Neonatal pneumonia

INTRODUCTION — Pneumonia is an important cause of neonatal infection and accounts for significant morbidity and mortality, especially in developing countries [1,2].

The epidemiology, microbiology, clinical manifestations, diagnosis, and treatment of neonatal pneumonia are reviewed here. Neonatal sepsis is discussed separately:

●(See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates".)

●(See "Management and outcome of sepsis in term and late preterm neonates".)

●(See "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation".)

●(See "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation".)

TIMING OF ONSET

●Early-onset pneumonia – Early-onset pneumonia is variably defined as within 48 hours to six days of birth. For the purpose of this topic review, we define early-onset as before 72 hours of age.

●Late-onset pneumonia – Late-onset pneumonia is generally defined as onset of symptoms at ≥72 hours of age.

ROUTES OF ACQUISITION — The timing of onset and likely pathogens vary depending on the route of acquisition.

●Early-onset pneumonia – Early-onset pneumonia (ie, before 72 hours of age) is acquired from the mother by one of three routes:

•Intrauterine aspiration of infected amniotic fluid.

•Transplacental transmission of organisms from the mother to the fetus through the placental circulation.

•Aspiration of infected amniotic fluid during or after birth. The neonate can aspirate vaginal colonizing organisms, leading to respiratory colonization and, in some cases, pneumonia.

●Late-onset pneumonia – Late-onset pneumonia (ie, at ≥72 hours of age) can occur in two settings:

•Neonates presenting from the community – Late-onset infections (including pneumonia) occurring in term and near-term newborns who were discharged home after the initial birth hospitalization are most commonly due to maternal vertical transmission, resulting in initial neonatal colonization that evolves into later infection. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Pathogenesis'.)

•Neonates hospitalized since birth – Hospital-acquired late-onset infections (including pneumonia) in neonates who remain in the hospital since birth (eg, preterm infants) more commonly result from horizontal transmission from direct contact with care providers or environmental sources. Disruption of the intact skin or mucosa, which can be due to invasive devices (eg, endotracheal tubes, intravascular catheters), increases the risk of late-onset infection. (See "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Late-onset sepsis (LOS)'.)

PATHOLOGY — The pathologic changes vary depending on the type of organism. Bacterial pneumonia is characterized by inflammation of the pleura, infiltration or destruction of bronchopulmonary tissue, and leukocyte and fibrinous exudate within alveoli and the bronchi/bronchioles [3]. Bacteria often are seen within the interstitial spaces, alveoli, and bronchi/bronchioles [4]. Viruses typically cause an interstitial pneumonia.

EPIDEMIOLOGY

Incidence — In resource-abundant settings, the estimated incidence of pneumonia is <1 percent among full-term infants and up to 10 percent in preterm, extremely low birth weight infants (ie, birth weight <1000 g) who require mechanical ventilation [5-7].

Pneumonia is a major cause of mortality among extremely low birth weight infants, accounting for nearly 30 percent of deaths in this population in one series [8].

In resource-limited settings, pneumonia is a major contributor to infant mortality. The World Health Organization estimated that in 2015, pneumonia caused >900,000 deaths worldwide in children under five years old, with the majority of deaths occurring in infants <1 year old [9]. In one study conducted in a rural area in central India, mortality secondary to pneumonia in the first month was 29 per 1000 live births; more than one-half of all pneumonia deaths in children occurred in newborns [10]. These figures may underestimate the burden of neonatal pneumonia in resource-limited settings because many newborns do not receive medical care.

Risk factors — Risk factors vary depending on the timing of onset.

●Early-onset pneumonia – Risk factors associated with early-onset pneumonia are the same as those associated with early-onset sepsis and include [3,6]:

•Prematurity and low birth weight

•Maternal chorioamnionitis (also referred to as intraamniotic infection)

•Premature or prolonged rupture of membranes

•Maternal group B streptococcus colonization

•Maternal intrapartum fever

●Late-onset pneumonia – Risk factors associated with late-onset pneumonia include [3,6,11]:

•Prematurity and low birth weight

•Invasive mechanical ventilation, particularly for a prolonged duration

•Use of gastric acid blocking agents (eg, histamine type 2 (H2) blockers)

•Anomalies of the airway (eg, choanal atresia, tracheoesophageal fistula, and cystic adenomatoid malformations)

•Severe underlying pulmonary disease

•Prolonged hospitalization

•Neurologic impairment resulting in aspiration of gastrointestinal contents

Hospital-acquired viral infections occasionally are traced to poor handwashing or overcrowding [12].

