Healthcare Associated Healthcare Associated PneumoniaPneumonia

Barbara G. Bielska, M.D.Barbara G. Bielska, M.D.Clarian Arnett HealthClarian Arnett Health

Infectious Diseases DepartmentInfectious Diseases Department

DefinitionsDefinitions

HCAP-signs, symptoms and radiographic presence HCAP-signs, symptoms and radiographic presence of PNA in CAP patients with recent contact with the of PNA in CAP patients with recent contact with the healthcare systemhealthcare system

HAP- 48-72 hrs after hospital admissionHAP- 48-72 hrs after hospital admission VAP- 48-72 hrs after endotracheal intubationVAP- 48-72 hrs after endotracheal intubation

Epidemiology of PneumoniaEpidemiology of Pneumonia

Leading cause of infectious diseases related death globally Leading cause of infectious diseases related death globally and in the USand in the US

CDC (2006) more than 56 K deaths CDC (2006) more than 56 K deaths 1.2 mln out of 35 mln annual US hospitalizations1.2 mln out of 35 mln annual US hospitalizations US expenditures > $8 billion annuallyUS expenditures > $8 billion annually 300K cases of HAP/y with associated mortality rate 30-70%300K cases of HAP/y with associated mortality rate 30-70% HAP lengthens hospital stay by 7-9 daysHAP lengthens hospital stay by 7-9 days

Healthcare Associated PneumoniaHealthcare Associated PneumoniaATS/IDSA Guidelines 2005ATS/IDSA Guidelines 2005

Hospitalization for 2 days or more in the preceding 90 daysHospitalization for 2 days or more in the preceding 90 days Residence in the NH or ECFResidence in the NH or ECF Home infusion therapy ( including abx)Home infusion therapy ( including abx) Chronic dialysis within 30 daysChronic dialysis within 30 days Home wound careHome wound care Family member with a MDR pathogenFamily member with a MDR pathogen

HCAP as clinical entityHCAP as clinical entity

Large, heterogeneous patient population with a Large, heterogeneous patient population with a poorly defined conglomeration of risk factors that poorly defined conglomeration of risk factors that may increase the risk of infection with a drug may increase the risk of infection with a drug resistant pathogenresistant pathogen

HCAP DefinitionsHCAP Definitionsby Studyby Study

Kollef at al 2005 ( hospitalization in 30 d, transfer Kollef at al 2005 ( hospitalization in 30 d, transfer from other facility, chronic HD)from other facility, chronic HD)

Carratala at al 2007 (hospitalization in 90 d, NH Carratala at al 2007 (hospitalization in 90 d, NH /ECF residence, home infusions/IV therapy, /ECF residence, home infusions/IV therapy, attended hospital/HD clinic past 30 d, IV attended hospital/HD clinic past 30 d, IV chemotherapy past 30 d)chemotherapy past 30 d)

Shorr at al 2008 (hospitalization in past 90 d, Shorr at al 2008 (hospitalization in past 90 d, NH/ECF, chronic dialysis, immunocompromised NH/ECF, chronic dialysis, immunocompromised state) state)

HACP Definitions by StudyHACP Definitions by Study

Venditti at al 2009 ( hospitalization/surgery in the Venditti at al 2009 ( hospitalization/surgery in the past 180 d, NH/ECF, attended hospital/HD clinic in past 180 d, NH/ECF, attended hospital/HD clinic in the past 30 d, IV chemotherapy in the past 30 d) the past 30 d, IV chemotherapy in the past 30 d)

Shindo at al 2009 ( hospitalization in past 90 d, Shindo at al 2009 ( hospitalization in past 90 d, NH/ECF, home infusions/ IV therapy, NH/ECF, home infusions/ IV therapy,

chronic dialysis, home wound care, chronic dialysis, home wound care,

The Magnitude of the HCAP PopulationThe Magnitude of the HCAP PopulationCAP vs. HCAP by studyCAP vs. HCAP by study

