Lumbar Puncture and Meningitis in Infants with Proven Early- or Late-Onset Sepsis: An Italian Prospective Multicenter Observational Study.

Background: To evaluate the rates of lumbar puncture (LP) in infants with culture-proven sepsis. Study design: We prospectively enrolled 400 infants with early- or late-onset sepsis due to Group B streptococcus (GBS) or Eschericha coli, diagnosed within 90 days of life. Rates of LP and potential variables associated with LP performance were evaluated. Moreover, cerebrospinal fluid (CSF) characteristics and results of the molecular analysis were investigated. Results: LP was performed in 228/400 (57.0%) infants; 123/228 LPs (53.9%) were performed after antibiotic initiation, hampering the ability to identify the pathogen in the CSF culture. However, polymerase chain reaction increased the probability of positive results of CSF analysis compared to microbiological culture (28/79, 35.4% vs. 14/79, 17.7%, p = 0.001). Severe clinical presentation and GBS infection were associated with higher LP rates. The rate of meningitis was 28.5% (65/228). Conclusions: Rates of LP are low in culture-proven neonatal sepsis and antibiotics are frequently given before LP is carried out. Thus meningitis may be underestimated, and the chances of giving an effective therapy to the newborn are reduced. LP should be performed before the start of antibiotics when there is a clinical suspicion of infection.

Timing of Symptoms of Early-Onset Sepsis after Intrapartum Antibiotic Prophylaxis: Can It Inform the Neonatal Management?

The effectiveness of "inadequate" intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003-2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined "active" when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an "inactive" IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP "adequate" seems the pathogen's antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

Escherichia coli Is Overtaking Group B Streptococcus in Early-Onset Neonatal Sepsis.

The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00-0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00-0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02-0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics.

Surgical Antimicrobial Prophylaxis in Pediatric Patients Undergoing Plastic Surgery: A RAND/UCLA Appropriateness Method Consensus Study.

For many years, it was clearly shown that surgical procedures might be associated with surgical site infection (SSI). Many scientific institutions prepared guidelines to use in surgery to reduce abuse and misuse of antibiotics. However, in the general guidelines for surgical antibiotic prophylaxis, plastic surgical procedures are not addressed or are only marginally discussed, and children were almost systematically excluded. The main aim of this Consensus document is to provide clinicians with recommendations on antimicrobial prophylaxis for pediatric patients undergoing plastic surgery. The following scenarios were considered: clean plastic surgery in elective procedures with an exclusive skin and subcutis involvement; clean-contaminated/contaminated plastic surgery in elective procedures with an exclusive skin and subcutis involvement; elective plastic surgery with use of local flaps; elective plastic surgery with the use of grafts; prolonged elective plastic surgery; acute burns; clean contused lacerated wounds without bone exposure; high-risk contused lacerated wounds or with bone exposure; contused lacerated wound involving the oral mucosa; plastic surgery following human bite; plastic surgery following animal bite; plastic surgery with tissue expander insertion. Our Consensus document shows that antimicrobial perioperative prophylaxis in pediatric patients undergoing plastic surgery is recommended in selected cases. While waiting the results of further pediatric studies, the application of uniform and shared protocols in these procedures will improve surgical practice, with a reduction in SSIs and consequent rationalization of resources and costs, as well as limiting the phenomenon of antimicrobial resistance.

Antimicrobial Prophylaxis for Urologic Procedures in Paediatric Patients: A RAND/UCLA Appropriateness Method Consensus Study in Italy.

