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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.

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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
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)


Infection1
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)


Lower respiratory tract infections epidemiological data
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


Lower respiratory tract infections social problems
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


Pneumonia
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


Pneumonia classification
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


Community acquired pneumonia
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



Pneumonia of unknown etiology
Pneumonia of unknown etiology

  • The newborn

    Group B Streptococcus

    Escherichia coli

    Staphylococci

    Listeria monocytogenes

    Tuberculosis

    Herpes simplex virus

    TORCH agents


Pneumonia of unknown etiology1
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


Pneumonia of unknown etiology2
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


Pneumonia of unknown etiology3
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


Mycoplasmal respiratory infection
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


Staphylococcal respiratory infections
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


Staphylococcal respiratory infections1
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


Pneumococcal pneumonia
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


Aspiration pneumonia
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


Pneumocystis carinii pneumonia
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


Pneumocystis carinii pneumonia1
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


Pulmonary aspergillosis
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


Pulmonary aspergillosis1
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


Recurrent bacterial pneumonias
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


Microbiologic implications
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


Microbiologic implications1
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


Streptococcus pneumoniae
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


S pneumoniae antimicrobial resistance
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%


S pneumoniae antimicrobial resistance1
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


S pneumoniae preferred therapy
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)


S pneumoniae preferred therapy1
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


Haemophilus influenzae
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


H influenzae antimicrobial susceptibility
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


H influenzae preferred therapy
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)


Moraxella catarrhalis
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


M catarrhalis antimicrobial susceptibility
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


M catarrhalis preferred therapy
M. catarrhalis - preferred therapy

  • 1st choice therapy

    -cefuroxime

    -ampicillin/sulbactam or amoxicillin/clavulanate

  • Alternative agents

    -tetracycline

    -TMP/SMX

    -macrolide

    -fluoroquinolones


Atypical pneumonias
Atypical pneumonias

  • Mycoplasma pneumoniae

  • Chlamydia pneumoniae

  • Legionella pneumophila

  • Viruses

    Other

  • Pneumocystis carinii

  • Chlamydia trachomatis

  • Rickettsiae

  • Fungi


Respiratory manifestations of mycoplasmal infection
Respiratory manifestations of mycoplasmal infection

  • Pharyngitis

  • Sinusitis

  • Myringitis

  • Otitis media

  • Croup

  • Bronchitis

  • Bronchiolitis

  • Bronchopneumonia

  • Pneumonia with pleural effusion


Mycoplasma pneumoniae
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


Characteristic features of mycoplasma pneumoniae lower airway infection
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


M pneumoniae preferred therapy
M. pneumoniae – preferred therapy airway infection

  • 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)


Nonrespiratory manifestations of mycoplasmal infection
Nonrespiratory manifestations of mycoplasmal infection airway 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


Nonrespiratory manifestations of mycoplasmal infection1
Nonrespiratory manifestations of mycoplasmal infection airway infection

  • Gastrointestinal tract

    -hepatitis

    -pancreatitis

    -protein-losing hypertrophic gastropathy

  • Cardiovascular system

    -myocarditis

    -pericarditis

    -cardiac dilatation with heart failure

  • Joints

    -monoarticular transient arthritis


Chlamydia pneumoniae
Chlamydia pneumoniae airway infection

  • 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


Chlamydia pneumoniae preferred therapy
Chlamydia pneumoniae – preferred therapy airway infection

  • 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


Legionella pneumophila
Legionella pneumophila airway infection

  • 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


Legionella pneumophila preferred therapy
Legionella pneumophila – preferred therapy airway infection

  • 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


Empiric initial therapy for cap
Empiric (initial) therapy for CAP airway infection

  • 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


Empiric initial therapy for cap1
Empiric (initial) therapy for CAP airway infection

  • 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


Empiric initial therapy for cap2
Empiric (initial) therapy for CAP airway infection

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


Empiric initial therapy for cap3
Empiric (initial) therapy for CAP airway infection

Moderate CAP requiring hospitalization

  • Iv ampicillin/sulbactam, cefuroxime, ceftriaxone or cefotaxime plus an oral macrolide

