Hospital Acquired Pneumonia. Pneumonia that occurs 48 hrs or more after admission, which was not incubating at the time of admission. Hospital Acquired

Hospital Acquired PneumoniaHospital Acquired PneumoniaHospital Acquired PneumoniaHospital Acquired Pneumonia

Pneumonia that occurs 48 hrs or more after admission, which was not incubating at the time of admission.


American Thoracic Society. Am J Respir Crit Care Med 2005;171:388-416.

Epidemiology Common hospital-acquired infection 25% of all ICU acquired infections 2nd most common type of nosocomial infection after UTI. Incidence increases by 6-20 fold in patients being ventilated

mechanically. Occurs at the rate of 5-10 cases per 1000 hospital

admissions





Epidemiology Associated with substantial morbidity Has an associated crude mortality of 30-70% In ICU nearly 90% episodes of HAP occur during

mechanical ventilation. Hospital stay increases by 7-9 days per patient Produce an excess cost of more than $40,000 per

patient

Pneumonia developing in a patient receiving mechanical ventilation for longer than 48–72 hours after tracheal intubation. [1]

What is VAP?What is VAP?What is VAP?What is VAP?


Ventilator Associated Pneumonia (VAP) – Key Points -Ventilator Associated Pneumonia (VAP) – Key Points -Ventilator Associated Pneumonia (VAP) – Key Points -Ventilator Associated Pneumonia (VAP) – Key Points -

VAP is 15% of all hospital acquired infections Incidence = 9% to 27% of patients on ventilators Increased avg. hospital stay 1 to 3 weeks Mortality = 13% to 55% Added costs of $40,000 - $50,000 per stay

Centers for Disease Control and Prevention, 2003. Rumbak, M. J. (2000). Strategies for prevention and treatment. Journal of Respiratory Disease, 21 (5), p. 321;

Risk of VAP is highest early in the course of hospital stay, and is estimated to be

3%/day during the first 5 days of ventilation,

2%/day during Days 5 to 10 of ventilation, and

1%/day thereafter

Ventilator Associated Pneumonia (VAP) – Key Points -Ventilator Associated Pneumonia (VAP) – Key Points -Ventilator Associated Pneumonia (VAP) – Key Points -Ventilator Associated Pneumonia (VAP) – Key Points -



Pathogenesis

PathogenesisInvasion of the lower respiratory tract by:

Aspiration of oropharyngeal/GI organisms

Inhalation of aerosols containing bacteria

Hematogenous spread


MMWR, January 3,1997/vol.46/No.RR-1

Microaspiration may occur in up to 45% of healthy volunteers during sleep

Oropharynx of hospitalized patients is colonized with various pathogenic bacterias depending on the severity and type of underlying illness

Multiple factors are associated with higher risk of colonization with pathogenic bacteria and higher risk of aspiration




Pathogenesis

Colonization Aspiration

HAPHAPHAPHAP

MRSA*

Intubation & mechanical ventilation Supine positioning Inadequate infection control practices Inadequate surveillance of ICU infections Nasal intubation Emergent or re-intubation Underlying pulmonary disease Enteral feeding

Risk FactorsRisk FactorsRisk FactorsRisk Factors


Antimicrobial therapy in the preceding 90 days Current hospitalization for >5 days or recent hospitalization

(<90 days) High rate of antibiotic resistance in hospital or ward Transfer from nursing home or rehab center Hospitalization for 2 days or more in the preceding 90 days Home infusion therapy (including antibiotics) Family member with multidrug – resistant pathogen Immunosuppressive disease and/or therapy

Risk Factors for MDR Pathogens Causing HAP/ VAPRisk Factors for MDR Pathogens Causing HAP/ VAP


Early onset VAP occurs on day 1-4 of intubation Late onset occurs on or after day 5 Early onset often associated with more pan-sensitive,

endogenous pathogens and has a better prognosis Late onset often associated with multi-drug resistant

pathogens (MDRs) and has poorer prognosis Patients recently hospitalized or transferring from an

extended care facility are more likely to harbor resistant pathogens

Early Vs. Late Onset VAPEarly Vs. Late Onset VAP


Avoid intubation by using noninvasive ventilatory support

Shorten intubation period with switch to noninvasive ventilatory support

Inflate pilot balloon to 20 mm to diminish aspiration of subglottic secretions

Remove subglottic secretions by periodic oral suctioning or by employing double-lumen catheter with continuous subglottic suction

Preventive StrategiesPreventive Strategies


Head of bed elevation to 30 – 45 degrees demonstrated a threefold reduction in the incidence of ICU – acquired HAP.

