The impact of the early onset neonatal sepsis calculator on antibiotic initiation: a single center study in Israel.

To evaluate the effect of implementation of the Kaiser Permanente (KP) early onset sepsis (EOS) calculator in infants born at 34 week's gestation or more on antibiotic utilization and length of hospitalization. A single center, retrospective cohort study included all neonates born in Soroka Medical Center at 34 weeks gestation or more between January 1st, 2015, and January 1st, 2019, with a predefined maternal risk factor for EOS. Two cohorts of neonates were compared during two time periods, before and after the implementation of the KP calculator. Multivariable logistic and linear regressions were performed to assess the effect of the KP calculator on antibiotic treatment and length of hospitalization. Also, an interrupted time series (ITS) analysis was used to assess the time trends of the two periods. The study included 3858 neonates in the pre-implementation period and 3081 neonates in the post-implementation cohort. The use of the calculator resulted in a significant reduction (46%) in antibiotics treatment for suspected EOS (5.1 vs. 9.4%, P < 0.001). The ITS analysis demonstrated a sharp decline in the slope of antibiotic treatment in the post intervention period: (b = -0.14, p-value = 0.08). The length of hospitalization was significantly reduced in the post-implementation cohort from 62 to 60 h (p-value < 0.001) with no clinical significance. The incidence of EOS was similar in both groups.    Conclusion: A significant reduction in antibiotic treatment was demonstrated after the implementation of the KP calculator without an increase incidence of EOS. The calculator is a powerful accessory decision-making tool that can be used safely in combination with, but not replacing, thorough clinical assessment. What is Known: • The EOS calculator is a useful tool that leads to a significant reduction in preemptive antibiotic utilization. What is New: • The EOS calculator is sensitive when applied to the whole-nursery. • The calculator is useful in different populations, also when women are not routinely screened for GBS.

Early versus late-onset necrotizing enterocolitis in very low birth infants in the neonatal intensive care unit.

BACKGROUND: Necrotizing enterocolitis (NEC), one of the most severe emergencies in neonates, is a multifactorial disease with diverse risk factors. OBJECTIVES: 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). PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Our data support the hypothesis that EO-NEC has significant different clinical and microbiological attributes compared to LO-NEC.

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

BACKGROUND: Fever 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. METHODS: A 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. RESULTS: The 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. CONCLUSION: This 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.

Urinary tract infection in young infants discharged from the emergency room with normal urinalysis.

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.

Performance of risk stratification criteria in the management of febrile young infants younger than three months 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 < 0.001). Fever without localising signs was diagnosed in 1028 (45.6%) infants and 499 (48.5%) were hospitalised; 26% were stratified as high-risk and 74% as low-risk. Bedouin infants rates were more likely to be at high-risk (p = 0.001) and hospitalised (p < 0.001) than Jewish infants. With regard to low-risk infants, the incidence rates were higher before two months than two to three months of age (73.3 vs. 59%, p < 0.001), as were the hospitalisation rates (46.3 vs. 20.1%, p < 0.001). No differences were recorded for the hospitalisation rates of Bedouin and Jewish infants between the three daily shifts. CONCLUSION: Major differences were recorded in hospitalisation rates, risk stratification and management of Bedouin and Jewish infants with fever without localising signs.

Neonatal Risk Factors for Colonization with Extended-Spectrum Beta-Lactamase-Producing Bacteria in the Neonatal Intensive Care Unit.

BACKGROUND: 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. OBJECTIVES: To determine independent risk factors for colonization of infants with ESBL-producing bacteria in the NICU. METHODS: 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. RESULTS: 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 (P < 0.05). 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. CONCLUSIONS: Future studies should focus on maternal colonization and possible strategies for preventing vertical transmission of ESBL strains to high-risk neonates.

Comparison of early onset sepsis and community-acquired late onset sepsis in infants less than 3 months of age.

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 (<7 days) and CA-LOS (7-90 days) episodes recorded between 2007 and 2013 were reviewed. Univariate and multivariate analyses were performed. RESULTS: 70 EOS and 114 CA-LOS episodes were recorded. The respective mean ± SD annual rates per 1,000 live-births were 0.66 ± 0.16 and 1.03 ± 0.23. Prematurity (42.9 % vs. 17.0 %), premature rupture of membranes (PROM; 22.9 % vs. 1.9 %), leukopenia (29.0 % vs. 11.6 %), thrombocytopenia (44.9 % vs. 14.3 %) and Streptococcus agalactiae infections (22.7 % vs. 8.1 %) were more common in EOS. Fever (25.4 % vs. 79.1 %) and Streptococcus pneumoniae infections (1.3 % vs. 12.9 %) were less common in EOS. In both groups, Gram-negative bacteria predominated (~60 %). Longer hospitalization duration (23.3 ± 25.1 vs. 10.3 ± 8.6 days) and higher case fatality rate (20.0 % vs. 5.3 %) were noted in EOS. Antibiotic resistance rates to empiric EOS and CA-LOS treatments were 0.0 % and 1.2 %, respectively. In multivariate analysis, adjusting for prematurity and ethnicity, PROM, central line, low Apgar-score, low birth-weight, ventilation support and non-vaginal delivery were risk factors for EOS. Normal temperature, thrombocytopenia and leukopenia characterized EOS. CONCLUSION: EOS and CA-LOS rates were low in Jewish compared with Bedouin infants. EOS was characterized by higher rates of perinatal risk factors, S. agalactiae infections, normal temperature, thrombocytopenia, leukopenia and mortality, while fever and S. pneumoniae infections were common in CA-LOS. Current initial antibiotic regimens seem adequate, considering the susceptibility patterns of the isolated pathogens.

