Nosocomial Pneumonias In Critical Illness


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Edward Omron MD, MPH, FCCP
Pulmonary and Critical Care Medicine
Morgan Hill, CA 95037

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  • Staphlococcus
  • Streptococcus
  • Klebsiella pneumonia
  • Hemophilus influenzae pneumonia
  • Nosocomial Pneumonias In Critical Illness

    1. 1. Nosocomial Pneumonias In Critical Illness Edward M. Omron MD, MPH, FCCP Pulmonary and Critical Care
    2. 2. History <ul><li>44 year-old woman presents with 4 days cough, chills, dyspnea and fever </li></ul><ul><li>Hemoptysis with right sided pleuritic chest pain x 2 days </li></ul><ul><li>Unable to walk due to dyspnea </li></ul><ul><ul><li>35 pack year tobacco use </li></ul></ul><ul><ul><li>Long term cocaine use </li></ul></ul><ul><ul><li>Tested HIV negative 3 months earlier </li></ul></ul>
    3. 3. Physical Exam <ul><li>Respiratory distress </li></ul><ul><li>Temp 101.8 F </li></ul><ul><li>Heart Rate 110 </li></ul><ul><li>Blood pressure 80/55 mm Hg </li></ul><ul><li>Dullness to percussion on right side with crackles </li></ul>
    4. 4. Initial Tests <ul><li>ECG: Sinus Tachicardia with LVH </li></ul><ul><li>WBC: 18,600 </li></ul><ul><li>Creatinine: 1.5, BUN 47 </li></ul><ul><li>ABG </li></ul><ul><ul><li>pH 7.32 </li></ul></ul><ul><ul><li>PaCO2 = 47 mm Hg </li></ul></ul><ul><ul><li>PaO2 = 58 mm Hg on 4 L NC </li></ul></ul><ul><ul><li>PaO2/FIO2 = 175 </li></ul></ul>
    5. 5. ER Chest X-RAY
    6. 6. What is the most likely pathogen in this patient? <ul><li>S pneumoniae </li></ul><ul><li>H influenzae </li></ul><ul><li>S aureus </li></ul><ul><li>P aeroginosa </li></ul><ul><li>K pneumoniae </li></ul><ul><li>M tuberculosis </li></ul><ul><li>Other </li></ul>
    7. 7. Initial Treatment in the ER <ul><li>Right IJ central venous access </li></ul><ul><li>Fluid bolus 1 Liter 0.9% LR </li></ul><ul><li>Oxygen converted to 40% venturi mask </li></ul><ul><li>Bipap on the way </li></ul><ul><li>Albuterol / Atrovent neb treatments </li></ul><ul><li>Transduced CVP < 8 mm Hg after fluid bolus and second 1 L 0.9% LR given </li></ul><ul><li>Svo2 = 70%, appropriate oxygen extraction </li></ul><ul><li>GOAL DIRECTED THERAPY IS JUST AS IMPORTANT </li></ul><ul><li>AS CORRECT EMPIRIC ANTIBIOTICS! </li></ul>
    8. 8. SEPTIC SHOCK PRESENT SBP ≤ 90 mmHg or MAP ≤ 65 mmHg OR Lactate ≥ 4 mmol/L PLUS Clinical Picture c/w Infection Fluid bolus 20 ml/kg (.9 NaCl or LR) PLUS Vasopressors if MAP is judged to be critically low SBP < 90 mmHg, or MAP < 65 mmHg, or Lactate > 4 mmol/L CVP < 8 mmHg Insert CVP Catheter Boluses crystalloid or colloid equivalent until CVP > 8 mmHg Check MAP Assess ScvO2 Achieve ALL Goals? < 70% Dobutamine or RBCs depending on HCT MAP ≥ 65 Resuscitation complete. Establish re-evaluation intervals. YES
    9. 9. What antibiotic regimen would you prescribe in the ER? <ul><li>Beta Lactam </li></ul><ul><li>Respiratory quinolone </li></ul><ul><li>3 rd Generation Cephalosporin+macrolide </li></ul><ul><li>3 rd Generation Cephalosporin+ respiratory quinolone </li></ul><ul><li>Carbapenem </li></ul><ul><li>Carbapenem+ aminoglycoside </li></ul><ul><li>Vancomycin+ respiratory quinolone </li></ul><ul><li>Linazolid + respiratory quinolone </li></ul>
    10. 10. Initial antibiotics given in the ER <ul><li>Ceftriaxone 2 gram and levofloxacin 750 mg </li></ul><ul><li>Rationale: </li></ul><ul><ul><li>Most likely diagnosis was thought to be CAP (Streptococcus pneumo +/- H influ) </li></ul></ul><ul><ul><li>Atypical pathogen coverage for legionella </li></ul></ul>
    11. 11. Pneumonia Normal Lung Pneumonia: inflammatory cells and debri in alveolar spaces Lobar Pneumonia
    12. 12. Deep Tracheal Aspirate? Gram positive cocci in clusters?
