key: cord-0034972-6go0b54o
authors: Boza Costagliola, María Lina
title: Community-Acquired Pneumonia
date: 2020-02-01
journal: Pediatric Respiratory Diseases
DOI: 10.1007/978-3-030-26961-6_31
sha: 68c58020c41546a7fd223371426c9fba1c7f1bfe
doc_id: 34972
cord_uid: 6go0b54o

Community-acquired pneumonia is an infection of the small airways and pulmonary parenchyma that develops in the outpatient setting. Despite the development of new antibiotics and vaccines, pneumonia is still a disease that occurs frequently in children under 5 years of age and is one of the main causes of mortality, especially in developing countries. The biggest challenge in treating pneumonia is to determine the agent, which depends on age, disease severity, immunological condition, geographic location, epidemiological situation, and immunizations. The classic clinical picture presents with fever, coughing, and difficulty in breathing. The physical examination shows tachypnea, reduced breath sounds, and fine crackles. Wheezing may be present in infants with viral pneumonia. The chest X-ray is considered an important tool to confirm the disease diagnosis and may guide specific treatment. Acute-phase reactants have a low sensitivity and specificity to distinguish between virus and bacteria. Microbiological identification does not have a clinical impact for most children with community-acquired pneumonia. Bronchoalveolar lavage may be considered for immunocompromised patients. Antibiotic treatment is empirical based on the best possible etiology, depending on the patient’s age and epidemiological timing. Amoxicillin is the treatment of choice for Streptococcus pneumoniae, and azithromycin is preferred for Mycoplasma pneumoniae.

Community-acquired pneumonia (CAP) is an infection of the distal part of the breathing airway and the pulmonary parenchyma in the extrahospital environment.

In spite of the development of new antibiotics and vaccines, community-acquired pneumonia is still a frequently occurring disease, which usually presents in children under 5 years of age. It is one of the main causes of mortality annually worldwide, especially in developing countries: 2 million deaths, of which 20% correspond to children. In Chile, it is the main cause of pediatric hospital-M. L. Boza Costagliola (*) Pediatrics, Respiratory diseases, University of Chile, Santiago, Chile 31 ization during winter and spring, corresponding to 52% of hospital admissions to the hospital in the first 2 years of life. It is the first cause of late infant mortality, with a 0.18/1000 ratio in children under 1 year old (2010), although it has experimented a dramatic decrease since 1990, when the mortality rate of community-acquired pneumonia was 60% (see Minsal 2013) . Currently, the infection caused by the human immunodeficiency virus (HIV) has increased the number of deaths caused by pneumonia (with a risk six times higher in comparison to those not infected), particularly in underdeveloped countries.

The biggest challenge in pneumonia is to determine the causative agent. The identification depends on such factors as age, disease severity, immunological condition, geographic location, year season, epidemiological situation, and immunizations. Therefore, identification of the causative agent varies between 10% and 85%, depending on the method used.

Etiology differs according to the patient's age. In newborns, group B Streptococcus and gramnegative bacteria are the most common agents; in infants, the most common agent is usually a virus, corresponding to 50% to 60% in Chile, for example, whereas in developed countries this percentage increases to 80%. Among the viral agents, respiratory syncytial virus (RSV) is the most frequent agent, and adenovirus causes the most serious disease (B7h serotype). Among common etiological agents, we can mention influenza, parainfluenza, and metapneumovirus: human metapneumovirus (hMPV) causes about 7% to 20% of lower respiratory infections in this age group. In past years, rhinovirus and coronavirus have also been described as causing community-acquired pneumonia.

Bacterial etiology increases with age: as many as 50% of hospitalized children are older than 5 years. Streptococcus pneumoniae causes the most common bacterial infection at any age, about 20-30%. It is predominant during winter and spring times. Other bacteria include Haemophilus influenzae, which is a rare causative agent because of mandatory vaccination, although nontypified serotypes can cause serious presentations: Staphylococcus aureus, which has a quick and serious progression, but currently is exceptional; and Streptococcus pyogenes, which has a variable clinical course, but may cause serious disease with shock and pulmonary suppuration.

