Transcript Antibiotic Review - Stoller Design Group

Module 2 (of 3): Antibiotic Review*
Review of selected antimicrobials
By Keith Teelucksingh, PharmD
Infectious Disease Pharmacist, Kaiser Permanente Vallejo
With contributions by Linh Van, PharmD
Infectious Disease Pharmacist, Kaiser Permanente Oakland
See Notes
Goals


Build upon pharmacists’ basic knowledge of
selected broad-spectrum antibiotics
Provide contemporary clinical information on
appropriate use, spectrum of activity, clinical
pearls and other considerations of selected
antibiotics.
Objectives
Upon completion of this module, the participant will
be able to:
1. Elaborate on the spectrum activity for the βlactam-related antibiotics, aztreonam,
vancomycin, clindamycin, metronidazole and
the fluoroquinolones
2. Discuss the appropriate clinical uses of the
broad spectrum β-lactam-related antibiotics
and vancomycin
Objectives
3.
4.
Describe the appropriate use of the antianaerobic agents clindamycin and
metronidazole when combined with other
anaerobically active antibiotics
Describe the appropriate use of β-lactam agents
and vancomycin agents for the treatment of
certain bacteria
Antibiotics to be Covered



β-Lactams
 Penicillins
 Cephalosporins
 Carbapenems
Monobactams
 Aztreonam
Quinolones
 Moxifloxacin
 Ciprofloxacin

Other
 Clindamycin
 Metronidazole
 Vancomycin
Adapted from Brett Heintz, PharmD, BCPS
β-Lactams


Natural penicillins: penicillin
Penicillinase-resistant penicillins: nafcillin,
dicloxacillin



Aminopenicillins: ampicillin, amoxicillin
Extended spectrum penicillins: pipercillin, ticarcillin
β-lactam/β-lactamase inhibitor combinations:
Zosyn®, Unasyn®, Augmentin®, Timentin®
Penicillins
Penicillin G (IV)
 Used for treatment of



Neurosyphilis, endocarditis due to susceptible
pathogens
Infections due to penicillin (PCN) susceptible (S)
organisms: Group A & B Streptococci, Clostridium
perfringes (gas gangrene)
If organism is PCN S (does not produce
penicillinase, e.g., Staphylococcus aureus)
penicillin, amoxicillin, ampicillin can all be used
Penicillins
Penicillin G
 Side effects




Allergic reactions (rash, blood dyscrasias,
anaphylaxis) -> discussed in more detail in
Module 3
Interstitial nephritis
Hyperkalemia
Phlebitis
Penicillins
Nafcillin



Coverage: Staphylococcus aureus (MSSA) 
drug of choice
Not as active versus other Gm +
 Does not cover Enterococcus, not as good as
penicillin for S. pneumoniae, S. pyogenes
Hepatobiliary clearance
 No need to adjust in renal dysfunction
Note: Even though nafcillin is not renally eliminated, it
still can cause interstitial nephritis
Penicillins
Nafcillin


When interpreting susceptibilities:
 oxacillin = nafcillin
Susceptibility to nafcillin predicts susceptibility
to cefazolin/cephalexin
Penicillins
Nafcillin

Side Effects
 Interstitial nephritis


Neutropenia


Still monitor serum creatinine if on long course
Usually seen with longer courses
Phlebitis


Usually occurs when given peripherally
Use central venous catheter or isotonic solution
Penicillins
Ampicillin/amoxicillin
 Drug of choice for Enterococcus spp. infections


Amoxicillin (PO)



If isolate is ampicillin/amoxicillin sensitive
Higher dose used for S. pneumoniae (otitis media,
pharyngitis)
Enterococcal UTI
Ampicillin (IV)


Serious infections due to Enterococcus spp.
Listeria (unpasteurized cheeses) infections  typically
added for coverage in meningitis
Penicillins
Ampicillin: clinical applications

Endocarditis/bacteremia


No one agent is bactericidal against Enterococcus
spp.


