Lower Respiratory Tract Lower Respiratory Tract InfectionsInfections

Méhes Leonóra, MDMéhes Leonóra, MDDepartment of Infectious and Pediatric Department of Infectious and Pediatric

ImmunologyImmunology

2012.11.072012.11.07

LRTI - BronchiolitisLRTI - Bronchiolitis

viral infectionviral infection

severe symptoms severe symptoms - - young infants, young infants, < 2 y, peak: < 2 y, peak: iinfants aged 3-6 monthsnfants aged 3-6 months

self-limiting conditionself-limiting condition, RSV, RSV

Other causes: parainfluenza, Influenza B, echovirus, Other causes: parainfluenza, Influenza B, echovirus, Rhinovirus, Adenovirus, MycoplasmaRhinovirus, Adenovirus, Mycoplasma

CoughCough, d, dyspneayspnea, w, wheezingheezing, p, poor feedingoor feeding, , hhypothermia or hyperthermiaypothermia or hyperthermia

Th: humidified oxygen, nebulized epinephrin, Th: humidified oxygen, nebulized epinephrin, mechanical ventillation, bronchodilator, mechanical ventillation, bronchodilator, corticosteroid, ribavirincorticosteroid, ribavirin

CAPCAP

Typical bacterial pathogensTypical bacterial pathogens: S: Streptococcus treptococcus pneumoniaepneumoniae (penicillin-sensitive and -resistant (penicillin-sensitive and -resistant strains), strains), Haemophilus influenzaeHaemophilus influenzae (ampicillin- (ampicillin-sensitive and -resistant strains), sensitive and -resistant strains), Moraxella Moraxella catarrhaliscatarrhalis (all strains penicillin-resistant) (all strains penicillin-resistant)

CAP is usually acquired via inhalation or aspiration CAP is usually acquired via inhalation or aspiration of pulmonary pathogenic organisms of pulmonary pathogenic organisms

Aspiration pneumonia is the only form of CAP Aspiration pneumonia is the only form of CAP caused by multiple pathogens (eg, caused by multiple pathogens (eg, aerobic/anaerobic oral organisms).aerobic/anaerobic oral organisms).

Patients with CAP who have impaired splenic Patients with CAP who have impaired splenic function may develop overwhelming pneumococcal function may develop overwhelming pneumococcal sepsis, potentially leading to death within 12-24 sepsis, potentially leading to death within 12-24 hours, regardless of the antimicrobial regimen used. hours, regardless of the antimicrobial regimen used.

DiagnosisDiagnosis

Sputum Gram stainSputum Gram stain

Blood cultureBlood culture

Blood tests: liver, renal function, CBC, ESR, CRP levelBlood tests: liver, renal function, CBC, ESR, CRP level

Hypophosphataemia + hematuria – LegionellosisHypophosphataemia + hematuria – Legionellosis

Cold agglutinin level – MycoplasmaCold agglutinin level – Mycoplasma

Serology: Clamydia, Mycoplasma, LegionellaSerology: Clamydia, Mycoplasma, Legionella

Periferal smear: impaired splenic function: Howell-Jolly Periferal smear: impaired splenic function: Howell-Jolly bodiesbodies

Urinary antigen test: S.pneumoniae, Legionella serotype I Urinary antigen test: S.pneumoniae, Legionella serotype I (80%)(80%)

Chest X-ray, CT scanChest X-ray, CT scan

Bronchoscopy: BALBronchoscopy: BAL

Staphylococcus aureus:Staphylococcus aureus: secondary to influenza secondary to influenza

ICU: polymicrobial infections (K.pneumoniae, ICU: polymicrobial infections (K.pneumoniae, P.aeruginosa)P.aeruginosa)

gram-negative pathogens (eg, gram-negative pathogens (eg, EnterobacterEnterobacter species, species, SerratiaSerratia species, species, Stenotrophomonas Stenotrophomonas maltophilia, Burkholderia cepaciamaltophilia, Burkholderia cepacia) rarely cause ) rarely cause CAP.CAP.

Atypical pneumonia: zoonotic atypical: Atypical pneumonia: zoonotic atypical: ChlamydiaChlamydia psittacipsittaci, , Francisella tularensis, Coxiella burnetiiFrancisella tularensis, Coxiella burnetii (Q (Q fever).fever).

