OVERVIEW OF ANTIMICROBIAL

STEWARDSHIP
MAJDI N. AL-HASAN, MBBS
ASSOCIATE PROFESSOR OF MEDICINE
DIRECTOR, ANTIMICROBIAL STEWARDSHIP PROGRAM
DEPARTMENT OF MEDICINE
DIVISION OF INFECTIOUS DISEASES
UNIVERSITY OF SOUTH CAROLINA SCHOOL OF MEDICINE

DISCLOSURES
I do not have any relevant relationships to disclose pertaining to this
presentation today.

Majdi N. Al-Hasan, MBBS

OBJECTIVES
Discuss the rationale for
antimicrobial stewardship.
Integrate evidence-based practices
to improve antimicrobial therapy.
Utilize tools to achieve
antimicrobial stewardship goals.

BACKGROUND
Increasing complexity of patient
care over the past two decades:
Aging population
Increasing use of medical devices
Central venous catheters
Prosthetic heart valves
Implantable cardiac devices
Prosthetic joints
Brain/spinal stimulators

BACKGROUND
Increasing proportion of immunecompromised patients
Advancements in cancer treatment
Hematological and solid organ transplantation
Corticosteroids and other immunosuppressive agents (TNF inhibitors,
etc.)
HIV

BACKGROUND
Classification of infections based on
site of acquisition:
Hospital-acquired (nosocomial)
Community-onset
Healthcare-associated
Community-acquired

BACKGROUND
Inappropriate empirical antimicrobial
therapy is associated with increased
mortality in patients with serious
infections:
Sepsis
Bloodstream infections (BSI)

Paul M et al. AAC 2010; 54: 4851-63

Retamar P et al. AAC 2012; 56: 472-8

Kumar A et al. Duration of hypotension before initiation of

effective antimicrobial therapy is the critical determinant of
survival in human septic shock. Crit Care Med 2006

BACKGROUND
All this pressure has prompted an
increase in the use of broad-spectrum
antimicrobial therapy in very complex
patients with serious infections.
Unfortunately, that has been extrapolated
for treatment of less complex patients
with less serious infections.

BACKGROUND
Excessive antibiotic use has driven
antimicrobial resistance rates high
both in hospitals and community.
Vicious cycle of increasing use of
antibiotics and further increase in
antimicrobial resistance rates.

STAPHYLOCOCCUS AUREUS

El Atrouni et al. Temporal trends in the incidence of Staphylococcus aureus

bacteremia in Olmsted County, Minnesota. Clin Infect Dis 2009.

ESCHERICHIA COLI

Al-Hasan et al. Antimicrobial resistance trends of Escherichia coli

bloodstream isolates. J Antimicrob Chemother 2009.

ESBLS AND CRES

Increasing incidence rate of extended
spectrum beta-lactamase (ESBL) producing
E. coli and Klebsiella spp in Europe and USA.
Carbapenem-resistant Enterobacteriaceae
(CRE) are increasingly reported
Klebsiella pneumonia carbapenemase (KPC) in 2001
New Delhi Metallo-beta-lactamase (NDM) in 2009

MMWR 2013; 62: 165-70

MDRS
Hospitals continue to fight
outbreaks of infections due to
multi-drug resistant (MDR)
organisms:
MDR Pseudomonas aeruginosa
MDR Acinetobacter baumanii
Vancomycin-resistant enterococci (VRE)

NO SHORT-TERM SOLUTION
Despite all of this increase in
complexity of care and
antimicrobial resistance, there is
paucity of antimicrobial
development
Very few novel antimicrobial agents for treatment of Gram-negative
infections
Free market rules
New antibiotics are at early phases of development

WHAT IS THE SOLUTION?

Making the best of currently
available antimicrobial agents

CASE #1
A 56-year old gentleman with ESRD on
hemodialysis through HD catheter
misses HD once due to feeling unwell.
He is found to have a temperature of 101.8
F next HD session.
One dose of IV vancomycin is administered
after HD without obtaining any work up.

CASE #1
He still reports subjective fever on
the following HD session. HD is
stopped prematurely due to relative
hypotension.
Another dose of IV vancomycin is
given and hes admitted to the
hospital for observation.

CASE #1
He remains febrile for 2 days in the
hospital and still doesnt feel better.
IV vancomycin is switched to IV
daptomycin. Still no cultures are
obtained.
On the 3rd night of hospital stay, he is
transferred to the ICU due to hypotension
requiring vasopressors.

