Acute infections Acute infections of the lower airways of the lower airways

in childrenin childrenAleksandra Szczawińska-PopłonykAleksandra Szczawińska-Popłonyk

Department of Pediatric Pneumonology, Department of Pediatric Pneumonology, Allergology and Clinical ImmunologyAllergology and Clinical Immunology

Karol Marcinkowski University Karol Marcinkowski University

of Medical Sciences of Medical Sciences

PoznańPoznań

InfectionInfection The specific and nonspecific defense The specific and nonspecific defense

mechanisms keep the bronchial tree mechanisms keep the bronchial tree sterile beyond the first bronchial sterile beyond the first bronchial bifurcationbifurcation

A certain amount of microorganisms must A certain amount of microorganisms must both avoid mucociliary clearance and both avoid mucociliary clearance and resist destruction by the humoral or resist destruction by the humoral or cellular defense mechanismscellular defense mechanisms

Large amounts of the organisms reach the Large amounts of the organisms reach the LRT through aspirationLRT through aspiration

The invading microorganisms have The invading microorganisms have particular characteristics- eg. a marked particular characteristics- eg. a marked capacity to adhere to epithelium (Influenza capacity to adhere to epithelium (Influenza virus, other viruses, Mycoplasma virus, other viruses, Mycoplasma pneumoniae, Bordetella pertussis)pneumoniae, Bordetella pertussis)

InfectionInfection Microorganisms avoid immune defence Microorganisms avoid immune defence

system:system:- Encapsulated bacteria (pneumococci, Encapsulated bacteria (pneumococci,

Klebsiella pneumoniae, Haemophilus Klebsiella pneumoniae, Haemophilus influenzae) are resistant to phagocytosis influenzae) are resistant to phagocytosis

- Some bacteria are resistant to Some bacteria are resistant to mechanisms of intracellular killing, other mechanisms of intracellular killing, other (Haemophilus influenzae, Neisseria, (Haemophilus influenzae, Neisseria, streptococci) produce IgA protease, which streptococci) produce IgA protease, which degrades IgA antibodiesdegrades IgA antibodies

There is a defect in mucociliary clearance There is a defect in mucociliary clearance by the inhalation of number of irritants by the inhalation of number of irritants (industrial pollution, tobacco smoke), (industrial pollution, tobacco smoke), microorganisms (viruses: Influenza, microorganisms (viruses: Influenza, Morbilli, bacteria: B.pertussis, Morbilli, bacteria: B.pertussis, H.influenzae)H.influenzae)

Lower respiratory tract infectionsLower respiratory tract infectionsepidemiological dataepidemiological data

A global health problem: four milion A global health problem: four milion children die each year for respiratory tract children die each year for respiratory tract infectionsinfections(98-99% in the developing countries)(98-99% in the developing countries)

Children aged 1-5 yrs in an urban area have 6-8 Children aged 1-5 yrs in an urban area have 6-8 episodes of RTI each year, in the country 3-5episodes of RTI each year, in the country 3-5

Only a small proportion of these infections Only a small proportion of these infections concern the lower respiratory tract;concern the lower respiratory tract;the difference between industrialized and the difference between industrialized and developing countries doesn’t concern the developing countries doesn’t concern the incidence but the severity of infectionsincidence but the severity of infections

Even if only in exceptional cases infections lead Even if only in exceptional cases infections lead to serious complications, they cause suffering and to serious complications, they cause suffering and impairement of the individual child impairement of the individual child

Lower respiratory tract infectionsLower respiratory tract infectionssocial problemssocial problems

Respiratory tract infections account for a Respiratory tract infections account for a large proportion of physician consultationslarge proportion of physician consultations

The significant proportion of the resources The significant proportion of the resources of out-patient care expand on RTIof out-patient care expand on RTI

Sickness absence and medicine cost Sickness absence and medicine cost society a lot of money: society a lot of money:

57% of acute illnesses57% of acute illnesses

50% number of days restricted activity50% number of days restricted activity

42% of the lost working days42% of the lost working days

60% of the lost school days 60% of the lost school days

PneumoniaPneumonia DefinitionDefinitionPneumonia is defined as inflammation in the Pneumonia is defined as inflammation in the

lung parenchyma, the portion distal to the lung parenchyma, the portion distal to the terminal bronchioles and comprising the terminal bronchioles and comprising the respiratory bronchioles, alveolar ducts, respiratory bronchioles, alveolar ducts, alveolar sacs and alveolialveolar sacs and alveoli

PathogenesisPathogenesisOrganisms reach the lung to cause pneumonia by Organisms reach the lung to cause pneumonia by

one of four routes:one of four routes:- - inhalation of microbes present in the airinhalation of microbes present in the air- aspiration of organisms from the naso- or - aspiration of organisms from the naso- or oropharynx (the most common cause of bacterial oropharynx (the most common cause of bacterial pneumonia)pneumonia)- hematogenous spread from a distant focus of - hematogenous spread from a distant focus of infectioninfection- direct spread from a contiguous site of infection - direct spread from a contiguous site of infection or penetrating injury or penetrating injury

Pneumonia - classificationPneumonia - classification

By anatomic distribution: By anatomic distribution: lobar, lobular, segmental, lobar, lobular, segmental, bronchopneumoniabronchopneumonia

By dominant histological lesions:By dominant histological lesions:alveolar exudation, involvement of alveolar exudation, involvement of interstitial tissue or bothinterstitial tissue or both

By etiological factor:By etiological factor:infections (viral, bacterial, mycotic, other), infections (viral, bacterial, mycotic, other), aspiration, drug / radiation pneumonia, aspiration, drug / radiation pneumonia, Loeffler syndrome, hypersensitivity Loeffler syndrome, hypersensitivity pneumonitispneumonitis

By the place where infection is acquired:By the place where infection is acquired:community-acquired pneumonia, hospital-community-acquired pneumonia, hospital-acquired (nosocomial) pneumoniaacquired (nosocomial) pneumonia

Community-acquired pneumoniaCommunity-acquired pneumonia In the United States CAP remains an important In the United States CAP remains an important

cause of morbidity and mortality:cause of morbidity and mortality:-more than 3 million cases occur annually-more than 3 million cases occur annually-results in more than 900 000 hospitalizations -results in more than 900 000 hospitalizations and more than 60 000 deathsand more than 60 000 deaths

Only 20-30% of CAP occur in young, previously Only 20-30% of CAP occur in young, previously healthy individuals without comorbiditieshealthy individuals without comorbidities

Mortality is high (15-30%) in patients with Mortality is high (15-30%) in patients with predisposing risk factors including:predisposing risk factors including:-old age-old age-history of cigarette smoking and COPD-history of cigarette smoking and COPD-chronic ethanol abuse-chronic ethanol abuse-cardiac disease-cardiac disease-diabetes mellitus-diabetes mellitus-malignancy-malignancy-renal insufficiency-renal insufficiency-corticosteroid or immunosuppressive therapy-corticosteroid or immunosuppressive therapy

Etiology of pneumoniasEtiology of pneumonias

Community-Community-acquiredacquired

Hospital-Hospital-acquiredacquired

Strep. pneumoniaeStrep. pneumoniae

Staph. aureusStaph. aureus

H. influenzaeH. influenzae

P. aeruginosaP. aeruginosa

Legionella sp.Legionella sp.

