Antibiotics and ICU Infections
Jill Williams, ACNP-BC
Vanderbilt University Medical Center
Medical Intensive Care Unit
Objectives
• Discuss strategies for antibiotic stewardship
• Review mechanisms of action (MOA) for
antibiotics
• Discuss common ICU infections and antibiotic
therapies including drug levels
Antibiotic Stewardship
• What is it?
– Program to monitor use of antibiotics
– Coordinated effort between pharmacist and medical
team
• Why do we need it?
– To help achieve optimal clinical outcomes
– Minimize development of resistant strains of bacteria
– Decrease healthcare costs R/T toxicity and adverse
events
Antibiotic Stewardship – How?
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Identify patient risk factors
Know the hospital or unit antibiogram
Review previous lab results and susceptibilities
Consult with your pharmacist
Monitor drug levels when appropriate
Collaborate with an infectious disease specialist
Structure of Bacteria
www.americanaquariumproducts.com
Antibiotic Mechanism of Action
Extended Spectrum Beta Lactamases
• ESBLs
– Increasing cause of nosocomial infections
– Becoming prevalent in the community
– Higher mortality rates, longer hospital stays
• Action of ESBLs
– Open beta lactam ring on the antibiotic
– Opening of beta lactam ring = deactivation of
antibiotic
ESBL’s
• Common Culprits
– Klebsiella pneumoniae
– Klebsiella oxytoca
– Escherichia coli
• Resistance
– 3rd generation cephalosporins and monobactams
• Lab Testing
– Check sensitivities
– Resistance to ceftazidime, ceftriaxone, or cefepime =
high likelihood of ESBL
ESBL Risk Factors
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Hospital LOS*
ICU LOS*
Central venous catheters
Arterial catheters
Emergent abdominal
surgery
• Gut colonization
• Presence jejunostomy or
gastrostomy tube
• Prior antibiotics
• Residence in long-term
care facility*
• Severity of illness
• Presence of urinary
catheter
• Hemodialysis*
• Ventilatory assistance
Treatment
• Carbapenem family of antibiotics
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Only proven therapeutic option for infections
Imipenem✴
Meropenem✴
Doripenem
Ertapenem
• Duration of treatment
– No longer than indicated with other antibiotics
– Ex: 10-14 days depending on infection
Carbapenems
Drug
Dose
Duration
Comments
Imipenem
500mg IV q 6-8
hours
7-14 days
depending on
severity of
infection
Adjust dose for
renal impairment;
lowers seizure
threshold vs.
meropenem
Meropenem
500mg – 1gram
IV q 8 hours
Dependent on
severity of
infection
No renal
adjustment
needed
Doripenem
500mg q8 hrs
7-14 days
Newer drug;
renally dose
5-14 days
Not active against
pseudomonas;
not recommended
for ICU
Ertapenem
1 gram daily
Methicillin Resistant Staph
Aureus (MRSA)
• Risk factors
– Prior cephalosporin or
quinolone use
– HIV infection
– Long-term indwelling
dialysis catheters
– Residence in long-term
care facility
MRSA Treatment
• Bacteremia**
– Vancomycin
• 15 – 20 mg/kg based
on actual body weight
• Frequency of dose
dependent on renal
function
OR
– Daptomycin
• 6mg/kg/dose IV daily
• 8-10mg/kg/dose IV
daily for complicated
infections
• Pneumonia
– Vancomycin
• 15 – 20 mg/kg based on
actual body weight
• Frequency of dose
dependent on renal
function
OR
– Linezolid
• 600mg IV or PO BID
– NO Daptomycin
• Poor lung penetration
Vancomycin
• Treats multiple infections
– Endocarditis, osteomyelitis, bacteremia, HCAP, meningitis
• Optimal level 15 – 20 mg/L
• Keep level > 10 mg/L to avoid potential antimicrobial
resistance
• Trough level = most effective measurement of levels
– Draw 30 min prior to 5th dose
Vancomycin Nephrotoxicity
• Definition:
– > 50% increase in Serum Creatinine over baseline on
consecutive serum measurements (over 2 days) in the absence
of alternative explanations
• Increased risk toxicity:
– Elderly, longer course of treatment, concomitant nephrotoxic
