AUTHOR INFORMATION

Section 1 of 11

Authored by Lakshmi V Atkuri, MD, Assistant Professor, Section of Emergency Medicine, University of Texas Health Science Center at Houston

Coauthored by Laura E Ferguson, MD, FAAP, Associate Professor of Pediatrics, Division of Community and General Pediatrics, University of Texas Medical School at Houston; Director, Pasadena Health Center; Brent R King, MD, Associate Professor of Emergency Medicine and Pediatrics, University of Texas Health Science Center at Houston; Chair, Department of Emergency Medicine, Memorial Hermann Hospital, Lyndon B Johnson General Hospital

Lakshmi V Atkuri, MD, is a member of the following medical societies: American Academy of Pediatrics

Edited by Garry Wilkes, MD, Director, Emergency Medicine, Adjunct Associate Professor, Edith Cowan University, Department of Emergency Medicine, Bunbury Health Service; Robert Konop, PharmD, Director, Clinical Account Management, Ancillary Care Management, Inc; Grace M Young, MD, Associate Professor, Department of Pediatrics, University of Maryland Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Richard G Bachur, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Division of Emergency Medicine, Children's Hospital of Boston

Author's Email:	Lakshmi V Atkuri, MD
Editor's Email:	Garry Wilkes, MD

eMedicine Journal, March 23 2006, VOLUME 7, Number 3

INTRODUCTION

Section 2 of 11

Background: Pneumonia (ICD10: P23.9) is one of several infections of the lower respiratory tract that may be observed in children. The other lower respiratory tract diseases, croup (laryngotracheobronchitis), bronchitis, and bronchiolitis (to which pneumonia is closely related), are beyond the scope of this article and are not discussed further. The World Health Organization (WHO) has defined pneumonia solely on the basis of clinical findings obtained by visual inspection and timing of the respiratory rate.

It is important for the physician to understand that the typical causes and presentations of pneumonia in infants and children are variable, depending upon the child's age and underlying medical condition.

Pathophysiology: Pneumonia results from inflammation of the alveolar space and may compromise air exchange. While often complicating other lower respiratory infections such as bronchiolitis or laryngotracheobronchitis, pneumonia may also occur via hematogenous spread or aspiration. Most commonly, this inflammation is the result of invasion by bacteria, viruses, or fungi, but it can occur as a result of chemical injury.

Four stages of lobar pneumonia have been described. In the stage of congestion (first 24 h), the lung is grossly doughy in consistency, and, microscopically, it is characterized by vascular congestion and alveolar edema. Many bacteria and a few neutrophils are present. The stage of red hepatization (2-3 d), so called because of its similarity to the consistency of liver, is characterized by the presence of many erythrocytes, neutrophils, desquamated epithelial cells, and fibrin within the alveoli. In the stage of gray hepatization (2-3 d), the lung is gray-brown to yellow because of fibrinopurulent exudate, disintegration of red cells, and hemosiderin. The final stage of resolution is characterized by resorption and restoration of the pulmonary architecture. Fibrinous inflammation may extend to and across the pleural space, causing a rub heard by auscultation, and it may lead to resolution or to organization and pleural adhesions.

Bronchopneumonia, a patchy consolidation involving one or more lobes, usually involves the dependent lung zones, a pattern attributable to aspiration of oropharyngeal contents. The neutrophilic exudate is centered in bronchi and bronchioles, with centrifugal spread to the adjacent alveoli.

In interstitial pneumonia, patchy or diffuse inflammation involving the interstitium is characterized by infiltration of lymphocytes, macrophages, and plasma cells. The alveoli do not contain a significant exudate, but protein-rich hyaline membranes similar to those found in adult respiratory distress syndrome (ARDS) may line the alveolar spaces. Bacterial superinfection of viral pneumonia can also produce a mixed pattern of interstitial and alveolar airspace inflammation.

Miliary pneumonia is a term applied to multiple, discrete lesions resulting from the spread of the pathogen to the lungs via the bloodstream. The varying degrees of immunocompromise in miliary tuberculosis, histoplasmosis, and coccidioidomycosis may manifest as granulomas with caseous necrosis to foci of necrosis. Miliary herpesvirus, cytomegalovirus, or varicella-zoster virus infection in severely immunocompromised patients results in numerous acute necrotizing hemorrhagic lesions.

Factors that bypass or inactivate local defenses (eg, tracheostomy tubes, immotile cilia syndrome) predispose the child to pneumonia. The result is loss of surfactant activity with local collapse and consolidation.

Pneumonia may be classified by the causative organism, the anatomic location, or the tissue response.

Frequency:

• In the US: A WHO Child Health Epidemiology Reference Group publication cites the incidence of community-acquired pneumonia among children younger than 5 years in developed countries as approximately 0.026 episodes per child year.

  In a recent prospective multicentric study of 154 immunocompetent children with acute community-acquired pneumonia, comprehensive investigation combining microbiologic, serologic, biochemical, and experimental molecular tests were performed and a pathogen was identified in 79% of children. Bacteria accounted for 60%, of which 73% were due to Streptococcus pneumoniae, Mycoplasma pneumoniae, and Chlamydia pneumoniae were detected in 14% and 9%, respectively. Viruses were documented in 45% of children. Notably, 23% of the children had concurrent acute viral and bacterial disease.

  In the study, preschool-aged children had as many episodes of atypical bacterial lower respiratory infections as older children. Children with typical bacterial or mixed bacterial/viral infections had the greatest inflammation and disease severity. Multivariable analyses revealed that high temperature (38.4°C) within 72 hours after admission and the presence of pleural effusion were significantly associated with bacterial pneumonia.

  Thompson et al reported annual influenza-associated hospitalizations in the United States by hospital discharge category, discharge type, and age group (Thompson, 2004). After elderly persons, the second highest rates of influenza-associated hospitalizations were in children younger than 5 years. However, the relative risk for an influenza-associated hospitalization relative to death was 270 in this age group compared to 11 in those in the 50-64 years age range.