M. pneumoniaeM. pneumoniae

Ch. pneumoniaeCh. pneumoniae

EnterobacteriaceaeEnterobacteriaceae

AnaerobicAnaerobic

30-70%30-70%

3-9%3-9%

8-20%8-20%

<2%<2%

2-8%2-8%

2-15%2-15%

2-6%2-6%

4-12%4-12%

5-15%5-15%

3-8%3-8%

10-20%10-20%

1-8%1-8%

12-20%12-20%

<4%<4%

rarerare

rarerare

30-50%30-50%

2-20%2-20%

Pneumonia of unknown etiologyPneumonia of unknown etiology

The newbornThe newborn

Group B StreptococcusGroup B Streptococcus

Escherichia coliEscherichia coli

StaphylococciStaphylococci

Listeria monocytogenesListeria monocytogenes

TuberculosisTuberculosis

Herpes simplex virusHerpes simplex virus

TORCH agentsTORCH agents

Pneumonia of unknown etiologyPneumonia of unknown etiology Infants 1-3 months of ageInfants 1-3 months of age

Group B StreptococcusGroup B StreptococcusEscherichia coliEscherichia coliHaemophilus influenzae type bHaemophilus influenzae type bStreptococcus pneumoniaeStreptococcus pneumoniaeChlamydia trachomatisChlamydia trachomatisUreaplasma urealyticumUreaplasma urealyticumPneumocystis cariniiPneumocystis cariniiCytomegalovirusCytomegalovirusRespiratory syncytial virusRespiratory syncytial virusParainfluenzae virusParainfluenzae virusAdenovirusAdenovirus

Pneumonia of unknown etiologyPneumonia of unknown etiology

Children 3 months to 5 years of ageChildren 3 months to 5 years of age

-respiratory viruses 75%-respiratory viruses 75%

Respiratory syncytial virusRespiratory syncytial virus

AdenovirusAdenovirus

Parainfluenzae virusParainfluenzae virus

Influenzae virusInfluenzae virus

Streptococcus pneumoniaeStreptococcus pneumoniae

Haemophilus influenzae type bHaemophilus influenzae type b

Klebsiella pneumoniaeKlebsiella pneumoniae

Staphylococcus aureusStaphylococcus aureus

Pneumonia of unknown etiologyPneumonia of unknown etiology

Children 6 years of age to adultsChildren 6 years of age to adultsMycoplasma pneumoniaeMycoplasma pneumoniaeRespiratory viruses: Parainfluenzae virus, Respiratory viruses: Parainfluenzae virus, RSV, AdenovirusRSV, AdenovirusInfluenzae virusInfluenzae virusStreptococcus pneumoniaeStreptococcus pneumoniaeStaphylococcus aureusStaphylococcus aureusHaemophilus influenzaeHaemophilus influenzaeKlebsiella pneumoniaeKlebsiella pneumoniaeChlamydia pneumoniaeChlamydia pneumoniae

Mycoplasmal respiratory infectionMycoplasmal respiratory infection

The most commonly recognized clinical syndrome The most commonly recognized clinical syndrome following Mycoplasma pneumoniae infection is following Mycoplasma pneumoniae infection is bronchopneumoniabronchopneumonia

Additional respiratory illnesses include pharyngitis, Additional respiratory illnesses include pharyngitis, sinusitis, croup, bronchitis, bronchiolitissinusitis, croup, bronchitis, bronchiolitis

Superinfection with typical bacteria is infrequentSuperinfection with typical bacteria is infrequent Treatment: because of the absence of the cell Treatment: because of the absence of the cell

wall, Mycoplasma is resistant to beta-lactams, but wall, Mycoplasma is resistant to beta-lactams, but is exceptionally sensitive to: is exceptionally sensitive to:

macrolids (Erythromycin, Clarithromycin, macrolids (Erythromycin, Clarithromycin, Roxithromycin, Azithromycin)Roxithromycin, Azithromycin)

tetracyclines – over the age of 8 yrtetracyclines – over the age of 8 yr quinolones – over the age of 16 yrquinolones – over the age of 16 yr

Staphylococcal respiratory infectionsStaphylococcal respiratory infections

Upper airway infection due to Staph. Upper airway infection due to Staph. aureus: pharyngitis, tonsillitis, otitis media, aureus: pharyngitis, tonsillitis, otitis media, sinusitis, tracheitis complicating viral sinusitis, tracheitis complicating viral croupcroup

Pneumonia may be primary Pneumonia may be primary (hematogenous) or secondary after viral (hematogenous) or secondary after viral infection (influenza)infection (influenza)

Staphylococci lead to necrotizing pneumonia and Staphylococci lead to necrotizing pneumonia and common complications are: pyopneumothorax, common complications are: pyopneumothorax, empyema, bronchopleural fistula, pneumatoceleempyema, bronchopleural fistula, pneumatocele

Therapy: always should be initiated with Therapy: always should be initiated with penicillinase-resistant antibiotic penicillinase-resistant antibiotic – – 90% of staphylococci are resistant to 90% of staphylococci are resistant to penicillinpenicillin

Staphylococcal respiratory infectionsStaphylococcal respiratory infections

Recommended antibiotics:Recommended antibiotics: Methicillin, nafcillin, oxacillinMethicillin, nafcillin, oxacillin Clindamycin, lincomycinClindamycin, lincomycin Vancomycin and its new generation Vancomycin and its new generation

derivative teikoplanine when bacteria are derivative teikoplanine when bacteria are resistant to semisynthetic penicillins resistant to semisynthetic penicillins (MRSA)(MRSA)Reports of increasing incidence of Vancomycin-Reports of increasing incidence of Vancomycin-resistant strains (Scandinavia, Japan, USA)resistant strains (Scandinavia, Japan, USA)

RifampicinRifampicin ImipenemImipenem Ciprofloxacin and other quinolonesCiprofloxacin and other quinolones Trimethoprime-sulfamethoxazoleTrimethoprime-sulfamethoxazole

Pneumococcal pneumoniaPneumococcal pneumonia

Streptococcus pneumoniae is the most common Streptococcus pneumoniae is the most common cause of bacterial infections of the lungscause of bacterial infections of the lungsalthough the incidence of pneumococcal although the incidence of pneumococcal pneumonia has declined over the last decadespneumonia has declined over the last decades

In older children and adults clinical In older children and adults clinical manifestations are typical: manifestations are typical: shaking chills, high fever, cough, chest pain, and shaking chills, high fever, cough, chest pain, and development of lobar pneumoniadevelopment of lobar pneumoniaPleural effusion and empyema are typical Pleural effusion and empyema are typical complicationscomplications