medications, possibly increased serum trough levels
• Reduce toxicity:
– Monitor levels with fluctuating renal function
Vancomycin Resistant Enterococci
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Occurs in intestine and female urinary tract
Distinguish between active infection and colonization
E. Faecalis and E. faecium most common forms
More than 90% cases E. faecium
Limited studies for most effective drug
No official ID Guidelines
Treatment based on available
data:
– Linezolid 600mg PO/IV BID OR
– Daptomycin 6mg/kg/dose daily**
Fungal Infections
Risk Factors Disseminated Disease
• Duration of antibiotics
– > 6 days
• Number of antibiotics
– ≥ 3 therapies
• Renal failure
• Central venous catheters
• Steroid use
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Gram negative sepsis
Cancer
Burns
Multiple trauma
Diabetes mellitus
Total parenteral nutrition
Neutropenic vs. Nonneutropenic
Common Fungal Species
• Candida
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C. albicans
C. tropicalis
C. parapsilosis
C. glabrata
C. krusei
C. lusitaniae
• Aspergillus
Treatment Options
• Azoles
– Fluconazole, voriconazole, itraconazole,
posaconazole
• Echinocandins
– Micafungin, caspofungin, anidulafungin
• Polyenes
– Amphotericin B + lipids
Drug
Fluconazole
Itraconazole
Voriconazole
Posaconazole
Bioavailability
Metabolism
> 90% IV and
PO
Highly
variable
>90%
<50%
Adverse
Effects
Comments
>80% excreted
unchanged in
urine
Alopecia
Chapped lips
Active agst
yeast;
itraconazole
better for fungi
Extensive in
liver
HTN
Hyperkalemia
Peripheral
Edema
Capsule and
solution NOT
interchangeable
Cardiac toxicity
Rash
Periostitis
Penetrates
CSF; adjust for
hepatic
impairment
Extensive in
liver
Liver
GI symptoms
Torsades
Increased
concentration
with increased
administration
Drug Dosing
Fluconazole*
• Esophageal Candida: 400 mg load; 200mg
qday
• Invasive disease: 800mg load; 400mg
qday
Itraconazole
• Histoplasmosis: 200 – 400 mg qday
• Allergic bronchopulmonary aspergillosis:
200 mg BID
Voriconazole
• Candidemia: Load: 6 mg/kg IV q12hr x 2
doses; Maintenance: 3 – 4 mg/kg q12 hrs
• Aspergillosis: Load: 6 mg/kg IV q12hr x 2
doses; Maintenance: 4 mg/kg IV q12 hr
Drug Dosing
Posaconazole
• Prophylaxis: 200 mg PO TID**
• Salvage therapy: 200 mg PO QID
Serum Drug Levels
• Itraconazole
– Check level after steady state achieved (suggested 2 weeks)
– For invasive fungal infections: >3 mcg/mL by bioassay
– Linear relationship between increased levels and toxicity
• Voriconazole
– Check 4 – 7 days into therapy (TROUGH level)
– Invasive fungal infections: 1 mg/L → < 5.5 mg/L
• Posaconazole
– No official guidelines for therapeutic levels
– Suggestion: Trough level
• Prophylaxis: ≥ 0.5 mcg/mL
• Severe infection: ≥ 0.7 mg/mL
Echinocandins
Indication
Caspofungin
Micafungin
Anidulafungin
Esophageal
candidiasis
No loading
MD*: 50 mg QD
No loading
MD: 150 mg QD
Loading: 100mg
MD: 50 mg QD
Candidemia
Loading: 70 mg
MD: 50 mg QD
No loading
MD: 100 mg QD
Loading: 200 mg
MD: 100 mg QD
No loading
MD: 100 mg QD
Loading: 200 mg
MD: 100 mg QD
Other Candida
infections
Loading: 70 mg
MD: 50 mg QD
Febrile
Neutropenia
Loading: 70 mg
MD: 50 mg QD
N/A
N/A
Invasive
Aspergillosis
Loading: 70 mg
MD: 50 mg QD
N/A
N/A
Prophylactic
Stem Cell
N/A
No loading
MD: 50 mg QD
N/A
Clostridium Difficile Guidelines
Severity of
Disease
Initial Treatment
Duration of
Treatment**
Mild to Moderate
Metronidazole
500mg TID
10-14 days
10-14 days
Moderate to Severe
Vancomycin
125mg PO QID
Recurrence†
(non-severe)
Metronidazole
500mg TID
10-14 days
Recurrence
(severe)
Vancomycin
500mg QID +
Metronidazole 500mg
IV TID
10-14 days
References
• Society of Critical Care Medicine. (2009). ICU infection in an
era of multi-resistance; selected proceedings from the 8th
summer conference in intensive care medicine. Mount
Prospect: Certified Fiber Sourcing.