• Internationally: The WHO Child Health Epidemiology Reference Group (Rudan, 2004) data, based on 28 studies, estimated the median global incidence of clinical pneumonia to be 0.28 episodes per child-year. The 25-75% interquartile range was 0.21-0.71. This equates to an annual incidence of 150.7 million new cases, of which 11-20 million (7-13%) are severe enough to require hospital admission. Ninety five percent of all episodes of clinical pneumonia in young children worldwide occur in developing countries.

Mortality/Morbidity: According to the WHOs Global Burden of Disease 2000 Project, lower respiratory infections were the second leading cause of death in children younger than 5 years (about 2.1 million [19.6%]).

• Most children are treated as outpatients and fully recover. However, in young infants and immunocompromised individuals, the death rate is much higher.

• Certain rare infectious agents are associated with a higher death rate.

• In studies of adults with pneumonia, a higher mortality rate is associated with abnormal vital signs, immunodeficiency, and certain organisms.

Race: Pneumonia affects children of all races; however, certain conditions that may predispose to pneumonia have racial predilections. For example, cystic fibrosis is far more common in white children. Children with sickle cell anemia are at increased risk for pneumonia even when compliant with antibiotic prophylaxis and fully immunized.

Age: Pneumonia in the pediatric population is most common in infants and toddlers and least common in adolescents and young adults.

CLINICAL

Section 3 of 11

History: In children, the etiologic agent, the age of the patient, and underlying illnesses all affect the historical features of the illness.

• Neonates

• As hospital stays for newborn infants have become shorter and the popularity of freestanding birthing centers has increased, it is possible for some conditions that have traditionally been diagnosed in the newborn nursery, instead, to present in the ED.

• The infant may present with tachypnea; signs of respiratory distress, such as grunting, flaring, and retractions; lethargy; poor feeding; or irritability. Fever may not be present in newborns; however, hypothermia and temperature instability may be observed.

• Severely affected infants may be cyanotic.

• Those infants who are less ill appearing are more likely to have nonspecific complaints, such as irritability or poor feeding.

• Cough is unusual in the newborn period.

• Early-onset group B streptococci infection usually presents via ascending perinatal infection as sepsis or pneumonia within the first 24 hours of life. Chlamydia trachomatis pneumonia often exists with conjunctivitis and presents during the second or third week of life.

• Infants

• After the first month of life, cough is the most common presenting symptom.

• Infants may have a history of antecedent upper respiratory symptoms.

• Depending upon the degree of illness, tachypnea, grunting, and retractions may be noted. Vomiting, poor feeding, and irritability are also common.

• Infants with bacterial pneumonia often are febrile, but those with viral pneumonia or pneumonia caused by atypical organisms may have a low-grade fever or may be afebrile. The child's caretakers may complain that the child is wheezing or has noisy breathing. In many cases, these sounds are actually upper airway noises.

• Toddlers and preschool children

• A history of an upper respiratory illness before the onset of symptoms is common.

• Cough is the most common presenting symptom.

• Vomiting, particularly post-tussive emesis, may be present. Chest pain is common. Abdominal pain or tenderness is not an uncommon symptom of lower lobe pneumonia and chest pain, although this usually represents pleuritic involvement in children with viral syndromes.

• The presence and degree of fever is dependent upon the organisms involved. Similarly, the symptoms of respiratory compromise may be observed in severe cases.

• Older children and adolescents

• Atypical organisms, such as Mycoplasma, are more common in these patients.

• In addition to the symptoms observed in younger children, adolescents may have other constitutional symptoms, such as headache, pleuritic chest pain, and vague abdominal pain. Vomiting, diarrhea, pharyngitis, and otalgia/otitis are other common symptoms.

Physical: Early in the physical examination, it is important to identify and treat respiratory distress, hypoxemia, and hypercarbia. Signs such as grunting, flaring, severe tachypnea, and retractions should prompt the clinician to provide immediate respiratory support. An assessment of oxygen saturation by pulse oximetry should be performed early in the evaluation of all children with respiratory symptoms. When appropriate and available, side-stream capnography may be useful in the evaluation of children with potential respiratory compromise. Severely affected children with respiratory distress not responsive to supplemental oxygen should undergo tracheal intubation.

• The examination of patients not in respiratory distress should begin with observation. “Shirt off, lights on” is a good phrase for this process. The examiner should simply observe the patient's respiratory effort and count the respirations for a full minute. This procedure will allow for the identification of subtle signs of respiratory embarrassment and other important findings, such as splinting. In infants, observation should include an attempt at feeding, unless the baby has extreme tachypnea. The baby who is doing well at rest may decompensate during feeding.

• Auscultation is perhaps the most important portion of the examination of the child with respiratory symptoms. The examination often is very difficult in infants and young children for several reasons.

• Babies and young children often cry during the physical examination making accurate auscultation difficult. When young infants cry, it usually is because they are uncomfortable. They may, for example, be hungry or may find the stethoscope or the examiner's hand to be cold. The best chance of success lies in prewarming hands and instruments and in using a pacifier to quiet the infant. The opportunity to listen to a sleeping infant should never be lost.

• Older infants and toddlers may cry because they are ill or uncomfortable, but, most often, they have stranger anxiety. For these children, it is best to spend a few minutes with the parents in the child's presence. If the child sees that the parent trusts the examining physician then he or she may be more willing to let the examiner approach. A small toy may help to gain the child's trust. Any part of the examination using instruments should be deferred as long as possible, because the child may find the medical equipment frightening. Occasionally, if the child is allowed to hold the stethoscope for a few minutes, it becomes less frightening. Even under the best of circumstances, it is difficult to examine a toddler. If the child is asleep when the physician begins the evaluation, auscultation should be performed early.