CASE #1
Blood cultures obtained in the ICU
grow Gram-negative bacilli. Cefepime is
added and HD catheter is removed.
However, course progresses to severe
sepsis (multi-organ failure) and septic
shock (BP not responding to
vasopressor therapy) and patient
expires on hospital day #4.

KEY POINTS: DIAGNOSIS IS THE KEY

An infectious disease diagnosis is not
complete unless all of the following
components are established:
Clinical syndrome (---itis)
Microbiological etiology
Host

Mark Wilhelm, MD
Mayo Clinic, Rochester, MN

KEY POINTS:
MICROBIOLOGICAL DX
Empiricism will carry you for 48 hours
at best, then youre left alone in
the dark without any guidance
unless youve done the appropriate
diagnostic work-up upfront:
Cultures (blood, urine, sputum, CSF, bone, tissue)
Antigens
PCRs

KEY POINTS: EMPIRICISM

Possible directions of blind
empiricism:
Clinical improvement: cant discharge home on broad-spectrum IV
antimicrobial regimen.
Clinically stable: cant continue broad-spectrum antibiotics due to side
effects.
Clinical deterioration: low-yield cultures after few days of antibiotics,
cant keep adding antibiotics, may be too little too late

WHAT IS THE SOLUTION?

Making the best of currently
available antimicrobial agents
Determining microbiological etiology of infections

PICTURES-PLEASE OBSERVE

CASE #2
A 72-year old lady with DM is admitted
to the hospital with purulent drainage
from superficial diabetic foot ulcer.
On exam: T 99.4, BP 138/78, PR 82.
2x2 cm superficial ulcer in dorsal right
big toe with some purulence, but no
surrounding erythema or warmth.
Peripheral pulses are present, but weak.

CASE #2
Patient was started on broad-spectrum
antibiotics, including IV vancomycin and
piperacillin-tazobactam prior to surgical
consultation for possible debridement.
No evidence of osteomyelitis on MRI.
On hospital day #4, she undergoes I&D of ulcer.
Tissue cultures grow group B Streptococcus.
However, broad-spectrum antibiotics are
continued.

CASE #2
On day #7 of hospitalization, she
develops fever, watery diarrhea and
leukocytosis of 27K.
Diabetic foot ulcer site
demonstrates continued clinical
improvement.

KEY POINTS: EMPIRICISM, AGAIN

No need to start empiric antibiotics
prior to surgical I&D and cultures
in patients with diabetic foot
infections, including chronic
osteomyelitis in the absence of:
Surrounding cellulitis
High fever with hypotension
Limb-threatening complications

KEY POINTS: EMPIRICISM, AGAIN

No need for empiric Gram-negative
coverage in superficial diabetic foot
ulcer infections
Most superficial ulcer infections are caused by Gram-positive bacteria:
staphylococci, streptococci and enterococci
In non life- or limb-threatening infections, waiting for tissue Gram stain
results is very unlikely to impact patient outcome (risk outweighs benefit)
Early surgical debridement (source control) is more important than
antibiotics

KEY POINTS: DE-ESCALATION

After culture (and in vitro
antimicrobial susceptibility testing)
results are back, it is essential to
reassess empirical regimen:
Escalation: if clinically significant isolate is resistant to empirical
regimen
De-escalation: narrowest spectrum, safest, cheapest, most effective
single antimicrobial agent for treatment of that particular infection

KEY POINTS: DE-ESCALATION

In the given case, multiple
opportunities were missed to deescalate therapy:
Gram-positive cocci on Gram stain: vancomycin monotherapy should
be effective.
Beta-hemolytic streptococci (groups A, B, C, etc): 100% susceptibility
to penicillin G

WHAT IS THE SOLUTION?

Making the best of currently
available antimicrobial agents
Determining microbiological etiology of infections
Empirical therapy based on most probable etiology
Early de-escalation of antimicrobial therapy

CASE #3
A 23-year old lady with chronic sinusitis. She
presents to clinic with low-grade fever, runny
nose with yellowish drainage and sinus
tenderness on exam.
She received a short course of azithromycin
for similar symptoms 3 months prior to this
episode and amoxicilin-clavulanate 7 months
earlier.
She is prescribed levofloxacin this time.

