1 / 71

Acute infections of the lower airways in children

Acute infections of the lower airways in children. Aleksandra Szczawińska-Popłonyk Department of Pediatric Pneumonology, Allergology and Clinical Immunology Karol Marcinkowski University of Medical Sciences Poznań. Infection.

guy-william
Download Presentation

Acute infections of the lower airways in children

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Acute infections of the lower airways in children Aleksandra Szczawińska-Popłonyk Department of Pediatric Pneumonology, Allergology and Clinical Immunology Karol Marcinkowski University of Medical Sciences Poznań

  2. Infection • The specific and nonspecific defense mechanisms keep the bronchial tree sterile beyond the first bronchial bifurcation • A certain amount of microorganisms must both avoid mucociliary clearance and resist destruction by the humoral or cellular defense mechanisms • Large amounts of the organisms reach the LRT through aspiration • The invading microorganisms have particular characteristics- eg. a marked capacity to adhere to epithelium (Influenza virus, other viruses, Mycoplasma pneumoniae, Bordetella pertussis)

  3. Infection • Microorganisms avoid immune defence system: • Encapsulated bacteria (pneumococci, Klebsiella pneumoniae, Haemophilus influenzae) are resistant to phagocytosis • Some bacteria are resistant to mechanisms of intracellular killing, other (Haemophilus influenzae, Neisseria, streptococci) produce IgA protease, which degrades IgA antibodies • There is a defect in mucociliary clearance by the inhalation of number of irritants (industrial pollution, tobacco smoke), microorganisms (viruses: Influenza, Morbilli, bacteria: B.pertussis, H.influenzae)

  4. Lower respiratory tract infectionsepidemiological data • A global health problem: four milion children die each year for respiratory tract infections (98-99% in the developing countries) • Children aged 1-5 yrs in an urban area have 6-8 episodes of RTI each year, in the country 3-5 • Only a small proportion of these infections concern the lower respiratory tract; the difference between industrialized and developing countries doesn’t concern the incidence but the severity of infections • Even if only in exceptional cases infections lead to serious complications, they cause suffering and impairement of the individual child

  5. Lower respiratory tract infectionssocial problems • Respiratory tract infections account for a large proportion of physician consultations • The significant proportion of the resources of out-patient care expand on RTI • Sickness absence and medicine cost society a lot of money: 57% of acute illnesses 50% number of days restricted activity 42% of the lost working days 60% of the lost school days

  6. Pneumonia • Definition Pneumonia is defined as inflammation in the lung parenchyma, the portion distal to the terminal bronchioles and comprising the respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli • Pathogenesis Organisms reach the lung to cause pneumonia by one of four routes: - inhalation of microbes present in the air - aspiration of organisms from the naso- or oropharynx (the most common cause of bacterial pneumonia) - hematogenous spread from a distant focus of infection - direct spread from a contiguous site of infection or penetrating injury

  7. Pneumonia - classification • By anatomic distribution: lobar, lobular, segmental, bronchopneumonia • By dominant histological lesions: alveolar exudation, involvement of interstitial tissue or both • By etiological factor: infections (viral, bacterial, mycotic, other), aspiration, drug / radiation pneumonia, Loeffler syndrome, hypersensitivity pneumonitis • By the place where infection is acquired: community-acquired pneumonia, hospital-acquired (nosocomial) pneumonia

  8. Community-acquired pneumonia • In the United States CAP remains an important cause of morbidity and mortality: -more than 3 million cases occur annually -results in more than 900 000 hospitalizations and more than 60 000 deaths • Only 20-30% of CAP occur in young, previously healthy individuals without comorbidities • Mortality is high (15-30%) in patients with predisposing risk factors including: -old age -history of cigarette smoking and COPD -chronic ethanol abuse -cardiac disease -diabetes mellitus -malignancy -renal insufficiency -corticosteroid or immunosuppressive therapy

  9. Etiology of pneumonias

  10. Pneumonia of unknown etiology • The newborn Group B Streptococcus Escherichia coli Staphylococci Listeria monocytogenes Tuberculosis Herpes simplex virus TORCH agents

  11. Pneumonia of unknown etiology • Infants 1-3 months of age Group B Streptococcus Escherichia coli Haemophilus influenzae type b Streptococcus pneumoniae Chlamydia trachomatis Ureaplasma urealyticum Pneumocystis carinii Cytomegalovirus Respiratory syncytial virus Parainfluenzae virus Adenovirus

