Epidemiology and Etiology

Community-acquired pneumonia (CAP) is one of the most important health problems affecting children worldwide, and is the leading single cause of mortality in children younger than 5 years of age, especially in low- and middle-income countries. Annually, there are 4–5 million deaths reported in children younger than 5 years of age, and pneumonia is estimated to account for approximately 1 million of these.

The estimated median global incidence of pneumonia in 2010 in children younger than 5 years of age was 0.22 episodes per child-year, 11.5% of which are sufficiently severe to require hospitalization; this was at least 25% lower than previous estimates a decade earlier. The estimated incidence for high-income countries is 0.015 episodes per child-year.

The proportion of pneumonia cases obtained from efficacy estimates of vaccine trials was used to demonstrate the burden of pneumonia caused by Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Over 13 million new cases of pneumococcal pneumonia were estimated, with a global yearly incidence of 2228 cases per 100,000 children younger than 5 years of age, ranging from 462/100,000 cases in Europe to 3397/100,000 cases in Africa. The case fatality rate ranged from 2% in the Western Pacific to 11% in Africa. The estimated global incidence of Hib pneumonia in the absence of vaccination was 1304 per 100,000 children younger than 5 years of age.

A recent prospective study, including more than 2300 children in the United States, reported an overall incidence of radiologically confirmed CAP requiring hospitalization of 15.7 cases per 10,000 children and 62.2 cases per 10,000 among children younger than 2 years. In South Africa, a birth cohort study following 697 infants during the first year of life has shown that the incidence of clinically defined pneumonia was 0.27 episodes per child-year, with 23% of those classified as severe pneumonia.

Pneumonia can be caused by several different microorganisms, with viruses and bacteria being the most frequent agents. Viruses are, by far, the most prevalent cause of pneumonia throughout childhood, with the highest burden observed among infants. However, pathogens are epidemiologically interconnected, and coinfections, both with two or more viruses, or with viruses and bacteria, are very common. Coinfection rates up to 75% are commonly reported in infants.

There are substantial age-related differences in the etiology of CAP during childhood ( Table 25.1 ). From birth to 28 days of life, most CAP is caused by group B streptococci, or Gram-negative enteric bacteria, although respiratory syncytial virus (RSV) also has a prominent role in this age group. Beyond the neonatal period, RSV, influenza, and human metapneumovirus are among the most common viruses associated with a diagnosis of pneumonia. Chlamydia pneumoniae and particularly Mycoplasma pneumoniae infections occur more often in school-age children and during adolescence, although there are many reports of these agents causing CAP in younger children as well. In the first 6 months of life, Chlamydia trachomatis, a variety of respiratory viruses, Bordetella pertussis (see Chapter 32 ), or even Ureaplasma urealyticum may have a role (data are inconsistent).

The frequency rates for S. pneumoniae, the most prevalent bacteria causing CAP, are less affected by age. S. pneumoniae is a common pathogen throughout both infancy and childhood ; however, the incidence, severity, and complications from pneumococcal pneumonia have substantially reduced since the introduction of pneumococcal conjugate vaccine (PCV).

Various pneumococcal serotypes have been associated with CAP, with specific and distinct prevalence rates in different parts of the world. The majority of the most important serotypes are included in PCV, especially the 13 valent pneumococcal vaccine (PCV13).

Hib was a more frequent cause of CAP, before the widespread use of Hib immunization. It is still an important cause of CAP in countries where these vaccines are not universally available. Hib is more frequently observed in children younger than 5 years of age. Nontypable H. influenzae may be more frequently associated with pneumonia than S. pneumoniae in immunocompetent and immunized children, as shown in studies from low- and middle-income countries. Recently, several studies have reported on the impact of new conjugate vaccines (Hib and PCV) on pneumonia incidence, severity, and complications (see section “ Prevention ” of this chapter).

As for other pathogens, pneumonia secondary to Streptococcus pyogenes is an infrequent cause of CAP nowadays; bacteremia or scarlet fever are more frequently diagnosed, especially among small children. Chickenpox ( Varicella zoster virus) pneumonia may be associated with group A streptococcus since it seems to transiently affect host defenses and predispose to infection from commensal bacteria.

