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. 2010 Jan 25;54(4):1627–1632. doi: 10.1128/AAC.01788-09

In Vitro Activity of Ceftaroline against 623 Diverse Strains of Anaerobic Bacteria ▿

D M Citron 1,*, K L Tyrrell 1, C V Merriam 1, E J C Goldstein 1,2
PMCID: PMC2849373  PMID: 20100877

Abstract

The in vitro activities of ceftaroline, a novel, parenteral, broad-spectrum cephalosporin, and four comparator antimicrobials were determined against anaerobic bacteria. Against Gram-positive strains, the activity of ceftaroline was similar to that of amoxicillin-clavulanate and four to eight times greater than that of ceftriaxone. Against Gram-negative organisms, ceftaroline showed good activity against β-lactamase-negative strains but not against the members of the Bacteroides fragilis group. Ceftaroline showed potent activity against a broad spectrum of anaerobes encountered in respiratory, skin, and soft tissue infections.

With the continuing emergence of novel patterns of resistance to commonly used antimicrobial agents, alternative therapies are needed to treat serious infections. Ceftaroline is a novel, parenteral, broad-spectrum cephalosporin that exhibits bactericidal activity against Gram-positive organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus, and multidrug-resistant Streptococcus pneumoniae (MDRSP) strains, as well as common Gram-negative pathogens (8, 12, 14, 16, 18-22). Ceftaroline is currently in development for the treatment of complicated skin and skin structure infections and community-acquired pneumonia.

Anaerobic bacteria are common pathogens in a variety of pleuropulmonary infections, including aspiration pneumonia, lung abscesses, and empyema (1, 3, 6, 15). However, many laboratories do not culture for anaerobes (9), diminishing awareness of the role of anaerobes in these infections. The main anaerobic pathogens isolated from these infections include Prevotella melaninogenica (∼25%), Prevotella intermedia (∼30%), Fusobacterium species (∼39%), Gram-positive cocci (∼30%), and Veillonella species (∼35%) (7). Cephalosporins such as cefoxitin have been used for the therapy of aspiration pneumonias. Although cefoxitin is active against most respiratory anaerobes, it has poor activity against the newer resistant strains of members of the family Enterobacteriaceae and MRSA. The activity of ceftaroline against Gram-positive anaerobes is similar to that of amoxicillin-clavulanate, and non-β-lactamase-producing Gram-negative strains generally have low ceftaroline MICs (present study), suggesting that ceftaroline might have an adequate spectrum of activity for therapy for some cases of aspiration pneumonia.

To investigate the broader potential of ceftaroline, we compared its in vitro activity against 623 unique clinical isolates of anaerobic bacteria representing 5 Gram-negative bacterial genera and 17 Gram-positive bacterial genera to the activities of ceftriaxone, metronidazole, clindamycin, and amoxicillin-clavulanate.

The reference agar dilution procedure described in CLSI document M11-A7 was used (5). The organisms were recovered from a variety of clinical specimens and were stored at −70°C in 20% skim milk. Identification was accomplished by standard phenotypic methods or by partial 16S rRNA gene sequencing for strains that could not be identified phenotypically (13, 17). Quality control strains Bacteroides fragilis ATCC 25285, Clostridium difficile ATCC 700057, and Staphylococcus aureus ATCC 29213 were included on each day of testing.

The antimicrobial agents were obtained as follows: ceftaroline was from Forest Laboratories, Inc. (New York, NY); ceftriaxone, vancomycin, and metronidazole were from Sigma-Aldrich, Inc. (St. Louis, MO); and amoxicillin and clavulanate were from GlaxoSmithKline (Research Triangle Park, NC). The agar dilution plates were prepared on the day of testing.

The strains were taken from the freezer and transferred twice to ensure purity and good growth. Cell paste from 48-h cultures was suspended in brucella broth to achieve the turbidity of a 0.5 McFarland standard, and the mixture was applied to plates with a Steers replicator to deliver approximately 105 CFU/spot. The plates were incubated for 44 h at 37°C in an anaerobic chamber. The MIC was the lowest concentration that completely inhibited growth or that resulted in a marked reduction in growth compared with that for the drug-free growth control (5).

A summary showing the MIC range, MIC50, MIC90, and percent susceptibility is presented in Table 1. The cumulative ceftaroline MIC distributions for all groups of strains are displayed in Table 2.

TABLE 1.