ETIOLOGY

●Bacterial pathogens – Group B streptococcus and Escherichia coli account for most cases of bacterial pneumonia in neonates [2,6]. Other important bacterial pathogens include Klebsiella spp, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and Chlamydia trachomatis [2]. Gram-negative organisms (eg, Serratia, Enterobacter, Pseudomonas, Citrobacter) are increasingly recognized, particularly in preterm neonates with late-onset pneumonia [13]. Listeria monocytogenes and Mycobacterium tuberculosis are uncommon but important causes.

Bacterial pathogens in early- and late-onset pneumonia are generally similar to those identified in early- and late-onset sepsis, as summarized in the table (table 1) and discussed in detail separately. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Etiologic agents'.)

Some bacterial pathogens have characteristic features:

•S. aureus and Klebsiella pneumoniae are often associated with extensive tissue damage, abscess formation, and empyema [3].

•S. aureus, Klebsiella spp, E. coli, Serratia marcescens, Enterobacter cloacae, S. pneumoniae, and Pseudomonas aeruginosa may cause pneumatoceles [14-16].

•C. trachomatis has a long incubation period and typically is associated with pneumonia occurring beyond two weeks of age. (See "Chlamydia trachomatis infections in the newborn", section on 'Pneumonia'.)

•Citrobacter diversus, frequently associated with brain abscesses in neonates, can also cause lung abscess [14].

One bacterial pathogen, Ureaplasma urealyticum, has been linked potentially to the development of bronchopulmonary dysplasia in preterm infants. This is discussed separately. (See "Mycoplasma hominis and Ureaplasma infections", section on 'Neonatal disease' and "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis", section on 'Infection'.)

●Viral pathogens – Viral lower respiratory tract infection in neonates can occur from:

•Transplacental transmission (from a mother who acquires the infection in pregnancy)

•Perinatal transmission (from the mother at the time of birth), or

•Postnatal acquisition (from family members/caregivers who are in contact with the newborn or from nosocomial spread within the care unit)

Important viral pathogens in the newborn include:

•Herpes simplex virus – Herpes simplex virus pneumonia occurs in 33 to 54 percent of disseminated herpes simplex virus infections and usually is fatal despite treatment [17,18]. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Disseminated disease'.)

•Cytomegalovirus (CMV), which can be acquired in utero (ie, congenital CMV) or postnatally (eg, from breast milk or transfusion). (See "Congenital cytomegalovirus infection: Clinical features and diagnosis" and "Overview of cytomegalovirus infections in children", section on 'Early postnatal infection'.)

•Enterovirus and parechovirus, which tend to cause systemic illness (sepsis-like picture). (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Neonates'.)

•Respiratory syncytial virus (RSV). (See "Respiratory syncytial virus infection: Clinical features and diagnosis in infants and children".)

•Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). (See "COVID-19: Overview of pregnancy issues", section on 'Risk of vertical transmission'.)

•Other respiratory viral pathogens (eg, influenza virus, parainfluenza virus, adenovirus). (See "Seasonal influenza in children: Clinical features and diagnosis" and "Parainfluenza viruses in children" and "Pathogenesis, epidemiology, and clinical manifestations of adenovirus infection".)

●Fungal pathogens – Candida spp and other fungal pathogens are important pathogens causing systemic infections in neonates, particularly in extremely low birth weight infants [19]. Infants receiving prolonged antibiotic therapy and/or corticosteroids are at increased risk for invasive infection. (See "Clinical manifestations and diagnosis of Candida infection in neonates", section on 'Invasive infection'.)