Orally intubate; nasal intubation prevents drainage of sinuses, increasing risk of sinusitis and VAP

Use oro-gastric instead of nasal-gastric tube for gastric drainage/nutrition

Check gastric residual and prevent distention

More Preventive StrategiesMore Preventive StrategiesMore Preventive StrategiesMore Preventive Strategies


Minimize use of antibiotics to decrease selection pressure on resident flora that produces MDR’s

Tightly control glucose levels to reduce risk of infection

Provide optimal nutrition early – TPN vs. enteral


More Preventive StrategiesMore Preventive StrategiesMore Preventive StrategiesMore Preventive Strategies

* 43 series (3650 episodes) 1984 – 2003, etiology confirmed by blood, BAL or PSB cultures

Luna CM et al. Archiv Bronconeumol 2005;41: 439

Common Pathogens of VAPCommon Pathogens of VAPCommon Pathogens of VAPCommon Pathogens of VAP

25%

20%

15%

10%

5%

0%P. aeruginosa Acinetobacter

spp

GNEB Haemophilus S. aureus S. Pneumoniae Other

Pathogens of VAP in different World AreasPathogens of VAP in different World AreasPathogens of VAP in different World AreasPathogens of VAP in different World Areas

Luna CM et al. Archiv Bronconeumol 2005;41: 439

USA Europe Latin America

25%

20%

15%

10%

5%

0%

30%

S. aureus

P. Aeruginosa

Acinetobacter spp

S. Maltophilia

Enterobacteriaceae*Haemophilus spp

Objective2

Objective1

Avoid the emergenceof multidrug-resistant

microorganisms

Immediate Rx. of patients with VAP

TreatmentTreatmentTreatmentTreatment

HAP treatment recommendations was published in 2008 for Asian Countries

by Asian HAP Working Group

HAP & VAP are difficult to treat serious infections Many treatment options available ATS/IDSA guidelines may not be applicable in

Asian scenario Different clinical practices in Asian countries:

Availability of specific antibiotics & formulations Difference in cost of antibiotics

Song JH and Asian HAP Working Group, Am J of Inf Control; vol 36; issue 4 May 2008; S83-S92

Need for Asian HAP GuidelinesNeed for Asian HAP GuidelinesNeed for Asian HAP GuidelinesNeed for Asian HAP Guidelines

Other factors: different epidemiologic, etiologic and resistance

patterns (markedly higher incidences of MRSA & MDR pathogens in Asia)


Need for Asian HAP GuidelinesNeed for Asian HAP GuidelinesNeed for Asian HAP GuidelinesNeed for Asian HAP Guidelines

To address these issues the Asian – Pacific Research Foundation for Infectious Diseases, together with the Asian Network for Surveillance developed consensus treatment recommendations for HAP in Asian Countries based on the current epidemiologic situation in the asia.

To address these issues the Asian – Pacific Research Foundation for Infectious Diseases, together with the Asian Network for Surveillance developed consensus treatment recommendations for HAP in Asian Countries based on the current epidemiologic situation in the asia.


The first working group meeting held in Kuala Lumpur, Malaysia and brought together physician from 10 Asian countries (Malaysia,

Thailand, Shina, South Korea, India, Taiwan, Hong Kong, Pakistan, Philippines and Singapore).

The first working group meeting held in Kuala Lumpur, Malaysia and brought together physician from 10 Asian countries (Malaysia,

Thailand, Shina, South Korea, India, Taiwan, Hong Kong, Pakistan, Philippines and Singapore).

Methodology AdoptedMethodology AdoptedMethodology AdoptedMethodology Adopted

Reviewed Existing governmental & institutional guidelines in Asian

Countries (only few Asian countries have guidelines ATS/ IDSA guidelines International epidemiologic data National or Local data from the 10 Asian countries

representatives Information regarding clinical practices in Asian

countries.