  • Ofloxacin for penicillin-allergic patients

    Severe life threatening or multilobar CAP requiring hospitalization

  • Ceftriaxone plus high-dose iv erythromycin

  • Ceftriaxone plus iv fluoroquinolone (ofloxacin, ciprofloxacin)

  • Piperacillin/tazobactam plus iv eythromycin

  • Piperacillin/tazobactam plus a fluoroquinolone

  • Fluoroquinolone (ofloxacin, ciprofloxacin) for penicillin-allergic patients


Anaerobic pleuropulmonary infections
Anaerobic pleuropulmonary infections airway infection

  • Anaerobes may have a primary role in a spectrum of pleuropulmonary syndromes: acute pneumonitis, necrotizing pneumonia with cavitation, lung abscess, empyema

  • Anaerobes have been implicated as either sole or concomittant pathogens in 70-97% of aspiration pneumonias or primary lung abscess

  • In aspiration occuring in the comunity, streptococci, H. influenzae and anaerobes may be involved

  • Aspiration pneumonia in patients in hospitals and with comorbidities may include an admixture of anaerobes and enteric Gram negative bacilli


Antibacterial susceptibility of anaerobes
Antibacterial susceptibility of anaerobes airway infection

  • Bacteroides fragilis and virtually all anaerobes are susceptible to: imipenem, metronidazole, extended-spectrum penicillins with beta-lactamase inhibitors

  • Clindamycin is active against most anaerobes

  • Penicillin G and ampicillin have exquisite activity against normal oral anaerobes, but more than 90% of B. fragilis are resistant

  • Activity of cephalosporins against anaerobes is modest; the most active are cephamycins (cefotetan, cefoxitin)

  • Aztreonam, fluoroquinolones, TMP/SMX have poor anaerobic activity


Preferred therapy for community acquired lung abscess and aspiration pneumonia
Preferred therapy for community-acquired lung abscess and aspiration pneumonia

  • Community-acquired aspiration pneumonia or lung abscess in patients without serious associated diseases can be treated with narrow-spectrum agents:

  • Penicillin G for uncomplicated cases

  • Clindamycin for complicated lung abscess or penicillin failure

  • Ampicillin/sulbactam when concomittant infection with enteric Gram(-) bacilli suspected

  • Oral antibiotics (penicillin V, clindamycin, amoxicillin/clavulanate) may be substituted following clinical response to parenteral therapy

  • Alternatively: cefotetan and extended-spectrum penicillins with beta-lactamase inhibitors when infection with Gram(-) enteric bacilli coexists


Nosocomial pneumonia
Nosocomial pneumonia aspiration pneumonia

  • Pneumonia develops in 0,5-2% of hospitalized patients and has been associated with mortality rate of 30-60%

  • Aerobic enteric Gram(-) bacilli are responsible for 65-85% of nosocomial pneumonias

  • Enterobacteriaceae (Klebsiella, Enterobacter) account for 30-50% of nosocomial pneumonias

  • 15-20% are caused by Pseudomonas aeruginosa

  • Staphylococci and streptococci account for 10-25% of cases, usually in the context of polymicrobial pneumonia

  • Sporadic cases and epidemic outbreaks of nosocomial pneumonia are caused by Legionella, Pneumocystis carinii, Mycobacterium tuberculosis, viruses and invasive fungi

  • Anaerobes are less important as primary pathogens, but may coexist in polymicrobial infections


Acinetobacter sp
Acinetobacter sp. aspiration pneumonia

  • Acinetobacter accounts for only 1-3% of nosocomial pneumonias, but the rate is higher- 5-15% in mechanically ventilated ICU patients primarily newborns

  • Mortality rates for Acinetobacter pneumonia exceed 50%

  • Antimicrobial susceptibility:

  • Acinetobacter are highly resistant to multiple antibiotics: ampicillin, 1st and 2nd generation cephalosporins and in a lesser extent to aminoglycosides

  • Activity of 3rd generation cephalosporins is variable


Acinetobacter preferred therapy
Acinetobacter – preferred therapy aspiration pneumonia

  • 1st choice agents:

    -imipenem/cilastatin, antipseudomonal penicillins, ceftazidime in combination with aminoglycosides to confer synergy