• It is not unusual for children with respiratory symptoms to have a concomitant upper respiratory infection with copious upper airway secretions. This creates another potential problem, transmission of upper airway sounds. In many cases, the sounds created by upper airway secretions can almost obscure true breath sounds and lead to erroneous diagnoses. In young children, there is no effective way to remove these secretions without causing crying. If doubt exists as to the etiology of sounds heard through the stethoscope, the examiner should listen to the lung fields and then hold the stethoscope near the child's nose. If the sounds from both locations are approximately the same, the likely source of the abnormal breath sounds is the upper airway.

• Even when the infant or young child is quiet and has a clear upper airway, the child's normal physiology may make the examination difficult. The minute ventilation is the product of the respiratory rate and tidal volume. In young children, respiratory rate makes a very large contribution to the overall minute ventilation. In other words, babies take many shallow breaths as opposed to a few deep ones. Therefore, a subtle finding, particularly one at the pulmonary bases, can be missed. In order to create a few deeper breaths, the examiner need only apply gentle pressure to the chest or abdomen near the end of exhalation. This will force a bit more air out of the chest and allow expiratory noises, such as wheezing, to become more apparent. Additionally, the subsequent inspiration will be somewhat deeper, allowing fine crackles to be noted.

• The sine qua non for this disease has always been the presence of crackles (formerly called rales). Focal crackles in a febrile child without underlying lung disease is pneumonia until proven otherwise. However, not all children with pneumonia have crackles.

• Other examination findings suggestive of pneumonia include focal wheezing or whistling sounds and decreased breath sounds in one lung field.

• Similarly, certain more diffuse lung infections may result in generalized crackles or wheezing.

• Percussion may reveal important information. Occasionally, a child presents with a high fever and cough but without osculatory findings suggestive of pneumonia. In such cases, percussion often helps to identify an area of consolidation.

• Pneumonia may occur as a part of another generalized process. Therefore, signs and symptoms suggestive of other disease processes, such as rashes and pharyngitis, should be sought during the examination.

Causes: Pathogens implicated in pneumonia vary with the age of the pediatric patient, the underlying patient-specific risk factors, immunization status, and seasonality.

• Newborns and infants

• In the neonate, pathogens that may infect the infant via the maternal genital tract include group B streptococci, Escherichia coli and other fecal coliforms, and C trachomatis.
  • Group B streptococci most often is transmitted to the fetus in utero, usually as a result of colonization of the mother's vagina and cervix by the organism.

  • Affected infants commonly present within the first few hours after birth, but if infection is acquired during the delivery, the presentation may be delayed for a day or two.

  • The usual presenting symptoms include tachypnea, hypoxemia, and signs of respiratory distress.

  • Physical examination reveals diffuse fine crackles and the chest x-ray may demonstrate a ground glass appearance and air bronchograms.

• Newborns also may be affected by the bacteria and viruses that cause infections in older infants and children. Risk factors for infection include older siblings, group day care, and lack of immunization, particularly against pertussis.

• In the young infant, 1-3 months of age, continued concern about perinatally acquired pathogens mentioned above as well as the unusual Listeria monocytogenes remains. However, most pneumonia in this age group is community acquired and involves S pneumoniae, Staphylococcus aureus, and Haemophilus influenzae.
  • Although the young unimmunized or incompletely immunized infant remains at theoretical risk for H influenzae and pneumococcal disease, herd immunity gained from widespread immunization of the population has been generally protective.

  • Most lower respiratory disease in the young infant occurs during the respiratory virus season and may be viral in origin along with bronchiolitis. Beyond the newborn period, viruses cause most lower respiratory tract infections in infants. The most common agents are the parainfluenza viruses, influenza virus, adenovirus, and respiratory syncytial virus (RSV). The latter organism can be particularly dangerous to former premature infants and to those babies with underlying lung disease.

• Atypical organisms also cause infections in infants. Of these, C trachomatis, Ureaplasma urealyticum, cytomegalovirus, and Pneumocystis carinii (PCP) are the most common. Pneumocystis infects virtually all humans in early infancy; however, it causes severe symptoms only in debilitated or immunocompromised patients.

• Bordetella pertussis may affect infants. Only 80% of fully immunized children are protected against pertussis and that immunity to this disease wanes in late adolescence. Since infants have not completed the vaccination series and because adults are a potential reservoir for infection, both groups are at risk.

• S pneumoniae is by far the most common bacterial pathogen in this age group. In a recent study to evaluate the effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years for prevention of pneumonia, Black et al showed a 32.2% reduction in the first year of life and a 23.4% reduction between 1-2 years, but only a 9.1% reduction in children older than 2 years. Underimmunized infants may also be infected by H influenzae.

• Infection with S aureus is currently on the increase and complicated by lung abscess, parapneumonic effusions, and empyema (Mishaan, 2005).

• Young children

• Viruses usually infect toddlers and preschoolers. The usual culprits are those previously discussed.

• Children in this age group are also at risk for infection by M pneumoniae. Pneumococcus is by far the most common bacterial cause of pneumonia, although the lungs may be secondarily infected as a part of other generalized infections (eg, meningococcemia).

• Older children and adolescents

• M pneumoniae is a frequent cause of pneumonia among older children and adolescents.

• C pneumoniae can cause pneumonia along with a variety of other symptoms.

• Older adolescents may have lost their immunity to pertussis and may become infected by this organism. Unlike the whooping cough in infants, pertussis in older patients usually causes a paroxysmal cough, which persists for more than 3 weeks and may last up to 3 months.

• Bacterial pneumonia in this age group most often is caused by Pneumococcus species.

• Histoplasma capsulatum, which is found in nitrate rich soil, usually is acquired as a result of inhalation of spores. Chicken coops and other bird roosts and decaying wood are oft-cited sources. The infection is usually asymptomatic; however, infants and young children are at risk for symptomatic infection, which may cause respiratory distress and hypoxemia.

