Lyme Neuroborreliosis in Children: Etiology and Comparison of Clinical Findings of Lyme Neuroborreliosis Caused by: Borrelia garinii: and: Borrelia afzelii Background: Information on the etiology of Lyme neuroborreliosis (LNB) in children in Europe and the influence of Borrelia burgdorferi sensu lato species isolated from cerebrospinal fluid (CSF) on clinical presentation of LNB in children are limited. Methods: The study was monocentric. During its 17-year period, children younger than 15 years with presentation suggestive of LNB or confirmed Lyme borreliosis that had B. burgdorferi sensu lato isolated from CSF and had species of B. burgdorferi sensu lato identified by pulsed-field gel electrophoresis were included. Demographic and medical data were compared for children infected with Borrelia garinii to those infected with Borrelia afzelii. Results: One hundred and fifty-three children had B. burgdorferi sensu lato isolated from CSF. In 71/113 (62.8%) and 42/113 (37.2%) patients, B. garinii and B. afzelii, respectively, were identified. Patients infected with B. garinii did not report symptoms suggestive of central nervous system (CNS) involvement or any other symptoms more often than patients infected with B. afzelii. Compared with children infected with B. afzelii, children infected with B. garinii had erythema migrans less often (18.3% vs. 45.2%) but had positive meningeal signs (69.0% vs. 38.1%), CSF lymphocytic predominance (97.1% vs. 75.0%), and elevated albumin CSF/serum quotient (80.6% vs. 50.0%) more often. Conclusions: In Slovenia, LNB in children is more often caused by B. garinii, followed by B. afzelii. The clinical picture of LNB in children caused by B. garinii is not more often suggestive of CNS involvement, but CNS inflammation is more pronounced in children infected with B. garinii, compared with children infected with B. afzelii.

Area Deprivation as a Risk Factor for Methicillin-resistant Staphylococcus aureus Infection in Pediatric Cystic Fibrosis Background: In US cystic fibrosis (CF) patients, methicillin-resistant Staphylococcus aureus (MRSA) rates have tripled in the past 2 decades. Known clinical risk factors include exposure to a healthcare setting, Pseudomonas aeruginosa and CF-related diabetes. Area-level socio-environmental exposures have not been evaluated. We explored the association of area-level deprivation with MRSA prevalence in a pediatric CF Center in the Southeastern United States. Methods: Patients’ residential addresses were geocoded and linked to a composite Area Deprivation Index and Rural-Urban Commuting Area scores. The association of MRSA with Area Deprivation Index and Rural-Urban Commuting Area scores was evaluated using logistic regression with robust standard errors adjusted for sociodemographic covariates (age, sex, race, mother’s and father’s education and household income), clinical risk factors (P. aeruginosa, CF-related diabetes, hospitalizations and number of clinic visits) and clustering. Results: The study included all pediatric patients (N = 231; mean age 12) at a single CF Center. MRSA was present in 44% of subjects. Higher area-level deprivation was correlated with rural residence, lack of parental college education and lower household income (P < 0.001 for each). In a multiple regression model fully adjusted for patient-level sociodemographic covariates, clinical risk factors and clustering, neighborhood deprivation was associated with more than 2-fold increase in the odds of having MRSA [OR 2.26 (1.14–4.45), P < 0.05]. Conclusions: Neighborhood deprivation is a risk factor for MRSA in pediatric CF, doubling the odds of infection. Community-level socioeconomic risk factors should be considered when developing prevention strategies and treatment plans for MRSA infection in pediatric patients with CF.