The main aim of surgical antimicrobial prophylaxis (SAP) in urologic procedures is to prevent bacteraemia, surgical site infections (SSIs), and postoperative urinary tract infections (ppUTIs). Guidelines for SAP in paediatric urology are lacking. Only some aspects of this complex topic have been studied, and the use of antibiotic prophylaxis prior to surgical procedures seems to be more often linked to institutional schools of thought or experts' opinions than to rules dictated by studies demonstrating the most correct and preferred management. Therefore, the aim of this Consensus document realized using the RAND/UCLA appropriateness method is to provide clinicians with a series of recommendations on SAP for the prevention of bacteraemia, SSIs, and ppUTIs after urologic imaging and surgical procedures in paediatric patients. Despite the few available studies, experts agree on some basilar concepts related to SAP for urologic procedures in paediatric patients. Before any urological procedure is conducted, UTI must be excluded. Clean procedures do not require SAP, with the exception of prosthetic device implantation and groin and perineal incisions where the SSI risk may be increased. In contrast, SAP is needed in clean-contaminated procedures. Studies have also suggested the safety of eliminating SAP in paediatric hernia repair and orchiopexy. To limit the emergence of resistance, every effort to reduce and rationalize antibiotic consumption for SAP must be made. Increased use of antibiotic stewardship can be greatly effective in this regard.

Vertical Transmission of SARS-CoV-2 (COVID-19): Are Hypotheses More than Evidences?

In spite of the increasing, accumulating knowledge on the novel pandemic coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), questions on the coronavirus disease-2019 (COVID-19) infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending and have not been addressed so far. SARS-CoV-2, a RNA single-stranded virus, has been detected in the amniotic fluid, in the cord blood and in the placentas of the infected women. In the light of these findings, the theoretical risk of intrauterine infection for fetuses, or of peripartum infection occurring during delivery for neonates, has a biological plausibility. The extent of this putative risk might, however, vary during the different stages of pregnancy, owing to several variables (physiological modifications of the placenta, virus receptors' expression, or delivery route). This brief review provides an overview of the current evidence in this area. Further data, based on national and international multicenter registries, are needed not only to clearly assess the extent of the risk for vertical transmission, but also to ultimately establish solid guidelines and consistent recommendations. KEY POINTS: · Questions on the COVID-19 infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending so far.. · The theoretical risk of intrauterine infection for fetuses, or of neonatal infection during delivery for neonates, has a biological plausibility.. · A caution is recommended in the interpretation of clinical and laboratory data in neonates..

Epidemiology and complications of late-onset sepsis: an Italian area-based study.

BACKGROUND: Most studies regarding late-onset sepsis (LOS) address selected populations (i.e., neonates with low birth weight or extremely preterm neonates). Studying all age groups is more suitable to assess the burden of single pathogens and their clinical relevance. METHODS: This is a retrospective regional study involving paediatric departments and NICUs in Emilia-Romagna (Italy). Regional laboratory databases were searched from 2009 to 2012. Records of infants (aged 4 to 90 days) with a positive blood or cerebrospinal fluid (CSF) culture were retrospectively reviewed and analysed according to acquisition mode (whether hospital- or community-acquired). RESULTS: During the study period, there were 146,682 live births (LBs), with 296 patients experiencing 331 episodes of LOS (incidence rate: 2.3/1000 LBs). Brain lesions upon discharge from the hospital were found in 12.3% (40/296) of cases, with death occurring in 7.1% (23/296; 0.14/1000 LBs). With respect to full-term neonates, extremely preterm or extremely low birth weight neonates had very high risk of LOS and related mortality (> 100- and > 800-fold higher respectively). Hospital-acquired LOS (n = 209) was significantly associated with very low birth weight, extremely preterm birth, pneumonia, mechanical ventilation, and death (p< 0.01). At multivariate logistic regression analysis, catecholamine support (OR = 3.2), central venous line before LOS (OR = 14.9), and meningitis (OR = 44.7) were associated with brain lesions or death in hospital-acquired LOS (area under the ROC curve 0.81, H-L p = 0.41). Commonly identified pathogens included coagulase-negative staphylococci (CoNS n = 71, 21.4%), Escherichia coli (n = 50, 15.1%), Staphylococcus aureus (n = 41, 12.4%) and Enterobacteriaceae (n = 41, 12.4%). Group B streptococcus was the predominant cause of meningitis (16 of 38 cases, 42%). Most pathogens were sensitive to first line antibiotics. CONCLUSIONS: This study provides the first Italian data regarding late-onset sepsis (LOS) in all gestational age groups. Compared to full-term neonates, very high rates of LOS and mortality occurred in neonates with a lower birth weight and gestational age. Group B streptococcus was the leading cause of meningitis. Excluding CoNS, the predominant pathogens were Escherichia coli and Staphylococcus aureus. Neonates with hospital-acquired LOS had a worse outcome. Antibiotic associations, recommended for empirical treatment of hospital- or community-acquired LOS, were adequate.

