Antibiotics and ICU Infections
Jill Williams, ACNP-BCVanderbilt 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?
• 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
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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
• 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
– 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
Imipenem500mg IV q 6-8
hours
7-14 days depending on
severity of infection
Adjust dose for renal impairment;
lowers seizure threshold vs. meropenem
Meropenem500mg – 1gram IV
q 8 hours
Dependent on severity of infection
No renal adjustment
needed
Doripenem 500mg q8 hrs 7-14 daysNewer drug; renally dose
Ertapenem 1 gram daily 5-14 days
Not active against pseudomonas; not recommended for
ICU
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• 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
• Gram negative sepsis• Cancer• Burns• Multiple trauma• Diabetes mellitus• Total parenteral nutrition• Neutropenic vs. Non-
neutropenic
Common Fungal Species
• Candida– 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
DrugBioavail-
abilityMetabo-
lismAdverseEffects
Comments
Fluconazole> 90% IV and
PO
>80% excreted unchanged in
urine
AlopeciaChapped lips
Active agst yeast;
itraconazole better for fungi
ItraconazoleHighly
variableExtensive in
liver
HTNHyperkalemia
Peripheral Edema
Capsule and solution NOT interchange-
able
Voriconazole >90%Extensive in
liver
Cardiac toxicityRash
Periostitis
Penetrates CSF; adjust for
hepatic impairment
Posacon-azole
<50% LiverGI symptoms
Torsades
Increased concentration with increased administration
Drug Dosing
Drug Dosing
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 MicafunginAnidula-fungin
Esophageal candidiasis
No loadingMD*: 50 mg QD
No loadingMD: 150 mg QD
Loading: 100mgMD: 50 mg QD
CandidemiaLoading: 70 mgMD: 50 mg QD
No loadingMD: 100 mg QD
Loading: 200 mgMD: 100 mg QD
Other Candida infections
Loading: 70 mgMD: 50 mg QD
No loadingMD: 100 mg QD
Loading: 200 mg MD: 100 mg QD
Febrile Neutropenia
Loading: 70 mgMD: 50 mg QD
N/A N/A
Invasive Aspergillosis
Loading: 70 mgMD: 50 mg QD
N/A N/A
ProphylacticStem Cell
N/ANo loading
MD: 50 mg QDN/A
Clostridium Difficile GuidelinesSeverity of
DiseaseInitial Treatment Duration of
Treatment**
Mild to ModerateMetronidazole
500mg TID10-14 days
Moderate to SevereVancomycin
125mg PO QID10-14 days
Recurrence†
(non-severe)
Metronidazole500mg TID
10-14 days
Recurrence(severe)
Vancomycin500mg 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.), Drug-Induced 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). 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.
• 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
• 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* • Haemophilus
• Actinobacillus
• Cardiobacterium hominis
• Eikenella corrodens
• Kingella (Kingella kingae)
*slow growing gram (-) organisms; Normal part of human flora
• Escherichia coli• Bacteroides
• Infectious pancreatitis– Hepatitis B– CMV– Varicella-zoster– HSV– Mycoplasma– Legionella– Salmonella
• Bacteroides• Enterococcus• Escherichia coli• Klebsiella pneumoniae• Staphylococcus aureus• Streptococcus
• Escherichia coli• Enterococcus• Bacteroides• Streptococcus• Lactobacillus
• Clostridium difficile• Escherichia coli• Bacteroides• Campylobacter• Salmonella• Shigella
• Escherichia coli• Proteus mirabilis• Klebsiella• Pseudomonas
aeruginosa• Enterococcus