Summary of ceftaroline and comparator agent MICs, by species or group

Organism No. of isolates MIC (μg/ml)
 % susceptible % resistant
Range 50% 90%
Gram-negative bacteria
    Bacteroides fragilis 30
        Ceftaroline 4->64 16 64 NAa NA
        Ceftriaxone (≤16, ≥64)b 4->64 32 64 27 43
        Clindamycin (≤2, ≥8) 0.06->128 1 128 63 37
        Metronidazole (≤8, ≥32) 0.25-2 1 2 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.5-64 0.5 2 93 7
    Bacteroides thetaiotaomicron 20
        Ceftaroline 32->64 64 >64 NA NA
        Ceftriaxone (≤16, ≥64) 64->64 >64 >64 0 100
        Clindamycin (≤2, ≥8) 0.06->128 4 128 45 45
        Metronidazole (≤8, ≥32) 0.5-1 1 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.5-8 2 4 95 0
    Bacteroides fragilis group spp.c 26
        Ceftaroline 2->64 64 >64 NA NA
        Ceftriaxone (≤16, ≥64) 4->64 >64 >64 23 58
        Clindamycin (≤2, ≥8) 0.06->128 4 >128 42 50
        Metronidazole (≤8, ≥32) 0.5-2 1 2 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.125-32 2 8 77 4
    Prevotella bivia 20
        Ceftaroline 0.125->64 2 64 NA NA
        Ceftriaxone (≤16, ≥64) 0.125->64 2 >64 75 15
        Clindamycin (≤2, ≥8) 0.03->128 ≤0.03 >128 85 15
        Metronidazole (≤8, ≥32) ≤0.03-4 1 2 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-4 0.25 4 100 0
    Prevotella buccae 20
        Ceftaroline 0.125->64 0.5 64 NA NA
        Ceftriaxone (≤16, ≥64) 0.125->64 0.25 64 50 30
        Clindamycin (≤2, ≥8) ≤0.03->128 ≤0.03 >128 80 20
        Metronidazole (≤8, ≥32) 0.25-1 0.5 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.06-4 0.06 1 100 0
    Prevotella melaninogenica 18
        Ceftaroline ≤0.008-32 2 32 NA NA
        Ceftriaxone (≤16, ≥64) 0.03-32 2 32 78 0
        Clindamycin (≤2, ≥8) ≤0.03->128 ≤0.03 >128 72 28
        Metronidazole (≤8, ≥32) 0.06-2 0.5 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-2 0.125 2 100 0
    Prevotella intermedia 20
        Ceftaroline ≤0.008-64 1 16 NA NA
        Ceftriaxone (≤16, ≥64) 0.03-64 1 16 80 10
        Clindamycin (≤2, ≥8) ≤0.03->128 ≤0.03 16 85 15
        Metronidazole (≤8, ≥32) 0.125-2 0.25 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-1 0.06 0.5 100 0
    Prevotella spp.d 20
        Ceftaroline ≤0.008-32 2 32 NA NA
        Ceftriaxone (≤16, ≥64) ≤0.008-64 1 8 90 5
        Clindamycin (≤2, ≥8) ≤0.03->128 ≤0.03 128 70 30
        Metronidazole (≤8, ≥32) 0.06-8 0.5 2 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-2 0.125 1 100 0
    Porphyromonas asaccharolytica 21
        Ceftaroline ≤0.008-0.5 0.015 0.03 NA NA
        Ceftriaxone (≤16, ≥64) ≤0.008-1 0.06 0.06 100 0
        Clindamycin (≤2, ≥8) ≤0.03->128 ≤0.03 >128 81 19
        Metronidazole (≤8, ≥32) ≤0.03-0.25 0.06 0.125 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-≤0.03 ≤0.03 ≤0.03 100 0
    Porphyromonas somerae 10
        Ceftaroline ≤0.008-16 0.015 16 NA NA
        Ceftriaxone (≤16, ≥64) ≤0.008-64 0.015 64 80 20
        Clindamycin (≤2, ≥8) ≤0.03->128 ≤0.03 >128 80 20
        Metronidazole (≤8, ≥32) 0.25-0.5 0.5 0.5 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.5 ≤0.03 0.125 100 0
    Fusobacterium nucleatum 22
        Ceftaroline ≤0.008-0.125 ≤0.008 0.125 NA NA
        Ceftriaxone (≤16, ≥64) 0.015-1 0.125 0.5 100 0