Group B Streptococcus early-onset disease and observation of well-appearing newborns.

BACKGROUND: International guidelines lack a substantial consensus regarding management of asymptomatic full-term and late preterm neonates at risk for early-onset disease (EOS). Large cohorts of newborns are suitable to increase the understanding of the safety and efficacy of a given strategy. METHODS: This is a prospective, area-based, cohort study involving regional birth facilities of Emilia-Romagna (Italy). We compared cases of EOS (at or above 35 weeks' gestation) registered in 2003-2009 (baseline period: 266,646 LBs) and in 2010-2016, after introduction of a new strategy (serial physical examinations, SPEs) for managing asymptomatic neonates at risk for EOS (intervention period: 265,508 LBs). RESULTS: There were 108 cases of EOS (baseline period, n = 60; intervention period, n = 48). Twenty-two (20.4%) remained asymptomatic through the first 72 hours of life, whereas 86 (79.6%) developed symptoms, in most cases (52/86, 60.5%) at birth or within 6 hours. The median age at presentation was significantly earlier in the intrapartum antibiotic prophylaxis (IAP)-exposed than in the IAP-unexposed neonates (0 hours, IQR 0.0000-0.0000 vs 6 hours, IQR 0.0000-15.0000, p<0.001). High number of neonates (n = 531) asymptomatic at birth, exposed to intrapartum fever, should be treated empirically for each newborn who subsequently develops sepsis. IAP exposed neonates increased (12% vs 33%, p = 0.01), age at presentation decreased (median 6 vs 1 hours, p = 0.01), whereas meningitis, mechanical ventilation and mortality did not change in baseline vs intervention period. After implementing the SPEs, no cases had adverse outcomes due to the strategy, and no cases developed severe disease after 6 hours of life. CONCLUSIONS: Infants with EOS exposed to IAP developed symptoms at birth in almost all cases, and those who appeared well at birth had a very low chance of having EOS. The risk of EOS in neonates (asymptomatic at birth) exposed to intrapartum fever was low. Although definite conclusions on causation are lacking, our data support SPEs of asymptomatic newborns at risk for EOS. SPEs seems a safe and effective alternative to laboratory screening and empirical antibiotic therapy.

Usefulness of a flow chart for targeted screening of congenital cytomegalovirus-related hearing loss.

Around 90% of congenital cytomegalovirus infected neonates are asymptomatic at birth. Among the infected infants showing no clinical abnormalities, 7 to 15% or over may develop sensorineural hearing loss and only about 50% of these cases are detectable at birth. In 2013, the Neonatal Intensive Care Unit at Maggiore Hospital in Bologna (Italy) introduced a one-page flow chart aimed at identifying neonates with unapparent congenital cytomegalovirus infection by means of selective cytomegalovirus screening of patients who failed to pass a hearing screening test. Since its introduction, 83 infants have been referred to our clinic for sample collection and two cases of congenital cytomegalovirus-related sensorineural hearing loss were diagnosed and treated at the appropriate time.

Skin antisepsis with 0.05% sodium hypochlorite before central venous catheter insertion in neonates: A 2-year single-center experience.

AIM: The study reports a 2-year single-center experience of the practice of skin antisepsis using a 0.05% sodium hypochlorite solution before central venous catheter placement in neonates. METHODS: Eligible subjects included any hospitalized neonate who needed a central line for at least 48 hours. Infants were excluded if they had a generalized or localized skin disorder. An ad hoc Excel (Microsoft Corp, Redmond, WA) file was used to record the data from each patient. The catheter sites were monitored daily for the presence of contact dermatitis. Central line-associated bloodstream infection was diagnosed according to Centers for Disease Control and Prevention definition. RESULTS: One hundred five infants underwent central venous catheter placement and were enrolled. A total of 198 central lines were inserted. The median gestational age was 31 weeks (range, 23-41 weeks) and median birth weight was 1,420 g (range, 500-5,170 g). There were no signs of 0.05% sodium hypochlorite-related skin toxicity in any infant. Of 198 catheters (1,652 catheter-days) prospectively studied, 9 were associated with bloodstream infections (5.4 per 1,000 catheter-days). CONCLUSION: During the observation period, no local adverse effects were observed suggesting that 0.05% sodium hypochlorite may be a safe choice in this context.