Staphylococcus aureus pneumonia usually occurs secondary to inhalation of the pathogen. In rare cases, it can be the result of bacteremic spread, usually when there is a predisposing factor (e.g., a catheter, or use of intravenous [IV] drugs). S. aureus pneumonia tends to present as an acute, severe illness, especially because many first-line antibiotics commonly used to treat CAP do not provide appropriate coverage. Radiologic findings include bronchopneumonia with alveolar infiltrates, mostly unilateral. These infiltrates may coalesce and evolve to large areas of consolidation and cavitation. Destruction of bronchial walls may lead to air trapping and pneumatocele formation in at least 30% of cases. Pleural effusion and empyema are found in as many as 60% of the cases, and pneumothorax or pyopneumothorax are common complications. In the case of hematogenous spread of S. aureus, the radiologic picture is one of multiple bilateral pulmonary infiltrates that may cavitate. An increase in white blood cell counts is usual, but is not sufficiently sensitive or specific to suggest the etiologic diagnosis. Although the appearance of staphylococcal pneumatoceles may be dramatic, usually once the infection is controlled, the pneumatoceles resolve completely in the following few months.

In recent years, community-associated methicillin-resistant S. aureus (CA-MRSA) has been increasingly recognized in otherwise healthy adults and children. CA-MRSA usually affects younger patients compared to hospital-acquired MRSA, and it is often susceptible to clindamycin, trimethoprim-sulfamethoxazole, and tetracyclines. Many strains of CA-MRSA carry the gene for Panton-Valentine leukocidin, an exotoxin that is lethal to leukocytes, which causes tissue necrosis, skin lesions, necrotizing pneumonia, and necrotizing fasciitis.

Mycobacterium tuberculosis should also be considered in the differential diagnosis of acute pneumonia, especially in high endemic areas (see Chapter 29 ). A recent systematic review reported 7.5% positive cultures in children with acute pneumonia, especially in endemic areas with a tuberculosis yearly incidence higher than 50 cases per 100,000 people.

Pathogenesis

The upper airways are commensally colonized by a variety of organisms, differently from the lower respiratory tract, which, until recently, was considered to be sterile. However, evolving knowledge of the human microbiome, using high-throughput sequencing-based studies, has shown that the lower airways are transiently or even chronically colonized. Upper respiratory infections usually precede lower respiratory tract invasion by microorganisms, such as bacteria and viruses. Viruses usually reach the lower airways through contiguous spread and replication, and a similar mechanism of invasion is believed to occur with atypical bacteria. Microaspiration from the upper respiratory tract is the most common mechanism for most bacterial pneumonia. Macroaspiration, which is associated with an overwhelming inoculum, and hematogenous spread may also occur, with this latter mechanism more common in pneumonia caused by S. aureus. In children, significant aspiration may occur due to swallowing dysfunction, gastroesophageal reflux, or congenital malformations.

In the lower airways, the infectious process begins with an immune response leading to leukocyte infiltration, edema, and consequent small airway obstruction; this is followed by loss of tissue compliance, increase in airway resistance, atelectasis, abnormalities in ventilation-perfusion ratios, and necrosis. Virulence factors also facilitate the evasion of immune defenses, causing lung invasion and tissue destruction, such as occurs with the protein NS1 from some influenza strains, and with surface proteins of S. pneumoniae. Impairment of the epiglottic and cough reflexes, interruption of mucociliary clearance by virus-induced changes in ciliary structure and function, and virus-induced enhancement of bacterial adherence are some of the mechanisms believed to contribute to this chain of events, which eventually leads to pneumonia. Evidence suggests that tumor necrosis factor-alpha (TNF-α) and specific interleukins play a role in the exaggerated immune response observed in severe pneumonias. Both humoral and cellular immune responses are crucial to protect children against pneumonia.

Clinical Features

Radiologic Findings

In general, chest radiographs are standard practice in hospitalized children for whom a diagnosis of pneumonia is being considered. In the early clinical stages of disease, patients with bacterial pneumonia may have normal chest radiographs. There is also significant variation in the interpretation of these radiographs in children, with considerable intraobserver and interobserver disagreement. Specificity ranges from 42% to 100% in different studies because of the varying definitions of pneumonia. Whether accuracy is improved by adding lateral chest radiographs is controversial, as studies have shown conflicting results. WHO criteria for the standardization of chest radiograph interpretation defined primary end-point pneumonia as consolidation (“a dense opacity that may be a fluffy consolidation of a portion or whole of a lobe or of the entire lung, often containing air bronchograms”) or pleural effusion, and such an approach is reported to improve agreement. When comparing the presence of any infiltrate (end-point or other infiltrates not matching this definition), agreement was lower.

