Transcript Slides

Objectives
 Recognize that respiratory tract infection is the most frequent
indication for antimicrobial use in the hospital
 Identify categories of pneumonia that inform empiric antimicrobial
selection
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Community-acquired Pneumonia
Hospital-acquired Pneumonia
Ventilator-associated Pneumonia
Healthcare-associated Pneumonia
 Discuss data that drives regimen optimization and duration
 Review best practice regarding antimicrobial use for acute
exacerbation of chronic bronchitis
 Understand that antibiotics are NOT indicated for acute bronchitis in
immune-competent hosts nor for prophylaxis of COPD exacerbations
AMS at PAMC
 6,900 interventions since program inception
 1,900 of 6,900 (28%) relate to respiratory infections
 By far the most common type of intervention
 Types of interventions
 Medication class change
 Duration of therapy
 IV to PO
 Respiratory-related AMS interventions represent “lowhanging fruit” and are “bread-n-butter” to an active AMS
program
Community-acquired
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Pneumonia
 Pneumonia in patients WITHOUT risk factors for nosocomial
organisms
 Subcategories
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Outpatient
Severe (ICU) vs. non-severe
Structural lung disease that increases Pseudomonas risk
Aspiration pneumonia and lung abscess
 Organisms
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Pneumococcus, Haemophilus, Moraxella
Legionella, Mycoplasma, Chlamydia
Structural lung disease: above plus Pseudomonas
Alcoholic with bloody sputum: above plus enteric GNR (Klebsiella)
Lung abscess or empyema: above plus oral anaerobes
CAP Empiric Rx1
 Outpatients: Amox/clav 875/125mg plus azithromycin 500mg
 No monotherapy with doxycycline or azithromycin (pneumococcus
sensitivity <90%)
 Ceftriaxone 1-2g plus Azithromycin 500 mg regardless of
severity
 If anaphylactic PCN Allergy: Levofloxacin 750mg (add aztreonam if
ICU)
 Structural lung disease:
 Pip/tazo or cefepime PLUS atypical Rx (use quinolone if empiric
pseudomonas coverage <90% with monotherapy)
 Lung abscess and aspiration “pleuropulmonary syndrome”:
 (Ceftriaxone plus metronidazole) OR amp/sulbactam
 Aspiration at time of intubation/suctioning or from vomiting does
NOT require anaerobic coverage
Azithromycin
 500mg PO or IV x 3 days2,3
 Multiple studies and meta-analysis support short course 500
mg dosing
 Azithromycin is the preferred form of atypical
coverage in severe illness
 Combination therapy decreases mortality in bacteremic
pneumococcal illness4
 Azithromycin plus beta-lactam is associated with decreased
mortality in ICU-severity CAP vs. quinolone plus betalactam5
 Small increased MI risk (OR 1.17) outweighed by survival
benefit in elderly veterans (HR 0.73) 14
Intensive Care Med (2010) 36:612–620
Duration of therapy 1,6,7
 Switch to PO as soon as hemodynamically stable and taking PO
 Stop after the following durations assuming afebrile >24h and
hemodynamically stable:
 5 days if no immune-compromise* or structural lung disease
 7 days if moderate immune compromise or structural lung disease
 10-14 days if poor clinical response, inappropriate initial therapy, or
severe immune compromise
 Duration for pneumonia with uncomplicated pneumococcal
bacteremia is the SAME!! (i.e. 5 days ok if adequate response,
ok to swap to PO as per usual protocol)
*Organ transplant, HIV, chemotherapy, chronic prednisone >10mg, immune-suppressing medications
Clinical
Infectious
Diseases
2012;54(11):158
1–7
Levofloxacin 750 mg (7)
 Levofloxacin 750 mg x 5d duration EQUIVALENT cure
rates to 500mg x 10d
Is atypical coverage really necessary?
 CAP START study, NEJM 201515
 Randomized trial of Beta-lactam vs. Beta-lactam plus
azithromycin vs. quinolone monotherapy in non-severe
inpatient CAP
 Therapy could be altered for medical reasons
 Netherlands, 2283 patients conducted 2011 to 2013
 No difference in 90 day mortality, length of stay, or
complication rate
N Engl J Med 2015;372:1312-23.
Is Atypical Rx Needed?9
BMJ Open 2015;5:e006892
HAP, VAP, and HCAP10
 Pneumonias associated with hospital stay, antibiotic exposure,
and/or colonization with resistant organisms
 Early onset HAP <5d from admit is treated like CAP but
WITHOUT atypical coverage
 VAP and HCAP are assumed to be at risk for resistant organisms
including MRSA and resistant gram-negative rods
 Data supporting this conclusion is high quality in VAP but weak in
HAP and especially HCAP which was extrapolated from other
types of infections in patients with specific risk factors
 “The guideline recognizes the variability of bacteriology from one
hospital to another and from one time period to another and
recommends taking local microbiologic data into account when
adapting treatment recommendations to any specific clinical
setting”
Healthcare-associated
Pneumonia
 New category in 2005 IDSA/ATS guidelines10
HAP, VAP, HCAP Algorithm10
 Lower respiratory tract cultures should be obtained from all patients
prior to antibiotic start or change
 Do not unduly delay abx while awaiting cultures
 Empiric regimen to cover MRSA and Pseudomonas in addition to early
HAP organisms guided by institutional epidemiologic data
 Is MRSA common in the community?
