[ACUTE OTITIS MEDIA BACTERIOLOGY IN CHILDREN YOUNGER THAN THREE MONTHS IN THE LAST 16 YEARS].

BACKGROUND: Only scant information is available regarding the bacteriology of acute otitis media (AOM) in neonates. OBJECTIVES: To investigate the bacteriology of AOM post the introduction of Pneumococcal Conjugate Vaccine (PCV13) in children younger than 3 months and its relation to the mode of delivery. METHODS: Retrospective bacteriological analysis of middle ear fluids taken from children younger than 60 months suffering from AOM. The effect of PCV13 and mode of delivery, caesarian section vs vaginal delivery, on AOM bacteriology was evaluated and compared between children younger than 3 months (group 1) and children aged 3-60 months (group 2). RESULTS: The prevalence of Streptococcus pneumoniae (S.pneumoniae) and Enterobacteriaceae (E.bact) was higher in group 1 compared to group 2, 47.1% vs 35.8% and 12.3% vs 4.3%, respectively (p<0.001), while that of Haemophilus influenza (H. influenzae) and Group A streptococcus (GAS) was higher in group 2 compared to group 1, 40.3% vs 30.1% and 17.5% vs 8.3% respectively (p<0.001). The mode of delivery did not affect AOM bacteriology. The introduction of PCV13 yielded in an increase in the prevalence of GAS (7% to 15%, P<0.001) in group 1. CONCLUSIONS: S. pneumoniae and E. bact are more common AOM pathogens in neonates. Also, the prevalence of GAS was increased in this age group following the introduction of PCV13. DISCUSSION: Our results are applicable towards the formulation AOM treatment guidelines in neonates. This study contributed additional information on a topic that has not been adequately researched so far - neonatal AOM.

High Rates of ESBL-producing and Gentamycin-resistant Gram-negative Bacteria During the First Week of Life: A Multicenter Cross-sectional Study Among Infants Younger Than 2 Months With Urinary Tract Infection.

INTRODUCTION: Reducing the risk of renal scarring in infants with urinary tract infection (UTI) necessitates timely and effective administration of antimicrobial treatment. The Israeli Medical Association recommends the empirical use of gentamicin and ampicillin for febrile infants younger than 2 months with suspected UTI. We aimed to assess the prevalence of Extended Spectrum Beta-Lactamase (ESBL)-producing and gentamicin-resistant Gram-negative UTI among infants younger than 2 months. METHODS: A multicenter retrospective cross-sectional study of infants younger than 2 months with UTI who visited Clalit Health Services pediatric emergency departments between January 1, 2016, and December 31, 2021. The primary outcome measure was the prevalence of ESBL-associated and gentamicin-resistant UTI. The secondary outcome measure was the factors associated with such resistant bacteria. RESULTS: Overall, 1142 infants were included. Sixty-five (5.7%) and 64 (5.6%) infants had gentamicin-resistant and ESBL-producing Gram-negative UTI, respectively. Forty-two percent of ESBL-associated UTI were gentamicin-resistant. Higher ESBL rates were found during first week of life (14.8% versus 4.1%-7.7%; P = 0.009). Similarly, higher rates of gentamicin resistance were found in this age group (11.2%). Admission rate to pediatric intensive care units (ICUs) was higher in infants with ESBL-associated UTI (9.8% versus 3.5%; P = 0.015). Gestational bacteriuria, previous neonatal ICU admission or gender were not associated with either gentamicin or ESBL-producing resistance. CONCLUSIONS: Our findings support the current recommendations for empirical intravenous treatment. However, modification of the treatment protocol should be considered for infants younger than 7 days, who had higher rates of ESBL-producing and gentamicin-resistant Gram-negative UTI.

Compared perinatal outcomes of two prophylactic antibiotic regimens for preterm premature rupture of membranes: a randomized controlled trial.

