NEONATAL SEPSIS MEDICAL CARE FOLLOWUP

Neonatal Sepsis Medical Care: Initiate treatment immediately because of the neonate's immunologic weaknesses for fighting infection. Begin antibiotics as soon as diagnostic tests are performed. Additional therapies have been investigated for the treatment of neonatal sepsis; however, no unequivocal proof that these treatments are beneficial exists. These additional therapies include granulocyte transfusion, intravenous immune globulin (IVIG) replacement, exchange transfusion, and the use of recombinant cytokines.

• In the United States and Canada, the most current approach to treat early-onset neonatal sepsis syndrome includes combined IV aminoglycoside and penicillin antibiotic therapy. This provides coverage for gram-positive organisms, especially GBS, and gram-negative bacteria, such as E coli. The specific antibiotics to be used are chosen on the basis of maternal history and prevalent trends of organism colonization in individual nurseries.

o If infection appears to be nosocomial, direct coverage at organisms implicated in hospital-acquired infections, including S aureus, S epidermis, and Pseudomonas species. Most strains of S aureus produce beta-lactamase, which makes them resistant to penicillin G, ampicillin, carbenicillin, and ticarcillin. Vancomycin has been favored for this coverage; however, concern exists that overuse of this drug may lead to vancomycin-resistant organisms, thereby eliminating the best response to these resistant organisms. Cephalosporins are attractive in the treatment of nosocomial infection because of their lack of dose-related toxicity and adequate serum and CSF concentration; however, resistance by gram-negative organisms has occurred with their use. Do not use ceftriaxone in infants with hyperbilirubinemia because it displaces bilirubin from serum albumen. Resistance and sensitivities for the organism are used to indicate the most effective drug.

o Aminoglycosides and vancomycin are both ototoxic and nephrotoxic; have caution when using them. Check the serum level after 48 hours of treatment to determine if levels are above those required for a therapeutic effect. The dosage amount or interval may need to be changed to ensure adequate but nontoxic coverage. A serum level may be warranted when the infant's clinical condition has not improved to ensure that a therapeutic level has been reached. In addition, perform renal function and hearing screening to determine any short- or long-range toxic effects of these drugs.

o If cultures are negative but the infant has significant risk for sepsis and/or clinical signs, the clinician must decide whether to provide continued treatment. Three days of negative cultures should provide confidence in the data; however, a small number of infants with proven sepsis at postmortem had negative cultures during their initial sepsis workup. Management is further complicated if the mother received antibiotic therapy before delivery, especially close to delivery. This may result in negative cultures in the infant who is still ill. Review all diagnostic data, including cultures, maternal and intrapartal risk factors, CSF results, the CBC and differential radiographs, and the clinical picture to determine the need for continued therapy. Treatment for 7-10 days may be appropriate, even if the infant has negative cultures at 48 hours.

o The clinician may require different antibiotic choice, dosage, and/or treatment time if the infant has bacterial meningitis. Perform a follow-up lumbar puncture within 24-36 hours after antibiotic therapy has been initiated to determine if the CSF is sterile. If organisms are still present, modification of drug type or dosage is required to adequately treat the meningitis. Continue antibiotic treatment for 2 weeks after sterilization of the CSF or for a minimum of 2 weeks for gram-positive meningitis and 3 weeks for gram-negative meningitis, whichever period is longest. Chloramphenicol or trimethoprim-sulfamethoxazole has been shown to be effective in the treatment of highly resistant bacterial meningitis.

• Granulocyte transfusion has been shown to be suitable for infants with significant depletion of the storage neutrophil pool; however, the documentation of storage pool depletion requires a bone marrow aspiration, and the granulocyte transfusion must be administered quickly to be beneficial. The number of potential adverse effects, such as graft versus host reaction, transmission of CMV or hepatitis B, and pulmonary leukocyte sequestration, is considerable. Therefore, this therapy remains an experimental treatment.

• IVIG has been considered for neonatal sepsis to provide type-specific antibodies to improve opsonization and phagocytosis of bacterial organisms and to improve complement activation and chemotaxis of neonatal neutrophils; however, difficulties with IVIG therapy for neonatal sepsis exist. The effect has been transient, and adverse effects associated with the infusion of any blood product can occur. Dose-related problems with this therapy decrease its usefulness in neonatal populations.