 Does mono-therapy against Pseudomonas cover >90% of isolates or is
double-Pseudomonas therapy required until sensitivities are known?
 Once cultures return, narrow to single drug and treat for 7 days
UNLESS non-lactose fermenting gram negative rod (Pseudomonas,
Acinetobacter, Stenotrophomonas)11 ,13
 Duration 14 days for NLF GNR due to increased relapse risk
 If high quality lower respiratory tract cultures were obtained prior to
antibiotics, are negative at 48-72h, and the patient is improved
antibiotics should usually be STOPPED!!10, 12
Approach in Anchorage
 Make sure lower respiratory tract cultures are ordered!
 Early onset HAP
 Ceftriaxone
 Late onset HAP or VAP/HCAP:
 Vancomycin dosed to goal trough 15-20
 Cefepime 1g q8h (or 2g q12h)
 Cefepime is active against >90% of our enteric GNRs and Pseudomonas, is
less nephrotoxic than pip/tazo when combined with vancomycin, has no
unnecessary anaerobic coverage, and is in adequate supply
 Above dosing determined by examining probability of target attainment
(PTA) based on the MIC 90 at our institutions
 Aggressively narrow/stop once cultures back
 No atypical or anaerobic coverage required
IDSA/ATS HCAP Definition is
probably overly inclusive
 Current thinking is that a large amount of present abx
overuse/misuse in the US is due to HCAP since 2005
Clinical Infectious Diseases 2013;57(10):1373–83
Novel HCAP Definition16
Acute Exacerbation of COPD
 Chronic bronchitis or emphysema with worsening
respiratory symptoms
 GOLD 2015 guidelines form management standards17
 Data supports antibiotic use for moderate to severe
exacerbation only and is based on limited placebo
controlled data and meta-analysis that suggest near-term
mortality benefit18,19
 To qualify for antibiotics, patient must have:
 Increased dyspnea and sputum PURULENCE, or
 Require mechanical ventilation (ETT or BiPAP)
Antibiotic choice for AECOPD
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“The choice of the antibiotic should be based on the local bacterial resistance
pattern.”17
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“…aminopenicillin with or without clavulanic acid, macrolide, or
tetracycline…usually 5 – 10 days.”17
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There is no compelling data to drive empiric selection. Weak quality data suggests
that augmentin, macrolide, and quinolones perform equally poorly, but that
quinolones might decrease risk of near-term recurrent exacerbation17-21
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At ANMC we pulled our own data
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Large % not getting cultures
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Bugs mirror CAP organisms but occasionally include S aureus or Pseudomonas
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We encourage obtaining cultures and use usual CAP regimens for 5 days (guided
by culture data when available) for inpatients.
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Outpatients with mild exacerbation do not require sputum cultures or antibiotics.
Azithromycin vs Levofloxacin
for AECOPD
 Retrospective review of 19,608 patient given either
quinolone or macrolide for AECOPD20
Daily prophylactic azithromycin
for COPD?
 Taken daily for 1 year, exacerbation averaged 1.48 vs. 1.83
(HR 0.73) in patients on daily azithromycin 250 mg22
 Hearing loss over 1 year higher in treatment group and more
resistant organisms developed
 “…treatment is not recommended because of an
unfavorable balance between benefits and side
effects…the use of antibiotics, other than for treating
infectious exacerbations of COPD and other bacterial
infections, is currently not indicated.”17
Antibiotics are NOT indicated
for acute bronchitis
 Period!!!23-25
 No improvement in symptoms
 Increase in side effects vs. placebo
References
1.
Clinical Infectious Diseases 2007; 44:S27–72
10.
Am J Respir Crit Care Med Vol 171. pp 388–
416, 2005
2.
Eur Respir J, 1995, 8, 398–402
11.
JAMA. 2003 Nov 19;290(19):2588-98.
3.
Journal of Antimicrobial Chemotherapy
(2001) 48 ,691-703
12.
Am J Respir Crit Care Med 2000;162:505–511.
4.
Am J Respir Crit Care Med Vol 170. pp 440–
444, 2004
13.
Cochrane Database Syst Rev. 2015 Aug
24;8:CD007577.
5.
Intensive Care Med (2010) 36:612–620
14.
JAMA. 2014 June 4; 311(21): 2199–2208
6.
Clinical Infectious Diseases 2012;54(11):1581–
7
15.
N Engl J Med 2015;372:1312-23.
7.
Drugs 2008; 68 (13): 1841-1854
16.
Clinical Infectious Diseases 2013;57(10):1373–
83
8.
Clinical Infectious Diseases 2003; 37:752–60
17.
http://www.goldcopd.org/uploads/users/files/
GOLD_Report_2015.pdf Accessed 3/28/16
9.
BMJ Open 2015;5:e006892
18.
Cochrane Database Syst Rev 2006: CD004403
References (2)
19.
Chest 2008: 133;756-66
20.
Journal of Hospital Medicine 2010;5:261–267
21.
Eur Respir J 2007; 29: 1127–1137
22.
N Engl J Med 2011;365:689-98.
23.
Ann Intern Med. 2016;164:425-434
24.
Cochrane Database Syst Rev.
2014;3:CD000245
25.
BMJ. 2013;347:f5762.