Recurrent or Persistent Pneumonia

Recurrent or Persistent Pneumonia

1. APPROACH TO A CHILD WITH RECURRENT OR PERSISTENT PNEUMONIA MODERATOR:DR.SAROJ KUMAR BY:DR. KESHAV CHANDRA

2. PNEUMONIA Pneumonia, defined as inflammation of the lung parenchyma. is the leading infectious cause of death globally among children younger than 5 yr, accounting for an estimated 920,000 deaths each year( 1/3 of all under 5 death due to infection). In India 35,000 to 37,000 death per annum is reported in child under 5 yr of age due to community acquired pneumonia accounting for 13-16% of total mortality.(2010 Indian data)

3. WHO has defined pneumonia solely based on clinical findings, looking for : - respiratory rate - presence of chest retraction

4. ADVANTAGES OF REVISED WHO PNEUMONIA simplify the management of pneumonia at outpatient level. Increased access to antibiotic treatment closer to home . Reduce substantially the no of referrals for hospitalisation. One oral antibiotic for the treatment of both fast breathing pneumonia and chest indrawing pneumonia

5. Pneumonia child needs hospitalisation Age < 6months Sickle cell anemia with acute chest syndrome. Multiple lobe involvement. Immunocompromised state. Toxic appearance. Moderate to severe respiratory distress Requirement of supplemental oxygen Dehydration No response to appropriate oral antibiotic therapy. Complicated pneumonia( pleural effusion, empyema , abscess, bronchopleural fistula,ARDS , sepsis, extrapulmonary inf. such as meningitis, arthritis, osteomyelitis,endocarditis )

6. Etiological Agents:

7. S. pneumoniae , H. influenzae , and S. aureus are the major causes of hospitalization and death from bacterial pneumonia among children in developing countries. The incidence of pneumonia caused by H. influenzae or S. pneumoniae has been significantly reduced in areas where routine immunization has been implemented. Viral pathogens are the most common causes of lower respiratory tract infections in infants and children older than 1 mo but younger than 5 yr of age.

8. Pneumonia Etiologies Grouped by Age of the Patient Age group Frequent pathogen In decreasing order Neonates (<3 wk ) Group B streptococcus, Escherichia coli, other Gram-negative bacilli, Streptococcus pneumoniae , Haemophilus influenzae (type b,* nontypeable ) 3 wk-3 mo Respiratory syncytial virus, other respiratory viruses (rhinoviruses, parainfluenza viruses, influenza viruses, human metapneumovirus , adenovirus), S. pneumoniae , H. influenzae (type b,* nontypeable ); if patient is afebrile , consider Chlamydia trachomatis 4 mo-4 yr RSV, other respiratory viruses (rhinoviruses, parainfluenza viruses, influenza viruses, human metapneumovirus , adenovirus), S. pneumoniae , H. influenzae (type b,* nontypeable ), Mycoplasma pneumoniae , group A streptococcus ≥5 yr M. pneumoniae , S. pneumoniae , Chlamydophila pneumoniae , H. influenzae (type b,* nontypeable ), influenza viruses, adenovirus, other respiratory viruses, Legionella pneumophila

9. Etiological agent of pneumonia (Indian children) Age group Common cause Less common cause 0 -2 months Klebsiella pneumoniae E.coli Other gram negative bacteria Staphylococcus S. pneumoniae H.influenzae Anaerobes Viruses- CMV,Herpes 2 months-5 yrs S.pneumoniae H.influenzae S.aureus K.pneumoniae Chlamydia,mycoplasma Viruses— RSV, Parainfluenzae,influenza . Adenovirus, Pertusis , M.tuberculosis > 5 Yrs S.Pneumoniae Mycoplasma chlamydia H.Influenzae S.aureus M.tuberculosis Viruses--- Adenovirus, EBV,Influenza virus,Parainfluenza viruse

10. CLASSIFICATION 1. Based on Anatomical location;-- Lobar pneumonia —consolidation of a large portion of a lobe or of an entire lobe Bronchopneumonia —patchy, suppurative infammation of the bronchi and surrounding alveoli. The patchy consolidation may affect one or several lobes and is usually bilateral. Interstitial pneumonia- - inflammation that is within the alveolar wall rather than the alveolar air space. The infiltrate tends to be lymphocytes and macrophages, and hyaline membranes may line the alveolar spaces

11. 2. Based on the origin of infection :-- Community acquire pneumonia- Nosocomial pneumonia-

12. 3. Based on etiology classified into bacterial, viral , fungal, parasitic, atypical, parasitic, aspiration pneumonia. Bacterial pneumonia most often occurs when respiratory tract organisms colonize the trachea and subsequently gain access to the lungs. When bacterial infection is established in the lung parenchyma, the pathologic process varies according to the invading organism.