Kollef ’05- CAP-69.2%, HCAP-30.8%Kollef ’05- CAP-69.2%, HCAP-30.8% Micek ‘’07 and Shorr’ 08- CAP-32.6%, HCAP- 67.4%Micek ‘’07 and Shorr’ 08- CAP-32.6%, HCAP- 67.4% Carratala ’07- CAP-82.7%, HCAP- 17.3%Carratala ’07- CAP-82.7%, HCAP- 17.3% Venditti’ 09- CAP- 71.2%, HCAP-28.8%Venditti’ 09- CAP- 71.2%, HCAP-28.8% Shindo ’09- CAP- 62%, HCAP- 38%Shindo ’09- CAP- 62%, HCAP- 38% Avarage CAP-63.9%, HCAP- 36.5%Avarage CAP-63.9%, HCAP- 36.5% % HCAP of community dwelling adults hospitalized for % HCAP of community dwelling adults hospitalized for

pneumoniapneumonia

Etiology and Outcomes HCAP vs. CAPEtiology and Outcomes HCAP vs. CAP

Micek at al ’07single center retrospective cohort analysis Micek at al ’07single center retrospective cohort analysis ( US) 2003-05( US) 2003-05

HCAP (n- 431), CAP (n-208)HCAP (n- 431), CAP (n-208) S.aureus (% MRSA) 44.5% (68.8), 25.5% (47.1)S.aureus (% MRSA) 44.5% (68.8), 25.5% (47.1) S.pneumoniae 10.4%, 40.9%S.pneumoniae 10.4%, 40.9% P.aeruginosa 25.5% , 4.8%P.aeruginosa 25.5% , 4.8% H. influenzae 4.2%, 17.3%H. influenzae 4.2%, 17.3% Legionella sp.Legionella sp. 0.2%, 3.4%0.2%, 3.4% HLS not provided, In hospital mortality 24.6% VS. 9.1%HLS not provided, In hospital mortality 24.6% VS. 9.1%

Etiology and Outcomes HCAP vs. CAPEtiology and Outcomes HCAP vs. CAP

Venditti at al ’09 multicenter prospective Venditti at al ’09 multicenter prospective observational study ( Italy, 55 hosp. ’07)observational study ( Italy, 55 hosp. ’07)

HCAP (n-90), CAP (n-49)HCAP (n-90), CAP (n-49) Variable no pathogen dataVariable no pathogen data HLS in days, mean 18.7 vs. 14.7 , p-value<0.05HLS in days, mean 18.7 vs. 14.7 , p-value<0.05 In hospital mortality 17.8% vs. 6.7%, p-value <0.05In hospital mortality 17.8% vs. 6.7%, p-value <0.05

Etiology and Outcomes HCAP vs. CAPEtiology and Outcomes HCAP vs. CAP

Shindo at al ’09 single center retrospective observational Shindo at al ’09 single center retrospective observational study (Japan), 2005-07study (Japan), 2005-07

HCAP (n-141), CAP (n-230)HCAP (n-141), CAP (n-230) Pathogen (%, culture positive)Pathogen (%, culture positive) S. pneumoniae -13.5, 19.1S. pneumoniae -13.5, 19.1 S.aureus (% MRSA)- 9.9 (35.7), 6.1 (14.3)S.aureus (% MRSA)- 9.9 (35.7), 6.1 (14.3) Pseudomonas sp.-5.7, 1.7Pseudomonas sp.-5.7, 1.7 No pathogen identified- 45.4, 52.6No pathogen identified- 45.4, 52.6 Previous abx past 90 d (%)-63.1, 20.9Previous abx past 90 d (%)-63.1, 20.9 In hospital mortality %- 21.3, 7.4In hospital mortality %- 21.3, 7.4

HCAP or Drug Resistant PNAHCAP or Drug Resistant PNA

Variables independently associated with resistant Variables independently associated with resistant pathogen : MRSA, P.aeruginosa, ESBL Klebsiella pathogen : MRSA, P.aeruginosa, ESBL Klebsiella sp /other non fermenting GNR’s, sp /other non fermenting GNR’s,

Recent hospitalization, 3 moRecent hospitalization, 3 mo Nursing Home residence/ LTCF, poor functional Nursing Home residence/ LTCF, poor functional

statestate Long term hemodialysisLong term hemodialysis ICU admissionICU admission Broad spectrum antibiotics use, 3 moBroad spectrum antibiotics use, 3 mo

Patient’s Risk for Resistant PathogenPatient’s Risk for Resistant Pathogen

Knowledge of reason for prior admissionKnowledge of reason for prior admission Duration of prior hospitalizationDuration of prior hospitalization Receipt of antibiotic therapyReceipt of antibiotic therapy Known MDR pathogen circulating in community or hospitalKnown MDR pathogen circulating in community or hospital Immunosuppressive disease present or therapy givenImmunosuppressive disease present or therapy given Search for drug resistant pathogen specific risk factor is complicated Search for drug resistant pathogen specific risk factor is complicated

by study’s statistical power, selection bias, limitations of case control by study’s statistical power, selection bias, limitations of case control study designstudy design

Limited evidence for community dwellersLimited evidence for community dwellers

HCAP, HAP, VAPHCAP, HAP, VAPDiagnosisDiagnosis

Difficult, no reliable tools to determine if patient has PNADifficult, no reliable tools to determine if patient has PNA No reliable methods to determine causative pathogen when PNA No reliable methods to determine causative pathogen when PNA

presentpresentSampling methods for ventilator-associated pneumonia: Validation using different histologic and microbiological references. Crit Care Med. 28: 2000; 2799-2804.