BACKGROUND: Prophylactic antibiotic use in preterm premature rupture of membranes is associated with significantly reduced intra-amniotic infection and improved neonatal outcome, although data are insufficient to determine the optimal antibiotic regimen. Ampicillin resistance has changed the epidemiology of neonatal sepsis. OBJECTIVE: This study aimed to determine the efficacy of two antibiotic regimens in prolonging the latency period in women with preterm premature rupture of membranes. STUDY DESIGN: This randomized-controlled trial was conducted in 3 tertiary university-affiliated hospitals. A total of 124 women with preterm premature rupture of membranes at <37 weeks of gestation were randomized into two antibiotic prophylactic protocols: ampicillin + roxithromycin and cefuroxime + roxithromycin. The latency period length, neonatal adverse outcomes, and maternal infectious morbidity, including intrauterine infection, intrapartum fever, postpartum antibiotic treatment, endometritis, and wound infection, were measured and compared. RESULTS: Maternal infectious morbidity was higher in the ampicillin group than in the cefuroxime group (17.7% vs 6.5%; 1-sided P value =.048). The pathogen distribution among placenta, membrane, cord, and uterine cultures differed between the groups (P=.017). Enterobacteriaceae spp. cultures were identified in 68.6% of the cultures in the ampicillin group and 43.2% in the cefuroxime group (P=.036). The composite neonatal adverse outcome was higher in the ampicillin group than in the cefuroxime group (55 [88.7%] vs 46 [74.2%]; 1-sided P value =.03). The proportion of primiparas with a latency period >4 days was significantly higher in the cefuroxime group than in the ampicillin group (odds ratio, 3.69; 95% confidence interval, 1.175-11.607; P=.025). CONCLUSION: In combination with roxithromycin, the use of cefuroxime, as a prophylactic in women with premature rupture of membranes at <37 weeks of gestation, showed longer pregnancy in primiparas and less maternal and neonatal morbidity than the use of ampicillin. Further larger studies are needed to support our results.

Two decades of otitis media in northern Israel: Changing trends in the offending bacteria and antibiotic susceptibility.

OBJECTIVE: Bacteriology and antibiotic resistance trends changed considerably following introduction of the pneumococcal conjugate vaccines (PCV) 7 and 13, with differences between geographic regions. The objective of this study was to evaluate changes in acute otitis media (AOM) bacteriology and antibiotic susceptibility from the pre-vaccination period (2002-2008) to after the introduction of PCV13 (2010-2019) in northern Israel. METHODS: Data were collected from 3277 middle ear fluid (MEF) cultures and 4822 common AOM-generating pathogens of children aged <5 years with otitis media, taken during 2002-2019. Age of the child, bacteriology, and antibiotic resistance were compared between 2002 and 2008, the pre-vaccination period when no vaccination was available and 2010-2019 when PCV13 was introduced. RESULTS: The mean age of the children in the pre-vaccination and the vaccination periods was 18.7 ± 13.7 and 15.7 ± 12.5 months, respectively (p < 0.001); the mean age of those with group A streptococcus (GAS) positive cultures was older, p < 0.001.The prevalence of Streptococcus pneumoniae (S. pneumoniae) decreased between those periods, from 47% to 25.8%, p < 0.001, Haemophilus influenzae (H. influenza) increased from 38.4% to 47.1%, p < 0.001, GAS increased from 12.9% to 23.8%, p < 0.001, and Moraxella catarrhalis (M. cat) increased but not statistically significant from 1.7% to 3.1%. The yearly number of positive MEF cultures decreased from 395.1 to 205.6, p < 0.001. The antibiotic sensitivity rate of almost all antibiotics increased between the two study periods. CONCLUSION: The most common MEF bacteria in northern Israel today is H. influenzae. Comparing the pre-vaccination to the vaccination period, the incidence of S. pneumonia-positive cultures decreased while GAS and H. influenza cultures increased. The age of children with positive cultures increased, and the antibiotic sensitivity rate increased. Key This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The Yield of Targeted Examination for the Detection of Symptomatic Congenital Cytomegalovirus Infection.