Ampicillin 2g IV q 4h
Bactericidal when combined with aminoglycoside
(AG)
If treating endocarditis, addition of AG is strongly
recommended

Formal ID consult recommended
Penicillins
Pharmacokinetic considerations



Bioavailability (oral)
 Amoxicillin, Dicloxacillin > Ampicillin> PCN VK
High concentration in urine
All need to be adjusted in renal dysfunction
 Exceptions: nafcillin, dicloxacillin
Penicillins
Ampicillin/amoxicillin

Side effects (in general, similar to penicillin)
 Allergic reactions
 Rash
 Eosinophilia
 Leukopenia
Extended Spectrum Penicillins *
Piperacillin


Good activity vs. Pseudomonas and Enterococcus
Less active vs. E. coli
TicarcillinNF



Good activity vs. Pseudomonas (alternative to
piperacillin)
Less active than piperacillin vs. Enterococcus
Not commercially available
NF = non formulary
 See Notes
βL/βLi* combinations
Unasyn® (ampicillin/sulbactam)
Augmentin® (amoxicillin/clavulanic acid)
Zosyn® (piperacillin/tazobactam)
Timentin® (ticarcillin/clavulanic acid) NF
*βL/βLi = β-lactam/β-lactamaseinhibitor
NF = non-formulary
βL/βLi combinations



All will cover ampicillin-sensitive Enterococci
All have excellent activity vs. anaerobes
 B. fragilis, Prevotella spp.
Unasyn® and Augmentin® do not cover
Pseudomonas

Addition of βLi adds activity against:
 Bacteroidies (anaerobes), β-lactamase producing
Gm – (E. coli, Klebsiella, Serratia) & Gm +
(Enterococci, MSSA)
βL/βLi combinations *
Unasyn® (ampicillin/sulbactam)



Good for Gm +
 MSSA/Strep spp./Enterococcus spp.
Uses: Diabetic foot ulcers, cellulitis, communityacquired pneumonia, mild community-acquired GI
infections (diverticulitis)
Variable Gm - coverage
 E. coli has high resistance
 Best in class for Acinetobacter (if isolate S)
See Notes
βL/βLi combinations
Augmentin® (amoxicillin/clavulanic acid)






Gram + coverage similar to Unasyn®
Sometimes more active versus Gram – pathogens
such as E. coli and Klebsiella spp. than Unasyn®
Only PO option in class
GI tolerance poor
Uses: diverticulitis, cellulitis
Good oral step-down therapy
βL/βLi combinations
Zosyn® (piperacillin/tazobactam)



Expanded coverage compared to Unasyn®
Similar to Timentin® may be slightly more active
versus certain bacteria (E. coli)
Good activity vs. Pseudomonas


The addition of tazobactam to piperacillin adds NO
extra activity vs. Pseudomonas
For confirmed pseudomonal infections, increase dose to
4.5g IV q6h (renal function permitting) to maximize its
pharmacodynamic properties vs. Pseudomonas
βL/βLi combinations *
Zosyn® (piperacillin/tazobactam)


Clinical uses: severe intra-abdominal infections,
health care-associated (HCA) infections, including
pneumonia/ventilator-associated pneumonia
Use should be reserved for patients with risk
factors for nosocomial/drug resistant pathogens:

Skilled nursing facility residents, previous antibiotics
exposure, exposure to health care environment,
immunocompromised patients
See Notes
βL/βLi combinations
Timentin® (ticarcillin/clavulanicacid)NF


Per previous slide, very similar coverage
compared to Zosyn®
May be used as alternative agent for infections
due to Stenoptrophomonasmaltophilia
NF = non-formulary
βL/βLi combinations
Side effects: overall, very similar to penicillins

Zosyn®


Thrombocytopenia has been seen with longer
courses of therapy and higher doses (i.e.,
Pseudomonal dosing)
Ticarcillin/Timentin®

Ticarcillin has been shown to impair platelet
function  may prolong bleeding time but unclear
whether this is clinically significant
Carbapenems


The most potent antibiotic in theβ-lactam class
These agents should be used only when no other
antibiotic options are available or appropriate




Meropenem (Merrem®)
Ertapenem (Invanz®)
Imipenem/cilastin (Primaxin®) NF
Doripenem (Doribax®) NF
NF = non-formulary
Carbapenems *

Spectrum of activity


Broadest coverage including Gm+, Gm- (especially
drug resistant species -> see below and notes),
anaerobic coverage
All cover MSSA, Enterococcus (ampicillin sensitive)*,
Streptococcus spp.