The burden of early-onset sepsis in Emilia-Romagna (Italy): a 4-year, population-based study.

OBJECTIVE: To provide the first Italian data on pathogens causing early-onset sepsis (EOS) and their antimicrobial susceptibility, after the successfully prevention of Group B streptococcus (GBS) EOS. METHODS: Retrospective area-based cohort study from Emilia-Romagna (Italy). Cases of EOS registered (from 2009 to 2012) in all gestational age neonates were reviewed. RESULTS: Live births (LB) numbered 146 682. Ninety neonates had EOS and 12 died (incidence rates of 0.61 and 0.08/1000 LB, respectively). EOS and mortality were the highest among neonates with a birth weight <1000 g (20.37/1000 LB and 8.49/1000 LB, respectively). The most common pathogens were GBS (n = 27, 0.18/1000 LB) and Escherichia coli (n = 19, 0.13/1000 LB). Most infants affected by E. coli EOS were born preterm (n = 13), had complications (n = 4) or died (n = 7). Among 90 isolates tested, only 3 were resistant to both first line empirical antibiotics. Multivariate logistic regression analysis showed that low gestational age, caesarean section and low platelet count at presentation were significantly associated with death or brain lesions (area under ROC curve = 0.939, H-L = 0.944, sensitivity 76.0%, specificity 90.7%). CONCLUSIONS: GBS slightly exceeds E. coli as a cause of EOS. However, E. coli is the prominent cause of death, complications and in most cases affects preterm neonates. Empirical antimicrobial therapy of EOS seems appropriate.

Outbreak of ampicillin/piperacillin-resistant Klebsiella pneumoniae in a neonatal intensive care unit (NICU): investigation and control measures.

Klebsiella pneumoniae is a frequent cause of infectious outbreaks in Neonatal Intensive Care Units (NICUs). The aim of this paper is to describe an outbreak occurred in a 13-bed NICU and the control measures adopted in order to interrupt the chain of transmission. We described the microbiological investigations, the NICU staff compliance to the infection control measures by means of a specifically designed check-list and the control measures adopted. Six cases of primary bloodstream infections sustained by ampicillin/piperacillin-resistant Klebsiella pneumoniae were observed over a two-month period. One culture obtained from a 12% saccarose multiple-dose solution allowed the growth of Klebsiella pneumoniae. During the inspections performed by the Hospital Infection Control Team, using the check-list for the evaluation of the NICU staff compliance to the infection control measures, several breaches in the infection control policy were identified and control measures were adopted. In our case the definition of a specific check-list led to the adoption of the correct control measures. Further studies would be helpful in order to develop a standard check-list able to identify critical flows in the adhesion to the guidelines. It could be used in different NICUs and allow to obtain reproducible levels of infection control.

Group B streptococcus late-onset disease: 2003-2010.