Therapy: drug of choice is penicillin in the dose Therapy: drug of choice is penicillin in the dose 100 000 units/kg/24hr parenterally for 2-3 weeks100 000 units/kg/24hr parenterally for 2-3 weeks

Aspiration pneumoniaAspiration pneumonia

Relationship between gastro-esophageal Relationship between gastro-esophageal reflux, dysfunctional swallowing, therapy reflux, dysfunctional swallowing, therapy of respiratory disorders (theophylline, oral of respiratory disorders (theophylline, oral beta-agonists) and aspiration pneumoniabeta-agonists) and aspiration pneumonia

Superinfection with mouth flora- Superinfection with mouth flora- predominantly anaerobes occurs in predominantly anaerobes occurs in previously healthy non-hospitalized previously healthy non-hospitalized patientspatientsTreatment: Clindamycin, penicillinsTreatment: Clindamycin, penicillins

Chronically ill hospitalized patients may be Chronically ill hospitalized patients may be infected with Gram-negative flora infected with Gram-negative flora (Pseudomonas, Klebsiella, E.coli); in these (Pseudomonas, Klebsiella, E.coli); in these patients additional coverage with patients additional coverage with aminoglycosides, imipenem or both is aminoglycosides, imipenem or both is indicated indicated

Pneumocystis carinii pneumoniaPneumocystis carinii pneumonia Epidemic form in infants between 3 and 6 moEpidemic form in infants between 3 and 6 mo Sporadic form accounts for majority of cases; Sporadic form accounts for majority of cases;

occurs in children and adults with occurs in children and adults with

primary (SCID, XLA) or secondary (AIDS) primary (SCID, XLA) or secondary (AIDS) immunodeficiencies, malignancies (leukemia), immunodeficiencies, malignancies (leukemia), organ transplant receipientsorgan transplant receipients

In immunocompromised hosts PCP, if untreated, is fatal In immunocompromised hosts PCP, if untreated, is fatal within 3-4 weekswithin 3-4 weeks

Therapy: Trimethoprim (15-20 mg/kg/24hr) + Therapy: Trimethoprim (15-20 mg/kg/24hr) + sulfamethoxazole (75-100 mg/kg/24hr) iv for 2-sulfamethoxazole (75-100 mg/kg/24hr) iv for 2-4 weeks4 weeks

For patients who fail to respond to TP-SMX: For patients who fail to respond to TP-SMX: Pentamidine isethionate 4 mg/kg/24hr 1x dailyPentamidine isethionate 4 mg/kg/24hr 1x daily

Pneumocystis carinii pneumoniaPneumocystis carinii pneumonia

Alternative treatment of PCP:Alternative treatment of PCP:

Atovaquone and trimetexate glucuronateAtovaquone and trimetexate glucuronate

Trimethoprime and dapsoneTrimethoprime and dapsone

Clindamycin and primaquineClindamycin and primaquine Chemoprophylaxis:Chemoprophylaxis:

Trimethoprim 5 mg/kg/24hr + Trimethoprim 5 mg/kg/24hr + sulfamethoxazole 25 mg/kg/24hrsulfamethoxazole 25 mg/kg/24hr

Pentamidine by aerosolPentamidine by aerosol

Dapsone and pyrimethamineDapsone and pyrimethamine

Pulmonary aspergillosisPulmonary aspergillosis

Depending on the type of exposure and Depending on the type of exposure and condition of the host, different pulmonary condition of the host, different pulmonary manifestation may ensue:manifestation may ensue:

Allergic bronchopulmonary aspergillosis without Allergic bronchopulmonary aspergillosis without infection or tissue invasion (the most common infection or tissue invasion (the most common aspergillus-related disease), most cases in aspergillus-related disease), most cases in patients with chronic pulmonary disease (asthma, patients with chronic pulmonary disease (asthma, CF)CF)

Allergic alveolitis in the case of ongoing exposure Allergic alveolitis in the case of ongoing exposure in allergic patientsin allergic patients

Aspergillus pneumonia if the colonisation occurs Aspergillus pneumonia if the colonisation occurs and infection developsand infection develops

Invasive disease or necrotizing pneumonia in Invasive disease or necrotizing pneumonia in immunodeficient patientsimmunodeficient patients

Aspergillus mycetoma resulting from infection of Aspergillus mycetoma resulting from infection of an extant cavityan extant cavity

Pulmonary aspergillosisPulmonary aspergillosis

Treatment:Treatment: Aerosolized amphotericin B or direct Aerosolized amphotericin B or direct

instillation of the drug into the trachea instillation of the drug into the trachea

(Liposomal amphotericin Ambisome)(Liposomal amphotericin Ambisome) Systemic amphotericin B iv or 5-Systemic amphotericin B iv or 5-

fluorocytosinefluorocytosine Itraconazole with systemic steroidsItraconazole with systemic steroids

Recurrent bacterial pneumoniasRecurrent bacterial pneumonias

Primary or secondary immunodeficiencyPrimary or secondary immunodeficiency Cystic fibrosisCystic fibrosis Ciliary dyskinesiaCiliary dyskinesia Tracheo-esophageal fistulaTracheo-esophageal fistula Cleft palateCleft palate Congenital bronchiectasesCongenital bronchiectases Gastro-esophageal reflux and aspiration Gastro-esophageal reflux and aspiration

syndromessyndromes Increased pulmonary blood flowIncreased pulmonary blood flow Foreign body aspirationForeign body aspiration

Microbiologic implicationsMicrobiologic implications Streptococcus pneumoniae is the most Streptococcus pneumoniae is the most

important bacterial pathogen in all age important bacterial pathogen in all age groups, accounting for 30-70% of CAPgroups, accounting for 30-70% of CAP

Mycoplasma pneumoniae is the causative Mycoplasma pneumoniae is the causative agent in 20-30% of adults younger than agent in 20-30% of adults younger than age 35, but accounts for only 1-9% of CAP age 35, but accounts for only 1-9% of CAP in older adultsin older adults

Legionella pneumophila accounts for only Legionella pneumophila accounts for only 2-10% of CAP, but is second to 2-10% of CAP, but is second to pneumococcus as a cause of death from pneumococcus as a cause of death from CAPCAP

Chlamydia pneumoniae is implicated in 2-Chlamydia pneumoniae is implicated in 2-8% of CAP, but severe pneumonias are 8% of CAP, but severe pneumonias are rare with this pathogenrare with this pathogen

Haemophilus influenzae accounts for 5-Haemophilus influenzae accounts for 5-18% of CAP in adults with high rate in 18% of CAP in adults with high rate in smokers with COPDsmokers with COPD

Microbiologic implicationsMicrobiologic implications

Staphylococcus aureus accounts for 3-8% Staphylococcus aureus accounts for 3-8% of CAP in adults, primarily in patients with of CAP in adults, primarily in patients with risk factors and following influenzarisk factors and following influenza

Enteric Gram(-) rods, predominantly Enteric Gram(-) rods, predominantly Enterobacteriaceae account for 3-8% of Enterobacteriaceae account for 3-8% of CAP; only in patients with comorbiditiesCAP; only in patients with comorbidities