BACKGROUND: The incidence of congenital cytomegalovirus (CMV) infection in Israel is 0.7%. Only 10-15% are symptomatic. Valganciclovir has been shown to improve hearing and neurodevelopmental outcomes in neonates with symptomatic congenital CMV infection. Targeted examination of infants who fail routine neonatal hearing screening or have clinical or laboratory findings suggestive of symptomatic congenital CMV infection may be a cost-effective approach. OBJECTIVES: To assess the possibility of targeted examination for the detection of newborns with symptomatic congenital CMV infection. METHODS: A prospective observational study was conducted in 2014-2015 at two medical centers in northern Israel. Included were all newborns who were tested in the first 3 days of life by polymerase chain reaction (PCR) for urine CMV DNA (n=692), either for failure the hearing screening (n=539, 78%), clinical or laboratory findings suggestive of symptomatic congenital CMV infection, or primary CMV infection during pregnancy (n=153, 22%). RESULTS: During the study period 15,433 newborns were born. The predicted rate of infection was 10-15% (symptomatic) of 0.7% of newborns, namely 0.07-0.105% or 10-15 infants. In fact, 15 infants (0.11%, 95% confidence interval 0.066-0.175) were diagnosed with symptomatic congenital CMV infection, 2/539 (0.37%) in the failed hearing group and 13/153 (8%) in the clinical/laboratory findings group. The incidence of symptomatic congenital CMV infection was within the predicted range. CONCLUSIONS: Targeted examination of only 4.5% (n=692) of newborns detected the predicted number of infants with symptomatic congenital CMV infection in whom valganciclovir therapy is recommended.

Risk Factors for Mortality among Newborns with Neonatal Seizures.

OBJECTIVE: The aim of the study is to examine the incidence and risk factors for death among neonates who developed neonatal seizures (NS) in an ethnically distinctive community with high consanguinity rate in Israel. METHODS: Retrospective study was conducted at a single institution on data between January 2001 and January 2016. All neonates diagnosed with NS developed up to age 28 days were included. Mortality was defined as death within the first year of life. RESULTS: Of all 69,460 neonates born during the study period, 118 (1.7 per 1,000 live births) developed NS; 35 (29.7%) died within the first year while 83 (70.3%) survived. The leading causes of death were developmental brain malformation (31.4%), genetic/metabolic (20%), hypoxic ischemic encephalopathy (20%), intracranial hemorrhage (11.4%) and infections (11.4%). Any consanguinity between the parents was found in 18 and 14.6% among the survivors and deceased groups, respectively (p = 0.24). Developmental brain malformations that lead to death were present in 3.6 and 31.4% in the survivors and deceased groups, respectively (p = 0.001; relative risk 8.70; 95% confidence interval 2.58-29.27). Stepwise backward logistic regression analysis revealed that developmental brain malformations (p < 0.0001), use of more than one antiepileptic medication (p = 0.006), and multiorgan failure (p = 0.004) were significant risk factors that predicted death. CONCLUSION: The results of the current study show that developmental brain malformations that cause NS were the leading risk factor for death.

A novel extended prophylactic antibiotic regimen in preterm pre-labor rupture of membranes: A randomized trial.

OBJECTIVES: Prophylactic antibiotic use in preterm pre-labor rupture of membranes (PPROM) is associated with a significant reduction in intra-amniotic infection and improved neonatal outcome. However, data is insufficient to determine the optimal antibiotic regimen. Considering the rise in Escherichia coli and Klebsiella pneumonia early-onset sepsis rate and the emergence of ampicillin resistance, our aim is to compare the efficiency of two antibiotic regimens in prolonging pregnancy and reducing infectious morbidity. DESIGN: This multicenter randomized unblinded controlled prospective trial compared two antibiotic prophylactic protocols in PPROM: ampicillin + roxithromycin vs. cefuroxime + roxithromycin in 84 women with PPROM, from 12/2015-12/2019. RESULTS: The median latency period was significantly longer (p = 0.039) in the cefuroxime + roxithromycin group (4.63 [0.59-50.18] days) than in the ampicillin + roxithromycin group (2.3 [0.15-58.3] days). Neonatal admission to neonatal intensive care unit rate, hospitalization length, neonatal respiratory distress syndrome, neonatal fever, and need for respiratory support or mechanical ventilation, were similar between the groups. K. pneumonia cultures were significantly more frequent in the ampicillin + roxithromycin group. None of the cultures were group B Streptococcus positive. CONCLUSIONS: To prolong latency period and reduce gram-negative early-onset sepsis, cefuroxime + roxithromycin is recommended as the first-line protocol in PPROM. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02819570.