  • Alternative agents:

    -TMP/SMX, fluoroquinolones may be active but variable

  • Choice of agent should depend on results of susceptibility testing


Klebsiella pneumoniae
Klebsiella pneumoniae aspiration pneumonia

  • K. pneumoniae accounts for 5-9% of nosocomial pneumonias and for 1-5% of CAP in debilitated patients

  • High rate of bacteriemia and and suppurative complications are noted

  • Antimicrobial susceptibility:

  • Resistant to penicillin and ampicillin

  • Highly susceptible to cefuroxime, 3rd generation cephalosporins, imipenem, aztreonam, fluoroquinolones, aminoglycosides, TMP/SMX

  • Klebsiella pneumoniae producing plasmid-mediated extended spectrum beta-lactamases that confer resistance to ceftazidime have been isolated in Europe and in the USA


Klebsiella pneumoniae preferred therapy
Klebsiella pneumoniae – preferred therapy aspiration pneumonia

  • 1st choice antibiotics:

    -2nd or 3rd generation cephalosporins

    -aminoglycosides may be added for synergy in fulminant or refractory cases

  • Alternative agents:

    -imipenem, fluoroquinolone, aztreonam, TMP/SMX

  • Epidemics of infections caused by beta-lactamase producing K. pneumoniae correlate with extensive use of cephalosporin monotherapy and may be curtailed by switching to extended-spectrum penicillins or imipenem/cilastatin


Pseudomonas aeruginosa
Pseudomonas aeruginosa aspiration pneumonia

  • P. aeruginosa accounts for 15-20% of nosocomial pneumonias; the rates are even higher in ventilated ICU patients (20-30%)

  • P. aeruginosa is a rare cause of CAP except among patients with specific risk factors:

    bronchiectasis, CF, tracheostomy, granulocytopenia, immunosuppressive or corticosteroid therapy, iv drug abuse

  • Mortality from P. aeruginosa pneumonia is 50-70%

  • In 30-50% of patients relapses or antimicrobial resistance develops


P aeruginosa antimicrobial susceptibility
P. aeruginosa – antimicrobial susceptibility aspiration pneumonia

  • P. aeruginosa is resistant to most antibiotics

  • Antipsedomonal penicillins are active against 80-95% of strains; piperacillin is the most potent

  • Among cephalosporins only ceftazidime and cefoperazone are considered active

  • Other agents with antipseudomonal activity include imipenem, aztreonam, ciprofloxacin and aminoglycosides

  • Piperacillin and ceftazidime in combination with an aminoglycoside are preferred therapy; imipenem/cilastatin or ciprofloxacin should be reserved for infections resistant to beta-lactams


P aeruginosa preferred therapy
P. aeruginosa – preferred therapy aspiration pneumonia

  • The preferred therapy is piperacillin or ceftazidime in combination with aminoglycoside

  • Imipenem in combination with aminoglycoside should be reserved for resistant strains

  • Alternative agents: ciprofloxacin or aztreonam combined with aminoglycoside

  • Imipenem or ciprofloxacin used as monotherapy may lead to rapid development of resistance

  • Aminoglycosides are inadequate as single agents but are important to confer with synergistic killing


Staphylococcus aureus
Staphylococcus aureus aspiration pneumonia

  • Coagulase-positive Staph. aureus may cause both community- and hospital-acquired pneumonia

  • Staphylococci rarely cause CAP in previously healthy hosts; specific risk factors include:

    influenza, diabetes mellitus, iv drug abuse, iv lines and catheters, malignancies

  • Staph. aureus accounts for 15-30% of nosocomial pneumonia; these infections are often polymicrobial

  • 15-40% of nosocomial isolates are methicillin-resistant (MRSA); risk factors for acquisition of MRSA include: prior antibiotic use, prior nasal carriage, transmission from medical personnel, trauma, diabetes, renal failure, burns and use of corticosteroids

  • Prognosis for pneumonia depends on the severity and extend of comorbidities: mortality rates for pneumonia caused by methicillin-sensitive Staph. aureus range from 5 to 15%, in patients with MRSA may exceed 40%