Aspergillosis is a rare cause of neonatal pneumonia that is frequently fatal [20]. Aspergillus infection can occur in clusters, particularly during hospital renovations [21].

●Other pathogens – Occasionally, early-onset pneumonia is seen in patients with congenital toxoplasmosis and syphilis [22]. (See "Congenital toxoplasmosis: Clinical features and diagnosis" and "Congenital syphilis: Clinical manifestations, evaluation, and diagnosis".)

CLINICAL PRESENTATION

●Early-onset pneumonia – Early-onset pneumonia presents with findings that may include:

•Respiratory distress, beginning at or soon after birth

•Apnea

•Temperature instability

•Tachycardia and/or poor perfusion, sometimes progressing to septic shock (see "Neonatal shock: Etiology, clinical manifestations, and evaluation")

•Other nonspecific signs of infection (eg, lethargy, metabolic acidosis, abdominal distension)

•Newborns with severe infection may have associated persistent pulmonary hypertension (see "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis")

These signs are not specific for pneumonia, and respiratory distress also can be caused by noninfectious causes (table 2). (See 'Differential diagnosis' below.)

●Late-onset pneumonia – Late-onset pneumonia is heralded by changes in the overall condition of the newborn. Nonspecific signs may include:

•Apnea

•Tachypnea and/or respiratory distress

•Poor feeding and/or emesis

•Abdominal distention

•Jaundice, emesis, and

•Tachycardia and/or hemodynamic instability

•Ventilator-dependent infants may have increased oxygen and ventilator requirements or purulent tracheal secretions

EVALUATION — Neonates with suspected bacterial pneumonia should undergo evaluation including laboratory tests, cultures, and chest radiography. If viral infection is suspected, appropriate viral testing should be performed.

Sepsis evaluation — Because signs of pneumonia in neonates are nonspecific, neonates with sudden onset of respiratory distress or other signs of systemic illness should undergo a full sepsis evaluation, which at a minimum should include a blood culture. The diagnostic evaluation for suspected neonatal sepsis is discussed in detail separately. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Laboratory tests' and "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Evaluation'.)

Microbiologic testing

●Cultures – Cultures of blood and cerebrospinal fluid should be obtained. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Laboratory tests' and "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Symptomatic neonates'.)

In infants who are intubated, Gram stain and culture of tracheal aspirates should be performed [23-26]. In chronically ventilated patients, growth of bacteria from tracheal aspirate may represent true infection or colonization [27]. In this setting, polymicrobial growth, low levels of growth, and/or growth of nonpathogenic bacteria are more suggestive of contamination or colonization rather than infection. (See "Tracheobronchitis associated with tracheostomy tubes and endotracheal intubation in children", section on 'Culture'.)

In patients with pleural effusions, if pleural fluid is sampled for therapeutic reasons, it can be sent for Gram stain and culture. It is generally unnecessary to perform pleural fluid sampling solely for the purpose of obtaining a culture.

●Viral testing – If a viral etiology is suspected, testing should include polymerase chain reaction testing (ie, respiratory viral panel) and viral cultures. If a congenital or perinatally acquired infection is suspected (eg, congenital cytomegalovirus, herpes simplex virus), appropriate viral testing should be performed, as described separately. (See "Congenital cytomegalovirus infection: Clinical features and diagnosis", section on 'Approach to testing' and "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Detection of HSV'.)

●Testing for C. trachomatis – If C. trachomatis infection is suspected (eg, if the neonate was born to a mother with a history of untreated C. trachomatis infection or no prenatal care), testing should be performed using a nucleic acid amplification test on a nasopharyngeal sample, as discussed separately. (See "Chlamydia trachomatis infections in the newborn", section on 'Diagnosis'.)

●Fungal cultures – If there is clinical suspicion for invasive fungal infection (eg, preterm neonate receiving broad-spectrum antibiotics), it may be appropriate to obtain fungal cultures in addition to bacterial cultures. This is discussed separately. (See "Clinical manifestations and diagnosis of Candida infection in neonates", section on 'Invasive infections'.)