Drugs of choice for ESBL* infections
Good empiric coverage for Acinetobacter*, Citrobacter,
Pseudomonas*
*-
except ertapenem
 See Notes
Carbapenems *

Differences in spectrum of activity



Imipenem ≈ meropenem
Meropenem usually has lower minimum inhibitory
concentration (MIC) to Gm - pathogens  not
usually clinically significant
Ertapenem

Not clinically active vs. Enterococcus, Pseudomonas,
Acinetobacter

Not a good empiric choice for health care
associated infections
 See Notes
Carbapenems

Differences in spectrum of activity:
NF
 Doripenem




Same coverage as meropenem/imipenem
 May be useful for highly multidrug-resistant
organisms
Lower MIC to certain pathogens in vitro
Less likely to select for resistance in certain
bacterial subpopulations
At present, not much advantage over meropenem
for most indications
NF = non-formulary
Carbapenems

Clinical uses


Severe intra-abdominal infections, heath careassociated infections* including pneumonia,
ventilator-associated pneumonia, serious infections
due to ESBL-producing organisms, meningitis**
Use should be reserved for patients with risk factors
for nosocomial/drug-resistant pathogens (see
Zosyn® slide)
* - except ertapenem; ** - meropenem only
Carbapenems

Side effects


Hypersensitivity/allergic reactions
 Uncommon
 Low cross-reactivity in patients with penicillin
allergy (see Module 3 of this series)
Seizures
 Usually associated with imipenem and occurs in
patients with poor renal function where dose not
adjusted accordingly, previous seizure history may
also predispose
Carbapenems

Drug interaction


Valproic acid and meropenem decreases valproic
acid levels (may apply with all carbapenems).
Monitor valproic acid levels more frequently or use
alternative antibiotic.
Monobactams
Aztreonam (only drug in class, Azactam®):


Monocylic β-lactam ring (traditional β-lactams are
bicyclic) i.e., structurally different
Active against Gm - ONLY including Pseudomonas


Gm – coverage similar to ceftazidime (they have structurally
similar side chains)
Side effects: rash


Can be safely used in patients with Type I penicillin allergy
Caution if patient has ceftazidime allergy (see Module 3)
 Currently on backorder; use only when no other options
are available
*Program Learning*
1.
2.
3.
What is the drug of choice for ampicillin-sensitive
Enterococcus? Besides the drug of choice, what
other beta-lactam(s) would work?
Which penicillins cover MRSA?
What are the penicillins that would cover MSSA?
*Program Learning Answers*
1.
What is the drug of choice for ampicillin
sensitive Enterococcus? Besides the drug of
choice, what other beta-lactam(s) would work?
Ampicillin is the drug of choice. Amoxicillin,
penicillin, piperacillin, ticarcillin, imipenem,
meropenem would also be appropriate choices. No
cephalosporin covers Enterococcus. Ertapenem has
variable activity. Aztreonam has no gm + coverage.
*Program Learning Answers*
2.
3.
Which penicillins cover MRSA? None. No β-lactam
agent covers MRSA.
What are the penicillins that would cover MSSA?
Nafcillin, dicloxacillin, Zosyn®, Timentin®,
Augmentin®, Unasyn®. If isolate is PCN-susceptible
(this indicates that isolate does not produce
penicillinase), then also can use penicillin,
amoxicillin or ampicillin.
*Program Learning Answers*

A patient with resistant Pseudomonas aeruginosa
wound infection has been on meropenem in-house
and the MD plans to give ertapenem as a home IV
infusion. His rationale is that ertapenem is a once
daily medication as opposed to three times daily for
meropenem. Is this appropriate? Why?
*Program Learning Answers*