• Blastomyces dermatitides is a dimorphic yeast, which is found in certain geographic locations, most notably the Ohio and Mississippi River valleys. As with histoplasmosis, blastomycosis is acquired by inhalation of spores. Although 3 distinct forms of infection exist, the most common is acute pneumonia, which most often resolves without treatment.

• Cryptococcus neoformans is a common infection among pigeon breeders, but it is unusual in other immunocompetent individuals. It may occur in as many as 5-10% of patients with AIDS. In immunocompetent patients, this organism causes no symptoms or a mild pneumonia and requires no treatment.

• Mycobacterial pneumonia has recently been noted with increasing frequency in some inner city areas. Children in homeless shelters and group homes and those with household contacts are at particular risk. Similarly, the diagnosis must be considered in immunocompromised children.

• RSV is a common cause of viral lung infections. Serious infections with this organism usually occur in infants with underlying lung disease.

• The herpesviruses rarely may cause pneumonia. In infants, the usual agent is herpes simplex and, in older children, pneumonia may complicate common varicella infections.

• Influenza A is a less common pathogen.

• Legionella species is not an important pathogen in the pediatric population and is almost never observed in immunocompetent children.

• Children with cystic fibrosis may be infected with various organisms such as S aureus, Pseudomonas aeruginosa, Burkholderia cepacia, and other multidrug-resistant organisms.

• Not all pneumonia is caused by infectious agents. Children who have severe gastroesophageal reflux may develop chemical pneumonitis secondary to recurrent aspiration. Inhalation of certain chemicals or smoke may cause pulmonary inflammation.

DIFFERENTIALS

Section 4 of 11

Acute Respiratory Distress Syndrome
Asthma
Bronchitis
Pediatrics, Respiratory Distress Syndrome
Pneumonia, Aspiration
Pneumonia, Bacterial
Pneumonia, Empyema and Abscess
Pneumonia, Immunocompromised
Pneumonia, Mycoplasma
Smoke Inhalation

Other Problems to be Considered:

Pediatric AIDS

WORKUP

Section 5 of 11

Lab Studies:

• There are very few laboratory studies that are particularly useful in the evaluation of the child with pneumonia.

• While it is true that many of the etiologic organisms may be identified by culture or immunofluorescent antibody techniques, in practice, these are too costly and time consuming for routine use. Furthermore, the results of such tests are rarely available in less than several hours, thus making them even less useful to the emergency clinician.

• Complete blood count

• In cases of pneumococcal pneumonia, the WBC count is often dramatically elevated. However, this test is nonspecific and of little true utility in the management of outpatients. Nonetheless, some have suggested that the WBC count be used to guide further testing in febrile infants and children who have a significantly elevated WBC count and no other source of infection. Some have advocated obtaining a chest x-ray even in the absence of physical examination findings.

• The CBC should be considered in very ill children and in those with possible immunocompromise.

• Cultures

• Blood culture results are rarely positive in children with pneumonia. This includes cases of suspected pneumococcal disease. Among those with high fever and leukocytosis, bacteremia rates approach 10%.

• Blood cultures should be obtained when the patient is critically ill, immunocompromised, or has persistent symptoms. Additionally, blood cultures are useful in patients with high fever and large areas of consolidation—mostly to make a microbiologic diagnosis. Special consideration should be made of obtaining blood cultures in patients with multiple small areas of consolidation that might indicate septic emboli as in endocarditis.

• Sputum cultures and immunofluorescent antibody testing should be reserved for unusual cases or very ill patients.

• Sputum Gram stain

• In the cooperative older child with a productive cough, a sputum Gram stain may be obtained.

• In order to be useful, the specimen must contain less than 10 epithelial cells and more than 25 WBC per high-powered field. Very few children are able to cooperate with such a test.

• Consideration should be given for rapid viral testing in young infants with simple infiltrates.

Imaging Studies:

• For many years, the criterion standard test for the diagnosis of pneumonia has been the 2-view plain chest x-ray (CXR). However, when chest radiographs are subjected to blinded readings, they may not differentiate between viral disease and bacterial disease.
  • Several studies flatly state that no radiologic features exist that can be used to differentiate between these two major etiologic classes (Courtoy, 1989). Another study concluded that radiographic findings have less discriminatory value than does measurement of C-reactive protein, erythrocyte sedimentation rate, or the WBC count and the differential count (Ponka, 1983).

  • In contrast, using data from a large Finnish series, Korppi et al (1993) concluded that an alveolar (equivalent to a lobar) infiltrate is an insensitive but reasonably specific indication of bacterial infection. At either extreme (from typical bronchiolitis with scattered infiltrates to dense lobar pneumonia with a large pleural effusion), the level of diagnostic certainty provided by radiologic findings increases.

• For M pneumoniae, Guckel (1989) described 3 different patterns of infiltration with equal frequency: (1) peribronchial and perivascular interstitial infiltrates, (2) patchy consolidations, and (3) homogeneous acinar consolidations like groundglass. The lower fields of the lungs were mostly affected. Enlargement of the hilar glands was a common finding. Pleural effusion was rare.

• In viral pneumonias, 4 common radiographic findings were detected: parahilar peribronchial infiltrates, hyperexpansion, segmental or lobar atelectasis, and hilar adenopathy (Wildin, 1988).

• Although no radiographic findings are specific for C pneumoniae, a combination of the clinical and radiographic findings strongly suggests the diagnosis before laboratory diagnosis is available. In a study of 125 cases of Chlamydia pneumonia, Radkowski et al demonstrated that most chest films showed bilateral hyperexpansion and diffuse infiltrates with a variety of radiographic patterns including interstitial, reticular nodular, atelectasis, coalescence, and bronchopneumonia. Pleural effusion and lobar consolidation were not seen (Radkowski, 1981).