Contemporary Microbiology and Antimicrobial Treatment of Complicated Appendicitis: The Value of a Short-term Study Background: Antimicrobial stewardship interventions to curtail the use of third-generation cephalosporins and antipseudomonal penicillins for the treatment of complicated appendicitis in children are challenging given the tendency to treat complicated disease with broad-spectrum antimicrobials. Reasons for this are unclear, but there is a paucity of contemporary microbiologic data associated with the child presenting with either acute perforated or gangrenous appendicitis. This study aimed to justify the appropriateness of an empiric regimen consisting of ampicillin, tobramycin/gentamicin plus metronidazole and to analyze duration of postoperative therapy. Methods: We conducted a retrospective cohort study from February 1, 2017, to October 31, 2018, in children who underwent appendectomy or interventional radiologic drainage for primary complicated appendicitis. The primary outcome was the proportion of patients who had a pathogen isolated from peritoneal fluid culture that was not susceptible to the recommended empiric therapy. The secondary outcomes were the total duration of antimicrobial therapy and the proportion of patients with a postoperative infectious complication within 30 days after intervention. Results: Of 425 children with primary acute appendicitis, 158 (37%) had complicated appendicitis at presentation. Culture was performed in 53 (40%) of the 133 who underwent a surgical or interventional radiologic intervention. The group with peritoneal cultures was more likely to present with longer symptom duration before admission [3 (interquartile range, 2–5) vs 2 (interquartile range, 1–2) days; P < 0.001] and with purulent peritonitis [47% (25/53) vs 13% (10/80); P < 0.001]. The most common pathogens isolated were anaerobes (81%), Escherichia coli (74%) and Streptococcus anginosus group (62%). Only 4% of isolated bacteria were resistant to empiric therapy. Postoperative infectious complications were documented in 23 (17%) patients and were not associated with the presence of a resistant pathogen or the choice of antimicrobial agents but with more severe disease and higher C-reactive protein values (303 vs 83 mg/L; P=0.03) at presentation. Conclusions: In a cohort of previously healthy children presenting with complicated appendicitis requiring surgical drainage, the most common bacteria from peritoneal cultures continue to be S. anginosus, aminoglycoside-susceptible Gram-negative bacilli and anaerobes. In an attempt to reduce extended-spectrum cephalosporin use, these data were useful in supporting the use of metronidazole with ampicillin and an aminoglycoside, rather than third-generation cephalosporins.

Intravenous Artesunate for Imported Severe Malaria in Children Treated in Four Tertiary Care Centers in Germany: A Retrospective Study Background: Intravenous artesunate (ivA) is the standard treatment for severe malaria. Data systematically evaluating the use of ivA in pediatric patients outside malaria-endemic regions are limited. The aim of this case series was to summarize efficacy and safety of ivA for imported severe malaria in children in Germany. Methods: Our retrospective case series included pediatric patients with imported severe malaria treated with at least 1 dose of ivA (Artesun, Guilin Pharmaceutical; Shanghai, China) at 4 German tertiary care centers. Severe malaria was defined according to World Health Organization criteria. Results: Between 2010 and 2018, 14 children with a median [interquartile range (IQR)] age of 6 (1;9.5) years were included. All children were of African descent. All but 2 patients had Plasmodium falciparum malaria; 1 child had P. vivax malaria and 1 child had P. falciparum and P. vivax co-infection. Median (IQR) parasitemia at admission in patients with P. falciparum was 9.5% (3;16.5). Patients were treated with 1–10 [median (IQR) 3 (3;4)] doses ivA. All but one patient received a full course of oral antimalarial treatment. Parasite clearance was achieved within 2–4 days, with the exception of 1 patient with prolonged clearance of peripheral parasitemia. Three patients experienced posttreatment hemolysis but none needed blood transfusion. Otherwise ivA was safe and well tolerated. Conclusions: ivA was highly efficacious in this pediatric cohort. We observed episodes of mild to moderate posttreatment hemolysis in approximately one-third of patients. The legal status and usage of potentially lifesaving ivA should be evaluated in Europe.