    13. 13. Deep Tracheal Aspirate? Spherical gram positive cocci arranged in chains or pairs?
    14. 14. Deep Tracheal Aspirate? Gram negative bacillary organisms?
    15. 15. Deep Tracheal Aspirate? Gram negative coccobacillary forms?
    16. 16. Gram-positive bacteria, the purple crystal violet stain is trapped by the layer of peptidoglycan which forms the outer layer of the cell. Gram-negative bacteria, the outer membrane prevents the stain from reaching the peptidoglycan layer in the periplasm. The outer membrane is then permeabilized by acetone treatment, pink safranin counterstain is trapped by the peptidoglycan layer.
    17. 17. Follow Up <ul><li>Urine legionella antigen negative </li></ul><ul><li>Deep tracheal aspirate: </li></ul><ul><ul><li>PMNS 4+, gram + cocci in clusters 4+ which later grew out MRSA </li></ul></ul><ul><li>Blood Cultures: MRSA, PVL+ or CA-MRSA </li></ul><ul><li>Community Acquired MRSA </li></ul>
    18. 18. Community Acquired MRSA Sensitivity in this patient <ul><li>Oxacillin Resistant </li></ul><ul><li>Fluoroquinolone Intermediate </li></ul><ul><li>Macrolide Resistant </li></ul><ul><li>Cephalosporin Resistant </li></ul><ul><li>Gentamycin Sensitive </li></ul><ul><li>Vancomycin Sensitive </li></ul><ul><li>Clindamycin Sensitive </li></ul><ul><li>Linezolid Sensitive </li></ul><ul><li>Bactrim Sensitive </li></ul>
    19. 19. What antibiotic would you have prescribed now? <ul><li>Vancomycin </li></ul><ul><li>Linazolid </li></ul><ul><li>Daptomycin </li></ul><ul><li>Tigecycline </li></ul><ul><li>Clindamycin </li></ul><ul><li>Bactrim </li></ul><ul><li>Respiratory quinolone </li></ul><ul><li>Other </li></ul>
    20. 20. CA-MRSA Pneumonia <ul><li>MRSA is an increasing threat in all forms of pneumonia </li></ul><ul><li>CA-MRSA is the newest threat to hospitalized patients with pneumonia </li></ul><ul><li>“ Superbug” </li></ul><ul><ul><li>Enhanced antibiotic resistance </li></ul></ul><ul><ul><li>Higher mortality than MSSA strains </li></ul></ul><ul><ul><li>Expresses multiple virulence factors </li></ul></ul>
    21. 21. CA-MRSA Virulence <ul><li>Delays in the administration of an appropriate antibiotic and clinician failure recognize risk factors for MRSA pneumonia is a factor in excess mortality </li></ul>
    22. 22. Panton-Valentine Leukocidin (PVL) Toxin <ul><li>Potent mediator of inflammation and activator of leukocytes </li></ul><ul><li>PVL destroys leukocytes by creating lytic pores </li></ul><ul><li>Genes for PVL are found in CA-MRSA isolates and is associated with CA-MRSA mortality (SCC IV) </li></ul>
    23. 23. MRSA Virulence
    24. 24. CA-MRSA: 48 hours of destruction Admission 48 hours later
    25. 25. MRSA as a CA and HA Pathogen CA-MRSA HA-MRSA Invasive High percentage of soft tissue infections High rate of infection Susceptible to non-beta-lactams (so far) Invading the hospital SCC type IV Less likely to cause soft tissue infection Growing cause of pneumonia Multiresistant May be becoming less prevalent in hospital SCC type I, II, III MRSA = methicillin-resistant S aureus CA = community-acquired HA = hospital-acquired SCC = Staphlococcal cassette cartridge
