In Vitro Activity of Ceftobiprole against Aerobic and Anaerobic Strains Isolated from Diabetic Foot Infections

Abstract

Against 443 aerobic and anaerobic bacteria isolated from diabetic foot infections, ceftobiprole MICs (g/ml) at which 90% of the isolates tested were inhibited were as follows: methicillin-resistant Staphylococcus aureus, 1; methicillin-susceptible S. aureus and Staphylococcus lugdunensis, 0.5; Anaerococcus prevotii, 0.125; Finegoldia magna, 0.5; Peptoniphilus asaccharolyticus, 1; Peptostreptococcus anaerobius, 4; Escherichia coli and Enterobacter species, 0.125; Klebsiella species, 2; and Pseudomonas aeruginosa, 8.Diabetic foot infections (DFIs) are common complications and account for ϳ20% of all hospitalizations for Ͼ18 million diabetics in the United States (1, 2). Early-stage DFIs are generally due to Staphylococcus aureus, and 20% of hospitalized DFI patients grow methicillin-resistant S. aureus (MRSA) (7); more-advanced DFIs involve aerobic gram-negative rods, and 45% also involve anaerobes (4.1 to 5.8 bacterial species isolated per specimen, composed of 2.9 to 3.5 aerobes and 1.2 to 2.6 anaerobes) (6 Ceftobiprole (BAL 9141) is a new broad-spectrum pyrrolidinone cephem antimicrobial active against S. aureus bacteria, including MRSA and vancomycin-intermediate S. aureus, vancomycin-resistant Enterococcus faecalis (but not ampicillin-resistant enterococci), other gram-positive organisms, and many gram-negative rods except Proteus vulgaris or extended-spectrum beta-lactamase (ESBL)-producing strains of Enterobacteriaceae (3,5,8,9,15), but data on its activity against anaerobes are limited (14).Consequently, we studied the activity of ceftobiprole against 443 aerobic and anaerobic strains isolated from pretreatment cultures (2001 to 2004) obtained after debridement from patients with symptomatic, complicated DFIs at 52 domestic clinical study sites and sent to our lab via overnight courier. All isolates (Table 1) were identified by standard criteria (10, 11). Standard antimicrobial laboratory powders were supplied by the manufacturers and reconstituted accordingly.Anaerobic susceptibility testing was performed by the agar dilution method according to CLSI standard M11-A6 (12) with a final inoculum of 10 5 CFU/spot. Plates were incubated at 37°C for 44 to 48 h in an anaerobic chamber (Anaerobe Systems, California). Aerobic isolates were subcultured onto Trypticase soy blood agar and tested by the broth microdilution method using cation-adjusted Mueller-Hinton broth, with lysed horse blood supplementation for streptococci and corynebacteria (4, 13). The trays were prepared in-house with serial twofold dilutions of the drugs by using the Quick-Spense apparatus (Sally Spring Instrument Co. Inc., Germantown, MD) and stored at Ϫ70°C until use. Colonies were suspended from overnight growth and added to the trays for a final inoculum of approximately 5 ϫ 10 5 CFU/ml. The trays were incubated for 18 to 24 h and examined.Results are presented in Table 1. The ceftobiprole quality control strain MICs were as follows: S. aureus ATCC 29213, 0.25 g/ml, seven times; 0.5 g/ml, twice; Escherichia coli ATCC 25922, 0.03 g/ml, onc...

From Clinical Microbiology to Infection Pathogenesis: How Daring To Be Different Works forStaphylococcus lugdunensis

“…In addition, one S. lugdunensis isolate was resistant to erythromycin. There have also been single reports of S. lugdunensis isolates resistant to streptomycin (86), tetracycline (183), penicillin (183), gentamicin (83), ceftazidime (74), and aminoglycosides and macrolides (60). A single case report described the emergence of resistance to rifampin and ciprofloxacin that correlated with treatment of a persistent S. lugdunensis infection that manifested over 3 years as septic arthritis of both knees, vertebral osteomyelitis, and aortic and mitral valve endocarditis (98).…”

“…Fifteen bloodstream isolates exhibited susceptibility to many common antimicrobials, including penicillin (51). Fifteen S. lugdunensis isolates from diabetic foot infections were susceptible to eight out of nine agents tested, including ceftobiprole, a new broad-spectrum cephalosporin (74).…”

Emerging agents to combat complicated and resistant infections: focus on ceftobiprole

“…15,32 Ceftobiprole MIC 90 values of 8 to 16 µg/mL for ceftazidime-susceptible P. aeruginosa, while MIC 90 values of 16 to 64 µg/mL for ceftazidime-resistant isolates have been reported. 12,13,15,20 In the surveillance study published by Fristche et al 21 ceftobiprole was equal in potency to ceftazidime and 2-fold more potent than cefepime against P. aeruginosa. Pillar et al 18 reported that, as was observed with Enterobacteriaceae, the activity of ceftobiprole and cefepime against P. aeruginosa and Acinetobacter spp.…”

“…15 These results are consistent with those reported in other studies. 12,13,20 Ceftobiprole showed more activity than ceftriaxone against Citrobacter freundii and against Enterobacter cloacae.…”

“…8,9 Spectrum of activity Ceftobiprole is active against S. aureus, including MRSA and vancomycin-intermediate S. aureus (VISA), coagulase-negative staphylococci (CNS), Enterococcus species (including vancomycin-resistant but not ampicillinresistant enterococci), pneumococci, some anaerobes, and Gram-negative bacilli (with similar activity to third-and fourth-generation cephalosporins, with the exception of Proteus vulgaris). 5,[10][11][12][13][14] Ceftobiprole is not active against extended-spectrum beta-lactamase (ESBL) producing strains of Enterobacteriaceae. 13,15,16 Published MIC data for a range of microorganisms are shown in Table 1.…”