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Necrotizing enterocolitis (NEC), one of the most severe emergencies in neonates, is a multifactorial disease with diverse risk factors. To compare between the clinical and laboratory characteristics of premature infants diagnosed with early-onset NEC (EO-NEC) and those with late-onset NEC (LO-NEC). Enrolled infants were identified from prospective local data collected for the Israel National very low birth weight (VLBW

Necrotizing enterocolitis (NEC), one of the most severe emergencies in neonates, is a multifactorial disease with diverse risk factors.To compare between the clinical and laboratory characteristics of premature infants diagnosed with early-onset NEC (EO-NEC) and those with late-onset NEC (LO-NEC).Enrolled infants were identified from prospective local data collected for the Israel National very low birth weight (VLBW, 1500 g) infant database and from the local electronic patient files data base for the period 1996-2017.Overall, 95 VLBW infants (61, 64.21% EO-NEC and 34, 35.87% LO-NEC) were enrolled. EO-NEC infants had higher rate of IVH grade 3 and 4 (26.2% vs 2.9%, p = 0.005) and were more likely to undergo surgery (49.2% vs 26.5%, p = 0.031). LO-NEC infants had a higher incidence of previous bloodstream infections (35.3% vs 8.2%, p = 0.002) compared to EO-NEC. In multivariable analysis models, surgical intervention was associated with EO-NEC (OR: 4.627, p = 0.013) as well as PDA and positive blood culture prior to the NEC episode.Our data support the hypothesis that EO-NEC has significant different clinical and microbiological attributes compared to LO-NEC.

BackgroundFever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome.MethodsA national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004–2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys.ResultsThe study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3–88). Median fever duration was 4 weeks (range, 2–9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4–445), 95% had complete recovery; 3 patients remained with ocular sequelae.ConclusionThis is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease.

Background Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. Methods We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. Findings On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). Interpretation Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. Funding Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

Background: The aims of this study were to evaluate the incidence of congenital cytomegalovirus (CMV) in term and near-term infants who fail hearing screen (target screening), the incidence of cong...

Summary Background Preterm infants are at high risk for extended-spectrum-beta-lactamase-producing Enterobacteriaceae (ESBL-E) sepsis and neonatal intensive care unit (NICU) outbreaks. Maternal colonization with ESBL-E may be precursory to mother-to-child transmission. However, there is no consensus regarding surveillance of pregnant women for ESBL-E colonization. Aim To identify pairs of mothers and infants harbouring same-strain ESBL-E colonization and to determine whether maternal transmission may play a role in increasing ESBL-E carriage in preterm infants. Methods This was a one-year analysis from an ongoing, prospective ESBL-E surveillance of mothers of premature infants and their offspring. Mother–infant pairs colonized with the same bacteria underwent strain analysis using pulsed-field gel electrophoresis (PFGE). Clinical parameters were collected from the hospital computerized records. Findings Between January 2015 and January 2016, 313/409 (76.5%) mothers and all 478 (100%) infants were screened for ESBL-E colonization; carriage rates were 21.5% and 14.8%, respectively. Four (5.6%) colonized infants developed late-onset sepsis and two (2.8%) died. Twenty-five mother–infant pairs colonized with the same bacterial strain were identified; a subgroup of 10 pairs of isolates underwent PFGE, and 70% displayed an identical PFGE fingerprint. No similarities were found between isolates recovered from unrelated neonates and mothers. ESBL-E colonization was found significantly earlier in infants of mothers colonized at birth (P Conclusions ESBL-E carriage rates in mothers and NICU infants with non-negligible maternal–neonatal ESBL-E transmission in the study region indicate that maternal colonization surveillance and/or further infection control interventions should be considered.