  12. Pneumonia of unknown etiology • Children 3 months to 5 years of age -respiratory viruses 75% Respiratory syncytial virus Adenovirus Parainfluenzae virus Influenzae virus Streptococcus pneumoniae Haemophilus influenzae type b Klebsiella pneumoniae Staphylococcus aureus

  13. Pneumonia of unknown etiology • Children 6 years of age to adults Mycoplasma pneumoniae Respiratory viruses: Parainfluenzae virus, RSV, Adenovirus Influenzae virus Streptococcus pneumoniae Staphylococcus aureus Haemophilus influenzae Klebsiella pneumoniae Chlamydia pneumoniae

  14. Mycoplasmal respiratory infection • The most commonly recognized clinical syndrome following Mycoplasma pneumoniae infection is bronchopneumonia Additional respiratory illnesses include pharyngitis, sinusitis, croup, bronchitis, bronchiolitis Superinfection with typical bacteria is infrequent • Treatment: because of the absence of the cell wall, Mycoplasma is resistant to beta-lactams, but is exceptionally sensitive to: • macrolids (Erythromycin, Clarithromycin, Roxithromycin, Azithromycin) • tetracyclines – over the age of 8 yr • quinolones – over the age of 16 yr

  15. Staphylococcal respiratory infections • Upper airway infection due to Staph. aureus: pharyngitis, tonsillitis, otitis media, sinusitis, tracheitis complicating viral croup • Pneumonia may be primary (hematogenous) or secondary after viral infection (influenza) Staphylococci lead to necrotizing pneumonia and common complications are: pyopneumothorax, empyema, bronchopleural fistula, pneumatocele • Therapy: always should be initiated with penicillinase-resistant antibiotic – 90% of staphylococci are resistant to penicillin

  16. Staphylococcal respiratory infections Recommended antibiotics: • Methicillin, nafcillin, oxacillin • Clindamycin, lincomycin • Vancomycin and its new generation derivative teikoplanine when bacteria are resistant to semisynthetic penicillins (MRSA) Reports of increasing incidence of Vancomycin-resistant strains (Scandinavia, Japan, USA) • Rifampicin • Imipenem • Ciprofloxacin and other quinolones • Trimethoprime-sulfamethoxazole

  17. Pneumococcal pneumonia • Streptococcus pneumoniae is the most common cause of bacterial infections of the lungs although the incidence of pneumococcal pneumonia has declined over the last decades • In older children and adults clinical manifestations are typical: shaking chills, high fever, cough, chest pain, and development of lobar pneumonia Pleural effusion and empyema are typical complications • Therapy: drug of choice is penicillin in the dose 100 000 units/kg/24hr parenterally for 2-3 weeks

  18. Aspiration pneumonia • Relationship between gastro-esophageal reflux, dysfunctional swallowing, therapy of respiratory disorders (theophylline, oral beta-agonists) and aspiration pneumonia • Superinfection with mouth flora- predominantly anaerobes occurs in previously healthy non-hospitalized patients Treatment: Clindamycin, penicillins • Chronically ill hospitalized patients may be infected with Gram-negative flora (Pseudomonas, Klebsiella, E.coli); in these patients additional coverage with aminoglycosides, imipenem or both is indicated

  19. Pneumocystis carinii pneumonia • Epidemic form in infants between 3 and 6 mo • Sporadic form accounts for majority of cases; occurs in children and adults with primary (SCID, XLA) or secondary (AIDS) immunodeficiencies, malignancies (leukemia), organ transplant receipients • In immunocompromised hosts PCP, if untreated, is fatal within 3-4 weeks • Therapy: Trimethoprim (15-20 mg/kg/24hr) + sulfamethoxazole (75-100 mg/kg/24hr) iv for 2-4 weeks For patients who fail to respond to TP-SMX: Pentamidine isethionate 4 mg/kg/24hr 1x daily

  20. Pneumocystis carinii pneumonia • Alternative treatment of PCP: Atovaquone and trimetexate glucuronate Trimethoprime and dapsone Clindamycin and primaquine • Chemoprophylaxis: Trimethoprim 5 mg/kg/24hr + sulfamethoxazole 25 mg/kg/24hr Pentamidine by aerosol Dapsone and pyrimethamine

  21. Pulmonary aspergillosis Depending on the type of exposure and condition of the host, different pulmonary manifestation may ensue: • Allergic bronchopulmonary aspergillosis without infection or tissue invasion (the most common aspergillus-related disease), most cases in patients with chronic pulmonary disease (asthma, CF) • Allergic alveolitis in the case of ongoing exposure in allergic patients • Aspergillus pneumonia if the colonisation occurs and infection develops • Invasive disease or necrotizing pneumonia in immunodeficient patients • Aspergillus mycetoma resulting from infection of an extant cavity