• Recombinant human cytokine administration to stimulate granulocyte progenitor cells has been studied as an adjunct to antibiotic therapy. These therapies have shown promise in animal models, especially for GBS sepsis, but require pretreatment or immediate treatment to demonstrate efficacy. The use of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) has been studied in clinical trials, but their use in clinical neonatology remains experimental.

• The infant with sepsis may require treatment aimed at the overwhelming systemic effects of the disease. Cardiopulmonary support and intravenous nutrition may be required during the acute phase of the illness until the infant's condition stabilizes. Monitoring of blood pressure, vital signs, hematocrit, and platelets is vital.

Surgical Care: If hydrocephalus associated with neonatal meningitis occurs, and progressive accumulation of CSF is present, placing a ventriculoperitoneal (VP) shunt may be necessary to drain off the excess fluid. The immediate complications of shunt placement are overdrainage, equipment failure, disconnection, migration of catheter, or shunt infection. Abdominal obstruction, omental cysts, and perforation of the bladder, gall bladder, or bowel occur infrequently. The VP shunt may cause long-term neurologic complications, including slit-ventricle syndrome, seizures, neuro-ophthalmological problems, and craniosynostosis; however, the outcome for children with VP shunt placement is generally good with careful follow-up.

Consultations:
• Infectious disease consultation is useful, especially if the infant is not responding to treatment and/or if an unusual clinical sign is present, such as an unknown rash.
• If neonatal meningitis is identified, consultation with a pediatric neurologist may be necessary for assistance with the initial short-term care or for subsequent outpatient follow-up of neurologic sequelae.
• Consultation with a pediatric pharmacologist may be helpful for advice on dosage and/or antibiotic changes that are necessary because of inadequate or toxic levels obtained with therapeutic monitoring.

Diet: The neonate may need to be given nothing by mouth (NPO) during the first days of treatment because of gastrointestinal symptoms or poor feeding. Consider parenteral nutrition to ensure that the patient's intake of calories, protein, minerals, and electrolytes is adequate during this period. Feeding may be restarted via a nasogastric tube for the infant with serious compromise. Encourage that breast milk be given because of the immunologic protection it provides.

Activity: The infant with temperature instability needs thermoregulatory support with a radiant warmer or incubator. Also, encouraging parental contact is important to ease the stress for parents and continue the bonding between the parents and child.

MEDICATION
Some of the antibiotics commonly used to treat neonatal sepsis syndrome are ampicillin, gentamicin, cefotaxime, vancomycin, metronidazole, erythromycin, and piperacillin. The choice of antibiotic agents should be based on the specific organisms associated with sepsis, sensitivities of the bacterial agent, and prevalent nosocomial infection trends in the nursery. Viral infections, such as herpes and fungal infections, can masquerade as bacterial infections.

Drug Category: Antibiotics -- Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Category: Antivirals -- A viral infection, such as HSV, may masquerade as bacterial sepsis. At the onset of the infection, treatment must be initiated promptly to effectively inhibit the replicating virus.

Drug Category: Antifungals -- Fungal infections can masquerade as bacterial infections and/or may appear at the end of prolonged antibacterial therapy. Their mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

FOLLOW-UP
Further Outpatient Care: The primary care provider should follow up with the infant within one week of discharge from the hospital. The infant can be evaluated for superinfection associated with antibiotic therapy, especially if the therapy was prolonged. Determine if the feeding regimen and activity have returned to normal. Stress to the family the importance of adhering to the immunization schedule.

Transfer:
• The infant may require transfer to a level III perinatal center, especially if he or she requires cardiopulmonary support and/or parenteral nutrition.
• The multidisciplinary services available are necessary when treating a neonate with acute compromise.

Deterrence/Prevention: The Committee on Infectious Diseases of the AAP recommends that obstetric care include a strategy to manage early-onset GBS disease. Treat women with GBS bacteriuria during pregnancy when it is diagnosed and at delivery. The committee also recommends that women who have previously given birth to an infant with GBS disease be intrapartally treated. Practitioners should use either a strategy based on screening the mother or a strategy based on the presence of intrapartum risk factors to minimize the risk of early-onset GBS disease.

Complications: Infants with meningitis may acquire hydrocephalus and/or periventricular leukomalacia. They may also have complications associated with the use of aminoglycosides, such as hearing loss and/or nephrotoxicity.

Prognosis: With early diagnosis and treatment, infants are not likely to experience long-term health problems associated with neonatal sepsis; however, if early signs and/or risk factors are missed, the mortality rate increases. Residual neurologic damage occurs in 15-30% of neonates with septic meningitis.