Risk Factors for Recurrent Community-associated Clostridiodes Difficile Infection in Children Background: Recurrence of community-associated (CA) Clostridiodes difficile infection (CDI) approaches 30%. Studies on risk factors and treatment of choice for pediatric CA-CDI are scarce with variable recommendations. Methods: This was a retrospective cohort study of the electronic health records of children 1–17 years with stool specimens sent for C. difficile at Kaiser Permanente Northern California from January 01, 2012 to December 31, 2016. Children with (1) CA disease, (2) confirmatory C. difficile laboratory testing with no other identified causes of diarrhea and (3) clinical symptoms consistent with CDI were defined as cases. Recurrent CA-CDI was defined using the above-described case criteria and onset of diarrhea within 8 weeks of primary CA-CDI. Results: Of the 7350 children with stool samples sent for C. difficile testing, 408 had primary CA-CDI. Forty-five (11%) experienced a recurrence. Using multivariable logistic regression, inflammatory bowel disease [odds ratio (OR) 7.5; 95% confidence interval (CI): 2.6–21.1] and cancer (OR 6.3; 95% CI: 1.6–24.1) diagnoses were risk factors for recurrent disease. Compared with children of Caucasian race, those with multi/other/unknown race had an OR of 3.03 (95% CI: 1.04–8.82) of recurrence. There was no statistically significant difference in the type or duration of therapy as a predictor for recurrent CA CDI. Six percent of children who received metronidazole were switched to vancomycin due to subjective metronidazole allergy or intolerance or metronidazole treatment failure. Conclusions: Recurrent CA-CDI in children in our population is less common than previously reported. This study supports first-line treatment with the standard, short course metronidazole in most cases of primary CA-CDI.

Identification of Norovirus and Human Parechovirus in Patients With Hand, Foot and Mouth Disease Syndrome Background: Hand, foot and mouth disease (HFMD) is caused mostly by enteroviruses. However, other viral agents also can cause similar syndromes, and hence, the infections they cause are often misdiagnosed clinically. To determine non-enterovirus etiologic agents in HFMD-like cases, we screened enterovirus-negative samples collected from the patients who were clinically diagnosed as HFMD in China. Methods: Two hundred enterovirus-negative samples were collected previously in Wenzhou city of Zhejiang province, China. Both high throughput sequencing and RT-PCR were used to screen viral agents. In addition, their clinical features were analyzed. Results: Norovirus (NoV) and human parechovirus (HPeV) were identified from 22 (11.00%) and 9 (4.50%) samples, respectively. In addition, the complete genome sequences were recovered from 4 NoV-positive samples, and the VP1/3Dpol gene sequences were recovered from 5 HPeV-positive samples. Phylogenetic analyses of the NoV sequences revealed that they were closely related to those circulated in other regions of China. Notably, 4 genotypes of HPeVs, including HPeV-1, HPeV-4, HPeV-5 and HPeV-14, were found, indicating high genetic diversity of the virus. Frequent recombination between various genotypes was also observed in the HPeVs. Although most of the patients presented with the clinical features of HFMD, 4 patients infected with NoV GII.4 and 3 patients infected with HPeV-1 (1) and HPeV-4 (2) were characterized with diarrhea. Finally, tonsillitis, convulsion and granulocytopenia were observed in 1 NoV GII.4 patient, while liver dysfunction was found in 1 NoV GII.17 patient. Conclusions: These data reveal the variety of agents in the cases clinically diagnosed as HFMD.

Norovirus Activity and Genotypes in Sporadic Acute Diarrhea in Children in Shanghai During 2014–2018 Background: Based on the impact public health of norovirus and the current progress in norovirus vaccine development, it is necessary to continuously monitor the epidemiology of norovirus infection, especially in children who are more susceptible to norovirus. Objectives: To monitor the activity and genotypes of norovirus infection in sporadic diarrhea in Shanghainese children during 2014–2018. Study design: Acute diarrheal cases were prospectively enrolled in the outpatient setting. Real-time reverse transcription-polymerase chain reaction was used for screening norovirus GI and GII genogroups. Dual norovirus genotypes were identified based on the partial capsid and polymerase gene sequences. Results: Of the 3422 children with diarrhea, 510 (14.9%) were positive for noroviruses with 13 (2.5%) strains being GI genogroup and 497 (97.5%) strains being GII genogroup. Five distinct capsid GII genotypes were identified, including GII.4-Sydney/2012 (71.8%), GII.3 (13.8%), GII.17 (7.8%), GII.2 (6.0%), GII.6 (0.3%) and GII.8 (0.3%). Seven polymerase GII genotypes were identified, including GII.Pe (77.0%), GII.P12 (11.0%), GII.P17 (9.0%), GII.P16 (2.1%), and GII.P7, GII.P8 and GII.P2 in each (0.3%). Eleven distinct polymerase/capsid genotypes were identified with GII.Pe/GII.4-Sydney/2012 (74.2%), GII.P12/GII.3 (11.7%) and GII.P17/GII.17 (7.7%) being common. GII.P17/GII.17 strains were detected since September 2014. Recombinant GII.P16/GII.2 strains were detected since December 2016. Conclusions: Norovirus is a major pathogen causing diarrhea in Shanghainese children. GII.Pe/GII.4-Sydney/2012 strains remained the predominant genotype. The emergence of GII.P17/GII.17 and GII.P16/GII.2 strains in sporadic diarrhea was consistent with norovirus-associated outbreaks attributable to these 2 novel variants in China. Continuous monitoring norovirus genotypes circulating in pediatric population is needed for current vaccine development.

