Bradley, John S. MD
Although pneumonia is one of the most common infections in childhood, national guidelines had not previously been created by the American Academy of Pediatrics, the Pediatric Infectious Diseases Society, or the Infectious Diseases Society of America. With an increasing need to create evidence-based guidelines that could address appropriate use of the antimicrobials for infants and children, a collaboration between these professional organizations was established that ultimately included pediatricians; pediatric subspecialists in infectious diseases, pulmonology, hospital medicine, surgery, emergency medicine, and critical care medicine; as well as infectious disease/epidemiology experts from the Centers of Disease Control and Prevention (CDC).1 Early in the guidelines writing process, it became clear that owing to the vulnerable nature of children, invasive diagnostic techniques to establish bacterial etiology had rarely been performed in pneumonia studies, particularly those taking place in outpatient settings in children with less severe disease. Without a clear microbiologic diagnosis, the impact of antimicrobial therapy was difficult to define. Importantly, 19 areas of investigation were ultimately identified as priorities for clinical research for community-acquired pneumonia (CAP) in children.
The guidelines focus on both office-based management and hospital management for infants and children who are otherwise healthy, without immune-compromising comorbidities. Mycobacterial and fungal disease were not addressed. Both diagnosis and treatment, as well as the prevention of infection through immunization are highlighted. The key recommendations that challenge current practice (some abbreviated for this article) are presented below.
As with all Infectious Diseases Society of America guidelines, the strength of the recommendation and the quality of the evidence are included with each of the 92 recommendations.
1. Children and infants who have moderate to severe CAP, as defined by several factors, including respiratory distress and hypoxemia (sustained saturation of peripheral oxygen, 90% at sea level) should be hospitalized for management, including skilled pediatric nursing care (strong recommendation; high-quality evidence).
2. Infants younger than 3 months to 6 months of age with suspected bacterial CAP are likely to benefit from hospitalization (strong recommendation; low-quality evidence).
3. Children and infants with suspected or documented CAP caused by a pathogen with increased virulence, such as community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) should be hospitalized (strong recommendation; low-quality evidence).
4. Children and infants for whom there is concern about careful observation at home or who are unable to comply with therapy or unable to be followed up should be hospitalized (strong recommendation; low-quality evidence).
5. Routine measurement of the complete blood cell count (CBC) is not necessary in all children with suspected CAP managed in the outpatient setting; but in those with more serious disease, it may provide useful information for clinical management in the context of the clinical examination and other laboratory and imaging studies (weak recommendation; low-quality evidence).
6. Blood cultures should not be routinely performed in nontoxic fully immunized children with CAP managed in the outpatient setting (strong recommendation; moderate-quality evidence).
7. Routine chest radiographs are not necessary for the confirmation of suspected CAP in patients well enough to be treated in the outpatient setting (strong recommendation; high-quality evidence).
8. Antimicrobial therapy is not routinely required for preschool-aged children with CAP because viral pathogens are responsible for most clinical diseases (strong recommendation; high-quality evidence).
9. Amoxicillin should be used as first-line therapy for previously healthy, appropriately immunized infants, preschool children, school-aged children, and adolescents with mild to moderate CAP suspected to be of bacterial origin. Amoxicillin provides appropriate coverage for Streptococcus pneumoniae, the most prominent invasive bacterial pathogen (strong recommendation; moderate-quality evidence).
10. Macrolide antibiotics should be prescribed for treatment of children (primarily school-aged children and adolescents) evaluated in an outpatient setting, with findings compatible with CAP caused by atypical pathogens. Laboratory testing for Mycoplasma pneumoniae should be performed if available in a clinically relevant time frame (weak recommendation; moderate-quality evidence).
With the widespread availability of pulse oximetry in pediatric offices, clinics, and emergency departments, the use of the saturation of peripheral oxygen to assess hypoxemia and the need for hospitalization has taken much of the difficulty out of the medical assessment of the irritable crying child with pneumonia.
With high rates of immunization with conjugate pneumococcal and Haemophilus influenzae, type b vaccines, the incidence of bacteremia, particularly pneumococcal pneumonia with bacteremia, is very low, and blood cultures are no longer routinely required. With the effectiveness of the current vaccines, infants who now present for care with pneumonia in the outpatient setting are even more likely to have viral lower respiratory tract infections, rather than bacterial pneumonia. The ability of the CBC to differentiate between viral and bacterial illness is not sufficient to justify routinely obtaining this test in the outpatient setting. Similarly, the requirement for routine chest radiography in every child, well enough to be managed as an outpatient and suspected of having pneumonia, cannot be justified by published data, which suggest that chest radiography offers little beyond a good history and physical examination by an experienced clinician.