Not appropriate because ertapenem does not cover
Pseudomonas. The carbapenems with activity against
Pseudomonas are imipenem, meropenem and
doripenem.
Cephalosporins





These compounds are structurally related to the
penicillins due to presence of β-lactam ring.
This will only focus on cephalosporins used
commonly in the inpatient setting
1st generation
2nd generation
3rd generation
4th generation
Cephalosporins



No cephalosporins cover Enterococcus
No cephalosporins cover MRSA
None are active versus ESBL-producing organisms


All cephalosporins, including 3rd generation, are
rendered inactive
Cefepime still may be used for certain infections but
should consult with ID clinician before using
Cephalosporins
1st generation

Cefazolin (Ancef®)
 Proteus, E. coli, Klebsiella (PEK), MSSA,
Streptococcus spp.
 Better for Streptococcus spp. than nafcillin
(cellulitis)

Cephalexin (Keflex®), cefadroxil (Duricef®)


Both with similar coverage to cefazolin
Both are well absorbed orally
 Cefadroxil - less frequent dosing
Cephalosporins
1st generation

Uses


Cefazolin
 Cellulitis, MSSA infections, surgical prophylaxis
Cephalexin, cefadroxil
 UTI, skin/soft tissue infections due to MSSA or
Strep spp.
Cephalosporins
2nd generation

Cefuroxime (PO/IV), cefaclor (PO)



Coverage: PEK (see 1st generation slide) +
Haemophilus, Neisseria = HNPEK
More gram negative coverage, less Staph coverage
Cephamycins (IV): cefotetan, cefoxitin



Only cephalosporins that cover anaerobes
Both active vs. B. fragilis  be aware that resistance
is increasing
Used for pelvic inflammatory disease, surgical
prophylaxis in ObGyn and colorectal surgery
Cephalosporins *
3rd generation

Ceftriaxone (Rocephin®), cefotaxime (IV only)
 HNPEK + Serratia = HNPEKS
 Not as reliable for Staph
 Good Pneumococcus activity, good meningeal


penetration
Multiple uses: UTI, SBP, meningitis, pneumonia
Cefpodoxime, cefdinir, cefixime (all PO)

Cefixime use should be reserved for treatment of
STDs
Cephalosporins
3rd generation

Ceftriaxone


Has numerous indications but only a few require
doses higher than 1g:
 2g IV q24h (endocarditis and osteomyelitis)
 2g IV q12h (meningitis)
No adjustment needed for renal dysfunction
Cephalosporins
3rd generation

Ceftazidime (Fortaz®)



Coverage is broadened compared with others in 3rd
generation to include Pseudomonas
 Only other cephalosporin which covers
Pseudomonas is cefepime
Not so good for Staphylococcus, Streptococcus
Used for empiric treatment of febrile neutropenia,
has decent meningeal penetration
Cephalosporins
4th generation

Cefepime (Maxipime®)NF




Similar to ceftazidime, covers Pseudomonas and may
be slightly more active vs. some Gm – organisms
Better Gm + coverage than ceftazidime but still not as
good as 1st generation cephalosporins
Used in febrile neutropenia, health care-associated
infections, meningitis
May be used in certain infections/situations when
treating ESBL infections consult ID clinician
NF = non-formulary
Cephalosporins

Side effects
 Similar to penicillins


Allergic reactions
Blood dyscrasias

Rare
*Program Learning*
1.
2.
Which cephalosporins do not need renal adjustment?
How is ceftriaxone dosed for these disease states?