Other less frequent agents include Chlamydia trachomatis, which is an infection acquired through the birth canal, with a clinical onset between 2 to 12 weeks of life. It does not include fever, but it does involve tachypnea, rhinitis, conjunctivitis, and coughing fits. A hemogram shows eosinophilia, and the chest X-ray is unspecific, but shows interstitial pattern predominance. Bordetella pertussis causes a whooping cough clinical syndrome and mainly interstitial pulmonary compromise. Atypical agents such as Mycoplasma pneumoniae and Chlamydia pneumoniae are common causes agents in children between the ages of 5 and 10 years, respectively (Table 31.1) .

Coinfection with different pathogens is possible. The most frequent combinations are RSV or influenza virus with Streptococcus pneumoniae, in 30% of the cases, and Mycoplasma pneumoniae with Streptococcus pneumoniae or Chlamydia pneumoniae in 15% of cases (Table 31 .2). 

The following factors protect the respiratory system from infections:

1. Mechanics: nasal filter of inhaled air, gag reflex, cough reflex, and mucociliary clearance 2. Immunological, involving: alveolar macrophages, immunoglobulins, local inflammatory response, complement, cytokines, antiproteases, lysozyme, fibronectins 3. Immune cellular response.

Under normal circumstances, mucociliary clearance removes efficiently inhaled agents; however, if the inoculum is big, the agent is especially aggressive, or the defense mechanisms are altered, the pulmonary parenchyma will develop an infection. The inhalation of infectious agents (virus or bacteria), or the aspiration of germs through the mouth and upper airway (bacteria), is common. Contiguous hematogenous spread or endogenous reactivation, as in tuberculosis, is rare.

Bacteria cause alveolar damage accompanied by inflammatory exudate, edema, fibrin, and afterward, invasion of polymorphonuclear leukocytes. General resolution is complete almost always, with no functional compromise. Virus cause epithelial damage which may progress to necrosis and diffuse alveolar damage in varying degrees. There is evidence suggesting that the virus could be a factor for the increase of bacterial infections, because it may take advantage of the alterations of the mechanical or immunological barrier of the host.

The clinical picture fluctuates in seriousness and depends on age, etiological agent, and extension. The classic triad is fever, cough, and respiratory distress Nevertheless, cough may appear later, because there are a few receptors in the lower airways that are only irritated when cellular lysis and inflammatory exudate appear.

In the newborn, when there is a history of premature membrane rupture related to respiratory distress during the first hours of life, along with cardiovascular collapse, group B Streptococcus must be suspected. Infants under 3 months old frequently present with tachypnea, usually above 60 breaths per minute, along with a retraction of the soft chest structures. This is frequently associated to unspecific symptoms such as hypothermia, hyperthermia, fatigue food intolerance, 

somnolence, diarrhea, or apnea. High fever must alert the clinician to rule out septic shock secondary to a respiratory infection. In older infants, there is usually a history of upper airway symptoms with coughing and rhinorrhea. Soon after, fever, tachypnea (>50/min), general status deterioration, and grunting and nasal flaring appear. High fever, especially in those under 2 years old, can be related to the seriousness of the disease, although it is not a sign that can be used to determine a specific etiology. Preschool and school-age children present with high fever, accompanied by shivers, coughing, and chest pain (pain resembling a side stitch). Abdominal pain may be present when there is compromise of the inferior lobules, and often acute appendicitis must be ruled out, particularly in school-age children. Pain in the shoulder area suggests pleural compromise. Dry or productive cough, rhinorrhea, general discomfort, headache, myalgia, and abdominal pain are nonspecific signs that may or may not accompany bacterial and viral infections. Physical examination results vary and fluctuate depending on the age of the patient. Tachypnea is a very sensitive sign in patients under 5 years old. Younger infants and newborns present with reduced breath sounds but only a few crackles. Condensation syndrome-bronchophony, dullness when percussing, bronchial murmur, and fine crackles-is frequently present in children over 2 years of age. Crackles have a sensitivity of 75% and specificity less than 60%. Wheezing may be present in infants with viral pneumonia or, in children over 5 years old with atypical pneumonia agents such as Mycoplasma pneumoniae. A normal respiratory examination does not rule out pneumonia, especially during the first 48 h, named the "silent period."

Diagnosis suspicion is mainly clinical.

No routine chest X-rays are needed for the diagnosis in the ambulatory setting, and administration of treatment must not be delayed. However, the chest X-ray is considered the gold standard to confirm the diagnosis of community-acquired pneumonia, except when acquired very early (24 h) in the clinical progression when sensibility is low.