Aim We describe the clinical, microbiologic, therapeutic, and outcome characteristics of infants under three months of age with a positive urine culture reported after discharge from emergency department with normal urinalysis. Methods We enrolled all infants with a urine culture obtained during an emergency room visit during 2004-2012, discharged without antibiotic therapy and subsequently reported with a positive urine culture. Results Three hundred and ninety-three positive urine cultures were reported; 46/393 (11.7%, 42 in patients under two months of age) had positive urine cultures following normal urinalysis at first visit. Fifteen (33%) had positive urine cultures at second visit; 11/15 (73%) infants with second positive urine culture were under one month of age, eight were asymptomatic and seven had mild symptoms at second visit. Pathogens isolated in all 15 infants were identical between first and second visit. All 27 infants re-examined at second visit at the emergency room were hospitalised, completed sepsis work/up and received antibiotic treatment. None developed serious bacterial infections. Conclusion We propose a new management approach for young infants with normal urinalysis and positive urine culture and suggest restricting the management option including hospitalisation, sepsis work/up and antibiotic treatment at second visit only to infants under one month of age.

AIM We evaluated the diagnosis, risk stratification and management of febrile infants under three months of age who presented to an Israeli paediatric emergency room (ER). METHODS This retrospective study enrolled all febrile infants examined in the paediatric ER of Soroka Medical Center during 2010-2013. The patients were classified into low-risk and high-risk subgroups and compared by age and ethnicity. RESULTS Overall, 2251 febrile infants (60.5% of Bedouin and 34.4% of Jewish ethnicity) were enrolled. Hospitalisation rates were higher among Bedouin vs. Jewish infants (55 vs. 39.8%, p

Background The etiology of acute childhood diarrhea often eludes identification. We used a case-control study-stool archive to determine if nucleic acid tests for established and newly identified viruses diminish our previously published 32% rate of microbiologically unexplained episodes. Methods Using polymerase chain reaction, we sought to detect noroviruses GI and GII, classic and novel astroviruses, and human bocaviruses (HBoVs) 2, 3, and 4 among 178 case and 178 matched control stool samples and St. Louis and Malawi polyomaviruses among a subset of 98 case and control stool samples. We calculated adjusted odds ratios and 95% confidence intervals using conditional logistic regression. Results Noroviruses were more common in cases (GI, 2.2%; GII, 16.9%) than in controls (GI, 0%; GII, 4.5%) (adjusted odds ratio, 5.2 [95% confidence interval, 2.5-11.3]). Astroviruses and HBoVs 2, 3, and 4 were overrepresented among the cases, although this difference was not statistically significant. Malawi polyomavirus was not associated with case status, and St. Louis polyomavirus was identified in only 1 subject (a control). When identified in cases, HBoVs 2, 3, and 4 were frequently (77%) found in conjunction with a bona fide diarrheagenic pathogen. Thirty-five (20%) case and 3 (2%) control stool samples contained more than 1 organism of interest. Overall, a bona fide or plausible pathogen was identified in 79% of the case stool samples. Preceding antibiotic use was more common among cases (adjusted odds ratio, 4.5 [95% confidence interval, 2.3-8.5]). Conclusion Noroviruses were found to cause one-third of the diarrhea cases that previously had no identified etiology. Future work should attempt to ascertain etiologic agents in the approximately one-fifth of cases without a plausible microbial cause, understand the significance of multiple agents in stools, and guide interpretation of nonculture diagnostics.

Extended-spectrum beta-lactamase (ESBL) production is the most common antimicrobial resistance mechanism in the neonatal intensive care unit (NICU), with colonization and blood stream infections being a major threat to this population. Since 2013, all NICU admissions at our facility were screened twice weekly for ESBL colonization.To determine independent risk factors for colonization of infants with ESBL-producing bacteria in the NICU.A retrospective case study of ESBL-colonized infants vs. controls (matched by date of birth and gestational age) was conducted in the NICU of Soroka University Medical Center, Israel, between 2013 and 2014. Epidemiological, laboratory, and clinical data were extracted from medical files. Univariable and multivariable analyses were used to assess associations between ESBL colonization and possible clinical risk factors.Of 639 admissions during the study period, 87 were found to be ESBL-colonized (case infants) and were matched to 87 controls. Five case infants became infected (5.7%) with ESBL strains. Klebsiella pneumoniae was the most common isolated bacteria. The mean time from admission to colonization was 15 days. Univariable analysis showed an association of male gender and highest Apgar score at 1 and 5 minutes with ESBL colonization (P0.05). Multivariable analysis yielded only a possible association of higher Apgar score at 1 and 5 minutes (hazard ratio [HR] 1.515, 95% confidence interval [95%CI] 0.993-2.314; HR 1.603, 95%CI 0.958-2.682, respectively) with ESBL colonization.Future studies should focus on maternal colonization and possible strategies for preventing vertical transmission of ESBL strains to high-risk neonates.