13. M. pneumoniae attaches to the respiratory epithelium, inhibits ciliary action, and leads to cellular destruction and an inflammatory response in the submucosa . As the infection progresses, sloughed cellular debris, inflammatory cells, and mucus cause airway obstruction, with spread of infection occurring along the bronchial tree, as is seen in viral pneumonia. S. pneumoniae produces local edema that aids in the proliferation of organisms and their spread into adjacent portions of lung, often resulting in the characteristic focal lobar involvement .

14. Group A streptococcus lower respiratory tract infection typically results in more diffuse lung involvement with interstitial pneumonia with frequent pleural involvement. S. aureus pneumonia manifests as confluent bronchopneumonia, which is often unilateral and characterized by the presence of extensive areas of hemorrhagic necrosis and irregular areas of cavitation of the lung parenchyma, resulting in pneumatocele and empyema .

15. Viral pneumonia usually results from spread of infection along the airways, accompanied by direct injury of the respiratory epithelium, which results in airway obstruction from swelling, abnormal secretions, and cellular debris. The small caliber of airways in young infants makes such patients particularly susceptible to severe infection. Viral infection of the respiratory tract can also predispose to secondary bacterial infection by disturbing normal host defense mechanisms. Up to 30% of patients with known viral infection, particularly influenza viruses, may have coexisting bacterial pathogens.

16. Bacterial pneumonia Bacterial pneumonia is often associated with an elevated WBC count, in the range of 15,000-40,000/mm3 , predominance of polymorphonuclear leukocytes Confluent lobar consolidation seen(pneumococcal) Fever is of high grade. Crackles + Viral pneumonia In viral pneumonia, the WBC count can be normal or elevated but is usually not higher than 20,000/mm3 , with a lymphocyte predominance . characterized by hyperinflation with bilateral interstitial infiltrates and peribronchial cuffing. Low grade fever.and associated with prodromes . Wheezing +

17. Recurrent pneumonia is defined as:- 2 or more episodes in a single year or 3 or more episodes ever, with radiographic clearing between occurrences. Persistent pneumonia is defined as clinical symptoms along with radiological abnormality to continue beyond 1 month or more despite treatment.

18. The incidence of ARIs in developing countries varies from 4-8 episode per child per year. Almost 10% of these episodes are of pneumonia and of these 10% are severe pneumonia and require hospitalisation . The cause of recurrent pneumonia or persistent pneumonia overlap each other; therefore approach to such patient is similar.

19. Underlying disease for Recurrent or Persistent Pneumonia 1.Congenital malformation: Airways : Cleft palate, laryngeal cleft Pierre robin syndrome Tracheoesophageal fistulae(H-Type) Tracheomalacia , bronchomalacia,laryngomalacia Lungs:- Pulmonary hypoplasia Pulmonary sequestration, congenital cystic adenomatoid malformation, congenital lobar emphysema Bronchogenic cyst and tumour Cardiovascula r: Congenital heart defect especially with left to right shunt

20. 2.Aspirations: Gastroesophageal reflex Esophageal motilty disorder, stricture, diverticulum Foreign body aspiration Pharyngeal incoordination causing swallowing abnormality Neuromuscular disorder 3.Defect in clearance of airway secretions: Cystic fibrosis Abnormality of ciliary structure or function( kartagener syndrome Airway compression ( mediastenal tubercular lymhadenopathy , bronchogenic cyst or neoplasm) 4.Disorder of local/ systemic immunity: Primary immunodeficiency Acquired immunodeficiencies - HIV Immunosuppresive therapy Malnutrition

21. Lodha et al. in a study from tertiary care hospital in north India reported cause of recurrent pneumonia (excluding cystic fibrosis and TB) as :- Aspiration-24% Immunodeficiency-16% Structural abnormality-9% Others-29% No cause could be identified in 15%

22. Etiological organisms Etiological agents responsible for recurrent or persistent pneumonia may depend on cause of underlying illness and treatment received. Immunocompetent children may get infected with usual organisms in beginning. With recurrent administration of antibiotic and hospitalisation , they may get infection with unusaul organisms including Gm Negative Bacilli. Immunocompromised host may get infected with unusual organism including Gm negative bacilli, fungi, pneumocystis jirovecii , etc.