A considerable proportion of children younger than 5 years of age with fever and leukocytosis, and without a well-defined source of infection, may have radiographic abnormalities consistent with pneumonia. In a study by Bachur and colleagues, 26% of the patients younger than 5 years of age who presented to the emergency department with fever, leukocytosis greater than 20,000 cells/mm ³ , and no clinical findings suggestive of pneumonia, had a confirmed diagnosis of pneumonia on radiograph. Therefore a plain chest radiograph is part of the investigation of nonspecific clinical signs of infection in this age group.

Because chest radiographs do not change the outcome of LRTIs, guidelines do not recommend them for children older than 2 months of age who are cared for in an outpatient setting.

Although alveolar or lobar pneumonia ( Fig. 25.1 ) is more frequently observed in infection from typical bacteria, when compared with interstitial pneumonia (which occurs more frequently in viral pneumonia or with Mycoplasma or Chlamydia infection), it is usually impossible to make an etiologic diagnosis based on a chest radiograph. No follow-up radiographs are needed to evaluate a CAP with good clinical response, except for cases of round pneumonias, lobar collapse, or whenever clinical deterioration may occur.

Pneumococcal pneumonia. Positive blood cultures for Streptococcus pneumoniae. Dense consolidation of right upper and middle lobes with air bronchogram. (A) Anteroposterior view. (B) Lateral view.

Recent reports have shown that bedside lung ultrasound (US) may be an option for the diagnosis of pneumonia in children. The accuracy is similar or higher than chest radiographs, with the possibility of bedside use and avoidance of radiation exposure. However, this technique requires specialized training, and further studies are needed.

Computed tomography (CT) scans should not be used routinely unless another underlying diagnosis is suspected (e.g., a tumor or abscess) because of radiation concerns, and because less invasive imaging techniques usually suffice for diagnosis and management. A possible exception would be in cases where a surgical approach is being considered.

Some studies have also compared lung magnetic resonance imaging (MRI) to conventional chest radiography. High agreement was reported, with greater sensitivity of MRI for complications, such as lung abscess and necrosis, with the advantage of it being a radiation-free procedure. However, the role of MRI is yet to be determined, since accuracy is not clearly superior, and it is not readily available in most settings; also, it requires sedation or a cooperative patient, and is more expensive than traditional methods.

Etiologic Diagnosis

Confirmation of pneumonia etiology may be difficult. Various approaches have been used to try to address this issue. Diagnostic methods for etiologic identification can be divided into microbiologic, immunologic, and molecular methods of detection (see Chapter 22 ). The gold standard for etiologic diagnosis in CAP is either by collecting direct lung specimens or by performing a bronchoalveolar lavage (BAL), but these methods are unacceptable for routine clinical purposes. BAL in children is helpful in nonresponding patients with severe infections, and for nosocomial or life-threatening infections. Blood cultures are positive in less than 10% of the samples and should be considered only in hospitalized children or those with complicated pneumonia. Repeating blood cultures to document resolution of bacteremia is not recommended for patients who are clinically improving, except for those with S. aureus pneumonia.

A sputum examination is a viable alternative for respiratory sampling. It is practical for adolescents and school-aged children and can be induced in young children, but it should be interpreted with caution because upper airway commensals, which can be pathogenic in the lower airways, are usually contaminants. Bacterial cultures of the throat or nasopharynx do not correlate well with lung parenchyma and are more likely to confound than to help, with the known exception of the high correlation between upper and lower airway cultures in sick patients with cystic fibrosis.

Pleural fluid cultures may grow potential pathogens, but the usual practice of empiric antibiotic use in the early phases of pneumonia decreases the sensitivity of this method. However, pleural fluid should be cultured whenever technically accessible, unless the effusion is too small or when clinical recovery is uneventful.

Diagnosis and Differential Diagnosis

Pneumonia should be suspected in children with fever, cough, tachypnea, lower chest indrawing, or crackles on chest auscultation. However, no single clinical feature has sufficient accuracy to diagnose pneumonia. Abdominal pain or nausea, when associated with fever, can present as the sole clinical finding in pneumonia affecting the lower pulmonary lobes.