    26. 26. Healthcare Associated MRSA Infections <ul><li>Prevalence </li></ul><ul><ul><li>60% of ICU acquired S. aureus strains are MRSA </li></ul></ul><ul><ul><li>11% increase over the past 5 years </li></ul></ul><ul><ul><li>50% of non-ICU hospital acquired S. aureus strains are MRSA </li></ul></ul><ul><ul><li>31% of S. aureus strains seen in hospital outpatients are MRSA </li></ul></ul>
    27. 27. Risk Factors for Healthcare Associated MRSA <ul><li>Extended care facilities patients </li></ul><ul><li>Diabetes Type I </li></ul><ul><li>Hemodialysis / peritoneal dialysis </li></ul><ul><li>Prolonged hospitalization </li></ul><ul><li>ICU admission </li></ul><ul><li>Indwelling vascular catheters </li></ul><ul><li>Recent or frequent antimicrobial usage </li></ul>
    28. 28. Healthcare Associated MRSA Sensitivities <ul><li>Oxacillin Resistant </li></ul><ul><li>Fluoroquinolone Resistant </li></ul><ul><li>Macrolide Resistant </li></ul><ul><li>Cephalosporin Resistant </li></ul><ul><li>Gentamycin Resistant </li></ul><ul><li>Clindamycin Resistant </li></ul><ul><li>Vancomycin Sensitive </li></ul><ul><li>Linezolid Sensitive </li></ul><ul><li>Bactrim Sensitive </li></ul>
    29. 29. Risk Factors for CA-MRSA Infection <ul><li>Injecting drug users </li></ul><ul><li>Homeless persons </li></ul><ul><li>Competitive athletes, prisoners, soldiers </li></ul><ul><li>Ethnic populations (Native americans…) </li></ul><ul><li>Men who have sex with men </li></ul><ul><li>Recent or frequent antimicrobial use </li></ul><ul><li>Sometimes no risk factors identified </li></ul>
    30. 30. Community Acquired MRSA <ul><li>CA-MRSA is an emerging pathogen among patients without established risk factors </li></ul><ul><ul><li>No recent hospitalization </li></ul></ul><ul><ul><li>Immunocompetant </li></ul></ul><ul><ul><li>No injecting drug use </li></ul></ul><ul><ul><li>No residence in long-term facilities </li></ul></ul>
    31. 31. Community Acquired MRSA <ul><li>Almost 90% of cases are skin infections first detected as clusters of abscesses </li></ul><ul><ul><li>Sports, Jails, military recruits </li></ul></ul><ul><ul><li>Furuncles </li></ul></ul><ul><ul><li>Impetigo </li></ul></ul><ul><ul><li>Necrotizing soft tissue infections </li></ul></ul><ul><ul><li>Osteomyelitis </li></ul></ul><ul><ul><li>Pneumonia </li></ul></ul>
    32. 32. CA-MRSA pneumonia <ul><ul><li>Associated with influenza outbreaks </li></ul></ul><ul><ul><li>Up to 25% of bacterial superinfections after influenza </li></ul></ul>
    33. 33. Clinical Presentation CA-MRSA <ul><li>High Fever </li></ul><ul><li>Severe necrotizing pneumonia </li></ul><ul><li>Leukopenia </li></ul><ul><li>Respiratory Failure </li></ul><ul><li>Shock </li></ul><ul><li>Majority require ICU admission with severe protracted illness and morbidity </li></ul><ul><li>Panton-Valentine Leukocidin gene (specialized centers) </li></ul>
    34. 34. Treatment of CA-MRSA Pneumonia <ul><li>FDA Approved </li></ul><ul><ul><li>Vancomycin </li></ul></ul><ul><ul><li>Linazolid </li></ul></ul><ul><li>Other Treatments </li></ul><ul><ul><li>Clindamycin </li></ul></ul><ul><ul><li>Trimethoprim/Sulfamethazole (Bactrim) </li></ul></ul><ul><ul><li>Doxycycline/Minocycline </li></ul></ul><ul><ul><li>Rifampin (with vancomycin) </li></ul></ul>