• Brandt, L. J., & Feuerstadt, P. (2011). Clostridium difficile:
Epidemiology, transmission, and treatment. Infectious Disease
Special Edition, 14, 75-83.
• Martin, S. J., Micek, S. T., & Wood, G. C. (2012). Antimicrobial
resistance is an adverse drug event. In J. Papadopoulos, B.
Cooper, S. Kane-Gill, S. Corbett & J. Barletta (Eds.), DrugInduced Complications in the critically ill patient: A guide for
recognition and treatmentMount Prospect: Society of Critical
Care Medicine.
References
• Rybak, M., Lomaestro, B., Rotschafer, J. C., Moellering Jr, R.,
Craig, W., Billeter, M., Dalovisio, J. & Levine, D. (2009).
Therapeutic monitoring of vancomycin in adult patients: A
consensus review of the american society of health system
pharmacists, the infectious disease society of america, and
the society of infectious disease pharmacists. American
Journal Health System Pharmacists, 66, 82-98. Retrieved from
http://www.ajhp.org
• Liu, C., Bayer, A., Cosgrove, S., & Daum, R. (2011). Clinical
practice guidelines but the infectious diseases society of
america for the treatment of methicillin-resistant
staphylococcus aureus infections in adults and children.
Clinical Infectious Diseases, 52(3), e18-e55. Retrieved from
http://cid.oxfordjournals.org
References
• Kelly, C. P., & LaMont, J. T. (2013, March). Clostridium difficile
in adults:treatment. Retrieved from www.uptodate.com
• Ashley, E. D., & Perfect, J. R. (2013, June). Pharmacology of
azoles. Retrieved from www.uptodate.com
• www.cdc.gov
• http://www.idsociety.org
• Kauffman, C. A., & (2013, July). Treatment of candidemia and
invasive candidiasis in adults. Retrieved from
www.uptodate.com
• Chen, L. F., & Drew, R. H. (2013, April). Pharmacology of
antimicrobial agents for treatment of methicillin-resistant
staphylococcus aureus and vancomycin resistant
enterococcus. Retrieved from www.uptodate.com
References
• Munoz-Price, L. S., & Jacoby, G. A. (2013, April). Extendedspectrum beta-lactamases. Retrieved from
www.uptodate.com
• Runyon, B. A., & (2013, July). Spontaneous bacterial peritonitis
in adults: Treatment and prophylaxis. Retrieved from
www.uptodate.com
• Sucher, A. J., Chahine, E. B., & Balcer, H. E. (2009).
Echinocandins: The newest class of antifungals. The Annals of
Pharmacotherapy, 43, 1647-57.
• The following slides exhibit various anatomical
systems and common organisms responsible for
infections.
• Streptococcus
– S. Viridans
– S. Mutans
• Fusobacterium
(Leimerre’s disease)
• Staphylococcus
– S. aureus
– S. epidermidis
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Strep pneumoniae
Haemophilus influenzae
Bordetella
Staph. aureus
Legionella pneumophilia
Mycobacterium
tuberculosis
• Histoplasmosis
• Enterobacteriaceae
• Infective Endocarditis
– Streptococcus viridans
(50% of all cases)
– Staphylococcus aureus
– Enterococcus
– HACEK organisms*
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Haemophilus
Actinobacillus
Cardiobacterium hominis
Eikenella corrodens
Kingella (Kingella kingae)
*slow growing gram (-) organisms;
Normal part of human flora
• Escherichia coli
• Bacteroides
• Infectious pancreatitis
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Hepatitis B
CMV
Varicella-zoster
HSV
Mycoplasma
Legionella
Salmonella
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Bacteroides
Enterococcus
Escherichia coli
Klebsiella pneumoniae
Staphylococcus aureus
Streptococcus
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Escherichia coli
Enterococcus
Bacteroides
Streptococcus
Lactobacillus
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Clostridium difficile
Escherichia coli
Bacteroides
Campylobacter
Salmonella
Shigella
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Escherichia coli
Proteus mirabilis
Klebsiella
Pseudomonas
aeruginosa
• Enterococcus