Brain abscesses caused by group A Streptococcus (GAS) are infrequently encountered in children. We present two cases of brain abscess (one cerebellar and one located in the temporal lobe) due to GAS infection occurring in close temporal proximity in previously healthy young children living in different geographic areas of southern Israel. The relevant literature since 2000, in the context of recent epidemiological data reporting an increase in the incidence of invasive GAS infections, is reviewed.

Aim: To identify maternal and neonatal factors that increase suspicion of early sepsis in Very Low Birth Weight neonates with respiratory distress syndrome. Methods: The cohort included 282 neonates born at Soroka Medical Centre 1996–2000. Definitions of ‘high’ and ‘low’-suspicion groups for early sepsis were based on comparison between neonates with early sepsis and the remaining cohort. Univariate analysis and logistic regression were used to compare between groups. Results: The incidence of early sepsis in the cohort was 1.8%, and 94% received antibiotics following delivery. Comparing with the remaining cohort, the five neonates with early sepsis had increased incidence of positive maternal cultures, use of antenatal antibiotics, lower 1 min Apgar scores and tendency to leucopenia. A ‘low-suspicion’ group comprised 38% of the cohort and did not include any neonates with early sepsis. This group were more frequently treated with antenatal steroids and delivered by Caesarean section compared to the ‘high-suspicion’ group, but otherwise there were no clinical and laboratory differences. Conclusion: Although the incidence of early sepsis is low almost all neonates received antibiotics. A ‘low-suspicion’ group was defined and the role of antibiotic treatment in this group needs to be determined.

Background We compared demographic and clinical characteristics of early-onset sepsis (EOS) and community-acquired late onset sepsis (CA-LOS) in infants. Methods Our medical center is the sole hospital in southern-Israel, enabling incidence calculations. EOS (

A high prevalence of maternal group B Streptococcus (GBS) carriage and an extremely low incidence of invasive neonatal disease have been reported from southern Israel. In order to obtain insight into this discrepancy, this study was performed to determine the population structure of GBS from asymptomatic pregnant women living in this area. Seventy-two strains from maternal GBS carriers were characterized using multilocus sequence typing (MLST). Epidemiologic characteristics of the carriers and their newborns, including demographic variables, obstetric status, and general health parameters, were collected by means of a postpartum interview and a review of the relevant medical records. The MLST analysis grouped the bacteria into six different lineages (clonal complexes). Lineage ST-2 was prevalent among Bedouin-Arabs (p=0.01) and lineage ST-22 among Jews (p=0.001). Lineage ST-17 was prevalent among carriers who emigrated after 1997 from western nations of the former USSR (p

We describe a child with interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency caused by a homozygous IL12RB1 large deletion who presented at the age of 1 year with recurrent, often asymptomatic episodes of bacteremia caused by group D Salmonella species. No mycobacterial disease or other unusual infection was present. The episodes of salmonellosis were caused by an identical serovar during a period of 18 months. This is the first case of inherited IL-12Rbeta1 deficiency diagnosed after isolated, recurrent salmonellosis.

The aims of this study were to determine the risk factors in, and the clinical and laboratory characterizations of, Shigella bacteremia, as well as the subspecies of Shigella, and the antibiotic susceptibility. A retrospective study of all patients younger than 18 years of age with documented Shigella bacteremia from January 1989 through December 2001 was conducted. Fifteen children with Shigella bacteremia were treated at our center. The mean age (± SD) was 20.5 months (± 34.2), median 7 months. Thirteen (87%) patients failed to gain weight. The mean duration of diarrhea was 14.7 days. Patients were hospitalized for a mean (± SD) of 13.5 days (±9.2). There were no fatalities in our study sample. The vast majority (86.7%) of the Shigella isolates were flexneri. Most isolates were susceptible to ceftriaxone, ciprofloxacine, and gentamicin but resistant to ampicillin and trimethoprim/sulfamethoxazole.

