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

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

Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis

To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in children with bacterial meningitis, bioactive IL-12 (p70) and the inactive subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF) from 35 children with bacterial meningitis and 10 control subjects. The production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF-alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40 as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL-6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10, those of IFN-gamma were significantly higher in patients with pneumococcal meningitis than in children with meningitis caused by Haemophilus influenzae and Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may contribute to the natural immunity against microorganisms in the CSF compartment during the acute phase of bacterial meningitis

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

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 (