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Abstract:
The current incidence of neonatal sepsis in the United States varies from less than 1 to 8.1 per 1000 live births. The incidence of bacterial meningitis is about one-third of the number of infants with sepsis. The mortality is 20 to 30% and many survivors are severely impaired. Group B streptococcus and Escherichia coli are the most frequent causes of meningitis. Because of the difficulty of clinical diagnosis, many infants receive presumptive therapy for suspected sepsis or meningitis although few have documented infection. Between 5 and 10% of newborn infants born in the United States receive antimicrobial agents in the nursery, usually a penicillin and an aminoglycoside. To lower the continued high mortality and morbidity of meningitis due to gram-negative enteric bacilli, collaborative randomized trials evaluated the efficacy of gentamicin administered via the intrathecal route, gentamicin administered into the ventricle and most recently, the efficacy of moxalactam. Neither intrathecal or intraventricular drug, both in combination with parenteral drug, was advantageous when compared with parenterally administered drug alone. The mortality rate and number of days of culture positive cerebrospinal fluid were similar in infants who received moxalactam and ampicillin and infants who received amikacin and ampicillin. Adjunctive therapies including granulocyte transfusion, administration of hyperimmune gamma globulin and exchange transfusion are now under investigation. Initial studies of prevention of systemic bacterial infection by prophylactic ampicillin administered to the mother at delivery and use of group B streptococcal vaccine administered to susceptible women in the child bearing age show promise.
Insights
Neonatal sepsis and meningitis are serious threats, with high mortality and impairment rates. Intrathecal or intraventricular antibiotic administration did not improve outcomes compared to parenteral treatment alone.
Area of Science:
- Neonatal Medicine
- Infectious Diseases
- Pediatric Neurology
Background:
- Neonatal sepsis and bacterial meningitis affect thousands of infants annually in the US, carrying significant mortality and long-term morbidity.
- Group B Streptococcus and Escherichia coli are primary causative agents, complicating diagnosis and treatment due to clinical presentation variability.
- A substantial percentage of newborns receive empirical antibiotic therapy, highlighting diagnostic challenges and the need for effective treatments.
Purpose of the Study:
- To evaluate the efficacy of novel therapeutic strategies for neonatal meningitis caused by gram-negative enteric bacilli.
- To compare parenteral antibiotic therapy with intrathecal or intraventricular drug administration in neonates with meningitis.
- To assess the effectiveness of moxalactam versus ampicillin/amikacin regimens in treating neonatal meningitis.
Main Methods:
- Collaborative randomized trials were conducted to investigate the efficacy of gentamicin via intrathecal and intraventricular routes, alongside parenteral administration.
- The study compared outcomes in infants treated with moxalactam and ampicillin versus those treated with amikacin and ampicillin.
- Data on mortality rates and cerebrospinal fluid culture positivity were analyzed to determine treatment effectiveness.
Main Results:
- Neither intrathecal nor intraventricular gentamicin administration, in conjunction with parenteral therapy, offered advantages over parenteral treatment alone.
- Mortality rates and the duration of positive cerebrospinal fluid cultures were comparable between the moxalactam/ampicillin and amikacin/ampicillin groups.
- Adjunctive therapies like granulocyte transfusions and hyperimmune gamma globulin are under investigation, with prophylactic ampicillin and group B streptococcal vaccines showing early promise for prevention.
Conclusions:
- Direct central nervous system administration of antibiotics is not superior to parenteral therapy for neonatal meningitis.
- Current treatment regimens show similar efficacy, necessitating further research into adjunctive therapies and preventative strategies.
- Preventive measures, including maternal prophylactic antibiotics and vaccination, hold significant potential for reducing the incidence of neonatal bacterial infections.