Favourable outcome in the treatment of carbapenem-resistant Enterobacteriaceae urinary tract infection with high-dose tigecycline

Brust, Karen; Evans, Ann M.; Plemmons, Robert M.

doi:10.1093/jac/dku185

Cited by 20 publications

(5 citation statements)

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“…Additionally, approximately 50% of septicemia and over 70% of urinary infections are caused by Enterobacteriaceae (11)(12)(13). Carbapenems (imipenem, meropenem and ertapenem), which have broad antibacterial spectra as well as high antibacterial activities and stability to β-lactamases, are potent antibiotics for treating infections induced by Gram-negative bacteria (14).…”

Section: Discussionmentioning

confidence: 99%

Mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates

Han

et al. 2017

Exp Ther Med

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Abstract. Carbapenemase-producing ʻsuper bacteriaʼ, particularly NDM-1 and its variants, have become a major public health concern worldwide. The present study aimed to explore the molecular mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates. Seventy-eight non-repeated Enterobacteriaceae strains resistant to any carbapenem were screened at the First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between December 2011 and December 2015. Outer membrane porin (OMP) proteins were detected using SDS-PAGE. Carbapenemases, extended-spectrum β-lactamases (ESBLs) and plasmid AmpC enzyme genes were detected using polymerase chain reaction (PCR). PCR and SDS-PAGE demonstrated that 60.3% (47/78) of the strains produced carbapenemases, of which 33.3% (26/78) produced KPC-2 carbapenemase, suggesting that the strains resisted carbapenems primarily through carbapenemases. SDS-PAGE showed that the OMP proteins in the majority of carbapenem-resistant Enterobacteriaceae (CRE) strains were deleted or decreased compared with those in the sensitive strains. Of the 44 Klebsiella strains, 59.1% (26/44) did not express or expressed less OmpK35 or OmpK36. Among the 34 strains of other enterobacteria, 97.1% (33/34) did not express or expressed less OmpC or OmpF. Of all CRE strains, 35.9% (28/78) lost at least one OMP protein, indicating that the strains resisted carbapenems also by producing ESBLs and/or plasmid AmpC enzyme, as well as by losing OMP proteins. The resistance of clinically isolated CRE strains may primarily be attributed to the production of carbapenemases, and may also involve the deletion of OMP proteins or mutation of OMP genes.

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Section: Discussionmentioning

confidence: 99%

Mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates

Han

et al. 2017

Exp Ther Med

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“…Tigecycline, the first glycycline antimicrobial, was used to treat serious infections, especially those caused by XDR Enterobacteriaceae and Acinetobacter species. , Recently, two plasmid-mediated high-level tigecycline resistance tet (X)-variant genes ( tet (X3) and tet (X4)) were reported in Enterobacteriaceae and Acinetobacter spp. from animals, animal-derived food, and even humans, , which greatly threaten the treatment values of the last-resort antibiotic tigecycline.…”

Section: Introductionmentioning

confidence: 99%

Dissemination of the tet(X)-Variant Genes from Layer Farms to Manure-Receiving Soil and Corresponding Lettuce

Wei

Zhang

et al. 2021

Environ. Sci. Technol.

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The occurrence of high-level tigecycline resistance tet(X) variant genes represents a new transferable resistance crisis to food safety and human health. Here, we investigated the abundance of tet(X)-variant genes [tet(X), tet(X1) to tet(X6)] in 33 samples collected from layer manures, manured/un-manured soils, and corresponding lettuce from three provinces in China. The results showed the occurrence of tet(X)/(X2), tet(X3), and tet(X4) in 24 samples. The detection rate of tet(X)/(X2) (23/24) is higher than that of tet(X3) (7/24) and tet(X4) (2/24), and tet(X)/tet(X2) and tet(X3) were found to be enriched and more abundant in most manured soil and several lettuce samples from manured soils than that from manure samples. Twenty six tigecycline-resistant bacteria were isolated, and tet(X)-variant genes were found to be disseminated not only by bacterial clone spreading but also via multidrug resistance plasmids. The total concentrations of tet(X)-variant genes showed significantly positive correlations (R = 0.683, p < 0.001) with ISCR2. Two veterinary tetracyclines (tetracycline and oxytetracycline) and other classes of antimicrobials (enrofloxacin, azithromycin, thiamphenicol, and florfenicol) showed significant correlations with the total concentrations of tet(X)-variant genes (R = 0.35–0.516, p < 0.05). The findings indicate the transmission of tet(X)-variant genes from layer manures to their receiving environmental soils and lettuce and highlight the contribution of veterinary antimicrobials to the spread of tet(X)-variant genes.

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“…While more published experience is needed to further determine the effectiveness of high dose once daily tigecycline dosing in treating various serious systemic infections, our recent and ongoing experience at Winthrop-University Hospital has demonstrated that a PK/PD based tigecycline once daily regimen is optimal and PI based low/split dosing was suboptimal and was associated with treatment failures [ 23 , 24 , 25 , 26 ]. Once daily HDT is safe and optimally effective.…”

Section: Discussionmentioning

confidence: 99%

Once Daily High Dose Tigecycline Is Optimal: Tigecycline PK/PD Parameters Predict Clinical Effectiveness

Baron

Cai

Klein

et al. 2018

JCM

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Objective: The clinical effectiveness of tigecycline depends on appropriate use, and PK/PD (pharmacokinetic/pharmacodynamic) parameters related to dose and dosing interval. Methods: In our 600-bed university-affiliated teaching hospital, we conducted a tigecycline efficacy review over a three-month period in 34 evaluable patients. Parameters assessed included clinical response, cure or treatment failure, once daily as q12h dosing, maintenance dosing, high dose vs. standard loading regimens, adverse effects, and the effect of infectious disease consultation on outcomes. Results: We found once daily high dose tigecycline (HDT) was highly effective in treating serious systemic infections due to MDR Gram-positive/negative pathogens as well as C. difficile colitis. Adverse effects were infrequent and limited to mild nausea/vomiting. Once daily HDT was highly effective, and the few treatment failures were related to suboptimal/split dosing regimens. Conclusion: Once daily HDT was highly effective when used to treat susceptible pathogens and when optimally dosed, i.e., 200–400 mg (IV) loading dose ×1, followed by a once daily maintenance dose of 100–200 mg (IV) q24h.

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Favourable outcome in the treatment of carbapenem-resistant Enterobacteriaceae urinary tract infection with high-dose tigecycline

Cited by 20 publications

References 5 publications

Mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates

Mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates

Dissemination of the tet(X)-Variant Genes from Layer Farms to Manure-Receiving Soil and Corresponding Lettuce

Once Daily High Dose Tigecycline Is Optimal: Tigecycline PK/PD Parameters Predict Clinical Effectiveness

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