In the name of God

Bacterial B. Sobouti M.D. Assistant professor of pediatric infectious diseases

TUMS ‐ IUMS

١ is an inflammation of the caused by a bacterial pathogen. PPineumonias may be cllifidassified in anattiomic terms, such as lobar pneumonia, , and interstitial pneumonia. The disease usually is categorized by the etiologic agent, however, as in pneumococcal or staphylococcal pneumonia.

٢ Microbiology y S. Pneumonia (1, 3, 6, 7, 14, 18, 19, 23) y HHIfl. y S. Aureus (CA-MRSA) y Group A strep . y B. Pertussis y Gram negative bacilli y GBS y Legionella y Bacillus anthracis y Bartonella henselae y Francisella tularensis y Leptospirosis y Anaerobic

٣ EPIDEMIOLOGY The respiratory pathogens S. pneumoniae, H. influenzae, group A streptococci, and S. aureus are common inhabitants of the upper . These organisms may be isolated from many healthy children, and it is important to differentiate the many children who are colonized (i, e., multiplication of microorganisms without signs or symptoms of disease and without immuneresponse), children who have asyypmptomatic or inapparent infection (i. e., multiplication of organisms without signs or symptoms of disease but with immune response), and children with disease (i. e., clinical signs or symptoms that result from multiplication of microorgg)anisms). Colonization may persist for several months. The reason for colonization in some individuals and inapparent infection or disease in others is unknown.

۴ CLINICAL GUIDELINES The guidelines include assessment of , nutrition, lethargy and color (presence or absence of cyanosis, measurement of the RR, observation of chest wall movement to detect retractions, and auscullitation for stridor and wheezes.

۵ y Very severe pneumonia: central cyanosis and inability to drink. y Severe pneumonia: chest indrawing, without cyanosis, and the ability to drink y Pneumonia: no chest indrawing, but sustained tachypnea [>60 breaths/min for infants <2 months old, > 50 breaths/min for children 2‐12 months old, > 40 breaths/min for children 1‐5 years old] y No pneumonia: cough in the absence of chest indrawing and tachypnea.

۶ Suggested management includes hospitalization and administration of parenteral antibiotics for children with very severe and severe pneumonia, home care and administration of oral antibiotics for children with pneumonia, and no antibiotics but assessment and treatment of other problems for children with cough but without signs of severe respiratory illness.

٧ CLINICAL MANIFESTATIONS The signs and symptoms of bacterial pneumonia vary with the bacterial pathogen, the age of the patient, and the severity of the disease. Some organisms are associated with specific pattern of disease, such as the lobar pneumonia of S. pneumoniae and the empyema, abscess, and pneumatocele formation caused by S. aureus; however, any of these manifestations may result from infection caused by any of the bacterial pathogens. In young infants, signs may be nonspecific, and findings may be sparse on physical examination. Radiologic evidence of pneumonia may be found in infants who appear to have minimal disease or whose signs are more likely to be associated with upper respiratory tract infection. In older children, most cases are mild, and undoubtedly many cases occur and remain unrecognized because signs of disease do not warrant radiography of the chest. A child with pneumonia who requires hospitalization represents a small but unknown fraction of all children with pneumonia.

٨ Symptoms and signs of pneumonia in children may be classified for convenience into five categories: (1) nonspecific manifestations of infection and toxicity, (2) general signs of lower respiratory tract disease, (3) signs of pneumonia, (4) signs of pleural fluid, and (5) signs of extltrapulmonary disease. NifiNonspecific manifes ta tions of iifnfec tion and toxicity include fever, headache, malaise, gastrointestinal complaints, restlessness, and apprehension. Rigors may occur and vary from symptoms of chilliness to a sign of teeth –chattering chills.

٩ General signs of lower respiratory tract disease include tachypnea; dyspnea, including shallow or grunting respirations; cough; expectoration of sputum; and flaring of the alae nasae. Because of the importance of tachypnea as a sign of lower respiratory tract disease, reference values for normal patients should be known. Respiratory rates are correlated inversely with age during the first 3 years of life and vary from a median of 47 breaths/min in the first months of life to 38 breaths/min at the end of the first year to 28 breaths/min by 3 years of age. In older children, rates are 15 to 25 breaths/min. subjects who are asleep have lower respiratory rates than do awake subjects. On the basis of these data, definitions of tachypnea for the purpose of diagnosing lower respiratory tract infection are 50 breaths/min in infants 1 to 11 months old, 40 breaths/min in children 1 to 4 years old, and 30 breaths/min in children 5 years old or older.

١٠ Other general signs of pneumonia include a protective position and abdominal findings. The patient may lie on the affected side of the lung with legs drawn up because of chest pain. Abdominal distention may result from gastric dilation because of swallowed air or paralytic ileus. The may be displaced downward by the right diappghragm or may be enlarged if congestive heart failure complicates the pneumonia.

