Bacterial meningitis: Mechanisms of disease and therapy

Bacterial meningitis continues to be a serious infectious disease with a high morbidity and mortality in young children. Early recognition and initiation of adequate treatment are the major determinants for a good outcome. Recent advances in our understanding of the host inflammatory response by cytokines may result in the use of new therapeutic strategies. Such modulation of the inflammatory response may reduce the incidence of sequelae and death. The use of steroids as adjunctive therapy in children with bacterial meningitis probably has beneficial effects although the available data are still controversial. Additionally, studies in experimental meningitis models indicate that non-steroidal anti-inflammatory drugs and monoclonal antibodies against bacterial products, cytokines and CD18 on leucocytes reduce the extent of the meningeal inflammation. Human studies to evaluate the efficacy of these immune modulators are expected to start soon. However, prevention of bacterial meningitis by conjugate vaccines againstStreptococcus pneumoniae andNeisseria meningitidis will be the most promising development in the next decade

Recurring staphylococcal scalded skin syndrome in a very low birth weight infant: A case report

Introduction. Staphylococcal scalded skin syndrome is an extensive desquamative erythematous condition caused by exfoliative toxins of Staphylococcus aureus. This disease usually affects neonates and generally responds rapidly to antibiotic therapy. Case presentation. We describe the case of a premature baby boy, weighing 1030 g, born after 26 6/7 weeks gestation, who developed two episodes of Staphylococcal scalded skin syndrome on days 19 and 48 of life. Cultures obtained during the first period did not reveal Staphylococcus aureus, but diagnosis was based on typical clinical grounds. Although the initial diagnosis was irritation by the fixation material of a nasal continuous positive airway pressure tube, the infant showed rapidly progressing skin blistering and exfoliation, characteristic of Staphylococcal scalded skin syndrome. After administration of antibiotic treatment, complete recovery was seen. In the second period, diagnosis of Staphylococcal scalded skin syndrome was made clinically and confirmed by results of microbiologic investigations. Staphylococcus aureus was cultured from the nose, skin lesions and the pharynx. The strain appeared to produce exfoliative toxin A. The clinical response to similar antibiotic treatment was identical to the first period of Staphylococcal scalded skin syndrome. Conclusion. This case report discusses an unusual presentation of recurring Staphylococcal scalded skin syndrome in a baby with a very low birth weight

Implementation of a children's hospital-wide central venous catheter insertion and maintenance bundle

Background: Central venous catheter-associated bloodstream infections in children are an increasingly recognized serious safety problem worldwide, but are often preventable. Central venous catheter bundles have proved effective to prevent such infections. Successful implementation requires changes in the hospital system as well as in healthc

Stratified Management for Bacterial Infections in Late Preterm and Term Neonates:Current Strategies and Future Opportunities Toward Precision Medicine

Bacterial infections remain a major cause of morbidity and mortality in the neonatal period. Therefore, many neonates, including late preterm and term neonates, are exposed to antibiotics in the first weeks of life. Data on the importance of inter-individual differences and disease signatures are accumulating. Differences that may potentially influence treatment requirement and success rate. However, currently, many neonates are treated following a “one size fits all” approach, based on general protocols and standard antibiotic treatment regimens. Precision medicine has emerged in the last years and is perceived as a new, holistic, way of stratifying patients based on large-scale data including patient characteristics and disease specific features. Specific to sepsis, differences in disease susceptibility, disease severity, immune response and pharmacokinetics and -dynamics can be used for the development of treatment algorithms helping clinicians decide when and how to treat a specific patient or a specific subpopulation. In this review, we highlight the current and future developments that could allow transition to a more precise manner of antibiotic treatment in late preterm and term neonates, and propose a research agenda toward precision medicine for neonatal bacterial infections.</p

Necrotising enterocolitis and mortality in preterm infants after introduction of probiotics: A quasi-experimental study

Evidence on the clinical effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in preterm infants is conflicting and cohort studies lacked adjustment for time trend and feeding type. This study investigated the association between the introduction of routine probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum; Infloran ®) on the primary outcome 'NEC or death'. Preterm infants (gestational age <32 weeks or birth weight <1500 gram) admitted before (Jan 2008-Sep 2012; n = 1288) and after (Oct 2012-Dec 2014; n = 673) introduction of probiotics were compared. Interrupted time series logistic regression models were adjusted for confounders, effect modification by feeding type, seasonality and underlying temporal trends. Unadjusted and adjusted analyses showed no difference in 'NEC or death' between the two periods. The overall incidence of NEC declined from 7.8% to 5.1% (OR 0.63, 95% CI 0.42-0.93, p = 0.02), which was not statistically significant in the adjusted models. Introduction of probiotics was associated with a reduced adjusted odds for 'NEC or sepsis or death' in exclusively breastmilk-fed infants (OR 0.43, 95% CI 0.21-0.93, p = 0.03) only. We conclude that introduction of probiotics was not associated with a reduction in 'NEC or death' and that type of feeding seems to modify the effects of probiotics

Culture-negative early-onset neonatal sepsis - at the crossroad between efficient sepsis care and antimicrobial stewardship