Characteristics of hospitalised patients with influenza in 2015-2016 in northern Israel: three circulating strains and continued fear of 2009 A/H1N1.

This study aimed to characterise children and adults diagnosed with influenza who were admitted to three medical centres in northern Israel in the winter of 2015-2016, a unique season due to infection with three types of influenza strains: A/H1N1, A/non-H1N1 and B. Data were collected retrospectively from medical records. Influenza A/H1N1 infected mainly adults (61% vs. 16% in children, P < 0.001) while influenza B was the common type in children (54% vs. 28% in adults, P < 0.001). Adults (36% vs. 5% in children, P < 0.001) and patients infected with A/H1N1 had higher rates of pneumonia (34% vs. 16% and 14% in influenza B and A/non-H1N1, respectively, P = 0.002). Treatment with oseltamivir was prescribed to 90% of patients; adults had higher rates of treatment (96% vs. 84% in children, P = 0.002) as well as patients infected with A/H1N1 (96% vs. 86% in influenza B and A/non-H1N1, respectively, P = 0.04). Oseltamivir was given after a mean of 3.6 days of symptoms. Preferential infection of adults by A/H1N1 was evident in Israel in 2015-2016; pneumonia rates were higher in adults and in A/H1N1-infected patients. Oseltamivir was prescribed to most patients but especially to those infected with A/H1N1, and was given relatively late in the course of the disease.

Validation of a Novel Assay to Distinguish Bacterial and Viral Infections.

BACKGROUND: Reliably distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-proteins (tumor necrosis factor-related apoptosis-inducing ligand, interferon γ-induced protein-10, and C-reactive protein [CRP]) was developed to assist in differentiation between bacterial and viral disease. METHODS: We performed double-blind, multicenter assay evaluation using serum remnants collected at 5 pediatric emergency departments and 2 wards from children ≥3 months to ≤18 years without (n = 68) and with (n = 529) suspicion of acute infection. Infectious cohort inclusion criteria were fever ≥38°C and symptom duration ≤7 days. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results. Assay performers were blinded to the reference standard. Assay cutoffs were predefined. RESULTS: Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum. The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity (95% confidence interval: 87.8%-99.8%) and 89.8% specificity (85.6%-94.0%); 11.7% had an equivocal assay outcome. The assay outperformed CRP (cutoff 40 mg/L; sensitivity 88.2% [80.4%-96.1%], specificity 73.2% [67.6%-78.9%]) and procalcitonin testing (cutoff 0.5 ng/mL; sensitivity 63.1% [51.0%-75.1%], specificity 82.3% [77.1%-87.5%]). CONCLUSIONS: Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.

The herd effects of infant PCV7/PCV13 sequential implementation on adult invasive pneumococcal disease, six years post implementation; a nationwide study in Israel.

