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COVID-19 Mortality from Secondary Acquired Infections
How life has changed: COVID-19 and AMRPresidential Advisory Council on Combating Antibiotic-Resistant Bacteria9 September 2020
Cornelius J. Clancy, M.D.Chief, Infectious Diseases VA Pittsburgh Healthcare SystemAssociate Chief, Infectious DiseasesDirector, XDR Pathogen Lab andMycology Research UnitUniversity of Pittsburgh
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Why do COVID-19 patients die?
Postmortem histopathology images from Sekulic et al. Am J Clin Path 2020; Hanley et al. Lancet Microbe 2020.
Diffuse alveolar damage causing acute respiratory distress syndrome (ARDS)
Thromboembolic disease
Multisystem organ failure Immune depletion and dysregulation
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Do patients die of secondary infections?
of COVI-19 autopsies have histopathologic findings in lungs that are consistent with superimposed bronchopneumonia or pulmonary infection137%
● Findings due to superimposed infection or COVID-19?● Very limited microbiology and AMR data● More often focal process rather than diffuse disease● Often not recognized or treated with antimicrobials ante-mortem
Images from Sekulic et al. Am J Clin Path 2020; Hanley et al. Lancet Microbe 2020. 1. Histopathologic findings: Intra-alveolar PMN infiltrates or abscess/empyema, in absence of classic viral pneumonia histopathology. N=106/289, from review of data from 51 peer-reviewed publications through 28 August 2020, includes hospital- and community-based deaths
Sizeable minority of COVID-19 decedents die with, but not necessarily from, superimposed bacterial
or (less often) fungal infections
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Types of COVID-19 secondary infections
Microbiology and AMR will reflect local epidemiology
and host risk factors
Lung: P. aeruginosa, K. pneumoniae, C. koseri, S. maltophiliaUrine: E. Coli, Proteus, K. pneumoniae
● MDR, ESBL, CRE infections diagnosedBlood: S. aureus, coag negative Staph, Strep spp., Candida
Bloodstream infections● Endocarditis, septic emboli, abscesses
Urinary tract infectionsSkin and soft tissue infectionsClostridiodes difficile infections
Co-infections● Community acquired pneumonia, urinary tract infection, skin/soft tissue
infection, C difficile infection, febrile neutropeniaSecondary infections
● Hospital/ventilator pneumonia, bloodstream infection, urinary tract infection, C. difficile infection
VAPHS experience, through 7/31/20
No co- or secondary infxn, 72%
Present w co-infxn, 9%
Develop secondary infxn, 19%
Buehrle et al. Antimicrob Agents Chemother 2020
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COVID-19: Antimicrobial stewardship strategies
Gp 1. No antimicrobials
41%
Gp 2. Empiric treatment, no infxn diagnosed
31%
Gp 3. Treat for co-infxn
9%
Gp 4. Treat for secondary infxn, 19%
Stewardship group Stewardship objectives1. No treatment Limit unnecessary use, include rapid
diagnostics (negative predictive values)2. Empiric treatment
Target most likely pathogens, rapid de-escalation, limit duration, aggressive diagnostic testing (NPVs)
3. Treat co-infection Promote narrow spectrum, short course, oral
4. Treat secondary infection
Target nosocomial pathogens, promote narrow spectrum, short course
Buehrle et al. Antimicrob Agents Chemother 2020
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1400
1600
1800
2000
2200
2400
Antib
iotic
Day
s of
The
rapy
(DO
T)
1/18 3/18 5/18 7/18 9/1811/181/19 3/19 5/19 7/19 9/1911/191/20 3/20 5/20
Actual Predicted
2000
2500
3000
3500
4000
Bed
days
of c
are
1/18 3/18 5/18 7/18 9/1811/181/19 3/19 5/19 7/19 9/1911/191/20 3/20 5/20
Actual Predicted
Impact of COVID-19 on hospital antibiotic use
580
600
620
640
660
Day
s of
The
rapy
per
100
0 Be
d D
ays
of C
are
1/18 3/18 5/18 7/18 9/1811/181/19 3/19 5/19 7/19 9/1911/191/20 3/20 5/20
Actual Predicted
7080
9010
011
0D
OT/
1000
BD
OC
3/18
6/18
9/18
12/18 3/1
96/1
99/1
912
/19 3/20
6/20
Actual Predicted
3040
5060
70D
OT/
1000
BD
OC
3/18
6/18
9/18
1218 3/1
96/1
99/1
912
/16 3/20
6/20
Actual Predicted
VAPHS Days of therapy (DOT) VAPHS bed days of care (BDOC) VAPHS DOT/1,000 BDOC
Non-antipseudomonal PNCsDOT/1,000 BDOC
MacrolidesDOT/1,000 BDOC
Significantly increased DOT/1000 BDOC of agents vs. CAP ● Patients with CAP/suspected CAP disproportionately presenting to hospital?● Over-treatment of suspected CAP?