        Clindamycin (≤2, ≥8) ≤0.03-0.5 0.06 0.06 100 0
        Metronidazole (≤8, ≥32) ≤0.03-0.25 ≤0.03 0.25 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.5 ≤0.03 0.06 100 0
    Fusobacterium necrophorum 22
        Ceftaroline 0.015-0.06 0.03 0.06 NA NA
        Ceftriaxone (≤16, ≥64) ≤0.008-0.125 0.015 0.03 100 0
        Clindamycin (≤2, ≥8) ≤0.03-0.25 ≤0.03 0.06 100 0
        Metronidazole (≤8, ≥32) 0.06-0.25 0.125 0.25 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-1 0.125 0.5 100 0
    Fusobacterium mortiferum 10
        Ceftaroline 1-64 8 32 NA NA
        Ceftriaxone (≤16, ≥64) 16->64 >64 >64 10 90
        Clindamycin (≤2, ≥8) ≤0.03-0.25 0.06 1 100 0
        Metronidazole (≤8, ≥32) 0.25-2 0.5 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.25-8 4 8 80 0
    Fusobacterium varium 10
        Ceftaroline 0.015-0.5 0.25 0.5 NA NA
        Ceftriaxone (≤16, ≥64) 0.15-8 1 8 100 0
        Clindamycin (≤2, ≥8) 0.06-64 2 4 90 10
        Metronidazole (≤8, ≥32) 0.25-0.5 0.25 0.5 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.125-2 1 2 100 0
    Veillonella spp. 19
        Ceftaroline 0.015-1 0.125 0.5 NA NA
        Ceftriaxone (≤16, ≥64) 0.03-8 4 8 79 16
        Clindamycin (≤2, ≥8) ≤0.03->128 0.125 128 79 21
        Metronidazole (≤8, ≥32) 1-8 2 8 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-8 0.25 4 95 0
Gram-positive bacteria
    Anaerococcus prevotii-Anaerococcus tetradiuse 20
        Ceftaroline ≤0.008-2 0.03 0.125 NA NA
        Ceftriaxone (≤16, ≥64) 0.03-32 0.25 0.5 95 0
        Clindamycin (≤2, ≥8) ≤0.03->128 0.5 128 60 40
        Metronidazole (≤8, ≥32) 0.125-4 1 2 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-8 ≤0.03 0.125 95 0
    Finegoldia magna 19
        Ceftaroline 0.03-1 0.25 0.5 NA NA
        Ceftriaxone (≤16, ≥64) 2-8 4 8 100 0
        Clindamycin (≤2, ≥8) 0.06->128 2 >128 53 37
        Metronidazole (≤8, ≥32) 0.06-1 0.5 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.25 0.125 0.25 100 0
    Parvimonas micra 22
        Ceftaroline 0.015-0.5 0.06 0.25 NA NA
        Ceftriaxone (≤16, ≥64) 0.125-2 0.5 1 100 0
        Clindamycin (≤2, ≥8) 0.06-128 0.25 16 86 14
        Metronidazole (≤8, ≥32) 0.125-1 0.25 0.25 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-1 0.125 0.5 100 0
    Peptoniphilus asaccharolyticus 21
        Ceftaroline ≤0.008-0.25 0.06 0.25 NA NA
        Ceftriaxone (≤16, ≥64) 0.03-1 0.125 0.25 100 0
        Clindamycin (≤2, ≥8) ≤0.03->128 0.125 >128 76 24
        Metronidazole (≤8, ≥32) 0.125-2 1 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.06 ≤0.03 0.06 100 0
    Peptostreptococcus anaerobius-Peptostreptococcus stomatisf 23
        Ceftaroline 0.125-8 0.5 4 NA NA
        Ceftriaxone (≤16, ≥64) 0.5-16 2 8 100 0
        Clindamycin (≤2, ≥8) ≤0.03-32 ≤0.03 0.25 96 4
        Metronidazole (≤8, ≥32) 0.125-1 0.5 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-32 0.125 0.5 91 9
    Anaerobic Gram-positive coccig 22
        Ceftaroline ≤0.008-8 0.06 1 NA NA
        Ceftriaxone (≤16, ≥64) 0.03-64 0.25 16 91 5
        Clindamycin (≤2, ≥8) ≤0.03->128 0.125 64 73 27
        Metronidazole (≤8, ≥32) 0.25->64 1 4 91 9
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-4 0.06 0.5 100 0
    Actinomyces spp.h 13
        Ceftaroline ≤0.008-0.25 0.015 0.25 NA NA
