Pneumonia: The long or short end of the stick? Mitch Prasad, BScP - PowerPoint PPT Presentation

Staph aureus Pneumonia: The long or short end of the stick? Mitch Prasad, BScP Pharmacy Resident 2016-2017 Antimicrobial Stewardship Rotation, BH 1

Objectives 1. To highlight some of the differences between the 2016 and 2005 IDSA HAP/VAP Guidelines 2. To evaluate the evidence on treatment duration for HAP/VAP infections, particularly those caused by MRSA 2

Meet the Patient: DL 79 y/o Female, 56 kg admitted on August 20 th ID ↑SOB, ↓energy ( Dx: Sepsis 2 0 to pneumonia +/- UTI) CC HPI Recent prolonged admission for urosepsis and pneumonia complicated by ARDS requiring ICU admission and intubation Further complicated by pneumothorax and deconditioning Queen’s Park for rehab  Discharged August 17th SOB, ↓energy x 2 days Woke up in the middle of the night, fell, found by daughter in morning EHS called Allergies Penicillin G (hives); tolerates cephalosporins Social Private dwelling in Burnaby with husband history No alcohol/drug use Ex-smoker (quit 40 years ago) 3

Meet the Patient: DL • Recent hospitalization history – Burnaby hospital (June 4-July 14): • ARDS 2 O CAP • Developed UTI – Queen’s Park (July 15 -20): • Rehab • Pneumothorax  RCH – RCH (July 20-Aug 10) – Queen’s Park (Aug 10 -17) 4

PMH/MPTA PMH MPTA • Post-pneumothorax Salbutamol 100 mcg 2 puffs hourly prn • Ipratropium 20 mcg 2 puffs QID • Fluticasone/salmeterol 125/25 mcg 1 puff BID HTN • CAD (remote MI) Nitroglycerin spray q5minutes SL PRN CP • Paroxysmal Afib Diltiazem 240 mg ER po daily • Apixaban 5 mg po bid • Insomnia/Anxiety Zopiclone 7.5 po mg HS • Melatonin 6 mg HS • Chronic back pain Pregabalin 75 mg po HS • Acetaminophen 1g po TID 5

Review of Systems (Aug 20) Vitals Tmax: 38 BP 96/65 HR 107 CNS GCS 14, mildly confused HEENT No concerns CVS ECG: QTc = 435 ms, sinus tachycardia SOB, RR 22, O 2 sat 77% on RA  95% 4LNP RESP CXR: Extensive left-sided bronchopneumonia GI/liver Soft, non-tender GU No complaints of dysuria, urgency, frequency UA: (+) nitrites, leukocyte esterase 100 (H), trace blood Renal BUN 4 SCr 62 mmol/L eGFR 83 mL/min Lytes Normal Heme WBC 12.7 (H) Hgb 102 (L) Neutrophils 10.5 (H) CRP 174.2 (H) MSK/Derm No concerns 6

ID History/C&S Date Culture site C+S Antibiotics received July: Sputum MRSA S: Doxycycline, TMP/SMX, vancomycin (Expectorated) Enterococcus faescalis Aug 20-23: hospitalized, sepsis 2 O pneumonia + UTI Aug 20 Urine C: pending Vancomycin 1500 mg IV STAT x 1D (Aug 20) Sputum Vancomycin 750 mg IV Q12H x (expectorated) 6 days (Aug 21-26) Blood Ceftriaxone 1g IV Q24H x 6 days (Aug 20-25) Urine – resulted Aug 23 C: klebsiella pneumonia >100 mCFU/L S: cefotaxime, CTX, cefazolin, cephalexin, amox/clav, pip/tazo, tobramycin, gentamicin, ciprofloxacin, nitrofurantoin R: ampicillin Sputum – Aug 23 C: MRSA resulted S: doxycycline, TMP/SMX, vancomycin Aug 23 Blood No Growth after 5 days incubation Aug 23: Antimicrobial Stewardship Review 7

