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
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Antimicrobial Stewardship Rotation, BH
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ID 79 y/o Female, 56 kg admitted on August 20th CC ↑SOB, ↓energy (Dx: Sepsis 20 to pneumonia +/- UTI) 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 history Private dwelling in Burnaby with husband No alcohol/drug use Ex-smoker (quit 40 years ago)
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PMH MPTA Post-pneumothorax
HTN CAD (remote MI)
Paroxysmal Afib
Insomnia/Anxiety
Chronic back pain
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Vitals Tmax: 38 BP 96/65 HR 107 CNS GCS 14, mildly confused HEENT No concerns CVS ECG: QTc = 435 ms, sinus tachycardia RESP SOB, RR 22, O2sat 77% on RA 95% 4LNP 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) Neutrophils 10.5 (H) Hgb 102 (L) CRP 174.2 (H) MSK/Derm No concerns
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Date Culture site C+S Antibiotics received July: Sputum (Expectorated) MRSA S: Doxycycline, TMP/SMX, vancomycin Enterococcus faescalis Aug 20-23: hospitalized, sepsis 2O pneumonia + UTI Aug 20 Urine Sputum (expectorated) Blood C: pending
Vancomycin 1500 mg IV STAT x 1D (Aug 20) Vancomycin 750 mg IV Q12H x 6 days (Aug 21-26) Ceftriaxone 1g IV Q24H x 6 days (Aug 20-25)
Aug 23 Urine – resulted C: klebsiella pneumonia >100 mCFU/L
S: cefotaxime, CTX, cefazolin, cephalexin, amox/clav, pip/tazo, tobramycin, gentamicin, ciprofloxacin, nitrofurantoin R: ampicillin
Aug 23 Sputum – resulted C: MRSA
S: doxycycline, TMP/SMX, vancomycin
Aug 23 Blood
No Growth after 5 days incubation
Aug 23: Antimicrobial Stewardship Review 7
Sepsis/PNA/UTI
SOB
HTN CAD (remote MI)
Paroxysmal Afib
Insomnia
Chronic back pain
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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.
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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
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
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– New onset of fever – Purulent sputum – Leukocytosis – Decline in oxygenation
drug reactions, pulmonary hemorrhage, or ARDS
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Pneumonia
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MSSA Abx-sensitive GNBs
Enterobacter, proteus, serratia MDR Pathogens
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Pneumonia
Increasing evidence from studies that patients defined as HCAP are NOT at high risk for MDR pathogens
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17 Choose:
A: G(+) Antibiotics with MRSA Activity B: G(-) Antibiotics with Antipseudomonal Activity (β- lactams) C: G(-) Antibiotics with Antipseudomonal Activity (non β-lactam) Vancomycin 15mg/kg IV q8-12h Piperacillin-tazobactam 4.5 g IV q6h Ciprofloxacin 400 mg IV q8h Levofloxacin 750 mg IV q24h Linezolid 600 mg IV q12h Cefepime 2g IV q8h Ceftazadime 2g IV q8h Amikacin 15-20 mg/kg IV q24h Gentamicin 5-7 mg/kg IV q24h Tobramycin 5-7 mg/kg IV q24h Imipenem 500 mg IV q6h Meropenem 1 g IV q8h Colistin 5mg/kg IV x 1 (load) 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
18 Not high risk of Mortality and no factors increasing MRSA risk Not high risk of mortality but WITH MRSA risk High risk of mortality or IV Abx use within prior 90 days (Cover MSSA if 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 Ceftazadime 2g IV q8h Cefepime 2g IV q8h OR Ceftazadime 2g IV q8h Levofloxacin 750 mg IV daily Levofloxacin 750 mg IV daily OR ciprofloxacin 400 mg IV q8h Levofloxacin 750 mg IV daily OR ciprofloxacin 400 mg IV q8h Imipenem 500 mg IV q6h OR meropenem 1g IV q8h Imipenem 500 mg IV q6h OR meropenem 1g IV q8h Imipenem 500 mg IV q6h OR 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 (trough: 15-20) OR linezolid 600 mg IV q12h Vancomycin 15mg/kg IV q8-12h (trough: 15-20) OR linezolid 600 mg IV q12h
19 Not high risk of Mortality and no factors increasing MRSA risk Not high risk of mortality but WITH MRSA risk High risk of mortality or IV Abx use within prior 90 days (Cover MSSA if 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 Ceftazadime 2g IV q8h Cefepime 2g IV q8h OR Ceftazadime 2g IV q8h Levofloxacin 750 mg IV daily Levofloxacin 750 mg IV daily OR ciprofloxacin 400 mg IV q8h Levofloxacin 750 mg IV daily OR ciprofloxacin 400 mg IV q8h Imipenem 500 mg IV q6h OR meropenem 1g IV q8h Imipenem 500 mg IV q6h OR meropenem 1g IV q8h Imipenem 500 mg IV q6h OR 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 (trough: 15-20) OR linezolid 600 mg IV q12h Vancomycin 15mg/kg IV q8-12h (trough: 15-20) OR linezolid 600 mg IV q12h
Ceftriaxone 1g IV Q24H Vancomycin 750 mg IV Q12H
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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”
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Patients with HAP and VAP
rather than a longer duration”
duration of antibiotics may be indicated”
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Patients with HAP/VAP caused by suspected methicillin- resistant staphylococcal aureus
Antibiotics for short duration (7-8 days)
Antibiotics for long duration (10-14 days)
Mortality Eradication of infection
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Medline (=48)