Indian Panel MembersIndian Panel MembersIndian Panel MembersIndian Panel Members

Indraprastha Apollo hospital SGR Hospital Christian Medical College


HAP working Group ObservationsHAP working Group ObservationsHAP working Group ObservationsHAP working Group Observations

Knowledge gaps between evidence or data on epidemiology, etiology, and antibiotic resisitance of pathogens causing HAP and VAP in Asian countries

Evidence based recommendations difficult to implement because of fewer data


Treatment RecommendationsTreatment RecommendationsTreatment RecommendationsTreatment Recommendations

Initial Approach to Empirical TherapyInitial Approach to Empirical TherapyInitial Approach to Empirical TherapyInitial Approach to Empirical Therapy

HAP or VAP Suspected

Evaluation• Risk Factors for MDR pathogen• Time of onset (early or late )• Local microbiologic data and resistance pattern• Patient status• LRT sample Gram Stain• Allergy to medication• Underlying co-morbidities• Formulary restrictions• Cost

Select Empirical Antibiotic therapy


Initial Empiric Antibiotic treatment for early onset HAP Initial Empiric Antibiotic treatment for early onset HAP (Table I)(Table I)Initial Empiric Antibiotic treatment for early onset HAP Initial Empiric Antibiotic treatment for early onset HAP (Table I)(Table I)

Potential Pathogen Recommended Regimen* Strep. Pneumoniae$ H. Influenza MSSA Antibiotic – sensitive enteric Gram

–ve bacilli: E coli K. pneumoniae Enterobacter sp. Proteus sp. S. marcescens

3rd generation cephalosporins (ceftriaxone, cefotaxime) or Fluoroquinolones (moxifloxacin, levofloxacin) or ß-lactum/ß-lactamase inhibitor (amoxicillin/clavulanic acid; ampicillin/

sulbactum) or Carbepenms (ertapenem) or 3rd generation cephalosporins + macrolide or monobactum + clindamycin (for ß-lactum – allergic patients

*Antibiotic options should depend on local epedimiology of etiologic pathogens.$ The frequency of macrolide-resistant S. pneum and MDR S pneum is increasing; levofloxacin or moxifloxacin ae preferred to ciprofloxacin and the role of other new quinolones has not been established.


Initial Empiric Antibiotic treatment for late onset HAP Initial Empiric Antibiotic treatment for late onset HAP (Table II)(Table II)Initial Empiric Antibiotic treatment for late onset HAP Initial Empiric Antibiotic treatment for late onset HAP (Table II)(Table II)

Potential Pathogen Recommended RegimenPathogens Listed in table I and MDR pathogens Pseudomonas aeruginosa K. pneumoniae (ESBL+) *

Acinetobacter sp. *

MRSA

Legionella pneumophilia *

Antipseudomonal cephalosporins (cefepime, ceftazidime) or Antipseudomonal carbepene (imipenem or meropenem) or ß-lactum/ß-lactamase inhibitor (piperacillin - tazobactum) +/- Fluoroquinolone (ciprofloxaccin or levofloxacin) or Aminoglycoside (amikacin, gentamicin or tobramycin)

Cefoperazone / sulbactum + fluoroquinolones or aminoglycosides + ampicillin/ sulbactum (if sulbactum is not available

or Fluoroquinolones(ciprofloxacin) + aminoglycoside + linezolid or glycopeptide

(vancomycin or teicoplanin)$ + azithromycin of fluoroquinolone

*if an ESBL strain such as K. pneum or an Acinetobacter sp. Is suspected the a carpenem is a reliable choice. If L. pneumophilia is suspected then the combination antibiotic regimen should include a macrolide (eg. Azithromycin) or a fluoroquinolone (eg. Ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside.$ If MRSA risk factors are presenr or there is a high incidence locally.


Initial Empiric Antibiotic treatment for early onset VAP Initial Empiric Antibiotic treatment for early onset VAP (Table III)(Table III)Initial Empiric Antibiotic treatment for early onset VAP Initial Empiric Antibiotic treatment for early onset VAP (Table III)(Table III)

Potential Pathogen Recommended RegimenPathogens Listed in table I and MDR

pathogens Pseudomonas aeruginosa K. pneumoniae (ESBL+)

Acinetobacter sp.

MRSA

Antipseudomonal cephalosporins (cefepime) or Antipseudomonal carbepene (imipenem or meropenem) or ß-lactum/ß-lactamase inhibitor (piperacillin – tazobactum) +/- Fluoroquinolone (ciprofloxaccin or levofloxacin) or Aminoglycoside (amikacin, gentamicin or tobramycin) +/- Linezolid or glycopeptide ( vancomycin or teicoplanin)


Initial Empiric Antibiotic treatment for late onset HAP Initial Empiric Antibiotic treatment for late onset HAP (Table IV)(Table IV)Initial Empiric Antibiotic treatment for late onset HAP Initial Empiric Antibiotic treatment for late onset HAP (Table IV)(Table IV)

Potential Pathogen Recommended RegimenMDR pathogens Pseudomonas aeruginosa K. pneumoniae (ESBL+)

Acinetobacter sp.

