4/3/2017 CLINICAL PEARLS: UPDATES IN THE MANAGEMENT OF NOSOCOMIAL PNEUMONIA DISCLOSURE LEARNING OBJECTIVES

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1 CLINICAL PEARLS: UPDATES IN THE MANAGEMENT OF NOSOCOMIAL PNEUMONIA BILLIE BARTEL, PHARMD, BCCCP APRIL 7 TH, 2017 DISCLOSURE I have had no financial relationship over the past 12 months with any commercial sponsor with a vested interest in this presentation. OBJECTIVES Pharmacist Develop appropriate recommendations for empiric treatment of nosocomial pneumonia Describe the recommended duration of antibiotic treatment for most patients with nosocomial pneumonia Technician Identify antibiotic agents commonly prescribed for empiric treatment of nosocomial pneumonia Recognize the importance of antibiotic de-escalation 1

2 HAP/VAP GUIDELINE PEARLS Healthcare-associated pneumonia (HCAP) Diagnosis Empiric antibiotic therapy De-escalation Duration of therapy GRADE CRITERIA All IDSA guideline recommendations now evaluated using GRADE system 2

3 DEFINITIONS OF NOSOCOMIAL PNEUMONIA Definitions of nosocomial pneumonia: Hospital-acquired pneumonia (HAP): pneumonia occurring 48 hours or more after a hospital admission Ventilator-associated pneumonia (VAP): pneumonia that occurs 48 hours or more after intubation Healthcare-associated pneumonia (HCAP): pneumonia in a patient with recent exposure to the healthcare system o Recent hospitalization, resides in a nursing home or long-term care facility, receive IV antibiotics within 90 days, received home infusion therapy, wound care, or dialysis within 30 days, or has a family member with a MDRO ATS and IDSA. Am J Resp Crit Care Med 2005; 171: HCAP HCAP removed from the guidelines: Many patients with HCAP are not at high risk for MDROs Additional patient-specific risk factors are important determinants of risk for MDROs Recommendations for empiric coverage of MDROs among community dwelling patients with pneumonia will likely be based on validated risk factors, not solely on whether or not the patient had previous contact with the healthcare system HCAP or some modification of it may be included in the CAP guidelines update (expected summer 2017) HAP/VAP DIAGNOSIS Microbiologic methods: Noninvasive sampling with semi-quantitative cultures is preferred over invasive sampling with quantitative cultures (weak recommendation, low quality evidence) o Endotracheal aspiration vs. bronchoscopic techniques Biomarkers: Procalcitonin and CRP testing are not recommended to determine whether or not to initiate empiric antibiotic treatment (strong recommendation, moderate quality evidence/weak recommendation, low quality evidence) 3

4 EMPIRIC TREATMENT Recommend antibiotic selection focus on facility-specific and unitspecific antibiogram data MRSA prevalence >10-20% Gram negative susceptibility patterns Balance benefits of adequate initial therapy with risks of overtreatment Advantages Adequacy of empiric therapy Disadvantages Increased drug toxicity Increased risk of superinfection, C. difficile Increased costs COMMON PATHOGENS HAP: Enteric gram negative bacilli Staphylococcus aureus Pseudomonas aeruginosa Streptococcus pneumoniae Haemophilus influenzae VAP: Enteric gram negative bacilli Staphylococcus aureus MRSA in ~50% of Staph pneumonia cases Pseudomonas aeruginosa Acinetobacter baumannii Sievert et al. Infect Control Hosp Epidemiol 2013; 34:1-14. Jones et al. Clin Infect Dis 2010; 51(suppl 1):S81-7. RISK FACTS F MDR HAP/VAP 2.01 (CI ) 2.5 (CI ) 3.01 (CI ) VAP HAP 5.17 (CI ) 12.3 (CI ) Odds Ratio 4