The Epidemiology of Herpes Zoster in the United States During the Era of Varicella and Herpes Zoster Vaccines: Changing Patterns Among Children No abstract available

Risk Factors for Influenza Virus Related Severe Lower Respiratory Tract Infection in Children Background: Influenza virus is one of the most common respiratory pathogens for all age groups and may cause seasonal outbreaks. Our aim was to identify risk groups and factors associated with severe clinical course including mortality in children with influenza-related lower respiratory tract infection (LRTI). Methods: We conducted a retrospective study in children hospitalized with influenza virus LRTI from 2008 to 2018. Data on demographic features, influenza type, viral coinfection, primary and secondary bacterial infections (SBIs), time of onset of antiviral treatment, comorbidities, hospitalization length, pediatric intensive care unit admission/invasive mechanical ventilation (IMV) need and mortality were collected from medical records. Results: There were 280 patients hospitalized with LRTI and median hospitalization length was 9 days. Congenital heart disease, neuromuscular disease, SBIs and late-onset antiviral treatment were independent risk factors for prolonged hospital stay (P < 0.05). Pediatric intensive care unit admission was present in 20.4% (57) of the patients and 17.1% (48) of all patients required IMV. SBIs, lymphopenia, neutrophilia, immunosuppression and human bocavirus coinfection were independent risk factors for IMV support (P < 0.05). Eighteen patients died and immunosuppression, lymphopenia and SBIs were independent risk factors for mortality (P < 0.05). Conclusions: Presence of comorbidity, SBIs, neutrophilia and lymphopenia at admission identified as risk factors for severe influenza infections including need for IMV and death. Although several studies showed that antiviral treatment reduce hospitalization, complications and mortality, there is a lack of prospective trials and patients for antiviral therapy should be carefully chosen by the clinician.

Flavobacteriaceae Bacteremia in Children: A Multicenter Study Background: The Flavobacteriaceae family includes rare pathogens in children; Chryseobacterium indologenes and Elizabethkingia meningosepticum are the most common pathogenic species, with a wide range of clinical presentations and high mortality rate. Although rare, diagnosis is important due to inherent resistance to multiple antibiotics, especially those typically prescribed for empiric treatment of aerobic Gram-negative bacterial infections. Methods: A multicenter retrospective study conducted in 5 Israeli hospitals, describing Flavobacteriaceae bacteremia confirmed by positive blood culture from 1998 to 2018. Results: Thirteen cases were included; 9 isolates were C. indologenes. Bacteremia was nosocomial or healthcare-associated in all cases. Bacteremia was associated with young age (median, 1 year, range 24 days–17 years), with only 2 (15.4%) cases in neonates, Central line-associated bloodstream infection as a source (5/13, 38%) and malignancy (7/13, 54.8%). Thirty-day all-cause mortality was 23% (3/13). Ninety-one percent of isolates were susceptible to trimethoprim-sulfamethoxazole, 82% to piperacillin-tazobactam and 92% to ciprofloxacin. Conclusions: C. indologenes and E. meningosepticum are rare, nosocomial- or healthcare-associated pediatric bacteremia pathogens. Bacteremia was associated with young age, but in contrast to the literature, the majority of our cases were older than the neonatal age period. In addition, they were associated with central line-associated bloodstream infection and malignancy. The most adequate antibiotics according to resistance patterns were ciprofloxacin, trimethoprim-sulfamethoxazole and piperacillin-tazobactam.