We describe an outbreak of Acinetobacter baumannii in a neonatal intensive care unit (NICU), and our investigation to determine the source and mode of transmission and identify the population at risk. A case (infected infant) was defined as a patient hospitalized in the NICU during the outbreak period, with clinical signs of sepsis and isolation of A. baumannii. In colonized infants, A. baumannii was isolated from body surfaces without signs of infection. Infected infants were separated and treated by a different medical team. Cultures were taken from working surfaces and along the infant's admission passage from the delivery room to the NICU. The outbreak strain was identified by pulsed-field gel electrophoresis (PFGE). Nine cases and eight colonized infants met the definition criteria. Cases were younger than colonized infants with regard to gestational age and age of diagnosis and had lower birthweights (P

Our study investigates the causative pathogens of hospital-acquired conjunctivitis in our neonatal intensive care unit and their susceptibility patterns. Coagulase-negative Staphylococcus was the most common bacterium, 22.1% of all isolates. The frequency of the pathogens changed during neonates' stay; Klebsiella pneumoniae (from 18% to 6.9%) and Escherichia coli (from 16% to 4.8%) decreased, whereas methicillin-susceptible Staphylococcus aureus (from 4% to 12.7%) and Enterococcus spp (from 1% to 5.3%) increased. Gram-positive cocci showed high resistant patterns. Our study indicates that the distribution of bacteria causing hospital-acquired conjunctivitis in our neonates shifted from gram-negative to gram-positive microorganisms during their neonatal intensive care unit stay. The resistance patterns are worrisome among gram-positive cocci.

Fungal endocarditis in children is most commonly a complication of palliative or curative surgery for congenital heart disease, rheumatic valvulitis and prolonged indwelling central venous and umbilical catheters. We describe here the case of a 3-y-old patient with chronic diarrhoea and prolonged total parenteral alimentation who developed severe C. tropicalis endocarditis and was treated successfully using a liposomal preparation of amphotericin-B (AmBisome) without surgical intervention.

Pneumococcal nasopharyngeal colonization is important for transmission of the organisms. We assessed the ability of two tetravalent conjugate vaccines administered in early infancy to prevent carriage of vaccine-related pneumococci.A vaccine containing pneumococcal type 6B, 14, 19F and 23F polysaccharide conjugated to tetanus toxoid (Pnc-T) and a vaccine containing the same four polysaccharides conjugated to diphtheria toxoid (Pnc-D) were compared with placebo, in a double blinded study (25 infants per group). Vaccines (or placebo) were injected at 2, 4 and 6 months of age. At 12 months of age a native (nonconjugate) polysaccharide vaccine was administered as a booster. Serum type-specific anticapsular antibody concentrations were measured and nasopharyngeal cultures were obtained at 2, 4, 6, 7, 12 and 13 months of age.In general carriage of all pneumococci (vaccine- and non-vaccine-related) was low at age 2 months and increased with age. However, for the vaccine-related serotypes (6A, 6B, 14, 19F and 23F) carriage was not increased with age in Pnc-D or Pnc-T recipients. Of all cultures obtained after the full primary series, 7 of 72 (10%), 3 of 62 (5%) and 19 or 70 (27%) were positive for the vaccine-related pneumococcal serotypes among the Pnc-D, Pnc-T and placebo recipients, respectively (P = 0.001 for Pnc-D vs. placebo; P = 0.014 for Pnc-T vs. placebo). Most of the antibiotic-resistant isolates belonged to the vaccine-related serotypes.A significant reduction in the carriage of vaccine-related strains after administration of conjugate vaccines was observed. These preliminary results suggest that transmission of specific pneumococcal serotypes most often associated with disease and antibiotic resistance may at least partially be controlled by immunization.

