Congenital Pneumonia Treatment & Management

Therapy in infants with neonatal pneumonia is multifaceted. The goals of therapy are to eradicate infection and provide adequate support of gas exchange to ensure the survival and eventual well being of the infant.

Evidence-supported options for targeted treatment of inflammation independent of antimicrobial therapy are severely limited.^[23] There is considerable speculation that current antimicrobial agents, directed at killing invasive organisms, may transiently worsen inflammatory cascades and associated host injury because dying organisms release proinflammatory structural and metabolic constituents into the surrounding microenvironment. This is not to imply that eradication of invasive microbes should not be a goal; however, other methods of eradicating pathogens or methods of directly dealing with the pathologic inflammatory cascades await further definition.

Drainage of a restrictive or infected effusion or empyema may enhance clearance of the infection and will improve lung mechanics.

Even if the infection is eradicated, many hosts develop long-lasting or permanent pulmonary changes that adversely affect lung function, quality of life, and susceptibility to later infections.

In pneumonia resulting from noninfectious causes, the quest for targeted, effective, and safe anti-inflammatory therapy may be of even greater importance.

Go to Pneumonia, Pediatric and Afebrile Pneumonia Syndrome for more complete information on these topics. Additionally, see Surgical Treatment of Infections of the Lung, Pleura, and Mediastinum for more complete information on this topic.

Initial empiric antibiotics are selected according to the susceptibility pattern of the likely pathogens, experience at the institution, and knowledge of delivery of drugs to the suspected infected sites within the lung. Empiric use of azithromycin or other macrolides for presumed Ureaplasma infection is not currently evidence based and should be reserved for infants who have that organism recovered from a normally sterile site or who are critically ill and do not have a more likely cause of infection.^{[24, 25]}

Because bacteremia is common as both a cause and a consequence of congenital pneumonia, attaining an adequate plasma concentration of the antimicrobial agent via a parenteral route is essential. Alveolar delivery of antibiotics typically occurs via diffusion of non–protein-bound drug and is usually satisfactory if plasma concentrations and alveolar perfusion are adequate.

At most institutions, initial empiric therapy consists of ampicillin and either gentamicin or cefotaxime. Dosage regimens vary according to gestational and postnatal age, as well as renal function. Observational studies have suggested increased adverse outcomes, including an increased risk of death, in neonates who receive cefotaxime rather than gentamicin as a routine component of initial empiric neonatal treatment.^{[26, 27]}

Whether the adverse outcomes with cefotaxime are causal, coincidental, or secondary to some other associated factor is unclear. Nevertheless, in some circumstances (eg, renal dysfunction, hearing or ear abnormalities, gram-negative central nervous system infection, maternal myasthenia gravis, high local incidence of gentamicin-resistant but cefotaxime-sensitive organisms), cefotaxime may be preferable to gentamicin.

Isolation of a specific pathogen from a normally sterile site in the infant allows revision of therapy to the drug that is least toxic, has the narrowest antimicrobial spectrum, and is most effective. Dosing intervals for ampicillin, cefotaxime, gentamicin, and other antimicrobial agents typically require readjustment in the face of renal dysfunction or once the infant is older than 7 days (if the infant still requires antimicrobial therapy).

If gram-negative pneumonia is suspected and beta-lactam antibiotics are administered, some data suggest that continuous exposure to an antimicrobial concentration greater than the mean inhibitory concentration for the organism may be more important than the amplitude of the peak concentration. Intramuscular or intravenous therapy with the same total daily dose but more frequent dosing may be advantageous if the infant fails to respond to conventional dosing. Comparative data to confirm the superiority of this approach are lacking. Whether this approach offers any advantage with use of agents other than beta-lactams is unclear.

Studies in human adults have demonstrated that aminoglycosides reach the bronchial lumen marginally when administered parenterally, although alveolar delivery is satisfactory.^{[28, 29]} Endotracheal treatment with aerosolized aminoglycosides has been reportedly effective for marginally susceptible organisms in bronchi, whereas cefotaxime appears to attain adequate bronchial concentrations via the parenteral route. Limited in vitro and animal data suggest that cefotaxime may retain more activity than aminoglycosides in sequestered foci, such as abscesses, although such foci are rare in congenital pneumonia, and adequate drainage may be more important than antimicrobial selection.