Nonzoonotic atypical: LeNonzoonotic atypical: Legionellagionella species, species, M M pneumoniae,pneumoniae, ChlamydiaChlamydia pneumoniae -pneumoniae -15% of all 15% of all CAP casesCAP cases

a variety of pulmonary and extrapulmonary findings (eg, a variety of pulmonary and extrapulmonary findings (eg, CAP plus diarrhea)CAP plus diarrhea)

bbacterial CAPacterial CAP: f: fever, productive coughever, productive cough, p, pleuritic chest leuritic chest pain.pain.

atypical CAPatypical CAP: : subacute subacute, , 1 or more extrapulmonary 1 or more extrapulmonary featuresfeatures

LegionellaLegionella pneumonia pneumonia:: productive or nonproductive productive or nonproductive coughcough

M pneumoniaeM pneumoniae or or ChlamydiaChlamydia pneumoniaepneumoniae:: nonproductive nonproductive cough.cough.

Zoonotic CAP: patZoonotic CAP: patients with tularemia have had recent ients with tularemia have had recent close contact with rabbits or have recently been bitten by close contact with rabbits or have recently been bitten by a tick. a tick.

Etiology - microbiEtiology - microbi

S. pneumoniaeS. pneumoniae inf multiple letality >> inf multiple letality >> Mycoplasma Mycoplasma pneumoniaepneumoniae infinfStreptococcus pneumoniaeStreptococcus pneumoniae etiol not excluded etiol not excludedMycoplasma pneumoniae,Chlamydophila Mycoplasma pneumoniae,Chlamydophila pneumoniaepneumoniae:: macrolid, doxycyclin, fluoroqmacrolid, doxycyclin, fluoroq Legionella pneumophilaLegionella pneumophila: : macrolid, fluoroqmacrolid, fluoroq S. pneumoniaeS. pneumoniae strains 95 %: strains 95 %: ampicillin/amoxicillin, ampicillin/amoxicillin, cephalosporin (cefuroxim, cefotaxim, ceftriaxon), cephalosporin (cefuroxim, cefotaxim, ceftriaxon), carbapen (ertapenem, imipenem, meropenem)carbapen (ertapenem, imipenem, meropenem) 3rd gen 3rd gen levofloxacinlevofloxacin, 4th gen , 4th gen moxifloxacinmoxifloxacin (resp (resp fluroq) good spectrum against fluroq) good spectrum against S. pneumoniaeS. pneumoniae macrolid derivatives macrolid derivatives S. pneumoniae S. pneumoniae efficacy the efficacy the samesamemultiresistant multiresistant G - microb, G - microb, S.aureusS.aureus

Risk factorsRisk factorsS. pneumoniaeS. pneumoniae - - 40%, childhood, elderly, severe 40%, childhood, elderly, severe basic diseasebasic diseaseYoung adult: Young adult: Mycoplasma pneumoniaeMycoplasma pneumoniae elderly, with risk factors: G - bacilli (elderly, with risk factors: G - bacilli (Haemophilus Haemophilus influenzaeinfluenzae, , E. coli, Klebsiella pneumoniaeE. coli, Klebsiella pneumoniae))Aspiration pneumoniaAspiration pneumoniaviral pneumonia – immunocompetent, viral pneumonia – immunocompetent, spontaneously healedspontaneously healedPoor prognosis: Poor prognosis:

elderly (>65 y) elderly (>65 y) basic diseases basic diseases

chronic cardio-pulmonarychronic cardio-pulmonaryhepatic, renal insufficiencyhepatic, renal insufficiencyneoplasianeoplasiaimmunodeficiency immunodeficiency diabetes mellitusdiabetes mellitussmokersmoker

Scoring systemsScoring systems

CURB65CURB65: : CConfusion, onfusion, UUrea, rea, RRespiratory rate, espiratory rate, BBlood lood pressure (systolic value pressure (systolic value 90, diastolic value 90, diastolic value 60 60 mmHg), 65 (y)mmHg), 65 (y)

CRB65CRB65 – each 1 point – each 1 point0 0 - moderately severe status, mortality rate <3%, - moderately severe status, mortality rate <3%, ambulantory th ambulantory th 1-2 1-2 - severe st, mort. rate 10%, 2 p = - severe st, mort. rate 10%, 2 p = hospitalizationhospitalization3-4 -3-4 - very severe st, mort rate 15-40%, ICU very severe st, mort rate 15-40%, ICU treatmenttreatment