Moraxella catarrhalis accounts for only 1-Moraxella catarrhalis accounts for only 1-2% of CAP; more common in patients with 2% of CAP; more common in patients with COPDCOPD

Viruses are implicated in 5-15% of CAP; Viruses are implicated in 5-15% of CAP; most cases occur in winter monthsmost cases occur in winter months

Streptococcus pneumoniaeStreptococcus pneumoniae

S. pneumoniae accounts for 30-70% of CAP and S. pneumoniae accounts for 30-70% of CAP and has been associated with most fatalitieshas been associated with most fatalities

S. pneumoniae can affect previously healthy S. pneumoniae can affect previously healthy individuals, but has a predilection for the elderly individuals, but has a predilection for the elderly and for patients with preexisting diseaseand for patients with preexisting disease

Outbreaks of severe, invasive infections may Outbreaks of severe, invasive infections may occur in nursing homes, chronic care facilitiesoccur in nursing homes, chronic care facilities

S. pneumoniae is the leading cause of pneumonia S. pneumoniae is the leading cause of pneumonia in all age groups;in all age groups;empiric therapy for CAP should always cover empiric therapy for CAP should always cover S. pneumoniaeS. pneumoniae

Penicillin-resistant and often multiply antibiotic-Penicillin-resistant and often multiply antibiotic-resistant strains are increasing and threaten the resistant strains are increasing and threaten the future efficacy of antibioticsfuture efficacy of antibiotics

S. pneumoniae - antimicrobial resistanceS. pneumoniae - antimicrobial resistance

Resistance to penicillins, tetracyclines, Resistance to penicillins, tetracyclines, macrolides, macrolides, trimethoprim/sulfamethoxazole, trimethoprim/sulfamethoxazole, cephalosporins has increased dramatically cephalosporins has increased dramatically over the past three decadesover the past three decades

Resistance to antibiotics reflects the Resistance to antibiotics reflects the pattern of antibiotic usepattern of antibiotic use

Penicillin resistance is chromosomally Penicillin resistance is chromosomally mediated and results from alterations in mediated and results from alterations in penicillin-binding proteinspenicillin-binding proteins

In France, Spain and Eastern Europe 15-In France, Spain and Eastern Europe 15-40% of pneumococci exhibit high-grade 40% of pneumococci exhibit high-grade resistance to penicillin; in the USA high-resistance to penicillin; in the USA high-grade resistance has only recently grade resistance has only recently emerged and is estimated for 1-7%emerged and is estimated for 1-7%

S. pneumoniae - antimicrobial resistanceS. pneumoniae - antimicrobial resistance Risk factors for penicillin resistance: age under 6 yrs, Risk factors for penicillin resistance: age under 6 yrs,

prior use of beta-lactam antibiotics and nosocomial prior use of beta-lactam antibiotics and nosocomial acquisitionacquisition

Penicillin resistant strains are often resistant to Penicillin resistant strains are often resistant to tetracyclines, erythromycin and TMP/SMXtetracyclines, erythromycin and TMP/SMX

Resistance to quinolones is unrelated to penicillin Resistance to quinolones is unrelated to penicillin susceptibilitysusceptibility

Erythromycin resistant strains are resistant to other Erythromycin resistant strains are resistant to other macrolides and are usually resistant to penicilline and macrolides and are usually resistant to penicilline and tetracyclinetetracycline

Cephalosporin-resistant strains have also increasedCephalosporin-resistant strains have also increased Most penicillin- and erythromycin resistant strains Most penicillin- and erythromycin resistant strains

remain susceptible to imipenem, cefotaxime amd remain susceptible to imipenem, cefotaxime amd ceftriaxoneceftriaxone

In the USA 6-30% of pneumococci are resistant to In the USA 6-30% of pneumococci are resistant to tetracyclinetetracycline

All pneumococci are susceptible to vancomycin, All pneumococci are susceptible to vancomycin, irresspective of susceptibilities to other class of irresspective of susceptibilities to other class of antibiotics antibiotics

S. pneumoniae - preferred therapyS. pneumoniae - preferred therapy For susceptible strains or in areas where For susceptible strains or in areas where

rates of of penicillin-resistance are low:rates of of penicillin-resistance are low:-Penicillin G 4-10 million units iv-Penicillin G 4-10 million units iv-Penicillin V 500 mg q.i.d. orally-Penicillin V 500 mg q.i.d. orally

As empiric therapy when penicillin As empiric therapy when penicillin resistance is suspected:resistance is suspected:-Cefotaxime 1g q8hr or ceftriaxone 1g -Cefotaxime 1g q8hr or ceftriaxone 1g q24hrq24hr

For strains resistant to penicillin and For strains resistant to penicillin and cephalosporins:cephalosporins:-Vancomycin (100% active)-Vancomycin (100% active)-Imipenem/cilastin (active against more -Imipenem/cilastin (active against more than 90% of isolates)than 90% of isolates)

S. pneumoniae - preferred therapyS. pneumoniae - preferred therapy

Alternative agents:Alternative agents:

-macrolide antibiotic (eg. erythomycin, -macrolide antibiotic (eg. erythomycin, clarithromycin, azithromycin)clarithromycin, azithromycin)

-beta-lactams and clindamycin are usually -beta-lactams and clindamycin are usually activeactive

-tetracyclines and TMP/SMX inconsistent -tetracyclines and TMP/SMX inconsistent

(6-30% are resistant)(6-30% are resistant) Penicillin G is less expensive and less toxic Penicillin G is less expensive and less toxic

than alternative agents and should be than alternative agents and should be used for susceptible strains used for susceptible strains

Haemophilus influenzaeHaemophilus influenzae

H. influenzae accounts for 5-18% of H. influenzae accounts for 5-18% of pneumonias, both community- and pneumonias, both community- and hospital-acquiredhospital-acquired

Both typeable (encapsulated, especially Both typeable (encapsulated, especially type b) and nontypeable type b) and nontypeable (nonencapsulated) strains can cause the (nonencapsulated) strains can cause the diseasedisease

H. influenzae is a common commensal-H. influenzae is a common commensal-colonizes the oropharynx in 20-40% of colonizes the oropharynx in 20-40% of healthy individualshealthy individuals

H. influenzae pneumonia and bronchitis H. influenzae pneumonia and bronchitis characteristically affect smokers, elderly characteristically affect smokers, elderly and debilitated patients, but may also and debilitated patients, but may also afect previously healthy individualsafect previously healthy individuals

H. influenzae - antimicrobial susceptibilityH. influenzae - antimicrobial susceptibility

Antimicrobial resistance has increased Antimicrobial resistance has increased dramatically in the past three decadesdramatically in the past three decades

By the early 1980s, beta-lactamase-producing By the early 1980s, beta-lactamase-producing ampicillin resistant strains emergedampicillin resistant strains emerged

Ist-generation cephalosporins and erythromycin Ist-generation cephalosporins and erythromycin are nor reliable – only 40-60% of strains are are nor reliable – only 40-60% of strains are susceptiblesusceptible