Recovery of a specific pathogen from a normally sterile site (eg, blood, urine, cerebrospinal fluid) permits narrowing the spectrum of antimicrobial therapy and may thus reduce the selection of resistant organisms and costs of treatment. Repeated culture of the site after 24-48 hours is usually warranted to ensure sterilization and to assess the efficacy of therapy.

Endotracheal aspirates are not considered to represent a normally sterile site, although they may yield an organism that is a true invasive pathogen. Reculture of an endotracheal aspirate that identified the presumptive pathogen in a particular case may not be helpful because colonization may persist even if tissue invasion has been terminated.

Decreasing respiratory support requirements, clinical improvement, and resolution revealed on radiographs also support the efficacy of therapy.

When appropriate, assess plasma antibiotic concentrations to ensure adequacy and reduce the potential for toxicity. Failure to recover an organism does not exclude an infectious etiology; continuation of empiric therapy may be advisable unless the clinical course or other data strongly suggests that a noninfectious cause is responsible for the presenting signs.

Although meconium is usually sterile, most clinicians opt for adjunctive antimicrobial therapy when meconium was present in the amniotic fluid because concurrent aspiration of pathogens or antecedent bacteremia as a cause of intrauterine meconium passage and subsequent aspiration usually cannot be excluded.

Continue to perform careful serial examinations for evidence of complications that may warrant a change in therapy or dosing regimen, surgical drainage, or other intervention.

The duration of antimicrobial therapy for neonatal pneumonia has not been rigorously assessed in comparative trials. Most clinicians treat infants for 7-10 days if clinical signs resolve rapidly. If positive results on culture were found at a normally sterile site, continuing treatment for 7-10 days following sterilization is prudent. Longer periods of therapy may be warranted if a sequestered focus, such as empyema or abscess, is seen or if metastatic infection develops. Herpes simplex infection with central nervous system involvement may require 21 or more days of antiviral treatment.

Adequate gas exchange depends not only on alveolar ventilation, but also on perfusion and gas transport capacity of the alveolar perfusate (ie, blood). Preservation of pulmonary and systemic perfusion is essential, using volume expanders, inotropes, afterload reduction, blood products, and other interventions (eg, inhaled nitric oxide) as needed. Excellent lung mechanics do little good if perfusion is not simultaneously adequate.

Criteria for institution of and weaning from supplemental oxygen and mechanical support are similar to those for other neonatal respiratory diseases. Be aware that lung disease in these patients is often structurally heterogeneous, with subpopulations of normally inflated, hyperinflated, atelectatic, obstructed, fluid-filled, and variably perfused alveoli that may require multiple adjustments of ventilatory pressures, flows, rates, times, and modalities.

A number of respiratory management issues require special consideration in newborn infants in whom pneumonia is suspected. These include airway patency, ventilatory support, and pulmonary hypertension.

Airway patency

Assurance of airway patency may be more challenging in neonates with pneumonia because of the often profuse, potentially obstructive secretions and mucopurulent exudates of variable viscosity. Judicious suctioning is warranted. Deep suctioning should be avoided because it can cause airway trauma and swelling, which, in turn, may cause large airway obstruction.

Gentle vibration and percussion is used in some centers to mobilize the secretions, although appropriately designed studies do not support routine use of this technique. At least one report cautions that long-term routine percussion may be associated with brain injury in premature infants with a birth weight less than 1500 g.^[30] Potential benefit may exceed potential risks with targeted use in specific infants with secretion problems.

Use of mucolytic agents, such as acetylcysteine or recombinant DNase, may be required to mobilize dense inspissated secretions but also may induce bronchospasm and be poorly tolerated.

Any endotracheal tube requires careful positioning and may require periodic replacement to ensure patency. Endotracheal perfluorocarbon and exogenous surfactant lavage have both been suggested as possible means of safely mobilizing thick potentially obstructive material, including meconium, even from distal airways. Bronchoscopic removal may be plausible if the airway is sufficiently large.