3.
4.
Community-acquired pneumonia, endocarditis,
osteomyelitis, meningitis
Which cephalosporins have anaerobic coverage?
Which cephalosporins cover Pseudomonas?
*Program Learning Answers*
1.
2.
Which cephalosporins do not need renal
adjustment? Ceftriaxone only. All other
cephalospsorins need to be adjusted for renal
dysfunction.
How is ceftriaxone dosed for these disease states?
CAP: 1g iv q24h, Endocarditis/Osteomyelitis: 2g iv
q24h, Meningitis: 2g iv q12h
*Program Learning Answers*
3.
4.
Which cephalosporins have anaerobic
coverage? Cefoxitin and cefotetan; both are
2nd generation cephalosporins.
Which cephalosporins cover Pseudomonas?
Ceftazidime and cefepime.
Fluoroquinolones






These are potent antibiotics that have excellent
oral bioavailability
Ciprofloxacin
Moxifloxacin
LevofloxacinNF
Trovafloxacin (off market - hepatotoxic)
Gatifloxacin (off market - dysglycemias)
NF = non-formulary
Fluoroquinolones *

Good options for certain disease states


Used as second-line treatment for Tuberculosis
(TB)


Moxifloxacin in CAP
If presenting with upper lobe pneumonia and TB
suspected, do NOT give a quinolone
Overuse has lead to increased resistance

While the fluoroquinolones are potent antibiotics,
bacteria have the capacity to rapidly develop resistance
to these agents, especially under repeated exposure
 See Notes
Fluoroquinolones


Excellent oral bioavailability
Use should be reserved for cases where other
agents cannot be used



i.e., patients with severe penicillin allergy
If an isolate is resistant to one quinolone, consider
it resistant to all quinolones
Only drug in class with anaerobic activity is
moxifloxacin
Fluoroquinolones

Ciprofloxacin



Limited Gm+ activity
 Poor S. pneumoniae coverage
Active against Enterobacteraciae, Pseudomonas
 Resistance rates will vary per institution, get an
idea of antibiogram/susceptibilities at your area
of practice
Can be used for Enterococcus spp. UTIs
 If isolate susceptible, do not use for any other
type of Enterococcus infection (i.e., bacteremia)
Fluoroquinolones

LevofloxacinNF


S. pneumoniae coverage is better than
ciprofloxacin but not as good as moxifloxacin
Has activity versus Enterobacteriaciae,
Pseudomonas

Not much advantage over ciprofloxacin for most
Gm - pathogens
NF = non-formulary
Fluoroquinolones

Moxifloxacin

Coverage:
 Most active fluoroquinolone for S. pneumoniae
 Excellent anaerobic coverage ->B. fragilis
 Similar Gram – activity compared to other
fluoroquinolones but no activity vs.
Pseudomonas


Uses:
 Community-acquired pneumonia, intra-abdominal
infections
No need for renal adjustment
Fluoroquinolones

Drug interactions

Divalent/trivalent containing products (Ca2+, Mg2+,
Al3+, antacids)
 Can decrease oral absorption up to 90 percent,
similar effect with tube feeds
 Concentration dependent antibiotics so need to
treat interactions that  bioavailability seriously
 Administer separately per manufacturer
recommendation
Fluoroquinolones

Drug Interactions



Warfarin
 Increased INR, risk of bleeding
Cardiac meds
 Caution when used with other meds that can
prolong QTc interval
Consult package information for other interactions
Fluoroquinolones

Side effects





CNS  more common in elderly
Interstitial nephritis
 Rare
QTc prolongation
Cartilage toxicity
 Precaution in very young and elderly
N/V/D
 Most common side effect
*Program Learning*
1.
2.
A patient has been admitted for community-acquired
pneumonia, placed on ceftriaxone and azithromycin,
and is doing well. Upon discharge, which antibiotic
would you recommend?
A patient is admitted for suspected pneumonia from
home. The chest X-ray shows right upper lobe lesion.
Patient also has a three-week history of weight loss and
night sweats and a history of + PPD test. What
antibiotic class would you want to avoid and why?
*Program Learning Answers*
1.
The patient has been admitted for communityacquired pneumonia, placed on ceftriaxone and
azithromycin, and is doing well. Upon discharge,
which antibiotic would you recommend? Moxifloxacin.
This is a recommended therapy in the CAP guidelines.
*Program Learning Answers*
2.
A patient is admitted for suspected pneumonia from
home. The chest X-ray shows right upper lobe lesion.
Patient also has a three-week history of weight loss
and night sweats and a history of + PPD test. What
antibiotic class would you want to avoid and why?
Fluoroquinolones, especially newer generations like
moxifloxacin. These have activity against TB and can
potentially mask infection by partially treating it.
Clindamycin

