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
I do not have any relevant relationships to disclose
pertaining to this presentation today.
Majdi N. Al-Hasan, MBBS
 Discuss the rationale for antimicrobial
stewardship.
 Integrate evidence-based practices to improve
antimicrobial therapy.
 Utilize tools to achieve antimicrobial stewardship
goals.
 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
 Increasing proportion of immune-compromised
patients
 Advancements in cancer treatment
 Hematological and solid organ transplantation
 Corticosteroids and other immunosuppressive agents
(TNF inhibitors, etc.)
 HIV
 Classification of infections based on site of
acquisition:
 Hospital-acquired (nosocomial)
 Community-onset
 Healthcare-associated
 Community-acquired
 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
 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.
 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.
El Atrouni et al. Temporal trends in the incidence of Staphylococcus aureus
bacteremia in Olmsted County, Minnesota. Clin Infect Dis 2009.
Al-Hasan et al. Antimicrobial resistance trends of Escherichia coli
bloodstream isolates. J Antimicrob Chemother 2009.
 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
 Hospitals continue to fight outbreaks of infections
due to multi-drug resistant (MDR) organisms:
 MDR Pseudomonas aeruginosa
 MDR Acinetobacter baumanii
 Vancomycin-resistant enterococci (VRE)
 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
 Making the best of currently available
antimicrobial agents
 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.
 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 he’s
admitted to the hospital for observation.
 He remains febrile for 2 days in the hospital and
still doesn’t 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.
 Blood cultures obtained in the ICU grow Gram-
negative bacilli. Cefepime is added and HD
catheter is removed.
 However, course progresses to severe sepsis (multiorgan failure) and septic shock (BP not responding
to vasopressor therapy) and patient expires on
hospital day #4.
 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
 Empiricism will carry you for 48 hours at best,
then you’re left alone in the dark without any
guidance unless you’ve done the appropriate
diagnostic work-up upfront:
 Cultures (blood, urine, sputum, CSF, bone, tissue)
 Antigens
 PCRs
 Possible directions of “blind empiricism”:
 Clinical improvement: can’t discharge home on broadspectrum IV antimicrobial regimen.
 Clinically stable: can’t continue broad-spectrum
antibiotics due to side effects.
 Clinical deterioration: low-yield cultures after few days
of antibiotics, can’t keep adding antibiotics, may be too
little too late
 Making the best of currently available
antimicrobial agents
 Determining microbiological etiology of infections
 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.
 Patient was started on broad-spectrum antibiotics,
including IV vancomycin and piperacillintazobactam 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.
 On day #7 of hospitalization, she develops fever,
watery diarrhea and leukocytosis of 27K.
 Diabetic foot ulcer site demonstrates continued
clinical improvement.
 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
 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
 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
 In the given case, multiple opportunities were
missed to de-escalate 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
 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
 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.
 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.
 Antimicrobial stewardship starts in the office
 Differentiating viral from bacterial upper
respiratory tract infections
 Differentiating clinical failures from recurrences
 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.)
 A 51-year old gentleman undergoes left hemi-
colectomy 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 imipenem-cilastin.
 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.
 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
 Patients with infections due to carbapenem-
resistant Gram-negative 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
 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
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 Improve the outcome of hospitalized patients with
serious infections
 Optimize empirical antimicrobial therapy
 Faster delivery of antimicrobial therapy
 Elimination of discordant definitive antimicrobial
therapy
 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 broadspectrum antimicrobial therapy
 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
 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
 Re-evaluate empirical antimicrobial regimen
based on:
 Gram stain
 Culture results
 In vitro antimicrobial susceptibility testing
 Clinical response
 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
 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
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