Criteria of severe pneumoniaCriteria of severe pneumonia

Major criteria (first visit):Major criteria (first visit):mechanical ventillation mechanical ventillation vasopressor therapy (> 4 hours) (septic shock)vasopressor therapy (> 4 hours) (septic shock)Minor criteria (first visit):Minor criteria (first visit):Respiration rate Respiration rate 30/min30/minSevere respiratory insuff. (PaO2/FiO2 Severe respiratory insuff. (PaO2/FiO2 250)250)multilobular infiltratemultilobular infiltrate- desorientation- desorientation- uraemia- uraemia- leucopenia- leucopenia- thrombocytopenia- thrombocytopenia- hypothermia- hypothermia- aggressiv fluid supplementation, hypotension- aggressiv fluid supplementation, hypotension1 major or 3 or more minor criteria1 major or 3 or more minor criteria

TreatmentTreatmentsevere septicaemia, septic shock – first ab dosis severe septicaemia, septic shock – first ab dosis within 1 hourwithin 1 hourSample taking for microbiological exam.Sample taking for microbiological exam.Efficacy of the chosen ab – severity of clinical Efficacy of the chosen ab – severity of clinical situationsituationParenteral administration, sequential therapyParenteral administration, sequential therapyDeescalationDeescalationLength of treatment: good response to th: 7-10 days Length of treatment: good response to th: 7-10 days (radiol. positivity for weeks)(radiol. positivity for weeks)legionellosis treament: 3 wlegionellosis treament: 3 w

TreatmentTreatment

Typical +atypical coverageTypical +atypical coverage

Monotherapy: doxycyclin, resp quinolons, tigecyclinMonotherapy: doxycyclin, resp quinolons, tigecyclin

Combination: Ceftriax + doxyc/ azithro / resp quinolonCombination: Ceftriax + doxyc/ azithro / resp quinolon

12-14 day sequential therapy: iv – oral12-14 day sequential therapy: iv – oral

Avoid empiric macrolide monotherapyAvoid empiric macrolide monotherapy: : 25% of 25% of S S pneumoniaepneumoniae strains are naturally resistant to all strains are naturally resistant to all macrolidesmacrolides

MonotherapyMonotherapy: : doxycyclinedoxycycline/ / resp quinoloneresp quinolone

highly penicillin-resistant highly penicillin-resistant S pneumoniaeS pneumoniae infections infections: b: beta eta lactamslactams, , doxycyclinedoxycycline, , respiratory quinolonesrespiratory quinolones

Very highly penicillin-resistant Very highly penicillin-resistant S pneumoniaeS pneumoniae (MIC 6 (MIC 6 µg/mL)µg/mL): : ceftriaxoneceftriaxone

Chest X-ray: after 1 weekChest X-ray: after 1 week

Empirical ab gr.1Empirical ab gr.1

Ambul treat pn: < 65 y, without any basic Ambul treat pn: < 65 y, without any basic diseasedisease

CRB65 score = 0CRB65 score = 0amoxicillinamoxicillin ( (min 3 g/d) ormin 3 g/d) or macrolid or macrolid or doxycyclindoxycyclin

penicillin allergy: penicillin allergy: resp fluoroq resp fluoroq macrolid derivmacrolid deriv monotherapy monotherapy No improvement within 48 h, chest X ray, lab No improvement within 48 h, chest X ray, lab parameters parameters Resp fluoroq (levofloxacin, moxifloxacin)Resp fluoroq (levofloxacin, moxifloxacin)

Empir th gr. 2Empir th gr. 2Ambul treat pneumonia: basic disease a/o > 65 y Ambul treat pneumonia: basic disease a/o > 65 y

CRB65 score =1 CRB65 score =1 amoxi/clav, cefuroxim +/- macrolid amoxi/clav, cefuroxim +/- macrolid oror resp fluoroq resp fluoroq (levofloxacin, moxifloxacin)(levofloxacin, moxifloxacin)parent th: parent th: ceftriaxon, cefuroxim +/- macrolidceftriaxon, cefuroxim +/- macrolid

- letal: < 5 %, finally 20 % hospit- letal: < 5 %, finally 20 % hospit- hospit decision within 48 h- hospit decision within 48 h

