Violet-Blue Light Arrays at 405 Nanometers Exert Enhanced Antimicrobial Activity for Photodisinfection of Monomicrobial Nosocomial Biofilms.

Light-emitting diodes (LEDs) demonstrate therapeutic effects for a range of biomedical applications, including photodisinfection. Bands of specific wavelengths (centered at 405 nm) are reported to be the most antimicrobial; however, there remains no consensus on the most effective irradiation parameters for optimal photodisinfection. The aim of this study was to assess decontamination efficiency by direct photodisinfection of monomicrobial biofilms using a violet-blue light (VBL) single-wavelength array (SWA) and multiwavelength array (MWA). Mature biofilms of nosocomial bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus) were grown on 96-well polypropylene PCR plates. The biofilms were then exposed to VBL for 2,700 s (SWA) and 1,170 s (MWA) to deliver 0 to 670 J/cm2, and the antibacterial activity of VBL was assessed by comparing the seeding of the irradiated and the nonirradiated biofilms. Nonirradiated groups were used as controls. The VBL arrays were characterized optically (spectral irradiance and beam profile) and thermally. The SWA delivered 401-nm VBL and the MWA delivered between 379-nm and 452-nm VBL, albeit at different irradiances and with different beam profiles. In both arrays, the irradiated groups were exposed to increased temperatures compared to the nonirradiated controls. All bacterial isolates were susceptible to VBL and demonstrated reductions in the seeding of exposed biofilms compared with the nonirradiated controls. VBL at 405 nm exerted the most antimicrobial activity, exhibiting reductions in seeding of up to 94%. Decontamination efficiency is dependent on the irradiation parameters, bacterial species and strain, and experimental conditions. Controlled experiments that ameliorate the heating effects and improve the optical properties are required to optimize the dosing parameters to advance the successful clinical translation of this technology.IMPORTANCE This study reports the efficacy of VBL and blue light (BL) and their antimicrobial activity against mature biofilms of a range of important nosocomial pathogens. While this study investigated the antibacterial activity of a range of wavelengths of between 375 and 450 nm and identified a specific wavelength region (∼405 nm) with increased antibacterial activity, decontamination was dependent on the bacterial species, strain, irradiation parameters, and experimental conditions. Further research with controlled experiments that ameliorate the heating effects and improve the optical properties are required to optimize the dosing parameters to advance the successful clinical translation of this technology.

A feasibility, pharmacokinetic and frequency-escalation trial of intraperitoneal chemotherapy in high risk gastrointestinal tract cancer.

AIMS: To assess the feasibility, pharmacokinetics and maximum tolerable frequency (MTF) of intraperitoneal (IP) 5-fluorouracil and leucovorin (FU/LV) added, as a regional boost, to intravenous chemotherapy after resection of gastrointestinal cancer. METHODS: Fifty-three patients were recruited following gastrointestinal cancer resection (43 colon; 10 stomach/small bowel) with serosal involvement. Peritoneal ports were implanted and IP fluid distribution evaluated ultrasonically. Twelve patients were studied for pharmacokinetics; 44 (41 evaluable) for MTF. Treatment was weekly intravenous bolus FU/LV for 6 months; to this was added IP FU/LV (400/20 mg/m(2) in 1500 ml 4% icodextrin) with increasing frequency from 4 weekly to 1 weekly in four successive cohorts. RESULTS: Peritoneal fluid distribution was excellent. Intraperitoneal FU exposure (AUC) after IP treatment was >1000-fold plasma AUC after IP treatment (regional pharmacokinetic advantage), and >100-fold plasma AUC after intravenous treatment (regional therapeutic advantage). IP therapy was well tolerated if given every 4, 3 or 2 weeks, but not weekly: 11/13, 7/8, 10/13 and 0/7 patients respectively completed treatment without IP modification in these cohorts. Problems with peritoneal access occurred in 20% of patients. CONCLUSION: Adding fortnightly IP FU/LV to a standard intravenous regimen is safe, tolerable and provides high peritoneal FU exposure. More reliable peritoneal access is needed to improve the feasibility of this otherwise promising therapeutic approach.

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma.

We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m-2 on day 1; capecitabine 850 mg m-2 12-hourly on days 1-9. Level 2: as level 1 but capecitabine 1000 mg m-2. Level 3: as level 2 but irinotecan 180 mg m-2. Level 4: as level 3 but capecitabine 1250 mg m-2. In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3-4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16-52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study.