1. Antibiotics and ICU Infections
Jill Williams, ACNP-BC
Vanderbilt University Medical Center
Medical Intensive Care Unit

2. Objectives
• Discuss strategies for antibiotic stewardship
• Review mechanisms of action (MOA) for
antibiotics
• Discuss common ICU infections and antibiotic
therapies including drug levels

3. 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

4. Antibiotic Stewardship – How?
• 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

5. Structure of Bacteria
www.americanaquariumproducts.com

6. Antibiotic Mechanism of Action

7. 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

8. 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

9. ESBL Risk Factors
• 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

10. Treatment
• Carbapenem family of antibiotics
– 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

11. 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
Ertapenem 1 gram daily 5-14 days
Not active against
pseudomonas;
not recommended
for ICU

12. 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

13. 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

14. 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

15. 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

16. Vancomycin Resistant Enterococci
• 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**

17. Fungal Infections

18. Risk Factors Disseminated Disease
• Duration of antibiotics
– > 6 days
• Number of antibiotics
– ≥ 3 therapies
• Renal failure
• Central venous catheters
• Steroid use
• Gram negative sepsis
• Cancer
• Burns
• Multiple trauma
• Diabetes mellitus
• Total parenteral nutrition
• Neutropenic vs. Non-
neutropenic

19. Common Fungal Species
• Candida
– C. albicans
– C. tropicalis
– C. parapsilosis
– C. glabrata
– C. krusei
– C. lusitaniae
• Aspergillus

20. Treatment Options
• Azoles
– Fluconazole, voriconazole, itraconazole,
posaconazole
• Echinocandins
– Micafungin, caspofungin, anidulafungin
• Polyenes
– Amphotericin B + lipids

21. Drug
Bioavail-
ability
Metabo-
lism
Adverse
Effects
Comments
Fluconazole
> 90% IV and
PO
>80% excreted
unchanged in
urine
Alopecia
Chapped lips
Active agst
yeast;
itraconazole
better for fungi
Itraconazole
Highly
variable
Extensive in
liver
HTN
Hyperkalemia
Peripheral
Edema
Capsule and
solution NOT
interchange-
able
Voriconazole >90%
Extensive in
liver
Cardiac toxicity
Rash
Periostitis
Penetrates
CSF; adjust for
hepatic
impairment
Posacon-
azole
<50% Liver
GI symptoms
Torsades
Increased
concentration
with increased
administration

22. Drug Dosing
• Esophageal Candida: 400 mg load; 200mg
qday
• Invasive disease: 800mg load; 400mg
qday
Fluconazole*
• Histoplasmosis: 200 – 400 mg qday
• Allergic bronchopulmonary aspergillosis:
200 mg BID
Itraconazole
• 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
Voriconazole

23. Drug Dosing
• Prophylaxis: 200 mg PO TID**
• Salvage therapy: 200 mg PO QID
Posaconazole

24. 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

25. Echinocandins
Indication Caspofungin Micafungin
Anidula-
fungin
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
Other Candida
infections
Loading: 70 mg
MD: 50 mg QD
No loading
MD: 100 mg QD
Loading: 200 mg
MD: 100 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

26. Clostridium Difficile Guidelines
Severity of
Disease
Initial Treatment Duration of
Treatment**
Mild to Moderate
Metronidazole
500mg TID
10-14 days
Moderate to Severe
Vancomycin
125mg PO QID
10-14 days
Recurrence†
(non-severe)
Metronidazole
500mg TID
10-14 days
Recurrence
(severe)
Vancomycin
500mg QID +
Metronidazole 500mg
IV TID
10-14 days

27. 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.), Drug-
Induced Complications in the critically ill patient: A guide for
recognition and treatmentMount Prospect: Society of Critical
Care Medicine.

28. 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

29. 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

30. References
• Munoz-Price, L. S., & Jacoby, G. A. (2013, April). Extended-
spectrum 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.

31. • The following slides exhibit various anatomical
systems and common organisms responsible for
infections.

32. • Streptococcus
– S. Viridans
– S. Mutans
• Fusobacterium
(Leimerre’s disease)
• Staphylococcus
– S. aureus
– S. epidermidis

33. • Strep pneumoniae
• Haemophilus influenzae
• Bordetella
• Staph. aureus
• Legionella pneumophilia
• Mycobacterium
tuberculosis
• Histoplasmosis
• Enterobacteriaceae

34. • Infective Endocarditis
– Streptococcus viridans
(50% of all cases)
– Staphylococcus aureus
– Enterococcus
– HACEK organisms*
• Haemophilus
• Actinobacillus
• Cardiobacterium hominis
• Eikenella corrodens
• Kingella (Kingella kingae)
*slow growing gram (-) organisms;
Normal part of human flora

35. • Escherichia coli
• Bacteroides

36. • Infectious pancreatitis
– Hepatitis B
– CMV
– Varicella-zoster
– HSV
– Mycoplasma
– Legionella
– Salmonella

37. • Bacteroides
• Enterococcus
• Escherichia coli
• Klebsiella pneumoniae
• Staphylococcus aureus
• Streptococcus

38. • Escherichia coli
• Enterococcus
• Bacteroides
• Streptococcus
• Lactobacillus

39. • Clostridium difficile
• Escherichia coli
• Bacteroides
• Campylobacter
• Salmonella
• Shigella

40. • Escherichia coli
• Proteus mirabilis
• Klebsiella
• Pseudomonas
aeruginosa
• Enterococcus