Antibiotics: Selected Topics
Steven Park, MD/PhD
Director, Antimicrobial Stewardship Program
Division of Infectious Diseases
UCI Medical Center
Case 1
 60 yo male admitted for fevers and dysuria.
Underwent TURP one week ago for BPH
 History of previous pyelonephritis secondary to
BPH
 On admission, temperature 102. BP stable.
Pulse 105 but after a liter of fluid comes down to
84
 WBC 20 with left shift; creatinine 1.0; UA with
140 wbc. Urine sent for culture. Blood cultures
drawn. Patient started on ceftriaxone.
 Patient does not look ill. Complaining of dysuria.
Case 1 continued
 Laboratory calls you the next day and tells
you both urine and blood are growing gram
negative rods
 Still febrile
 CBC 28
 Blood pressure and pulse ok
Next step?
a.
b.
c.
d.
e.
Continue ceftriaxone
Start Zosyn
Start cefepime
Start ciprofloxacin
Start meropenem
Next step?
a.
b.
c.
d.
e.
Continue ceftriaxone
Start Zosyn
Start cefepime
Start ciprofloxacin
Start meropenem
UCI Antibiogram 2014
Case 2
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60 yo male transferred from SNF for fever
Has been on TPN and has PICC line
Febrile with leukocytosis
Patient looks ill
Chest xray clear. UA negative
You suspect PICC line infection. Patient
placed on vancomycin and Zosyn
 Creatinine 2.8. Previous 1.0.
Case 2 continued
 Next day patient’s blood pressure drops and
patient intubated
 Levophed and ADH required to maintain BP
 Nurse about to start phenylephrine
 You remove the PICC line
 Lab calls and states that blood is growing
gram negative rods which appear lactose
negative
 You stop vancomycin
Next step?
a.
b.
c.
d.
e.
Continue Zosyn
Stop Zosyn and start meropenem
Stop Zosyn and start cefepime
Stop Zosyn and start cefepime and amikacin
Stop zosyn and start cefepime and
ciprofloxacin
Next step?
a.
b.
c.
d.
e.
Continue Zosyn
Stop Zosyn and start meropenem
Stop Zosyn and start cefepime
Stop Zosyn and start cefepime and amikacin
Stop zosyn and start cefepime and
ciprofloxacin
Lactose fermenters
 Characteristic of gram negative organisms
 Ability of organism to use lactose as food
source
 Fermenters: E. coli, Enterobacter, Klebsiella
 Non-fermenters: Pseudomonas,
Acinetobacter, Stenotrophomonas
UCI Antibiogram 2014
Case 2 continued
 Patient improves on cefepime and amikacin.
Next day only on Levophed
 Cultures come back Pseudomonas sensitive
to cefepime, meropenem, ciprofloxacin,
amikacin, resistant to Zosyn
 Creatinine 3.2
Next step?
a.
b.
c.
d.
Continue cefepime and amikacin
Change to cefepime and ciprofloxacin
Continue cefepime only
Change to meropenem
Next step?
a.
b.
c.
d.