Common complications of staphylococcal pneumonia
Common complications of staphylococcal pneumonia aspiration pneumonia

  • Empyema

  • Pyopneumothorax

  • Pneumatoceles

  • Bronchopleural fistula

  • Septic lesions in other organs

  • Metastatic abscesses in soft tissues


Staph aureus antimicrobial susceptibility
Staph. aureus – antimicrobial susceptibility aspiration pneumonia

  • Most isolates are resistant to penicillin and ampicillin, but are susceptible to antistaphylococcal penicillins: oxacillin, nafcillin, cloxacillin and cefazolin

  • Ceftazidime has only modest activity against staphylococci

  • MRSA is resistant to all beta-lactams

  • The antipseudomonal penicillins and imipenem/cilastin are active against methicillin-sensitive strains

  • Clindamycin, fluoroquinolones or TMP/SMX may be active against methicillin-sensitive or methicillin-resistant strains, but this is variable


Methicillin resistant staph aureus antimicrobial susceptibility
Methicillin-resistant Staph. aureus – aspiration pneumoniaantimicrobial susceptibility

  • Methicillin resistance results from alterations of PBPs, which also confer resistance to cephalosporins

  • MRSA strains are commonly resistant to other classes of antibiotics: erythromycin, clindamycin, tetracycline, aminoglycosides

  • Vancomycin is highly active against MRSA strains and is the drug of choice; teicoplanin has similar activity, less toxicity and a longer half-life

  • Clindamycin, quinolones, TMP/SMX may be used to treat some strains of MRSA


Staph aureus preferred therapy
Staph. aureus –preferred therapy aspiration pneumonia

Methicillin-susceptible Staph. aureus:

  • Preferred therapy

    -oxacillin or cloxacillin only for monomicrobial infections caused by methicillin-susceptible strains

    -vancomycin uniformly active for both methicillin-susceptible and resistant strains

  • Alternative agents:

    cefazolin, clindamycin, imipenem

    Methicillin-resistant Staph. aureus:

  • Preferred therapy: vancomycin

  • Alternatively for patients intolerant of vancomycin:

    clindamycin, imipenem, TMP/SMX


Empiric therapy for nosocomial pneumonia
Empiric therapy for nosocomial pneumonia aspiration pneumonia

  • Monotherapy with broad-spectrum beta-lactams

    - Monotherapy with ceftazidime, cefoperazone or imipenem/cilastin is associated with favorable response in 65-88% of cases of nosocomial pneumonia

  • Alternative agents: antipseudomonal penicillins/ beta-lactamase inhibitors, imipenem/ cilastin

  • In nosocomial pneumonias when Pseudomonas aeruginosa, Acinetobacter or Serratia is a causative agent, monotherapy is associated with high rate of clinical and bacteriologic failure and is not recommended

  • Monotherapy with beta-lactam may be adequate for nosocomial pneumonia caused by E. coli, Klebsiella and Proteus

  • Combination of beta-lactams with aminoglycosides limits the emergence of antimicrobial resistance and ensures synergistic microbicidal activity


Pulmonary complications of hiv infection
Pulmonary complications of HIV infection aspiration pneumonia

  • Viral

    CMV, RSV, HSV, Parainfluenza, Influenza, Adenovirus

  • Bacterial

    Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Mycobacterium tuberculosis, Mycobacterium avium-intracellulare complex

  • Fungal

    Pneumocystis carinii, Candida, Aspergillus, Histoplasma, Cryptococcus, Coccidioides


Conditions leading to or mimicking pneumonia
Conditions leading to or mimicking pneumonia aspiration pneumonia

  • Aspiration syndromes

  • Inhalation of toxic fumes, burn injuries

  • Radiation injury

  • Drug-induced pulmonary disease

  • Alveolitis (hypersensitivity pneumonitis)

  • ARDS

  • Haemosiderosis and pulmonary haemorrhage

  • Prominent or persistent thymus beyond the age of 4 yrs

  • Congenital abnormalities

  • Bronchiolitis obliterans organizing pneumonia

  • Connective tissue diseases, granulomatous vasculitides

  • Pulmonary embolism

  • Pulmonary edema

  • Pulmonary neoplasms



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