In Vitro Activities of Ceftobiprole and Doripenem Tested against Frequently Encountered Aerobic and Facultative Gram‐Positive and Gram‐Negative Bacterial Pathogens Isolated from Patients in Canadian Hospitals in 2007
Bibliographic record
Abstract
BACKGROUND: In 2008, ceftobiprole was approved by Health Canada for the treatment of patients with complicated skin and skin structure infections including diabetic foot infections; approval of ceftobiprole by the United States Food and Drug Administration is pending. Doripenem is currently under review by Health Canada and was approved by the United States Food and Drug Administration in 2007 for the treatment of patients with complicated intra‐abdominal infections and complicated urinary tract infections, including pyelonephritis. OBJECTIVES: To determine the in vitro activities of ceftobiprole and doripenem using a collection of frequently isolated aerobic and facultative bacteria cultured from patient blood, urine, respiratory and wound specimens in 12 Canadian hospitals in 2007. MEtHODS: Isolates were tested for their susceptibility to a panel of antimicrobial agents using the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS: Ceftobiprole inhibited all isolates of methicillin‐resistant Staphylococcus aureus (n=385), methicillin‐resistant Staphylococcus epidermidis (n=20), methicillin‐susceptible S aureus (n=1095) and methicillin‐susceptible S epidermidis (n=108) at a minimum inhibitory concentration (MIC) of 2 μg/mL or less; all isolates of Streptococcus pyogenes (n=105) were inhibited by ceftobiprole at 0.06 μg/mL or less. All isolates of S aureus (MIC 4 μg/mL or less) and S pyogenes (MIC 0.5 μg/mL or less) tested were susceptible to ceftobiprole. Greater than 99% of extended‐spectrum beta‐lactamase (ESBL)‐negative Escherichia coli (n=1528) and Klebsiella pneumoniae (n=436) were susceptible to ceftobiprole (MIC 1 μg/mL or less); against other genera/species of Enterobacteriaceae, susceptibility to ceftobiprole ranged from 80.7% for Enterobacter cloacae (n=166) to 99.2% for Proteus mirabilis (n=119). Ceftobiprole was less active against Pseudomonas aeruginosa (n=633) (90% of isolates inhibited at a concentration of 32 μg/mL [MIC90]) than Enterobacteriaceae. Doripenem inhibited 90% of isolates of E coli (n=1577) and K pneumoniae (n=456), including ESBL‐producing isolates (n=69), and E cloacae at a concentration of 0.06 μg/mL or less; doripenem and meropenem had MIC90s of 8 μg/mL for the isolates of P aeruginosa tested. Doripenem demonstrated in vitro activity indistinguishable from that of meropenem against Gram‐positive pathogens. CONCLUSIONS: All isolates of methicillin‐resistant S aureus tested were susceptible to ceftobiprole (MIC 4 μg/mL or less), differentiating it from any other currently marketed beta‐lactam. Doripenem demonstrated potent activity (MIC90 0.5 μg/mL or less) against all isolates of Enterobacteriaceae tested, including ESBL‐producing E coli and K pneumoniae, and as potent activity as meropenem (MIC90 8 μg/mL) against P aeruginosa. The current study demonstrated both ceftobiprole and doripenem to be promising broad‐spectrum antibacterial agents.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".