNo relevant conflicts of interest to declare.

Clinical and Microbiological Characteristics of Primary Bacteremia Caused by Klebsiella pneumoniae: A Post-Hoc Analysis of Prospective Nationwide Surveillance

Clinical and Microbiological Characteristics of Primary Bacteremia Caused by Klebsiella pneumoniae: A Post-Hoc Analysis of Prospective Nationwide Surveillance

Research Highlights

Treating and diagnosing opportunistic infections in immunosuppressed patients remains a very important aspect for all clinicians working in the field of transplantation. Candidiasis is the most common fungal infection in hospitalized patients, and for this reason, the correct diagnosis of some of the important Candida albicans or non-albicans Candida species is essential, as invasive candidiasis caused by non-albicans is associated with higher resistance rates.1,2 Mylonakis and coworkers estimated mortality rates in patients who received antifungal therapy immediately after blood cultures to be 24% while a delayed treatment starting on days 2 and 3 increased mortality rates to 37% and 41%, respectively. Candida species are traditionally diagnosed by using microscopy, histopathology, culture, plating samples on chromogenic culture media as well as identifying enzyme, metabolite, structural components of the cell wall (1,3-β-D-glucan), antibody (antimannan) or antigen (mannan). PCR testing comes with shortcomings as well and has not yet been accepted as standard of care. Blood cultures and 1,3-β-D-glucan assays have not been specific for Candida leading to potential false-positive results. Rapid Identification of Medically Important Candida Isolates Using High Resolution Melting Analysis Nemcova E, Cernochova M, Ruzicka F, Malisova B, Freiberger T, Nemec P. PloS ONE. 2015;10(2):e0116940 In this report, the authors describe a combination of real-time polymerase chain reaction (PCR) and high-resolution melting analysis (HRMA) for the rapid detection of 25 medically important Candida species. Real-time PCR followed by HRMA showed reproducible melting peaks for 21 of 25 Candida species. Misidentification occurred with C. orthopsilosis, C. metapsilosis, and C. fabianii. Clinically, the correct diagnosis of C. parapsilosis is significant as this strain is less susceptible to antifungals. Notably all C. parapsilosis were clearly distinguishable from other strains using this method. This is the widest range of Candida species ever tested and identified using the HRMA method including a large number of 143 clinical isolates covering 23 species for validation. Real-time PCR followed by HRMA appears as an efficient and simple method diagnosing most candida species. Of note, the diagnosis can be made within 6 hours based on HRMA compared to 24 to 48 hours with the biochemical methods. T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Mylonakis E, Clancy CJ, Ostrosky-Zeichner L, et al. Clin Infect Dis. 2015;60(6):892–899 A nanodiagnostic method using a manual application of T2 magnetic resonance (T2MR) was used in this study to diagnose 5 Candida species: C. albicans, C. tropicalis, C. Krusei, C. glabrata and C. parapsilosis. A total of 250 blood culture samples were manually supplemented with clinically relevant titres of the above Candida species and 50 samples were used as negative controls. These samples formed the contrived or control arm of the study, and they were randomly inserted into the 2264 clinical specimens to check how different titres of Candida would react to the methodology. A total of 463 samples were excluded for technical errors or invalid results. The results of the primary analysis showed an overall specificity of 99.4% per assay and 98.1% per patient. Importantly, the mean time to obtain a negative result was only 4.2 hours compared to longer than 120 hours for a blood culture (BCT). There were 31 discordant cases between T2MR and blood culture: 2 had positive BCT and negative T2MR and 29 negative BCT but positive T2MR. This can be related to either false-positive T2MR or false negative BCT. The BCT methods are known to have poor sensitivity, and clinical samples are shown to be positive in only 38% of proven invasive candidiasis.3 Therefore, it is very likely that these cases represent Candida species infections that were missed by BCT. Importantly, this new technology has a high sensitivity in identifying non-albicans Candida like C. glabrata for which this test has an overall sensitivity of 84%. This study represents the first extensive clinical trial using T2MR technology. REFERENCES Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39(3):309–317. Chi HW, Yang YS, Shang ST, et al. Candida albicans versus non-albicans bloodstream infections: the comparison of risk factors and outcome. J Microbiol Immunol Infect. 2011;44(5):369–375. Avni T, Leibovici L, Paul M. PCR diagnosis of invasive candidiasis: systematic review and meta-analysis. J ClinMicrobiol. 2011;49(2):665–670.

Pediatric Invasive Haemophilus influenzae Infections in Israel in the Era of Haemophilus influenzae Type b Vaccine

The conjugated Haemophilus influenzae (Hi) type b vaccine caused a marked decrease in invasive Hi disease rates. Nonencapsulated Hi infection now constitutes most invasive Hi morbidity and mortality. This study examines invasive Hi infection incidence in Israel in the postvaccine era years, 2003-2012, and characterizes the epidemiology, clinical diagnosis and case fatality rates of invasive Hi disease in children <15 years of age. An ongoing, nationwide prospective surveillance program for invasive Hi infections in Israel. Epidemiologic and clinical data were collected. Diagnoses were classified as meningitis, pneumonia, bacteremia/sepsis and other clinical foci. Overall, 389 cases of invasive Hi infections were identified; 242 (62%) nontypable Hi (NTHi), 103 (26%) Hi type b (Hib) and 41 (11%) encapsulated non-b Hi (enbHi). Children <1 year of age accounted for 51% of the overall disease. Invasive Hi disease incidence in children <15 years of age was stable with a mean annual incidence (per 100,000) of 2.0 ± 0.4. The highest incidence of invasive Hi infections was among infants <1 year with rates of 6.2, 4.9, 1.6 and 12.7 for NTHi, Hib, enbHi and total Hi, respectively. The clinical diagnoses of NTHi and enbHi were similar, but differed from Hib with the former presenting mostly as isolated sepsis/bacteremia and the latter primarily as meningitis. Among children with invasive Hib infection, 40% were classified as vaccine failure. In the post-Hib vaccination era, invasive Hi morbidity and mortality are largely attributed to NTHi sepsis. Still, with the changing epidemiology of invasive Hi, continued surveillance of all Hi strains is justified.