Diagnostic imaging

●Chest radiography – The chest radiograph is the main diagnostic test for confirming the diagnosis of pneumonia. Bilateral pulmonary opacities or focal infiltrates with air bronchograms are the characteristic findings [6,28,29]. However, the radiographic findings are variable. Occasionally, the chest radiograph will be normal (eg, if obtained early in the course) [30]. In addition, the appearance can overlap with other types of neonatal lung disease. For example, some neonates may have diffuse hazy opacities that appear similar to respiratory distress syndrome in preterm infants [31-33]. Others may have coarse irregular opacities similar to the appearance of meconium aspiration syndrome [29]. The clinical context can generally distinguish between these diagnoses. In uncertain cases, the presence of pleural effusions can support the diagnosis of pneumonia since effusions are common in neonatal pneumonia and less common in respiratory distress syndrome or meconium aspiration syndrome [29].

●Lung ultrasound – In experienced hands, lung ultrasound has good sensitivity and specificity for diagnosing common neonatal respiratory diseases, including pneumonia [34,35]. The characteristic ultrasound findings of pneumonia in neonates are hypoechoic areas of consolidation with irregular margins and air bronchograms [36]. However, the diagnostic accuracy varies considerably depending on the experience and expertise of the operator. For this reason, lung ultrasound is not a routine part of the evaluation of neonates with suspected pneumonia.

DIAGNOSIS — The diagnosis of neonatal pneumonia is based upon a combination of clinical, radiographic, and microbiologic findings. Characteristic chest radiograph findings (ie, bilateral pulmonary opacities or focal infiltrates with air bronchograms) in the appropriate clinical setting (ie, acute onset of respiratory symptoms and other signs of infection) are generally sufficient to establish the diagnosis. Positive cultures from blood or tracheal aspirates help confirm the diagnosis, but they are not required. Similarly, abnormal inflammatory markers (eg, high or low white blood cell count) are supportive findings but are not required.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of neonatal pneumonia includes other causes of respiratory distress that may present in the newborn period, including (table 2):

●Disorders of transition (eg, transient tachypnea or the newborn, respiratory distress syndrome) (see "Overview of neonatal respiratory distress and disorders of transition" and "Transient tachypnea of the newborn")

●Meconium aspiration syndrome (see "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis")

●Pneumothorax (see "Pulmonary air leak in the newborn", section on 'Pneumothorax')

●Congenital malformations (eg, congenital diaphragmatic hernia, congenital pulmonary airway malformation) (see "Congenital diaphragmatic hernia in the neonate" and "Congenital pulmonary airway malformation")

●Congenital heart disease (large ventricular septal defect, total anomalous pulmonary venous connection, patent ductus arteriosus, truncus arteriosus) (see "Identifying newborns with critical congenital heart disease", section on 'Respiratory symptoms')

The clinical history, microbiologic testing, and radiographic findings can generally distinguish pneumonia from other causes of respiratory distress.

MANAGEMENT

Supportive care — Neonates with pneumonia can deteriorate rapidly. Thus, neonates with respiratory compromise should be managed in the neonatal intensive care unit setting where they can receive close cardiopulmonary monitoring and support. The following supportive measures are important components of management:

●Maintaining a neutral thermal environment

●Maintaining adequate oxygenation and perfusion (see "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn")

●Prevention of hypoglycemia and metabolic acidosis (see "Management and outcome of neonatal hypoglycemia")

●Maintenance of normal fluid and electrolyte status (see "Fluid and electrolyte therapy in newborns")

Severely ill patients may require ventilatory, volume, and/or vasopressor support to maintain adequate oxygenation and perfusion. (See "Overview of mechanical ventilation in neonates" and "Neonatal shock: Etiology, clinical manifestations, and evaluation".)

Bacterial pneumonia

Initial empiric therapy — Empiric parenteral antibiotic therapy is started pending culture results. The choice of empiric regimen is based upon whether the infection is of early or late onset.

Once a specific organism is identified, therapy is modified according to the susceptibility pattern. (See 'Definitive therapy' below.)