Prevention or reduction of atelectasis may reduce bacterial growth and/or bacterial translocation.^[31]

Comparative trials of sufficient size to document the safety and efficacy of these approaches are sparse.

Ventilatory support

Ventilatory support may be rendered unusually challenging by alveoli with variable degrees of inflation from the unpredictable distribution of surfactant inactivation, partial airway obstruction, and fluid exudation.

Take care to ensure that the airway pressures required to attain alveolar stability interfere as little as possible with myocardial function, venous return, and alveolar perfusion.

The use of high-frequency or patient-triggered ventilatory techniques may offer better recruitment of alveolar lung volume, but data are sparse.

Exogenous surfactant may be beneficial in selected infants. Although randomized controlled trials in human infants for this indication are lacking, animal studies and an increasing number of clinical reports have suggested the adjunctive utility of exogenous surfactant.^{[32, 33]} Many clinicians elect to administer surfactant when mechanical ventilation is required with greater than 60% oxygen concentration. Time to clinical response and requirement for multiple doses are both reported to be greater than in infants with respiratory distress syndrome.

A guideline from the American Academy of Pediatrics (AAP) advises that rescue treatment with surfactant may be considered for infants with hypoxic respiratory failure attributable to secondary surfactant deficiency (eg, meconium aspiration syndrome or pneumonia).^[34] However, the AAP notes that is important for medical personnel to have the requisite technical and clinical expertise to administer surfactant safely and to deal with multisystem illness.

Pulmonary hypertension

Pulmonary hypertension with significant intrapulmonary and extrapulmonary shunting is not uncommon with pneumonia, especially in postterm, term, and near-term infants with sufficient pulmonary vascular smooth muscle to develop systemic or suprasystemic pulmonary vascular resistance.

The optimal therapeutic strategy for pulmonary hypertension remains unresolved. Increased systemic vascular resistance, paralysis, inhaled nitric oxide^[35] and/or infused epoprostenol are vigorously used by many clinicians, whereas others advocate less aggressive approaches.

A randomized collaborative trial in the United Kingdom demonstrated that extracorporeal membrane oxygenation (ECMO) was significantly better than conventional therapy in preventing death; however, infants with pneumonia comprised only a fraction of the total study population.^[36] Among all newborn infants who are sick enough to require ECMO, those with an underlying diagnosis of pneumonia have a higher mortality rate than those with all noninfectious diseases, except congenital diaphragmatic hernia.^[37]

Red blood cells should be administered to achieve a hemoglobin concentration of 13-16 g/dL in the acutely ill infant, to ensure optimal oxygen delivery to the tissues.

Delivery of adequate amounts of glucose and maintenance of thermoregulation, electrolyte balance, and other elements of neonatal supportive care are also essential.

Attempts at enteral feeding often are withheld in favor of parenteral nutritional support until respiratory and hemodynamic status is sufficiently stable.

If appropriate respiratory, hemodynamic, or nutritional support cannot be safely and effectively administered at the hospital of birth, stabilize the neonate and transfer to a tertiary care neonatal intensive care unit.

Consider intrapartum antibiotic chemoprophylaxis with penicillin or another appropriate antimicrobial agent in mothers at risk for early-onset group B streptococcal disease. Risk factors are as follows:

• Known colonization of birth canal by group B Streptococcus
• Premature delivery
• Membrane rupture more than 18 hours before delivery
• Intrapartum fever
• Group B streptococcal bacteriuria
• History of previous infant with early-onset neonatal group B streptococcal infection

Consult the Red Book for the most current recommendations for infants at risk for group B streptococcal sepsis/pneumonia.^[38]

Prevention strategies may include antepartum and intrapartum broad-spectrum antibiotic treatment in mothers with preterm rupture of membranes or in whom chorioamnionitis is suspected.

In the presence of particulate amniotic fluid meconium, suction the trachea immediately after birth if the infant is not vigorous.^[39]

Currently, there is little evidence demonstrating the potential efficacy of the following interventions in neonates:

• Elevating the head
• Use of antireflux medications
• Differential policies for oral care and changes of suction and ventilator tubing
• Other potential interventions