23. Approach to a child with recurrent or persistent pneumonia Detailed clinical history and examination with preliminary investigations including X ray film of chest gives clues about underlying illness in majority of cases.

24. Detailed clinical history Age of onset :- Symptoms from neonatal period or early infancy indicate possibility of malformation or severe immune deficiency disoders . Details of the episodes:- Detail history of the first episodes, course of illness, aggravating factors, details of the treatment etc., may give important clues for underlying cause. Respiratory distress at birth followed by recurrent pneumonia and persistence wet cough since infancy point toward possibility of primary ciliary dyskinesia or cystic fibrosis.

25. Past history/ associated complaints:- Recurrent infection involving respiratory and gastrointestinal infection suggest a possibility of humoral immune deficiency. Recurrent fungal infections indicate a possibility of T cell or phagocytic defect. History of foreign body aspiration followed by recurrent respiratory infection is a common cause of pneumonia in preschool age group. If the recurrent pneumonia is due to immune defciency , and the patient does not have signifcant infections outside the respiratory tract, then the immunodefciency is likely to be a B-cell problem. The infectious agent is often a common respiratory tract pathogen.

26. Immunoglobulin ( Ig ) G deficiency, IgG subclass deficiency, and IgA deficiency are all associated with recurrent sinopulmonary infections. If the child has poor growth and serious infections in other organ systems, the immunode ciency is more likely to be in the cell–mediated system or in the phagocytic portion of the immune system. These infections can be due to common respiratory pathogens or opportunistic pathogens .

27. Perinatal history:- H/O delayed passage of meconiumat birth suggest cystic fibrosis. Maternal infection during pregnancy may give clue to intrauterine infection. Family history:- H/O similar illness in other siblings suggests inherited disorders like cystic fibrosis, primary ciliary dyskinesia , or immune deficiency disorders. A family history of tuberculosis in adult patient suggests tuberculosis as cause of persistent pneumonia. Environmental history:- Increase level of pollutant including PM2.5 & PM10 predisposes to recurrent chest infection and increased morbidity. Exposure to birds may suggests hypersensitivity pneumonitis . Feeding history:- Choking during feeding may suggest repeated aspiration. Excessive crying during feeding or abdominal distension after feed suggest H-type TE fistula. Vomiting after feed or coughing at the end of feeding may suggest gastroesophageal reflux.

28. Physical examination A general and systemic examination is important in all clinical illness. Oral thrush and fungal infection give clue for phagocytic defect. Generalised lyphadenopathy suggests tuberculosis or HIV infection. Absence or atrophic tonsil indicate possibility of B cell disorder agammaglobulinemia . Presence of cleft plate give clue for aspiration pneumonia . Nasal regurgitation during feeding may be due to cleft palate or pharyngeal incoordination . Situs inversus suggests diagnosis of immotile cilia syndrome. Chronicity and severity of illness is indicated by growth retardation, persistent respiratory difficulty, hypoxia , clubbing, hyperinflammation or reduced volume of hemithorax .

29. Investigations Common investigation for diagnosis of underlying disease for recurrent and persistent pneumonia include imaging, documentation of swallowing defect, bronchoscopy , investigation for gastroesophageal reflux , cystic fibrosis, and immune deficiency disoders .

30. Imaging:- diagnosis of recurrent/persistent pneumonia is based on abnormality in xray film of chest.. Scolisis—prediposes to recurrent chest infection Persistent lesion in lt lower lobe may indicate possibility of sequestration. Presistent lesion in rt upper lobe suggest recurrent aspiraion . Ct chest is important tool to confirm the structural abnomality suspected in chest xray . Fibreoptic bronchoscopy is one of the most important tool in diagnostic work up . It helps in identification of various airway anomaly and intraluminal pathology. Additionaly it helps in identification of etilogical agents by obtaining bronchoalveolar lavage . For documentation of GERD, Investigation include barium esophagogram , 24-hr esophageal PH monitoring. Recurrent aspiration due to any cause can be assessed by presence of lipid laden macrophages in brochoalveolar lavage

31. Videofluoroscopic swallow study has been suggested for documentation of aspiration. In suspected cystic fibrosis, documentation of elevated sweat chloride of more than 60 meq /L or demonstration of two abnormal mutation is required. Screening of primary ciliary dyskinesia is done by using nasal nitric oxide. In children with clinical phenotype of primary ciliary dyskinesia and nasal nitric oxide is less than 77nl/minute-- one may classify as probable primary ciliary dyskinesia . Immune deficiency workup is indicated in children with recurrent infection in multiple organ system. Immunoglobulin profile with screening for T- cell, B- cell and phagocytic function can be performed.

