Antibiotic Review

By: Maggie Kline, PharmD

PGY-1 Pharmacy Resident, IU Health Bloomington Hospital
January 11th, 2021
 Objectives

Identify spectrum of activity and adverse effects for

common antibiotics used in the inpatient setting
Understand how PK/PD parameters impact antibiotic
dosing
Discuss common strategies to facilitate antibiotic
stewardship

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 3

J Infect Chemother. 2015 May;21(5):319-29.

GP GN
Staphylococcus E. coli
Streptococcus Klebsiella
Enterococcus Proteus
Clostridium Pseudomonas
Bacillus Acinetobacter

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GP GN
Staphylococcus E. coli
Streptococcus Klebsiella
Enterococcus Proteus
Clostridium Pseudomonas
Bacillus Acinetobacter

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Mechanism of Action

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Beta-Lactam Antibiotics

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 Beta-lactams

Beta-lactam antibiotics bind PBP

(penicillin-binding proteins) and inhibit
cross-linking of peptidoglycan.  Loss Class Adverse Events:
of cell wall integrity  Bacteria -hypersensitivity
undergo lysis  Bactericidal -seizures
-interstitial nephritis

Resistance:
1) Altered PBPs
2) Beta-lactamase
3) GN: Decreased
penetration
through membrane

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 Spectrum of Activity: Beta-lactams
Strep MSSA Entero- PM, Serratia, P. ADA BDA
ccocus KP, Citrobacter, Aerugino
EC, HI Enterobacter a
PCN X X

Nafcillin, X X X
oxacillin

Amp/Amox X X +/- X

Amox/clav, X X X X X X
amp/sulb*

Pip/tazo X X X X X (induces X X X
AmpC)
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 Strep MSSA Enter- PM, KP, Serratia, P. ADA BDA
Spectrum of Activity: Cephalosporins
occocus EC, HI Citrobacter, aerugin-
Enterobacter osa
1st gen: X X X X
cefazolin,
cephalexin
2nd gen: X X X X
cefaclor,
cefuroxime
2nd X X X X X
generation
cephamycins
3rd gen: X X X (AmpC) Ceftaz X
ceftriaxone, (↑MIC) only
ceftazidime,
cefepodoxime
4th gen X X X X X X
cefepime

Ceftaroline X Y, X X (AmpC) X
MRSA 10
 Spectrum of Activity: More beta-lactams

Strep MSSA Enter- PM, KP, Serratia, P. ADA BDA

occocus EC, HI Citrobacter, aerugin-
Enterobacter osa
Meropenem X X X X X X X X

Imipenem/cil X X X X X X X X
astatin

Ertapenem X X X X X X

Aztreonam X X X

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 Patient Case #1
A pt with a history of MRSA and a severe penicillin allergy
is to start on broad spectrum antibiotics for coverage of a
severe diabetic foot infection. The patient went to the
beach last week, so the provider wants to cover for P.
aeruginosa.
Vancomycin + Zosyn
Vancomycin + cefepime + metronidazole
Vancomycin + aztreonam
Cefazolin + Ciprofloxacin IV

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 Patient Case #2
A 77 YOM with T2DM is on
vancomycin for a wound,
with the following post-
debridement wound culture.
What do you recommend for
continued IV therapy?
Add meropenem.
Stop vancomycin and start
meropenem.
Change to ciprofloxacin.
 Stop vancomycin and
start cefepime.
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Gram Positive Agents
Vancomycin, Daptomycin, Linezolid

Others (not covered): Quinupristin-Dalfopristin; Telavancin; Oritavancin;

Dalbavancin

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 Vancomycin

MOA: Inhibits cell wall synthesis

by binding to D-Ala-D-Ala chain

Adverse effects: nephrotoxicity,

ototoxicity, Red Man syndrome
(decrease rate), extravasation

Resistance: Modification of D-Ala-

D-Ala binding site

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 Vancomycin

Spectrum: Gram positive only

(Except VRE)

Uses:
Drug of choice for MRSA
Blood stream infections
including endocarditis
SSTI
PO vanc for C. difficile

