Transcript Slajd 1 - Announcements: Poznan University of Medical

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
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)
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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)
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Lower respiratory tract infections
epidemiological data
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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
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
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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
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, hospitalacquired (nosocomial) pneumonia
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Community-acquired pneumonia
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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
Etiology of pneumonias
Community- Hospitalacquired
acquired
Strep. pneumoniae
Staph. aureus
H. influenzae
P. aeruginosa
Legionella sp.
M. pneumoniae
Ch. pneumoniae
Enterobacteriaceae
Anaerobic
30-70%
3-9%
8-20%
<2%
2-8%
2-15%
2-6%
4-12%
5-15%
3-8%
10-20%
1-8%
12-20%
<4%
rare
rare
30-50%
2-20%
Pneumonia of unknown etiology
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The newborn
Group B Streptococcus
Escherichia coli
Staphylococci
Listeria monocytogenes
Tuberculosis
Herpes simplex virus
TORCH agents
Pneumonia of unknown etiology
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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 etiology
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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 etiology
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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
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
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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)
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Staphylococci lead to necrotizing pneumonia and
common complications are: pyopneumothorax,
empyema, bronchopleural fistula, pneumatocele
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Therapy: always should be initiated with
penicillinase-resistant antibiotic
– 90% of staphylococci are resistant to
penicillin
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 Vancomycinresistant strains (Scandinavia, Japan, USA)
Rifampicin
 Imipenem
 Ciprofloxacin and other quinolones
 Trimethoprime-sulfamethoxazole
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Pneumococcal pneumonia
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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
Relationship between gastro-esophageal
reflux, dysfunctional swallowing, therapy
of respiratory disorders (theophylline, oral
beta-agonists) and aspiration pneumonia
 Superinfection with mouth florapredominantly 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
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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
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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
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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
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Pulmonary aspergillosis
Depending on the type of exposure and
condition of the host, different pulmonary
manifestation may ensue:
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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 aspergillosis
Treatment:
 Aerosolized amphotericin B or direct
instillation of the drug into the trachea
(Liposomal amphotericin Ambisome)
 Systemic amphotericin B iv or 5fluorocytosine
 Itraconazole with systemic steroids
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
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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 28% of CAP, but severe pneumonias are
rare with this pathogen
 Haemophilus influenzae accounts for 518% of CAP in adults with high rate in
smokers with COPD
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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 12% of CAP; more common in patients with
COPD
 Viruses are implicated in 5-15% of CAP;
most cases occur in winter months
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Streptococcus pneumoniae
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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 antibioticresistant strains are increasing and threaten the
future efficacy of antibiotics
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 1540% of pneumococci exhibit high-grade
resistance to penicillin; in the USA highgrade resistance has only recently
emerged and is estimated for 1-7%
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S. pneumoniae - antimicrobial resistance
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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
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)
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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
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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 commensalcolonizes 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
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H. influenzae - antimicrobial susceptibility
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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
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 betalactamase negative strains)
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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
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M. catarrhalis - antimicrobial susceptibility
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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
1st choice therapy
-cefuroxime
-ampicillin/sulbactam or
amoxicillin/clavulanate
 Alternative agents
-tetracycline
-TMP/SMX
-macrolide
-fluoroquinolones
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Atypical pneumonias
Mycoplasma pneumoniae
 Chlamydia pneumoniae
 Legionella pneumophila
 Viruses
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Other
 Pneumocystis carinii
 Chlamydia trachomatis
 Rickettsiae
 Fungi
Respiratory manifestations of mycoplasmal
infection
Pharyngitis
 Sinusitis
 Myringitis
 Otitis media
 Croup
 Bronchitis
 Bronchiolitis
 Bronchopneumonia
 Pneumonia with pleural effusion
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Mycoplasma pneumoniae
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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
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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
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)
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Nonrespiratory manifestations of
mycoplasmal infection
Skin:
-erythema multiforme
-maculopapular rush
-Stevens-Johnson syndrome
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CNS:
-meningoencephalitis
-aseptic meningitis
-transverse myelitis
-cerebellar ataxia
-Guillain-Barre syndrome
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Blood:
-hemolytic anaemia
-thrombocytopenia
-coagulation defects
Nonrespiratory manifestations of
mycoplasmal infection
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Gastrointestinal tract
-hepatitis
-pancreatitis
-protein-losing hypertrophic gastropathy
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Cardiovascular system
-myocarditis
-pericarditis
-cardiac dilatation with heart failure
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Joints
-monoarticular transient arthritis
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 5080% 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
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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 1421 days
 Alternative agents:
-oral macrolides
-fluoroquinolones
 Empiric therapy with tetracyclines should
be considered for patients with protracted
bronchitis or CAP refractory to betalactams
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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
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Legionella pneumophila – preferred therapy
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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
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
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Empiric (initial) therapy for CAP
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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, noncompliance
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 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
Empiric (initial) therapy for CAP
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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
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
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Antibacterial susceptibility of anaerobes
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Bacteroides fragilis and virtually all anaerobes
are susceptible to: imipenem, metronidazole,
extended-spectrum penicillins with betalactamase 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
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Community-acquired aspiration pneumonia or
lung abscess in patients without serious
associated diseases can be treated with narrowspectrum 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
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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 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
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Acinetobacter – preferred therapy
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
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Klebsiella pneumoniae
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
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Klebsiella pneumoniae producing plasmidmediated extended spectrum beta-lactamases
that confer resistance to ceftazidime have been
isolated in Europe and in the USA
Klebsiella pneumoniae – preferred therapy
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 betalactamase producing K. pneumoniae
correlate with extensive use of
cephalosporin monotherapy and may be
curtailed by switching to extendedspectrum penicillins or imipenem/cilastatin

Pseudomonas aeruginosa
P. aeruginosa accounts for 15-20% of
nosocomial pneumonias; the rates are
even higher in ventilated ICU patients (2030%)
 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 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
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
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Staphylococcus aureus
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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 methicillinresistant (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
Empyema
 Pyopneumothorax
 Pneumatoceles
 Bronchopleural fistula
 Septic lesions in other organs
 Metastatic abscesses in soft tissues

Staph. aureus – antimicrobial susceptibility
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 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
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
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
Viral
CMV, RSV, HSV, Parainfluenza, Influenza,
Adenovirus
 Bacterial
Streptococcus pneumoniae, Haemophilus
influenzae, Staphylococcus aureus,
Escherichia coli, Klebsiella pneumoniae,
Pseudomonas aeruginosa, Mycobacterium
tuberculosis, Mycobacterium aviumintracellulare complex
 Fungal
Pneumocystis carinii, Candida, Aspergillus,
Histoplasma, Cryptococcus, Coccidioides

Conditions leading to or mimicking pneumonia
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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
 Thank
you for your
attention