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Purpose: The continued emergence of multidrug resistant bacterial infections and the decline in discovery of new antibiotics are major challenges for health care throughout the world. This situation has heightened the need for novel antimicrobial therapies as alternatives to traditional antibiotics. The combination of metallic nanoparticles and laser exposure has been proposed as a strategy to induce physical damage to bacteria, regardless of antibiotic sensitivity. The purpose of this study was to test the antibacterial effect of antibody-targeted gold nanoparticles combined with pulsed laser irradiation., Methods: Gold nanoparticles conjugated to antibodies specific to Staphylococcus aureus peptidoglycan were incubated with suspensions of methicillin-resistant and methicillin-sensitive S. aureus (MRSA and MSSA). Bacterial suspensions were then exposed to 8 ns pulsed laser irradiation at a wavelength of 532 nm and fluences ranging from 1 to 5 J/cm(2). Viability of the bacteria following laser exposure was determined using colony forming unit assays. Scanning electron microscopy was used to confirm the binding of nanoparticles to bacteria and the presence of cellular damage., Results: The laser-activated nanoparticle treatment reduced the surviving population to 31% of control in the MSSA population, while the survival in the MRSA population was reduced to 58% of control. Significant decreases in bacterial viability occurred when the laser fluence exceeded 1 J/cm(2), and this effect was linear from 0 to 5 J/cm(2) (r (2)=0.97). Significantly less bactericidal effect was observed for nonfunctionalized nanoparticles or functionalized nanoparticles without laser activation., Conclusion: Laser-activated nanoparticles targeted to S. aureus surface antigens significantly reduced the percentage of viable organisms and represents a promising new treatment modality that could be used either alone or as an adjunct to existing, conventional antibiotic therapy.

Purpose: To determine the penetration of orally administered trimethoprim (TMP)-sulfamethoxazole (SMX) into the aqueous and vitreous cavity of noninflamed human eyes., Methods: Nine adult patients undergoing cataract surgery and 10 adult patients undergoing pars plana vitrectomy were given 3 doses of oral TMP-SMX every 12 hours before the surgery. Aqueous and blood samples were collected from patients undergoing cataract surgery; vitreous and blood samples were collected from patients undergoing vitrectomy. The levels of TMP and SMX were analyzed using high-performance liquid chromatography and were compared with the mean minimum inhibitory concentrations (MIC) of potential ocular pathogens., Results: TMP-SMX was present in all samples. Among eyes undergoing cataract surgery, the mean concentrations of TMP in aqueous and blood were 0.341 ± 0.141 μg/mL (mean ± SD) and 1.501 ± 0.433 μg/mL and of SMX were 5.259 ± 0.929 μg/mL and 11.835 ± 2.100 μg/mL, respectively. Among eyes undergoing vitrectomy, the mean concentrations of TMP in vitreous and blood were 1.864 ± 0.807 μg/mL and 4.591 ± 2.979 μg/mL and of SMX were 5.910 ± 2.705 μg/mL and 39.289 ± 15.469 μg/mL, respectively. MIC levels were achieved against many bacterial pathogens, including methicillin-resistant Staphylococcus aureus., Conclusions: TMP-SMX penetrates both the aqueous and vitreous cavities when given orally. The components reach therapeutic inhibitory concentrations in the ocular cavity against many potential pathogens.

Four different antibiotics, delivered individually to rabbit eyes via hydrophilic intraocular lenses soaked in the drug solution prior to implantation, were measured in aqueous and vitreous humor samples from the eyes. To meet this analytical need, we developed a sensitive, high performance liquid chromatographic (HPLC) method for measuring the concentrations of moxifloxacin, gatifloxacin, linezolid, and cefuroxime in the ocular tissue. Separations were carried out on a LichroSpher RP-18 column, maintained at room temperature. The fluoroquinolones were eluted with a mobile phase consisting of 20% acetonitrile, in 0.1% trifluoroacetic acid (pH 3.0) with 30 mM tetrabutylammonium chloride. Linezolid and cefuroxime were eluted with 25% acetonitrile in 25 mM Na acetate buffer, pH 5.0. All elutions were isocratic. With ultraviolet detection, the lower limit of quantitation (LLOQ) for these compounds approached 1 ng (on-column injection). By using fluorescence detection, the LLOQ for the fluoroquinolones improved to 200 pg. The overall accuracy of the method was >or=90%. With minor modifications, the method was optimized for each of the agents, and the resulting analytical sensitivity made the method suitable for clinical investigations of the ocular penetration of these drugs., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)