Current Medications • Sepsis/PNA/UTI Vancomycin 750 mg IV Q12H x until Aug 26 • Ceftriaxone 1g IV Q24H until Aug 25 • SOB Salbutamol 100 mcg 2 puffs hourly prn • Ipratropium 20 mcg 2 puffs QID • Fluticasone/salmeterol 125/25 mcg 2 puff BID HTN • CAD (remote MI) Nitroglycerin spray q5minutes SL PRN CP • Paroxysmal Afib Diltiazem 240 mg ER po daily • Apixaban 5 mg po bid • Insomnia Zopiclone 7.5 po mg HS • Melatonin 6 mg HS • Chronic back pain Pregabalin 75 mg po HS • Acetaminophen 975 mg po TID 8

DTPs 1) DL may be at risk of experiencing unresolved PNA infection secondary to a potentially inadequate duration of antibiotics (7 days), and would benefit from a reassessment of her antibiotic therapy. 2) DL is at risk of adverse effects of broad-spectrum antibiotics (=MDR, C. difficile infection) secondary to receiving broad- spectrum treatment with ceftriaxone and vancomycin, and would benefit from a reassessment of her antibiotic therapy. 9

Goals of therapy for DL • Eradicate infection: achieve clinical cure • Prevent infection relapse • Prevent complications of infection (e.g. septicemia) • Minimize ADR of therapies • Improve quality of life • Prevent mortality 10

Pneumonia pathophysiology 1,2 Depends on amount and virulence of microorganisms in the lower respiratory tract and the host response Routes of bacterial entry into trachea 1) Microaspiration of oropharyngeal pathogens 2) Leakage of bacteria around ETT cuff 3) Inhalation of pathogens from aerosols and direct inoculation 4) Hematogenous spread 1) Infected IV catheters 2) Bacterial translocation from GIT lumen 11

Pneumonia: diagnosis 1 • Radiologic infiltrate that is new or progressive AND • Clinical findings suggesting infection – New onset of fever – Purulent sputum – Leukocytosis – Decline in oxygenation • DDx: CHF, atelectasis, pulmonary thromboembolism, pulmonary drug reactions, pulmonary hemorrhage, or ARDS 12

Pneumonia: Categories 2005 IDSA HAP/VAP Guidelines 1 Pneumonia HAP/VAP VAP HCAP HAP 13

Pneumonia: Categories 2005 IDSA HAP/VAP Guidelines 1 S. Pneumoniae MDR Pathogens H. Influenzae - Pseudomonas MSSA - ESBL klebsiella Abx-sensitive GNBs - Acinetobacter - e. coli, klebsiella, - MRSA Enterobacter, - Legionella proteus, serratia 14

Pneumonia: Categories 2016 IDSA HAP/VAP Guidelines 1 Pneumonia HAP/VAP VAP HCAP HAP Increasing evidence from studies that patients defined as HCAP are NOT at high risk for MDR pathogens 15

Risk Factors for MDR Pathogens 1,3 2005 Vs 2016 16

VAP Empiric Therapy 3 A: G(+) Antibiotics with MRSA B: G(-) Antibiotics with C: G(-) Antibiotics with Antipseudomonal Activity ( β - Activity Antipseudomonal Activity (non β -lactam) lactams) Vancomycin 15mg/kg IV q8-12h Piperacillin-tazobactam 4.5 g IV Ciprofloxacin 400 mg IV q8h q6h Levofloxacin 750 mg IV q24h Linezolid 600 mg IV q12h Cefepime 2g IV q8h Amikacin 15-20 mg/kg IV q24h Ceftazadime 2g IV q8h Gentamicin 5-7 mg/kg IV q24h Tobramycin 5-7 mg/kg IV q24h Imipenem 500 mg IV q6h Colistin 5mg/kg IV x 1 (load) Meropenem 1 g IV q8h followed by 2.5 mg x (1.5xCrCl+30) IV q12h (maintenance) Polymyxin B 2.5-3.0 mg/kg/d divided bid IV Aztreonam 2g iv q8h Choose: • one G+ option from Column A • one G- option from Column B • one G- option from Column C 17

