Athanasios Michos

ASEPTIC MENINGITIS IN CHILDREN: ANALYSIS OF 506 CASES

Background Non-polio human enteroviruses are the leading cause of aseptic meningitis in children. The role of enterovirus PCR for diagnosis and management of aseptic meningitis has not been fully explored. Methodology/Principal Findings A retrospective study was conducted to determine the epidemiological, clinical, and laboratory characteristics of aseptic meningitis and to evaluate the role of enterovirus PCR for the diagnosis and management of this clinical entity. The medical records of children who had as discharge diagnosis aseptic or viral meningitis were reviewed. A total of 506 children, median age 5 years, were identified. The annual incidence rate was estimated to be 17/100,000 children less than 14 years of age. Most of the cases occurred during summer (38%) and autumn (24%). The dominant clinical symptoms were fever (98%), headache (94%) and vomiting (67%). Neck stiffness was noted in 60%, and irritation in 46% of the patients. The median number of CSF cell count was 201/mm3 with polymorphonuclear predominance (>50%) in 58.3% of the cases. Enterovirus RNA was detected in CSF in 47 of 96 (48.9%) children tested. Children with positive enterovirus PCR had shorter hospitalization stay as compared to children who had negative PCR or to children who were not tested (Pu200a=u200a0.01). There were no serious complications or deaths. Conclusions Enteroviruses accounted for approximately one half of cases of aseptic meningitis. PCR may reduce the length of hospitalization and plays important role in the diagnosis and management of children with aseptic meningitis.

Macrolide resistance in Streptococcus pyogenes: prevalence, resistance determinants, and emm types ☆ ☆☆

To investigate the antimicrobial resistance trends and the distribution of emm types of group A streptococci (GAS), we examined 1160 clinical isolates of GAS collected between 2003 and 2006. Susceptibilities to commonly used antimicrobial agents were determined by Etest, and macrolide resistance genes were detected by polymerase chain reaction (PCR). GAS isolates were typed by polymerase chain reaction PCR and sequencing of emm gene. The rates of resistance to erythromycin (ERY), clindamycin, azithromycin, tetracycline, and chloramphenicol were 14.9%, 1.4%, 14.9%, 18.9%, 0.6%, respectively. None of the isolates exhibited resistance to penicillin, ceftriaxone, linezolid, moxifloxacin, rifampicin, or vancomycin. Macrolide resistance increased from 12.1% in 2003 to 18.8% in 2006 (P = 0.02). Of 173 ERY-resistant GAS isolates, 93 (53.7%) harbored the mefA gene, 70 (40.4%) the ermA, and 10 (5.8%) the ermB. Eighty percent of the observed emm types are covered by the proposed 26-valent GAS vaccine. Among 173 ERY-resistant isolates, the predominant emm types were 12 (19.5%), 77 (17.9%), and 4 (16.8%), and among 770 ERY-susceptible isolates, the predominant types were 1 (18.8%), 12 (17.5%), 28 (13.8%). The observed antimicrobial resistance trends and the distribution of specific emm types have implications in guiding empiric therapy and in developing vaccine strategies to prevent GAS infections.

Epidemiology of invasive childhood pneumococcal infections in Greece.

A retrospective study was conducted to identify the epidemiologic characteristics of invasive pneumococcal infections among children <14y of age in our geographic region. During a 5‐y period, from 1995 to 1999, 590 cases of invasive pneumococcal infection were identified in Aghia Sophia Childrens Hospital, Athens, Greece. The male to female ratio was 1.4:1 and 64% of patients were younger than 5 y of age. The overall annual incidence rate was estimated as 44/ 100000 children <14y of age, whereas the incidence rate for children <5y of age was 100/ 100000. The most common types of infections were pneumonia (472 cases; 133 definite and 339 probable), bacteraemia without focus (79 cases), and meningitis (33 cases). A seasonal variation of invasive pneumococcal infections was noted, with two peaks‐one during spring and the other during autumn. Only two cases with meningitis died and one developed permanent neurological sequelae, representing a case‐fatality rate for meningitis of 6%. Serogroups 14, 19, 6, 18, 23, 4 and 9 were the most prevalent, comprising 77% of 92 serotyped isolates.