    35. 35. Vancomycin <ul><li>Prevents peptidoglycan formation </li></ul><ul><li>Remains 1 st line empiric treatment option at some institutions </li></ul><ul><li>Dosing needs to be optimized to achieve trough levels of 15-20 mcg/mL </li></ul><ul><li>Treatment successful in 35-57% of patients </li></ul><ul><li>Potential problems </li></ul><ul><ul><li>Poor tissue concentrations in the lung </li></ul></ul><ul><ul><li>No effect on toxin production at ribosomal level </li></ul></ul><ul><ul><li>Increasing trough does not appear to improve outcome </li></ul></ul><ul><li>Dosing and Frequency: 15 mg/kg IV q12 hours. </li></ul>
    36. 36. Linazolid <ul><li>New class of synthetic antimicrobial angents </li></ul><ul><ul><li>Oxazolidones </li></ul></ul><ul><li>Enhanced pulmonary penetration relative to vancomycin: ELF 100% vs 18% </li></ul><ul><li>Equal efficacy, possibly better, more expensive </li></ul><ul><li>Thrombocytopenia (uncommon) </li></ul><ul><li>Reversible non-selective MAO inhibitor </li></ul><ul><ul><li>Serotonin syndrome </li></ul></ul><ul><li>Affects toxin production </li></ul><ul><li>No adjustment necessary for renal dysfunction </li></ul><ul><li>Dosing and frequency: 600 mg IV/po q12 </li></ul>
    37. 37. Other Treatments <ul><li>CA-MRSA isolates retain susceptibility to several non B-lactam antibiotics </li></ul><ul><ul><li>Clindamycin </li></ul></ul><ul><ul><li>Trimethoprim/Sulfamethazole (Bactrim) </li></ul></ul><ul><ul><li>Doxycycline/Minocycline </li></ul></ul><ul><li>Efficacy not established clinically </li></ul><ul><ul><li>Not appropriate as first line therapy </li></ul></ul>
    38. 38. ICU patient develops fever <ul><li>56 yo male with COPD and CAP on mechanical ventilation treated with solumedrol, ceftriaxone, levofloxacin for CAP </li></ul><ul><li>Develops fever to 102 F and new, copius purulent sputum with increased FIO2 requirement on day 5 </li></ul><ul><li>An ICU Fever workup is initiated? </li></ul>
    39. 39. Fever in the ICU <ul><li>Noninfectious Causes </li></ul><ul><ul><li>Inflammatory </li></ul></ul><ul><ul><ul><li>Medications </li></ul></ul></ul><ul><ul><ul><ul><li>(antibiotics, anticonvulsants) </li></ul></ul></ul></ul><ul><ul><ul><li>Blood products </li></ul></ul></ul><ul><ul><ul><li>Vasculitis </li></ul></ul></ul><ul><ul><ul><li>Pancreatitis </li></ul></ul></ul><ul><ul><ul><li>Interstitial and eosinophillic pneumonias </li></ul></ul></ul><ul><ul><ul><li>Aspiration pneumonitis </li></ul></ul></ul><ul><ul><ul><li>ARDS </li></ul></ul></ul>
    40. 40. Fever Workup <ul><li>Noninfectious causes </li></ul><ul><ul><li>Vascular </li></ul></ul><ul><ul><ul><li>DVT or PE, Mesenteric Ischemia </li></ul></ul></ul><ul><ul><ul><li>Hemorrhage into brain, lung, or adrenal glands </li></ul></ul></ul><ul><ul><li>Metabolic </li></ul></ul><ul><ul><ul><li>Hyperthyroidism </li></ul></ul></ul><ul><ul><ul><li>ETOH withdrawal, DT’s </li></ul></ul></ul><ul><ul><ul><li>Neuroleptic malignant syndrome, malignant hyperthermia </li></ul></ul></ul><ul><ul><li>Neoplasia </li></ul></ul>