Knowledge of fungal colonization patterns in very low birth weight infants (VLBWI) admitted to the neonatal intensive care unit (NICU) is essential in understanding the process of fungal infections in neonates. We analyzed prospectively, during 2009-2010, the patterns and dynamics of fungal colonization in VLBWI, including timing, colonization sites, and species involved.Weekly skin, oropharynx, and rectum/stool surveillance fungal cultures were collected from admission until discharge in VLBWI in the NICU. None received antifungal prophylaxis.Overall, 118 VLBWI provided 1723 samples; 34 (29%) had 104 positive samples at least once during the first 10 hospitalization weeks. Thirty-nine (33%) weighed1000 g; 68 were delivered by cesarean section. Candida albicans (57/104, 55%) and Candida parapsilosis (26/104, 25%) were the main fungi isolated. Eight (24%) VLBWI were colonized during the first week and 23 (68%) during the second week. No differences in colonization were recorded between cesarean section and vaginally delivered VLBWI. The colonization risk at least once during the first 10 weeks was 23% for skin, 14% for oropharynx, 27% for rectum/stool, and 38% for any anatomic site sampled. Persistent colonization was recorded in 5/34 (15%), while transient colonization was found in 14/34 (41%) VLBWI; 16/34 (47%) were discharged or died colonized with Candida spp. Candidemia was diagnosed in 4 (3%) VLBWI and previous/simultaneous colonization was found in 3/4.The cumulative risk of colonization, at any sampled site and at least once during follow-up, was high. Initial colonization occurred most often during the first 2 weeks of life. Colonization dynamics were characterized by various persistence, disappearance, and recolonization patterns. Candidemia was rare.

Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine. Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children. The vaccines had no effect on carriage of non-vaccine-type pneumococci. In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001). No effect was seen after vaccination with the nonconjugate vaccine. One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs. 14%, P = .042). Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.

Background Preterm infants are at high risk for extended spectrum β-lactamase producing Enterobacteriaceae (ESBL-E) sepsis and neonatal intensive care unit (NICU) outbreaks. There is no consensus regarding surveillance of pregnant women for ESBL-E colonization. However, neonatal screening is accepted in order to prevent NICU’s transmissions by contact isolation. We hypothesized that a significant proportion of ESBL-E colonized infants in our NICU were due to mother-to-child transmission. The aim of this study was to molecularly identify pairs of mothers and offspring ESBL-E colonization. Methods The Soroka University Medical Center serves the entire population of southern Israel with an estimated 17,000 deliveries per year. This was a one year analysis from an ongoing, prospective, active rectal ESBL-E colonization surveillance of mothers of premature infants and their offspring. Pairs of mothers and infants colonized with the same bacteria underwent molecular identification by pulse-field gel electrophoresis (PFGE). Results Between January 2015 and February 2016, 311(76%) out of 407 mothers and all 477(100%) infants were screened for ESBL-E colonization; carriage rates were 21.5% and 14.9%, respectively. Four (5.6%) carrier infants developed late onset sepsis and 2 (2.8%) died. Mothers of 47% (28) ESBL-E carrier infants were colonized at delivery; comparison of the characteristics between colonized infants of positively and negatively screened mothers is presented in Table 1. Twenty-three (34.3%) colonized mothers delivered 25 infants who were found to be colonized with the same bacterial strain according to species’ identification and antibiogram. A subgroup of 10 mother-infant dyads underwent PFGE and 70% shared identical molecular fingerprint patterns. No similarities were found between isolates recovered from unrelated neonates and mothers. Conclusion High ESBL-E carriage rates in mothers and NICU’S infants, in our region, with a non-negligible maternal-neonatal ESBL-E colonization transmission illuminates the importance of maternal ESBL colonization surveillance and further consideration regarding infectious control preventive measurements. Disclosures All authors: No reported disclosures.