BACKGROUND: There is insufficient population-based data on group B streptococcus (GBS) late-onset disease (LOD). Risk factors and routes of GBS transmission are poorly understood. METHODS: A prospective, cohort study was conducted to collect incidence data on LOD and evaluate GBS infections over an 8-year period (2003-2010). Starting from January 2007, maternal rectovaginal and breast milk cultures were routinely collected on confirmation of the LOD diagnosis to assess maternal GBS culture status. RESULTS: The incidence rate of LOD was 0.32 per 1000 live births (1.4 and 0.24 per 1000 live births for preterm and term newborns, respectively). The registered cases of LOD (n = 100) were classified as sepsis (n = 57), meningitis (n = 36), or focal infection (n = 7). Thirty neonates were preterm (2 had recurrent infection); 68 were term. Four infants died (3 early preterm, 1 term). At the time the LOD diagnosis was confirmed, 3 (6%) of 53 mothers had GBS mastitis, and 30 (64%) of 47 carried GBS at the rectovaginal site. Early (7-30 days) LOD presentation was associated with neonatal brain lesions or death (odds ratio: 0.96 [95% confidence interval: 0.93-0.99]). Intrapartum antibiotic exposure was significantly associated with mild (12 of 22) rather than severe (11 of 45; P = .03) LOD. CONCLUSIONS: Preterm neonates had the highest rates of LOD and mortality. Most mothers carried GBS at the time of the LOD diagnosis, whereas 6% had mastitis. Intrapartum antibiotics were associated both with delayed presentation of symptoms and milder LOD.

Group B Streptococcus early-onset disease in Emilia-romagna: review after introduction of a screening-based approach.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections. Early-onset infections have decreased in recent years but, despite considerable efforts poured into prevention, cases continue to occur. OBJECTIVES: To analyze trends and identify determining factors for the persistence of the GBS infections. To evaluate the impact of antenatal screening and intrapartum chemoprophylaxis on the clinical presentation of the infection. METHODS: A prospective cohort, population-based study has been ongoing in Emilia-Romagna (Italy) since 2003. Invasive GBS infections, observed between 2003 and 2008 in infants aged < 7 days were analyzed. RESULTS: Among 214,120 live births, 61 early-infections were observed. Fourteen infants (23.0%) were born preterm. Among 47 infants who were delivered at term, 28 were born to mothers who had no risk factors and 7 were born to mothers who had none other than GBS colonization. Forty-one women at term had been screened prenatally; among them, only 10 were documented as GBS culture-positive.Disease severity was highest in infants at lower gestational ages, but most meningitis cases were observed in term infants born to mothers who were GBS culture-negative at screening.Nine newborns had culture-proven infection despite having received intrapartum antibiotics. They were born to mothers with > or =1 obstetrical risk factors and 5 mothers had been treated during labor with macrolides. CONCLUSION: Most infections presented in infants whose mothers had been screened as GBS culture-negative. Missed opportunities for prevention contributed more than prophylaxis failures to the early-onset disease burden.

Group B streptococcal infections in a northern region of Italy.

BACKGROUND: Group B streptococcus is a leading cause of neonatal bacterial infections. Despite adoption of preventive strategies, cases of infection continue to occur and there is concern that widespread antimicrobial prophylaxis might delay rather than prevent disease onset, increasing the rates of late-onset diseases. OBJECTIVES: The purpose of this study was to determine the incidence and clinical features of early- and late-onset group B streptococcus disease in a northern region of Italy where a screening-based approach had been proposed. METHODS: A population-based study was prospectively conducted in Emilia-Romagna, Italy. Infections that occurred during 2003-2005 in infants aged <3 months were analyzed. RESULTS: Among 112,933 live births, 56 cases of invasive disease (30 early- and 26 late-onset disease) were observed, giving an annual group B streptococcus disease incidence of 0.50 per 1000 live births. Eleven infants with early-onset disease showed no signs of illness or were mildly ill, whereas 19 had moderate-to-severe symptoms, and culture-proven meningitis was found in 2. Risk factors were detected in 12 women. Twenty-two mothers had antenatal screening; 5 were group B streptococcus colonized, but 17 were culture-negative. Prophylaxis was administered in 3 women. Three infants with late-onset diseases were mildly ill, whereas 23 had moderate-to-severe symptoms. Risk factors were found in 7 mothers. Late-onset diseases were clinically more severe than early-onset diseases; meningitis was diagnosed in 12 infants, and 4 of 26 died. CONCLUSIONS: The incidence of early-onset disease was low. Some early infections were still observed because of negative screening results or missed opportunity for prevention. Late-onset diseases accounted for most meningitis cases and deaths. Strict adherence to protocols and adoption of optimal culture methods would further improve prevention of early-onset disease, but the aim of future strategies should be the prevention of all invasive diseases.