Other Tests:

• On occasion, it may be prudent to perform skin testing to identify tuberculosis. However, before such testing is undertaken, it is important that the patient and the physician clearly understand how the test will be interpreted and what actions will be taken in case of a positive result.

• Cold agglutinins

• In the young child or school-aged child with pneumonia, particularly the patient with a gradual onset of symptoms and a prodrome consisting of headache and abdominal symptoms, a bedside cold agglutinins test may help confirm the clinical suspicion of mycoplasmal infection.

• This test is easily performed by placing a small amount of blood in a specimen tube containing anticoagulant and inserting this into a cup filled with ice water. After a few minutes in the cold water, the tube is held up to the light, tilted slightly, and slowly rotated. Small clumps of red blood cells coating the tube are indicative of a positive test result.

• Unfortunately, this test has positive results only in about one half of cases of mycoplasmal infection, and many other infections and conditions cause a positive cold agglutinin test result.

• Urine latex agglutination test

• This test may help to identify certain organisms; however, current technology does not allow all strains of common infectious agents to be identified.

• It is rarely obtained during the acute management of the child with pneumonia.

Procedures:

• When a child has a significant pleural effusion identified on CXR, a thoracentesis should be performed.

• This test is diagnostic and therapeutic in that it can help to identify the source of infection and can relieve respiratory distress.

• Fluid recovered from the pleural space should be sent for Gram stain and culture, along with other routine studies.

• If the thoracentesis reveals an empyema, a thoracostomy tube may be required.

TREATMENT

Section 6 of 11

Prehospital Care:

• Prehospital care of the child with pneumonia is limited to respiratory support.

• Pulse oximetry should be performed during the prehospital evaluation of such children, and supplemental oxygen should be administered.

• Children who are in severe respiratory distress should undergo tracheal intubation if unable to maintain oxygenation or decreasing levels of consciousness.

Emergency Department Care:

• Identifying and treating respiratory distress, hypoxemia, and hypercarbia is important. Grunting, flaring, severe tachypnea, and retractions should prompt immediate respiratory support.

• The vast majority of children diagnosed with pneumonia in the ED will be treated as outpatients with oral antibiotics.

• A confirmatory CXR may be performed in these patients but is often unnecessary. Although a chest radiograph is not required to make the diagnosis of pneumonia, numerous studies have shown the inaccuracy of clinical diagnosis as compared to radiographic diagnosis of pneumonia.

• Appropriate antibiotics for children who are very febrile with focal findings strongly suggestive of pneumococcal disease include amoxicillin, penicillin, and the combination of erythromycin and sulfisoxazole. Many cephalosporins and the other macrolide antibiotics are also acceptable alternatives. All other children should receive erythromycin, alone or in combination with sulfisoxazole, or receive azithromycin or clarithromycin.

• Viral pneumonia

• RSV: Serious infections with this organism usually occur in infants with underlying lung disease. Aerosolized ribavirin can be given to severely affected infants. This drug is very unlikely to be administered in the ED because concerns have been raised about exposure of health care workers and nonaffected patients to this drug. Therefore, it is usually administered in an isolation room and then only to severely affected infants. RSV-specific antibody is now available and is being administered to children who are at high risk.

• Herpesvirus: In infants, the usual agent is herpes simplex, and, in older children, pneumonia may complicate common varicella infections. Acyclovir is available for treatment of these pneumonias.

• Influenza A pneumonia that is particularly severe or when it occurs in a high-risk patient may be treated with amantadine. Little data is available on the impact of other anti-influenza agents (eg, oseltamivir) on influenza pneumonia.

• Children who are toxic appearing may require resuscitation and respiratory support.

• CXR should be performed to identify the presence of an effusion/empyema.

• Antibiotic therapy should include vancomycin (particularly in areas where penicillin resistant streptococci have been identified) and a cephalosporin. Cefuroxime is a good choice because it has activity against staphylococci.

Consultations: Consultation is not needed in the care of most children with pneumonia.

• Children who have underlying diseases may benefit from consultation with the specialist involved in their long-term care. For example, most children with cystic fibrosis are monitored by a pulmonologist. He or she may be invaluable in the treatment of these patients.

• Consultation with a pediatric infectious disease specialist may be appropriate in the treatment of a child with persistent or recurrent pneumonia.

MEDICATION

Section 7 of 11

The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

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

Drug Name	Amoxicillin (Amoxil, Trimox) -- Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria. Appropriate first-line agent in children in whom pneumococcal disease is strongly suspected. It offers the advantages of being relatively palatable and having a tid-dosing schedule. It has limited activity against gram-negative bacteria due to resistance.
Adult Dose	250-500 mg PO tid; not to exceed 1500 mg/d
Pediatric Dose	40 mg/kg/d PO divided tid 5 kg: 62.5 mg PO tid 5-10 kg: 125 mg PO tid >10 kg: 250 mg PO tid
Contraindications	Documented hypersensitivity
Interactions	Reduces the efficacy of oral contraceptives; probenecid increases serum concentrations
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in patients who are allergic to cephalosporin antibiotics; appearance of a rash should be carefully evaluated to differentiate a nonallergic ampicillin rash from a hypersensitivity reaction; rash and GI upset are adverse effects

Drug Name	Penicillin VK (Beepen-VK, Pen Vee K) -- Inhibits the biosynthesis of cell wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations are reached and most effective during the stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. May be used as an alternative to amoxicillin in treatment of outpatients with pneumonia in whom pneumococcal disease is strongly suspected. Penicillin has limited activity against gram-negative bacteria.
Adult Dose	250-500 mg PO qid; not to exceed 2000 mg/d
Pediatric Dose	40 mg/kg/d PO divided qid
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase effectiveness by decreasing clearance; tetracyclines are bacteriostatic, causing a decrease in the effectiveness of penicillins when administered concurrently
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in renal impairment and in patients who are allergic to cephalosporin antibiotics; rash and GI upset are adverse effects

