Pneumonias: HAP/HCAP/VAP

1. Pneumonias: HAP/HCAP/VAP • Kendra McAnally, D.O. • Pulmonary/Critical Care • Lung Transplant • Ochsner Clinical Foundation • New Orleans, LA

2. Financial Disclosures • None

3. Understand the likely pathogens responsible for HAP/HCAP/CAP based on length of hospitalization and risk factors. • Know which organisms are associated with increased mortality. • Utilize the recommended antibiotic treatment based on understood pathogens. • Be familiar with the role of diagnostic testing in the evaluation and treatment of these pneumonias.

4. Definitions • Hospital Acquired Pneumonia (HAP) • Ventilator Associated Pneumonia (VAP) • Healthcare Associated Pneumonia (HCAP)

5. Definitions • HAP: pneumonia that occurs 48 hours or more after admission and did not appear to be incubating at the time of admit. • VAP: A type of HAP acquired at 48-72 hours after intubation. • HCAP: non hospital patient with healthcare contact • IV therapy, wound care, chemotherapy within 30 days • Nursing home or long term care facility (SNF/LTAC) • Hospitalization >2 days ore more in past 90 days • Attendance at hospital or HD within 30 days • ATS/IDSA Am J Respir Crit Care Med. 2005;171: 388-416

6. HCAP • Added as a category of pneumonia in the 2005 ATS/IDSA guidelines as an increased risk for patients who may have been exposed to multidrug-resistant (MDR) pathogens from community settings. • Overgeneralization? and current recommendations for empiric therapy?

7. Four Major Principles Underlie the Management of HAP, VAP and HCAP • Avoid untreated or inadequately treated HAP, VAP or HCAP, failure to do so is a consistent factor associated with increased mortality. • Recognize the variability of bacteriology from one hospital to another, one department from another and one time period to another. • Avoid the overuse of antibiotics by focusing on accurate diagnosis, tailoring therapy and limit duration of therapy to the minimal effective period. • Apply prevention strategies aimed at modifiable risk factors.

8. Epidemiology • HAP is the second most common nosocomial infection in the US • HAP increased hospital stay by an average of 7-9 days per patient • Estimated occurrence of 5-10 cases per 1,000 hospital admissions • HAP accounts for up to 25% of all ICU infections and more than 50% of antibiotics prescribed

9. Epidemiology • Early onset HAP and VAP (first 4 days) carries a better prognosis with better bacterial sensitivities. • Patients with hospitalization or prior antibiotic use within last 90 days should be treated as late onset HAP or VAP due to risk of MDR bacteria. • Late onset HAP and VAP (5 days plus) • MDR pathogens • Increased morbidity/mortality

10. Epidemiology • HAP-associated mortality remains the leading cause of death among hospital-acquired infections: estimated at 20-50%. • Studies not relating co-founding factors- age, debility, stroke, MI, etc.

11. Epidemiology • Crude mortality of HAP is 30-70%, but may be due to underlying disease rather than pneumonia. • Attributable mortality is 33-50%. • Worse outcomes in patients with bacteremia (esp Pseudomonas aeruginosa or Acinetobacter species), medical rather than surgical illness, ineffective antibiotic therapy.

12. Etiology: HAP, VAP and HCAP • Aerobic gram-negative bacteria: • P. aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Acinetobacter species • Gram-positive cocci • Staphylococcus aureus (50% in ICU due to MRSA) • More common in patients with diabetes mellitus, head trauma and those hospitalized in the ICU. • Oropharyngeal commensals (viridans group streptococci, coag-negative Staph, Neisseria species and Corynebacterium) may be relevant in mostly immunocompromised patients.

13. VAP etiology Other Staph areus Pseudomonas

14. H. influenzae C. pneumoniae M. pneumoniae S. pneumoniae Other/unknown 50% 44% 10% 14% 17% 7% Etiology of CAP Among Hospitalized Patients S. pneumoniae M. pneumoniae 40% C. pneumoniae 30% H. influenzae Gram-negbacilli 20% S.aureus 10% L. pneumophila Other/unknown 0% Common CAP Pathogens Mandell LA, et al. Clin Infect Dis. 2000;31:383-421.

15. HCAP Pathogens More Similar to HAP than CAP Kollef MH,et al. Chest .2005;128:3854-62.

16. Mean Mortality Rates in Patients with CAP, HCAP, HAP or VAP P<.0001 P<.0001 P>.05 Kollef MH, et al. Chest. 2005;128:3854-62.