    41. 41. Fever in the ICU <ul><li>Infectious Sources </li></ul><ul><ul><li>UTI </li></ul></ul><ul><ul><li>Vascular Devices (central line) </li></ul></ul><ul><ul><li>Respiratory (pneumonia, abscess, sinusitis, empyema) </li></ul></ul><ul><ul><li>Wound Infection </li></ul></ul><ul><ul><li>Skin / Soft Tissue (decubitus or cellulitis) </li></ul></ul><ul><ul><li>Gastro (C. difficile, typhlitis, hepatitis, cholecystitis) </li></ul></ul><ul><ul><li>Prosthetic valves or devices (endocarditis) </li></ul></ul><ul><ul><li>Meningitis (unusual except in head trauma or ICP monitor in place) </li></ul></ul>
    42. 42. ICU Fever Workup <ul><li>Initial Workup </li></ul><ul><ul><li>Blood and Urine Cultures </li></ul></ul><ul><ul><li>CXR </li></ul></ul><ul><ul><li>Amylase, Lipase, Liver associated enzymes </li></ul></ul><ul><ul><li>Doppler’s Lower Extremities (upper too if central line) </li></ul></ul><ul><ul><li>Lukens’s trap if on ventilator for deep tracheal aspirate </li></ul></ul>
    43. 43. Deep Tracheal Aspiration Technique <ul><li>Change in-line suction system to reduce URT contamination </li></ul><ul><li>Attach in-line suction to lukens trap </li></ul><ul><li>100% FIO 2 on ventilator </li></ul><ul><li>Infuse 5 cc normal saline “bullet’s” </li></ul><ul><li>Advance in-line suction to left/right mainstem bronchi and aspirate back into lukens trap </li></ul><ul><li>Gram stain, respiratory, fungal, and AFB culture </li></ul><ul><li>Equivalent to bronchoalveolar lavage with quantitative culture of lavage fluid </li></ul><ul><ul><li>NEJM 2006; 355: 2619-2630 </li></ul></ul>
    44. 44. Deep Tracheal Aspiration Technique Closed suction in-line catheter system Lukens Traps
    45. 45. ICU Fever Workup <ul><li>Subsequent studies </li></ul><ul><ul><li>Bronchoscopy, echocardiogram, RUQ Ultrasound </li></ul></ul><ul><ul><li>CT of Brain, Chest, Abdomen, Pelvis </li></ul></ul><ul><ul><li>Eye exam </li></ul></ul><ul><ul><li>Thoracentesis, paracentesis, and / or lumbar puncture </li></ul></ul><ul><ul><li>Random cortisol and ACTH stimulation test </li></ul></ul><ul><ul><li>Connective tissue markers: ANA, ANCA, CRP … </li></ul></ul>
    46. 46. <ul><li>This patient is diagnosed with ventilator associated pneumonia </li></ul><ul><li>What initial therapy would you give? </li></ul><ul><li>Why is it important to get it right from the start? </li></ul>
    47. 47. Therapy and Response <ul><li>The patient is started on Linezolid 600 mg IV q12, Zosyn 4.5 gm IV PTD, and Tobramycin 7 mg/kg PTD based on the local hospital epidemiology for infection </li></ul><ul><li>A deep tracheal aspirate is performed and sent for gram stain, resp. culture, acid-fast bacilli smear and fungal smear and culture </li></ul>
    48. 48. <ul><li>What if a deep tracheal aspirate or bronchoscopic lavage revealed the following? </li></ul>
    49. 49. Gram-negative bacillary organisms? Aerobic rod shaped organism (+) Catalase test, (+) oxidase test Virulence: Exotoxin A and S, endotoxin
    50. 50. Gram-negative bacillary rods? Encapsulated, non-motile Facultative anaerobe and Lactose fermentating Extended spectrum beta-lactamase producers (ESBL)