Continue cefepime and amikacin
Change to cefepime and ciprofloxacin
Continue cefepime only
Change to meropenem
Empiric treatment of gram negative
bacteremia
 Really depends on how sick the patient is and
how much you need to be right initially
 After sensitivities back, can narrow down
antibiotics
 No need to routinely double cover
Pseudomonas
 Rely on your local antibiogram
Case 1
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Patient stable
Nosocomial pathogen possible
Evidence that patient was failing ceftriaxone
Willing to take 50% chance of missing ESBL
Case 2
 Patient in septic shock
 Your empiric therapy has to cover the
pathogen even at the expense of kidneys
 We knew that ESBL or CRE was not a factor
because of lactose negative GNR
 If it was, would have used meropenem
instead of cefepime
Gram negative agents
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Penicillins
Cephalosporins
Carbapenems
Fluoroquinolones
Aminoglycosides
Polymixins
Aztreonam
New agents
Penicillins
 Penicillin, oxacillin, nafcillin, dicloxacillin really
no gram negative coverage
 Amoxicillin/clavulanate (Augmentin) and
ampicillin/sulbactam (Unasyn) has some gram
negative coverage including anaerobes (not
reliable for E. coli so do not use for abdominal
infections). Can use for aspiration pneumonia
 Piperacillin/tazobactam (Zosyn) broadest
coverage including pseudomonas and anaerobes
 Zosyn sometimes active against ESBL and can
use in the urine
Cephalosporins
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Gram negative coverage increases as you go from 1st
to 3rd generation and gram positive coverage
decreases
Only ceftazidime and cefepime will cover
pseudomonas
Ceftazidime has no gram positive coverage
Limited anaerobic coverage except cefoxitin and
cefotetan
Cefepime sometimes active against ESBL and can use
in the urine
No enterococcal coverage
Carbapenems
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Ertapenem, imipenem, and meropenem
Most reliable agents against ESBL
Meropenem and imipenem will cover pseudomonas
Ertapenem will not cover pseudomonas and
enterococcus and penicillin resistant S. pneumoniae
Meropenem considered better than imipenem for
gram negatives
Imipenem considered better than meropenem for
gram positives
Some concern with imipenem and seizure threshold
Fluoroquinolones
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Levofloxacin, ciprofloxacin, moxifloxacin
Broad gram negative coverage including
pseudomonas (not moxifloxacin)
Pretty good gram positive coverage (levofloxacin,
moxifloxacin better than ciprofloxacin)
Moxifloxacin has better anaerobic coverage and can
use for abdominal infection
Need to add Flagyl to levofloxacin and ciprofloxacin
for abdominal infections
Watch out for QT prolongation and tendinitis and
tendon rupture
Aminoglycosides
 Amikacin, gentamicin, tobramycin
 Excellent gram negative coverage including
pseudomonas
 No gram positive coverage
 Very little tissue penetration
 Good for bacteremia, endovascular infections,
and urine infections
 Nephrotoxic and ototoxic
 Need to measure levels
Polymixins
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Polymixin E (Colistin), polymixin B
Stopped using decades ago. Started using again 10
years ago due to MDR gram negative infections
Excellent gram negative coverage including
pseudomonas, acinetobacter, ESBL, CRE
No gram positive coverage
Limited tissue penetration
Good for bacteremia, endovascular infections
Doesn’t concentrate in urine like aminoglycosides but
still nephrotoxic
Aztreonam
 Purely gram negative agent including
coverage for pseudomonas
 Not active against ESBL or CRE
 Can use in penicillin allergic patients
 Can not use it for patients allergic to
ceftazidime
New gram negative agents
Ceftolozane/Tazobactam (ZERBAXA)
• Recently FDA approved
• Has in vitro activity against gram negative pathogens including Pseudomonas and
most ESBL enterobacteriaceae
• Limited activity against gram positive pathogens
• Equally effective as Levaquin for complicated urinary tract infections
• Equally effective as Meropenem for complicated intra-abdominal infections
(included ESBL) when combined with Flagyl
• Limited activity against Acinetobacter
Ceftazidime/Avibactam (AVYCAZ)
• Recently FDA approved
• Has in vitro activity against gram negative pathogens including Pseudomonas and
most ESBL enterobacteriaceae and some CRE
• Limited activity against gram positive pathogens
• Equally effective as Imipenem for complicated urinary tract infections
• Equally effective as Meropenem for complicated intra-abdominal infections when
combined with Flaygl
• Limited activity against Acinetobacter
Case 3
 70 yo male with Parkinson’s disease admitted for frequent
falls
 Fell today and hit head. CT with small subdural hematoma
and patient admitted
 Denies fevers, chills, sob, cough, dysuria. Complaining of
fatigue more than usual.
 He thinks he needs his Parkinson medications adjusted
 On admission, afebrile, blood pressure stable.
 Looks tired but not ill
 WBC 14 with 85% neutrophils but no left shift
 UA negative
 Blood cultures drawn
Case 3 continued
 Next day lab informs you that ¼ blood culture
bottles with Staphylococcus aureus,
sensitivities pending
 Patient doing well. Wants to go home.
Afebrile. WBC 15.
Next step?
a.
b.
c.
d.
e.
Start vancomycin
Start daptomycin
Start linezolid
Start Bactrim
No antibiotics since it is probably
contaminant given only ¼ bottles and patient
with no signs of infection
Next step?
a.
b.
c.
d.
e.