  22. Pulmonary aspergillosis Treatment: • Aerosolized amphotericin B or direct instillation of the drug into the trachea (Liposomal amphotericin Ambisome) • Systemic amphotericin B iv or 5-fluorocytosine • Itraconazole with systemic steroids

  23. Recurrent bacterial pneumonias • Primary or secondary immunodeficiency • Cystic fibrosis • Ciliary dyskinesia • Tracheo-esophageal fistula • Cleft palate • Congenital bronchiectases • Gastro-esophageal reflux and aspiration syndromes • Increased pulmonary blood flow • Foreign body aspiration

  24. Microbiologic implications • Streptococcus pneumoniae is the most important bacterial pathogen in all age groups, accounting for 30-70% of CAP • Mycoplasma pneumoniae is the causative agent in 20-30% of adults younger than age 35, but accounts for only 1-9% of CAP in older adults • Legionella pneumophila accounts for only 2-10% of CAP, but is second to pneumococcus as a cause of death from CAP • Chlamydia pneumoniae is implicated in 2-8% of CAP, but severe pneumonias are rare with this pathogen • Haemophilus influenzae accounts for 5-18% of CAP in adults with high rate in smokers with COPD

  25. Microbiologic implications • Staphylococcus aureus accounts for 3-8% of CAP in adults, primarily in patients with risk factors and following influenza • Enteric Gram(-) rods, predominantly Enterobacteriaceae account for 3-8% of CAP; only in patients with comorbidities • Moraxella catarrhalis accounts for only 1-2% of CAP; more common in patients with COPD • Viruses are implicated in 5-15% of CAP; most cases occur in winter months

  26. Streptococcus pneumoniae • S. pneumoniae accounts for 30-70% of CAP and has been associated with most fatalities • S. pneumoniae can affect previously healthy individuals, but has a predilection for the elderly and for patients with preexisting disease • Outbreaks of severe, invasive infections may occur in nursing homes, chronic care facilities • S. pneumoniae is the leading cause of pneumonia in all age groups; empiric therapy for CAP should always cover S. pneumoniae • Penicillin-resistant and often multiply antibiotic-resistant strains are increasing and threaten the future efficacy of antibiotics

  27. S. pneumoniae - antimicrobial resistance • Resistance to penicillins, tetracyclines, macrolides, trimethoprim/sulfamethoxazole, cephalosporins has increased dramatically over the past three decades • Resistance to antibiotics reflects the pattern of antibiotic use • Penicillin resistance is chromosomally mediated and results from alterations in penicillin-binding proteins • In France, Spain and Eastern Europe 15-40% of pneumococci exhibit high-grade resistance to penicillin; in the USA high-grade resistance has only recently emerged and is estimated for 1-7%

  28. S. pneumoniae - antimicrobial resistance • Risk factors for penicillin resistance: age under 6 yrs, prior use of beta-lactam antibiotics and nosocomial acquisition • Penicillin resistant strains are often resistant to tetracyclines, erythromycin and TMP/SMX • Resistance to quinolones is unrelated to penicillin susceptibility • Erythromycin resistant strains are resistant to other macrolides and are usually resistant to penicilline and tetracycline • Cephalosporin-resistant strains have also increased • Most penicillin- and erythromycin resistant strains remain susceptible to imipenem, cefotaxime amd ceftriaxone • In the USA 6-30% of pneumococci are resistant to tetracycline • All pneumococci are susceptible to vancomycin, irresspective of susceptibilities to other class of antibiotics

  29. S. pneumoniae - preferred therapy • For susceptible strains or in areas where rates of of penicillin-resistance are low: -Penicillin G 4-10 million units iv -Penicillin V 500 mg q.i.d. orally • As empiric therapy when penicillin resistance is suspected: -Cefotaxime 1g q8hr or ceftriaxone 1g q24hr • For strains resistant to penicillin and cephalosporins: -Vancomycin (100% active) -Imipenem/cilastin (active against more than 90% of isolates)

  30. S. pneumoniae - preferred therapy • Alternative agents: -macrolide antibiotic (eg. erythomycin, clarithromycin, azithromycin) -beta-lactams and clindamycin are usually active -tetracyclines and TMP/SMX inconsistent (6-30% are resistant) • Penicillin G is less expensive and less toxic than alternative agents and should be used for susceptible strains

