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)
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
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
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, hospital acquired (nosocomial) 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
Etiology of pneumonias
Strep. pneumoniae Staph. aureus H. influenzae P. aeruginosa Legionella sp.
M. pneumoniae Ch. pneumoniae Enterobacteriaceae Anaerobic Community acquired 30-70% 3-9% 8-20% <2% 2-8% 2-15% 2-6% 4-12% 5-15% Hospital acquired 3-8% 10-20% 1-8% 12-20% <4% rare rare 30-50% 2-20%
Pneumonia of unknown etiology
The newborn Group B Streptococcus Escherichia coli Staphylococci Listeria monocytogenes Tuberculosis Herpes simplex virus TORCH agents
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 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 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
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
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 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
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 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
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 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
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 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
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
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 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
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
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 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
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 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
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
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 beta lactamase negative strains)
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
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
Atypical pneumonias
Mycoplasma pneumoniae Chlamydia pneumoniae Legionella pneumophila Viruses 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
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
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)
Nonrespiratory manifestations of
Skin:
mycoplasmal infection
-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 infection
Gastrointestinal tract -hepatitis -pancreatitis -protein-losing hypertrophic gastropathy Cardiovascular system -myocarditis -pericarditis -cardiac dilatation with heart failure 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 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
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 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
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
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
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
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
Antibacterial susceptibility of anaerobes
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
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
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
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
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 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
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
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 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
Staphylococcus aureus
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
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 avium intracellulare complex Fungal Pneumocystis carinii, Candida, Aspergillus, Histoplasma, Cryptococcus, Coccidioides
Conditions leading to or mimicking 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