Start vancomycin
Start daptomycin
Start linezolid
Start Bactrim
No antibiotics since it is probably
contaminant given only ¼ bottles and patient
with no signs of infection
Case 3 continued
 Next day the other 3 bottles are positive and
organism identified as MRSA with vancomycin
MIC<0.5; sensitive to daptomycin, linezolid,
synercid, gentamicin, rifampin, Bactrim
 TTE shows 0.5 cm vegetation of native mitral
valve
 Vancomycin continued with good trough levels
 5 days later, patient doing well but blood still
growing MRSA. Vancomycin MIC still <0.5
Next step?
In addition to looking for another source of
infection:
a. Keep vancomycin
b. Start daptomycin
c. Add gentamicin to vancomycin
d. Add rifampin to vancomycin
e. Start linezolid
Next step?
In addition to looking for another source of
infection:
a. Keep vancomycin
b. Start daptomycin
c. Add gentamicin to vancomycin
d. Add rifampin to vancomycin
e. Start linezolid
Staphylococcus aureus
 Staphylococcus aureus should not be treated as
a contaminant
 Vancomycin is still the mainstay of therapy
 Combination therapy only for prosthetic valve
endocarditis (gentamicin, rifampin) and
hardware associated osteomyelitis with
retention of hardware (rifampin)
 Think about failure after 7 days of persistent
cultures
 IDSA guidelines high dose daptomycin with
another agent recommended if true failure (B-III)
Antimicrobial failure is rare
 Usually due to lack of source control
Abscess
 Natural course of disease rather than
antimicrobial failure
Aspiration pneumonia
Endovascular infections
Other staphylococcus aureus infections
Vancomycin
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Still the mainstay therapy
Indicated for all infections
Be careful with acute kidney injury
Some concern over efficacy recently but this
is debatable (MIC creep)
 Only 14 cases of vancomycin resistant
staphylococcus aureus in US total
Daptomycin
 FDA approved for right sided endocarditis and
skin/soft tissue infection
 Can’t use for pneumonia
 Can increase CPK
 Can become resistant during treatment
 Reports of eosinophilic pneumonia
Clindamycin
 FDA approved for serious S. aureus (not MRSA)
infections
 Used in children with MRSA infections causing septic
arthritis, osteomyelitis, pneumonia, and
lymphadenitis
 Excellent tissue penetration except brain
 Inducible resistance can be present so lab needs to D
zone test
 Used mainly for skin/soft tissue infections in adults
 But based on pediatric data, probably can use in
pneumonia, osteomyelitis, septic arthritis
 Excellent bioavailability
Linezolid
 FDA approved for skin/soft tissue infection and
pneumonia
 Can cause serotonin syndrome in patients taking SSRI’s
 Myelosuppression (reversible), neuropathy side
effects (not reversible)
 Less resistance reported than daptomycin
 No clear evidence that linezolid better than
vancomycin for nosocomial pneumonia
 Not recommended for bacteremia (bacteriostatic) and
failures reported
Tetracyclines
 Doxycycline FDA approved for skin/soft tissue
infection due to S. aureus
 Data lacking for more invasive infections
 Minocycline may still work if resistant to
doxycycline
 Tygacil also improved for intra-abdominal
infections. Don’t use for bacteremia.
Bactrim
 Not FDA approved for any S. aureus infection
 Still used quite a bit for skin/soft tissue
infection
 Data lacking for invasive infections
 Recent open label randomized trial failed to
show non-inferiority of Bactrim versus
vancomycin (OR 1.4)
Synercid
 FDA approved for skin/soft tissue infections
 Rarely used these days
 Usually now for VRE resistant to daptomycin
and linezolid
 High incidence of arthralgias
Ceftaroline
 5th generation cephalosporin
 FDA approved for community acquired
pneumonia and skin/soft tissue infection
 Has gram negative coverage in addition to
MRSA coverage
 $400 per day
MRSA: Treatment of serious infections
 For endocarditis, bacteremia, pneumonia,
osteomyelitis, necrotizing fasciitis, vancomycin is
still first line
 Daptomycin for bacteremia, endocarditis,
osteomyelitis, necrotizing fasciitis
 Linezolid for pneumonia
 Clindamycin for pneumonia (based on data on
pediatrics) and skin/soft tissue infections,
osteomyelitis, septic arthritis
 Bactrim and doxycycline for skin/soft tissue
infections
Case 4
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45 yo female is admitted with C. difficile colitis
C. difficile PCR positive with NAP1 strain
Multiple episodes of diarrhea per day
Patient febrile with WBC 22K
Creatinine 1.8 (previously normal)
Tachycardic which responds to 1 liter NS
Abdomen mildly distended and tender
CT scan with colitis in descending colon but no
ileus
Next step?
a.
b.
c.
d.