●Early-onset pneumonia – For early-onset pneumonia (ie, before 72 hours of age), we suggest initial empiric coverage with ampicillin and gentamicin. However, local antibiotic susceptibility patterns should also be considered. For example, in centers with a high prevalence of gentamicin resistance among gram-negative isolates, an alternative aminoglycoside (eg, amikacin) should be used [37,38].

Dosing of ampicillin and gentamicin is based upon the infant's weight, renal function, postnatal age, and postmenstrual age [39]. Refer to the drug monographs for details.

Ampicillin is effective against group B streptococcus, most other strains of streptococci, L. monocytogenes, and some gram-negative bacteria. Ampicillin plus an aminoglycoside also has synergistic activity against many of these organisms [40].

Third-generation cephalosporins, although active against many gram-negative organisms, should generally not be used for suspected early-onset sepsis or pneumonia. Gram-negative bacilli can rapidly develop resistance to cephalosporins by either inducible or chromosomally mediated beta-lactamase activity [41,42]. In addition, a large observational study found that the risk of death from early-onset sepsis was increased in neonates who received cefotaxime as initial empiric treatment compared with those who received gentamicin [43].

●Late-onset pneumonia – The choice of empiric therapy for late-onset pneumonia is influenced by the clinical setting (ie, whether the neonate has been hospitalized since birth or is presenting from the community) and local susceptibility patterns.

For most infants ≥72 hours old, we suggest an empiric regimen that includes:

•Ampicillin or vancomycin, plus

•An aminoglycoside (typically gentamicin) or an extended-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime)

Vancomycin should generally be included in the regimen for neonates with hospital-acquired pneumonia (eg, preterm neonates who remain hospitalized since birth) and for those presenting from the community in settings where the prevalence of methicillin-resistance among S. aureus isolates is high (eg, >10 percent). If preliminary culture results indicate S. aureus infection, nafcillin should be added to the empiric regimen pending antimicrobial susceptibility results. Including both vancomycin and nafcillin in the empiric regimen optimizes activity against both methicillin-resistant and methicillin-susceptible S. aureus. This issue is discussed in greater detail separately. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Empiric antimicrobial therapy'.)

Dosing of these medications is based upon the infant's weight, renal function, postnatal age, and postmenstrual age. Refer to the drug monographs for details. Once a specific organism is identified, therapy is modified according to the susceptibility pattern. (See 'Definitive therapy' below.)

Definitive therapy

Culture-positive pneumonia — For infants who have microbiologically proven pneumonia (ie, based upon positive cultures from tracheal aspirates and/or positive blood cultures in conjunction with clinical evidence of pneumonia), antibiotic therapy should be tailored based upon susceptibility testing of the isolated pathogen.

The usual treatment duration for uncomplicated pneumonia is 7 to 10 days.

The agent used depends upon the isolated pathogen:

●Group B streptococcus – Penicillin or ampicillin are the preferred agents for treatment of group B streptococcus, as summarized in the table (table 3) and discussed in detail separately. (See "Group B streptococcal infection in neonates and young infants", section on 'Definitive therapy'.)

●E. coli – In patients with ampicillin-sensitive E. coli infections, ampicillin monotherapy is administered for definitive therapy.

For patients with ampicillin-resistant E. coli, the choice of definitive therapy is based upon the susceptibility profile. An expanded-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime) is often employed if the isolate is susceptible or an appropriate aminoglycoside.

●Other gram-negative bacteria – Antimicrobial treatment of infections caused by Klebsiella, Enterobacter, Serratia, Pseudomonas, or other gram-negatives should be selected based upon the susceptibility profile of the organism. Single-agent therapy is sufficient in most cases.

Infections caused by multidrug-resistant, gram-negative bacilli, including those caused by extended-spectrum beta-lactamase-producing organisms or those with hyperproduction of beta-lactamases, should be treated with meropenem [44]. Consultation with an infectious disease specialist is advised.

●S. aureus – Treatment of methicillin-susceptible S. aureus infection should be completed with nafcillin. Cefazolin is a reasonable alternative. (See "Staphylococcus aureus bacteremia in children: Management and outcome".)