The activity of tetracyclines is modestThe activity of tetracyclines is modest More than 90% of strains are susceptible to More than 90% of strains are susceptible to

TMP/SMXTMP/SMX Virtually all isolates are susceptible to :Virtually all isolates are susceptible to :

ampicillin/sulbactam, cefuroxime, IIIrd-generation ampicillin/sulbactam, cefuroxime, IIIrd-generation cephalosporins, imipenem, fluoroquinolones, new cephalosporins, imipenem, fluoroquinolones, new macrolides, extended-spectrum penicillinsmacrolides, extended-spectrum penicillins

H. influenzae - preferred therapyH. influenzae - preferred therapy 1st choice agents1st choice agents

-ampicillin/sulbactam, cefuroxime or -ampicillin/sulbactam, cefuroxime or ceftriaxoneceftriaxone-oral agents for mild infections or following -oral agents for mild infections or following initial parenteral therapy: initial parenteral therapy: amoxicillin/clavulanate, cefuroxime axetil, amoxicillin/clavulanate, cefuroxime axetil, TMP/SMXTMP/SMX

Alternative agentsAlternative agents-TMP/SMX, fluoroquinolones -TMP/SMX, fluoroquinolones -azithromycin or clarithromycin (activity of -azithromycin or clarithromycin (activity of erythromycin is inconsistent)erythromycin is inconsistent)-ampicillin or amoxicillin (only for beta--ampicillin or amoxicillin (only for beta-lactamase negative strains)lactamase negative strains)

Moraxella catarrhalisMoraxella catarrhalis M. catarrhalis is part of normal flora of the M. catarrhalis is part of normal flora of the

upper respiratory tract and is an important upper respiratory tract and is an important pathogen in otitis media, sinusitis and pathogen in otitis media, sinusitis and acute exacerbations of chronic bronchitisacute exacerbations of chronic bronchitis

M. catarrhalis accounts for 1-3% of CAP; M. catarrhalis accounts for 1-3% of CAP; most frequently in the winter monthsmost frequently in the winter months

More than 80% of lower respiratory tract More than 80% of lower respiratory tract infections caused by M. catarrhalis occur infections caused by M. catarrhalis occur in patients with COPD or underlying in patients with COPD or underlying diseasesdiseases

Probably not important as a nosocomial Probably not important as a nosocomial pathogenpathogen

M. catarrhalis - antimicrobial susceptibilityM. catarrhalis - antimicrobial susceptibility

The first beta-lactamase(penicillinase)-producing The first beta-lactamase(penicillinase)-producing strains of M. catarrhalis were described in 1977; now strains of M. catarrhalis were described in 1977; now 50-85% of isolates are resistant to penicillin 50-85% of isolates are resistant to penicillin

Penicillins with beta-lactamase inhibitors, TMP/SMX, Penicillins with beta-lactamase inhibitors, TMP/SMX, macrolides, 2nd or 3rd generation cephalosporins, macrolides, 2nd or 3rd generation cephalosporins, tetracycline, fluoroquinolones are active against tetracycline, fluoroquinolones are active against beta-lactamase positive or negative strainsbeta-lactamase positive or negative strains

Beta-lactamase negative strains are susceptible to Beta-lactamase negative strains are susceptible to penicillin, ampicillin and beta-lactamspenicillin, ampicillin and beta-lactams

Beta-lactamase producing M. catarrhalis may confer Beta-lactamase producing M. catarrhalis may confer antimicrobial resistance among coinfecting antimicrobial resistance among coinfecting pathogens (a phenomenon of indirect pathogenicity) pathogens (a phenomenon of indirect pathogenicity) resulting in clinical resistance of beta-lactamase resulting in clinical resistance of beta-lactamase negative strains of H. influenzae and Strep. negative strains of H. influenzae and Strep. pneumoniae pneumoniae

M. catarrhalis - preferred therapyM. catarrhalis - preferred therapy

1st choice therapy1st choice therapy-cefuroxime-cefuroxime-ampicillin/sulbactam or -ampicillin/sulbactam or amoxicillin/clavulanateamoxicillin/clavulanate

Alternative agentsAlternative agents-tetracycline-tetracycline-TMP/SMX-TMP/SMX-macrolide-macrolide-fluoroquinolones-fluoroquinolones

Atypical pneumoniasAtypical pneumonias

Mycoplasma pneumoniaeMycoplasma pneumoniae Chlamydia pneumoniaeChlamydia pneumoniae Legionella pneumophilaLegionella pneumophila VirusesViruses

OtherOther Pneumocystis cariniiPneumocystis carinii Chlamydia trachomatisChlamydia trachomatis RickettsiaeRickettsiae FungiFungi

Respiratory manifestations of mycoplasmal Respiratory manifestations of mycoplasmal infectioninfection

PharyngitisPharyngitis SinusitisSinusitis MyringitisMyringitis Otitis mediaOtitis media CroupCroup BronchitisBronchitis BronchiolitisBronchiolitis BronchopneumoniaBronchopneumonia Pneumonia with pleural effusionPneumonia with pleural effusion

Mycoplasma pneumoniaeMycoplasma pneumoniae

M. pneumoniae accounts for 2-14% of CAPM. pneumoniae accounts for 2-14% of CAP M. pneumoniae has a striking predilection for M. pneumoniae has a striking predilection for

younger patients; often spares older individuals younger patients; often spares older individuals M. pneumoniae accounts for 20-30% of CAP in M. pneumoniae accounts for 20-30% of CAP in

adolescents and adults younger than age 35; 2-adolescents and adults younger than age 35; 2-9% of CAP among adults age 40-60 and only 1% 9% of CAP among adults age 40-60 and only 1% of pneumonias in adults over age 60of pneumonias in adults over age 60

Epidemics of M. pneumoniae infections may occur Epidemics of M. pneumoniae infections may occur in families, schools, institutions; prolonged in families, schools, institutions; prolonged contact is necessary for transmission of infectioncontact is necessary for transmission of infection

Pneumonia caused by M. pneumoniae occurs in Pneumonia caused by M. pneumoniae occurs in only 3-10% of exposed individualsonly 3-10% of exposed individuals

M. pneumoniae is rarely implicated as a M. pneumoniae is rarely implicated as a nosocomial pathogen nosocomial pathogen

Characteristic features of Mycoplasma Characteristic features of Mycoplasma pneumoniae lower airway infectionpneumoniae lower airway infection

Infections occur throughout the yearInfections occur throughout the year The occurence of mycoplasmal illness is closely The occurence of mycoplasmal illness is closely

related to the patient’s age:related to the patient’s age:-mild or subclinical infections in children younger -mild or subclinical infections in children younger than 4 yrsthan 4 yrs-the peak incidence in schoolchildren 5-15 yrs of -the peak incidence in schoolchildren 5-15 yrs of ageage