Spectrum of activity



S. aureus  check sensitivities of isolate before
using, Strep spp.
Was once highly active against anaerobic gut
bacteria but resistance has been increasing through
the years
 Still has relatively good activity against oral flora
anaerobic species
No appreciable Gm - activity
Clindamycin

Role/clinical uses

Used in combination with other antibiotics for
necrotizing fasciitis to decrease toxin production
from bacteria (Strep spp.)

Ribosomal binding prevents production of
destructive proteins

Used in combination with other anaerobically
active antibiotics for this disease state
Clindamycin

Role/clinical uses



Still used frequently for dental infections,
surgical prophylaxis
 Especially in patients with penicillin allergy
Commonly used as prophylaxis/treatment in
head and neck procedures
Poorly GI tolerated, may predispose patients to
C. difficile colitis
Metronidazole

Spectrum of activity


Only covers anaerobic bacteria  very little
resistance, excellent activity
Gram (+) and Gram (-) anaerobes





Bacteriodes spp.
Prevotella spp.
Clostridium spp. (including C. difficile)
Fusobacterium spp.
Covers some parasitic organisms as well
Metronidazole

Used in




C. difficile colitis
Infections where anti-anaerobic coverage is
desired or used in combination with other
antibiotics which do not have anaerobic activity
Surgical prophylaxis (colorectal, vaginal,
abdominal)
Bacterial vaginosis, trichomoniasis
Metronidazole

Treatment of C. difficile colitis



Still first-line agent for uncomplicated, mildmoderate cases
If severe case (definitions of severity may differ),
PO vancomycin usually used
IV metronidazole can be used to treat but not
optimal (PO route will get highest concentration to
area of infection)
Metronidazole

Drug interactions




Warfarin
 Increased INRs, consider using PO vancomycin
Lithium
EtOH
 Disulfiram-like reaction with EtOH
Side effects

Metallic taste, dark urine
Double Anaerobic Coverage *

There is no need to add extra anaerobic
coverage (in the form of clindamycin or
metronidazole) to antibiotics with anaerobic
coverage*


There are consequences in gut colonization
It is redundant and unnecessary
* - Carbapenems, βL/βLi combos, moxifloxacin, tigecycline
See Notes
Double Anaerobic Coverage

It may be appropriate to have double
anaerobic coverage in these situations:


Adding metronidazole to anaerobically active
antibiotics for treatment of C. difficile diarrhea.
 Should be stopped promptly if C. difficile assay
is negative
Adding clindamycin to anaerobically active
antibiotics for treatment of necroitzing fasciitis
*Program Learning*
1.
2.
3.
What is the spectrum of activity for clindamycin?
A patient with Serratia bacteremia is started on
clindamycin. What is wrong with this?
A patient with hospital-acquired pneumonia, on
Zosyn®, is started on metronidazole. Under what
circumstance would this be appropriate?
*Program Learning Answers*
1.
2.
What is the spectrum of activity for clindamycin?
Anaerobic bacteria, check sensitivities before
using for either Staphylococci and Streptococci.
A patient with Serratia bacteremia is started on
clindamycin. What is wrong with this?
Clindamycin has no appreciable Gm – activity.
*Program Learning Answers*
3.
A patient with hospital-acquired pneumonia, on
Zosyn®, is started on metronidazole. Under what
circumstance would this be appropriate?
If patient has diarrhea and C. difficile is
suspected (stool sample should be sent for C.
difficile tests). Otherwise Zosyn® has excellent
anaerobic activity.
Vancomycin



Inhibits cell wall synthesis, bactericidal.
Crosses blood-brain barrier if inflamed.
Spectrum: Gm + ONLY


MRSA, Enterococcus, Coagulase Negative Staph
spp., Strep spp.
Clostridium difficile (when used via oral route).
Vancomycin

Delayed killing against S. aureus and
MRSA  especially with high inoculum size
(in vitro).
**If S. aureus isolate is β-lactam sensitive
(i.e MSSA), use β-lactam antibiotic 
better killing, better outcomes.
Vancomycin

Still considered by many the drug of choice vs.
MRSA but is a controversial issue.