To identify maternal and neonatal factors that increase suspicion of early sepsis in Very Low Birth Weight neonates with respiratory distress syndrome.The cohort included 282 neonates born at Soroka Medical Centre 1996-2000. Definitions of 'high' and 'low'-suspicion groups for early sepsis were based on comparison between neonates with early sepsis and the remaining cohort. Univariate analysis and logistic regression were used to compare between groups.The incidence of early sepsis in the cohort was 1.8%, and 94% received antibiotics following delivery. Comparing with the remaining cohort, the five neonates with early sepsis had increased incidence of positive maternal cultures, use of antenatal antibiotics, lower 1 min Apgar scores and tendency to leucopenia. A 'low-suspicion' group comprised 38% of the cohort and did not include any neonates with early sepsis. This group were more frequently treated with antenatal steroids and delivered by Caesarean section compared to the 'high-suspicion' group, but otherwise there were no clinical and laboratory differences.Although the incidence of early sepsis is low almost all neonates received antibiotics. A 'low-suspicion' group was defined and the role of antibiotic treatment in this group needs to be determined.

Bloodstream infections are a significant cause of mortality and morbidity in premature and low-birth-weight infants; due to non-specific manifestations, ‘rule out sepsis’ evaluations are commonly performed in the age group. After evaluation, broad spectrum antibiotics are administered while awaiting the results of bacterial cultures that have a yield of not more than 25%–27%.1 ,2 Viral causes of sepsis-like syndromes in the neonatal intensive care unit (NICU) have been underexplored, especially in the PCR era. Because a large majority of putatively septic episodes fail to yield a bacterial pathogen, we hypothesised that culture-negative septic episodes in very low-birth-weight NICU patients might have a viral origin. The objective of the study was to identify non-respiratory viral causes of sepsis-like illness. Infants …

Background. We compared the safety and immunogenicity of two combined diphtheria-tetanus-pertussis-inactivated poliovirus vaccines containing either acellular (Pa, SmithKline Beecham Biologicals) or whole cell (Pw, Pasteur Merieux Connaught) pertussis components, mixed with a Haemophilus influenzae type b polysaccharide polyribosylribitol phosphate-tetanus conjugate vaccine in an open, randomized study in healthy infants. Design. The combined vaccines were given at 2, 4, 6 and 12 months of age, and serum samples were obtained at ages 2, 6, 7, 12 and 13 months. Adverse events were obtained by diary cards. Results. The Pa group (n = 101) had a clearly lower incidence of both local and systemic adverse events than the Pw group (n = 100). Immunogenicity was comparable for the diphtheria and tetanus components, but significantly superior for pertussis toxin, filamentous hemagglutinin, pertactin and polioviruses 1, 2 and 3 in the Pa group. Both groups had an appropriate response with regard to H. influenzae type b polysaccharide polyribosylribitol phosphate, but the dynamics of the response were significantly different: geometric mean concentrations (micrograms per ml) after the second, third and booster doses were 1.27, 5.06 and 23.12 in the Pa group and 2.72, 6.66 and 13.59 in the Pw group, respectively (P = 0.0002 after second dose; P = 0.0005 after booster). Conclusion. The presently studied diphtheria, tetanus, acellular pertussis-H. influenzae b vaccine conjugated to tetanus toxoid combination was at least as immunogenic as the diphtheria, tetanus, whole cell pertussis-H. influenzae b vaccine conjugated to tetanus toxoid combination, with a significantly better safety profile. This is of obvious importance in countries where inactivated poliovirus vaccine is part of the routine infant immunization programs.