Recurrent infections in adults every 4-7 yrsRecurrent infections in adults every 4-7 yrs Respiratory route of infectionRespiratory route of infection Incubation period 1-3 wkIncubation period 1-3 wk Gradual onset of the respiratory illness: Gradual onset of the respiratory illness:

headache, general malaise, upper airway headache, general malaise, upper airway infection symptoms, dyspnea, dry hacking cough infection symptoms, dyspnea, dry hacking cough intensifying in the course of the disease, feverintensifying in the course of the disease, fever

The severity of symptoms usually greater than The severity of symptoms usually greater than the condition suggested by the physical signsthe condition suggested by the physical signs

M. pneumoniae – preferred therapyM. pneumoniae – preferred therapy

Because Mycoplasma spp. lack a cell wall, Because Mycoplasma spp. lack a cell wall, beta-lactams and other cell-wall active beta-lactams and other cell-wall active antibiotics have no significant activityantibiotics have no significant activity

1st choice therapy1st choice therapy

-macrolide antibiotic -macrolide antibiotic

(erythromycin, azithromycin, (erythromycin, azithromycin, clarithromycin)clarithromycin)

-doxycycline 100 mg bid orally or iv-doxycycline 100 mg bid orally or iv Alternative agentsAlternative agents

-fluoroquinolones (ciprofloxacin, ofloxacin)-fluoroquinolones (ciprofloxacin, ofloxacin)

Nonrespiratory manifestations of Nonrespiratory manifestations of mycoplasmal infectionmycoplasmal infection Skin:Skin:

-erythema multiforme-erythema multiforme-maculopapular rush-maculopapular rush-Stevens-Johnson syndrome-Stevens-Johnson syndrome

CNS:CNS:-meningoencephalitis-meningoencephalitis-aseptic meningitis-aseptic meningitis-transverse myelitis-transverse myelitis-cerebellar ataxia-cerebellar ataxia-Guillain-Barre syndrome-Guillain-Barre syndrome

Blood:Blood:-hemolytic anaemia-hemolytic anaemia-thrombocytopenia-thrombocytopenia-coagulation defects-coagulation defects

Nonrespiratory manifestations of Nonrespiratory manifestations of mycoplasmal infectionmycoplasmal infection

Gastrointestinal tractGastrointestinal tract-hepatitis-hepatitis

-pancreatitis-pancreatitis

-protein-losing hypertrophic gastropathy-protein-losing hypertrophic gastropathy Cardiovascular systemCardiovascular system

-myocarditis-myocarditis

-pericarditis-pericarditis

-cardiac dilatation with heart failure-cardiac dilatation with heart failure JointsJoints

-monoarticular transient arthritis-monoarticular transient arthritis

Chlamydia pneumoniaeChlamydia pneumoniae

Within the genus Chlamydia there are Within the genus Chlamydia there are three species recognized: Ch.pneumoniae, three species recognized: Ch.pneumoniae, Ch.psittacci, Ch.trachomatisCh.psittacci, Ch.trachomatis

Clinical features are similar to M. Clinical features are similar to M. pneumoniae; fever and cough occur in 50-pneumoniae; fever and cough occur in 50-80% of patients80% of patients

Infections are often asymptomatic Infections are often asymptomatic (antichlamydial antibodies present in 26% (antichlamydial antibodies present in 26% of schoolchildren) of schoolchildren)

Associations of Chlamydia infections and Associations of Chlamydia infections and coronary artery disease, carotid coronary artery disease, carotid atherosclerosis, asthma, sarcoidosis have atherosclerosis, asthma, sarcoidosis have been suggested been suggested

Ch. pneumoniae may be an important Ch. pneumoniae may be an important infection trigger for asthma, CF and COPDinfection trigger for asthma, CF and COPD

Chlamydia pneumoniae – preferred therapyChlamydia pneumoniae – preferred therapy

Beta-lactams and aminoglycosides have Beta-lactams and aminoglycosides have no activityno activity

Tetracyclines and macrolids may shorten Tetracyclines and macrolids may shorten the duration of illnessthe duration of illness

Preferred therapy:Preferred therapy:-doxycycline or tetracycline orally for 14--doxycycline or tetracycline orally for 14-21 days21 days

Alternative agents:Alternative agents:-oral macrolides-oral macrolides-fluoroquinolones-fluoroquinolones

Empiric therapy with tetracyclines should Empiric therapy with tetracyclines should be considered for patients with protracted be considered for patients with protracted bronchitis or CAP refractory to beta-bronchitis or CAP refractory to beta-lactamslactams

Legionella pneumophilaLegionella pneumophila

Legionella spp. are endemic in the Legionella spp. are endemic in the community, accounting for 2-10% of CAP; community, accounting for 2-10% of CAP; nosocomial legionellosis is rare in most nosocomial legionellosis is rare in most hospitalshospitals

Risk factors for legionellosis and more Risk factors for legionellosis and more severe disease include advanced age, severe disease include advanced age, renal failure, cigarette smoking, ethanol renal failure, cigarette smoking, ethanol abuse, organ transplantation, abuse, organ transplantation, corticosteroids and severe underlying corticosteroids and severe underlying diseasedisease

Clinically pneumonia caused by Legionella Clinically pneumonia caused by Legionella is indistinguishable from other bacterial is indistinguishable from other bacterial pneumonias; common feture of CAP pneumonias; common feture of CAP caused by Legionella is progression of caused by Legionella is progression of pneumonia while taking antimicrobials pneumonia while taking antimicrobials

Legionella pneumophila – preferred therapyLegionella pneumophila – preferred therapy

Beta-lactams and aminoglycosides are not active Beta-lactams and aminoglycosides are not active against Legionellaagainst Legionella

1st choice antibiotics:1st choice antibiotics:

-intravenous erythromycin 1g q6hr iv; -intravenous erythromycin 1g q6hr iv;

substitute oral erythromycin 500mg qid following substitute oral erythromycin 500mg qid following clinical improvement and defervescence for 21 clinical improvement and defervescence for 21 daysdays

-rifampin may be synergistic in combination with -rifampin may be synergistic in combination with erythromycin in immunocompromised hostserythromycin in immunocompromised hosts

Alternative therapyAlternative therapy

-clarithromycin 500-1000mg bid for 21 days-clarithromycin 500-1000mg bid for 21 days

-ciprofloxacin 750mg bid or ofloxacin 400mg bid -ciprofloxacin 750mg bid or ofloxacin 400mg bid for 21 days for 21 days

Empiric (initial) therapy for CAPEmpiric (initial) therapy for CAP In most cases of pneumonia therapy is In most cases of pneumonia therapy is

empiricempiric Initial treatment of CAP should beInitial treatment of CAP should be

-sufficiently broad to cover most likely -sufficiently broad to cover most likely pathogenspathogens-avoiding polypharmacy and toxic or -avoiding polypharmacy and toxic or excessively expensive antimicrobialsexcessively expensive antimicrobials

Choice of empiric therapy should be Choice of empiric therapy should be modified based on clinical features as:modified based on clinical features as:-age-age-the presence of underlying disease-the presence of underlying disease-radiographic appearance-radiographic appearance-prior use of antimicrobials-prior use of antimicrobials-severity of pneumonia-severity of pneumonia