A prospective study of the patterns and dynamics of colonization with Candida spp. in very low birth weight neonates.

BACKGROUND: 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. METHODS: Weekly skin, oropharynx, and rectum/stool surveillance fungal cultures were collected from admission until discharge in VLBWI in the NICU. None received antifungal prophylaxis. RESULTS: Overall, 118 VLBWI provided 1723 samples; 34 (29%) had 104 positive samples at least once during the first 10 hospitalization weeks. Thirty-nine (33%) weighed < 1000 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. CONCLUSIONS: 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.

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study.

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.

Targeted and universal screen in term and preterm infants for congenital CMV infection.

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 congenital CMV infections in infants born before 33 weeks of gestation (universal screening) and the incidence of infants who need pharmacologic treatment for congenital CMV associated sensorineural hearing loss (SNHL).Methods: This was a retrospective cohort study that assessed two groups of infants born between 2014 and 2017. The first group consisted of infants born between 33 and 42 weeks gestation and the second group, of infants born before 33 weeks gestation. Targeted CMV screening was performed in the first group who either failed neonatal hearing screen or were growth retarded. Universal screen was performed in the second group of infants. CMV DNA was tested in urine samples using real time PCR soon after birth.Results: In the first group, 2078 infants were assessed, 19 (0.9%) were found to be CMV positive and in 9 (42%) valganciclovir treatment was initiated. In the second group, out of 549 urine samples/infants, none was positive for CMV DNA soon after birth.Conclusions: A joint strategy of targeted CMV screening in infants who fail hearing screen test with universal screen of premature infants can select infants at risk of hearing impairment due to congenital CMV soon after birth, allows for timely initiation of treatment and prevents dilemmas regarding congenital CMV diagnosis in infants who fail hearing screen in a later age until universal screen will be widely adopted.

Late onset sepsis: comparison between coagulase-negative staphylococci and other bacteria in the neonatal intensive care unit.

OBJECTIVE: To compare demographic and clinical features of neonates with late-onset sepsis due to coagulase-negative-staphylococcus with those due to other bacterial pathogens. STUDY DESIGN: Retrospective, population-based cohort study. Data on infants less than 90 days old diagnosed with late-onset bacterial sepsis in the neonatal intensive care unit were reviewed. Univariable and multivariable analysis were performed. RESULTS: Two hundred and sixteen sepsis episodes were identified: coagulase-negative-staphylococcus caused 113 (52.3%) and other pathogen 103 (47.7%). Patients with coagulase-negative-staphylococcus sepsis had lower gestational age and younger age at onset, higher rates of parenteral nutrition exposure and normal temperature, lower rates of necrotizing enterocolitis, meningitis and neutropenia than patients with sepsis caused by other pathogens. In multivariable analysis, parenteral nutrition was the only independent risk factor for coagulase-negative-staphylococcus sepsis (odds ratio: 3.5, 95% confidence interval: 1.4-8.6). CONCLUSIONS: Initial empiric treatment for suspected sepsis should be targeted for other pathogens than coagulase-negative-staphylococci and vancomycin treatment should be reserved for infants with specific risk factors and according to local antimicrobial susceptibility.

Group A streptococcal brain abscess in children: two case reports and a review of the literature.

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.

Case-Control Assessment of the Roles of Noroviruses, Human Bocaviruses 2, 3, and 4, and Novel Polyomaviruses and Astroviruses in Acute Childhood Diarrhea.

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.

Superficial skin infection caused by Streptococcus pneumoniae in children.

Pneumococcal superficial skin infections are rarely described. We present 3 cases of Streptococcus pneumoniae superficial skin infections in previously healthy children. In 2 cases, lesions occurred on facial skin; in the third case they occurred on the scrotal raphe. One isolate was fully penicillin-resistant.

Interleukin-12 receptor beta1 deficiency presenting as recurrent Salmonella infection.

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.

Shigella bacteremia: a retrospective study.

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.

Hospital-acquired conjunctivitis in a neonatal intensive care unit: Bacterial etiology and susceptibility patterns.

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.

Risk factors for early sepsis in very low birth weight neonates with respiratory distress syndrome.

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.