Drug Name	Cefuroxime (Zinacef) -- Second-generation cephalosporin maintains gram-positive activity that first-generation cephalosporins have; adds activity against Proteus mirabilis, H influenzae, Escherichia coli, Klebsiella pneumoniae, and Moraxella catarrhalis. Condition of patient, severity of infection, and susceptibility of microorganism determine proper dose and route of administration.
Adult Dose	250-500 mg PO q12h; 750-1500 mg IV/IM q8h
Pediatric Dose	Suspension: 30 mg/kg/d PO bid Tablets: 250 mg PO q12h IV: 150-200 mg/kg/d IV divided q8h
Contraindications	Documented hypersensitivity
Interactions	Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking cefuroxime; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patient receiving potent diuretics such as loop diuretics; coadministration with aminoglycosides increase nephrotoxic potential; probenecid increases levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Administer half dose if CrCl is 10-30 mL/min and one-quarter dose if <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy; caution in patients who are allergic to penicillin; skin rashes and GI upset are adverse effects

Drug Name	Cefpodoxime (Vantin) -- Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin binding proteins. The tablet should be administered with food.
Adult Dose	200 mg/dose PO q12h
Pediatric Dose	10 mg/kg/d PO divided bid
Contraindications	Documented hypersensitivity
Interactions	Probenecid increases the serum concentrations of cefpodoxime.
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in penicillin allergy, renal impairment; adverse effects include nausea, vomiting, and diarrhea

Drug Name	Cefprozil (Cefzil) -- Binds to one or more of the penicillin-binding proteins, which in turn inhibits cell wall synthesis and results in bactericidal activity.
Adult Dose	250-500 mg/dose PO q12h or 500 mg PO qd
Pediatric Dose	30 mg/kg/d PO divided bid
Contraindications	Documented hypersensitivity
Interactions	Probenecid increases effect of cefprozil; coadministration with furosemide and aminoglycosides increases nephrotoxic effects of cefprozil
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in penicillin allergy, renal impairment; adverse effects include nausea, vomiting, and diarrhea

Drug Name	Ceftriaxone (Rocephin) -- Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin binding proteins.
Adult Dose	1-2 g IV/IM qd
Pediatric Dose	50-75 mg/kg/d IV/IM qd; not to exceed 1 g
Contraindications	Documented hypersensitivity; not to be used in hyperbilirubinemic neonates
Interactions	Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; caution in breastfeeding women and allergy to penicillin; adverse effects include nausea, vomiting, and diarrhea; not to be used in newborns, as it causes hyperbilirubinemia

Drug Name	Cefotaxime (Claforan) -- Third-generation cephalosporin with gram-negative spectrum. Lower efficacy against gram-positive organisms.
Adult Dose	1-2 g IV/IM q6-8h; not to exceed 12 g/d
Pediatric Dose	<50 kg: 100-200 mg/kg/d IV/IM divided q6-8h >50 kg: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase cefotaxime levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe renal impairment; caution in breastfeeding women and allergy to penicillin; adverse effects include nausea, vomiting, and diarrhea; associated with severe colitis

Drug Name	Erythromycin (EES, Eryc, E-Mycin) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections. DOC for adults and children > 4 y, unless suspect pneumococcal disease. These agents are effective against many of the atypical organisms. Erythromycin is available in 4 forms: base, stearate, estolate, and ethylsuccinate. Erythromycin estolate causes the least GI distress.
Adult Dose	Base: 500 mg PO qid for 7 d Ethylsuccinate (EES): 800 mg PO qid for 7 d or 400-800 mg PO qid Base, stearate, or estolate: 250-500 mg PO qid
Pediatric Dose	Newborns: 50 mg/kg/d (base) PO divided qid for 14 d or 30-50 mg/kg/d (base and ethylsuccinate) PO divided q6-8h
Contraindications	Documented hypersensitivity; hepatic impairment
Interactions	Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis; may increase the toxicity of ergotamine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Drug Name	Erythromycin and sulfisoxazole (Pediazole) -- Erythromycin is a macrolide antibiotic with a large spectrum of activity. It binds to the 50S ribosomal subunit of the bacteria, which inhibits protein synthesis. Sulfisoxazole expands erythromycin’s coverage to include gram-negative bacteria. Sulfisoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid. Dose is based on the erythromycin component.
Adult Dose	250 mg PO qid (unlikely to be prescribed to adults)
Pediatric Dose	<2 months: Not recommended >2 months: 50 mg/kg/d divided tid/qid
Contraindications	Documented hypersensitivity; hepatic impairment; megaloblastic anemia due to folate deficiency; G-6-PD deficiency
Interactions	May enhance warfarin's anticoagulation action effects and hemorrhage could occur; thiopental anesthetic effects may be enhanced; risk of nephrotoxicity may increase when administered concurrently with cyclosporine; serum hydantoin levels may increase when administered concurrently with sulfisoxazole; methotrexate-induced bone marrow suppression may be enhanced when administered concurrently with sulfisoxazole; may increase sulfonylurea concentrations and cause hypoglycemia in diabetic patients; tolbutamide bioavailability may be prolonged when administered with sulfamethizole; coadministration with diuretics may increase incidence of thrombocytopenia with purpura; sulfonamides free-drug concentration may be increased when administered concurrently with indomethacin; sulfonamides when used concomitantly with methenamine mandelate may form a precipitate in acidic urine; probenecid and salicylates may displace sulfonamides from plasma albumin resulting in increased free-drug concentrations potentiating its toxicity; coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in liver; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur; caution in patients with renal dysfunction and HIV; maintain adequate fluid intake to prevent crystalluria and stone formation