Chest X-rays do not differentiate among bacterial, viral, or atypical agents, but a lobar condensation pattern suggests bacterial infection and an interstitial pattern suggests viral or atypical agent infection (Figs. 31.1 and 31.2). Chest X-rays are best when used to rule out pneumonial complications such as empyema or abscess. When the clinical picture shows a persistent fever after starting antibiotic treatment and/or dullness when percussing the chest, which can be presented as an acute respiratory difficulty syndrome, accompanied by hypoxemia, and/or hemodynamic instability, a chest X-ray is mandatory. This test also must be considered in patients with no response to treatment, lobar atelectasis, round-shaped consolidation, persistent symptoms, and complicated pneumonia.

A chest X-ray follow-up at 4 weeks must be done in cases of recurrent pneumonia, lobar atelectasis, suspicion of malformation, or slow-resolution pneumonia (Fig. 31.3) . Chest echography is useful when there is a suspicion of effusion to evaluate the amount and presence of septa or recollection areas.

White cell blood count, neutrophil count, C-reactive protein, sedimentation rate, and procalcitonin are not useful to identify the etiology. Several prospective studies have proven that acute-phase reactants have a low sensitivity and 

Microbiological identification does not have any clinical impact for most children with communityacquired pneumonia. Nevertheless, for patients undergoing the most serious course and/or hospitalized, etiological investigation is important. When facing the possibility of a viral etiology, direct immunofluorescence (DIF) or ELISA tests are useful, although it must be considered that for adenovirus the sensitivity is not greater than 50% in most cases. DIF on incubated cells (shell-vial technique) yields better results. It is advisable to request this technique in cases having negative results with a high clinical suspicion. Currently, the amplification of specific viral genome fragments has a high sensitivity and specificity. It uses minimum quantities of DNA, with the simultaneous detection of multiple virus; it is easy to standardize, with quick results (8 h), and therefore it is very useful in hospitalized patients. When facing the possibility of a bacterial infection, hematic cultures have a low positive rate, so they are considered only for patients who show poor clinical response. In infants, hematic culture yields poorly (around 2%) but it is similar in older children (about 10%). In patients with pleural effusion, direct pleural space, Gram stain, and culture are less than 30% positive. Nevertheless, cytochemical analysis can help to precisely locate an empyema. In older children, Gram stain and expectoration culture may be useful when there are agents that differ from those that usually colonize the upper airway, particularly when its intracellular location corresponds to macrophages or polymorphonuclear leukocytes. To validate the sample, it is necessary to have at least 25 white blood cells and fewer than 25 epithelial cells per field. Serum antigen detection for Streptococcus pneumoniae and Haemophilus influenzae in blood, urine, or pleural effusion liquid has a low specificity and sensitivity, yielding false-positives in nasopharyngeal colonization or in patients who have recently received immunization, and therefore they are not recommended. The combination of urine antigen with acute-phase reactants may be a good predictor for bacterial pneumonia. The effectiveness of the immune complex for Streptococcus pneumoniae has shown better specificity and sensitivity to diagnose Mycoplasma pneumoniae, and for Chlamydia pneumoniae serum tests such as IgM are used. They have the limitation of allowing the diagnosis only after the first week, and therefore they are not useful for early diagnosis.

Protein chain reaction (PCR) technique has a 73% sensitivity and a specificity of 94%, so the diagnosis can be done early and rapidly within the progression of the disease. Invasive methods such as bronchoalveolar lavage (BAL) may have better results, but their indication for community-acquired pneumonia is restricted to patients with a complicated course, generally with a poor response to empirical treatments, and when serological or fast microbiological methods (PCR, ELISA, DIF) have failed to yield a diagnosis. These observations are especially true for immunocompromised patients presenting with feverish neutropenia, lymphopenia, AIDS, or bone marrow or another organ transplant. When treating these patients, especially those in whom Pneumocystis jirovecii is suspected, it is suggested to obtain an induced sputum sample, which can be a noninvasive method that may be effective and secure in relationship to bronchoalveolar lavage.