17. 30 Pathogens Causing Nosocomial Pneumonia (Trends over Time)National Nosocomial Infections Surveillance System 25 S aureus 20 P aeruginosa Enterobacter spp. 15 E coli K pneumoniae 10 Serratia marcescens Acinetobacter spp 5 0 20031 19751 1992–19982 1. Gaynes R, et al. Clin Infect Dis .2005; 41:848-54. NNIS system report. Am J Infect Control. 2000; 28(6):429-48. 2. Richards MJ, et al. Infect Control Hosp Epidemiol. 2000; 21:510-5.

18. Etiology: Special Circumstances • HAP involving anaerobic organisms may follow aspiration in non-intubated patients, rare in VAP. • Patients who have used NIPPV. • HCAP in elderly patients of long term care facilities have pathogens that more closely resemble laste-onset HAP and VAP.

19. Pathogenesis • Number and virulence of organisms entering the lower respiratory tract and response of the host. • microaspiration of organisms which have colonized the upper respiratory/gastrointestinal tract • Hospitalized patients tend to become colonized with organisms in the hospital environment within 48 hours. • Common mechanisms include: mechanical ventilation, routine nursing care, lack of hand washing of all hospital personnel. • Disease state also plays a role: alteration in gastric pH due to illness, certain medications, malnutrition and supplemental feedings.

20. Multi-drug resistance • Gram negative bacilli • MDR: variably defined as resistance to at least 2-8 antibiotics that are usually used to treat common infections. • Pan-resistance: Gram negative organisms resistant to cephalosporins, beta-lactams and fluoroquinolones.

21. Microbiology • Common pathogens: • aerobic gram-negative rods: E coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter • gram positive cocci: Staphylococcus aureus-MRSA, MSSA, Streptococcus • Nosocomial pneumonia most often seen in immunocompromised patients which include viruses and fungal infections.

22. MDR: Pseudomonas Aeruginosa • Most common MDR gram-negative causing HAP/VAP. • Increasing resistance to piperacillin, ceftazidime, cefepime, imipenem and meropenem. • Currently, someMDR isolates of P. aeruginosa are susceptible to only polymyxin B.

23. MDR: Klebsiella, Enterobacter, and Serratia Species • Klebsiella are resistant to ampicillin and can acquire resistance to cephalosporins and aztreonam by producing extended-spectrum beta-lactamases (ESBLs). • ESBLs remain susceptible to carbapenems. • Citrobacter and Serratia may also produce ESBLs

24. MDR: Acinetobacter species, Stenotrophomonas Maltophilia and Burkholderia Cepacia • Acinetobacter has recently showed increased resistance to common antimicrobials. • More than 85% are susceptible to carbapenems, but resistance is increasing. • Sulbactam has become an alternative therapy. • S. maltophilia and B. cepacia are common colonizers of the respiratory tract. • Uniformly resistant to carbapenems • Usually susceptible to Bactrim, Timentin, or fluoroquinolone. • B. cepacia is also usually susceptible to ceftazidime and carbapenems.

25. MDR: Methicillin-Resistant Staphylococcus Aureus (MRSA) • Vancomycin-intermediate: MIC 8-16 mcg/ml • High-level vancomycin-resistant: MIC of 32-1024 mcg/ml • All have been sensitive to linezolid • Linezolid resistance has emerged, but currently is rare

26. MDR: Streptococcus pneumoniae and Haemophilus influenzae • Most likely associated with early-onset HAP in patients without other risk factors. • Frequently community acquired • Many strains or S. pneumoniae are penicillin resistant (penicillin binding proteins), these can also be resistant to cephalosporins, macrolides, tetracyclines, and clindamycin. • Despite in vitro resistance, usually have good outcomes with penicillins and cephalosporins. • All MDR strains are sensitive to vancomycin or linezolid and fluoroquinolones. • MDR resistance is rare in Haemophilus influenzae

27. Microbiology • Fungal pathogens: most common is Candida and Aspergillus • Most commonly in organ transplant or immunocompromised, neutropenic patients. • Aspergillus- contaminated air ducts or local construction. • Candida- common airway colonizer and rarely requires treatment.