  31. Haemophilus influenzae • H. influenzae accounts for 5-18% of pneumonias, both community- and hospital-acquired • Both typeable (encapsulated, especially type b) and nontypeable (nonencapsulated) strains can cause the disease • H. influenzae is a common commensal-colonizes the oropharynx in 20-40% of healthy individuals • H. influenzae pneumonia and bronchitis characteristically affect smokers, elderly and debilitated patients, but may also afect previously healthy individuals

  32. H. influenzae - antimicrobial susceptibility • Antimicrobial resistance has increased dramatically in the past three decades • By the early 1980s, beta-lactamase-producing ampicillin resistant strains emerged • Ist-generation cephalosporins and erythromycin are nor reliable – only 40-60% of strains are susceptible • The activity of tetracyclines is modest • More than 90% of strains are susceptible to TMP/SMX • Virtually all isolates are susceptible to : ampicillin/sulbactam, cefuroxime, IIIrd-generation cephalosporins, imipenem, fluoroquinolones, new macrolides, extended-spectrum penicillins

  33. H. influenzae - preferred therapy • 1st choice agents -ampicillin/sulbactam, cefuroxime or ceftriaxone -oral agents for mild infections or following initial parenteral therapy: amoxicillin/clavulanate, cefuroxime axetil, TMP/SMX • Alternative agents -TMP/SMX, fluoroquinolones -azithromycin or clarithromycin (activity of erythromycin is inconsistent) -ampicillin or amoxicillin (only for beta-lactamase negative strains)

  34. Moraxella catarrhalis • M. catarrhalis is part of normal flora of the upper respiratory tract and is an important pathogen in otitis media, sinusitis and acute exacerbations of chronic bronchitis • M. catarrhalis accounts for 1-3% of CAP; most frequently in the winter months • More than 80% of lower respiratory tract infections caused by M. catarrhalis occur in patients with COPD or underlying diseases • Probably not important as a nosocomial pathogen

  35. M. catarrhalis - antimicrobial susceptibility • The first beta-lactamase(penicillinase)-producing strains of M. catarrhalis were described in 1977; now 50-85% of isolates are resistant to penicillin • Penicillins with beta-lactamase inhibitors, TMP/SMX, macrolides, 2nd or 3rd generation cephalosporins, tetracycline, fluoroquinolones are active against beta-lactamase positive or negative strains • Beta-lactamase negative strains are susceptible to penicillin, ampicillin and beta-lactams • Beta-lactamase producing M. catarrhalis may confer antimicrobial resistance among coinfecting pathogens (a phenomenon of indirect pathogenicity) resulting in clinical resistance of beta-lactamase negative strains of H. influenzae and Strep. pneumoniae

  36. M. catarrhalis - preferred therapy • 1st choice therapy -cefuroxime -ampicillin/sulbactam or amoxicillin/clavulanate • Alternative agents -tetracycline -TMP/SMX -macrolide -fluoroquinolones

  37. Atypical pneumonias • Mycoplasma pneumoniae • Chlamydia pneumoniae • Legionella pneumophila • Viruses Other • Pneumocystis carinii • Chlamydia trachomatis • Rickettsiae • Fungi

  38. Respiratory manifestations of mycoplasmal infection • Pharyngitis • Sinusitis • Myringitis • Otitis media • Croup • Bronchitis • Bronchiolitis • Bronchopneumonia • Pneumonia with pleural effusion

  39. Mycoplasma pneumoniae • M. pneumoniae accounts for 2-14% of CAP • M. pneumoniae has a striking predilection for younger patients; often spares older individuals • M. pneumoniae accounts for 20-30% of CAP in adolescents and adults younger than age 35; 2-9% of CAP among adults age 40-60 and only 1% of pneumonias in adults over age 60 • Epidemics of M. pneumoniae infections may occur in families, schools, institutions; prolonged contact is necessary for transmission of infection • Pneumonia caused by M. pneumoniae occurs in only 3-10% of exposed individuals • M. pneumoniae is rarely implicated as a nosocomial pathogen

  40. Characteristic features of Mycoplasma pneumoniae lower airway infection • Infections occur throughout the year • The occurence of mycoplasmal illness is closely related to the patient’s age: -mild or subclinical infections in children younger than 4 yrs -the peak incidence in schoolchildren 5-15 yrs of age • Recurrent infections in adults every 4-7 yrs • Respiratory route of infection • Incubation period 1-3 wk • Gradual onset of the respiratory illness: headache, general malaise, upper airway infection symptoms, dyspnea, dry hacking cough intensifying in the course of the disease, fever • The severity of symptoms usually greater than the condition suggested by the physical signs