BACKGROUND: Introduction of pneumococcal conjugate vaccine (PCV) has nearly eliminated vaccine-type (VT) invasive pneumococcal disease (IPD) in children, yet the reported resulting reduction of adult IPD is variable. We present the indirect impact of sequential PCV7/PCV13 implementation in Israel on adult IPD. METHODS: An ongoing nationwide active surveillance was initiated on July 2009 when PCV7 was implemented (with Catch-up). PCV7 was gradually replaced by PCV13 since November 2010. Comorbidity and outcome data were collected from medical files. Incidence rates were calculated for overall and vaccine-type IPD. RESULTS: A total of 2579 IPD cases were diagnosed among a population of 5.0-5.5 million adults >18y (2009-2015). Incidence rates were 9.15/100,000 and 10.16/100,000 in the first and second study years, respectively. However, after PCV13 implementation, the rates decreased to 7.19 within four years, and remained stable in the two following years. Within 6years, PCV7-VT-IPD incidence decreased from 2.52 to 0.52 (79%) and PCV13-VT-IPD from 6.15 to 1.81 (71%). Concurrently, non-VT13 incidence increased from 2.99 to 5.25. Approximately 50% of all patients were adults ≥65y, in whom the decrease in PCV13-VT-IPD incidence was smaller and slower (65% vs. >80% decrease in adults <50y). CONCLUSIONS: Despite continued reduction in PCV13-VT-IPD, overall IPD was stable during the last two years due to serotype replacement. Yet, the significant decrease in adult IPD, six years post-PCV7/13 implementation emphasizes the importance of indirect protection in achieving overall population impact and should be considered when discussing the potential additional benefits of direct adult PCV vaccination.

Bronchiolitis in young infants: is it a risk factor for recurrent wheezing in childhood?

BACKGROUND: Acute bronchiolitis in infancy is considered a risk factor for recurrent wheezing episodes in childhood. The present study assessed prevalence, clinical manifestations and risk factors for recurrent wheezing events during the first 3 years of life and persistent wheezing events beyond this age in children hospitalized as young infants with acute bronchiolitis. METHODS: Two groups of children aged 6 years were included. The study group comprised 150 children with a history of hospitalization for bronchiolitis, with the first event at <6 months of age. The control group comprised 66 age- and sex-matched children with no history of bronchiolitis before 6 months of age. Children in both groups had been followed until 6 years of age by their pediatricians; data were obtained retrospectively by reviewing ambulatory records during children's visits in pediatricians' clinics. The data included epidemiological parameters, prevalence, age at onset, number of and treatments given for episodes of wheezing events prior to 6 years of age, pathogens detected, and severity of acute bronchiolitis in the study group. RESULTS: Overall, 58% and 27% of children in the study and control groups, respectively (P=0.001) had recurrent wheezing episodes prior to the age of 3 years. Children in the study group had earlier onset of recurrent wheezing, had more episodes of wheezing, and required more bronchodilator and systemic steroids treatments compared to the control group. CONCLUSION: Hospitalization within the first six months of life for acute bronchiolitis is an independent risk factor for recurrent wheezing episodes during the first 3 years of life.

A Case of Infective Endocarditis and Pulmonary Septic Emboli Caused by Lactococcus lactis.

Infective endocarditis is a rare condition in children with normal hearts. We present here a case of previously healthy eleven-year-old girl with infective endocarditis and pulmonary septic emboli caused by a very rare bacterial etiology (Lactococcus lactis). Identification of this pathogen was only made by polymerase chain reaction.

Topical Minocycline Foam for the Treatment of Impetigo in Children: Results of a Randomized, Double-Blind, Phase 2 Study.

BACKGROUND: Currently available treatment options for impetigo are limited by either systemic side effects (for oral therapy) or lack of ease of use (for topical ointment). A novel foam formulation of minocycline for topical use may improve convenience and treatment utilization for pediatric patients with impetigo. OBJECTIVE: To evaluate the safety and efficacy of topically applied minocycline foam (FMX-102 1% and 4%) in the treatment of impetigo and to determine the optimal therapeutic active ingredient concentration. METHODS: In this randomized, parallel-group, double-blind, comparative clinical trial, 32 subjects aged ≥2 years with a clinical diagnosis of pure impetigo, impetigo contagiosa, or uncomplicated blistering impetigo were randomized to treatment with FMX-102 1% or 4%, twice daily for 7 days. Subjects were followed for up to 7 days post-treatment. RESULTS: Clinical cure, defined as ≥80% cured lesions (fully recovered lesions, visually determined by investigators), was achieved by 57.1% and 50.0% of FMX-102 1% and 4% subjects, respectively, at the end of treatment (visit 3). Clinical success, defined as the absence of lesions, or the drying or improvement of treated lesions (decrease in size of affected area, lesion number, or both), was demonstrated in 81.3% and 78.6% of FMX-102 1% and 4% subjects, respectively, following 3 days of treatment (visit 2), in 92.3% and 100% of the respective subjects at the end of treatment, and in 100% in both groups at follow-up (visit 4). Bacteriologic success rates at the end of treatment, defined as complete pathogen eradication, were 85% and 74% in the FMX-102 1% and 4% groups, respectively. The bacteriologic success rate for MRSA infections was 100% (11/11), with no recurrences. Both FMX-102 1% and 4% were considered well tolerated and safe. CONCLUSION: Topical minocycline foam may be a safe and effective new treatment option for impetigo in children, including those with MRSA.