Severe Combined Immunodeficiency in Greek Children over a 20-Year Period

Severe combined immunodeficiencies (SCID) are a heterogeneous group of genetic disorders characterized by a blockade or impairment of both cellular and humoral immunity. Several epidemiological studies in different geographic areas have shown that the most common type of SCID affecting almost half of these patients is the X-linked common γ-chain (γc) deficiency. The objective of the study was to document the incidence and types of SCID in our area. We conducted a retrospective analysis of patients who were diagnosed with SCID in the major immunology center in Greece for a 20-year period. During the study period, 30 children from 27 unrelated families with final diagnosis of SCID were identified. The incidence of SCID in Greece is estimated at 1.7 cases per 100,000 live births. Out of 30 children, 19 were boys (63.3%) and 26 (86.7%) had Greek maternal origin. Lymphocyte immunophenotypes that were identified were T−B−NK+ in 12 (40%) children, T−B+NK− in six (20%), T−B+NK+ in three (10%), T−B−NK− in two (6.7%) and T+B+/−NK+ in seven (23.4%) (among them, four [13.4%] females with Omenn’s syndrome). Molecular diagnosis was available for 12 children: γc (2) with non Greek maternal origin, Jak3 (2), Rag1 (2), Artemis (3), ADA deficiency (2), PNP deficiency (1). Out of the 26 children of Greek maternal origin diagnosed with SCID representing 23 distinct families, only two (8.7%) had lymphocyte immunophenotype compatible with γc-chain gene mutation (no molecular testing or enough DNA was available for them at the time of diagnosis). Findings of the present study suggest that, for unknown reasons, mutations of the γc chain of several cytokine receptors have a rare occurrence in our area.

Pneumococcal Mastoiditis in Children Before and After the Introduction of Conjugate Pneumococcal Vaccines.

Objectives: To determine whether serotype distribution and antibiotic resistance of Streptococcus pneumoniae acute mastoiditis (AM) in children have changed in the post pneumococcal conjugate vaccines (PCVs) era. Methods: Medical records of pneumococcal AM cases, in a tertiary pediatric hospital were reviewed from January 1999 to December 2014. S. pneumoniae isolates were serotyped using the quellung reaction and tested for antibiotic susceptibility by E-test and for macrolide resistance genes by polymerase chain reaction. Results: Among 334 children with AM, S. pneumoniae was isolated from 89 (26.6%) with median age 22 months (interquartile range: 12–30 months). S. pneumoniae was recovered from ear fluid (58%), mastoid specimens (35.2%) and blood (6.8%). Resistance to penicillin, erythromycin and clindamycin was 12.4%, 49.4% and 18%, respectively. Distribution of pneumococcal serotypes before (1999–2005), after the introduction of PCV7 (2006–2010) and after PCV13 (2011–2014) was found: for the PCV7 serotypes 81%, 25% and 0% (P < 0.0001), for PCV13 additional serotypes 16.3%, 70.8% and 63.6% (P < 0.0001) and for non-PCV serotypes 2.3%, 4.1% and 36.3% (P = 0.0002), respectively. Significant increase was detected for the serotype 19A after PCV7, and this trend was not changed after PCV13 (2.3%, 50% and 50%, respectively; P < 0.0001). A significant proportion of resistant isolates to penicillin (54.5%) and erythromycin (34.8%) was identified as 19A. Conclusions: After the introduction of PCV7, a significant increase of serotype 19A and replacement of PCVs serotypes was identified. After PCV13, the overall proportion of pneumococcal mastoiditis and the incidence of serotype 19A were not significantly declined. A significant proportion of resistant isolates to penicillin and erythromycin is attributed to serotype 19A.

Rotavirus Gastroenteritis in a Neonatal Unit of a Greek Tertiary Hospital: Clinical Characteristics and Genotypes

Introduction Rotavirus (RV) infection in neonatal age can be mild or even asymptomatic. Several studies have reported that RV is responsible for 31%-87% of pediatric nosocomial diarrhea and causes gastroenteritis outbreaks in pediatric and neonatal units. Objectives Study clinical characteristics, genotypes and risk factors of RV infection in neonatal age. Methods A prospective study was conducted from April 2009 till April 2013 in the neonatal special care unit of the largest tertiary pediatric hospital of Greece. Fecal samples and epidemiological data were collected from each neonate with gastrointestinal symptoms. RV antigen was detected with a rapid immunochromatography test. RV positive samples were further genotyped with RT PCR and sequencing using specific VP7 and VP4 primers. Results Positive for RV were 126/415 samples (30.4%). Mean age of onset was 18 days. Seventy four cases (58%) were hospital acquired. Seasonality of RV infection did not differ significantly throughout the year with the exception of 4 outbreaks. Genotypes found during the study period were G4P[8] (58.7%), G1P[8] (14.7%), G12P[8] (9.3%), G3P[8] (9.3%), G12P[6] (5.3%), G9P[8] (1.3%) and G2P[4] (1.3%). RV cases presented with: diarrhea (81%), vomiting (26.2%), fever (34.9%), dehydration (28.6%), feeding intolerance (39.7%), weight loss (54%), whilst 19% of cases were asymptomatic. Comparing community with hospital acquired cases differences in clinical manifestations were found. Conclusions Significant incidence of nosocomially transmitted RV infection in neonatal age including asymptomatic illness exists. Genotypes causing nosocomial outbreaks are not different from community strains. Circulating vaccines can be effective in prevention of nosocomial RV infection through herd immunity.

Teeth and tongue discoloration after linezolid treatment in children.

We describe 3 children who developed teeth and tongue discoloration while receiving intravenous linezolid for 2 to 3 weeks. Linezolid was coadministered with piperacillin-tazobactam or meropenem. Teeth and tongue discoloration was reversible with dental cleaning after discontinuation of linezolid. We review the published pediatric and adult cases regarding teeth and tongue discoloration after linezolid administration.