Dataset Information

Pharmacokinetic and Pharmacodynamic Analysis of the Oxacephem Antibiotic Flomoxef against Extended-Spectrum β-Lactamase-Producing Enterobacterales from Dogs.

ABSTRACT: Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales-producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs using a pharmacokinetics-pharmacodynamics (PK-PD) approach. Five dogs were intravenously administered at a bolus dose of FMX (40 mg/kg body weight). Serum concentrations of FMX were calculated with high-performance liquid chromatography-tandem mass spectrometry, and then applied to determine PK indices based on a non-compartmental model. The cumulative fraction of response (CFR) was estimated based on the dissemination of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. From the results, the dosage regimens of 40 mg/kg every 6 and 8 h were estimated to attain a CFR of >90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. By contrast, all regimens had a CFR of <80% for ESBL-producing Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX every 6 and 8 h can be a non-carbapenem treatment for canine infections of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those of ESBL-producing Enterobacter cloacae.

SUBMITTER: Kusumoto M

PROVIDER: S-EPMC10816067 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Pharmacokinetic and Pharmacodynamic Analysis of the Oxacephem Antibiotic Flomoxef against Extended-Spectrum β-Lactamase-Producing Enterobacterales from Dogs.

Kusumoto Mizuki M Jitsuiki Makoto M Motegi Tomoki T Harada Kazuki K

International journal of molecular sciences 20240116 2

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales-producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs using a pharmacokinetics-pharmacodynamics (PK-PD) approach. Five dogs were intravenously administered at a bolus dose of FMX (40 mg/kg body ...[more]

PMID: 38256182

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Project description:BackgroundExtended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) are a serious threat among emerging antibiotic resistant bacteria. Particularly, the number of cases of ESBL-E infections reported in children has been increasing in recent years, and approved antibiotic treatments for this age group are limited. However, information regarding the prevalence of colonization in European children, risk factors associated with colonization, and the characteristics of the colonizing strains is scarce. The aims of this study were to determine the prevalence of ESBL-E colonization in fecal samples of apparently healthy schoolchildren, to identify lifestyle routines associated with colonization, and to characterize clonal relationships and mechanisms of resistance in ESBL-E isolates.MethodsA cohort of 887 healthy children (3-13 years old) from seven primary and secondary schools in the Madrid metropolitan area was recruited between April-June 2018, and sociodemographic information and daily habits were collected. Fecal samples were screened for ESBL-E carriage in selective medium. ESBL-E isolates were further characterized by assessing molecular epidemiology (PFGE and MLST), ESBL gene carriage, and antibiotic resistance profile. This information was analyzed in conjunction with the metadata of the participants in order to identify external factors associated with ESBL-E carriage.ResultsTwenty four ESBL-E, all but one Escherichia coli, were detected in 23 children (prevalence: 2.6%; 95% CI: 1.6-3.6%). Of these, seven contained the blaCTX-M-14 allele, five the blaCTX-M-15, five the blaSHV-12, three the blaCTX-M-27, three the blaCTX-M-32, and one the blaCTX-M-9. Significant clonal diversity was observed among the isolates that grouped into 22 distinct clusters (at <85% similarity of PFGE profile). ESBL-producing E. coli isolates belonged to 12 different STs, with ST10 (25%) and ST131 (17%) being the most frequent. Apart from ß-lactams, resistance to trimethoprim/sulfamethoxazole (46%), ciprofloxacin (33%), levofloxacin (33%), tobramycin (21%), and gentamicin (8%) were the most frequently detected.ConclusionThe prevalence of ESBL-E in the studied cohort of children was lower than the average colonization rate previously detected in Europe for both children and adults. E. coli was the main ESBL-producing species detected and CTX-M were the most frequently identified ESBLs. High ST diversity suggests polyclonal dissemination. Compared to other STs, ST131 isolates were associated with resistance to various antimicrobials.