J Drugs Dermatol. 2016;15(10):1238-1243.

Brucellosis Outbreak in Children and Adults in Two Areas in Israel.

Two parallel outbreaks of Brucella melitensis infection occurred in 2014 in two geographical areas in Israel. In two medical centers in northern Israel and one medical center in Jerusalem, 102 patients (58 children, 47 adults) were diagnosed with brucellosis. Most patients (N = 76, 72%) were Muslim Arabs, 28 (27%) were Druze, and one was Jewish. The source of infection was often traced to cheese from the Palestinian Authority. Biovar-1 was evident in 98% in northern Israel but only in 42% in Jerusalem. Most common manifestations were fever (82%) and osteoarticular symptoms (49%). The major differences between the geographic areas were ethnicity and duration until diagnosis. Compared with adults, children had higher rates of hospitalization (93% versus 64%, P = 0.001), osteoarticular symptoms (60% versus 36%, P = 0.05), elevated alanine aminotransferase (12% versus 0%, P = 0.01), and lower C-reactive protein (2.28 ± 2.08 versus 5.57 ± 6.3l mg/dL, P = 0.001). Two unrelated brucellosis outbreaks occurred in 2014 in two different geographic areas of Israel and were limited to sections of the Arab and Druze populations. Most of the demographic and clinical aspects of patients were not affected by geographic variability. Clinical and laboratory differences were found between children and adults emphasizing the nonuniformity of the disease in different age groups. Effective control of unpasteurized dairy foods, health education programs, and improved regional cooperation are required to control brucellosis in Israel.

Severe Acute Mastoiditis Admission is Not Related to Delayed Antibiotic Treatment for Antecedent Acute Otitis Media.

BACKGROUND: Delayed antibiotic treatment for acute otitis media (AOM) is recommended for children >6 months with nonsevere illness, no risk factors for complications or history of recurrent AOM. This study evaluates relationship between delayed antibiotic treatment for antecedent AOM and severity of subsequent acute mastoiditis admission. METHODS: A prospective observational study of children aged 0-14 years admitted with acute mastoiditis to 8 hospitals between 2007 and 2012 calculates rates of severe acute mastoiditis admission [defined by ≥1 of the following: complication (mastoid subperiosteal abscess, brain abscess and sagittal vein thrombosis), need for surgical procedure and duration of admission >6 days].Severe acute mastoiditis admissions in children with antecedent AOM treated with immediate antibiotics were compared with those with delayed antibiotic treatment. RESULTS: Antecedent AOM was diagnosed in 216 of 512 acute mastoiditis admissions (42.1%), of whom 159 (73%) immediately received antibiotics, and 57 (27%) had delayed antibiotic treatment. Higher rate of recurrent AOM was noted in the immediate compared with delayed antibiotic treatment group (29% vs. 8.7%, P = 0.0021). Complication rates were 19.5% versus 10.5% (P = 0.12), rates of surgical procedures required, 30% versus 10% (P = 0.0033); admission rates >6 days, 37% versus 29% (P = 0.28) for immediate antibiotic therapy and delayed antibiotic treatment. On logistic regression analysis, immediately treated AOM patients had increased need for surgery for acute mastoiditis with adjustment for history of recurrent AOM (relative risk: 3.2, 95% confidence interval: 1.4-7.0). CONCLUSIONS: Delayed antibiotic treatment for antecedent AOM is not associated with an increase in severity parameters in subsequent acute mastoiditis admission.