28. Microbiology • Viral Pathogens: low incidence in immunocompetent hosts. • Influenza A is the most common viral cause of HAP and HCAP in adults. • Risk for secondary bacterial infection “super-infection” • Streptococcus, H. influenza, Group A Streptococcus, S. aureus

29. VAP and HAP • Leading infectious causes of VAP include MSSA (9%), MRSA (18%), P. aeruginosa (18%), S. maltophilia (7%), Acinetobacter spp (8%) and others (9%) • HAP include, MSSA (13%), MRSA (20%), P. aeruginosa (9%), S. maltophilia (1%), Acinetobacter spp (3%), and others (18%)

30. HCAP • Most patients included in these studies were recently hospitalized or had been transferred from nursing home. • Retrospective cohort: 4543 patients with pneumonia occurring within five days of admission to US hospitals between 1/2002 and 12/2003: • S. aureus in HCAP and HAP were 47% and the CAP group was 26%. • Rate of MRSA infection was higher in HCAP and HAP (27% and 23%) and the CAP group was 9%. • Rate of P. aeruginosa had significant occurrence of 25% in HCAP patients. • Kollef MH, Shorr A, Tabak YP, et al. Epidemiology and outcomes of health-care associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005; 128:3854.

31. HCAP • Prospective observational analysis of 727 cases of pneumonia from Spain compared the etiology of 126 cases of HCAP and 601 cases of CAP: • Most common organism in both groups was S. pneumonia. • Drug resistance more common in HCAP. • Legionella was more common in CAP. • H. influenzae and GNR were more common in HCAP. • S. aureus was more common in patients with HCAP. • Carratala J, Mykeitiuk A, Fernandez-Sabe N, et al. Health care-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes. Arch Intern Med 2007; 167:1393.

32. HCAP • Multicenter, prospective observational study from 55 hospitals in Italy, 362 patients were hospitalized during two one-week periods. • 62 patients had CAP, 25% had HCAP, and 14% VAP • Higher mortality in HCAP patients (18% vs 7%) • Longer length of hospitalization (19% vs 15%) • The majority of patients classified as having HCAP were hospitalized within 180 days (longer than the 90 days which is the current definition of HCAP in the ATS/IDSA Guidelines) • Venditii M, Falcone M, Corrao S, et al. Outcomes of patients hospitalized with community-acquired, health care-associated, and hosptial-acquired pneumonia. Ann Intern Med 2009; 150:19.

33. MDR risk factors • Host risk factors for infection with MDR pathogens include: • Treatment with antibiotics within the preceding 90 days. • Current hospitalization of >4 days • High frequency of antibiotic resistance in the community or hospital unit • Immunosuppressive disease and/or therapy

34. HCAP and MDR • Specific risk factors for MDR pathogens associated with HCAP: • hospitalization for >/= 2 days within the last 90 days • severe illness • antibiotic therapy in the past 6 months • poor functional status as defined by ADL score • Immunosuppression

35. Modifiable Risk Factors • Strict infection control • Alcohol-based hand disinfection • Microbiologic surveillance with timely data on local MDR pathogens • Removal of invasive devices • Programs to reduce or alter antibiotic-prescribing practices

36. Modifiable Risk Factors: Intubation and Mechanical Ventilation • Intubation and mechanical ventilation increase the risk of HAP 6-21 fold. • NIPPV, data shows use to avoid reintubation may be associated with more incidence of HAP. • Sedation protocols to accelerate ventilator weaning. • Reintubation increases the risk of VAP • Oral gastric and tracheal tubes rather than nasal may reduce incidence of sinusitis and subsequent lower respiratory tract infection (HAP). • Limiting use of sedative and paralytic agents that depress cough. • Keep endotracheal cuff to >20 cm H2O

37. Modifiable Risk Factors: Aspiration, Body Position and Enteral Feeding • HOB >30 degrees during enteral feedings decreases risk for aspiration. • Post-pyloric feeding appears to be superior in a meta-analysis at reducing ICU-acquired HAP.

38. Modifiable Risk Factors: Modulation of Colonization: Oral Antiseptics and Antibiotics • Oropharyngeal colonization is an independent risk factor for ICU-acquired HAP by enteric gram-negative bacteria and P. aeruginosa • Oral antiseptic chlorhexidine significantly reduced rates of nosocomial infection in post-operative patients and is routinely used in the ICU as part of “oral care”. • Selective decontamination fo the digestive tract (SDD): using non-absorbable antibiotics either orally or through GT has shown benefit in reducing HAP/VAP. However not widely used in the US due to risk for drug resistance.

39. MDR: Stress Bleeding Prophylaxis, Transfusion, and Glucose Control • H2 blockers have shown an increased risk for VAP, risk vs. benefit for stress bleeding should be considered • Multiple studies have identified allogeneic blood products as a risk factor for post-operative pneumonia, and the time length of blood storage as another risk factor. Blood transfusion is usually limited to Hb <7 in the patient who has no active bleeding. • Hyperglycemia is an additional risk for blood stream infection, increased duration of mechanical ventilation increasing risk for HAP/VAP.