Empiric (initial) therapy for CAPEmpiric (initial) therapy for CAP

Parenteral antibiotics are preferred as initial Parenteral antibiotics are preferred as initial therapy in neonates, infants and children with therapy in neonates, infants and children with serious associated diseaseserious associated disease

Other factors warranting parenteral therapy Other factors warranting parenteral therapy include: respiratory distress, multilobar include: respiratory distress, multilobar pneumonia, hypoxemia, hypotension, non-pneumonia, hypoxemia, hypotension, non-compliancecompliance

Oral therapy should be reserved for patients:Oral therapy should be reserved for patients:-presenting no gastrointestinal symptoms that -presenting no gastrointestinal symptoms that preclude predictable oral absorptionpreclude predictable oral absorption-clinically not toxic, hypotensive, severely ill-clinically not toxic, hypotensive, severely ill-presenting pneumonia confined to a segment or -presenting pneumonia confined to a segment or bronchopneumoniabronchopneumonia-with no prior underlying disease-with no prior underlying disease

Empiric (initial) therapy for CAPEmpiric (initial) therapy for CAPEmpiric strategies for CAP patients Empiric strategies for CAP patients

with no comorbiditieswith no comorbiditiesMild CAP not requiring hospitalization:Mild CAP not requiring hospitalization:

Penicillin or ampicillin may be adequate Penicillin or ampicillin may be adequate for Strep. pneumoniae in communities for Strep. pneumoniae in communities where the rate of penicillin resistant where the rate of penicillin resistant pneumococci is lowpneumococci is low

2nd generation oral cephalosporin or 2nd generation oral cephalosporin or amoxicillin/ clavulanateamoxicillin/ clavulanate

Oral macrolide antibiotic is also Oral macrolide antibiotic is also recommended: covers atypicals, Strep. recommended: covers atypicals, Strep. pneumoniae and most strains of H. pneumoniae and most strains of H. influenzaeinfluenzae

Activity of fluoroquinolones against Strep. Activity of fluoroquinolones against Strep. pneumoniae is modest pneumoniae is modest

Empiric (initial) therapy for CAPEmpiric (initial) therapy for CAP

Moderate CAP requiring hospitalizationModerate CAP requiring hospitalization Iv ampicillin/sulbactam, cefuroxime, ceftriaxone Iv ampicillin/sulbactam, cefuroxime, ceftriaxone

or cefotaxime plus an oral macrolideor cefotaxime plus an oral macrolide Ofloxacin for penicillin-allergic patientsOfloxacin for penicillin-allergic patients

Severe life threatening or multilobar CAP requiring Severe life threatening or multilobar CAP requiring hospitalizationhospitalization

Ceftriaxone plus high-dose iv erythromycin Ceftriaxone plus high-dose iv erythromycin Ceftriaxone plus iv fluoroquinolone (ofloxacin, Ceftriaxone plus iv fluoroquinolone (ofloxacin,

ciprofloxacin)ciprofloxacin) Piperacillin/tazobactam plus iv eythromycinPiperacillin/tazobactam plus iv eythromycin Piperacillin/tazobactam plus a fluoroquinolonePiperacillin/tazobactam plus a fluoroquinolone Fluoroquinolone (ofloxacin, ciprofloxacin) for Fluoroquinolone (ofloxacin, ciprofloxacin) for

penicillin-allergic patientspenicillin-allergic patients

Anaerobic pleuropulmonary infectionsAnaerobic pleuropulmonary infections

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

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

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

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

Antibacterial susceptibility of anaerobesAntibacterial susceptibility of anaerobes Bacteroides fragilis and virtually all anaerobes Bacteroides fragilis and virtually all anaerobes

are susceptible to: imipenem, metronidazole, are susceptible to: imipenem, metronidazole, extended-spectrum penicillins with beta-extended-spectrum penicillins with beta-lactamase inhibitorslactamase inhibitors

Clindamycin is active against most anaerobesClindamycin is active against most anaerobes Penicillin G and ampicillin have exquisite Penicillin G and ampicillin have exquisite

activity against normal oral anaerobes, but activity against normal oral anaerobes, but more than 90% of B. fragilis are resistantmore than 90% of B. fragilis are resistant

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

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

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

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

Penicillin G for uncomplicated casesPenicillin G for uncomplicated cases Clindamycin for complicated lung abscess or Clindamycin for complicated lung abscess or

penicillin failurepenicillin failure Ampicillin/sulbactam when concomittant infection Ampicillin/sulbactam when concomittant infection

with enteric Gram(-) bacilli suspectedwith enteric Gram(-) bacilli suspected Oral antibiotics (penicillin V, clindamycin, Oral antibiotics (penicillin V, clindamycin,

amoxicillin/clavulanate) may be substituted amoxicillin/clavulanate) may be substituted following clinical response to parenteral therapyfollowing clinical response to parenteral therapy

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

Nosocomial pneumoniaNosocomial pneumonia Pneumonia develops in 0,5-2% of hospitalized Pneumonia develops in 0,5-2% of hospitalized

patients and has been associated with mortality rate patients and has been associated with mortality rate of 30-60%of 30-60%

Aerobic enteric Gram(-) bacilli are responsible for 65-Aerobic enteric Gram(-) bacilli are responsible for 65-85% of nosocomial pneumonias85% of nosocomial pneumonias

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

15-20% are caused by Pseudomonas aeruginosa15-20% are caused by Pseudomonas aeruginosa Staphylococci and streptococci account for 10-25% Staphylococci and streptococci account for 10-25%

of cases, usually in the context of polymicrobial of cases, usually in the context of polymicrobial pneumoniapneumonia

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

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

Acinetobacter sp.Acinetobacter sp. Acinetobacter accounts for only 1-3% of Acinetobacter accounts for only 1-3% of

nosocomial pneumonias, but the rate is nosocomial pneumonias, but the rate is higher- 5-15% in mechanically ventilated higher- 5-15% in mechanically ventilated ICU patients primarily newbornsICU patients primarily newborns

Mortality rates for Acinetobacter Mortality rates for Acinetobacter pneumonia exceed 50%pneumonia exceed 50%

Antimicrobial susceptibility:Antimicrobial susceptibility:- Acinetobacter are highly resistant to Acinetobacter are highly resistant to

multiple antibiotics: ampicillin, 1st and 2nd multiple antibiotics: ampicillin, 1st and 2nd generation cephalosporins and in a lesser generation cephalosporins and in a lesser extent to aminoglycosidesextent to aminoglycosides

- Activity of 3rd generation cephalosporins Activity of 3rd generation cephalosporins is variableis variable

Acinetobacter – preferred therapyAcinetobacter – preferred therapy

1st choice agents:1st choice agents:

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

Alternative agents:Alternative agents:

-TMP/SMX, fluoroquinolones may be active -TMP/SMX, fluoroquinolones may be active but variablebut variable