Before widespread use of the current 13-valent pneumococcal conjugate vaccine, and certainly, before the use of the conjugate vaccines against H influenzae, type b empiric broad-spectrum antibiotics for both penicillin-resistant pneumococci and β-lactamase–positive Haemophilus were required. With current national data from the CDC as well as epidemiologic data from collaborations of pediatric institutions, currently documented low penicillin resistance in pneumococcus allowed the guidelines writing group to recommend amoxicillin as first-line therapy. Although oral phenoxymethyl penicillin (penicillin V) was theoretically preferred as the most narrow-spectrum antimicrobial, the tolerability and pharmacokinetic characteristics were considered inferior to amoxicillin, leading the current recommendation.
That pediatric health care providers need to be alert to CA-MRSA as a pathogen was highlighted, although no unique clinical presentation of disease has been documented, or rapid office-based laboratory test is available to give evidence-based guidance to assist the primary care provider with this diagnosis.
Much discussion occurred around the issue of M pneumoniae infections in children. Surprisingly, very few prospectively collected clinical data have been published on the natural history of the disease or the impact of antimicrobials in children. Serologic or molecular techniques for diagnosis that are widely available to help the clinician with decision making in an office setting and have acceptable positive and negative predictive values are virtually unstudied in children. Not wishing to promote unnecessary macrolide use leading to antimicrobial resistance in the community, the guidelines writing group made a plea for clinicians to first test for Mycoplasma before prescribing antimicrobials. The group believed that a documented clinical need for better diagnostic tests that would lead to decreased antimicrobial use and resistance would encourage the development of these tests by companies.
1. A CBC count should be obtained for patients with severe pneumonia, to be interpreted in the context of the clinical examination and other laboratory and imaging studies (weak recommendation; low-quality evidence).
2. Blood cultures should be obtained in children requiring hospitalization for presumed bacterial CAP that is moderate to severe, particularly those with complicated pneumonia (strong recommendation; low-quality evidence).
3. Urinary antigen detection tests are not recommended for the diagnosis of pneumococcal pneumonia in children; false-positive tests are common (strong recommendation; high-quality evidence).
4. In patients with more serious disease, such as those requiring hospitalization or those with pneumonia-associated complications, acute-phase reactants may be used in conjunction with clinical findings to diagnose bacterial infection and assess response to therapy (weak recommendation; low-quality evidence).
5. Chest radiographs (posteroanterior and lateral) should be obtained in all patients hospitalized for management of CAP to document the presence, size, and character of parenchymal infiltrates and identify complications of pneumonia that may lead to interventions beyond antimicrobial agents and supportive medical therapy (strong recommendation; moderate-quality evidence).
6. Sensitive and specific tests for the rapid diagnosis of influenza virus and other respiratory viruses should be used in the evaluation of children with CAP. A positive influenza test may decrease both the need for additional diagnostic studies and antibiotic use while guiding appropriate use of antiviral agents in both outpatient and inpatient settings (strong recommendation; high-quality evidence).
7. Ampicillin or penicillin G should be administered to the fully immunized infant or school-aged child admitted to a hospital ward with CAP when local epidemiologic data document lack of substantial high-level penicillin resistance for invasive S pneumoniae (strong recommendation; moderate-quality evidence).
8. Empiric therapy with a third-generation parenteral cephalosporin (ceftriaxone or cefotaxime) should be prescribed for hospitalized infants and children who are not fully immunized, in regions where local epidemiology of invasive pneumococcal strains documents high-level penicillin resistance, or for infants and children with life-threatening infection, including those with empyema. Non–β-lactam agents, such as vancomycin, have not been shown to be more effective than third-generation cephalosporins in the treatment of pneumococcal pneumonia for the degree of resistance noted currently in North America (weak recommendation; moderate-quality evidence).
9. Empiric combination therapy with a macrolide (oral or parenteral), in addition to a β-lactam antibiotic, should be prescribed for the hospitalized child for whom M pneumoniae and C pneumoniae are significant considerations; diagnostic testing should be performed if available in a clinically relevant timeframe (weak recommendation; moderate-quality evidence).
