Antibiotic ReviewAntibiotic Review

ObjectivesObjectives

Overview of Overview of organismsorganisms

Review of Review of AntibioticsAntibiotics

Surgical Surgical ProphylaxisProphylaxis

Review of Review of OrganismOrganism

ss

Dipiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy. A Pathophysiologic Approach. 4th ed. Stamford, CT: Appleton & Lange, 1999: 1600.Dipiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy. A Pathophysiologic Approach. 4th ed. Stamford, CT: Appleton & Lange, 1999: 1600.

““Normal” Normal” Colonizing Colonizing

FloraFlora

Dipiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy. A Pathophysiologic Approach. 4th ed. Stamford, CT: Appleton & Lange, 1999: 1599.Dipiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy. A Pathophysiologic Approach. 4th ed. Stamford, CT: Appleton & Lange, 1999: 1599.

Antibiotic ClassesAntibiotic Classes

PenicillinsPenicillins CephalosporinsCephalosporins Monobactam Monobactam CarbapenemCarbapenem GlycopeptideGlycopeptide OxazolidiononeOxazolidionone

AminoglycosidesAminoglycosides MacrolidesMacrolides TetracyclineTetracycline SulfonamideSulfonamide NitroimidazoleNitroimidazole QuinolonesQuinolones

Antibiotic Antibiotic SpectrumSpectrum

Gilbet DN, Moellering RC, Eliopoulos GM, Sande MA. The Sanford Guide to Antimicrobial Therapy 2006. 36th ed. Sperryville, VA: Antimicrobial Therapy, INC., 2006: 53.Gilbet DN, Moellering RC, Eliopoulos GM, Sande MA. The Sanford Guide to Antimicrobial Therapy 2006. 36th ed. Sperryville, VA: Antimicrobial Therapy, INC., 2006: 53.

Antibiotic Antibiotic SpectrumSpectrum

Gilbet DN, Moellering RC, Eliopoulos GM, Sande MA. The Sanford Guide to Antimicrobial Therapy 2006. 36th ed. Sperryville, VA: Antimicrobial Therapy, INC., 2006: 54.Gilbet DN, Moellering RC, Eliopoulos GM, Sande MA. The Sanford Guide to Antimicrobial Therapy 2006. 36th ed. Sperryville, VA: Antimicrobial Therapy, INC., 2006: 54.

AntibiotiAntibiotic c

SpectruSpectrumm

Gilbet DN, Moellering RC, Eliopoulos GM, Sande MA. The Sanford Guide to Antimicrobial Therapy 2006. 36th ed. Sperryville, VA: Antimicrobial Therapy, INC., 2006: 55.Gilbet DN, Moellering RC, Eliopoulos GM, Sande MA. The Sanford Guide to Antimicrobial Therapy 2006. 36th ed. Sperryville, VA: Antimicrobial Therapy, INC., 2006: 55.

Antibiotic SpectrumAntibiotic Spectrum P

enic

illi

n

Naf

cill

in

Am

pici

llin

/am

oxic

illi

n

Aug

men

tin,

Una

syn

Tim

enti

n

Zos

yn

Imip

enem

Azt

reon

am

Cip

rofl

oxac

in

Mox

iflo

xaci

n

Cef

azol

in

Cef

oxit

in

Cef

tria

xone

Cef

epim

e

Cep

hale

xin

Cef

urox

ime

Gen

tam

icin

, tob

ram

ycin

Cli

ndam

ycin

Van

com

ycin

Bac

trim

Met

roni

dazo

le

Lin

ezol

id

Gram Positive

+ + + + + + + - - + + + + + + + - + + + - +

Gram Negative

- - - + + + + + + + +/- + - + +/- +/- + - - + - -

Anaerobe

- - - + + + + - - +/- - + - + - - - + + - + -

Pseudo.

- - - - + + + + + - - - - + - - + - - - - -

Renal dose

+ - + + + + + + + - + + - + + + + - - + - -

Vancomycin Vancomycin Dosing Dosing

NomogramNomogram

VancomyciVancomycin Dosing n Dosing

NomogramNomogram

Aminoglycoside DosingAminoglycoside Dosing

Pre-Op Dosing: 160mg or 240mgPre-Op Dosing: 160mg or 240mg Post-Op Dosing/ Treatment DosingPost-Op Dosing/ Treatment Dosing

If CrCl > 30 ml/min give 5 or 7mg/kg doseIf CrCl > 30 ml/min give 5 or 7mg/kg dose Random Level 8 hours after infusionRandom Level 8 hours after infusion Pharmacy to follow dosing per TDM ServicePharmacy to follow dosing per TDM Service

If CrCl < 30 ml/min – contact pharmacy If CrCl < 30 ml/min – contact pharmacy for dosingfor dosing