        Ceftriaxone (≤16, ≥64) ≤0.008-0.5 0.125 0.5 100 0
        Clindamycin (≤2, ≥8) ≤0.03->128 0.06 128 77 23
        Metronidazole (≤8, ≥32) >32->32 >32 >32 0 100
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.5 0.06 0.5 100 0
    Propionibacterium acnes 20
        Ceftaroline ≤0.008-0.125 ≤0.008 0.06 NA NA
        Ceftriaxone (≤16, ≥64) ≤0.008-0.125 0.015 0.06 100 0
        Clindamycin (≤2, ≥8) 0.125->128 0.125 0.125 95 5
        Metronidazole (≤8, ≥32) >32->32 >32 >32 0 100
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.25 ≤0.03 0.06 100 0
    Propionibacterium avidum 11
        Ceftaroline 0.015-0.25 0.25 0.25 NA NA
        Ceftriaxone (≤16, ≥64) 0.03-0.5 0.25 0.5 100 0
        Clindamycin (≤2, ≥8) 0.125-0.5 0.25 0.25 100 0
        Metronidazole (≤8, ≥32) >32->32 >32 >32 0 100
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.25 0.25 0.25 100 0
    Eggerthella lenta 17
        Ceftaroline 2-16 8 16 NA NA
        Ceftriaxone (≤16, ≥64) 16->64 >64 >64 6 94
        Clindamycin (≤2, ≥8) 0.06-8 0.5 2 94 6
        Metronidazole (≤8, ≥32) 0.5-1 0.5 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.5-1 1 1 100 0
    “Eubacterium” groupi 25
        Ceftaroline 0.015-0.25 0.125 0.25 NA NA
        Ceftriaxone (≤16, ≥64) 0.03-16 0.5 2 100 0
        Clindamycin (≤2, ≥8) ≤0.03->128 0.06 2 92 8
        Metronidazole (≤8, ≥32) 0.125-4 0.5 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.5 0.125 0.25 100 0
    Lactobacillus casei-Lactobacillus rhamnosus groupj 10
        Ceftaroline 0.25-8 0.5 1 NA NA
        Ceftriaxone (≤16, ≥64) 8->64 32 64 40 30
        Clindamycin (≤2, ≥8) 0.25-2 1 2 100 0
        Metronidazole (≤8, ≥32) >64->64 >64 >64 0 100
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.25-2 0.5 1 100 0
    Clostridium perfringens 20
        Ceftaroline ≤0.008-0.5 0.125 0.25 NA NA
        Ceftriaxone (≤16, ≥64) ≤0.008-4 0.5 2 100 0
        Clindamycin (≤2, ≥8) ≤0.03-2 0.25 1 100 0
        Metronidazole (≤8, ≥32) 0.5-4 2 4 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.125 0.03 0.125 100 0
    Clostridium ramosum 21
        Ceftaroline 1-2 1 1 NA NA
        Ceftriaxone (≤16, ≥64) 0.25-0.5 0.25 0.5 100 0
        Clindamycin (≤2, ≥8) 1->128 4 8 24 43
        Metronidazole (≤8, ≥32) 0.5-2 1 1 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-0.25 0.06 0.25 100 0
    Clostridium innocuum 21
        Ceftaroline 0.5-4 1 2 NA NA
        Ceftriaxone (≤16, ≥64) 8-32 8 16 95 0
        Clindamycin (≤2, ≥8) 0.125->128 0.5 >128 86 14
        Metronidazole (≤8, ≥32) 0.5-4 1 4 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.125-1 0.5 0.5 100 0
    Clostridium clostridioforme groupk 20
        Ceftaroline 0.25-2 1 2 NA NA
        Ceftriaxone (≤16, ≥64) 2->64 4 32 75 10
        Clindamycin (≤2, ≥8) ≤0.03-4 0.5 2 95 0
        Metronidazole (≤8, ≥32) ≤0.03-0.25 0.06 0.25 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) 0.25-1 0.5 0.5 100 0
    Clostridium spp., otherl 24
        Ceftaroline 0.015-16 0.5 16 NA NA
        Ceftriaxone (≤16, ≥64) 0.015->64 2 64 75 21
        Clindamycin (≤2, ≥8) ≤0.03->128 2 128 54 38
        Metronidazole (≤8, ≥32) 0.125-4 0.5 4 100 0
        Amoxicillin-clavulanate (≤4/2, ≥16/8) ≤0.03-2 0.125 1 100 0
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a