Pneumonia/ AND [(duration of therapy) OR (duration of antibiotic therapy)]
EMBASE (N=45)
[hospital acquired pneumonia/ or ventilator associated pneumonia/ or health care associated pneumonia/] AND [(duration of therapy) OR (duration of antibiotic therapy)] AND treatment duration AND [antibiotic therapy/ or antibiotic agent]
Cochrane Central
Register, Database
reviews (N=16) “duration of therapy” OR “duration of antibiotic therapy” AND "hospital acquired pneumonia" or "ventilator associated pneumonia" or "health care associated pneumonia“ AND “antibiotic therapy” OR “antibiotic agent”
Results relevant to PICO:
25 P ICU patients (≥16 years) with HAP (including VAP) diagnosed by clinical and/or radiological features and/or quantitative culture of respiratory specimens I Fixed “short” (≤8 days) duration of antibiotic therapy C Prolonged (including standard care) course of antibiotic therapy O Primary: 1. 28-day mortality 2. Recurrence of PNA 3. 28-day antibiotic-free days Secondary:
1. ICU mortality 2. In-hospital mortality 3. Clinical resolution of PNA 4. Relapse of PNA 5. Subsequent infection d/t resistant organisms 6. Duration of ICU stay 7. Duration of hospital stay 8. Duration of mechanical ventilation 9. Mechanical ventilation-free days 10. Mortality attributable to HAP Exclusions
Patients with haematological malignancy, chemically induced immunosuppression, or HIV/AIDS
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27 Contributing studies: Chastre 2003: 65.2% Kollef 2012: 26.7% Fekih Hassen 2009: 8.1%
28 Contributing studies: Chastre 2003: 72.4% Medina 2007: 15.6% Capellier 2012: 8.4% Fekih Hassen 2009: 3.7%
Chastre et al.
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30 Comparison of 8 vs 15 Days of Antibiotic Therapy for VAP in Adults Design
Inclusion
Exclusion
days antimicrobial treatment
days pre-infection Intervention
Comparator
Outcome
recurrence, and antibiotic-free days assessed 28 days after VAP onset
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Primary Outcome
NSD
recurrences NSD in all patients, MRSA and other bacteria Increased recurrence in non-fermenting GNB
8-days > 15-days [13.1 vs 8.7 (95% CI 3.1-5.6)] Secondary Outcomes
NSD
days NSD
NSD
NSD
NSD
NSD
Type of bias Risk Rationale Selection Bias Low
(Adequate sequence generation and allocation concealment) Performance Bias High
Detection Bias High
Attrition Bias Low
Reporting Bias Unclear
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Limitations
generalizability
Authors:
for ICU patients with microbiologically proven VAP
– Holds true for specific pathogens as well
therapy in pneumonia due to NF GNB (pseudomonas, Acinetobacter, stenotrophomonas)
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Ethan et al 20085: “the duration of therapy for nonbacteremic MRSA should be based on clinical judgment; most investigators would provide a minimum of 14 days of therapy” The Sandford Guide to Antimicrobial Therapy 20166: “Duration of treatment: 2-3 weeks if just pneumonia”
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et al 2003
– Only late onset VAP patients – No early onset VAP patients, HAP, no antibiotics in 15 days pre-infection – No extra-pulmonary infections – Excluded all that had “inappropriate” empiric therapy to start
shorter duration of therapy (≤8 days) is appropriate
– Not enough provided by this study to determine which duration of therapy is appropriate 38
MRSA:
For infections with culture results isolating MSSA, strep pneumonia, lactose fermenting GNBs (e. coli, klebsiella):
For non-lactose fermenting GNBs (pseudomonas, Acinetobacter):
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Decision: 1) Cefuroxime 250 mg po bid and doxycycline 100 mg po bid for a total duration of 14 days
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41 Efficacy Safety Frequency Vitals Afebrile, HR ≤100 T<36 or >38, HR>90 Daily while in hospital CNS N/a Confusion HEENT N/a N/a CVS BP back to baseline (~135/80 treated) BP ↑’d > baseline Systolic BP <90 Resp RR 14-20, RA, ↓SOB ↓’ing SpO2, RR>20, ↑SOB CXR: ↑consolidation GI/Abdo/Liver N/a NVD GU/renal Absence of UTI symptoms (dysuria, urgency, frequency) CVA tenderness SCr, CrCl MSK/Derm N/a Hives, Rash, arthralgia Heme WBC 4-11; Neut 2-8 ↑’ing WBC, Neutrophils Fluids/Lytes/Endo N/a N/a
August 24: Patient started cefuroxime 500 mg po bid and doxycycline 100 mg po bid Aug 25: Continued to improve in hospital
Aug 26- Aug 28:
symptoms
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1) Guidelines for the Management of Adults with Hospital-Acquired, Ventilator-Associated, and Healthcare-associated Pneumonia. American Thoracic Society and The Infectious Diseases Society of America. Am J Respir Crit Care Med. 2005;171:388-416. 2) Dipiro JT, editor. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York (NY): McGraw-Hill; 2008. P.3786-3811. 3) Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Infectious Diseases Society of America. Clinical Infectious Diseases. 2016;63:1-51. 4) Chastre et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults. JAMA. 2003;290(19):2588-98. 5) Rubinstein et al. Pneumonia caused by methicillin-resistant staphylococcus aureus. Clinical Infectious Diseases. 2008;46:S378-85. 6) Gilbert et al. The Sanford Guide to Antimicrobial Therapy 2016. Sperryville (VA): Antimicrobial Therapy, Inc; 2016. p.42. 45