Issues with increasing Staph MICs, PK/PD issues,
suboptimal clinical responses have all led to question
vancomycin as first-line therapy.
Newer drugs and new studies have also raised
questions.
Ongoing and controversial issue.
Vancomycin

Dosing and monitoring: Please see
institutional protocol as dosing, frequency of
monitoring and goal trough level ranges may
differ between facilities.

Review the recent consensus statement on
vancomycin monitoring.*
* - Rybak M, et al. 2009.
Vancomycin

Side effects



Nephrotoxicity with other nephrotoxic drugs.
Redman’s Syndrome
 This is an infusion-related reaction.
 Slow infusion rate if occurs (infuse over two hours);
may use diphenhydramine for symptomatic relief.
Blood dyscrasias
 Neutropenia, thrombocytopenia.
 Tend to be seen during longer treatment courses.
Vancomycin

Clinical uses



Serious infections where MRSA is suspected.
Therapy for Gm + infections in patients with
serious allergic reactions to β-lactam antibiotics.
Treatment for C. difficile colitis (given PO).
 Systemic infections cannot be treated with
vancomycin PO  localized to gut.
Vancomycin

Clinical uses


If initial cultures do not show MRSA, prescriber should
be contacted to review appropriateness
If not indicated, vancomycin should be discontinued as
quickly as possible to avoid:
 pressure for the development of VRE or selection of
other resistance
 potential toxicities
 unnecessary use of powerful antibiotic
*Program Learning*
1.
2.
3.
Patient with MSSA leg infection on vancomycin IV.
Patient has no allergies. Is there a better antibiotic?
True/false. Vancomycin is bactericidal.
An order is written to use high-dose PO vancomycin to
treat a MRSA cellulitis. Is this appropriate?
*Program Learning Answers*
1.
2.
Patient with MSSA leg infection on vancomycin
IV. Patient has no allergies. Is there a better
antibiotic? Yes. The β-lactams have better
killing activity vs. MSSA than vancomycin.
Nafcillin, dicloxacillin and cephalexin are
potential options.
True/False. Vancomycin is bactericidal. TRUE
*Program Learning Answers*
3.
An order is written to use high-dose vancomycin
given via oral route to treat a MRSA cellulitis. Is
this appropriate?
Vancomycin given PO is only effective against C.
difficile and is localized almost exclusively to the GI
tract. Conversely, IV vancomycin will not treat C.
difficile.
References
Chambers, H. Chapter 21: Penicillins and β- Lactam Inhibitors. Mandell, G.,
Bennett, J., Dolin, D. Mandell, Douglas and Bennett’s Principles and Practice of
Infectious Disease. 7th Edition. 2009.
 Andes, D., Craig, W. Chapter 22: Cephalosporins. Mandell, G., Bennett, J., Dolin,
D. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Disease. 7th
Edition. 2009.
Siu, LK. et al. Correlation of in vitro susceptibility testing results for amoxicillinclavulanate and ampicillin-sulbactam using a panel of beta-lactamase producing
Enterobacteriaceae. APMIS. 1998 Sep; 106(9):917-20.
Kacmaz, B., Sultan, N. In vitro susceptibilities of Escherichia coli and Klebsiella spp.
to ampicillin-sulbactam and amoxicillin-clavulanic acid. Jpn J Infect Dis. 2007
Jul;60(4):227-9.
Piperacillin. Drug Monograph. In: Klasco RK (Ed): DRUGDEX® System (electronic
version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at:
http://www.thomsonhc.com (cited:10/12/2009).
Piperacillin/tazobactam (Zosyn®). Drug Monograph. In: Klasco RK (Ed):
DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village,
Colorado, USA. Available at: http://www.thomsonhc.com (cited:10/12/2009).

