Energy-dependent accumulation of norfloxacin and porin expression in clinical isolates of Klebsiella pneumoniae and relationship to extended-spectrum beta-lactamase production

The relationships between porin deficiency, active efflux of fluoroquinolones, and extended-spectrum beta-lactamase (ESBL) production were determined for 53 clinical isolates of Klebsiella pneumoniae. Thirty-two ESBL-positive strains (including 22 strains expressing porins and 10 strains lacking porins) and 21 ESBL-negative strains were evaluated. Active efflux of norfloxacin was defined as a >/=50% increase in the accumulation of norfloxacin in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) in comparison with the corresponding basal value in the absence of CCCP. The quinolone resistance-determining regions of both gyrA and parC from 13 strains, representing all isolates with different porin profiles and with or without active efflux, were determined. Porin loss was significantly more common among ESBL-positive strains (10 of 32 [31.2%]) than among ESBL-negative strains (0 of 2 [0%]) (P < 0.01). Active efflux was observed in 7 of 10 (70%) strains lacking porins and in 4 of 43 (9.3%) strains producing porins (P < 0.001). The 11 strains showing active efflux corresponded to 3 of 21 (14.3%) ESBL-negative strains and 8 of 32 (25.5%) ESBL-positive strains (P > 0.05). Basal values of norfloxacin accumulation were higher in strains lacking active efflux than in those that had this mechanism (P < 0.05). In the absence of topoisomerase changes, the contribution of either porin loss or active efflux to fluoroquinolone resistance in K. pneumoniae was negligible. It is concluded that among K. pneumoniae strains of clinical origin, porin loss was observed only in those producing ESBL, and that a significant number of porin-deficient strains also expressed active efflux of norfloxacin. In terms of fluoroquinolone resistance, both mechanisms are significant only in the presence of topoisomerase modifications.     

Anti-oxidized low-density lipoprotein antibody levels are associated with the development of type 2 diabetes mellitus

Background  Anti-oxidized low-density lipoprotein (LDL) antibodies are associated with the oxidative capacity of plasma, but whether they protect or promote diabetes is unknown. We undertook a prospective study to determine the predictive capacity of anti-oxidized LDL antibodies for the onset of type 2 diabetes mellitus (T2DM).
Materials and methods  We selected 391 non-diabetic women aged 18–65 years. The subjects were classified as being normal (oral glucose test tolerance normal, OGTT-N), or having impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or T2DM according to their baseline glucose levels and after an OGTT. The same subjects were studied six years later. The levels of anti-oxidized LDL antibodies were classified as above or below the 50th percentile.
Results  Of the women who were OGTT-N at the start of the study and who had anti-oxidized LDL antibody levels below the 50th percentile, only 65·1% were still OGTT-N after 6 years versus 79·5% of those who had anti-oxidized LDL antibody levels above the 50th percentile ( P  = 0·015). Women who had IGT or IFG at the start of the study whose anti-oxidized LDL antibody levels were below the 50th percentile had a relative risk of 9·79 (95% confidence interval, 1·40–68·45) of developing diabetes ( P  < 0·001). Logistic regression analysis showed that the variables predicting the development of a carbohydrate metabolism disorder in the women after 6 years were body mass index ( P  < 0·001) and the levels of anti-oxidized LDL antibodies ( P  = 0·042).
Conclusions  Levels of anti-oxidized LDL antibodies are independent predictors for the development of T2DM in women.