Reconsidering the Current Preterm Premature Rupture of Membranes Antibiotic Prophylactic Protocol.

OBJECTIVE: The purpose of our study was to determine whether the current antibiotic regimen for preterm premature rupture of membranes (PPROM) is adequate for covering the current causative agents and sensitivities of chorioamnionitis and early-onset neonatal sepsis. STUDY DESIGN: During a 3-year period, we retrieved the results from placental and amniotic membrane cultures obtained at delivery in cases of maternal fever, chorioamnionitis, and PPROM, and from blood cultures obtained from neonates with early-onset sepsis (EOS) in three participating hospitals. Sensitivity of pathogens to antimicrobial agents was performed using routine microbiologic techniques. RESULTS: There were 1,133 positive placental or amniotic cultures, 740 (65.3%) were from gram-negative Enterobacteriaceae. There were 27 neonates diagnosed with EOS with positive blood cultures. Aerobic Enterobacteriaceae accounted for 14 cases (52%) and group B streptococcus for 7 cases (26%). Of the Escherichia coli and Klebsiella sp., only 38% were sensitive to ampicillin. CONCLUSION: Local pathogens and their antibiotic sensitivity profiles should be explored every few years and an effective antibiotic protocol chosen to cover the main pathogens causing chorioamnionitis and EOS. Consideration should be made for changing ampicillin in women with PPROM to a regimen with better coverage of gram-negative Enterobacteriaceae.

Early impact of PCV7/PCV13 sequential introduction to the national pediatric immunization plan, on adult invasive pneumococcal disease: A nationwide surveillance study.

BACKGROUND: PCV7 was introduced as a universal childhood vaccination in Israel on July 2009 and was gradually replaced by PCV13 from November 2010. We report data on adult invasive pneumococcal disease (IPD), two years post PCV13 implementation. METHODS: An ongoing nationwide active surveillance (all 27 laboratories performing blood/CSF cultures nationwide), initiated in 2009, providing all blood/CSF Streptococcus pneumoniae isolated from persons ≥18 years. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. Medical history and outcomes were recorded in ∼90%. RESULTS: Of 1809 IPD episodes, S. pneumoniae was isolated from the blood in 95% and most cases had pneumonia. Predisposing comorbidities were present in >70%. During the four study years, overall IPD incidence decreased from 9.2 to 7.2/100,000, incidence of pneumonia and particularly severe pneumonia cases decreased significantly from 6.6 to 4.7/100,000, (p=0.029). Vaccine type (VT7/VT13) serotypes decreased by 70%/57% within 4 years. This was accompanied by a 52% increase in non-VT13 strains. These changes were most apparent in winter. PCV impact was most pronounced in younger adults (39% decrease in overall IPD with only a non-significant increase in non-VT13 cases) while in those >65 years a non-significant decrease in overall IPD was observed with a 64% increase in non-VT13 cases. Non-VT13 serotypes that increased significantly were 12F, 15A 10A and 6C. A continuous reduction in isolates with penicillin MIC>0.06µg/ml was observed (26% to 11%, p<0.001). CONCLUSIONS: Four years after PCV7 and 2.5 years after PCV13 universal implementation in children, incidence of adult IPD caused by VT7 and VT13 decreased in all ages, mainly in younger adults. Despite increase in non-VT13 IPD, overall IPD decreased. Additional follow-up is needed to determine the long-term impact of PCV13.

[THE PREVALENCE OF SUBCLINICAL MYOCARDITIS AMONG YOUNG CHILDREN WITH ACUTE VIRAL INFECTION].

