eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Congenital Pneumonia: Treatment & Medication

Author: Roger G Faix, MD, Professor, Department of Pediatrics (Neonatology), University of Utah School of Medicine
Contributor Information and Disclosures

Updated: Oct 5, 2009

Treatment

Medical Care

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.²⁴ Considerable speculation suggests 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 eradicating invasive microbes should not be a goal; however, other methods of eradication or methods of directly dealing with the pathologic inflammatory cascades await further definition.

Even if the infection is eradicated, many hosts develop long-lasting or permanent pulmonary changes that affect lung function, the 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.

• Antimicrobial therapy
  • Initial empiric antibiotics are selected according to the susceptibility pattern of the likely pathogens, experience at the institution and tempered by knowledge of delivery of drugs to the suspected infected sites within the lung. Empiric use of azithromycin or other macrolide 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 with no more likely cause of infection.^25,26
  • Drainage of a restrictive or infected effusion or empyema may enhance clearance of the infection and improves lung mechanics.
  • Because congenital pneumonia frequently results from bloodstream infection or frequently seeds the circulation secondarily, attaining an adequate plasma concentration of the antimicrobial agent via a parenteral route is essential. Alveolar delivery of antibiotics typically occurs via diffusion of a free 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. A large observational study by Clark et al has suggested an increased risk of death in neonates who receive cefotaxime rather than gentamicin.²⁷ Subsequent observational studies have also suggested adverse outcomes associated with selection of cefotaxime as a routine component of initial empiric neonatal treatment.
  • Recovery of a specific pathogen from a normally sterile site (eg, blood, urine, cerebrospinal fluid) permits narrowing the spectrum of antimicrobial therapies and may thus reduce the selection of resistant organisms and costs of therapy. 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 site, although they may yield a pathogen that is a true invasive culprit. 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 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, 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.
• Respiratory support
  • 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 and weaning of supplemental oxygen and mechanical support are similar to those for other neonatal respiratory diseases.
  • Beware of lung disease 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.
• Hemodynamic support
  • RBCs should be administered to ensure 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 aspects of clinical care.
• Nutritional support: 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 and transfer the neonate to a tertiary care NICU.
• A number of respiratory management issues require special consideration in newborn infants in whom pneumonia is suspected.
  • Airway patency
    • Assurance of airway patency may be more challenging with pneumonia because of the often profuse, potentially obstructive secretions and mucopurulent exudates of variable viscosity.
    • Prevention or reduction of atelectasis may reduce bacterial growth and/or bacterial translocation.²⁸
    • 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 its routine use. 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.²⁹ 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.
    • 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.
    • 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.^30,31 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.
    • 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.
  • 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 oxide³² 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.³³ 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.³⁴

Medication

The frequency of bacterial infection as the primary cause or as a superimposed complication of pulmonary inflammation in general, and congenital pneumonia in particular, usually mandates antibiotic administration as the cornerstone of therapy.

Agents typically used initially include a combination of ampicillin and either gentamicin or cefotaxime. The selection of cefotaxime or gentamicin must be based on experience and considerations at each center and in each patient. Combination therapy provides reasonable antimicrobial efficacy against the pathogens that typically cause serious infection in the first days of life. Other agents or combinations may be appropriate for initial empiric therapy if justified by the range of pathogens and susceptibilities encountered in a particular clinical setting.

As noted above, numerous observational studies have suggested increased adverse outcomes associated with the empiric use of cefotaxime.^27,35 Whether this is causal, coincidental or secondary to some other associated factor is unclear. Despite the suggestive observations, in some circumstances (eg, renal dysfunction, hearing or ear abnormalities, gram-negative CNS infection, maternal myasthenia gravis, high 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 (IM) treatment or intravenous (IV) therapy with the same total daily dose but a more frequent dosing interval 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.^36,37 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.

Antibiotics

The frequency of bacterial infection as the cause or a major complication of congenital pneumonia usually mandates antibiotics as a cornerstone of therapy. Below are the most commonly used antibiotics in congenital pneumonia. Consultation of appropriate neonatal references, such as Neofax, is recommended. Similarly, an appropriate reference should be used when using adjunctive therapy such as bronchodilators, mucolytics, nitric oxide or epoprostenol.

Ampicillin (Omnipen, Polycillin, Principen)

This parenteral agent offers antimicrobial efficacy against many pathogens encountered in infections that occur in the first few days of life, including, but not limited to, group B Streptococcus, many types of other streptococci, L monocytogenes, and some strains of E coli, enterococci, and nontypeable H influenzae.

Cefotaxime (Claforan)

Arrests bacterial cell wall synthesis, which in turn inhibits bacterial growth. Third-generation cephalosporin with gram-negative spectrum. When administered parenterally, this agent offers antimicrobial efficacy against many gram-negative pathogens that are commonly encountered in the first few days of life, including E coli, nontypable H influenzae, Klebsiella species, and other enteric organisms. Crosses the blood-brain barrier into the CNS reasonably well and theoretically poses less risk of renal toxicity or ototoxicity than gentamicin and other aminoglycosides, which are the common alternatives. Less likely than gentamicin to interfere with function of neuromuscular junction in infants born to mothers with myasthenia gravis.
However, compared to gentamicin, cefotaxime is more costly, is associated with much more rapid emergence of resistant organisms in a closed environment (eg, NICU), has a slightly narrower range of susceptible gram-negative organisms, and has not been demonstrated to yield superior outcomes in a randomized controlled trial of neonatal patients.

Gentamicin

Aminoglycoside antibiotic for gram-negative coverage. Typically used in combination with agents against gram-positive organisms. When administered parenterally, this agent offers antimicrobial efficacy against many gram-negative pathogens commonly encountered in the first few days of life, including E coli, Klebsiella species, and other enteric organisms, as well as many strains of nontypable H influenzae,. Also variably effective against some strains of certain gram-positive organisms, including S aureus, enterococci, and L monocytogenes. Gentamicin crosses the blood-brain barrier into the CNS less well and theoretically poses greater risk of renal toxicity or ototoxicity than cefotaxime and other third-generation cephalosporins, which are the common alternatives.
Compared to cefotaxime, gentamicin is less costly, is associated with much less rapid emergence of resistant organisms in a closed environment (eg, NICU), and has a broader range of susceptible gram-negative organisms.
Gentamicin has been reported to offer additive or synergistic activity against enterococci when used with ampicillin.

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