Sepsis is a leading cause of mortality and morbidity in neonates. Presenting clinical symptoms are unspecific. Sensitivity and positive predictive value of biomarkers at onset of symptoms are suboptimal. Clinical suspicion therefore frequently leads to empirical antibiotic therapy in uninfected infants. The incidence of culture confirmed early-onset sepsis is rather low, around 0.4-0.8/1000 term infants in high-income countries. Six to 16 times more infants receive therapy for culture-negative sepsis in the absence of a positive blood culture. Thus, culture-negative sepsis contributes to high antibiotic consumption in neonatal units. Antibiotics may be life-saving for the few infants who are truly infected. However, overuse of broad-spectrum antibiotics increases colonization with antibiotic resistant bacteria. Antibiotic therapy also induces perturbations of the non-resilient early life microbiota with potentially long lasting negative impact on the individual's own health. Currently there is no uniform consensus definition for neonatal sepsis. This leads to variations in management. Two factors may reduce the number of culture-negative sepsis cases. First, obtaining adequate blood cultures (0.5-1 mL) at symptom onset is mandatory. Unless there is a strong clinical or biochemical indication to prolong antibiotics physician need to trust the culture results and to stop antibiotics for suspected sepsis within 36-48 h. Secondly, an international robust and pragmatic neonatal sepsis definition is urgently needed. Neonatal sepsis is a dynamic condition. Rigorous evaluation of clinical symptoms ("organ dysfunction") over 36-48 h in combination with appropriately selected biomarkers ("dysregulated host response") may be used to support or refute a sepsis diagnosis

Oral antibiotics for neonatal infections: a systematic review and meta-analysis

Background: Worldwide many neonates suffer from bacterial infections. Adequate treatment is important but is associated with prolonged hospitalization for intravenous administration. In older children, oral switch therapy has been proven effective and safe for several indications and is now standard care. Objectives: To evaluate the currently available evidence on pharmacokinetics, safety and efficacy of oral antibiotics and oral switch therapy in neonates (0–28 days old). Methods: We performed systematic searches in Medline, Embase.com, Cochrane, Google Scholar and Web of Science. Studies were eligible if they described the use of oral antibiotics in neonates (0–28 days old), including antibiotic switch studies and pharmacological studies. Results: Thirty-one studies met the inclusion criteria. Compared with parenteral administration, oral antibiotics generally reach their maximum concentration later and have a lower bioavailability, but in the majority of cases adequate serum levels for bacterial killing are reached. Furthermore, studies on efficacy of oral antibiotics showed equal relapse rates (

Hand disinfection in a neonatal intensive care unit: continuous electronic monitoring over a one-year period

<p>Abstract</p> <p>Background</p> <p>Good hand hygiene compliance is essential to prevent nosocomial infections in healthcare settings. Direct observation of hand hygiene compliance is the gold standard but is time consuming. An electronic dispenser with built-in wireless recording equipment allows continuous monitoring of its usage. The purpose of this study was to monitor the use of alcohol-based hand rub dispensers with a built-in electronic counter in a neonatal intensive care unit (NICU) setting and to determine compliance with hand hygiene protocols by direct observation.</p> <p>Methods</p> <p>A one-year observational study was conducted at a 27 bed level III NICU at a university hospital. All healthcare workers employed at the NICU participated in the study. The use of bedside dispensers was continuously monitored and compliance with hand hygiene was determined by random direct observations.</p> <p>Results</p> <p>A total of 258,436 hand disinfection events were recorded; i.e. a median (interquartile range) of 697 (559–840) per day. The median (interquartile range) number of hand disinfection events performed per healthcare worker during the day, evening, and night shifts was 13.5 (10.8 - 16.7), 19.8 (16.3 - 24.1), and 16.6 (14.2 - 19.3), respectively. In 65.8% of the 1,168 observations of patient contacts requiring hand hygiene, healthcare workers fully complied with the protocol.</p> <p>Conclusions</p> <p>We conclude that the electronic devices provide useful information on frequency, time, and location of its use, and also reveal trends in hand disinfection events over time. Direct observations offer essential data on compliance with the hand hygiene protocol. In future research, data generated by the electronic devices can be supplementary used to evaluate the effectiveness of hand hygiene promotion campaigns.</p

Whole-genome sequencing to explore nosocomial transmission and virulence in neonatal methicillin-susceptible Staphylococcus aureus bacteremia

BACKGROUND: Neonatal Staphylococcus aureus (S. aureus) bacteremia is an important cause of morbidity and mortality. In this study, we examined whether methicillin-susceptible S. aureus (MSSA) transmission and genetic makeup contribute to the occurrence of neonatal S. aureus bacteremia. METHODS: A retrospective, single-centre study was performed. All patients were included who suffered from S. aureus bacteremia in the neonatal intensive care unit (NICU), Erasmus MC-Sophia, Rotterdam, the Netherlands, between January 2011 and November 2017. Whole-genome sequencing (WGS) was used to characterize the S. aureus isolates, as was also done in comparison to reference genomes. Transmission was considered likely in case of genetically indistinguishable S. aureus isolates. RESULTS: Excluding coagulase-negative staphylococci (CoNS), S. aureus was the most common cause of neonatal bacteremia. Twelve percent (n = 112) of all 926 positive blood cultures from neonates grew S. aureus. Based on core genome multilocus sequence typing (cgMLST), 12 clusters of genetically indistinguishable MSSA isolates were found, containing 33 isolates in total (2-4 isolates per cluster). In seven of these clusters, at least two of the identified MSSA isolates were collected within a time period of one month. Six virulence genes were present in 98-100% of all MSSA isolates. In comparison to S. aureus reference genomes, toxin genes encoding staphylococcal enterotoxin A (sea) and toxic shock syndrome toxin 1 (tsst-1) were present more often in the genomes of bacteremia isolates. CONCLUSION: Transmission of MSSA is a contributing factor to the occurrence of S. aureus bacteremia in neonates. Sea and tsst-1 might play a role in neonatal S. aureus bacteremia