Chitotriosidase on treatment-naïve patients with Gaucher disease: A genotype vs phenotype study.

BACKGROUND: Chitotriosidase (ChT) is used as a biomarker for the follow-up of patients with Gaucher disease (GD), once his activity is extremely elevated and declines during ERT. However, some variants in the CHIT1 gene affect ChT activity. METHODS: To assess association between ChT genotype, and clinical/biochemical features of GD were performed CHIT1 genotyping for: c.1049_1072dup24, p.Gly102Ser, p.Gly354Arg, c.1155_1156 + 2delGAGT, c.1156 + 5_1156 + 8delGTAA, p.Ala442Val/Gly and the rearrangement delE/I-10. RESULTS: Were evaluated 42 patients with GD from Southern Brazil. Pretreatment ChT activity was available for 32 patients. Allelic frequencies found for dup24, p.Gly102Ser and p.Ala442Gly were 0.14, 0.32 and 0.12, respectively. Only one patient presented reduced ChT activity (dup24 homozygous). Comparison between wild homozygous and heterozygous for dup24 showed that both differ in relation to the ChT activity before (15,230 vs 6936 nmol/h/mL, p < .001), but not after treatment (5212 vs 3045 nmol/h/mL, p = .227). CONCLUSIONS: Pretreatment ChT activity was not correlated with clinical/biochemical features. There was a reduction of 63% in the ChT activity after 12 months on treatment (p < .001). There is no evidence that higher ChT levels are associated with a more severe symptomatology in untreated GD patients. The pretreatment ChT levels appear to be mainly dependent on the presence/absence of the dup24 allele.

Hetero- and adaptive resistance to polymyxin B in OXA-23-producing carbapenem-resistant Acinetobacter baumannii isolates.

BACKGROUND: Resistance rates to polymyxin B in surveillance studies have been very low despite its increasing use worldwide as the last resort therapy for multidrug-resistant Gram-negative bacilli. However, two other resistance phenotypes, hetero- and adaptive resistance, have been reported to polymyxin. We aimed to investigate the presence of polymyxin B hetero- and adaptive resistance and evaluate its stability in carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates. METHODS: CRAB isolates were recovered from hospitalized patients at three Brazilian hospitals. Hetero-resistance was determined by population analysis profile (PAP). Adaptive resistance was evaluated after serial daily passages of isolates in Luria-Bertani broth containing increasing polymyxin B concentrations. MICs of polymyxin B of colonies growing at the highest polymyxin B concentration were further determined after daily sub-cultured in antibiotic-free medium and after storage at -80°C, in some selected isolates. RESULTS: Eighty OXA-23-producing CRAB isolates were typed resulting in 15 distinct clones. Twenty-nine randomly selected isolates (at least one from each clone) were selected for hetero- resistance evaluation: 26 (90%) presented growth of subpopulations with higher polymyxin B MIC than the original one in PAP. No isolate has grown at polymyxin B concentrations higher than 2 mg/L. Polymyxin B MICs of subpopulations remained higher than the original population after daily passages on antibiotic-free medium but returned to the same or similar levels after storage. Twenty-two of the 29 isolates (at least one from each clone) were evaluated for adaptive resistance: 12 (55%) presented growth in plates containing 64 mg/L of polymyxin B. Polymyxin B MICs decreased after daily passages on antibiotic-free medium and returned to the same levels after storage. CONCLUSIONS: The presence of subpopulations with higher polymyxin B MIC was extremely common and high-level adaptive resistance was very frequent in CRAB isolates.