5 INCREASED RISK OF MDRO/MRSA HAP: Prior IV antibiotics within the last 90 days* >10-20% MRSA prevalence (or unknown) * Increases risk for MRSA/MDR Pseudomonas VAP: Prior IV antibiotics within the last 90 days* ARDS prior to VAP Acute renal replacement therapy prior to VAP Septic shock at time of VAP 5 or more days of hospitalization prior to VAP >10% MRSA prevalence (or unknown) MONOTHERAPY VS. COMBINATION THERAPY F HAP/VAP 2016 Cochrane Review: Outcome Mortality (28 to 30-day) Clinical cure (7 to 14-days) Odds Ratio (95% CI) 0.97 (0.73 to 1.30) 0.88 (0.56 to 1.36) Adverse events 0.93 (0.68 to 1.26) Aarts et al. Crit Care Med 2008; 36(1): Arthur et al. Cochrane Database Syst Rev DOI: / CD pub4 HAP EMPIRIC THERAPY Step 1: Need One Antibiotic to cover Pseudomonas and MSSA Step 2: If Risk Factors Increasing the Likelihood of MRSA Step 3: If High Risk of Mortality or Receipt of Intravenous Antibiotics During the Prior 90 days One of the following: Piperacillin/tazobactam 4.5 g IV q6h Cefepime 2g IV q8h Levofloxacin 750 mg IV daily Imipenem 500 mg IV q6h Meropenem 1 g q8h ADD: Vancomycin to target goal trough of mcg/ml Linezolid 600 mg IV q12h Risk factors include: IV antibiotics within 90 days >20% MRSA in hospital (or unknown) High mortality risk (septic shock or ventilatory support) ADD agent to double-cover Pseudomonas (avoid 2 beta-lactams): Piperacillin/tazobactam 4.5 g IV q6h Cefepime 2g IV q8h Ceftazidime 2g IV q8h Levofloxacin 750 mg IV daily Ciprofloxacin 400 mg IV q8h Imipenem 500 mg IV q6h Meropenem 1 g q8h Aztreonam 2g IV q8h Aminoglycoside (gentamicin, tobramycin, or amikacin) Risk factors include: IV antibiotics within 90 days High mortality risk (septic shock or ventilatory support) 5

6 VAP EMPIRIC THERAPY Step 1: Need One Antibiotic to cover Pseudomonas and MSSA Step 2: If Risk Factors Increasing the Likelihood of MRSA Step 3: If Risk Factors for Antimicrobial Resistance or >10% of Gram Negatives Resistant to First Agent One of the following: Piperacillin/tazobactam 4.5 g IV q6h Cefepime 2g IV q8h Levofloxacin 750 mg IV daily Imipenem 500 mg IV q6h Meropenem 1 g q8h * Avoid if alternative available ADD: Vancomycin to target goal trough of mcg/ml Linezolid 600 mg IV q12h Risk factors include: IV antibiotics within 90 days >10-20% MRSA in hospital (or unknown) ADD agent to double-cover Pseudomonas (avoid 2 beta-lactams): Piperacillin/tazobactam 4.5 g IV q6h Cefepime 2g IV q8h Ceftazidime 2g IV q8h Levofloxacin 750 mg IV daily Ciprofloxacin 400 mg IV q8h Imipenem 500 mg IV q6h Meropenem 1 g q8h Aztreonam 2g IV q8h Aminoglycoside* (gentamicin, tobramycin, or amikacin) Risk factors include: IV antibiotics within 90 days ARDS at time of VAP Acute RRT at time of VAP Septic shock 5 or more days in hospital >10% gram negative resistant to primary agent DE-ESCALATION De-escalation of empiric therapy is recommended over fixed therapy (weak recommendation, very low quality evidence) Current evidence evaluating effects of de-escalation in pneumonia is conflicting: Mortality, length of stay, recurrence of pneumonia, and development of resistance Advantages Disadvantages SHT VS. PROLONGED COURSE ANTIBIOTIC THERAPY Odds Ratio Pugh et al. Cochrane Database Syst Rev 2015;8:Cd Dimopoulos et al. Chest 2013; 144:

7 DURATION OF THERAPY Treatment duration of 7 days is recommended over a longer duration for both HAP and VAP (strong recommendation, moderate quality evidence) Includes HAP/VAP due to non-glucose-fermenting gram negative bacilli Suggest using procalcitonin levels with clinical criteria to guide discontinuation of antibiotic therapy (weak recommendation, low-quality evidence) ASSESSMENT For which of the following patients would the guidelines suggest empiric coverage with two antipseudomonal antibiotics for hospital-acquired pneumonia? A. A patient developing pneumonia on hospital day 4 B. A patient developing septic shock due to pneumonia on hospital day 4 C. A patient developing pneumonia three weeks after completing antibiotic therapy (including IV antibiotics) for osteomyelitis D. All of the above E. B and C only ASSESSMENT True or False: Vancomycin or linezolid are the recommended agents for empiric coverage of MRSA in patients with HAP or VAP. 7

8 ASSESSMENT True or false: Antibiotic de-escalation reduces costs, potential for adverse effects, and may decrease the likelihood of acquiring antibiotic resistance. ASSESSMENT True or False: A short course (i.e. 7 days) of antibiotic therapy is recommended for most patients with HAP or VAP over a longer duration. 8

9 REFERENCES 9