2-3 mg/kg dose 2-3 mg/kg dose 2 random levels to be ordered by pharmacy2 random levels to be ordered by pharmacy

All aminoglycosides monitored by TDM All aminoglycosides monitored by TDM ServiceService

Sinai Sinai AntibiogrAntibiogr

amam

TherapeuticsTherapeutics

Determine Source/Site of infectionDetermine Source/Site of infection Identify suspected pathogensIdentify suspected pathogens Choose appropriate therapy based on Choose appropriate therapy based on

the abovethe above Determine duration of therapyDetermine duration of therapy

Surgical ProphylaxisSurgical Prophylaxis

GoalsGoals Selection of antimicrobial Selection of antimicrobial

agentsagents Timing of administrationTiming of administration Duration of administrationDuration of administration

Goals of Surgical Goals of Surgical ProphylaxisProphylaxis

Prevention of post-op infection at surgical Prevention of post-op infection at surgical sitesite

Prevention of post-op infections morbidity & Prevention of post-op infections morbidity & mortalitymortality

Reduction in duration and cost of health Reduction in duration and cost of health carecare

Produce no adverse effectsProduce no adverse effects Have no adverse consequences for the Have no adverse consequences for the

microbial flora of the patient or the hospitalmicrobial flora of the patient or the hospital

Goals of Surgical Goals of Surgical ProphylaxisProphylaxis

Active against pathogen that is most likely Active against pathogen that is most likely to contaminate the woundto contaminate the wound

Give at an appropriate dosage and at a Give at an appropriate dosage and at a time to ensure adequate concentrations at time to ensure adequate concentrations at the incision site during the period of the incision site during the period of potential contaminationpotential contamination

SafeSafe Administered for the shortest effective Administered for the shortest effective

period to minimize adverse effects, period to minimize adverse effects, development of resistance, and cost.development of resistance, and cost.

Goals of Surgical Goals of Surgical ProphylaxisProphylaxis

Antibiotic use for Dirty and contaminated Antibiotic use for Dirty and contaminated procedures is not classified as prophylaxis, procedures is not classified as prophylaxis, but treatment for presumed infection.but treatment for presumed infection.

Prophylaxis typically not indicated for Prophylaxis typically not indicated for clean proceduresclean procedures

Justified for procedures involving Justified for procedures involving prosthetic placementprosthetic placement

Cardiothoracic, GI tract, head and neck, Cardiothoracic, GI tract, head and neck, neurosurgical, obstetric or gynecologic, neurosurgical, obstetric or gynecologic, orthopedic, urologic and vascularorthopedic, urologic and vascular

Selection of Selection of Antimicrobial AgentsAntimicrobial Agents

Based on cost, adverse-effect profile, Based on cost, adverse-effect profile, ease of administration, pharmacokinetic ease of administration, pharmacokinetic profile, and antibacterial activityprofile, and antibacterial activity

Activity against most common surgical Activity against most common surgical wound pathogenswound pathogens Clean-contaminated: effective against GI/GU Clean-contaminated: effective against GI/GU

organismsorganisms Clean: effective against Staph and StrepClean: effective against Staph and Strep

Selection Selection of of

AntimicroAntimicrobial bial

AgentsAgents

Selection Selection of of

AntimicroAntimicrobial bial

AgentsAgents

Timing of Antibiotic Timing of Antibiotic ProphylaxisProphylaxis

Delivery of drug to operative site Delivery of drug to operative site before contamination occursbefore contamination occurs

Ideal timing is 30 minutes to one hour Ideal timing is 30 minutes to one hour prior to incision (at time of induction prior to incision (at time of induction of anesthesia)of anesthesia) Flagyl given 1 hour priorFlagyl given 1 hour prior Vancomycin given 2 hours priorVancomycin given 2 hours prior

Duration of Antibiotic Duration of Antibiotic ProphylaxisProphylaxis

24 hours or less24 hours or less Cardiothoracic procedures- up to 72 hoursCardiothoracic procedures- up to 72 hours Coverage must be provided from time of Coverage must be provided from time of

incision to closure of incisionincision to closure of incision Re-administer if short-acting agent used or Re-administer if short-acting agent used or

surgery lasting longer than 6-8 hourssurgery lasting longer than 6-8 hours Re-administer if excessive bleeding or change Re-administer if excessive bleeding or change

in half-life of drug (i.e. extensive burns)in half-life of drug (i.e. extensive burns) May avoid re-administration of half-life is May avoid re-administration of half-life is

extended ( i.e. renal insufficiency)extended ( i.e. renal insufficiency)

Biliary Tract SurgeryBiliary Tract Surgery

Cholecystetomy, exploration of common Cholecystetomy, exploration of common bile duct, choledochoenterostomybile duct, choledochoenterostomy

