[Show abstract][Hide abstract]ABSTRACT: Sepsis is characterized as a systemic inflammatory response that results from the inability of the immune system to limit bacterial spread during an ongoing infection. In this condition the significant mediator of inflammation Platelet Activating Factor (PAF) and the coagulant factor thrombin are implicated. In animal models, treatment with PAF-antagonists or co-administration of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes.
We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both de novo/remodelling PAF biosynthesis and PAF degradation, respectively.
Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentration-depended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, while when combined they synergistically inhibited PAF. Higher concentrations of all antibiotics tested were needed in order to inhibit PAF induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of WRPs. Concentrations of these drugs similar to their IC50 values against PAF activity in WRPs, inhibited also in vitro PAF-CPT and Lyso-PAF-AT activities of rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit plasma-PAF-AH activity.
These newly found properties of antibiotics used in sepsis suggest that apart from their general actions, these drugs may present additional beneficial anti-inflammatory and anti-coagulant effects against the onset and establishment of sepsis by inhibiting the PAF/PAF-receptor and/or the thrombin/protease-activated-receptor-1 systems, and/or by reducing PAF-levels through both PAF-biosynthesis inhibition and PAF-catabolism induction. These promising in vitro results need to be further studied and confirmed by in vivo tests, in order to optimize the efficacy of antibiotic treatment in sepsis.
Full-text Article · Jul 2011 · Journal of Inflammation
[Show abstract][Hide abstract]ABSTRACT: Introduction: Interfacility transmission of R pathogens has been well documented. Considering the increasing frequency of isolation of EB-R in hospitals, a survey was performed to determine the prevalence of EB-R colonization among elderly residents in Greek LTCF. Methods: A total of 22 LTCF were randomly selected from the public sanitation list of Attica province. Urine, nasopharyngeal and wound samples were collected from 668 residents. We chose randomly 30% of the existing population from each LTCF (minimum sum 25 residents, age > 65 years). EB species were identified by API strips and underwent antimicrobial disk susceptibility testing, following the NCCLS guidelines. Confirmation of ESBL production was done by MIC broth microdilution and double disk diffusion, as per NCCLS. Results: The mean age of the residents was 86 years. 386 EB were isolated from 1418 samples (27,2%). Resistance to ampicillin (AMP), ampicillin-sulbactam (AM/SB), aminoglycosides (AMS), fluoroquinolones (FQ) and third-generation cephalosporines (Chep3) was analyzed. AMP and AM/SB resistant rates were 64% (leading bacteria: Proteus spp. 63% and Escherichia coli 51%) and 37% (leading isolates: Klebsiella spp. 57% and Proteus spp. 48%) respectively. 8,8% of the isolated EB were Chep3-R (Proteus spp. 16,7%, Klebsiella spp. 8,4% and E. coli 5,8% respectively). From Chep3-R EB, 52% were producing ESBL (leading isolates: E. coli 48% and Klebsiella spp. 39%). 66,5 % of the ESBL strains were also FQ- resistant. R to AMS was 24% (leading isolates: Providencia stuartii 70% and Proteus spp 28%) and R to FQ was 19% (leading isolates: Morganella morganii 45% and E. coli 22%). Conclusions: I. Resistance among EB to Chep3, FQ and AMS in Greek LTCF is worrisome. II. The close relationship between FQ-R and ESBL production is remarkable III. The high resistance of E. coli to FQ must be taken into consideration before the administration of empirical therapy.
[Show abstract][Hide abstract]ABSTRACT: In the era of highly active antiretroviral treatment (HAART), there are insufficient data regarding lipodystrophy syndromes in HIV-1-infected patients treated with regimens that do not include protease inhibitors (PIs). We studied changes in body composition in HIV-1-infected patients before and 2 years after starting a non-PI-containing antiretroviral treatment regimen.
We studied retrospectively the whole body dual energy X-ray absorptiometry (DEXA) scans of 23 PI-naive HIV-1-infected patients (17 males, six females), aged 37.4 +/- 9.3 years with mean CD4 count 401 +/- 130 cells/microL. Thirteen patients were on zidovudine (ZDV) + lamivudine (3TC) and 10 on ZDV + didanosine (ddI). Subjects were evaluated before the beginning of antiretroviral treatment and approximately 24 months later. For each patient body weight, CD4 T-cell counts, bone mineral content (BMC), bone mineral density (BMD) and whole body as well as regional fat and lean body mass were evaluated.
A significant decrease in BMC was observed, although the T scores remained within the normal limits. Our patients also exhibited a significant decrease in body weight due almost exclusively to fat loss, while lean mass was minimally affected. Fat loss was statistically significant in the arms and legs, but not in the trunk. The above changes were most prominent in the ZDV + 3TC treatment group; in this group of patients, fat loss was also evident in the trunk. Patients on ZDV + ddI, on the other hand, only showed a significant increase in their legs' lean mass; they preserved their total fat mass and exhibited no other significant changes between the two assessments.
Dual NRTI therapy contributes to fat loss and reduction of bone mineral content in otherwise healthy, clinically stable, PI-naive HIV-infected adults. Compared with patients on ZDV + ddI, patients on ZDV + 3TC had a more prominent fat loss in all body regions.