Optimizing Antibiotic Use in 2015
Jamie McCarrell, Pharm.D., BCPS, CGP
Assistant Professor, TTUHSC SOP/SOM
Objectives
• Review new antibiotics approved for use by the FDA
for various bacterial infections.
• Identify current trends in resistance for common
multi-drug resistant bacteria.
• Develop strategies for appropriately dosing
antibiotics in patients with varying degrees of renal
dysfunction.
• Outline major points from several landmark
guidelines for acute bacterial syndromes.
• Given a patient case, optimize antibiotic
pharmacotherapy to adequately treat the bacterial
infection while minimizing adverse effects.
2014-2015
NEW ANTIBIOTICS
Zerbaxa®
• Ceftolozane/tazobactam
• 5th generation cephalosporin
• Indications: Intra-abdominal infections,
complicated UTIs
• Key features:
– ~$100/gram (dosed 1.5 gm Q8h for 4-14 days)
– Covers Pseudomonas aeruginosa
– Must use with Flagyl for intra-abdominal
infections
– Crosses placenta, but Category B
Orbactiv®
• Oritavancin
• Lipoglycopeptide (inhibits cross-linking of cell
wall membrane)
• Indications: ABSSSI due to Gram (+) including
MRSA (but not VRE)
• Key Features:
– Single dose therapy (t1/2 = 245 hours!)
– Cost = $3480 for single dose
Dalvance®
• Dalbavancin
• Lipoglycopeptide (inhibits cross-linking of cell
wall membrane)
• Indications: ABSSSI due to Gram (+) infections
including MRSA
• Key Features:
– One dose with one follow-up dose 7 days later
– Cost: Initial dose = $3576, FU dose = $1788
Sivextro®
• Tedizolid
• Oxazolidinone
• Indications: ABSSI due to Gram (+) infections
including MRSA
• Key features:
– Price = $2124 (oral), $2820 (IV) for 6 days
– May be useful in linezolid-resistant infections
Kerydin®
•
•
•
•
Tavaborole
Oxaborole antifungal (inhibits tRNA synthesis)
Indications: onychomycosis
Key Features
– Duration of therapy: 48 weeks (daily)
– Cost/bottle = $589, which lasts 3 weeks
– Cost/treatment = $9,424
– Chance of cure = 6.5 – 9.1%
Jublia®
• Efinaconazole
• Azole antifungal, inhibits fungal cell
membrane synthesis
• Indications: Onychomycosis
• Key features:
– Duration of therapy: 48 weeks (daily)
– Cost/bottle = $539, which lasts 3 weeks
– Cost/treatment = $8,624
– Chance of cure = 15 – 17%
Xtoro®
•
•
•
•
Finafloxacin otic solution
Fluoroquinolone
Indications: Swimmer’s ear
Key features
– Covers Staph aureus and Pseudomonas
aeruginosa
– Approved 12/2014
– Cost info not yet available
TRENDS IN RESISTANCE
Vancomycin
• MIC “Creep” occurring
nationally
• Occurs in MSSA and MRSA
• Higher MICs associated with
higher rates of Tx failure and
mortality
• VRSA – multiple cases on
multiple continents
The “D-Test”
• “Erm” gene
• Induced by ERY
• Causes clinda
resistance
http://microblog.me.uk/wp-content/uploads/TheDtest.jpg
Carbapenemases
• Class A – Klebsiella pneumoniae carbapenemase (KPC)
• Class B – Metallo-β-Lactamases (MBL)
• Class D – OXA – 48 type
UNASYN
AMIKACIN
AMPICILLIN
AUGMENTIN
AZACTAM
ROCEPHIN
FORTAZ
CLAFORAN
ANCEF
ZINACEF
GENTAMICIN
ZOSYN
BACTRIM
TETRACYCLINE
TIMENTIN
TOBRAMYCIN
5
40
100
0
20
60
80
80
100
20
60
80
100 100
60
80
80
67
80
Enterobacter aerogenes
7
43
86
0
29
57
71
71
71
14
57
86
86
86
86
86
57
60
86
Enterobacter cloacae
19
37
89
0
11
47
74
68
79
5
26
89
100
84
84
95
74
57
89
Escherichia coli
102
44
99
35
81
79
84
84
86
76
80
83
100
68
94
70
62
90
81
Klebsiella oxytoca
8
62
100
0
75
62
62
75
62
50
75
88
100
88
100
88
88
75
100
Klebsiella pneumoniae
27
93
100
0
100
81
93
93
93
81
89
100 100 100 100
96
89
100 100
Pseudomonas aeruginosa
38
53
24
74
11
Proteus mirabilis
23
Stenotrophomonas maltophilia
5
Serratia marcesens
5
Shigella sonnei
0
Salmonella
1
84
78
100
74
100 100 100 100 100
87
100
20
0
100
100
0
0
100 100
The shaded areas represent a 10% or greater decrease in sensitivity.