40. Diagnosis • Difficult because the clinical findings are nonspecific. • 2005 ATS/IDSA guidelines on the management of adults with HAP, VAP and HCAP do not provide specific criteria.

41. Diagnosis • HAP, VAP or HCAP should be suspected in patients with a new or progressive infiltrate on lung imaging and clinical characteristics such as: • Fever • Purulent sputum • Leukocytosis • Decline in oxygenation • Radiographic findings plus two of the clinicalfindings. • 69% sensitivity and 75% specificity for pneumonia.

42. Diagnosis • A lower respiratory tract culture needs to be collected from all patients before antibiotic therapy, but collection of cultures should not delay the initiation of therapy in critical ill patients. • semiquantitative or quantitative culture data can be used for management of patients with HAP. • Lower respiratory tract cultures from bronchoscopy or tracheal aspirate, mostly applies to VAP.

43. Diagnosis • Quantitative cultures increase specificity of the diagnosis of HAP. • Negative lower respiratory tract cultures can be used to stop antibiotic therapy in a patient who has had cultures obtained in the absence of an antibiotic change in the past 72 hours.

44. Diagnosis • Comprehensive medical history • Chest xray (preferably PA and Lat) to identify infiltrate and possible complication such as effusion or cavitation • Arterial oxygenation saturation +/- ABG • Blood cultures • Patients with moderate/severe pleural effusion should undergo thoracentesis to rule out empyema or parapneumonic effusion. • Lower respiratory tract samples: sputum culture, BAL or tracheal aspirate. • A sterile culture of respiratory secretions in the absence of new antibiotic in the past 72 hours virtually rules out the presence of bacterial pneumonia. (Viral and Legionella still possible)

45. Summary of the management strategies for a patient with suspected hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), or healthcare-associated pneumonia (HCAP). The decision about antibiotic discontinuation may differ depending on the type of sample collected (PSB, BAL, or endotracheal aspirate), and whether the results are reported in quantitative or semiquantitative terms (see text for details).

46. Antibiotic Treatment of HAP

47. Initial empiric antibiotic therapy for hospital-acquired pneumonia or ventilator-associated pneumonia in patients with no known risk factors for multidrug-resistant pathogens, early onset, and any disease severity • ↵* See Table 5 for proper initial doses of antibiotics. • ↵† The frequency of penicillin-resistant S. pneumoniae and multidrug-resistant S. pneumoniae is increasing; levofloxacin or moxifloxacin are preferred to ciprofloxacin and the role of other new quinolones, such as gatifloxacin, has not been established.

48. Initial empiric therapy for hospital-acquired pneumonia, ventilator-associated pneumonia, and healthcare-associated pneumonia in patients with late-onset disease or risk factors for multidrug-resistant pathogens and all disease severity • ↵* See Table 5 for adequate initial dosing of antibiotics. Initial antibiotic therapy should be adjusted or streamlined on the basis of microbiologic data and clinical response to therapy. • ↵† If an ESBL+ strain, such as K. pneumoniae, or an Acinetobacter species is suspected, a carbepenem is a reliable choice. If L. pneumophila is suspected, the combination antibiotic regimen should include a macolide (e.g., azithromycin) or a fluoroquinolone (e.g., ciprofloxacin or levofloxacin) should be used rather than an aminoglycoside. • ↵‡ If MRSA risk factors are present or there is a high incidence locally.

49. Initial intravenous, adult doses of antibiotics for empiric therapy of hospital-acquired pneumonia, including ventilator-associated pneumonia, and healthcare-associated pneumonia in patients with late-onset disease or risk factors for multidrug-resistant pathogens • ↵* Dosages are based on normal renal and hepatic function. • ↵† Trough levels for gentamicin and tobramycin should be less than 1 μg/ml, and for amikacin they should be less than 4–5 μg/ml. • ↵‡ Trough levels for vancomycin should be 15–20 μg/ml.

50. Assessment of Non-Responders Wrong Organism Drug-resistant Pathogens: (Bacteria, Mycobacteria, Virus, Fungus) Inadequate Antimicrobial Therapy Wrong Diagnosis Atelectasis Pulmonary Embolism ARDS Pulmonary Hemorrhage Underlying Decease Neoplasm Complications Empyema or Lung Abscess Clostridium Difficile Colitis Occult Infection Drug Fever