١١ Signs of pnuemonia may be subtle in young infants. Percussion usually is not valuable in an infant or older child if distribution of the pneumonia is patchy. Dullness to percussion is associated more often in young children with the presence of pleural fluid than with the involvement of the ppyarenchyma of the lung. Auscultatory findings may include rales, but findings are less consistent than in older children. Abnormal findings in older children include dullness to percussion, decreased tactile and vocal fremitus on palpation, and decreased breath sounds and rales over involved areas on auscultation. Intercostal retraction indicates recruitment of accessory muscles, which becomes necessary to assist respiration when significant involvement of the lung is present.

١٢ Irritation of the pleura is accompanied by chest pain that may be severe and may limit chest movement. A friction rub may be detected over the involved area of pleura. As the effus ion enlarges, dyspnea may increase, btbut plitileuriticpain may diminish and become a dull ache. The pain of pleural irritation may be present at the site of inflammation. If the involved area includes the diaphragm, the pain may be referred to the posterior and lateral . Abdominal pain may be so severe as to suggest acute appendicitis. Pleural irritation over the right upper lobe may elicit meningismus, a sign of meningeal irritation without evidence of inflammation. Empyema may extend to involve the or pericardium, or it may penetrate the chest wall to manifest as a soft tissue abscess (i. e., empyema necessitatis). Signs of extension of empyema should be sought in a patient who does not respond appropriately to chemotherapy and surgical drainage.

١٣ Extrapulmonary infection, including abscesses of the skin and soft tissues, otitis media, , and mening,gitis, may occur concomitantly with bacterial pneumonia. Pericarditis and are particularly likely to be associated with pneumonia caused by H. influenzae type b.

١۴ DIAGNOSIS MICROBIOLOGIC DIAGNOSIS Effective chemotherapy is available to treat all forms of bacterial pneumonia in children. Optimal treatment requires definition of the etiologic agent, however. The physician must differentiate viral or mycoplasmal from bacterial pneumonia; if the agent is bacterial, the probable species must be considered. An effort should be made to obtain adequate materials, incldluding sputum, secretions from the posterior nasopharynx, and blood, for bacteriologic diagnosis. The physician also should consider tracheal aspiration in young children unable to produce sputum, thoracentesis when pleural fluid is present, percutaneous lung aspiration in children who are critically ill, and lung biopsy when tissue diagnosis is important. y Culture y PCR y Latex agglutination

١۵ Laboratory Tests Elevated white blood cell counts (>15,000 cells/mm3 ) frequently, but not invariably, occur in patients with bblacterial pneumonia. A white bloo d cell count less than 5000 cells/mm3 usually is associated with severe and overwhelming disease. Determinations of eryyythrocyte sedimentation rate and measurement of C‐reactive protein did not distinguish virus from bacterial pneumonia in finnish children. The presence of an immune response to infection may be used to document bacterial pneumonia in retrospect. Serologic tests for bacterial pathogens of importance in pneumonia are available only from investigative laboratories.

١۶ Chest Radiography Although the diagnosis of pneumonia may be suggested by clinical signs, pneumonia is defined by chest radiography. In addition to plain radiography, tomography and computed tomography may be used to provide special detail about cavitation, calcification, and patency of central airways. Radiographic findings may not correlate with clinical signs in young infants. Significant pneumonia may be found by radiography in the absence of clinical signs. may be identified only with the use of a radiograph taken in the lateral decubitus position. The radiologic pattern may lag behind clinical improvement for weeks to months. A should be obtained at the conclusion of the illness to determine that the pneumonia has clldeared and that no unddlierlying process, such as ffioreign body, congenital malformation, or residual , is present. The precise timing for performing such a study is uncertain, but it should be done when resolution is expected, approximately 4 to 6 weeks after initial signs appear.

١٧ The WHO working group established the following criteria: y Category 1. Consolidation/pleural effusion‐alveolar consolidation, a dense or fluffy opacity that occupies a portion or whole of a lobe or entire lung and that may or may not contain air bronchograms; or pleural effusion‐fluid in the lateral space and not just in the minor or oblique tissue; spatially associated with pulmonary parenchymal infiltrate or obliterated enough of the hemithorax to obscure an opacity. y Category 2. Interstitial pattern/infiltrate‐ the presence of linear patchy. Densities in lacy pattern involving both and featuring peribronchial thickening and multiple areas of atelectasis. y Categgyory 3. Absence of consolidation///infiltrate/effusion. y Category 4. Radiograph quality insufficient for reading.

١٨ Differential diagnosis The differential diagnosis of bacterial pneumonia includes nonbacterial and noninfectious causes of pulmonary disease. During each period of life, certain nonbacterial agents are prominent causes of pneumonia. Pneumonia in neonates may result from congenital infection or infection acquired at the time of delivery because of rubella, toxoplasmosis, herpes simplex infection. Cytomegalovirus infection, or syphilis. In infants 2 weeks to 6 months old, chlamydia trachomatis is an important cause of a syndrome of afebrile pneumonia. Throughout childhood, most pneumonias are caused by respiratory viruses, including adenoviruses, influenza viruses, parainfluenza viruses, respiratory syncytial virus, echoviruses, and coxsackieviruses A and B.

