1. Optimizing Antibiotic Use in 2015
Jamie McCarrell, Pharm.D., BCPS, CGP
Assistant Professor, TTUHSC SOP/SOM

2. 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.

3.
New antibiotics

4. 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

5. 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

6. 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

7. 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

8. 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%

9. 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%

10. 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

11. Trends in resistance

12. 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

13. The “D-Test” “Erm” gene Induced by ERY Causes clinda resistance
The “erm” gene…Can initially show resistance to ERY but susceptible to clinda…ERY will induce the erm gene and cause clindamycin resistance.
Clinically relevant why?

14. Carbapenemases Class A – Klebsiella pneumoniae carbapenemase (KPC)
Class B – Metallo-β-Lactamases (MBL)
Class D – OXA – 48 type

15. Systemic Gram Negative HOUSEWIDE
# of isolates
UNASYN
AMIKACIN
AMPICILLIN
AUGMENTIN
AZACTAM
ROCEPHIN
FORTAZ
CLAFORAN
ANCEF
ZINACEF
GENTAMICIN
PRIMAXIN
LEVAQUIN
ZOSYN
BACTRIM
TETRACYCLINE
TIMENTIN
TOBRAMYCIN
Citrobacter freundii 5 40
100 20 60 80 67
Enterobacter aerogenes 7 43 86 29 57 71 14
Enterobacter cloacae 19 37 89 11 47 74 68 79 26 84 95
Escherichia coli
102 44 99 35 81 76 83 94 70 62 90
Klebsiella oxytoca 8 75 50 88
Klebsiella pneumoniae 27 93 96
Pseudomonas aeruginosa 38 53 24 61
Proteus mirabilis 23 78 87 65
Stenotrophomonas maltophilia 25
Serratia marcesens
Shigella sonnei
Salmonella 1
The shaded areas represent a 10% or greater decrease in sensitivity.

16. 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

17. UTI – Geriatric Women Nitrofurantoin issues Bactrim issues
Beers criteria
CrCl cutoff (later slide)
Bactrim issues
New study…sudden death risk?
Hyperkalemia
Risk of INR fluctuations

18. 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!

19. Renal adjustment of antibiotics
More Isn’t Always Better
Renal adjustment of antibiotics

20. CrCl vs MDRD Levaquin® Desired Dose CrCl > 50 ml/min 20 – 49 ml/min
750 mg daily
750 mg Q48 hrs
750 mg x1, then 500 mg Q48 hrs
500 mg daily
500 mg x1, then 250 mg Q24 hrs
500 mg x1, then 250 mg Q48 hrs
250 mg daily
250 mg Q48 hrs
CrCl vs MDRD

21. 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

22. 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

23. 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

24. 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

25. Group work
Patient case