The differential diagnosis of CAP includes viral bronchiolitis, asthma, cardiogenic causes of tachypnea, interstitial lung diseases, and chemical pneumonitis, especially those secondary to aspiration syndromes. Infants and small children presenting with fever and respiratory signs are frequently sent for a chest radiograph and often receive antimicrobial treatment for a presumptive diagnosis of bacterial pneumonia. Importantly, a chest x-ray cannot reliably differentiate between viral and bacterial etiologies, which may coexist. Radiologic signs of bilateral interstitial lung infiltrates or atelectasis, signs of bronchitis (true wheeze on auscultation), and generalized hyperinflation, though not definitive markers, are very likely to indicate viral pneumonia ( Fig. 25.2 ).

Viral pneumonia in a 6-month-old infant with respiratory-syncytial-virus–positive nasopharyngeal aspirate. (A) Anteroposterior radiograph with bilateral interstitial infiltrates and patchy atelectasis. (B) Lateral radiograph with hyperinflated lungs; increased anteroposterior diameter, flattening of the diaphragm, and mediastinal air cushion.

Although “atypical” pneumonia is often described with several different presentations, in clinical practice neither signs nor symptoms alone, or with radiologic findings have sufficient accuracy to differentiate M. pneumoniae infections from other agents. Tuberculosis should always be considered as a possible diagnosis, especially among children living in, or in families that have recently moved from, endemic areas. Nonresolving pneumonia with persistence or recurrent radiologic findings should alert the physician to possible noninfectious primary causes or infection with bacterial agents, such as M. tuberculosis. Another important differential diagnosis is that of round pneumonia, since these and infected congenital malformations or thoracic masses may have similar radiologic presentations ( Fig. 25.3 ).

Round pneumonia. Opacity in the left upper segment, partially concealed by the mediastinal shadow.

General Management

Infants and children with CAP without danger signs can be safely cared for at home. In this situation, the child usually should be reexamined within 48 hours after beginning treatment. According to the most current guidelines, for infants aged less than 2 months, SaO ₂ of 90%–92% or less, cyanosis, a respiratory rate greater than 70 breaths per minute, difficulty breathing, intermittent apnea, grunting, an inability to feed, failure after oral therapy, severe malnutrition, or a family incapable of providing appropriate care, are all indications for hospital admission. In older children, the indicators are a SaO ₂ of 92% or less, cyanosis, respiratory rate greater than 50 breaths per minute, grunting, difficulty breathing, signs of dehydration, or a family incapable of providing appropriate observation or supervision.

General management for hospitalized children includes oxygen delivery through a mask or nasal cannula to keep oxygen saturation above 92%, antipyretics, and IV fluids if the child is unable to drink. Fluid intake should be carefully monitored because pneumonia can be complicated by hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone secretion. The benefit of nasogastric tube feeding should be weighed against its potential for respiratory distress due to the obstruction of a nostril, or by inducing gastroesophageal reflux.

Supplemental oxygen should be given when oxygen saturation is 92% or lower. In most mild cases, this can easily be administered via a nasal cannula, a head box, or a facemask.

No randomized, controlled trials have addressed the use of noninvasive ventilation for children with pneumonia. Respiratory failure, when present, should be managed appropriately and noninvasive ventilation may be used to avoid tracheal intubation. Children should be admitted to an intensive care facility with continuous cardiorespiratory monitoring capabilities when invasive ventilation is required, or pulse oximetry measurements are below 92% with the child on inspired oxygen concentrations of 50% or more.

There is no evidence for the usefulness of chest physiotherapy in the management of CAP; therefore it is not currently indicated.

Treatment With Antimicrobials

Since viruses are the main cause for many cases of CAP in childhood, it is appropriate to be cautious and not overtreat these rather common situations with antibiotics. However, therapeutic decisions can be difficult because most tests do not adequately differentiate viral from bacterial infection in an individual child. An additional issue is the fact that many patients harbor mixed viral and bacterial agents.

The problem of bacterial resistance to antibiotics has increased steadily in the last few years, so antibiotics should be used judiciously and narrow-spectrum agents used whenever appropriate. Prior antibiotic therapy, daycare attendance, travel, and coexisting morbidities are risk factors for resistance. It is also important to keep in mind that, in an era of effective vaccines against Hib and S. pneumoniae, previous antibiotic regimens may have to be reevaluated.

