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Amplification of Antimicrobial Resistance in Gut Flora of Patients Treated with Ceftriaxone

Tijdschriftbijdrage - e-publicatie

Although antibacterial therapy has an impact on human intestinal flora and the emergence of resistant bacteria, its role in the amplification of antimicrobial resistance and the quantitative exposure-effect relationship is not clear. An observational prospective study was conducted to determine whether and how ceftriaxone exposure is related to amplification of resistance in non-intensive care unit (non-ICU) patients. Serial stool samples from 122 extended-spectrum beta-lactamase-positive (ESBL+) hospitalized patients were analyzed by quantitative real-time PCR to quantify the resistant gene bla(CTX-M). Drug exposure was calculated for each patient by using a population pharmacokinetic model. Multi-and univariate regression and classification regression tree (CART) analyses were used to explore relationships between measures of exposure and amplification of bla(CTX-M) genes. Amplification of bla(CTX-M) was observed in 0% (0/11) of patients with no treatment and 33% (20/61) of patients treated with ceftriaxone. Stepwise regression analysis showed a significant association between amplification of bla(CTX-M) and the plasma area under the concentration-time curve from 0 to 24 h for the unbound fraction of the drug (fAUC(0-24)), the maximum concentration of drug in serum for the unbound fraction of the drug (fC(max)), and the duration of ceftriaxone therapy. Using CART analysis, amplification of bla(CTX-M) was observed in 11/16 (69%) patients treated for > 14 days and in 9/40 (23%) patients treated for <= 14 days (P = 0.0019). In the latter group, amplification was observed in 5/7 (71%) patients with an fAUC(0-24) of >= 222 mg . h/liter and in 4/33 (12%) patients with lower drug exposures (P = 0.0033). A similar association was found for an fC(max) of >= 30 mg/liter (63% versus 13%, P = 0.0079). A significant association was found between the amplification of bla(CTX-M) resistance genes and exposure to ceftriaxone. Both duration of treatment and degree of ceftriaxone exposure have a significant impact on the amplification of resistance genes.
Tijdschrift: Antimicrobial agents and chemotherapy
ISSN: 0066-4804
Volume: 61
Trefwoorden:A1 Journal article
BOF-keylabel:ja
BOF-publication weight:3
CSS-citation score:1
Auteurs:International
Authors from:Higher Education
Toegankelijkheid:Open