New infiltrate on CXR, fever, purulent sputum

other signs of clinical deterioration

Clinical method was shown to be specific for HAP in only 27 of 84 patients in a series reported by Fagon at al.

Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients. Chest. 103: 1993; 547-553

Conditions mimicking PNAConditions mimicking PNAin critically ill in critically ill

Congestive heart failure Pulmonary embolism Atelectasis Acute respiratory distress syndrome (ARDS) Pulmonary hemorrhage Drug reactions

Imperfect diagnostic testsImperfect diagnostic tests

Blood cultures, limited role, Blood cultures, limited role, sensitivity is only 8% to 20% Sputum neither sensitive, nor specificSputum neither sensitive, nor specific Tracheo-bronchial aspirates- high sensitivity, weakness- does not differentiate Tracheo-bronchial aspirates- high sensitivity, weakness- does not differentiate

between pathogen and colonizerbetween pathogen and colonizer

Hospital-acquired pneumonia: Risk factors, microbiology, and treatment. Chest. 119: 2001; 373S-384S. BAL, PSB’s do not differ from less invasive tests in terms of sensitivity, specificity

or, more importantly, morbidity and mortality luck of consensus on the role of invasive diagnostic testing for HAP, subject of

ongoing debate- Noninvasive versus invasive microbial investigation in ventilator-associated pneumonia: Evaluation of outcome. Am J Respir Crit Care

Med. 162: 2000; 119-125.

- Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia: A randomized trial. Ann Intern Med. 132: 2000; 621-630.

HCAP, HAP, VAPHCAP, HAP, VAPTreatmentTreatment

Delay in empiric antibiotics use, worse outcomeDelay in empiric antibiotics use, worse outcome International conference for the development of consensus on the diagnosis and treatment of ventilator-associated pneumonia. Chest. 120: 2001; 955-970.

Mortality with prompt abx use 30% vs. 91 % when delayed Nosocomial pneumonia: A multivariate analysis of risk and prognosis. Chest. 93: 1988; 318-324

Regimens in patients with no known risk factors for MDR pathogens, and who have early-onset pneumonia (within 5 days of hospitalization) should include coverage for Enterobacter spp., E. coli, Klebsiella spp., Proteus spp., and Serratia marcescens), Haemophilus influenzae and Streptococcus pneumoniae, MSS. aureus

HCAP, HAP, VAPHCAP, HAP, VAPTreatmentTreatment

ceftriaxone or a quinolone (e.g., ciprofloxacin or levofloxacin) or ampicillin-sulbactam or eratpenem

fluoroquinolone in the empirical regimen of patients with penicillin allergies

penicillin skin testing – a mean to decrease fluoroquinolones use

A pilot study of penicillin skin testing in patients with a history of penicillin allergy admitted to a medical ICU. Chest. 118: 2000; 1106-1108.

Antibiotics for Empirical Therapy of Hospital-Acquired Pneumonia * in Patients at Risk for Multidrug-Resistant Pathogens

Antibiotic Adult Dosage † Antipseudomonal cephalosporinCefepime 1-2 g every 8-12 hrCeftazidime 2 g every 8 hrCarbepenemsImipenem 500 mg every 6 hr or 1 g every 8 hrMeropenem 1 g every 8 hrBeta-lactam–beta-lactamase inhibitorPiperacillin-tazobactam 4.5 g every 6 hrAminoglycosidesGentamicin 7 mg/kg/dayTobramycin 7 mg/kg/dayAmikacin 20 mg/kg/dayAntipseudomonal quinolonesLevofloxacin 750 mg/dayCiprofloxacin 400 mg every 8 hrVancomycin 15 mg/kg every 12 hrLinezolid 600 mg every 12 hrGuidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005;171:388-416.