Background New vaccines against pneumococcal infections in infancy are needed. We assessed in young infants the safety and immunogenicity of two tetravalent vaccines containing pneumococcal 6B, 14, 19F and 23F polysaccharides conjugated to either tetanus toxoid (Pnc-T) or diphtheria toxoid (Pnc-D). Methods Pnc-T or Pnc-D containing 3 microg of polysaccharide of each of the four pneumococcal polysaccharides or placebo were given intramuscularly in a double blinded fashion (25 infants per group) at 2, 4 and 6 months of age. At 12 months of age all 75 children were boosted with a 23-valent nonconjugate polysaccharide pneumococcal vaccine. Serum type-specific anticapsular antibody concentrations were measured at 2, 4, 6, 7, 12 and 13 months of age. Adverse events occurring within 72 h after each injection were recorded. Results Both Pnc-T and Pnc-D were well-tolerated. Pnc-T and Pnc-D had higher antibody concentrations compared with placebo after primary immunity (type 6B, 1.66, 1.40 and 0.60 microg/ml, respectively; type 14, 4.81, 2.65 and 2.22 microg/ml, respectively; type 19F, 2.40, 3.48 and 0.83 microg/ml, respectively; type 23F, 0.96, 0.44 and 0.35 microg/ml, respectively). Proportions of infants with concentrations above 1.0 microg/ml were also higher in the vaccine recipients than in those given placebo. After booster with the nonconjugate polysaccharide vaccine, both geometric antibody concentration and proportion with concentrations > or =1.0 microg/ml were significantly higher among either Pnc-T or Pnc-D recipients than among placebo recipients. Conclusions Both Pnc-T and Pnc-D were well-tolerated, induced serotype-specific anticapsular antibodies and induced immunologic memory.

The immunogenicity and safety of a combined diphtheria, tetanus, pertussis and Haemophilus influenzae type b-tetanus conjugate vaccine (DTP-PRP-T) was compared to the same combination obtained by the reconstitution of H. influenzae type b-tetanus conjugate vaccine lyophilized (PRP-T) with liquid diphtheria-tetanus-pertussis vaccine (DTP). Two hundred and sixty-two healthy infants were randomized to receive a intramuscular injection of 0.5 ml of one of the above combination vaccines at 2, 4 and 6 months of age, and a subgroup of 134 infants received a booster dose at 12 months. Serum antibody levels to each vaccine component were measured at ages 2, 6, 7, 12 and 13 months. Systemic and local reactions were assessed during the first 3 days after each injection by diary cards distributed to the parents. After the third dose and booster administered at 12 months of age, significant equivalence between the groups was observed, and the geometric mean titer of anti H. influenzae type b capsular polysaccharide (Hib-CP) antibodies were 5.9 and 32.6 micrograms ml-1 for the liquid combination group and 5.8 and 19.4 for the lyophilized group, respectively. After the third dose, anti-Hib-PC antibody levels of > or = 1.0 microgram ml-1 and 0.15 microgram ml-1 were seen in 94% and 100%, respectively, of the liquid combination group and 90 and 99%, respectively of the lyophilized group. After the booster dose, levels of > or = 1.0 microgram ml-1 were observed in 100% and 93.5% of the liquid combination group and the lyophilized combination group, respectively. Systemic and local reactions to the vaccination were generally mild and did not differ significantly between the groups. We conclude that the liquid combination of DTP-PRP-T is safe and at least as immunogenic as the lyophilized preparation. This liquid preparation, like other combined vaccines may be helpful for planning vaccination programs with a reduced number of injections.

Nasopharyngeal carriage of Streptococcus pneumoniae was studied in 162 healthy infants at ages 2, 4, 6, 7, 12, and 13 months and in an additional 352 healthy children at ages 12, 15, 18, 21, and 24 months. Carriage was 26%, 39%, and 62% at 2, 12, and 24 months, respectively, and the respective resistance to > or = 1 antibiotic was 11%, 19%, and 27%. The presence of an older sibling or antibiotic treatment during the month preceding the culture was associated with carriage of resistant pneumococci in infants, whereas attendance at large day care centers was associated with carriage during the second year of life. Antibiotic resistance was detected in all 7 serotypes included in the candidate pediatric conjugate vaccines and was significantly more prevalent among vaccine-type pneumococci than among non-vaccine-type pneumococci. The use of conjugate vaccines may reduce the spread of resistant pneumococci.

A case of neonatal nosocomial pneumococcal sepsis acquired by patient-to-patient transmission and confirmed by phenotypic and genotypic typing is documented. To the best of our knowledge this is the first documented case of neonatal nosocomial person-to-person transmission.