    51. 51. Gram-negative organism that is rod shaped during rapid growth and coccobacillary in the stationary phase? Nonmotile, encapsulated, negative oxidase test No cytotoxins are produced (limited virulence) Can retain crystal violet and be incorrectly identified as gram positive.
    52. 52. Gram positive cocci in clusters? Golden yellow colonies on agar Catalase and coagulase positive Hemolysis on blood-agar Multiple virulence factors
    53. 53. VAP Pathogens PA: Pseudomonas aeruginosa SA: Staphylococcus aureus AS: Acinetobacter species Clinical Infectious Disease 2000; 321(suppl 4): s131-138
    54. 54. Definitions: The ATS/IDSA Guidelines <ul><li>HCAP </li></ul><ul><li>Includes HAP and VAP </li></ul><ul><li>Pneumonia in patients </li></ul><ul><ul><li>Hospitalized for  2 days in an acute care facility within 90 days of infection, residing in a nursing home or LTC facility </li></ul></ul><ul><ul><li>Attending a hospital or hemodialysis clinic </li></ul></ul><ul><ul><li>Receiving immunosuppressive therapy or wound care within 30 days of infection </li></ul></ul><ul><li>HAP </li></ul><ul><li>Pneumonia occurring  48 hours post–hospital admission </li></ul><ul><li>VAP </li></ul><ul><li>Pneumonia occurring  48-72 hours postintubation </li></ul>Am J Respir Crit Care Med. 2005;171:388-416. HAP=hospital-acquired pneumonia HCAP=healthcare-associated pneumonia LTC=long-term care; VAP=ventilator-associated pneumonia
    55. 55. Kollef et al. Chest 2005; 128:3854-3862
    56. 56. <ul><li>Regarding therapy, the new guidelines emphasize: </li></ul><ul><ul><li>use of early and appropriate therapy, in correct doses </li></ul></ul><ul><ul><li>avoiding excess use of antibiotics and de-escalating the initial therapy based on culture results and the patient’s clinical response </li></ul></ul><ul><ul><li>limiting the duration of therapy to the minimal effective period of time </li></ul></ul>Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia Am J Respir Crit Care Med 2005;171:388–416
    57. 57. Antibiotic therapy <ul><li>In patients with pneumonia, a lack of appropriate antimicrobial therapy is associated with increased mortality </li></ul><ul><li>There is clear evidence that antibiotic therapy should be given early to improve survival </li></ul><ul><li>A strong association between the administration of inappropriate antibiotic therapy and mortality has also been described in VAP </li></ul><ul><ul><li>Archives Internal Med 2004:164:637-644 </li></ul></ul><ul><ul><li>Chest 2002; 122:262-268 </li></ul></ul><ul><ul><li>AJRCCM 1997; 156:196-200 </li></ul></ul>
    58. 58. Relationship between the delay of antibiotic administration after the onset of shock and mortality of patients in septic shock Curr Opin Crit Care, Volume 13(5).October 2007.586–591 Early Antibiotic Therapy in Shock
