Inactivation of the antidiabetic drug acarbose by human intestinal microbial-mediated degradation.

Drugs can be modified or degraded by the gut microbiota, which needs to be considered in personalized therapy. The clinical efficacy of the antidiabetic drug acarbose, an inhibitor of α-glucosidase, varies greatly among individuals for reasons that are largely unknown. Here we identify in the human gut acarbose-degrading bacteria, termed Klebsiella grimontii TD1, whose presence is associated with acarbose resistance in patients. Metagenomic analyses reveal that the abundance of K. grimontii TD1 is higher in patients with a weak response to acarbose and increases over time with acarbose treatment. In male diabetic mice, co-administration of K. grimontii TD1 reduces the hypoglycaemic effect of acarbose. Using induced transcriptome and protein profiling, we further identify an acarbose preferred glucosidase, Apg, in K. grimontii TD1, which can degrade acarbose into small molecules with loss of inhibitor function and is widely distributed in human intestinal microorganisms, especially in Klebsiella. Our results suggest that a comparatively large group of individuals could be at risk of acarbose resistance due to its degradation by intestinal bacteria, which may represent a clinically relevant example of non-antibiotic drug resistance.

Comparison of dexamethasone intravitreal implant and intravitreal triamcinolone acetonide for the treatment of pseudophakic cystoid macular edema in diabetic patients.

BACKGROUND AND OBJECTIVE: Our objective was to investigate the efficacy and safety of dexa methasone (DEX) implant for the treatment of pseudophakic cystoid macular edema (PCME) in diabetic patients. STUDY DESIGN: This was a prospective, non-randomized, interventional case series of 43 participants. Eighteen patients were enrolled in the DEX implant group and 25 were enrolled in an intravitreal triamcinolone acetonide (IVTA) group. MAIN OUTCOME MEASURES: The primary efficacy measurement was the percentage of patients who gained improvements of more than ten letters in best corrected visual acuity (BCVA) during 6 months of follow-up. Other efficacy measurements included change in BCVA, change in central macular thickness (CMT), and number of retreatments. The primary safety evaluation was the percentage of patients with intraocular hypertension and variation in intraocular pressure (IOP) during 6 months of follow-up. Other adverse events, such as conjunctival hemorrhage, eye pain, secondary infection, endophthalmitis, noninfectious inflammation, retinal detachment, and implant migration, were also recorded during follow-up. RESULTS: At month 1, we observed that the percentage of patients gaining improvement of more than ten letters was similar in both groups (P = 0.625). As patients in the IVTA group were retreated several times, this effect persisted throughout the study (P = 0.941 at month 2, P = 0.553 at month 3, P = 0.856 at month 6). Variations in CMT were noticed at week 1 and reached their maximum at month 1. No significant difference was found between the two groups (P = 0.831 at week 1, P = 0.783 at month 1). At month 1, the variation in IOP reached its maximum in the DEX implant group and then decreased slightly. However, in the IVTA group, it increased continuously throughout the study. Conjunctival hemorrhage and eye pain were found in both groups, but both were rated as mild in severity, and no significant difference was found (P = 0.184, P = 0.766, respectively). CONCLUSION: Both IVTA and DEX implants could effectively restore visual function and recover morphological change in diabetic patients with PCME for at least 6 months, but repeated intravitreal injection was required in the IVTA group. DEX implant is well tolerated. We suggest that intravitreal injection of DEX implant is a promising new therapeutic option for diabetic patients with PCME.