Buehrle et al. Antimicrob Agents Chemother 2020
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0
200
400
600
800
1000
1200
1400
1600VAPHS outpatient prescriptions, Nov 2017-July 2020
510
1520
Pres
crip
tions
per
100
0 pe
rson
s
Aug 2014 Aug 2015 Aug 2016 Aug 2017 Aug 2018 Aug 2019
Amoxicillin
510
1520
Pres
crip
tions
per
100
0 pe
rson
s
Aug 2014 Aug 2015 Aug 2016 Aug 2017 Aug 2018 Aug 2019
Azithromycin
02
46
810
Pres
crip
tions
per
100
0 pe
rson
s
Aug 2014 Aug 2015 Aug 2016 Aug 2017 Aug 2018 Aug 2019
Amoxicillin/Clavulanate
Outpatient antibiotic useUS prescription fills, 2014-July 2020 (IQVIA NPA data)
Significant reductions in prescription fills in April 2020 for the ten most commonly prescribed outpatient antibiotics
● No significant rebound, April-July 2020: Azithromycin, amoxicillin-clavulanate, levofloxacin ● Rebound April-July 2020, but still below baseline: Amoxicillin, doxycycline
Prescription fills for outpatient antibiotics recommended against CAP or commonly used against respiratory tract infections remain significantly below baseline
● Patients not seeking care? Clinicians less likely to prescribe (unnecessary) agents?
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Will COVID-19 result in increased AMR? Pro• Antibiotic prescribing in excess of secondary
infections, suggesting inappropriate use• Many COVID-19 epicentres also AMR epicentres• Burden of antibiotic use in hospitalized patients
increased, even outside of epicentres• Reports of HAI outbreaks associated with
breakdowns in infection prevention• Effects of COVID-19 on public health infrastructure,
sanitation, healthcare delivery, governance may indirectly impact AMR and transmission
• Secondary infections may increase as COVID-19 treatment evolves (e.g., dexamethasone)
• Co-circulation of SARS-CoV-2 and influenza may fuel inappropriate antibiotic prescribing
• Overall antibiotic use in humans has decreased in many places
• Major determinant of AMR rates is spread, which may be decreased with COVID-19 travel restrictions, enhanced attention to infection prevention, etc.
• Better COVID-19 outcomes may decrease pools of high risk critically ill patients, including those on ventilators, receiving hemodialysis, etc.
• Increased emphasis on diagnosing respiratory viral infections may decrease inappropriate antibiotic treatment
• Data from southern hemisphere suggest that impact of influenza may be lessened by COVID-19 precautions
Clancy, Buehrle and Nguyen. J Antimicrob Chemother-AMR 2020; Collignon and Beggs. J Antimicrob Chemother-AMR 2020
COVID-19 and AMR story will be dynamic, and likely to differ from region to region, hospital to hospital, and unit to unit within hospitals
● AMR was a major problem before COVID-19, and it will remain a problem
Con
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COVID-19 and AMR: Needs moving forward
• Report our experiences and data• More rigorous microbiology and
definitions of superimposed infections in clinical and postmortem studies
• Surveillance data on antimicrobial use and AMR
• Education• It’s OK not to get/give an antibiotic• AMR has not gone away