Pneumonia33% Infective

Endocarditis26%

ABSSSI24%

IV catheter7%

Spinal abscess

5%

Prosthetic Device

3%

Unknown2%

Clinical Experience with Ceftaroline Fosamil (CPT) for Bloodstream Infections (BSI)

Anthony M. Casapao1, Katie E. Barber1, Christina K. Wong1, Viktorija O. Barr2, Leah M. Steinke3, Ryan P. Mynatt3, Susan L. Davis1, Keith S. Kaye3,4, Jason M. Pogue3, Michael J. Rybak1,4

Anti-Infective Research Laboratory, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 482011; Alexian Brothers Health System,

Arlington Heights, IL 600052; Detroit Medical Center, Detroit, MI 482013; School of Medicine, Wayne State University, Detroit, MI 482014

Abstract (UPDATED)

Objective: To retrospectively describe the outcomes of patients (pts) treated with CPT for BSI.

Methods: A multi-center, retrospective observational study of all consecutive pts who received more than 48 hours of CPT at the

Detroit Medical Center and Alexian Brothers Health System from January 2011 to November 2012. Pts receiving CPT therapy for

BSI were included for evaluation. Clinical and microbiological outcomes were analyzed. Clinical cure (CC) defined as infection

resolved at the end of CPT therapy and no additional therapy needed.

Results: Forty-two patients were treated with CPT for BSI: concomitant source of bacteremia include 14 (33%) pneumonia, 11

(26%) endocarditis, 10 (23%) acute bacterial skin and skin structure infection, 3 (7%) IV catheter-related infections, 2 (5%)spinal

abscesses, 1 (2%) prosthetic device and 1 (2%) unknown. Median APACHE II score was 13 (IQR 8-18) and Charlson Index of 4

(IQR 2-6). A pathogen was isolated in all 42 patients, with Staphylococcus aureus (SA) as the most common pathogen 98%

found in blood cultures. Thirty-six (86%) were methicillin-resistant SA (MRSA) and 5 (12%) were methicillin-susceptible SA. Two

of the MRSA isolates were daptomycin-nonsusceptible SA, 1 was heterogeneous vancomycin-intermediate SA, and 1 was

vancomycin-intermediate SA. Six (14%) were polymicrobial with a Gram-negative or another Gram-positive bacteria. Median CPT

MIC for SA was 0.5 mg/L (0.5-2). Median total length of stay was 19 days (IQR 13-29) and median duration of CPT was 10 days

(IQR 4-15). The most common CPT dosage (69%) was 600 mg Q12h and was adjusted for renal function. Thirty-eight (91%) pts

were given another antibiotic prior to the start of CPT with a median of 6 days (IQR 3-9) of prior antibiotic exposure. The median

length of time of clearance of BSI was 2 days (IQR 1-4.5). All pts were clinically evaluable and 37 (88%) achieved CC at the end

of CPT therapy. Overall, 5 (12%) pts died during hospitalization where 4 pts had clearance of blood cultures and 1 had persistent

BSI at the end of CPT. One (2%) had readmission for the same infection within 30 days after discharge.

Conclusion: The majority of pts had SA BSI treated with CPT as a salvage agent with a median of six days after receiving

another antibiotic and had favourable outcomes. Further research is necessary to clarify its clinical role in this infection manner

outside its approved label.

Results

Introduction

• Our objective was to evaluate the characteristics and outcomes of patients with bloodstream infections treated with CPT

including off-label dosing.

• A dual-center, retrospective cohort analysis conducted from January 2011 to November 2012 at the Detroit Medical Center

(Detroit, MI), an academic hospital system with 8 hospitals and Alexian Brothers Health System (Arlington Heights, IL), a

community hospital system with 4 hospitals.

• Consecutive adult patients with an infection treated with CPT for > 48h during hospitalization.

• Patient Characteristics and Clinical Data:

• Clinical data was collected from medical charts of patients

• Outcome assessments of clinically evaluable patients included documentation at end of CPT therapy outcome:

• Clinical cure: resolution of all signs and symptoms of infection with no further need of antibiotic treatment while on

CPT.

• Microbiological cure: in patients with follow up cultures defined as eradication of the infecting organism while on CPT.

• Length of hospital stay (LOS)

• Patients were also assessed for adverse reactions, readmission, and mortality.

• Microbiologic Assessments:

• Minimum inhibitory concentrations (MIC) were determined by Etest according to institutions’ clinical microbiology laboratory.

• Statistical Analysis:

• SPSS, version 21.0 (IBM SPSS Inc., Chicago, IL) was used to perform descriptive statistics including data frequencies and

distributions.

• Ceftaroline fosamil (CPT), is an advanced generation cephalosporin with bactericidal activity against Gram-positive and Gram-

negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA).

• US Food and Drug Administration (FDA) approved CPT for the treatment of acute bacterial skin and skin structure infections

(ABSSSI) and community-acquired bacterial pneumonia (CABP) in October 2010.

• There is limited evidence regarding the use of CPT in complicated infections.

Table 1. Baseline Characteristics

Address correspondence to: m.rybak@wayne.edu

• The majority of patients treated with CPT had favorable outcomes including S.

aureus bacteremia.