References
Ticarcillin/clavulanic acid (Timentin®). Drug Monograph. In: Klasco RK (Ed):
DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village,
Colorado, USA. Available at: http://www.thomsonhc.com (cited:10/12/2009).
Aztreonam. Drug Monograph. In: Klasco RK (Ed): DRUGDEX® System (electronic
version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at:
http://www.thomsonhc.com (cited:10/12/2009).
Reichardt, P. et al. Leukocytopenia, thrombocytopenia and fever related to
piperacillin/tazobactam treatment—a retrospective analysis in 38 children with cystic
fibrosis. Infection. 1999 Nov-Dec;27(6):355-6.
 Kaiser Regional Antibiogram, Northern California. 2009
American Thoracic Society; Infectious Disease Society of America. Guidelines for
the management of adults with hosptial-acquired, ventilator-associated and
healthcare-associated pneumonia. Am J Respir Crit Care Med. Vol 171. pp 388-416,
2005.
 Chambers, H. Chapter 23: Carbapenems and monobactams. Mandell, G., Bennett,
J., Dolin, D. Mandell, Douglas and Bennett’s Principles and Practice of Infectious
Disease. 7th Edition. 2009.

References
Paterson, D., Depestel D. Doripenem. Clin Infect Dis. 2009 Jul 15;49(2):291-8.
Spriet, I. Interaction between valproate and meropenem: a retrospective study.
Ann Pharmacother. 2007 Jul;41(7):1130-6.
ASHP Drug Product Shortages Management Resource Center.
www.ashp.org/drugshortages/current. Last accessed 10/12/2009.
Ramphal, R., Ambrose, P. Extended-spectrum beta-lactamases and clinical
outcomes: current data. Clin Infect Dis. 2006 Apr 15;42 Suppl 4:S164-72.
Long, R. et al. Empirical treatment of community-acquired pneumonia and the
development of fluoroquinolone-resistant tuberculosis. Clin Infect Dis. 2009;
48:1354-60.
Moxfloxacin. Drug Monograph. In: Klasco RK (Ed): DRUGDEX® System (electronic
version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at:
http://www.thomsonhc.com (cited:10/12/2009).
Clindamycin. Drug Monograph. In: Klasco RK (Ed): DRUGDEX® System (electronic
version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at:
http://www.thomsonhc.com (cited:10/12/2009).

References
Rybak, M. et al. Therapeutic monitoring of vancomycin in adult patients: A
consensus review of the American Society of Health-System pharmacists, the
Infectious Diseases Society of America and the Society of Infectious Diseases
Pharmacists. Am J Health-System Pharm. 2009;66:82-98.
Donskey, et al. Effect of antibiotic therapy on the density of vancomycin-resistant
enterococci in the stool of colonized patients.NEJM. 2000 Dec 28;343(26):1925-32.
 Murray, B., Esteban, N. Chapter 31: Glycopeptides (Vancomycin and teicolanin),
Streptogramins (Quinupristin-dalfoprsitin), and lipopeptides (daptomycin). Mandell,
G., Bennett, J., Dolin, D. Mandell, Douglas and Bennett’s Principles and Practice of
Infectious Disease. 7th Edition. 2009.
 Hooper, D., Strahilevitz, J. Chapter 35: Quinolones. Mandell, G., Bennett, J., Dolin,
D. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Disease. 7th
Edition. 2009.
Metronidazole. Drug Monograph. In: Klasco RK (Ed): DRUGDEX® System
(electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA.
Available at: http://www.thomsonhc.com (cited:10/12/2009).
Gerding, D. et al. Treatment of Clostridium difficie infection. Clin Infect Dis. 2008
Jan 15;46 Suppl1:S32-42.

.
This concludes Module 2: Antibiotic Review.
Please proceed to Module 3: Allergy Review.