MRSA

Antipseudomonal carbepene (imipenem or meropenem) or ß-lactum/ß-lactamase inhibitor (piperacillin - tazobactum) +/- Fluoroquinolone (ciprofloxaccin or levofloxacin) or Aminoglycoside (amikacin, gentamicin or tobramycin) +/- Linezolid or glycopeptide ( vancomycin or teicoplanin)

Cefoperazone / sulbactum + fluoroquinolones or aminoglycosides + ampicillin/ sulbactum (if sulbactum is not available +/- Linezolid or glycopeptide ( vancomycin or teicoplanin) or Fluoroquinolones(ciprofloxacin) + aminoglycoside +/- linezolid or glycopeptide (vancomycin or teicoplanin)


Treatment Recommendations for Treatment Recommendations for MDR pathogensMDR pathogens

Treatment Recommendations for Treatment Recommendations for MDR pathogensMDR pathogens

MRSAMRSAMRSAMRSA

First line treatment : Teicoplanin or Vancomycin. Teicoplanin as compared to Vancomycin has fewer

side effects and does not require serum monitoring levels.

Linezolid to be reserved as second tier agent.


P. AeruginosaP. AeruginosaP. AeruginosaP. Aeruginosa

First line : Piperacillin/ tazobactum or carbapenems +/- aminoglycosides or fluoroqinolone

Fluoroqinolones offer theoretical advantage of improved bioavailability in respiratory tract.

Ciprofloxacin or Levofloxacin Fluoroqinolones preferred in combination therapy

In unresponsive patients Polymyxin B or Colistin in combination with fluoroqinolone


Acinetobacter sp.Acinetobacter sp.Acinetobacter sp.Acinetobacter sp.

First Line: Cefoperazone/ sulbactam and/or tigecycline Sulbactam an enzyme inhibitor has direct activity against

Acinetobacter. In unresponsive patients : Polymyxin B or Colistin


Antibiotic regimens against specific antibiotic – Antibiotic regimens against specific antibiotic – resistant pathogensresistant pathogensAntibiotic regimens against specific antibiotic – Antibiotic regimens against specific antibiotic – resistant pathogensresistant pathogens

Pathogen Antibiotic Regimen

MRSA 1.Vancomycin or Teicoplanin2.Linezolid or tigecycline

MDR Pseudomonas Aeruginosa

1.Piperacillin/ tazobactum or carbapenems +/- aminoglycosides or fluoroqinolone

2.Polymixin B or Colistin

MDR Acinetobacter 1.Cefoperazone/ sulbactam and/or tigecyclinne2.Polymyxin B or Colistin

ESBL + K. pnumoniae 1.Carbapenems or tigecycline2.Piperacillin/ Tazobactam

ESBL + E. Coli 1.Carbapenems or tigecycline2.Piperacillin/ Tazobactam


Duration of TreatmentDuration of TreatmentDuration of TreatmentDuration of Treatment

Asian HAP Working Group recommends the initial empirical antibiotic treatment should continue for 7 to 14 days.

If MDR pathogen is identified then the treatment may be continued for up to 14 days.

Patient response should be evaluated frequently with consideration given to de-escalating therapy when appropriate.


Role of Teicoplanin

Glycopeptide antibiotics teicoplanin and Vancomycin is the First line therapy

against Nosocomial Pneumonia attributable to MRSA.

Teicoplanin in Nosocomial PneumoniaTeicoplanin in Nosocomial Pneumonia

Hunter J D Postgrad Med J 2006; 82: 172-178

ConclusionsConclusionsConclusionsConclusions

HAP/ VAP is one of the more frequent causes of nosocomial infection and the first one causing death.

MRSA incidence is on rise. MRSA is one of the most common cause of HAP/ VAP No definite guidelines present in Asian countries for

HAP/VAP ARFID & ANSORP recommended treatment for HAP/VAP Teicoplanin is the First line therapy in MRSA HAP/VAP

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Hospital Acquired Pneumonia. Pneumonia that occurs 48 hrs or more after admission, which was not incubating at the time of admission. Hospital Acquired