Project description:BackgroundVulnerable groups, such as pregnant women, are at increased risk of potentially life-threatening infections with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) for both mother and newborn. However, data regarding ESBL-E carriage and associated risk factors in Ghanaian pregnant women remain scarce.ObjectiveThis study aimed to determine the prevalence of ESBL-E carriage and its associated risk factors among pregnant women attending the antenatal clinic at the Korle Bu Teaching Hospital.MethodsA systematic sample of 700 pregnant women with gestational age ≥ 34 weeks attending the antenatal clinic at Korle Bu Teaching Hospital was included in the study. After administering a structured questionnaire to assess potential risk factors associated with ESBL-E carriage, patients were given a sterile stool container to submit at least 1 g of stool specimen. Recovered isolates from faecal specimens were identified using MALDI-TOF-MS technology. These isolates were then subjected to susceptibility testing and ESBL identification. A random subset of 24 ESBL-producing Escherichia coli isolates was whole-genome sequenced on the MiSeq Illumina platform. Risk factors associated with ESBL-E carriage were determined using multivariable logistic regression analysis.ResultsAmong the 700 pregnant women, 42% (294) carried ESBL-E. The predominant ESBL-producing Enterobacterales were Escherichia coli (95%). Fifty percent (50%) of ESBL-E were multidrug resistant isolates (MDRs). Whole-genome sequencing of 24 ESBL-producing E. coli isolates revealed that blaCTX-M-15 (96%) was the most prevalent ESBL gene type. Notably, most isolates belonged to commensal phylogenetic groups (A, B1, and C; 88%). Having a primary level of education (aOR 1.45, 95% CI 1.05-1.96) and consuming legumes as the main source of protein (aOR 0.17, 0.40-0.83) were significantly associated with intestinal carriage of ESBL-E.ConclusionThis study identified a high prevalence of ESBL-E and MDR-ESBL-E carriage among pregnant women. Our findings underscore the urgent need for public health interventions to control the spread of AMR.

Project description:BackgroundAntimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) in carriers of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) presents significant challenges. The abundance of ESBL-E rectal carriage has emerged as a potentially valuable tool for predicting ESBL-E-related VAP.MethodsThis single-center, retrospective study was conducted between October 2019 and April 2023 in the medical ICU of a university hospital. The relative abundance of ESBL-E rectal carriage (RAC) was calculated as the ratio of ESBL-E counts to the total number of aerotolerant bacteria. The aim was to evaluate the predictive value of RAC for diagnosing ESBL-E-related VAP in patients with confirmed VAP who were ESBL-E carriers.ResultsDuring the study period, 478 patients with ESBL-E carriage were admitted to the ICU, of whom 231 (48%) required mechanical ventilation. Eighty-three patients (17%) developed a total of 131 confirmed VAP episodes, of which 62 episodes (47%) were ESBL-E-related VAP. The median interval between the last rectal screening and VAP occurrence was 4 [3-7] days. RAC was not associated with ESBL-E-related VAP in the entire cohort (p = 0.39). Similar findings were observed in several sensitivity analyses, including the following subsets: recent and high-quality screening (interval between screening and VAP ≤ 7 days and bacterial load on rectal swab > 104 CFU/mL, p = 0.21); first VAP episodes only (p = 0.41); cases involving Escherichia coli exclusively (p = 0.08) or other ESBL-E strains (p = 0.29); and VAP associated with Gram-negative bacteria (p = 0.26) or Enterobacterales (p = 0.34). However, in a multivariable model, rectal colonization with non-Escherichia coli ESBL strains was independently associated with ESBL-E-related VAP (adjusted odds ratio [aOR] 1.213 [95% CI 1.005-1.463], p = 0.045).ConclusionRAC was not associated with confirmed VAP in ESBL-E carriers. Further studies are needed to explore effective strategies for improving AMS in ESBL-E carriers with suspected VAP.

Dataset Information

Pharmacokinetic and Pharmacodynamic Analysis of the Oxacephem Antibiotic Flomoxef against Extended-Spectrum β-Lactamase-Producing Enterobacterales from Dogs.

Publications

Pharmacokinetic and Pharmacodynamic Analysis of the Oxacephem Antibiotic Flomoxef against Extended-Spectrum β-Lactamase-Producing Enterobacterales from Dogs.

Similar Datasets

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