Antibiotics should be started whenever bacterial pneumonia is the most probable diagnosis. Since a definitive etiologic diagnosis is more the exception than the rule, usually antibiotics are started on an empirical basis. The local prevalence of CAP-causing agents should be considered.

Several randomized studies assessing different antibiotics for pneumonia have shown that children under 5 years with tachypnea or indrawing of the lower chest without danger signs can be safely treated with oral amoxicillin. Co-trimoxazole is no longer recommended, since it is less effective than amoxicillin. Furthermore, higher doses of amoxicillin, that is, 80–90 mg/kg per day in two doses, are more effective than a lower dose and are now recommended.

Some studies have recently reviewed the issue of treatment duration. A multicenter study from Pakistan, which enrolled 2188 children between the ages of 2 and 59 months, showed the equivalence of a 3-day or 5-day course of amoxicillin in the treatment of nonsevere pneumonia, as diagnosed by the WHO criteria. Of note were a low prevalence of positive radiographic findings (14%) and a relatively high rate (20%) of treatment failure, which suggests that there may have been a high proportion of viral pneumonia.

For severe pneumonia or very severe pneumonia, according to the WHO classification, there is no evidence supporting a shortened course, and patients should be treated with IV antibiotics. Interestingly, although not yet universally adopted as the standard of care, there is growing evidence from both adult and pediatric studies that the use of procalcitonin as a biomarker for bacterial infection allows for the reduction of antibiotic duration, without any increase in adverse outcomes in bacterial pneumonia.

Choice of Antibiotics

The choice of antibiotics is based on clinical features, prevalence data for different organisms in different age groups, and regional variations in pathogens. All current guidelines recommend oral amoxicillin as the first choice, and penicillin or ampicillin if IV treatment is required.

Penicillins (either intramuscular [IM], IV, or orally) can be used for most pneumococcal pneumonias, unless highly resistant strains are identified. The prevalence of penicillin resistance also varies widely throughout different countries and continents. The degree of penicillin resistance does not appear to cause adverse outcomes for hospitalized patients with a diagnosis of pneumococcal CAP, since high parenteral penicillin serum concentrations are obtained with usual dosage regimens, which are much higher than the observed levels of resistance for these bacteria. Hospitalized patients with pneumococcal pneumonia caused by strains with minimum inhibitory concentration (MIC) up to 2 µg/mL respond well to adequate doses of β-lactam antibiotics (e.g., 200,000–250,000 U/kg per day of penicillin). Susceptibility breakpoints have been revised due to the cumulative evidence of clinical improvement even with conventional doses of penicillin for strains that were previously considered intermediately resistant. Consequently, current breakpoints of resistant S. pneumoniae for parenteral penicillin in the case of nonmeningeal infections are ≤2 µg/mL (susceptible), 4 µg/mL (intermediate), and ≥8 µg/mL (resistant). However, for oral penicillin, the previous breakpoints are still valid, due to lower serum levels achieved with enteral presentations. High doses of oral penicillin, ampicillin, and amoxicillin have been recommended whenever intermediately susceptible pneumococcus strains are considered. As mentioned above, the WHO recommends oral amoxicillin in higher doses twice daily as the first-line treatment for pneumonia.

Vancomycin or teicoplanin should be reserved for severely ill patients, when coverage for highly resistant pneumococcus is desired, because overuse may lead to increased resistance from other pathogens. Antibiotic resistance is usually associated with changes in the penicillin-binding sites of the transpeptidases of the bacteria, and it may be associated with cross-resistance to other β-lactams and carbapenems. Worldwide, most resistant pneumococcus strains were from serogroups 23F, 6A, 6B, 9V, 19A, 19F, and 14; five of these are covered by the heptavalent PCV7, and all are included in the PCV13.

Resistance to macrolides is associated with the alteration of the 50S ribosomal binding site, preventing the drug from inhibiting protein synthesis, or the presence of efflux pumps to macrolides. Overall macrolide resistance is around 30%.

When a causative agent is known, narrow-spectrum antibiotics are preferred. Table 25.2 shows appropriate antibiotic choices, based on bacteriologic tests and MICs.