32. Treatment Treatment of recurrent or persistent pneumonia includes - treatment of underlying illness -control of current infection with appropriate antibiotics. To start with broad spectrum antibiotics after obtaining appropriate antibiotics samples. After result of microbiological test, antibiotic can be modified to narrow spectrum to avoid development of drug resistance.

33. Selection of Antimicrobial Therapy for Specific Pathogens

34. PATHOGEN PARENTERAL THERAPY ORAL THERAPY (STEP-DOWN THERAPY OR MILD INFECTION Streptococcus pneumoniae with MICs for penicillin ≤ 2.0 μ g/ mL Preferred: Ampicillin (150-200 mg/kg/day every 6 hr) or penicillin Alternatives: ceftriaxone (50-100 mg/kg/day every 12-24 hr) Preferred: amoxicillin (90 mg/kg/day in 2 doses or 45 mg/kg/day in 3 doses); Alternatives: second- or third generation cephalosporin ( cefpodoxime , cefixime ) S. pneumoniae resistant to penicillin, with MICs ≥ 4.0 μ g/ mL Preferred: ceftriaxone (100 mg/kg/day every 12-24 hr); Alternatives : ampicillin (300-400 mg/kg/day every 6 hr), levofloxacin Preferred: oral levofloxacin (16-20 mg/kg/day in 2 doses for children 6 mo to 5 yr and 8-10 mg/kg/day once daily for children 5-16 yr, Staphylococcus aureus , ( methicillin Susceptible) Preferred: c efazolin (150 mg/kg/day every 8hr) Alternatives: clindamycin (40 mg/kg/day every 6-8 hr) or vancomycin (40-60 mg/kg/day every 6-8 hr Preferred: oral cephalexin (75-100 mg/kg/day in 3 or 4 doses); Alternative: oral clindamycin (30-40 mg/kg/day in 3 or 4 doses

35. S. aureus , ( methicillin Resistant) Preferred: vancomycin (40-60 mg/kg/day every 6-8 hr Alternatives: linezolid (30 mg/kg/day every 8hr for children <12 yr old and 20 mg/kg/day every 12 hr for children ≥12 yr old) Preferred: oral clindamycin (30-40 mg/kg/day in 3 or 4 doses); Alternatives: oral linezolid (30 mg/kg/day in 3 doses for children <12 yr and 20 mg/kg/day in 2 doses for children ≥12 yr) Haemophilus influenza , typeable (A-F) or nontypeable Preferred: intravenous ampicillin (150-200 mg/kg/day every 6 hr) Alternatives: intravenous ciprofloxacin (30 mg/kg/day every 12 hr) or intravenous l evofloxacin Preferred: amoxicillin (75-100 mg/kg/day in 3 doses OR amoxicillin clavulanate Mycoplasma Pneumoniae / Chlamydophila pneumoniae Preferred: intravenous azithromycin (10mg/kg on days 1 and 2 of therapy; transition to oral therapy if possible); Alternatives: levofloxacin Preferred: azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2-5); Alternatives: clarithromycin (15 mg/kg/day in 2 doses

36. DURATION OF TREATMENT The optimal duration of antibiotic treatment for pneumonia has not been well established However, antibiotics should generally be continued until the patient has been afebrile for 72 hr, and the total duration should not be less than 10 days (or 5 days if azithromycin is used). Shorter courses (5-7 days) may also be effective, particularly for children managed on an outpatient basis In pneumonia due to staphylococcus, a total duration of 2 wks in uncomplicated, and 4-6 wks in complicated case.