• The primary source of BSI was pneumonia, endocarditis, and skin infection

• Patients were primarily treated with either 600mg IV Q12H or 600mg IV Q8H

• CPT was predominantly used as an alternative treatment option

• In conclusion, further research is necessary to better describe the clinical role

of CPT in these complicated infections outside of the FDA approved labels.

1. Product information. Telfaro (ceftaroline fosamil). St. Louis, MO: Forest Laboratories, Inc; April 2011.

2. Steed ME, Vidaillac C, Rybak MJ. Evaluation of ceftaroline activity versus daptomycin (DAP) against DAP-Nonsusceptible methicillin-resistant Staphylococcus aureus strains in an in vitro

pharmacokinetic/pharmacodyamic model. Antimicrob Agents Chemother. 2011 July;55(7):3522-3526.

3. Vidaillac C, Leonard SN, Rybak MJ. In vitro activity of ceftaroline against methicillin-resistant Staphylococcus aureus and heterogeneous vancomycin-intermediate S. aureus in a hollow fiber

model. Antimicrob Agents Chemother. 2009 Nov;53(11):4712-4717.

4. Ho TT, Cadena J, Childs LM, et al Methicillin-resistant Staphylococcus aureus bacteraemia and endocarditis treated with ceftaroline salvage therapy. J Antimicrob Chemother. 2012

May;67(5):1267-70.

Conclusions

References

23rd European Congress of Clinical Microbiology and Infectious Diseases Berlin, Germany 27-30 April 2013

P858

Table 2. Safety

Figure 1. Types of Infections Concomitantly with BSI

Pharmacotherapy

Purpose and Methods

• 41 (98%) patients had positive blood

cultures identified with S. aureus.

• 36 (88%) were MRSA

• 5 (12%) were MSSA

• Remaining patient had K. oxytoca BSI

with MRSA pneumonia

Figure 2. S. aureus CPT

susceptibilities. n = 21

• Median duration of CPT in hospital was 10 days (IQR 4-15)

• 38 (90%) were given another antimicrobial prior to the start of CPT

• CPT dose and frequency

• 29 (69%) were given 600 mg IV Q12h (label dose) with renal

adjustment

• 13 (31%) were given 600 mg IV Q8h (higher dose) with renal

adjustment

• 16 (38%) were given another antimicrobial in combination with CPT

• 9 (21%) were given with daptomycin for median of 12 days (IQR 6-18)

• 3 (7%) were given with clindamycin for 3 and 9 days

• 2 (5%) were given with rifampin for 2 and 11 days

• 1 (2%) was given with linezolid for 6 days

Clinical and Microbiological Outcomes

88%12%*

Clinical Outcome

Cure Failure

n = 24n = 13

n = 5

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Label Dose Higher Dose

Clinical Outcome and CPT Dosing

Cure Failure

0

2

4

6

8

10

12

0.5 0.75 1 2

Nu

mb

er

of

Iso

late

s

CPT Etest (mg/L)

NS

NS = nonsusceptible

Susceptible

• Five (12%) had a polymicrobial

infection

• 4 (12%) were Gram-negative

• E. coli, K. pneumoniae, S.

marcescens, & M.

catarrhalis

• 1 (2%) was E. faecalis

Patient Adverse

Outcome

Days

on CPT

Outcome

1 Acute interstitial

nephritis (AIN)

4 AIN improved when changed to

linezolid for MRSA BSI

2 Constipation 2 Continued on CPT

3 Hypokalemia 3 Continued on CPT and monitored

potassium with supplements

4 Purpuric rash 17 Papable rash on bilateral lower

extremities and alleviated with

changed to DAP for MRSA IE

5 Breakthrough

bacteremia

14 CPT for MRSA and K. oxytoca

pneumonia. MRSA cleared but had

breakthrough K. oxytoca bacteremia.

MIC elevated from 0.06 to 1 mg/L.

Baseline CharacteristicsMedian (IQR) or n (%)

(n = 42)

Age (years) 60 (49-75)

APACHE II Score 13 (8-18)

Charlson Comorbidity Score 4 (2-6)

Weight (kg) 75 (66-92)

Weight ≥ 100 kg 6 (14%)

Creatinine Clearance (mL/min) 37 (15-66)

Prior hospitalization (within 1 year) 25 (60)

ICU admission 23 (55)

Diabetes 14 (33)

Chronic Kidney Disease 15 (36)

Hemodialysis 11 (26)

Chronic Obstructive Pulmonary Disease 8 (19)

Previous antibiotics (3 months) 10 (24)

• Hospital mortality was 12% (5/42)

• 1 was re-admitted to hospital for

spinal abscess

• Potential synergy for clearance of

bloodstream

• Convenience was defined for cost

issues and switched to CPT rather

than daptomycin

19 (IQR 13-29)

6 (IQR 3-9)

5 (IQR 4-9)

2 (IQR 1-5)

0 5 10 15 20

Length of Stay

Time to Switch to CPT

Days of Positive Culture

Time to Clearance of Bloodwith CPT

Days During Hospitalization

62%

17%

6%

12%3%

Reason to use CPT

Disease Progression

Polymicrobial infection

Convenience cost

Pneumonia and BSI

Potential Synergy

Reasons for Clinical Failure (n =5)

• 2 expired while on CPT

• 2 discontinued CPT due to adverse event

• 1 organism persisted in blood cultures

*Disease States

that Failed:

1 ABSSSI

1 Endocarditis

3 Pneumonia