Antibiotics and ICU Infections

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