    59. 60. Management strategies summary HAP, VAP or HCAP suspected Obtain lower respiratory tract (LRT) sample for culture (quantitative, semi-quantitative, deep tracheal aspirate) and gram stain Unless there is both a low clinical suspicion for pneumonia and negative microscopy of LRT sample, begin empiric antimicrobial therapy using an algorithm and local microbiological data ATS/IDSA Guidelines. Am J Respir Crit Care Med 2005;171:388–416 Days 2 and 3: check cultures and assess clinical response: (temperature, WBC, chest X-ray, oxygenation, Purulent sputum, haemodynamic changes and organ function)
    60. 61. Management strategies summary Clinical improvement at 48–72 hours No Yes Cultures + Cultures – Cultures – Cultures + Adjust antibiotic therapy, search for other pathogens, complications, other diagnosis or other sites of infection Search for other pathogens, complications, other diagnoses or other sites of infection Consider stopping antibiotics De-escalate antibiotics, if possible, treat selected patients for 7–8 days and re-assess ATS/IDSA Guidelines. Am J Respir Crit Care Med 2005;171:388–416
    61. 62. Risk factors for MDR pathogens in HCAP, HAP, and VAP <ul><li>Prior antimicrobial therapy in preceding 90 days </li></ul><ul><li>Current hospitalisation of >5 days </li></ul><ul><li>High frequency of antibiotic resistance in the community or in the specific hospital unit </li></ul><ul><li>Presence of risk factors for HCAP: </li></ul><ul><ul><li>hospitalisation for >2 days in the preceding 90 days </li></ul></ul><ul><ul><li>residence in a nursing home or extended-care facility </li></ul></ul><ul><ul><li>home infusion therapy (including antibiotics) </li></ul></ul><ul><ul><li>chronic dialysis within 30 days </li></ul></ul><ul><ul><li>home wound care </li></ul></ul><ul><ul><li>family member with MDR pathogen </li></ul></ul><ul><li>Immunosuppressive disease and/or therapy </li></ul>
    62. 63. Initial empiric therapy, no known risk factors for MDR pathogens, early onset (< 5days) and any disease severity <ul><li>Streptococcus pneumoniae </li></ul><ul><li>Haemophilus influenzae </li></ul><ul><li>Methicillin-susceptible Staphyloccus aureus (MSSA) </li></ul><ul><li>Antibiotic-sensitive enteric Gram-negative bacilli (EGNB) </li></ul><ul><ul><li>Escherichia coli </li></ul></ul><ul><ul><li>Klebsiella pneumoniae </li></ul></ul><ul><ul><li>Enterobacter spp. </li></ul></ul><ul><ul><li>Proteus spp. </li></ul></ul><ul><ul><li>Serratia marcescens </li></ul></ul>Ceftriaxone OR Levofloxacin , moxifloxacin or ciprofloxacin OR Ampicillin/sulbactam OR Ertapenem
    63. 64. Initial empiric therapy with late onset (>5 days) or risk factors for MDR pathogens, and any disease severity <ul><li>MDR pathogens </li></ul><ul><ul><li>P. aeruginosa </li></ul></ul><ul><ul><li>K. pneumoniae ESBL </li></ul></ul><ul><ul><li>Acinetobacter spp. </li></ul></ul><ul><ul><li>MRSA </li></ul></ul>Anti-pseudomonal cephalosporin (cefepime, ceftazidime) OR anti-pseudomonal carbapenem (imipenem or meropenem) OR β -lactam/ β -lactamase inhibitor ( piperacillin/tazobactam ) PLUS Anti-pseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) OR aminoglycoside (amikacin, gentamicin or tobramycin ) PLUS Linezolid or vancomycin (if MRSA risk factors are present or there is a high incidence locally)