NA, not applicable.

b

Values in parentheses are the breakpoints for susceptibility, resistance (in μg/ml).

c

Bacteroides caccae (n = 6), B. distasonis (n = 3), B. merdae (n = 1), B. ovatus (n = 5), B. uniformis (n = 4), and B. vulgatus (n = 7).

d

Prevotella bergensis (n = 2), P. corporis (n = 1), P. denticola (n = 5), P. disiens (n = 5), P. loescheii (n = 3), P. nanceiensis (n = 2), P. oris (n = 1), and P. tannerae (n = 1).

e

Anaerococcus prevotii (n = 12) and A. tetradius (n = 8).

f

Peptostreptococcus anaerobius (n = 17) and P. stomatis (n = 6).

g

Anaerococcus lactolyticus (n = 1), Anaerococcus murdochii (n = 1), Anaerococcus octavius (n = 1), Anaerococcus vaginalis (n = 5), Anaerococcus species, no PCR match (n = 3), Gemella morbillorum (n = 1), Gemella sanguinis (n = 1), Peptoniphilus harei (n = 7), and Peptoniphilus lacrimalis (n = 2).

h

Actinomyces israelii (n = 1), A. meyeri (n = 2), A. neuii subsp. anitratus (n = 2), A. odontolyticus (n = 3), and A. turicensis (n = 5).

i

Atopobium parvulum (n = 1), Collinsella aerofaciens (n = 4), Eubacterium contortum (n = 1), Eubacterium cylindroides (n = 1), Eubacterium limosum (n = 8), Eubacterium saburreum (n = 2), Mogibacterium timidum (n = 3), Slackia exigua (n = 4), and Solobacterium moorei (n = 1).

j

Lactobacillus casei (n = 3) and L. rhamnosus (n = 7).

k

Clostridium aldenense (n = 4), C. bolteae (n = 5), C. citroniae (n = 3), C. hathewayi (n = 4), and C. clostridioforme (n = 4).

l

Clostridium barati (n = 1), C. bifermentans (n = 1), C. butyricum (n = 2), C. cadaveris (n = 2), C. celerecrescens (n = 1), C. difficile (n = 4), C. glycolicum (n = 2), C. hylemonae (n = 2), C. paraputrificum (n = 2), C. sordellii (n = 1), C. sphenoides (n = 1), C. subterminale (n = 1), C. symbiosum (n = 2), and C. tertium (n = 2).

TABLE 2.

Ceftaroline MIC distributions for Gram-negative and Gram-positive anaerobes

Organism group and organism Total Cumulative % of isolates with the following ceftaroline MIC (μg/ml):
≤0.008 0.015 0.03 0.06 0.125 0.25 0.5 1 2 4 8 16 32 64 >64
Gram-negative anaerobes
    Bacteroides fragilis 30 7 37 63 73 100
    Bacteroides fragilis group, othera 46 4 7 9 20 37 57 100
    Prevotella speciesb 98 3.1 4.1 12 18 27 37 43 50 55 63 74 82 91 96 100
    Porphyromonas speciesc 31 13 71 81 84 87 90 100
    Fusobacterium nucleatum/Fusobacterium necrophorumd 44 25 50 77 89 100
    Fusobacterium mortiferum 10 10 20 70 80 90 100
    Fusobacterium varium 10 20 30 80 100
    Veillonella species 19 5 32 84 89 95 100
        Total 288
Gram-positive anaerobes
    All Gram-positive coccie 127 10 20 30 47 61 82 92 96 97 98 100
    Propionibacterium and Actinomyces speciesf 44 43 57 64 77 82 100
    Lactobacillus casei-Lactobacillus rhamnosus groupg 10 20 80 90 100
    Eggerthella lenta 17 6 12 88 100
    “Eubacterium” group, otherh 25 8 20 28 92 100
    Clostridium perfringens 20 15 35 60 90 100
    Clostridium ramosum 21 90 100
    Clostridium innocuum 21 29 67 95 100
    Clostridium clostridioforme groupi 20 15 35 80 100
    Clostridium species, otherj 24 4 8 21 46 54 67 75 83 100
        Total 329
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a

Bacteroides thetaiotaomicron (n = 20), B. caccae (n = 6), B. distasonis (n = 3), B. merdae (n = 1), B. ovatus (n = 5), B. uniformis (n = 4), and B. vulgatus (n = 7).

b

Prevotella bivia (n = 20), P. buccae (n = 20), P. melaninogenica (n = 18), P. intermedia (n = 20), P. bergensis (n = 2), P. corporis (n = 1), P. denticola (n = 5), P. disiens (n = 5), P. loescheii (n = 3), P. nanceiensis (n = 2), P. oris (n = 1), and P. tannerae (n = 1).

c

Porphyromonas asaccharolytica (n = 21) and P. somerae (n = 10).

d

Fusobacterium nucleatum (n = 22) and F. necrophorum (n = 22).

e

Finegoldia magna (n = 19), Parvimonas micra (n = 22), Peptostreptococcus anaerobius (n = 17), Peptostreptococcus stomatis (n = 6), Anaerococcus prevotii (n = 12), Anaerococcus tetradius (n = 8), Anaerococcus lactolyticus (n = 1), Anaerococcus murdochii (n = 1), Anaerococcus octavius (n = 1), Anaerococcus vaginalis (n = 5), Anaerococcus species, no PCR match (n = 3), Gemella morbillorum (n = 1), Gemella sanguinis (n = 1), Peptoniphilus asaccharolyticus (n = 21), Peptoniphilus harei (n = 7), and Peptoniphilus lacrimalis (n = 2).