Choice of agent should depend on results Choice of agent should depend on results of susceptibility testingof susceptibility testing

Klebsiella pneumoniaeKlebsiella pneumoniae

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

High rate of bacteriemia and and High rate of bacteriemia and and suppurative complications are notedsuppurative complications are noted

Antimicrobial susceptibility:Antimicrobial susceptibility:- Resistant to penicillin and ampicillinResistant to penicillin and ampicillin- Highly susceptible to cefuroxime, 3rd Highly susceptible to cefuroxime, 3rd

generation cephalosporins, imipenem, generation cephalosporins, imipenem, aztreonam, fluoroquinolones, aztreonam, fluoroquinolones, aminoglycosides, TMP/SMXaminoglycosides, TMP/SMX

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

Klebsiella pneumoniae – preferred therapyKlebsiella pneumoniae – preferred therapy 1st choice antibiotics:1st choice antibiotics:

-2nd or 3rd generation cephalosporins-2nd or 3rd generation cephalosporins-aminoglycosides may be added for -aminoglycosides may be added for synergy in fulminant or refractory casessynergy in fulminant or refractory cases

Alternative agents: Alternative agents: -imipenem, fluoroquinolone, aztreonam, -imipenem, fluoroquinolone, aztreonam, TMP/SMXTMP/SMX

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

Pseudomonas aeruginosaPseudomonas aeruginosa

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

P. aeruginosa is a rare cause of CAP P. aeruginosa is a rare cause of CAP except among patients with specific risk except among patients with specific risk factors: factors: bronchiectasis, CF, tracheostomy, bronchiectasis, CF, tracheostomy, granulocytopenia, immunosuppressive or granulocytopenia, immunosuppressive or corticosteroid therapy, iv drug abusecorticosteroid therapy, iv drug abuse

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

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

P. aeruginosa – antimicrobial susceptibilityP. aeruginosa – antimicrobial susceptibility P. aeruginosa is resistant to most P. aeruginosa is resistant to most

antibioticsantibiotics Antipsedomonal penicillins are active Antipsedomonal penicillins are active

against 80-95% of strains; piperacillin is against 80-95% of strains; piperacillin is the most potentthe most potent

Among cephalosporins only ceftazidime Among cephalosporins only ceftazidime and cefoperazone are considered activeand cefoperazone are considered active

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

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

P. aeruginosa – preferred therapyP. aeruginosa – preferred therapy

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

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

Alternative agents: ciprofloxacin or Alternative agents: ciprofloxacin or aztreonam combined with aminoglycosideaztreonam combined with aminoglycoside

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

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

Staphylococcus aureusStaphylococcus aureus Coagulase-positive Staph. aureus may cause both Coagulase-positive Staph. aureus may cause both

community- and hospital-acquired pneumoniacommunity- and hospital-acquired pneumonia Staphylococci rarely cause CAP in previously Staphylococci rarely cause CAP in previously

healthy hosts; specific risk factors include:healthy hosts; specific risk factors include:influenza, diabetes mellitus, iv drug abuse, iv lines influenza, diabetes mellitus, iv drug abuse, iv lines and catheters, malignanciesand catheters, malignancies

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

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

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

Common complications of staphylococcal Common complications of staphylococcal pneumoniapneumonia

EmpyemaEmpyema PyopneumothoraxPyopneumothorax PneumatocelesPneumatoceles Bronchopleural fistulaBronchopleural fistula Septic lesions in other organsSeptic lesions in other organs Metastatic abscesses in soft tissuesMetastatic abscesses in soft tissues

Staph. aureus – antimicrobial susceptibilityStaph. aureus – antimicrobial susceptibility

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

Ceftazidime has only modest activity Ceftazidime has only modest activity against staphylococciagainst staphylococci

MRSA is resistant to all beta-lactamsMRSA is resistant to all beta-lactams The antipseudomonal penicillins and The antipseudomonal penicillins and

imipenem/cilastin are active against imipenem/cilastin are active against methicillin-sensitive strainsmethicillin-sensitive strains

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

Methicillin-resistant Staph. aureus – Methicillin-resistant Staph. aureus – antimicrobial susceptibilityantimicrobial susceptibility

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

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

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

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

Staph. aureus –preferred therapyStaph. aureus –preferred therapyMethicillin-susceptible Staph. aureus:Methicillin-susceptible Staph. aureus:

Preferred therapyPreferred therapy-oxacillin or cloxacillin only for -oxacillin or cloxacillin only for monomicrobial infections caused by monomicrobial infections caused by methicillin-susceptible strainsmethicillin-susceptible strains-vancomycin uniformly active for both -vancomycin uniformly active for both methicillin-susceptible and resistant methicillin-susceptible and resistant strainsstrains

Alternative agents: Alternative agents: cefazolin, clindamycin, imipenemcefazolin, clindamycin, imipenem

Methicillin-resistant Staph. aureus:Methicillin-resistant Staph. aureus: Preferred therapy: vancomycinPreferred therapy: vancomycin Alternatively for patients intolerant of Alternatively for patients intolerant of

vancomycin:vancomycin:clindamycin, imipenem, TMP/SMX clindamycin, imipenem, TMP/SMX

Empiric therapy for nosocomial pneumoniaEmpiric therapy for nosocomial pneumonia Monotherapy with broad-spectrum beta-lactamsMonotherapy with broad-spectrum beta-lactams-- Monotherapy with ceftazidime, cefoperazone or Monotherapy with ceftazidime, cefoperazone or

imipenem/cilastin is associated with favorable imipenem/cilastin is associated with favorable response in 65-88% of cases of nosocomial response in 65-88% of cases of nosocomial pneumoniapneumonia

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

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

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

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

Pulmonary complications of HIV infectionPulmonary complications of HIV infection ViralViral

CMV, RSV, HSV, Parainfluenza, Influenza, CMV, RSV, HSV, Parainfluenza, Influenza, AdenovirusAdenovirus

BacterialBacterial

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

FungalFungal

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

Conditions leading to or mimicking pneumoniaConditions leading to or mimicking pneumonia

Aspiration syndromesAspiration syndromes Inhalation of toxic fumes, burn injuriesInhalation of toxic fumes, burn injuries Radiation injuryRadiation injury Drug-induced pulmonary diseaseDrug-induced pulmonary disease Alveolitis (hypersensitivity pneumonitis)Alveolitis (hypersensitivity pneumonitis) ARDSARDS Haemosiderosis and pulmonary haemorrhageHaemosiderosis and pulmonary haemorrhage Prominent or persistent thymus beyond the age of 4 yrsProminent or persistent thymus beyond the age of 4 yrs Congenital abnormalitiesCongenital abnormalities Bronchiolitis obliterans organizing pneumoniaBronchiolitis obliterans organizing pneumonia Connective tissue diseases, granulomatous vasculitidesConnective tissue diseases, granulomatous vasculitides Pulmonary embolismPulmonary embolism Pulmonary edemaPulmonary edema Pulmonary neoplasmsPulmonary neoplasms

Thank you for your attentionThank you for your attention