CASE #3
She returns to the office one month later
with high fever, urinary frequency, dysuria
and back pain. She has Rt constoverterbral
angle tenderness on exam.
Urine dipstick in the office is suggestive of
UTI.
Blood work up shows leukocytosis with
left shift.

KEY POINTS: ANTIMICROBIAL

RESISTANCE

Antimicrobial stewardship starts in

the office
Differentiating viral from bacterial
upper respiratory tract infections
Differentiating clinical failures from
recurrences

KEY POINTS: ANTIMICROBIAL

RESISTANCE

Use of end-of-the-line antibiotic for

treatment of relatively minor
infections can be costly
Risk of colonization/infection with resistant organisms
Potential loss of important antimicrobial options for treatment of
future serious infections
Potential loss of all oral antimicrobial options
Complicated and increased cost of care (need for hospitalization, PICC
lines, IV antibiotics, etc.)

CASE #4
A 51-year old gentleman undergoes left hemicolectomy for colon cancer.
He receives ertapenem for pre-operative
surgical site prophylaxis.
He is discharged from the hospital to
rehabilitation. Serious drainage is noted from
the surgical wound at rehabilitation, so
patient is started empirically on imipenemcilastin.

CASE #4
He is readmitted to the hospital 14 days after
discharge with with fever and left lower
abdominal pain.
CT scan of abdomen and pelvis demonstrates
fluid collection in LLQ.
CT-guided aspiration is performed.
Cx of fluid grew carbapenem-resistant
Klebsiella pneumoniae (CRE) that is resistant
to all tested antibiotics except colistin.

KEY POINTS: RESISTANCE, AGAIN

Use of end-of-the-line antibiotic for
relatively minor indications
Ertapenem for surgical site prophylaxis!

Source control and cultures prior to

starting antibiotics
High inoculum of bacteria and low antibiotic concentration in the
abscess fluid create an optimal environment for development of
antimicrobial resistance

KEY POINTS: RESISTANCE, AGAIN

Patients with infections due to
carbapenem-resistant Gramnegative bacilli are often left
without any currently available
safe or effective treatment options:
CRE are often resistant to most available antibiotics
Remaining options are either ineffective, nephrotoxic or both
New agents are in early phases of development

WHAT IS THE SOLUTION?

Making the best of currently
available antimicrobial agents
Determining microbiological etiology of infections
Empirical therapy based on most probable etiology
Early de-escalation of antimicrobial therapy
Knowledge of local and regional antimicrobial resistance rates
Stratifying patients at risk of infections due to resistant
organisms
Utilizing tools to determine severity of illness scores
Antimicrobial stewardship programs

ANTIMICROBIAL STEWARDSHIP
GOALS
Improve the outcome of
hospitalized patients with serious
infections
Optimize empirical antimicrobial therapy
Faster delivery of antimicrobial therapy
Elimination of discordant definitive antimicrobial therapy

ANTIMICROBIAL STEWARDSHIP
GOALS
Reduce side effects and toxicities
associated with antimicrobial
therapy, including C. difficile
colitis
Early de-escalation of antimicrobial therapy
Discontinuation of antimicrobial therapy in patients without infections
Discourage unjustified non-stratified use of broad-spectrum
antimicrobial therapy

ANTIMICROBIAL STEWARDSHIP
GOALS
Reduce antimicrobial resistance
individually and collectively
Establish a culture of culture-guided antimicrobial therapy
Emphasize the importance of source control for successful treatment
of infections

ANTIMICROBIAL STEWARDSHIP
GOALS
Stratify patients when making empirical
antimicrobial treatment decisions
Likely microbiological etiology of infection
Site of infection acquisition
Local and regional antimicrobial resistance
rates
Risk factors for antimicrobial resistance
Severity of illness scores

ANTIMICROBIAL STEWARDSHIP
GOALS
Re-evaluate empirical antimicrobial
regimen based on:
Gram stain
Culture results
In vitro antimicrobial susceptibility testing
Clinical response

TOOLS TO ACHIEVE PROGRAM

GOALS
Education
Group sessions
One on one

Data generation and dissemination

Local and regional antibiograms
Microbiological etiology of common infections
Outcome of patients with serious infections

TOOLS TO ACHIEVE PROGRAM

GOALS
Research
Clinical therapeutics
Antimicrobial resistance trends
Effectiveness of clinical interventions

Development of local guidelines and

pathways for management of
common/serious infections
Power plans

Antimicrobial Stewardship
and Support Team
Pager # 352-1322