f

Propionibacterium acnes (n = 21), Propionibacterium avidum (n = 11), Actinomyces israelii (n = 1), Actinomyces meyeri (n = 2), Actinomyces neuii subsp. anitratus (n = 2), Actinomyces odontolyticus (n = 3), and Actinomyces turicensis (n = 5).

g

Lactobacillus casei (n = 3) and L. rhamnosus (n = 7).

h

Atopobium parvulum (n = 1), Collinsella aerofaciens (n = 4), Eubacterium contortum (n = 1), Eubacterium cylindroides (n = 1), Eubacterium limosum (n = 8), Eubacterium saburreum (n = 2), Mogibacterium timidum (n = 3), Slackia exigua (n = 4), and Solobacterium moorei (n = 1).

i

Clostridium aldenense (n = 4), C. bolteae (n = 5), C. citroniae (n = 3), C. hathewayi (n = 4), and C. clostridioforme (n = 4).

j

Clostridium barati (n = 1), C. bifermentans (n = 1), C. butyricum (n = 2), C. cadaveris (n = 2), C. celerecrescens (n = 1), C. difficile (n = 4), C. glycolicum (n = 2), C. hylemonae (n = 2), C. paraputrificum (n = 2), C. sordellii (n = 1), C. sphenoides (n = 1), C. subterminale (n = 1), C. symbiosum (n = 2), and C. tertium (n = 2).

The ceftaroline MIC50s for B. fragilis and other B. fragilis group species were 16 and 64 μg/ml, respectively, and the MIC90s were >64 μg/ml for both for B. fragilis and other B. fragilis group species. Ceftaroline was effective against all other Gram-negative, non-β-lactamase-producing strains and had activity similar to that of ceftriaxone. For Prevotella species, the ceftaroline MICs varied according to β-lactamase production, with the MIC50 and the MIC90 being 1 and 32 μg/ml, respectively. Most Porphyromonas species were susceptible to ceftaroline at ≤0.5 μg/ml; four β-lactamase-positive strains of Porphyromonas somerae (previously Porphyromonas levii), however, had ceftaroline MICs of 8 to 16 μg/ml. Fusobacterium nucleatum and Fusobacterium necrophorum, including two β-lactamase-positive strains, had a ceftaroline MIC50 and a ceftaroline MIC90 of 0.015 and 0.125 μg/ml, respectively. The bile-resistant Fusobacterium varium strains were susceptible to ceftaroline, with the highest MIC observed being 0.5 μg/ml, whereas Fusobacterium mortiferum had high MICs of ceftaroline (MIC90, 32 μg/ml), ceftriaxone (MIC90, >64 μg/ml), and amoxicillin-clavulanate (MIC90, 8 μg/ml). All Veillonella species were inhibited by ≤1 μg/ml ceftaroline.

Almost all of the Gram-negative species were susceptible to metronidazole; four strains of Veillonella species and one strain of Prevotella nanceiensis, however, showed elevated MICs of 4 to 8 μg/ml. Clindamycin resistance was present in 37% of B. fragilis strains, 43% of Bacteroides thetaiotaomicron strains, 45% of B. fragilis group species, 21% of Prevotella species, and 19% of Porphyromonas asaccharolytica strains. Resistance to amoxicillin-clavulanate at >8/4 μg/ml was present in one B. fragilis strain and one Bacteroides ovatus strain, both of which were also resistant to imipenem; however, 19% of the B. fragilis group species showed an intermediate-susceptible amoxicillin-clavulanate MIC.

Ceftaroline exhibited excellent activity against Gram-positive strains. The MIC50 and MIC90 for 127 strains of Gram-positive cocci were 0.125 and 0.5 μg/ml, respectively; and the MIC50 and MIC90 for 44 strains of Propionibacterium acnes, Propionibacterium avidum, and Actinomyces species were 0.015 and 0.25 μg/ml, respectively. The MIC50 and MIC90 for 106 strains of Clostridium species were 0.5 and 2 μg/ml, respectively, with higher MICs of 8 to 16 μg/ml being noted for 4 strains of Clostridium difficile, 1 strain of Clostridium celerecrescens, and 1 strain of Clostridium tertium. The MIC50 and MIC90 for 10 strains of vancomycin-resistant lactobacilli were 0.5 and 1 μg/ml, respectively. All “Eubacterium” group Gram-positive rods except Eggerthella lenta were inhibited by ≤0.25 μg/ml; the MIC50 and MIC90 for Eggerthella lenta were 8 and 16 μg/ml, respectively. Ceftaroline was four- to eightfold more active than ceftriaxone against Gram-positive organisms, with the MICs being the most similar to those of amoxicillin-clavulanate.