Drug Name	Clarithromycin (Biaxin) -- Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes causing RNA-dependent protein synthesis to arrest.
Adult Dose	250-500 mg PO bid
Pediatric Dose	15 mg/kg/d PO divided q12h
Contraindications	Documented hypersensitivity; coadministration of pimozide or cisapride
Interactions	Toxicity increases with coadministration of fluconazole and pimozide; clarithromycin effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, HMG CoA-reductase inhibitors; cardiac arrhythmias may occur with coadministration of cisapride; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies; abnormal metallic taste, nausea, diarrhea, and abdominal pain are adverse effects; not to refrigerate suspension

Drug Name	Azithromycin (Zithromax) -- Azithromycin inhibits RNA synthesis by binding to 50S ribosomal subunit.
Adult Dose	Day 1: 500 mg PO Days 2-5: 250 mg PO qd
Pediatric Dose	Day 1: 10 mg/kg PO once; not to exceed 500 mg/d Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d
Contraindications	Documented hypersensitivity; hepatic impairment; do not administer with pimozide
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients; adverse effects include nausea, vomiting, and diarrhea

Drug Category: Antiviral -- Inhibits DNA synthesis and viral replication.

Drug Name	Acyclovir (Zovirax) -- Inhibits activity of both HSV-1 and HSV-2. DOC for the treatment of pneumonia in children with herpes viruses (eg, herpes simplex, varicella). Patients experience less pain and faster resolution of cutaneous lesions when used within 48 h from rash onset.
Adult Dose	10 mg/kg/dose IV q8h; infuse over 1 h
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity of acyclovir
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in renal failure or when using nephrotoxic drugs (rapid IV infusion can cause renal injury)

Drug Name	Ribavirin (Virazole) -- For treatment of severe lower respiratory tract RSV infections in infants and children with an underlying compromising condition. Inhibits replication of RNA and DNA viruses.
Adult Dose	Reconstitute 6 g into 300 mL of sterile water to make a concentration of 20 mg/mL; administer as aerosol q12-18h/d for 3 d up to 7 d for RSV pneumonia
Pediatric Dose	2 g aerosolized over 2 h tid for 3 d using a Viratek small particle aerosol generator (SPAG-2)
Contraindications	Documented hypersensitivity to ribavirin or any component of the formulation; women of childbearing age who will not use contraception reliably; pregnancy, ClCr <50 mL/min; hemoglobinopathies (eg, thalassemia major, sickle cell anemia); patients with autoimmune hepatitis, anemia, or severe heart disease
Interactions	Concomitant use of ribavirin and nucleoside analogues may increase risk of developing lactic acidosis; concurrent use with didanosine has been noted to increase the risk of pancreatitis and/or peripheral neuropathy in addition to lactic acidosis
Pregnancy	X - Contraindicated in pregnancy
Precautions	Use with caution in patients requiring assisted ventilation because precipitation of the drug in the respiratory equipment may interfere with safe and effective patient ventilation; carefully monitor patients with COPD and asthma for deterioration of respiratory function

FOLLOW-UP

Section 8 of 11

Further Inpatient Care:

• Infants younger than 6 months, children with immunocompromise, children who appear toxic, and children in whom outpatient treatment has failed should be admitted for IV antibiotics. Many patients without distress are admitted for hydration, supplemental oxygen, and occasionally pain control due to concomitant pleuritis.

• In some admitted patients, further testing to identify the etiologic agent is warranted.

Further Outpatient Care:

• Most children with uncomplicated pneumonia recover without sequelae.

• In children who remain well appearing but have recurrent or chronic symptoms, further testing is warranted. Further testing may include skin testing to identify fungal pathogens and tuberculosis, sweat testing to identify cystic fibrosis, titers against rare organisms, and bronchoscopy.

In/Out Patient Meds:

• The initial outpatient treatment of children with pneumonia depends upon the clinical findings and the patient's age.

• Children in whom pneumococcal disease is suspected initially should be treated with amoxicillin or penicillin.

• Erythromycin alone or in combination with sulfisoxazole or an oral cephalosporin is an alternative.

• For most other children, particularly school-aged children, erythromycin alone or in combination with sulfisoxazole should be given. Other macrolide agents are acceptable alternatives to erythromycin.

• Children who are being admitted should be treated with cefuroxime or another broad-spectrum cephalosporin.

• Vancomycin may be added to the treatment of toxic-appearing children in areas where there is a high rate of penicillin resistance among pneumococcal isolates.

• Acyclovir is indicated for the treatment of pneumonia caused by herpesviruses.

Transfer:

• Infants and children being admitted for pneumonia may require transfer because they need admission to a critical care unit or because the hospital to which the child originally presented does not admit pediatric patients.

• Transfer should be considered when pneumonia complicates chronic illness. In such patients, the purpose of the transfer is continuity of care with the child's subspecialist.

• Since the great risk faced by children with pneumonia is respiratory compromise, the unit performing the transfer should feel comfortable with the full spectrum of respiratory support that may be required.

Deterrence/Prevention:

• Several vaccines exist that may prevent certain types of pneumonia.

• Heptavalent pneumococcal vaccine is recommended for all children in the United States.

• Influenza vaccines are recommended for young and those with chronic pulmonary disease including asthma.

• H influenzae type B vaccine is given to well children and has reduced the incidence of infections caused by this organism.

• Varicella vaccine has a dramatic impact upon the incidence of varicella.

• An injection of RSV specific immunoglobulins holds some promise for the prevention of severe RSV infections in certain infants. Likely candidates for this treatment are former premature infants and those with chronic heart and lung diseases.

Complications:

• Fortunately, most children with pneumonia recover without complications.

• Persistent effusions and empyemas are the most common serious complications of bacterial pneumonia.

• Pulmonary abscess

• Respiratory distress

• Sepsis

Prognosis:

• Patients who were placed on a protocol-driven pneumonia clinical pathway are more likely to have favorable outcomes.

