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Most likely diagnosis was thought to be CAP (Streptococcus pneumo +/- H influ)
Atypical pathogen coverage for legionella
Pneumonia Normal Lung Pneumonia: inflammatory cells and debri in alveolar spaces Lobar Pneumonia
Deep Tracheal Aspirate? Gram positive cocci in clusters?
Deep Tracheal Aspirate? Spherical gram positive cocci arranged in chains or pairs?
Deep Tracheal Aspirate? Gram negative bacillary organisms?
Deep Tracheal Aspirate? Gram negative coccobacillary forms?
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.
CA-MRSA: 48 hours of destruction Admission 48 hours later
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
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.
Gram positive cocci in clusters? Golden yellow colonies on agar Catalase and coagulase positive Hemolysis on blood-agar Multiple virulence factors
In patients with pneumonia, a lack of appropriate antimicrobial therapy is associated with increased mortality
There is clear evidence that antibiotic therapy should be given early to improve survival
A strong association between the administration of inappropriate antibiotic therapy and mortality has also been described in VAP
Archives Internal Med 2004:164:637-644
Chest 2002; 122:262-268
AJRCCM 1997; 156:196-200
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
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)
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
Risk factors for MDR pathogens in HCAP, HAP, and VAP
Prior antimicrobial therapy in preceding 90 days
Current hospitalisation of >5 days
High frequency of antibiotic resistance in the community or in the specific hospital unit
Presence of risk factors for HCAP:
hospitalisation for >2 days in the preceding 90 days
residence in a nursing home or extended-care facility
home infusion therapy (including antibiotics)
chronic dialysis within 30 days
home wound care
family member with MDR pathogen
Immunosuppressive disease and/or therapy
Initial empiric therapy, no known risk factors for MDR pathogens, early onset (< 5days) and any disease severity
Ceftriaxone OR Levofloxacin , moxifloxacin or ciprofloxacin OR Ampicillin/sulbactam OR Ertapenem
Initial empiric therapy with late onset (>5 days) or risk factors for MDR pathogens, and any disease severity
K. pneumoniae ESBL
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)
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
Absorption,distribution, metabolism, and elimination
Drug concentration at tissue site
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
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%