Dosed based on weight, renal

clearance
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 Daptomycin

MOA: Inserts lipophilic tail into cell

membrane  membrane
depolarization  bactericidal

Adverse Effects:
CPK Elevation (monitor),
rhabdomyolosis/myopathy
DRESS

Resistance: Target alteration

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 Daptomycin

Spectrum: Gram positive including VRE

Pearls:
-Hold statins!
-Dosed daily unless renal insufficiency
-Not active in lungs

Uses: SSTI, MRSA bacteremia including

endocarditis

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 Linezolid

MOA: Inhibit protein synthesis at

50S ribosome  Static
Adverse effects:
Acts as MAOI—hold serotonergic
drugs
Bone marrow suppression,
thrombocytopenia
Resistance: Binding site
alteration
Spectrum: Gram positive only
Pearls: Poor urinary elimination;
Good bioavailability; avoid
tyramine-rich foods
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 Patient Case #2
A pt with CKD3 being treated for cystitis with ceftriaxone
day 5. The urine culture results for Enterococcus as
below. How would you adjust therapy?
Continue ceftriaxone.
Change ceftriaxone to vancomycin
Change ceftriaxone to ampicillin
Stop therapy. Drug Sensitivity
Vancomycin S
Penicillin S
Ampicillin S
Daptomycin S 20

Linezolid S
More Antibiotic Classes

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 Fluoroquinolones
 Ciprofloxacin, moxifloxacin, and
levofloxacin

 Class Side Effects:

 Tendon rupture
 QTc prolongation
 Hypo- or hyperglycemia
 AMS
 DDIs

 MOA: Inhibit bacteria DNA gyrase  DNA  Resistance:

strand breaks  Bactericidal  1) Binding site change
 2) Efflux
 3) Decreased penetration
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 Fluoroquinolones
Ciprofloxacin Moxifloxacin Levofloxacin
Atypical Coverage X X X
S. pneumoniae X X
(“respiratory”)
Pseudomonas X X
Anaerobic X +/-
Urinary X X
Elimination
100% Oral X X
bioavailability

Uses: URIs, UTIs (not moxifloxacin), topical quinolones used for eye/ear
infections, GN bacteremia step-down therapy 23
Macrolides

Azithromycin, clarithromycin,
erythromycin

MOA: Inhibit protein synthesis at

50S ribosome  Static

Adverse effects:
GI upset
Hepatotoxicity
QTc prolongation

Resistance: Binding site

alteration, efflux 24
 Macrolides
Spectrum: S. pneumoniae, H. influenzae, Neisseria, Moarexlla,
atypicals (Legionella, Chlamydia, Mycoplasma, Mycobacterium
avium complex)

Uses: Respiratory tract infections, chlamydia, gonorrhea, MAC

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 Aminoglycosides
Gentamicin, tobramycin, amikacin

MOA: Inhibit protein synthesis at 30S

ribosome  bactericidal

Resistance:
Altered uptake
Altered site
AG-modifying enzymes

Adverse effects:
Nephrotoxicity, ototoxicity 26
 Aminoglycosides
Spectrum: GN and GP synergy

Uses: synergy with vancomycin for Enterococcus endocarditis, UTIs, dual

Pseudomonas coverage in HAP/VAP in select patients

Pearls: Can be given IV or IM Take advantage of concentration-dependent

killing to minimize AEs!

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 Aminoglycoside Dosing
Simulated concentration-versus-time
profile of once-daily (7 mg/kg q24h) and
conventional (1.5 mg/kg q8h) regimens for
patients with normal renal function.

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Antimicrob Agents Chemother. 1995;39(3):650-655.

 Tetracyclines
Doxycycline, minocycline, tetracycline

MOA: Inhibit protein synthesis at 30S

ribosome  bacteriostatic

Resistance:
Efflux
Enzymatic Inactivation

Adverse effects:
Photosensitivity
Tooth discoloration (avoid in
pediatrics <8 years, pregnancy, 29
lactation)
 Tetracyclines
Spectrum: GP, GN, atypicals, Rickettsiae

Doxycyline: CA-MRSA coverage, CAP, COPD

exacerbations, tick-borne illnesses, STIs (chlamydia and
gonorrhea); no renal adjustment