BACKGROUND: Viruses are the most prevalent ausative agents of myocarditis in young children. Studies have shown acute myocarditis in post mortem examinations during viral disease outbreaks. The aims of this study are to assess the prevalence of and risk factors for subclinical acute myocarditis in young children hospitalized with an acute viral disease. OBJECTIVES: Evaluation of the prevalence of asymptomatic myocarditis or decrease in heart functions during viral infection. METHODS: A prospective study was conducted between 1st January and 30th September, 2009. The study included 45 children 3-60 months old hospitalized with febrile illness with no clinical or microbiological evidence of acute bacterial infection. Serum levels of troponin were obtained, and ECG and echocardiography were performed in all the children. Parameters that determined myocarditis included: (1) ECG ST-T changes suggestive of myocarditis; (2) Increased serum troponin level; (3) Echocardiography findings including: shortening fraction less than 28%, left ventricle end diastolic diameter > than 2 standard deviations for age, abnormal mitral valve incompetence, or abnormal diastolic function. Clinical and epidemiological data were analyzed in order to determine parameters related to findings suggestive of silent acute myocarditis. RESULTS: In 16 (35%) children at least one parameter, and in 7 (16%) at least 2 parameters of acute myocarditis were found. Impaired diastolic function was found in 11 cases (69%), ECG changes in 5 children (35%, left ventricle dilatation in 4 (25%), and decreased shortening fraction in 3 cases (18%]. Other symptoms and signs of myocarditis were not found in any of the 16 children, and no clinical or epidemiological parameter was significantly associated with silent myocarditis. CONCLUSIONS: In a third of the patients, some evidence of myocardial dysfunction was documented. In seven of them (16% of all cases), there were two different categories of myocardial dysfunction. Those cases are suspected to be silent acute myocarditis. No clinical and epidemiological parameters associated with the disease were found. The clinical importance of this phenomenon should be determined by a long-term follow-up study. SUMMARY: In this preliminary study, we found a high prevalence of cardiac involvement in hospitalised children with viral infections. It seems that this cardiac involvement is due to acute sub-clinical myocarditis. The importance of these findings should be evaluated.

Early impact of sequential introduction of 7-valent and 13-valent pneumococcal conjugate vaccine on IPD in Israeli children <5 years: an active prospective nationwide surveillance.

BACKGROUND: The 7-valent pneumococcal conjugated vaccine (PCV7) was introduced to the Israeli national immunization plan (NIP) in July 2009 (administered at age 2, 4 and 12 months), with a fast reduction of invasive pneumococcal disease (IPD) caused by PCV7 serotypes. Starting in November 2010, PCV13 gradually replaced PCV7. AIM: To report the impact of PCV7/PCV13 sequential introduction on IPD in Israeli children <5 years. METHODS: An ongoing nationwide, prospective, population-based, active surveillance. All IPD episodes (Streptococcus pneumoniae isolated from blood and/or cerebrospinal fluid) from July 2004 through June 2013 were included. RESULTS: Overall, 2670 IPD episodes were recorded. Incidence of IPD caused by PCV7+6A serotypes during the PCV13 period vs. pre-PCV period decreased by 95% (Incidence Rate Ratio [IRR]=0.05; 95% CI=0.03-0.09). This reduction was observed in a two-step manner: 90% in the PCV7-period and further 5% in the PCV13-period. The rates of IPD caused by the 5 additional PCV13-serotypes (1, 3, 5, 7F, 19A; 5VT) increased initially by 47%, but subsequently decreased by 79%, resulting in an overall 70% reduction during the entire study period (IRR=0.30; 0.21-0.44). A two-fold increase in non-PCV13 serotypes IPD was observed (IRR=2.43; 1.73-3.66). In total, a 63% reduction of all-serotype IPD episodes was observed in children <5 years (69% and 48% in children <2 and 2-4 years old, respectively). CONCLUSIONS: After initiation of PCV NIP, a rapid and substantial 2-step IPD reduction was observed in children <5 years. The serotype-specific rate reduction reflected the sequential introduction of PCV7/PCV13.