  41. M. pneumoniae – preferred therapy • Because Mycoplasma spp. lack a cell wall, beta-lactams and other cell-wall active antibiotics have no significant activity • 1st choice therapy -macrolide antibiotic (erythromycin, azithromycin, clarithromycin) -doxycycline 100 mg bid orally or iv • Alternative agents -fluoroquinolones (ciprofloxacin, ofloxacin)

  42. Nonrespiratory manifestations of mycoplasmal infection • Skin: -erythema multiforme -maculopapular rush -Stevens-Johnson syndrome • CNS: -meningoencephalitis -aseptic meningitis -transverse myelitis -cerebellar ataxia -Guillain-Barre syndrome • Blood: -hemolytic anaemia -thrombocytopenia -coagulation defects

  43. Nonrespiratory manifestations of mycoplasmal infection • Gastrointestinal tract -hepatitis -pancreatitis -protein-losing hypertrophic gastropathy • Cardiovascular system -myocarditis -pericarditis -cardiac dilatation with heart failure • Joints -monoarticular transient arthritis

  44. Chlamydia pneumoniae • Within the genus Chlamydia there are three species recognized: Ch.pneumoniae, Ch.psittacci, Ch.trachomatis • Clinical features are similar to M. pneumoniae; fever and cough occur in 50-80% of patients • Infections are often asymptomatic (antichlamydial antibodies present in 26% of schoolchildren) • Associations of Chlamydia infections and coronary artery disease, carotid atherosclerosis, asthma, sarcoidosis have been suggested • Ch. pneumoniae may be an important infection trigger for asthma, CF and COPD

  45. Chlamydia pneumoniae – preferred therapy • Beta-lactams and aminoglycosides have no activity • Tetracyclines and macrolids may shorten the duration of illness • Preferred therapy: -doxycycline or tetracycline orally for 14-21 days • Alternative agents: -oral macrolides -fluoroquinolones • Empiric therapy with tetracyclines should be considered for patients with protracted bronchitis or CAP refractory to beta-lactams

  46. Legionella pneumophila • Legionella spp. are endemic in the community, accounting for 2-10% of CAP; nosocomial legionellosis is rare in most hospitals • Risk factors for legionellosis and more severe disease include advanced age, renal failure, cigarette smoking, ethanol abuse, organ transplantation, corticosteroids and severe underlying disease • Clinically pneumonia caused by Legionella is indistinguishable from other bacterial pneumonias; common feture of CAP caused by Legionella is progression of pneumonia while taking antimicrobials

  47. Legionella pneumophila – preferred therapy • Beta-lactams and aminoglycosides are not active against Legionella • 1st choice antibiotics: -intravenous erythromycin 1g q6hr iv; substitute oral erythromycin 500mg qid following clinical improvement and defervescence for 21 days -rifampin may be synergistic in combination with erythromycin in immunocompromised hosts • Alternative therapy -clarithromycin 500-1000mg bid for 21 days -ciprofloxacin 750mg bid or ofloxacin 400mg bid for 21 days

  48. Empiric (initial) therapy for CAP • In most cases of pneumonia therapy is empiric • Initial treatment of CAP should be -sufficiently broad to cover most likely pathogens -avoiding polypharmacy and toxic or excessively expensive antimicrobials • Choice of empiric therapy should be modified based on clinical features as: -age -the presence of underlying disease -radiographic appearance -prior use of antimicrobials -severity of pneumonia

  49. Empiric (initial) therapy for CAP • Parenteral antibiotics are preferred as initial therapy in neonates, infants and children with serious associated disease • Other factors warranting parenteral therapy include: respiratory distress, multilobar pneumonia, hypoxemia, hypotension, non-compliance • Oral therapy should be reserved for patients: -presenting no gastrointestinal symptoms that preclude predictable oral absorption -clinically not toxic, hypotensive, severely ill -presenting pneumonia confined to a segment or bronchopneumonia -with no prior underlying disease

  50. Empiric (initial) therapy for CAP Empiric strategies for CAP patients with no comorbidities Mild CAP not requiring hospitalization: • Penicillin or ampicillin may be adequate for Strep. pneumoniae in communities where the rate of penicillin resistant pneumococci is low • 2nd generation oral cephalosporin or amoxicillin/ clavulanate • Oral macrolide antibiotic is also recommended: covers atypicals, Strep. pneumoniae and most strains of H. influenzae • Activity of fluoroquinolones against Strep. pneumoniae is modest

More Related