Duration of treatmentDuration of treatment

No consensus, initial low suspicion, no No consensus, initial low suspicion, no change in clinical status- dc in 72 hrs change in clinical status- dc in 72 hrs Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med. 162: 2000; 505-511.

Guided by severity, time to clinical response, and the pathogenic organism

Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare associated-pneumonia. Am J Respir Crit Care Med. 171: 2005; 388-416.

Treat for at least 72 hours after a clinical response is achieved

International conference for the development of consensus on the diagnosis and treatment of ventilator-associated

pneumonia. Chest. 120: 2001; 955-970.

Recommendations for Assessing Response to Treatment

-Modifications of empirical therapy should be based on results of microbiology testing in conjunction with clinical parameters.

-Clinical improvement of HCAP usually takes 2 to 3 days and therefore therapy should not be changed during this period unless there is a rapid clinical decline. -Narrowing therapy to the most focused regimen possible on the basis of culture data (de-escalation of antimicrobials) should be considered for the responding patient.

-The nonresponding patient should be evaluated for possible MDR pathogens, extrapulmonary sites of infection, complications of pneumonia and its therapy, and mimics of pneumonia. -Testing should be directed to whichever of these causes is likely after physical examination of the patient.

Prevention MeasuresPrevention Measures

Based on expert opinion rather than hard data CDC published a set of 74 recommendations for preventing NAP ,

only 15 strongly supported by well-designed experimental or epidemiologic studies

14 out of those 15 dealt with surveillance, education, hand washing, sterilization, proper use of gloves, value of vaccination, and sanitation

Prophylactic antibiotics not be used routinely , only one supported by well-designed studies

Centers for Disease Control and Prevention. Guidelines for prevention of nosocomial pneumonia. MMWR Morb Mortal Wkly Rep. 46: 1997; 1-79.

Prevention MeasuresPrevention Measures

Proper hand washing, use of gloves, and measures to reduce contamination from respiratory therapy equipment

Universally recognized, often not performed, see observational study performed in an ICU setting 10% of health care workers washed their hands before having direct patient contact and only 32% washed their hands after patient contact

Risk factors for an outbreak of multi-drug-resistant Acinetobacter nosocomial pneumonia among intubated patients. Chest. 115: 1999; 1378-1382.

Reduction of HCAP IncidenceReduction of HCAP Incidence

Reduce immunosuppression, reduce sedation, avoid transportation of patients out of the ICU, and provide adequate nutrition

Oral placement of endotracheal or gastric tubes (sinusitis reduction)

Subglottic secretion drainage, continuous suction of oropharyngeal secretions in an effort to prevent pooling and thus aspiration

Semirecumbent position prevents aspiration of refluxed gastric contents

Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: A randomised trial. Lancet. 354: 1999; 1851-1858.

Reduction of HCAP IncidenceReduction of HCAP Incidence

Administration of prophylactic antibiotics or nonabsorbable antibiotics for the purpose of gastrointestinal decontamination

Not shown to influence mortality or length of stay, use of antibiotics in this manner may lead to the development of resistant organisms

International conference for the development of consensus on the diagnosis and treatment of ventilator-associated pneumonia. Chest. 120: 2001; 955-970.

Results regarding the role of histamine blockers in the development of HAP are conflicting

Antibiotics select out resistant or virulent organisms, 65% of PNA in vented patients who received prophylactic abx was caused by Acinetobacter and /or Pseudomonas sp.

In antibiotic-naïve patients, only 19% of infections were caused by these pathogens

Nosocomial pneumonia in patients receiving continuous mechanical ventilation. Prospective analysis of 52 episodes with use of a protected specimen brush and quantitative culture techniques. Am Rev Respir Dis. 139: 1989; 877-884.

Things to RememberThings to Remember

HACP, HAP, VAP = BAD for the patientHACP, HAP, VAP = BAD for the patient Quantitative diagnostic microbiology- controversial!Quantitative diagnostic microbiology- controversial! Cover likely bugs promptlyCover likely bugs promptly Know your local bugsKnow your local bugs De-escalate, shorten duration of therapyDe-escalate, shorten duration of therapy Specific regimen, combination therapy- no proven Specific regimen, combination therapy- no proven

benefitsbenefits

Things to DoThings to Do

Get patient’s HOB at 30-45 degreesGet patient’s HOB at 30-45 degrees Get the ET tube outGet the ET tube out Get the NG tube outGet the NG tube out Get of the ventilator as apGet of the ventilator as ap

THANK YOU THANK YOU