Empir th gr. 3Empir th gr. 3CAP + hospit CAP + hospit CRB65 score = 2CRB65 score = 2amoxi/clav, cefuroxim, ceftriaxon/cefotaximamoxi/clav, cefuroxim, ceftriaxon/cefotaxim + + macrolidmacrolid

or or resp fluoroqresp fluoroq

Empir ab: atypical microbiEmpir ab: atypical microbimultires G - bacil, ESBL+ Klebsiella spp., E.colimultires G - bacil, ESBL+ Klebsiella spp., E.coli - - ertapenem ertapenem P.aeruginosaP.aeruginosa: : imipenem, meropenem, doripenem, imipenem, meropenem, doripenem, ceftazidim, cefepimceftazidim, cefepim – an.: bronchiectasia, severe – an.: bronchiectasia, severe COPD, cystic fibrosisCOPD, cystic fibrosissteroid th: controversial, no effect on prognosis, no steroid th: controversial, no effect on prognosis, no evidence based th efficacyevidence based th efficacy

Empir th gr. 4Empir th gr. 4Severe, ICU Severe, ICU CRB65 score = 3 – 4 CRB65 score = 3 – 4 1. 1. Pseudomonas aeruginosaPseudomonas aeruginosa low incidence: low incidence:ceftriaxon/cefotaxim, carbapenem (ertapenem), ceftriaxon/cefotaxim, carbapenem (ertapenem), pip/tazo + macrolidpip/tazo + macrolid or or resp fluoroqresp fluoroq2. 2. Pseudomonas aeruginosaPseudomonas aeruginosa possible possibleCeftazidim, carbapenem (imipenem, meropenem), Ceftazidim, carbapenem (imipenem, meropenem), pip/tazo + ciproflpip/tazo + ciprofl or or beta-lact + aminogl + macrolidbeta-lact + aminogl + macrolid oror resp fluoroqresp fluoroqG – bacil: diabetes mellitus, COPD, alkoholism G – bacil: diabetes mellitus, COPD, alkoholism levofloxacin higher dose: levofloxacin higher dose: Streptococcus pneumonia, Streptococcus pneumonia, Pseudomonas aeruginosa, Klebsiella pneumoniaePseudomonas aeruginosa, Klebsiella pneumoniae (750-1000 mg/nap) (750-1000 mg/nap) aspir pneumonia: anaerob spectrum (not aspir pneumonia: anaerob spectrum (not metronidazol)metronidazol)

Influenza prim/sec pneumoniaInfluenza prim/sec pneumonia

Outbreak periodOutbreak periodinfluenza A és B virusinfluenza A és B virus early pn within 48 h: early pn within 48 h: oseltamivir, zanamivir oseltamivir, zanamivir Primary viral pneumonia:Primary viral pneumonia: rapid hospital, spec rapid hospital, spec antivir, antibact thantivir, antibact thSpec antivir th: Spec antivir th: oseltamiviroseltamivir 2x75 mg/d per os 2x75 mg/d per os+ + amoxi/clav oramoxi/clav or ceftriaxonceftriaxon or or moxifloxacin moxifloxacin or or levofloxacin levofloxacin Secondary, bacterial pneumonia:Secondary, bacterial pneumonia:Streptococcus pneumoniaeStreptococcus pneumoniae, , Staphylococcus aureusStaphylococcus aureusmoderately severe: moderately severe: amoxi/clav amoxi/clav 3x1,2 g/d (iv) 3x1,2 g/d (iv) severe: severe: ceftriaxon ceftriaxon 2 g/d or 2 g/d or moxifloxacin moxifloxacin 400 mg/d or 400 mg/d or levofloxacinlevofloxacin 500-1000 mg/d 500-1000 mg/d

VaccinationVaccination

Pneumococcal vaccinesPneumococcal vaccines: : prevent pneumococcal prevent pneumococcal bacteremia but not necessarily pneumococcal bacteremia but not necessarily pneumococcal pneumoniapneumonia

PrevPreveenarnar: 13-: 13-valent conjugate vaccinevalent conjugate vaccine, c, children hildren aged 6 weeks to 5 yearsaged 6 weeks to 5 years

23-valent vaccine (Pneumovax 23) is approved for 23-valent vaccine (Pneumovax 23) is approved for adults aged 50 years or older and persons aged 2 adults aged 50 years or older and persons aged 2 years or olderyears or older

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