Anti-C. difficile CD1021 Polyclonal antibody

Background: Fidaxomicin is a recommended treatment for Clostridioides difficile infection (CDI) and reduces CDI recurrence incidence versus vancomycin. An extended-pulsed fidaxomicin (EPFX) regimen further reduces recurrence frequency. However, the pharmacokinetic profile of fidaxomicin in an EPFX regimen is unknown. Objectives: To evaluate plasma and stool concentrations of fidaxomicin and its metabolite, OP-1118, after EPFX administration for CDI. Methods: In the Phase 3b/4 EXTEND trial, patients aged >= 60 years with toxin-confirmed CDI were randomized to receive EPFX (oral fidaxomicin twice daily, Days 1-5; once daily on alternate days, Days 7-25). Fidaxomicin and OP-1118 concentrations were determined using post-dose plasma samples obtained on Days 5 +/- 1, 12 +/- 1 and 25/26, and post-dose stool samples obtained on Days 5 +/- 1, 12 +/- 1 and 26 +/- 1. Results: Plasma samples from 14 patients were included in the pharmacokinetic analysis; 12 of these patients provided stool samples. Median (range) plasma concentrations of fidaxomicin on Day 5 +/- 1 and Day 25/26 were 0.0252 (0.0038-0.1220) mg/L and 0.0069 (0-0.0887) mg/L, respectively, and those of OP-1118 were 0.0648 (0.0142-0.3250) mg/L and 0.0206 (0-0.3720) mg/L, respectively. Median (range) stool concentrations of fidaxomicin and OP-1118 on Day 26 +/- 1 were 272.5 (0-524) mg/kg and 280.5 (0-1120) mg/kg, respectively. Conclusions: EPFX treatment maintained fidaxomicin stool concentrations above the C. difficile MIC 90 until Day 26 +/- 1. Systemic exposure to fidaxomicin and OP-1118 was Low throughout and there was no evidence of accumulation in plasma or stool during treatment.

Objective: Clostridium difficile (C. diff) infection leads to hundreds of nosocomial infections, and early diagnosis of this toxin-mediated disease is important. This paper aims to develop a microrobotic system and related methods that enable the automated and rapid detection of toxins secreted by C. diff that exist in patient's stool. Methods: We utilize the fluorescent magnetic spore-based microrobot (FMSM), a microscale mobile sensing tool, to efficiently detect C. diff toxins by utilizing its property of selective fluorescence responses to C. diff toxins. A plug-and-play (PnP) electromagnetic coil system integrated with fluorescence microscopy is developed for actuation, control and observation of FMSMs. In order to track in real time and accurately obtain the fluorescence parameters of a FMSM under varied background noise in fluorescence signal, an image gradient-based method is proposed. For accelerating the FMSM-toxin interaction in different samples, an automated navigation control scheme for the FMSM is proposed and implemented. Moreover, data post-processing methods that can optimally extract the fluorescence decay trend from the dense and fluctuated fluorescence data are developed. Results: This automated mobile detection process finishes within only 20 minutes, and the toxin detection result is immediately given by adopting the proposed system and methods. Experimental results on different biological samples confirm the qualitative detection capability. And, C. diff toxins are automatically detected from the clinical stool of infectious patients and the relationship between the fluorescence decay and the toxin concentration is calibrated for semi-quantitative detection purpose. Significance: The proposed automated microrobotic platform provides a rapid and low-cost detection technique for C. diff toxins, and it has good competency for future clinical use.