Clindamycin resistance was present in 37% of the Finegoldia magna strains and 40% of the strains in the Anaerococcus prevotii and Anaerococcus tetradius groups. All strains of Actinomyces, Propionibacterium, and Lactobacillus were resistant to metronidazole, as were one strain of anaerobic Gemella morbillorum and one strain of Gemella sanguinis. All except two Gram-positive strains were susceptible to amoxicillin-clavulanate; the exceptions were two strains of Peptostreptococcus anaerobius (MICs, 32 μg/ml).

Ceftaroline has been demonstrated to have excellent activity against strains commonly encountered in skin and respiratory infections, including MRSA, group A Streptococcus, MDRSP, and non-extended-spectrum β-lactamase (ESBL)-producing members of the family Enterobacteriaceae (8, 12, 14, 16, 18-22). The present study is the first to focus on the activity of ceftaroline against anaerobes and expands the known spectrum of species against which ceftaroline shows activity. The findings reported here are consistent with those of a limited study by Sader et al. (21).

Although ceftaroline has a low level of activity against most Bacteroides isolates, its use in combination with a β-lactamase inhibitor might overcome this resistance and increase the clinical potential of the use of ceftaroline against intra-abdominal infections and some skin and soft tissue infections. Many skin infections contain anaerobes that are predominantly Gram-positive anaerobic cocci and relatively few Bacteroides species (2, 10), suggesting that ceftaroline may have activity in these instances as well.

Our study confirmed the increasing resistance to clindamycin currently being reported by many investigators. Of particular interest was the resistance demonstrated by 2 of 19 strains of P. asaccharolytica, a species previously thought to be very susceptible to clindamycin (11). Additionally, four strains of P. somerae were β-lactamase producers, which is of interest because most studies do not report MICs for Porphyromonas and, to date, β-lactamase-producing strains have been a rare finding. We also noted an increase in the number of B. fragilis group strains with amoxicillin-clavulanate MICs reaching the intermediate level, similar to the increase in the ampicillin-sulbactam MICs reported in the CLSI M11-A7 supplement, which includes an antibiogram for the B. fragilis group (4).

Except for Bacteroides species and β-lactamase-producing Prevotella isolates, ceftaroline showed potent activity against a broad spectrum of anaerobic bacteria frequently recovered from a variety of clinical infections.

Acknowledgments

This study was supported by Forest Laboratories, Inc. Scientific Therapeutics Information, Inc., provided editorial assistance that was funded by Forest Laboratories, Inc.

Footnotes

▿

Published ahead of print on 25 January 2010.

