Multicenter Observational Study of Ceftaroline Fosamil for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

Evan J. Zasowski; Trang D. Trinh; Kimberly C. Claeys; Anthony M. Casapao; Noor Sabagha; Abdalhamid M. Lagnf; Kenneth P. Klinker; Susan L. Davis; Michael J. Rybak

doi:10.1128/AAC.02015-16

DOI: 10.1128/AAC.02015-16

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FIG 1
Kaplan-Meier curves for the time to clearance of bloodstream infection post-ceftaroline initiation in the efficacy population. (A) Ceftaroline monotherapy; (B) ceftaroline combination therapy.

TABLE 1

Baseline demographics, clinical characteristics, and outcomes of the efficacy population

Parameter	Value for group
Parameter	Overall (n = 126)	Monotherapy (n = 89)	Combination therapy (n = 37)
Demographics
Median age (yr) (IQR)	59 (45.5–66.8)	59 (48–67)	57 (45–66.5)
No. of male patients (%)	70 (55.6)	50 (56.2)	20 (54.1)
No. of patients of race (%)
African American	86 (68.3)	62 (69.7)	24 (64.9)
Caucasian	34 (27.0)	21 (23.6)	13 (35.1)
Hispanic/Latino	1 (0.8)	1 (1.1)	0
Other	5 (4.0)	5 (5.6)	0
No. of patients in hospital system (%)
Detroit Medical Center	83 (65.9)	52 (58.4)	31 (83.8)
UF Health-Shands Hospital	30 (23.8)	26 (29.2)	4 (10.8)
Henry Ford Hospital	13 (10.3)	11 (12.4)	2 (5.4)
Comorbidities and past medical history
No. of patients with comorbidity or past medical history (%)
Prior antibiotics (90 days)	33 (26.2)	24 (27.0)	9 (24.3)
Prior MRSA infection (1 yr)	20 (15.9)	14 (15.7)	6 (16.2)
Obesity	48 (38.1)	37 (41.6)	11 (29.7)
Diabetes mellitus	47 (37.3)	34 (38.2)	13 (35.1)
Chronic kidney disease	34 (27.0)	25 (28.1)	9 (24.3)
Chronic hemodialysis	26 (20.6)	19 (21.3)	7 (18.9)
Liver disease	20 (15.9)	13 (14.6)	7 (18.9)
Intravenous drug user	24 (19.0)	14 (15.7)	10 (27.0)
Malignancy	7 (5.6)	4 (4.5)	3 (8.1)
HIV/AIDS	8 (6.3)	3 (3.4)	5 (13.5)
Neutropenia^a	3 (2.4)	2 (2.2)	1 (2.7)
Median Charlson comorbidity index (IQR)	3 (2–5)	3 (2–5)	3 (2–5)
Clinical characteristics
No. of patients in intensive care unit (%)^b	45 (35.7)	31 (34.8)	14 (37.8)
Median APACHE II score (IQR)^b	16 (12–22)	16 (12–22)	16 (13–22)
No. (%) of patients with:
Lower respiratory tract source	41 (32.5)	30 (33.7)	11 (29.7)
Infective endocarditis source	31 (24.6)	20 (22.5)	11 (29.7)
Bone/joint source	26 (20.6)	20 (22.5)	6 (16.2)
Intravenous catheter source	20 (15.9)	16 (18.0)	4 (10.8)
Skin/soft tissue source	11 (8.7)	9 (10.1)	2 (5.4)
Other source	22 (17.5)	14 (15.7)	8 (21.6)
Polymicrobial BSI	10 (7.9)	6 (6.7)	4 (10.8)
Vancomycin-susceptible strain^c	125 (99.2)	88 (98.9)	37 (100.0)
Daptomycin-susceptible strain^c^,^d	116 (96.7)	80 (96.4)	36 (97.3)
Ceftaroline-susceptible strain^e	94 (96.9)	70 (95.9)	24 (100.0)
Treatment information
No. (%) of patients with:
Infectious diseases consult^f	113 (93.4)	79 (91.9)	34 (97.1)
Source control pursued^g	42 (34.7)	28 (32.9)	14 (38.9)
Prior directed therapy with vancomycin	107 (84.9)	74 (83.1)	33 (89.2)
Prior directed therapy with daptomycin	48 (38.1)	22 (24.7)	26 (70.3)
Ceftaroline dosing frequency
Every 8 h	66 (52.4)	52 (58.4)	14 (37.8)
Every 12 h	54 (42.9)	33 (37.1)	21 (56.8)
Every 24 h	6 (4.8)	4 (4.5)	2 (5.4)
Ceftaroline dose
600 mg	76 (60.3)	55 (61.8)	21 (56.8)
400 mg	19 (15.1)	14 (15.7)	5 (13.5)
300 mg	11 (8.7)	8 (9.0)	3 (8.1)
200 mg	20 (15.9)	12 (13.5)	8 (21.6)
Median ceftaroline inpatient duration (days) (IQR)	13 (5–21)	13 (5–22)	14 (4–17)
No. (%) of patients receiving combination therapy with:
Daptomycin	28 (22.2)		28 (75.7)
Vancomycin	3 (2.4)		3 (8.1)
Gentamicin	3 (2.4)		3 (8.1)
Rifampin	5 (4.0)		5 (13.5)
Outcomes
No. of patients achieving clinical success (%)	86 (68.3)	62 (69.7)	24 (64.9)
No. of patients with in-hospital mortality (%)	28 (22.2)	17 (19.1)	11 (29.7)
No. of patients with cleared BSI on ceftaroline (%)	115 (91.3)	79 (88.8)	36 (97.3)
Median BSI duration post-ceftaroline initiation (days) (IQR)	3 (1–4)	2 (1–4)	3 (1.5–5)
Median length of stay post-ceftaroline initiation (days) (IQR)	12 (8–20)	12 (8–18)	15 (8.5–22.5)

↵a Defined as an absolute neutrophil count of <500 cells/mm³ at ceftaroline initiation.
↵b At the time of the index culture.
↵c Susceptibility determined by Microscan, Vitek 2, BD Phoenix, or Etest.
↵d Daptomycin susceptibility were available for 120, 83, and 37 patients in the efficacy population and the monotherapy and combination therapy subgroups, respectively.
↵e Ceftaroline susceptibility was determined by Etest for 97, 73, and 24 patients in the efficacy population and the monotherapy and combination therapy subgroups, respectively.
↵f Infectious diseases consult status known for 121, 86, and 35 patients in the efficacy population and the monotherapy and combination therapy subgroups, respectively.
↵g Pursuit of source control known for 121, 85, and 36 patients in the efficacy population and the monotherapy and combination therapy subgroups, respectively.

TABLE 2

Multivariable logistic regression analysis of factors independently associated with treatment failure with ceftaroline in the efficacy population^a

Variable	Odds ratio (95% CI)	Adjusted odds ratio (95% CI)
APACHE II score	1.100 (1.037–1.166)	1.093 (1.044–1.145)
Malignancy	6.000 (1.111–32.405)	3.127 (1.009–9.686)
Lower respiratory tract source	2.632 (1.198–5.783)
Bone/joint source	0.442 (0.153–1.274)
Ceftaroline dose
600 mg
400 mg	3.856 (1.350–11.017)
300 mg	2.892 (0.785–10.651)
200 mg	2.314 (0.814–6.577)

↵a P = 0.574 as determined by a Hosmer-Lemeshow goodness-of-fit test and a variance inflation factor of <3 for all variables included for model entry. CI, confidence interval.