    64. 65. ATS-IDSA recommendations and principles <ul><li>All patients need a lower respiratory tract culture (bronchoscopically or deep tracheal aspirate- quantitative or qualitative) before antibiotic therapy </li></ul><ul><li>Should not delay the initiation of appropriate, broad-spectrum therapy in critically ill patients based on local hospital epidemiology </li></ul><ul><li>Negative LRT cultures can be used to stop antibiotic therapy in a patient who has had cultures obtained in the absence of a change in antibiotic in the past 72 hours </li></ul>
    65. 66. ATS-IDSA recommendations and principles <ul><li>Empiric therapy should include antibiotics from a different class than those the patient has recently received </li></ul><ul><li>Use short duration (5 days) of aminoglycoside when treating pseudomonas </li></ul><ul><li>De-escalation should be considered once data are available on the results of LRT cultures and the patient’s clinically responds. </li></ul><ul><li>Shorter duration of antibiotic therapy (7–8 days) is recommended for some patients with uncomplicated HAP </li></ul>
    66. 69. MRSA HCAP mortality by BAL semi-quantitative cultures Retrospective single-center cohort study of 102 patients Dr Kollef Optimization of Vancomycin PK indices did not correlate with mortality Chest 2006; 130: 947-955
    67. 72. Pharmacokinetics/Pharmacodynamics <ul><li>Pharmacokinetic parameters </li></ul><ul><ul><li>Route, dose, and frequency </li></ul></ul><ul><ul><li>Absorption,distribution, metabolism, and elimination </li></ul></ul><ul><li>Pharmacodynamic parameters </li></ul><ul><ul><li>Drug concentration at tissue site </li></ul></ul><ul><ul><li>Toxicology </li></ul></ul>
    68. 73. Pharmacokinetics and Pharmacodynamics C (mg/dL) AUC/MIC Vancomycin Linezolid MIC C max T (hours) T > MIC (B-lactams/Carbapenems) C max / MIC (aminoglycosides) C: Antimicrobial concentration AUC: Area Under Curve drug concentration against time MIC: Minimal inhibitory concentration Cmax: Maximum drug concentration
    69. 74. Antibiotic MIC Breakpoint (ug/mL) PK/PD Dose/ Frequency Lung Penetration Pseudomonas a. MRSA Ceftazidime ≤ 8 T> MIC 2 gm IV q8 ELF = 21% Pip/Tazo ≤ 64/4 T> MIC 4.5 gm IV q6 ELF = 57%/91% Imipenem ≤ 4 T> MIC 1 gm IV q8 LT = 60% Tobramycin ≤ 4 Cmax/MIC 7 mg/kg day IV ELF 42-153% Vancomycin ≤ 2 AUC/MIC 15 mg/kg q12 ELF = 18% Linezolid ≤ 4 AUC/MIC 600 mg IV q12 ELF = 100%
    70. 75. Prevention of Nosocomial Pneumonia <ul><li>Handwashing/disinfection(1) </li></ul><ul><li>NIV(1) </li></ul><ul><li>Orotracheal intubation(1) </li></ul><ul><li>Suctioning subglottic secretions (1) </li></ul><ul><li>Semi-erect position(1) </li></ul><ul><li>Weaning/Sedation protocols (2) </li></ul><ul><li>Adequate nursing/resp. therapist staffing (2) </li></ul><ul><li>Chlorhexidine oral decontamination (?) </li></ul><ul><li>Post-pyloric feeding to reduce aspiration (2) </li></ul>
    71. 76. References <ul><li>Mayo Clin Proc 2005;80(9): 1201-1208 </li></ul><ul><li>JAMA 2007; 297:1583-1593 </li></ul><ul><li>Chest 2005; 128: 3854-3862 </li></ul><ul><li>Am J Respir Crit Care Med 2005; 171: 388-416 </li></ul><ul><li>N Eng J Med 2006; 355: 2619-2630 </li></ul>