Treatment of methicillin-resistant S. aureus should be completed with vancomycin. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Treatment of neonates'.)

●C. trachomatis – Oral azithromycin is the preferred treatment for neonatal C. trachomatis infections, as discussed separately. (See "Chlamydia trachomatis infections in the newborn", section on 'Treatment'.)

●L. monocytogenes – Treatment of L. monocytogenes infections in neonates is summarized in the table (table 4) and discussed in detail separately. (See "Treatment and prevention of Listeria monocytogenes infection", section on 'Neonates'.)

Presumed bacterial pneumonia — For neonates who are diagnosed clinically with presumed bacterial pneumonia based upon consistent clinical and radiographic findings but who have negative cultures (including blood, cerebrospinal fluid, and, if intubated, tracheal aspirate), empiric parenteral antibiotic therapy is continued for at least 48 to 72 hours. Ongoing clinical assessment during this period determines whether further treatment is warranted. If the clinical course and radiographic findings are highly suggestive of pneumonia, antibiotic treatment is continued for 7 to 10 days. If the findings are not suggestive of pneumonia or an alternative etiology is identified, antibiotic therapy should be discontinued, as discussed in the next section.

Unlikely bacterial pneumonia — Empiric antibiotics are initiated in some infants due to abnormal chest radiograph findings and/or mild to moderate symptoms that subsequently resolve. In some cases, an alternative etiology for the symptoms is identified (eg, a viral infection or retained fetal lung fluid). In these neonates, empiric antibiotic therapy should be discontinued after 48 hours if the cultures are negative since bacterial pneumonia is unlikely in this setting.

Viral pneumonia — Treatments for specific viral etiologies of neonatal pneumonia are discussed in separate topic reviews:

●Herpes simplex virus – Treatment is according to the recommendations for disseminated disease (see "Neonatal herpes simplex virus infection: Management and prevention", section on 'Initial antiviral therapy')

●Congenital cytomegalovirus (see "Congenital cytomegalovirus infection: Management and outcome", section on 'Antiviral treatment')

●Respiratory syncytial virus and other viral lower respiratory tract infections (see "Respiratory syncytial virus infection: Treatment in infants and children" and "Bronchiolitis in infants and children: Treatment, outcome, and prevention")

●Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (see "COVID-19: Intrapartum and postpartum issues", section on 'Care of newborns of infected mothers')

OUTCOME — The prognosis of neonatal pneumonia depends upon the severity of the disease, gestational age of the patient, underlying medical conditions, and infecting organism. Most term neonates managed in resource-abundant settings recover well without long-term sequelae [3]. Preterm infants and neonates with preexisting lung disease (eg, bronchopulmonary dysplasia) or immune deficiency are at increased risk of morbidity and mortality [6].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sepsis in neonates" and "Society guideline links: Pediatric pneumonia".)

SUMMARY AND RECOMMENDATIONS

●Incidence – Pneumonia is a major contributor to infant mortality worldwide. In resource-abundant countries, the estimated incidence of pneumonia in full-term infants is <1 percent and up to 10 percent in extremely preterm infants who require mechanical ventilation. (See 'Introduction' above and 'Epidemiology' above.)

●Timing of onset – Neonatal pneumonia can be classified by the timing of onset as follows (see 'Timing of onset' above):

•Early-onset pneumonia (before 72 hours of age), which is generally acquired from the mother during labor or delivery. (See 'Routes of acquisition' above.)

•Late-onset pneumonia (at ≥72 hours of age) also can be caused by maternal transmission. However, in neonates who remain hospitalized since birth (eg, preterm infants), late-onset infection more commonly results from direct contact with care providers or environmental sources (ie, hospital-acquired infection). (See 'Routes of acquisition' above.)

●Etiology

•Bacterial pathogens – Group B streptococcus and Escherichia coli account for most cases of bacterial pneumonia in neonates. Other important bacterial pathogens are summarized in the table (table 1). (See 'Etiology' above.)