Table 25.2

Choice of Antibiotic Treatment for Community-Acquired Pneumonia When Typical Bacteria Are Identified

Pathogen	First Choice	Other
Streptococcus pneumoniae, penicillin susceptible or intermediate	Penicillin, ampicillin, or high-dose amoxicillin	Cefuroxime, ceftriaxone, azithromycin
S. pneumoniae, penicillin resistant (MIC ≥ 4 µg/mL)	Second- or third-generation cephalosporins for sensitive strains; vancomycin
Staphylococcus aureus	Methicillin/oxacillin	Vancomycin or teicoplanin (for MRSA)
Haemophilus influenzae	Amoxicillin	Amoxicillin/clavulanate, cefuroxime, ceftriaxone, other second- and third-generation cephalosporins
Moraxella catarrhalis	Amoxicillin/clavulanate	Cefuroxime

 

MIC, Minimum inhibitory concentration; MRSA, methicillin-resistant S. aureus.

In real-life situations, causative agents are rarely identified, and the choice of antibiotics is based on models that include both the age of the child and the clinical presentation.

Neonates with CAP can be treated with a combination, such as IV ampicillin and gentamicin. Methicillin/oxacillin may be the best choice if the clinical picture is suggestive of S. aureus infection. For symptomatic children between 3 weeks and 3 months of age with interstitial infiltrates visible on chest radiograph, if a viral etiology is not the most likely diagnosis, a macrolide should be used to cover for agents such as C. trachomatis, B. pertussis, and U. urealyticum. Children between 4 months and 5 years of age with CAP are most likely infected by pneumococcus, viral agents, or both, and amoxicillin, penicillin, or ampicillin are the drugs of choice (see Tables 25.1 and 25.2 ). Some experts suggest macrolides (e.g., azithromycin, clarithromycin, or erythromycin) as optional choices because they cover both typical and atypical bacteria. Of note, azithromycin has a distinct pharmacokinetic profile and it does not reach high serum levels, which is a potential disadvantage in the treatment of bacterial pneumonia. Pneumococci have become increasingly macrolide resistant, indicating that macrolides should be reserved as second-line treatment or for situations in which atypical infections are either probable or confirmed by laboratory tests.

Infants and young children with CAP can receive ampicillin, amoxicillin, penicillin, or even a third-generation cephalosporin orally, unless there is vomiting, or when the patient is so sick that hospitalization and parenteral antibiotics are needed. In a recent Cochrane review, three controlled trials comparing oral with parenteral antibiotics in severe pneumonia, according to the WHO criteria, were evaluated and there were no differences in outcomes between oral and parenteral antibiotics. Since children with serious signs and symptoms (e.g., inability to drink, cyanosis, and convulsions) were not included, no definitive conclusions can be drawn from the review for this specific group of patients. In regions of the world where Hib immunization is not available, clinicians should consider amoxicillin/clavulanate, cefprozil, cefdinir, cefpodoxime proxetil, cefuroxime, or ceftriaxone as drugs of choice. The addition of a β-lactamase inhibitor does not confer additional coverage for pneumococcus because this is not its resistance-associated mechanism.

Whenever there is a positive culture or a clinical picture suggestive of S. aureus, specific antibiotic coverage against this pathogen should be added (e.g., methicillin, oxacillin, clindamycin, or vancomycin in the case of MRSA strains).

The diagnosis of CA-MRSA should be considered in cases presenting with necrotizing pneumonia. Atypical bacteria causing CAP are not common in infancy and early childhood, and should be considered only in deteriorating cases. Recent data on the use of ceftaroline (a fifth-generation cephalosporin with anti-MRSA activity) in children suggest that it is effective against CA-MRSA pneumonia. Nonetheless, specific epidemiologic or treatment data on MRSA pneumonia in children are still very scarce. If the clinical and radiologic findings suggest the possibility of an atypical agent, then a macrolide is the first choice, and a β-lactam should be added in cases of poor response.

Both cefuroxime and cefixime should be considered as good options whenever cost is not a main issue. If atypical pneumonia is suspected, a macrolide or azalide (e.g., azithromycin) should be used for 5–7 days. The role of azithromycin, clarithromycin, and erythromycin is limited to extending the antimicrobial spectrum to atypical organisms, because these agents are relatively inactive against H. influenzae, and there is increasing resistance among S. pneumoniae. Thus, such choices should be tailored to treat organisms that do not respond to first-line therapy. Pneumonia in HIV-infected children may present with a broader spectrum of pathogens, requiring a specific pattern of antibiotic cover (see Chapter 66 ).

Table 25.3 and Box 25.1 summarize these recommendations, including suggested drug regimens.

Table 25.3

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