In Vitro Activity of Carbapenems Alone and in Combination With Amikacin Against KPC-Producing Klebsiella Pneumoniae
Bibliographic record
Abstract
BACKGROUND: Although carbapenems are the primary treatment strategy for invasive infections caused by ESBL bacteria, case reports of these pathogens with reduced carbapenem susceptibility have emerged. One potential treatment modality is to optimize the use of anti-infectives with combination therapy. We evaluated the activity of carbapenems alone and in combination with amikacin against these clinical isolates. METHODS: Time-kill studies evaluated ertapenem (ETP), imipenem (IPM), meropenem (MEM), and amikacin (AMK) against 4 non-duplicate clinical isolates of Klebsiella pneumoniae that were resistant to these antibiotics. Synergy was defined as ≥ 2 log(10) decrease CFU/mL at 24 h for the combination when compared with the most active single agent of the combination, plus the number of surviving organisms for the antimicrobial combination was ≥ 2 log(10) less than the initial inoculum. RESULTS: All isolates carried bla(KPC-3) and genes encoding TEM-1 and SHV-11/-36; and were resistant to carbapenems (MIC at ≥ 8 g/mL for ETP, MEM and IPM) and AMK (MIC 32 g/mL) using broth microdilution. As monotherapy, none of the carbapenems nor AMK achieved and maintained bactericidal activity defined as ≥ 99.9% or > 3 log(10) killing. From time-kill studies, synergy was demonstrated for MEM and IPM in combination with AMK over the entire 24 h against all isolates. In addition, MEM and IPM with AMK achieved and maintained bactericidal activity (≥ 99.9% killing) at 24 h against 2 and 1 isolate(s), respectively. Bactericidal activity and synergy were not observed for ETP combinations. CONCLUSIONS: The combination of MEM or IPM with AMK displayed synergistic activity against KPC-3-producing K. pneumoniae isolates. KEYWORDS: ESBL; Klebsiella pneumoniae; KPC; Carbapenemase; Time-kill; Meropenem; Amikacin; Imipenem; Ertapenem; Carbapenem; Synergy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".