100 100 100 100
0
100 100 100
LEVAQUIN
# of isolates
Citrobacter freundii
PRIMAXIN
Systemic Gram Negative
HOUSEWIDE
76
89
61
84
65
100
61
100
60
0
0
61
0
100
100 100 100 100 100
71
79
100
70
25
40
100
100 100 100 100 100 100
80
UTI- Adult Women
• Uncomplicated Cystitis
– Nitrofurantoin 100 mg PO BID x 5 days
– Bactrim DS, 1 tab PO BID X 3 days
– FQN
• 3 day regimens
• Side effects, resistance issues  reserve
– Beta-lactams
• 3-7 day regimens, only when recommended agents
can’t be used
• Amoxicillin or ampicillin NOT recommended for empiric
therapy
UTI – Geriatric Women
• Nitrofurantoin issues
– Beers criteria
– CrCl cutoff (later slide)
• Bactrim issues
– New study…sudden death risk?
– Hyperkalemia
– Risk of INR fluctuations
UTI – Geriatric Women
• Levofloxacin issues
–
–
–
–
–
Renal dose adjustments (later slide)
QTc prolongation
Mental status changes
Tendon rupture
Drug interactions
• Difficult to make a good choice…must consider all
aspects of the patient before deciding on empiric
therapy in the elderly!
More Isn’t Always Better
RENAL ADJUSTMENT OF
ANTIBIOTICS
Levaquin®
Desired Dose
CrCl
> 50 ml/min
CrCl
20 – 49 ml/min
CrCl
10 – 19 ml/min
750 mg daily
750 mg daily
750 mg Q48 hrs
750 mg x1, then 500
mg Q48 hrs
500 mg daily
500 mg daily
250 mg daily
250 mg daily
500 mg x1, then 250 500 mg x1, then 250
mg Q24 hrs
mg Q48 hrs
250 mg daily
CrCl vs MDRD
250 mg Q48 hrs
Vancomycin
• Loading dose of 25 – 30 mg/kg
• Maintenance: 15 – 20 mg/kg/dose every 8-12
hours (adjusted to desired trough)
– Note: MIC = 1 mcg/ml requires trough of 15
• Renal dysfunction:
– CrCl > 50: No adjustment
– CrCl 20 – 49: increase interval to Q24h
– CrCl < 20: Pharmacokinetic modeling
• Oral administration: No adjustments
Nitrofurantoin
• CrCl > 60 ml/min is required to get adequate
concentration
– Debatable…
• Pulmonary toxicity if not cleared
– Free radical formation = tissue damage
– Allergic and eosinophilic response as well
Other Antibiotics
• Safe to assume adjustments are needed…
• Nearly all antibiotics require some
adjustment.
• Can check drug references or package
labeling…or call the pharmacist!
• Benefits of proper dosing:
– Minimize adverse effects and kidney injury
– Minimize patient costs and QOL
Pneumonia Guidelines - Review
• IDSA – CAP
– Previously healthy, no Abx for 3 months
• Macrolide
• Alternative: Doxycycline
– Comorbidities OR inpatient
• Respiratory FQN: Levo, Moxi
• Beta-lactam + Macrolide (R & Z)
– ICU
• Beta-lactam + Resp FQN
• Alternative: Beta-lactam + Macrolide
Group work
PATIENT CASE