Mutant Prevention Concentrations of Doripenem and Meropenem Alone and in Combination with Colistin (Polymyxin E), Levofloxacin and Tobramycin in <i>Pseudomonas aeruginosa</i>
Notice bibliographique
Résumé
BACKGROUND: With a limited number of available antimicrobial agents to treat Pseudomonas aeruginosa infections, the prevention of emergence of antimicrobial resistance and its subsequent spread is critical. In the present study, the mutant prevention concentration (MPC) of doripenem was examined and compared with meropenem for its ability to prevent resistant mutant selection for P aeruginosa when used alone and in combination with the other antipseudomonal agents colistin (polymyxin E), levofloxacin and tobramycin. OBJECTIVE: To determine if two antimicrobial agents that possessed different mechanisms of action and separate demonstrated activities against P aeruginosa would produce a reduced MPC in combination compared with the MPC of each agent alone. METHODS: Twelve clinical isolates of P aeruginosa were plated on Mueller‐Hinton agar containing 1×, 2×, 4×, 8×, 16× and 32× the doripenem, imipenem or meropenem minimum inhibitory concentration (MIC), and also on agar containing doripenem or meropenem in combination with either tobramycin (6 μg/mL), colistin (2 μg/mL or 8 μg/mL), levofloxacin (8 μg/mL) or azithromycin (0.4 μg/mL). The MPC for each antimicrobial agent‐isolate combination was defined as the lowest antibiotic concentration that prevented the visible growth of mutant colonies at 48 h of incubation. The MPC/MIC (μg/mL) ratio was defined as the ratio of the MPC obtained to the original MIC. RESULTS: The MPC/MIC ratios of doripenem alone ranged from 8 to 32 for the twelve isolates tested compared with 32 for two isolates and greater than 32 for 10 isolates with imipenem, and 32 for three isolates and greater than 32 for nine isolates with meropenem. All antimicrobials tested exhibited markedly elevated MPCs compared with their original MICs with MPC/MIC ratios of 8 to 32 for doripenem, 32 to greater than 32 for imipenem, 32 to greater than 32 for meropenem, 32 to greater than 32 for colistin (tested at 2 μg/mL), 8 to 16 for levofloxacin and 8 to 32 for tobramycin. When a second antimicrobial was used in combination with doripenem, the MPC/MIC ratio decreased up to twofold for doripenem combined with colistin (2 μg/mL), decreased four‐ to 16‐fold for doripenem combined with colistin (8 μg/mL), decreased eight‐ to 32‐fold for doripenem combined with levofloxacin, and decreased four‐ to 16‐fold for doripenem combined with tobramycin. Adding a second antimicrobial in combination with meropenem resulted in the following decreases in MPC/MIC: no decrease for meropenem combined with colistin (2 μg/mL), four to greater than eightfold decrease for meropenem combined with colistin (8 μg/mL), four‐ to 16‐fold decrease for meropenem combined with levofloxacin, and two‐ to 16‐fold decrease for meropenem combined with tobramycin. For all antimicrobial combinations tested, doripenem yielded greater decreases in MPC/MIC ratios than did meropenem. CONCLUSION: The present study found that individual antipseudomonal antimicrobial agents tested against 12 clinical isolates of P aeruginosa had eight‐ to greater than 32‐fold higher MPCs than MICs, that combining doripenem or meropenem with a second active antipseudomonal agent with a different mechanism of action was more effective at preventing resistance selection than the two agents used individually, and finally, that doripenem was less likely than both imipenem and meropenem to select for spontaneous resistance mutants of P aeruginosa.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».