It is difficult to make an etiological differential diagnosis in pneumonia. For some recurrent events, other diseases may explain its origin (Table 31 .3). Most patients will respond to outpatient treatment. For infants, medical monitoring is recommended at 24 h, and for preschoolers this can be up to 48 h. Monitoring must be foreseen for worsening of the condition caused by food rejection, medication intolerance, increase in respiratory difficulty, irritability (persistent crying), or compromised consciousness. The use of antipyretics and analgesics is indicated to keep the child in better condition and to reduce the metabolic and oxygen requirements. The physician must insist that the caregivers look for medical advice in case of symptom worsening, axillar fever greater than 38.5°C for longer than 3 days, respiratory difficulty (tachypnea, cyanosis, rib retraction), food rejection, or notable weakness.

Kinesiotherapy is not indicated for pneumonia management. It does not accelerate the recovery process and may delay symptom progression. Cough assistance techniques, postural drainage, diaphragmatic reeducation, and early mobilization may help to expand poorly ventilated areas and improve symptoms of respiratory distress to achieve these objectives.

Antibiotic treatment is empirical, and given the difficulty in isolating the etiological agent, it should be based on the best possible etiology, depending on the patient's age and the epidemiological timing. In children under 5 years old, antibiotics should not be routinely indicated, because in most cases the disease will be caused by a virus. If bacterial etiology is suspected, amoxicillin should be prescribed at 80-100 mg/kg/day, fractioned every 12 h during 5 to 7 days (using a maximum of 2 g/day). In children who are over 5 years old, amoxicillin can be prescribed at 50-80 mg/kg/day. If there is poor oral tolerance, sodium penicillin should be used as follows: 200,000 U/kg/day IV every 12 h (maximum of 4 million U/day) until tolerance is recovered, and continue with oral amoxicillin. The use of macrolides is considered for older children who are suspected of having Mycoplasma pneumoniae, or Chlamydia pneumoniae, or penicillin allergy: azitromicin 10 mg/kg/day on a daily dosage, without food, for 5 days (maximum 500 mg/day); claritromicin 15 mg/kg/day every 12 h for 10 days (maximum 1 g/day); or erythromycin 50 mg/kg/day divided into four doses, for 10 days (maximum 2 g/day). As an alternative to macrolides use, quinolones can be indicated: daily levofloxacin in 10 mg/kg doses for 10 days. In epidemic episodes, influenza A virus must be ruled out, and early treatment with antivirals (oseltamivir) must be started.

• No clinical response to outpatient therapy • Vomiting and dehydration, which may make oral treatment difficult • Total or partial respiratory insufficiency: transcutaneous saturation <93% • Under 3 months of age, because of apnea and risk of cardiorespiratory arrest • Relevant comorbidity: cardiac, pulmonary, neuromuscular, immunological • Complicated pneumonia: effusion, excavated lesions • Serious disease: Hemodynamic instability, alteration of consciousness, seizures, toxic presentation

Oxygen for patients whose saturation is less than 93 mmHg in environment air. Avoid prolonged fasting, especially in infants who are under 1 year old. Because of this, it is recommended to administer fractionated feeding, feeding in small volumes, or through a small nasogastric tube, to avoid worsening the respiratory difficulty.

Newborns and infants who are under 6 weeks old: ampicillin 100 mg/kg/day every 8 h, IV, plus amikacin 15 mg/kg each 24 h, IV, during 7-10 days to ensure a good coverage for enteric gram-negative bacteria: group B Streptococcus, type D Enterococcus, and Listeria monocytogenes. After the first week of life, as an alternative to amikacin, cefotaxime can be indicated (150 mg/kg/day), given a lower risk of Listeria monocytogenes, which may require adding ampicillin to the synergic effect of an aminoglycoside. In patients with progressive worsening, or for whom a resistant Streptococcus pneumoniae is suspected, high doses of amoxicillin, of third-or second-generation cephalosporins, or IV ampicillin, should be used. Ampicillin, which is a derivative from penicillin, is a very good choice for patients who are under 24 months of age, and it has a similar efficiency to oral amoxicillin or parenteral cephalosporins, with a significantly lesser cost. The association of macrolides with a beta lactam antibiotic is indicated in hospitalized children when there is a strong suspicion of atypical agents. In the infections caused by Staphylococcus aureus, depending on the sensitivity, cloxacillin, clindamycin, or vancomycin is indicated.