Minocycline – acne treatment

Tetracycline: H. pylori

Pearls: IV:PO 1:1; separate administration from cations

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 Patient Case #4
A Covid-19 positive patient with a PMH of CKD4, CHF, and depression
taking atorvastatin, carvedilol, aspirin, and fluoxetine is being
admitted to the ICU for hypoxic respiratory failure requiring
mechanical ventilation. The CXR shows ground glass opacities and
the provider wants to cover for potential superimposed bacterial CAP.
What do you recommend?
Azithromcyin 500 mg IV x 3 + Ceftriaxone 1 gm Q24H
Moxifloxacin 400 mg IV daily
Unasyn renally dosed + doxycycline 100 mg IVPB Q12H
Zosyn renally-dosed + Vancomycin + doxycycline IVPB Q12H

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MOA: inhibit folic acid
pathway
Sulfamethoxazole/
Trimethoprim
Resistance: Mutation in
target enzymes

Adverse effects:
Hypersensitivity/rash
Skin reactions,
photosensitivity
Increase serum K+ and SCr
Crystalluria
Hemolytic anemia 32
 Sulfamethoxazole/Trimethoprim
Spectrum: S. aureus (including CA-MRSA), GN (not Pseudomonas), DOC for
Stenotrophomonas maltophilia; opportunistic pathogens (Pneumocystis,
Toxoplasmosis)

Uses: SSTI, UTI, Pneumocystis pneumonia prophylaxis/treatment

Pearls: Dosing is based on TMP

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 UTI-specific agents
Nitrofurantoin Fosfomycin
MOA Cell wall inhibitor Cell wall inhibitor
Spectrum E. coli, Klebsiella, VRE, E. Coli (including ESBLs,
Enterobacter, E. faecalis (including
S. aureus* VRE), and more
Place in therapy Cystitis only and CrCl Should reserve for
>60 MDR, uncomplicated
UTIs
AEs GI upset, brown urine GI upset
Pearls Mix powder in 3-4 oz
water ONCE

*Must rule out bacteremia; at IU Health this result must be uncovered by 34

request
 Clindamycin
MOA: binds 50S ribosomal subunit

Spectrum: GP (including CA-MRSA), anaerobes (no GN!)

Adverse effects: C. difficile colitis, nausea, vomiting, diarrhea

Uses: skin infections, alternative to PCN for some indications in beta-lactam

allergic patients for URIs such as pharyngitis, necrotizing fasciitis

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 Metronidazole
MOA: inhbiti protein synthesis

Spectrum: anaerobes and

protozoal infections

Uses: Intra-abdominal
infections, bacterial
vaginosis, trichomoniasis, C.
difficile

Adverse effects
Disulfram-like reaction with
EtOH
Metallic taste 36
 Patient Case #5
A 17 YOF presents to the ED complaining of dysuria, urinary
frequency flank pain, fevers for 3 days. What do you recommend
empirically?
Nitrofurantoin 100 mg PO BID 5 days
Ampicillin IV + Gentamicin 5 mg/kg
Fosfomycin 1 packet ONCE
Bactrim DS 1 tab Q12H 3 days
Relevant labs
Temp 102 deg F
WBC 13
HR 113
RR 18
BP 88/64 37
PK/PD Principles

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 PK/PD Parameters

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J Infect Chemother. 2015 May;21(5):319-29.

 PK/PD

40

Clin Infect Dis. 2007;44(1):79-86.

 41

Clin Infect Dis. 2007;44(1):79-86.

Antibiotic Stewardship

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 Stewardship Goals
Improve outcomes for the patient

Minimize resistance, adverse effects, cost

Goals:
Right patient
Right drug
Right dose / time
Right duration

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 Stewardship Tools
De-escalation using cultures/clinical course/local antibiogram

Dose optimization using PK/PD

Limiting use of broad spectrum antibiotics to patients who are at

risk for MDR pathogens

IV to PO conversions as appropriate to decrease cost and length of

stay

Clarifying suspected source of infection; obtaining source control

as able, differentiating true infection from colonization
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 Stewardship Tools: MRSA Nasal PCR
MRSA Nasal PCR has negative predictive value >99%
for MRSA pneumonia
Can allow for more rapid de-escalation of vancomycin
for pneumonia if negative

Antimicrob Agents Chemother. 2014;58(2):859-864. 45

Ann Pharmacother. 2019;53(6):627-638.

Antibiotic Review

By: Maggie Kline, PharmD

PGY-1 Pharmacy Resident, IU Health Bloomington Hospital
January 11th, 2021
mkline4@iuhealth.org