Risk of infection 5-20%Risk of infection 5-20% Higher risk of infection: bacteria in Higher risk of infection: bacteria in

bile, obesity, age > 70, acute episode of bile, obesity, age > 70, acute episode of cholecystitis or cholelithiasis within cholecystitis or cholelithiasis within previous 6 months, DM, h/o obstructive previous 6 months, DM, h/o obstructive jaundice or bile duct obstructionjaundice or bile duct obstruction

Biliary Tract SurgeryBiliary Tract Surgery

Organisms: E.coli, Klebsiella, Organisms: E.coli, Klebsiella, EnterococciEnterococci Less frequent: other gram negative, strep, Less frequent: other gram negative, strep,

staphstaph Occasionally: anaerobes (Clostridium sp.)Occasionally: anaerobes (Clostridium sp.)

Recommendation:Recommendation: Single dose of cefazolin at induction of Single dose of cefazolin at induction of

anesthesia for open procedures in biliary anesthesia for open procedures in biliary tracttract

No prophylaxis in laparoscopic No prophylaxis in laparoscopic cholecystectomiescholecystectomies

AppendectomyAppendectomy 80% are Uncomplicated (acute 80% are Uncomplicated (acute

inflammation)inflammation) Complicated (perforated or gangrenous; Complicated (perforated or gangrenous;

perotonitis, abcess formation)perotonitis, abcess formation) considered infection, not prophylaxisconsidered infection, not prophylaxis

9-30% risk of infection9-30% risk of infection Oragnisms: anaerobic and aerobic Oragnisms: anaerobic and aerobic

gram-negative enteric organismsgram-negative enteric organisms Bacteroides fragilis, E.coliBacteroides fragilis, E.coli Aerobic and anaerobic strep, staph and Aerobic and anaerobic strep, staph and

enterococcusenterococcus

AppendectomyAppendectomy

Recommendation:Recommendation: Cephalosporin with anaerobic and Cephalosporin with anaerobic and

aerobic activity at induction of aerobic activity at induction of anesthesiaanesthesia

For PCN allergy: metronidazole, For PCN allergy: metronidazole, gentamicin at induction of anesthesiagentamicin at induction of anesthesia

Colorectal SurgeryColorectal Surgery

30-60% risk of infection (<10% with 30-60% risk of infection (<10% with prophylaxis)prophylaxis) Rectal > intraperitoneal colon resectionRectal > intraperitoneal colon resection Surgeries > 3.5 hoursSurgeries > 3.5 hours Host defenses, age > 60, hypoalbuminemia, Host defenses, age > 60, hypoalbuminemia,

bacterial contamination of surgical wound, bacterial contamination of surgical wound, steroid therapy, malignancysteroid therapy, malignancy

Colorectal SurgeryColorectal Surgery

Organisms: B. fragilis, and other Organisms: B. fragilis, and other anaerobs (1,000-10,000 higher conc. anaerobs (1,000-10,000 higher conc. than aerobes), E.colithan aerobes), E.coli

Mechanical bowel preparation:Mechanical bowel preparation: Neomycin and erythromycin: 1gm 19, 18, 9 Neomycin and erythromycin: 1gm 19, 18, 9

hours before surgeryhours before surgery aerobic and anaerobic activity (Ancef, aerobic and anaerobic activity (Ancef,

Flagyl) at induction of anesthesiaFlagyl) at induction of anesthesia

ReferencesReferences Dipiro, JT, Talbert RL, Yee GC, Matzke GR, Wells Dipiro, JT, Talbert RL, Yee GC, Matzke GR, Wells

BG, Posey LM, editors. Pharmacotherapy. A BG, Posey LM, editors. Pharmacotherapy. A Pathophysiologic Approach. 4Pathophysiologic Approach. 4thth ed. Stamford, CT: ed. Stamford, CT: Appleton & Lange, 1999: 1599-1600.Appleton & Lange, 1999: 1599-1600.

Gilbet DN, Moellering RC, Eliopoulos GM, Sande Gilbet DN, Moellering RC, Eliopoulos GM, Sande MA. The Sanford Guide to Antimicrobial Therapy MA. The Sanford Guide to Antimicrobial Therapy 2006. 362006. 36thth ed. Sperryville, VA: Antimicrobial ed. Sperryville, VA: Antimicrobial Therapy, INC., 2006: 53-55.Therapy, INC., 2006: 53-55.

ASHP Comission on Therapeutics. ASHP ASHP Comission on Therapeutics. ASHP Therapeutic Guidelines on Antimicrobial Therapeutic Guidelines on Antimicrobial Prophylaxis in Surgery. Am J Health Syst Pharm Prophylaxis in Surgery. Am J Health Syst Pharm 1999; 56(18): 1839-1888.1999; 56(18): 1839-1888.