•Viral pathogens – Important viral causes of respiratory tract infections in the newborn include herpes simplex virus, cytomegalovirus, enterovirus, parechovirus, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and other respiratory viral pathogens (eg, influenza virus, parainfluenza virus, adenovirus). (See 'Etiology' above.)

•Fungal pathogens – Candida spp and other fungal pathogens are important pathogens causing systemic infections in extremely low birth weight infants. (See "Clinical manifestations and diagnosis of Candida infection in neonates", section on 'Invasive infection'.)

●Clinical presentation – Early-onset pneumonia commonly presents with respiratory distress beginning at or soon after birth. Other clinical manifestations, also seen in late-onset disease, are nonspecific and include temperature instability, apnea, lethargy, tachycardia, poor perfusion, tachypnea, and poor feeding. (See 'Clinical presentation' above.)

●Evaluation – Neonates with suspected bacterial pneumonia should undergo evaluation including laboratory tests, cultures, and chest radiography. If viral infection is suspected, appropriate viral testing should be performed. (See 'Evaluation' above.)

●Diagnosis – The diagnosis of neonatal pneumonia is based upon a combination of clinical, radiographic, and microbiologic findings. Characteristic chest radiograph findings (ie, bilateral pulmonary opacities or focal infiltrates with air bronchograms) in the appropriate clinical setting (ie, acute onset of respiratory symptoms and other signs of infection) are generally sufficient to establish the diagnosis. Positive cultures from blood or tracheal aspirates help confirm the diagnosis, but they are not required. (See 'Diagnosis' above.)

●Differential diagnosis – The differential diagnosis of neonatal pneumonia includes other causes of respiratory distress that may present in the newborn period, including (table 2) (see 'Differential diagnosis' above):

•Disorders of transition (eg, transient tachypnea or the newborn, respiratory distress syndrome) (see "Transient tachypnea of the newborn" and "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis")

•Meconium aspiration syndrome (see "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis")

•Pneumothorax (see "Pulmonary air leak in the newborn" and "Pulmonary air leak in the newborn", section on 'Pneumothorax')

•Congenital malformations (eg, congenital diaphragmatic hernia, congenital pulmonary airway malformation) (see "Congenital diaphragmatic hernia in the neonate" and "Congenital pulmonary airway malformation")

•Congenital heart disease (large ventricular septal defect, total anomalous pulmonary venous connection, patent ductus arteriosus, truncus arteriosus) (see "Identifying newborns with critical congenital heart disease")

●Management – Neonates with pneumonia can deteriorate rapidly. Thus, neonates with respiratory compromise should be managed in the neonatal intensive care unit setting where they can receive close cardiopulmonary monitoring and support. (See 'Supportive care' above.)

•Empiric therapy – Infants with pneumonia require empiric antibiotic therapy pending culture results. The choice of empiric antibiotic regimen is based upon the most likely pathogen, which varies depending upon timing of onset (early versus late onset) and clinical setting.

For most neonates with early-onset pneumonia (before 72 hours of age), we suggest initial empiric therapy with ampicillin and gentamicin (Grade 2C). (See 'Initial empiric therapy' above.)

For most neonates with late-onset pneumonia (at ≥72 hours of age), we suggest an empiric regimen that includes (Grade 2C):

-Ampicillin or vancomycin, plus

-An aminoglycoside (typically gentamicin) or an extended-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime)

A vancomycin-containing regimen is appropriate for neonates with hospital-acquired pneumonia (eg, preterm neonates who remain hospitalized since birth) and for those presenting from the community in settings where the prevalence of methicillin-resistance among Staphylococcus aureus isolates is high (eg, >10 percent). (See 'Initial empiric therapy' above.)

•Definitive therapy – When results of microbiologic tests are available, antibiotic therapy is directed toward the specific pathogen. The usual treatment duration for uncomplicated pneumonia is 7 to 10 days. (See 'Definitive therapy' above.)

●Prognosis – The prognosis of neonatal pneumonia depends upon the severity of the disease, gestational age of the patient, underlying medical conditions, and infecting organism. Most term neonates managed in resource-abundant settings recover well without long-term sequelae. (See 'Outcome' above.)