• The prognosis for most forms of pneumonia is excellent. Most cases of viral pneumonia resolve without treatment; common bacterial pathogens and atypical organisms respond to antimicrobial therapy.

• The prognosis for varicella pneumonia is somewhat more guarded.

• Staphylococcal pneumonia, although rare, can be very serious despite treatment.

• Immunocompromised children, those with underlying lung disease, and neonates are at high risk for severe sequelae.

• Some forms of viral pneumonia, particularly adenoviral disease, tend to cause bronchiolitis obliterans and hyperlucent lung syndrome.

Patient Education:

• Parents should be cautioned to look for the signs of increasing respiratory distress and to seek medical attention immediately should any of these signs appear.

• Most children treated with outpatient antibiotics will be much improved within 48 hours after the initiation of treatment. If such improvement does not occur, medical attention should be sought.

• For excellent patient education resources, visit eMedicine’s Pneumonia Center. Also, see eMedicine’s patient education articles Bacterial Pneumonia and Viral Pneumonia.

MISCELLANEOUS

Section 9 of 11

Medical/Legal Pitfalls:

• Attempting to treat young infants, usually younger than 6 months, as outpatients

• Failure to recognize and treat signs of respiratory compromise and sepsis

• Failure to give parents clear discharge instructions

TEST QUESTIONS

Section 10 of 11

CME Question 1: A neonate with pneumonia may have all following symptoms except which one?

A: Tachypnea
B: Fever
C: Cough
D: Irritability
E: Cyanosis

The correct answer is C: Cough is an unusual symptom in neonates.

CME Question 2: Which of the following techniques may be useful in the physical examination of the infant/child who may have pneumonia?

A: Warmed hands and instruments
B: A small toy
C: A few minutes spent talking to the parents
D: A gentle end-expiratory squeeze of the chest or abdomen
E: All of the above

The correct answer is E: All of the techniques described may be used to facilitate physical examination of infants and young children.

Pearl Question 1 (T/F): A 15-year-old adolescent presents with a low-grade fever, cough, headache, and mild abdominal cramping associated with diarrhea. The most likely diagnosis is pneumococcal pneumonia.

The correct answer is False: Mycoplasma pneumoniae and Chlamydia pneumoniae are possible culprits. Of the 2, C pneumoniae is more likely.

Pearl Question 2 (T/F): A blood sample is taken from a 15-year-old adolescent who presents with a low-grade fever, cough, headache, and mild abdominal cramping associated with diarrhea. It is placed on ice to be sent to the laboratory. After a few minutes, someone notes small clumps of RBCs on the sides of the tube. This is a positive cold agglutinins test.

The correct answer is True: The patient has a positive cold agglutinins test. The test was once used as a screening test for Mycoplasma infections. However, it has been demonstrated to be positive in only half of patients with proven Mycoplasma.

Pearl Question 3 (T/F): A 6-year-old child presents to the ED with a temperature of 40.3°C. He has a cough and vomiting. He looks nontoxic without any distress or splinting. On examination, focal crackles are noted. A chest x-ray is mandatory.

The correct answer is False: While many physicians would perform a CXR, this test will only confirm what is already known. As long as the patient is nontoxic, outpatient treatment is warranted.

Pearl Question 4 (T/F): Most cases of pneumonia in infants and children are caused by viruses.

The correct answer is True: Viruses cause most cases of pediatric pneumonia. The most common agents are the parainfluenza viruses, influenza virus, adenovirus, and respiratory syncytial virus (RSV).

BIBLIOGRAPHY

Section 11 of 11

• Black SB, Shinefield HR, Ling S, et al: Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia. Pediatr Infect Dis J 2002 Sep; 21(9): 810-5[Medline].
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• Guckel C, Benz-Bohm G, Widemann B: Mycoplasmal pneumonias in childhood. Roentgen features, differential diagnosis and review of literature. Pediatr Radiol 1989; 19(8): 499-503[Medline].
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• Michelow IC, Olsen K, Lozano J, et al: Epidemiology and clinical characteristics of community-acquired pneumonia in hospitalized children. Pediatrics 2004 Apr; 113(4): 701-7[Medline].
• Mishaan AM, Mason EO, Martinez-Aguilar G, et al: Emergence of a predominant clone of community-acquired Staphylococcus aureus among children in Houston, Texas. Pediatr Infect Dis J 2005 Mar; 24(3): 201-6[Medline].
• Musher DM, Spindel SJ: Community-acquired pneumonia. Curr Clin Top Infect Dis 1996; 16: 102-24[Medline].
• Ponka A, Sarna S: Differential diagnosis of viral, mycoplasmal and bacteraemic pneumococcal pneumonias on admission to hospital. Eur J Respir Dis 1983 Jul; 64(5): 360-8[Medline].
• Radkowski MA, Kranzler JK, Beem MO, Tipple MA: Chlamydia pneumonia in infants: radiography in 125 cases. AJR Am J Roentgenol 1981 Oct; 137(4): 703-6[Medline].
• Regelmann WE: Diagnosing the cause of recurrent and persistent pneumonia in children. Pediatr Ann 1993 Sep; 22(9): 561-8[Medline].
• Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H; WHO Child Health Epidemiology Reference Group: Global estimate of the incidence of clinical pneumonia among children under five years of age. Bull World Health Organ 2004 Dec; 82(12): 895-903[Medline][Full Text].
• Schidlow DV, Callahan CW: Pneumonia. Pediatr Rev 1996 Sep; 17(9): 300-9; quiz 310[Medline].
• Thompson WW, Shay DK, Weintraub E, et al: Influenza-associated hospitalizations in the United States. JAMA 2004 Sep 15; 292(11): 1333-40[Medline].
• Wildin SR, Chonmaitree T, Swischuk LE: Roentgenographic features of common pediatric viral respiratory tract infections. Am J Dis Child 1988 Jan; 142(1): 43-6[Medline].

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