Start po Flagyl
Start po vancomycin
Start fidaxomicin
Start po vancomycin and IV Flagyl
Next step?
a.
b.
c.
d.
Start po Flagyl
Start po vancomycin
Start fidaxomicin
Start po vancomycin and IV Flagyl
Case 4 continued
 Patient starts to get hypotensive requiring
levophed 10 mcg
 Transferred to unit
 WBC increases to 38K
 Still having profuse diarrhea
 No ileus on imaging
Next step?
a.
b.
c.
d.
Add po Flagyl
Add IV Flagyl
Add fidaxomicin
Add IV Flagyl and rectal vancomycin
Next step?
a.
b.
c.
d.
Add po Flagyl
Add IV Flagyl
Add fidaxomicin
Add IV Flagyl and rectal vancomycin
Treatment of C. difficile colitis
 Mild (leukocytosis<15K; creatinine<1.5 times baseline):
use po Flagyl
 Severe (leukocytosis>15; creatinine>1.5 times baseline):
use po vancomycin
 Severe, complicated (hypotension, megacolon, ileus): use
po vancomycin, IV Flagyl, rectal vancomycin (only with
ileus)
 Do not add IV Flagyl unless it is severe and complicated
 No evidence that increased doses of vancomycin better
but most physicians would do it
 Can get high serum levels of po vancomycin with
prolonged therapy in patients with renal failure
 New guidelines coming soon
Case 5
 83 yo female is admitted for prosthetic left hip
infection
 Had arthroplasty 2 years ago. 2 weeks ago started to
have pain. 4 days ago started to drain pus. Admitted
to Fountain Valley and vancomycin started and
transferred to UCI.
 Imaging with 5 cm abscess tracking to hardware
 Afebrile. Left hip with wound and drainage and some
surrounding erythema
 WBC 8.7
 Patient in no acute distress with stable vital signs
Case 5 continued
Assessment and Plan: 83 year old female with PMHx atrial fibrillation (on
eliquis), HTN, HL, DM, prior hip replacement presents for left hip abscess.
# left hip abscess: concern for infected hardware vs osteo. Patient not septic
at this time
- ortho consulted
- random vancomycin prior to starting vanc
- vancomycin, cefepime
- wound culture
- blood culture
- esr, crp
- CT hip
- XR hip
- norco prn
- q2d esr/crp
- discuss with patient/family in AM if they want to pursue surgery
Case 5 continued
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HOD3: ID consulted
Orthopedic service recommends surgery but patient refuses
Patient understands that antibiotics alone will not eradicate
infection and suppressive therapy likely
ID recommends stop antibiotics and get IR drainage
HOD4: IR guided drainage
HOD6: Discharged on vancomycin and ceftriaxone pending
cultures
Cultures negative
2 weeks later seen in ID clinic: creatinine 1.6 (baseline 0.8) with
supra-therapeutic vancomycin levels
Admitted to Fountain Valley for acute kidney injury likely due to
vancomycin toxicity
When do you have to start antibiotics right away? And
when should you wait until you can get proper
cultures?
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Make every attempt to get cultures if you know that treatment will
be prolonged
Hardware associated osteomyelitis
Diabetic foot infections
Endovascular infections
Decision to start antibiotics right away depends on the infection
and how the sick the patient is
Septic shock: Start right away
Meningitis: Start right away
Bad pneumonia: Start right away
Endocarditis: Depends
If symptoms have been going on for a while, safe to wait
If unsure, call ID fellow or Antimicrobial Stewardship Program
attending (me)
Case 5: In retrospect
 Antibiotics should never have gotten started
on this patient
 Patient should have gotten drainage before
broad spectrum antibiotics started
 Possible that vancomycin was not necessary
 Antibiotics can do harm sometimes
Who is hurt by unnecessary
antibiotics?
 Most: Patient
 Some: Society in general
 Least: Prescribing physician
The easy thing to do is prescribe antibiotics but it
may not be the right thing to do.
It takes a little bit of courage to not prescribe
antibiotics.