REFERENCES

  • 1.Bartlett, J. G.1993. Anaerobic bacterial infections of the lung and pleural space. Clin. Infect. Dis. 16(Suppl. 4):S248-S255. [DOI] [PubMed] [Google Scholar]
  • 2.Citron, D. M., E. J. Goldstein, C. V. Merriam, B. A. Lipsky, and M. A. Abramson.2007. Bacteriology of moderate-to-severe diabetic foot infections and in vitro activity of antimicrobial agents. J. Clin. Microbiol. 45:2819-2828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Civen, R., H. Jousimies-Somer, M. Marina, L. Borenstein, H. Shah, and S. M. Finegold.1995. A retrospective review of cases of anaerobic empyema and update of bacteriology. Clin. Infect. Dis. 20(Suppl. 2):S224-S229. [DOI] [PubMed] [Google Scholar]
  • 4.Clinical and Laboratory Standards Institute.2009. Acceptable anaerobe control strain ranges for minimal inhibitory concentration determination by broth microdilution and agar dilution testing and cumulative antimicrobial susceptibility report for Bacteroides fragilis group; informational supplement. CLSI document M11-S1. Clinical and Laboratory Standards Institute, Wayne, PA.
  • 5.Clinical and Laboratory Standards Institute.2007. Methods for antimicrobial susceptibility testing of anaerobic bacteria; approved standard, 7th ed. CLSI document M11-A7. Clinical and Laboratory Standards Institute, Wayne, PA.
  • 6.El-Solh, A. A., C. Pietrantoni, A. Bhat, A. T. Aquilina, M. Okada, V. Grover, and N. Gifford.2003. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am. J. Respir. Crit. Care Med. 167:1650-1654. [DOI] [PubMed] [Google Scholar]
  • 7.Finegold, S. M.1991. Aspiration pneumonia. Rev. Infect. Dis. 13(Suppl. 9):S737-S742. [DOI] [PubMed] [Google Scholar]
  • 8.Ge, Y., D. Biek, G. H. Talbot, and D. F. Sahm.2008. In vitro profiling of ceftaroline against a collection of recent bacterial clinical isolates from across the United States. Antimicrob. Agents Chemother. 52:3398-3407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Goldstein, E. J., D. M. Citron, P. J. Goldman, and R. J. Goldman.2008. National hospital survey of anaerobic culture and susceptibility methods. III. Anaerobe 14:68-72. [DOI] [PubMed] [Google Scholar]
  • 10.Goldstein, E. J., D. M. Citron, C. V. Merriam, Y. Warren, K. L. Tyrrell, and R. M. Gesser.2002. General microbiology and in vitro susceptibility of anaerobes isolated from complicated skin and skin-structure infections in patients enrolled in a comparative trial of ertapenem versus piperacillin-tazobactam. Clin. Infect. Dis. 35:S119-S125. [DOI] [PubMed] [Google Scholar]
  • 11.Hecht, D. W.2004. Prevalence of antibiotic resistance in anaerobic bacteria: worrisome developments. Clin. Infect. Dis. 39:92-97. [DOI] [PubMed] [Google Scholar]
  • 12.Jacqueline, C., J. Caillon, V. Le Mabecque, A. F. Miegeville, A. Hamel, D. Bugnon, J. Y. Ge, and G. Potel.2007. In vivo efficacy of ceftaroline (PPI-0903), a new broad-spectrum cephalosporin, compared with linezolid and vancomycin against methicillin-resistant and vancomycin-intermediate Staphylococcus aureus in a rabbit endocarditis model. Antimicrob. Agents Chemother. 51:3397-3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Jousimies-Somer, H. R., P. Summanen, D. M. Citron, E. J. Baron, H. M. Wexler, and S. M. Finegold.2002. Wadsworth-KTL anaerobic bacteriology manual. Star Publishing, Belmont, CA.
  • 14.Kanafani, Z. A., and G. R. Corey.2009. Ceftaroline: a cephalosporin with expanded Gram-positive activity. Future Microbiol. 4:25-33. [DOI] [PubMed] [Google Scholar]
  • 15.Marina, M., C. A. Strong, R. Civen, E. Molitoris, and S. M. Finegold.1993. Bacteriology of anaerobic pleuropulmonary infections: preliminary report. Clin. Infect. Dis. 16(Suppl. 4):S256-S262. [DOI] [PubMed] [Google Scholar]
  • 16.Morrissey, I., Y. Ge, and R. Janes.2009. Activity of the new cephalosporin ceftaroline against bacteraemia isolates from patients with community-acquired pneumonia. Int. J. Antimicrob. Agents 33:515-519. [DOI] [PubMed] [Google Scholar]
  • 17.Murray, P. R., E. J. Baron, J. H. Jorgensen, M. L. Landry, and M. A. Pfaller.2007. Manual of clinical microbiology, 9th ed. ASM Press, Washington, DC.
  • 18.Mushtaq, S., M. Warner, Y. Ge, K. Kaniga, and D. M. Livermore.2007. In vitro activity of ceftaroline (PPI-0903M, T-91825) against bacteria with defined resistance mechanisms and phenotypes. J. Antimicrob. Chemother. 60:300-311. [DOI] [PubMed] [Google Scholar]
  • 19.Parish, D., and N. Scheinfeld.2008. Ceftaroline fosamil, a cephalosporin derivative for the potential treatment of MRSA infection. Curr. Opin. Invest. Drugs 9:201-209. [PubMed] [Google Scholar]
  • 20.Sader, H. S., T. R. Fritsche, and R. N. Jones.2008. Antimicrobial activities of ceftaroline and ME1036 tested against clinical strains of community-acquired methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 52:1153-1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Sader, H. S., T. R. Fritsche, K. Kaniga, Y. Ge, and R. N. Jones.2005. Antimicrobial activity and spectrum of PPI-0903M (T-91825), a novel cephalosporin, tested against a worldwide collection of clinical strains. Antimicrob. Agents Chemother. 49:3501-3512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Talbot, G. H., D. Thye, A. Das, and Y. Ge.2007. Phase 2 study of ceftaroline versus standard therapy in treatment of complicated skin and skin structure infections. Antimicrob. Agents Chemother. 51:3612-3616. [DOI] [PMC free article] [PubMed] [Google Scholar]

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