Clinical evaluation of the role of ceftaroline in the management of community acquired bacterial pneumonia

Figures & data

Table 1 Spectrum of microbiological coverage

Gram-positive bacteria	Gram-negative bacteria
Staphylococcus aureus (MSSA and MRSA) Streptococcus pyogenes Streptococcus agalactiae Streptococcus pneumoniae Streptococcus dysgalactiae	Klebsiella pneumoniae Klebsiella oxytoca Escherichia coli Citrobacter koseri Citrobacter freundii Enterobacter cloacae Enterobacter aerogenes Haemophilus influenzae Haemophilus parainfluenzae Proteus mirabilis Moraxella catarrhalis

Abbreviations: MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus.

Table 2 Susceptibility for ceftaroline in in vitro studies

Pathogens	In vitro studies – MIC range (μg/mL)
	Sader^Citation27	Ge^Citation28	Brown^Citation29	Saravolatz^Citation30	Jacobs^Citation31	Jones^Citation32	Kaushik^Citation33
S. aureus			0.25 to 2			≤0.12 to 2
MRSA	0.12 to 2	0.12 to 2	0.5 to 1			≤0.25 to 2	0.25 to 2
MSSA	0.03 to 0.5	≤0.03 to 1	0.25 to 0.5			≤0.1 to 0.5	≤0.008 to 1
CA-MRSA				≤0.251
VISA/hVISA	0.25 to 4		0.25 to 2	≤0.251			0.25 to 4
VRSA			0.5 to 1	≤0.121
Streptococcus pneumoniae			0.015 to 0.5		≤0.008 to 0.5	≤0.008 to 0.5
Streptococcus pneumoniae PCN resistant	0.06 to 0.5	≤0.008 to 0.5	0.015 to 0.5		≤0.006 to 0.5		≤0.008 to 0.5
Streptococcus pneumoniae PCN susceptible	≤0.016 to 0.06	≤0.008 to 0.12	0.015 to 0.12				≤0.008 to 0.12
Streptococcus pyogenes Macrolide resistant		≤0.008 to 0.03	0.015 to 0.5
Moraxella catarrhalis	≤0.016 to 012	≤0.03 to 0.5	0.015 to 1			≤0.008 to 1	≤0.008 to 0.5
Haemophilus influenzae	≤0.016 to 0.25	≤0.008 to 2	0.015 to 0.25			≤0.008 to 0.12	≤0.008 to 0.25
Klebsiella pneumoniae	0.03 to 4	≤0.03 to >16	0.03 to 1			≤0.008 to >16	≤0.03 to 165
Escherichia coli	≤0.016 to 0.025	≤0.03 to >16	0.015 to 16			≤0.015 to >16	0.5 to >16
Enterobacter cloacae	0.03 to >32	≤0.03 to >16	0.06 to 2			≤0.015 to >16	≤0.03 to >16
Pseudomonas aeruginosa	4 to >32		0.5 to 32				1 to >128

Abbreviations: MIC, minimum inhibitory concentration; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; CA-MRSA, community acquired methicillin-resistant Staphylococcus aureus; VISA/hVISA, vancomycin-intermediate S. aureus/hetero-resistant VISA; VRSA, vancomycin-resistant S. aureus; PCN, penicillin.

Table 3 Clinical cure rates comparing ceftaroline against ceftriaxone in CAP patients enrolled in the FOCUS 1 and FOCUS 2 studies

Test of cure	FOCUS 1		FOCUS 2		Integrated FOCUS 1 and 2
	Ceftaroline	Ceftriaxone	Ceftaroline	Ceftriaxone	Ceftaroline	Ceftriaxone
	Primary outcomes n/N (%)
Clinical evaluable	194/224 (86.6)*	244/291 (83.8)	193/235 (82)	166/215 (77)	387/459 (84)*	349/449 (77)
Modified intent to treat efficacy	244/291 (83)	23/300 (77)	235/289 (81)	206/273 (75)	479/580 (82)*	439/573 (76)
	Secondary outcomes
Microbiologically evaluable	62/69 (89)*	54/71 (76)	69/85 (81)	57/76 (75)	131/154 (85)*	111/147 (75)
Streptococcus pneumoniae	24/27 (88.9)	20/30 (66)	35/42 (83.3)	28/40 (70)	59/69 (85.5)	48/70 (68)
Streptococcus pneumoniae PCN resistant	2/2 (100)	0/1 (0)	2/2 (100)	2/8 (25)	4/4 (100)	2/9 (22)
Staphylococcus aureus	8/10 (80)	9/14 (64)	10/15 (66.7)	9/16 (56)	18/25 (72)	18/30 (60)
Haemophilus influenzae	4/5 (80)	7/10 (70)	13/15 (86)	13/14 (92)	17/20 (85)	20/24 (83)
Klebsiella pneumoniae	7/8 (87)	3/5 (60)	7/7 (100)	7/8 (87)	14/15 (93)	10/13 (76)
Escherichia coli	8/8 (100)	5/7 (71)	2/4 (50)	4/6 (66)	10/12 (83)	9/13 (69)
Microbiological modified intent to treat efficacy	66/75 (88)*	60/80 (75)	72/90 (80)	66/88 (75)	138/165 (83)	126/168 (75)
PORT risk class III	136/150 (90)*	113/142 (79)	113/137 (82)	104/132 (78)	249/287 (86)*	217/274 (79)
PORT risk class IV	58/74 (78)	70/92 (76)	80/98 (81)	62/83 (74)	138/172 (80)	132/175 (75)
End of therapy	Secondary outcomes
Clinical evaluable	197/224 (87)*	188/234 (80)	102/235 (86)	172/215 (80)

* Note: P < 0.05 when comparing ceftaroline versus ceftriax.

Abbreviations: PCN, penicillin; PORT, Pneumonia Outcomes Research Team.

SaderHSFritscheTRKanigaKGeYJonesRNAntimicrobial activity and spectrum of PPI-0903M (T-91825), a novel cephalosporin, tested against a worldwide collection of clinical strainsAntimicrob Agents Chemother20054983501351216048970

 PubMed Web of Science ®Google Scholar

GeYBiekDTalbotGHSahmDFIn vitro profiling of ceftaroline against a collection of recent bacterial clinical isolates from across the United StatesAntimicrob Agents Chemother20085293398340718625769

 PubMed Web of Science ®Google Scholar

BrownSDTraczewskiMMIn vitro antimicrobial activity of a new cephalosporin, ceftaroline, and determination of quality control ranges for MIC testingAntimicrob Agents Chemother20095331271127419114671

 PubMed Web of Science ®Google Scholar

SaravolatzLDPawlakJJohnsonLBIn vitro activity of oritavancin against community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA) and daptomycin-non-susceptible S. aureus (DNSSA)Int J Antimicrob Agents2010361697220413274

 PubMed Web of Science ®Google Scholar

JacobsMRGoodCEWindauARActivity of ceftaroline against recent emerging serotypes of Streptococcus pneumoniae in the United StatesAntimicrob Agents Chemother20105462716271920308374

 PubMed Web of Science ®Google Scholar

JonesRNFarrellDJMendesRESaderHSComparative ceftaroline activity tested against pathogens associated with community-acquired pneumonia: results from an international surveillance studyJ Antimicrob Chemother201166Suppl 3iii69iii8021482572

 PubMed Web of Science ®Google Scholar

KaushikDRathiSJainACeftaroline: a comprehensive updateInt J Antimicrob Agents201137538939521420284

 PubMed Web of Science ®Google Scholar