The appearance of resistant Streptococcus is a worldwide concern, and its degree of resistance degree is variable, depending on geographic distribution. The risk of having an invasive disease caused by a resistant Streptococcus pneumoniae is related to being 5 years old or younger (specially under 2 years old), use of antibiotics within the precedent month, middle-ear infection, and daycare attendance. Resistance is caused by mutations of penicillin protein-binding (PPB) sites, with a reduction in the protein affinity that binds to the antibiotic. This genetic change is caused by the DNA acquisition from resistant species such as Streptococcus viridans. The reduction of the affinity could be countered by increasing the penicillin dosage or with the use of third-generation cephalosporins. Observations made in patients with community-acquired pneumonia caused by resistant Streptococcus pneumoniae who still have a good response to treatment have increased the chosen cutoff points to determine penicillin and cefotaxime resistance (CIM > 8 ug/ml).

Whenever a patient persists with fever after 48-72 h, the presence of some complication such as effusion, pleural empyema, abscess, pneumatocele, bacterial resistance, or choice of an inadequate antibiotic must be suspected. The presence of some extrapulmonary focus (pericardium, joints, meninges) must be ruled out. Pleural effusion or empyema is a possible complication in up to 40% of hospitalized children.

The use of vaccines for Bordetella pertussis, measles, Haemophilus influenzae, and influenza have reduced the occurrence of community-acquired pneumonia. Important effects have been registered in relation to its prevention and suppurative complications after the incorporation of vaccines for type B Haemophilus influenzae. The national rate of invasive disease reported for 2003 was of 2.5/100,000 inhabitants, and the effectivity prevention for the bacterial community-acquired pneumonia and empyema was 80%. It must be considered that 6% to 16% of infections caused by Haemophilus influenzae are caused by noncapsulated agents against which the vaccine offers no protection. Influenza vaccine has a double effect: it reduces virus infection rate in high-risk populations, and, as a parallel effect, it decreases bacterial communityacquired pneumonia caused by Streptococcus pneumoniae and Staphylococcus aureus, related to post-influenza virus infection. In Chile, when mandatory vaccination was introduced in 2000 for risk groups, pneumonia incidence was clearly reduced. For those children under 2 years old, 10-and 13-valent pneumococcal conjugate vaccines are less effective for preventing pneumonia (30%) than other invasive diseases such as sepsis and meningitis (97%). Both vaccines have a good immunogenicity and herd immunity. The 13-valent vaccine includes 1, 3, 4, 5, 6A, 6B, 7F, 9 V, 14, 18C, 19A, 19F, and 23F serotypes. Premature newborns, with chronic lung damage and other risk factors, must receive monoclonal antibody prophylaxis for syncytial respiratory virus.

Community-acquired pneumonia is still a prevalent disease in children. The etiological diagnosis cannot be done by X-ray studies, hemograms, or acute-phase reactants, so the development of materials for rapid diagnosis is an unmet need required to avoid the indiscriminant use of antibiotics, which is an important factor in the appearance of bacterial resistance. Penicillin derivatives, especially oral amoxicillin, continue to be the treatment of choice when Streptococcus pneumoniae is suspected; macrolides are used when a pneumonia caused by atypical agents is suspected, especially in schoolchildren more than 5 years old. Coverage with effective vaccines is important, according to the regional needs, which may contribute to the prevention of the disease. National programs, when systematically applied to have primary care coverage, have contributed to the significant decrease of morbidity and mortality.

Executive summary: the management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America

Recomendaciones para el manejo en niños de las neumonías adquiridas en la comunidad

Elevated inflammatory markers combined with positive pneumococcal urinary antigen are a good predictor of pneumococcal community-acquired pneumonia in children

British Thoracic Society guidelines for the management of community-acquired pneumonia in children

Management of communityacquired pneumonia in the era of pneumococcal resistance: a report from the drug-resistant Streptococcus pneumoniae therapeutic Working Group

Ambulatory visit rates and antibiotic prescribing for children with pneumonia

National hospitalization trends for pediatric pneumonia and associated complications

Streptococcus pneumoniae: epidemiology and risk factors, evolution of antimicrobial resistance, and impact of vaccines

Guía Clínica Auge Infecciones respiratorias agudas en menores de 5 años

13-Valent pneumococcal conjugate vaccine: a review of its use in infants, children, and adolescents

Chest radiograph in acute respiratory infections in children

Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children