37. Take home message Recurrent pneumonia is defined as:- 2 or more episodes in a single year or 3 or more episodes ever, with radiographic clearing between occurrences. Persistent pneumonia is defined as clinical symptoms along with radiological abnormality to continue beyond 1 month or more despite treatment. . The common condition predisposing are aspiration syndromes , structural abnormalities , cystic fibrosis and immunodeficiency disorders. Detailed history and examination are essential. Common performed investigation are chest xray , tuberculin test ,sweat chloride test , bronchoscopy & Bronchoalveolar lavage , CT chest and immunological studies. M anagement consists treating underline causes.

38. Non typable H. influezae H. influenzae type b conjugate vaccines have no effect on infections caused by nontypeable strains because nontypeable strains are nonencapsulated . And the conjugated vaccine WORKS on encapsulated strains.

39. Atypical Bacteria Atypical bacteria  are  bacteria  that do not color with  gram-staining  but rather remain colorless: they are neither Gram-positive nor Gram-negative. These include the  Chlamydia,  Legionella  and the  Mycoplasma  ,the  Rickettsiaceae  are also often considered atypical. Gram-positive bacteria have a thick  peptidoglycan  layer in their cell wall, which retains the  crystal violet  during Gram staining, resulting in a purple color. Gram-negative bacteria have a thin peptidoglycan layer which does not retain the crystal violet, so when  safranin  is added during the process, they stain red. The Chlamydia and Mycoplasma lack a peptidoglycan layer so do not retain crystal violet or safranin , resulting in no color. Ricketsiaceae are technically Gram-negative, but are too small to stain well, so are often considered atypical. Peptidoglycans are the site of action of  beta- lactam antibiotics  such as  penicillins  and  cephalosporins , so  chlamydia  and  mycoplasma  are naturally resistant to these drugs, which in this sense also makes them “atypical” in the treatment of their infections.  Macrolides  such as  erythromycin  however, are usually effective at such staining.

40. In 2011, the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA) published clinical practice guidelines for community-acquired pneumonia in children older than 3 mo of age. An infiltrate on chest radiograph ( posteroanterior and lateral views) supports the diagnosis of pneumonia; images may also identify a complication such as a pleural effusion or empyema . Viral pneumonia is usually characterized by hyperinflation with bilateral interstitial infiltrates and peribronchial cuffing (Fig. 428.2 ). Confluent lobar consolidation is typically seen with pneumococcal pneumonia (Fig. 428.3 ). The radiographic appearance alone does not accurately identify pneumonia etiology, and other clinical features of the illness must be considered. Repeat chest radiographs are not required for proof of cure for patients with uncomplicated pneumonia . Moreover, current PIDS–IDSA guidelines do not recommend that a chest radiograph be performed for children with suspected pneumonia (cough, fever, localized crackles, or decreased breath sounds) who are well enough to be managed as outpatients because imaging in this context only rarely changes management

41. Role of zn in pneumonia Zinc is thought to help decrease susceptibility to acute lower respiratory tract infections by regulating various immune functions, including protecting the health and integrity of the respiratory cells during lung inflammation or injury. Zinc is an important micronutrient supporting growth and normal function of the immune system. 8  Zinc deficiency results in growth impairment, anorexia, behavioural changes, and impaired immune function, leading to susceptibility to infections.

42. Surgical closure of a cleft lip is usually performed by 3 mo of age, when the infant has shown satisfactory weight gain and is free of any oral, respiratory, or systemic infection. In an otherwise healthy child, closure of the palate is usually done before 1 yr of age to enhance normal speech development.

43. Pierre Robin syndrome consists of micrognathia and is usually accompanied by a high arched or cleft palate (Fig. 337.1 ). The tongue is usually of normal size, but the floor of the mouth is foreshortened. The infant should be maintained in a prone or partially prone position so that the tongue falls forward to relieve respiratory obstruction. Some patients require tracheostomy . Mandibular distraction procedures in the neonate can improve mandibular size, enhance respiration, and facilitate oral feedings. Sufficient spontaneous mandibular growth can take place within a few months to relieve the potential airway obstruction. Often the growth of the mandible achieves a normal profile in 4-6 yr. Of children with Pierre Robin syndrome, 30–50% have Stickler syndrome

44. Esophageal atresia (EA) is the most common congenital anomaly of the esophagus, with a prevalence of 1.7 per 10,000 live births. Of these, >90% have an associated tracheoesophageal fistula (TEF). In the most common form of EA, the upper esophagus ends in a blind pouch and the TEF is connected to the distal esophagus (type C).