HAP Empiric Therapy 3 Not high risk of Mortality Not high risk of mortality but High risk of mortality or IV Abx use and no factors increasing WITH MRSA risk within prior 90 days (Cover MSSA if MRSA risk MRSA coverage not used) Pip/Tazo 4.5 g IV q6h Pip/Tazo 4.5 g IV q6h Pip/Tazo 4.5 g IV q6h Cefepime 2g IV q8h Cefepime 2g IV q8h OR Cefepime 2g IV q8h OR Ceftazadime 2g IV q8h Ceftazadime 2g IV q8h Levofloxacin 750 mg IV Levofloxacin 750 mg IV daily Levofloxacin 750 mg IV daily OR daily OR ciprofloxacin 400 mg IV q8h ciprofloxacin 400 mg IV q8h Imipenem 500 mg IV q6h Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR OR meropenem 1g IV q8h meropenem 1g IV q8h meropenem 1g IV q8h Aztreonam 2 g IV q8h Amikacin 15-20 mg/kg IV q24h Gentamicin 5-7 mg/kg IV q24h Tobramycin 5-7 mg/kg IV q24h PLUS: PLUS: Vancomycin 15mg/kg IV q8-12h Vancomycin 15mg/kg IV q8-12h (trough: 15-20) OR linezolid 600 (trough: 15-20) OR linezolid 600 mg mg IV q12h IV q12h 18

HAP Empiric Therapy 3 Not high risk of Mortality Not high risk of mortality but High risk of mortality or IV Abx use and no factors increasing WITH MRSA risk within prior 90 days (Cover MSSA if MRSA risk MRSA coverage not used) Pip/Tazo 4.5 g IV q6h Pip/Tazo 4.5 g IV q6h Pip/Tazo 4.5 g IV q6h Cefepime 2g IV q8h Cefepime 2g IV q8h OR Cefepime 2g IV q8h OR Ceftriaxone 1g IV Q24H Ceftazadime 2g IV q8h Ceftazadime 2g IV q8h Levofloxacin 750 mg IV Levofloxacin 750 mg IV daily Levofloxacin 750 mg IV daily OR daily OR ciprofloxacin 400 mg IV q8h ciprofloxacin 400 mg IV q8h Imipenem 500 mg IV q6h Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR OR meropenem 1g IV q8h meropenem 1g IV q8h meropenem 1g IV q8h Aztreonam 2 g IV q8h Amikacin 15-20 mg/kg IV q24h Gentamicin 5-7 mg/kg IV q24h Tobramycin 5-7 mg/kg IV q24h PLUS: PLUS: Vancomycin 15mg/kg IV q8-12h Vancomycin 15mg/kg IV q8-12h Vancomycin 750 mg IV (trough: 15-20) OR linezolid 600 (trough: 15-20) OR linezolid 600 mg Q12H mg IV q12h IV q12h 19

Physician’s Question “How long do I need to treat this MRSA pneumonia for?” 20

HAP/VAP Duration of Therapy 2005 IDSA HAP/VAP Guidelines 1 • “Efforts should be made to shorten the duration of therapy from the traditional 14 to 21 days to periods as short as 7 days , provided that the etiologic pathogen is not P. aeruginosa and that the patient has had a good clinical response with resolution of clinical features of infection ” 21

HAP/VAP Duration of Therapy 2016 IDSA HAP/VAP Guidelines 1 Patients with HAP and VAP • “We recommend a 7-day course of antimicrobial therapy rather than a longer duration” • “There exist situations in which a shorter or longer duration of antibiotics may be indicated” 22

Clinical Question Patients with HAP/VAP caused by suspected methicillin- P resistant staphylococcal aureus Antibiotics for short duration (7-8 days) I Antibiotics for long duration (10-14 days) C Mortality O Eradication of infection 23