10. Vancomycin or clindamycin (based on local susceptibility data) should be provided in addition to β-lactam therapy if clinical, laboratory, or imaging characteristics are consistent with infection caused by S aureus (strong recommendation; low-quality evidence).
11. The size of parapneumonic effusions is an important factor that determines management (strong recommendation; moderate-quality evidence).
12. The child’s degree of respiratory compromise is an important factor that determines management of parapneumonic effusions (strong recommendation; moderate-quality evidence).
13. Treatment courses of 10 days have been best studied, although shorter courses may be just as effective, particularly for more mild disease managed on an outpatient basis (strong recommendation; moderate-quality evidence).
In recognizing that hospitalized infants and children with more severe infections have a much higher rate of complications, including the occurrence of large pleural effusions, empyemas, and lung abscesses, routine CBC and chest radiography are still recommended. Ancillary tests for inflammation, such as sedimentation rate and V-reactive protein, are also suggested as options, although published data regarding the value of these tests in differentiating viral from bacterial pediatric lower respiratory tract infections document their limited value. The pneumococcal urinary antigen tests, useful for adults, have a high rate of false-positive results in children and therefore could not be recommended.
Given that viral lower respiratory tract infections are far more common than bacterial infections, even for inpatients, diagnostic testing for viral pathogens is now recommended. The recent wide availability of polymerase chain reaction–based tests for virtually all respiratory viral pathogens has allowed clinicians to diagnose viral CAP, rather than bacterial CAP, allowing more prudent antimicrobial use for hospitalized children. Furthermore, given that antiviral therapy for influenza pneumonia can easily be justified by the severity of infection that requires hospitalization, testing for influenza was also recommended for compatible disease during the winter season.
As explained earlier in the comments for outpatient CAP, ampicillin or penicillin G is recommended as preferred therapy for inpatients with suspected bacterial CAP in fully immunized children. However, for the unimmunized, or those with life-threatening infection, using more broad-spectrum agents that have been preferred in the past, such as ceftriaxone, is still recommended.
The issues regarding the difficulty in diagnosing Mycoplasma infections in outpatients are also a concern for hospitalized inpatients, particularly school-aged children and adolescents, leading to the recommendation to test and to include a macrolide in addition to ampicillin in the treatment regimen in certain situations. The concerns for the rare but devastating occurrence of staphylococcal pneumonia (including CA-MRSA) are again expressed for inpatients, with the recognition that there are currently no published data to support a clear clinical, CBC-based, or radiography-based differentiation between severe pneumococcal and staphylococcal diseases. When concerned, vancomycin should be added to the regimen, and investigation into the microbial etiology of infection should be undertaken.
For the first time in a national guideline, a defined approach to pleural effusions was presented, based largely on the published data and experience of many members of the writing group. An algorithm is presented on when to sample a pleural effusion, how to test an effusion, and how to manage an effusion. This consensus approach was created by medical and surgical specialists on the writing group.
The authors also hoped to provide evidence for short-course therapy of bacterial pneumonia but found that the published literature was heavily biased in favor of publications treating children at least 10 days, presumably based on clinical trial designs in an era when there was no perceived disadvantage to prolonged therapy. The few publications that did support short-course therapy uniformly failed to diagnose a bacterial pathogen in most of the children studied, making a conclusion about the efficacy of short-course therapy for bacterial CAP difficult to support.
1. Children should be immunized with vaccines for bacterial pathogens, including S pneumoniae, H influenzae type b, and pertussis to prevent CAP (strong recommendation; high-quality evidence).
2. All infants older than 6 months and all children and adolescents should be immunized annually with vaccines for influenza virus to prevent CAP (strong recommendation; high-quality evidence).
Of course, it is always better to prevent bacterial and influenzal CAP than to need to treat children with these infections. Data on the decreased incidence of pneumococcal pneumonia in those immunized with influenza vaccines are also included in the evidence summary. With universal immunization, the decreased incidence of bacterial pneumonia should further decrease the use of antimicrobials in the community, which should subsequently lead to even less antimicrobial resistance, allowing clinicians to continue to be able to offer effective therapy with well-studied, safe, well-tolerated, and cost-effective agents.
© 2012 Lippincott Williams & Wilkins, Inc.