١٩ Mycoplasma pneumoniae is an uncommon cause of pneumonia in preschool‐aged children, but is an important cause of pneumonia in school‐aged children, adolescents, and ygyoung adults. Nonbacterial pneumonias that are susceptible to available antimicrobial agents include disease caused by fungi (e.g., histoplasmosis, blastomycosis), Rickettsia (i. e., Q fever), and Chlamydia (i. e., TWAR agent and psittacosis). An important consideration is in children with persistent pulmonary disease who do not respond to penicillin or alternatives to penicillin. All children liv ing in areas that have a hig h rikisk for tubliberculosis shldhould have a tuberculin skin test if admitted to the hospital with a lower respiratory tract infection.

٢٠ Noninfectious causes of pulmonary lesions include aspiration of gastric contents, aspiration of foreign body, drug reactions, sequestration of lobe, congestive heart failure, atelectasis, , malignancy or tumor, alveolar proteinosis, pulmonary hemosiderosis, and desquamating interstitial pneumonia. Bacterial causes of acute empyema include S. aureus, S. pneumoniae, H. influenzae, gram‐negative bacilli, and anaerobic bacteria. Bloody exudates (when thoracentesis occurs without trauma) suggest malignancy, infarct of the lung, connective tissue disorder, pancreaticopleural fistula, or tuberculosis.

٢١ Management Therapy should be initiated promptly after bacterial pneumonia is diagnosed or strongly suspected. Initial therapy is guided by knowledge of the likely bacterial pathogens in the child’s age group because examination of the sputum or thltracheal aspitirate usually is unavaila ble in patien ts younger than schlhool age. The physician must decide whether hospitalization is required for optimal management of the child. Most children with mild to moderate disease can be treated at home. Hospitalization is required for children with severe disease who require hydration, oxygen, or observation; children who are toxic and have a significant degree of pulmonary dysfunction; and children whose families lack the ability to provide therapy and supportive care. Special concern is warranted for infants in the first year of life, when signs of are subtle and disease may ppgrogress rapypidly.

٢٢ Initial choice of antimicrobial agents by age group. y Neonatal pneumonia

y GBS (ampicillin/ penicillin G) (7‐10 days)

y Gram negative bacilli (Aminoglycoside) (7‐10 days)

y Staph. (PRP/Vancomycin/linezolid) (3‐6 wk)

٢٣ y Pneumonia in children 1 month to 10 years of age

y S. Pneumonia (penicillin/ampicillin – sulbactam/cephalosporins/vancomycin)

y H. influenza type b & nontypable (ampicillin‐sulbactam/cephalosporins)

y S. aureus (PRP/ViVancomycin/linezo lid)

y M. Pneumonia (Erythromycin/Azithromycin/clarithromycin)

y C. PPineumonia (EhErythromyci i/n/AihAzithromyc in/clihlarithromyci n)

٢۴ y Pneumonia in children 10 years of age or older

y S. Pneumonia

y M. Pneumonia

y AbiAnaerobic bibacteria

y C. Pneumonia

y H. IflInfluenza (in frequent ly )

٢۵ Adjuncts to antibiotic therapy Administration of antimicrobial agents is only part of the management of a child with pneumonia. Close observation, nursing care (including suction of excess secretions), and the following supportive measures are crucial: 1. Maintenance of flui d and elllectrolyte blbalance 2. Humidification provided by cool mist 3. Oxygen for severe dyspnea 4. Cleansing of the mouth 5. Sparing use of antipyretics because the temperature course provides a guideline for the therapeutic response 6. Probiotics

٢۶ More extensive procedures may be required in special circumstances, as follows: 1. Bronchoscopy is important in documenting the presence of a foreign body, tumor, or congenital anomaly. 2. Intubation of the or tracheotomy may be considered when the patient has ddffifficu lty clearing secretions and more efficient suction of the lower respiratory tree is required. 3. Drainage of pleural effusions may be necessary when an accumulation of fluid compromises respiration. 4. Intrapleural instillation of antibiotics or fibrinolytics should be considered in cases of empyema when the fluid is loculated because of fibrous adhesions.

٢٧ Prognosis In uncomplicated cases of pneumococcal pneumonia in children, the mortality rate is very low (<1%). A review of mortality from pneumonia in children in the United States, 1939 through 1996, identified reductions in mortality rates that were thought to reflect expanded access to medical care for poor children, in developing countries, pneumonia is a major cause of mortality, accounting for more than one fourth of deaths in children younger than 5 year old. Half of the pneumonia‐related mortality occurs in children younger than 1 year old. The WHO estimates that approximately 4 million childhood deaths are caused each year by pneumonia. Lung morphology and physiology usually return to normal after completion of appropriate antimicrobial therapy. is a rare occurrence; almost all children resolve thickened pleurae with no effect on lung growth and function. Even after hhiaving extensive disease associdiated wihith empyema caused by S. aureus or H. influenzae, children have normal growth and development and normal pulmonary function after recovery. Deaths still result from bacterial pneumonias; however, most deaths of children result from abrupt, overwhelming disease.

٢٨ Prevention y Pneumococcal vaccines y Hemophilus influenza vaccines y Influenza vaccine y Chemoprophylaxis [ pneumococcus in sickle cell anemia/ PCP(PJP) in HIV]

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