Effect of photodynamic therapy with 5-aminolevulinic acid and EDTA-2Na against mixed infection of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

BACKGROUND: The increasing abundance of drug-resistant bacteria is a global threat. Photodynamic therapy is an entirely new, non-invasive method for treating infections caused by antibiotic-resistant strains. We previously described the bactericidal effect of photodynamic therapy on infections caused by a single type of bacterium. We showed that gram-positive and gram-negative bacteria could be killed with 5-aminolevulic acid and 410 nm light, respectively. However, clinically, mixed infections are common and difficult to treat. OBJECTIVE: We investigated the bactericidal effects of photodynamic therapy on mixed infections of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. METHODS: We compared bacterial growth with and without photodynamic therapy in vitro. Then, in vivo, we studied mixed infections in a mouse skin ulcer model. We evaluated the rates of ulcer area reduction and transitions to healing in treated and untreated mice. In addition, a comparison was made between PDT and existing topical drugs. RESULTS: We found that photodynamic therapy markedly reduced the growth of both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, in culture, and it reduced the skin ulcer areas in mice. PDT was also more effective than existing topical medicines. CONCLUSION: This study showed that photodynamic therapy had antibacterial effects against a mixed infection of gram-positive and gram-negative bacteria, and it promoted skin ulcer healing. These results suggested that photodynamic therapy could be effective in both single- and mixed-bacterial infections.

Mathematical modelling for antimicrobial photodynamic therapy mediated by 5-aminolaevulinic acid: An in vitro study.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) using aminolaevulinic acid (ALA) is a promising alternative to antibiotic therapy. ALA administration induces protoporphyrin IX (PpIX) accumulation in bacteria, and light excitation of the accumulated PpIX generates singlet oxygen to bacterial toxicity. Several factors, including drug administration and light irradiation conditions, contribute to the antibiotic effect. Such multiple parameters should be determined moderately for effective aPDT in clinical practice. METHODS: A mathematical model to predict bacterial dynamics in ALA-aPDT following clinical conditions was constructed. Applying a pharmacokineticspharmacodynamics (PK-PD) approach, which is widely used in antimicrobial drug evaluation, viable bacteria count by defining the bactericidal rate as the concentration of singlet oxygen produced when PpIX in bacteria is irradiated by light. RESULTS: The in vitro experimental results of ALA-aPDT for Pseudomonas aeruginosa demonstrated the PK-PD model validity. The killing rate has an upper limit, and the lower power density for a long irradiation time can suppress the viable bacteria number when the light dosages are the same. CONCLUSIONS: This study proposed a model of bacterial viability change in ALA-aPDT based on the PK-PD model and confirmed, by in vitro experiments using PA, that the variation of bacterial viability with light-sensitive substance concentration and light irradiation power densities could be expressed. Further validation of the PK-PD model with other gram negative and gram positive strains will be needed.

[Continuous Interstitial Subcutaneous Fluid Glucose (ISFG) Measurement during Pre- and Intraoperative Periods for Highly Invasive Surgery].

BACKGROUND: Recently ERAS protocol has become common, and patients in our hospital drink preoperative oral fluid with carbohydrate nutrition. The present study evaluates interstitial subcutaneous fluid glucose (ISFG) with CGMS-Gold and ISFG variability is relevant to oral fluid. METHODS: The data was ISFG measurement with CGMS-Gold from 29 patients undergoing esophagus operation, liver resection, and pancreaticoduodenectomy in September 2011 to September 2012. We divided them into two groups. One was "preoperative (from having oral fluid to entering room) high ISFG group (H group : 11)" which showed preoperative peak ISFG over 200 mg x dl(-1). The other was "preoperative low ISFG group (N group: 18)" which showed preoperative peak ISFG under 200 mg x dl(-1). We compared preoperative and intraoperative (from entering to leaving room) peak ISFG in these groups. RESULTS: Preoperative peak ISFG was 267 ± 55 mg x dl(-1) in H group and 161 ± 16 mg x dl(-1) in N group. Intraoperative peak ISFG was 231 ± 75 mg x dl(-1) in H group and intraoperative peak ISFG was over 180 mg x dl(-1) in 9 patients. Intraoperative peak ISFG was 177 ± 50 mg x dl(-1) in N group and intraoperative peak ISFG was over 180 mg x dl(-1) in 7 patients. Preoperative high ISFG patients tended to show intraoperative high ISFG (P = 0.052); 6 patients were with diabetes mellitus and all the patients had pre- and intraoperative high ISFG. Thirteen patients without diabetes mellitus didn't show intraoperative high ISFG. CONCLUSIONS: This study suggested preoperative high ISFG group tended to show intraoperative high ISFG.

[Perioperative Management of a Patient with Hereditary Angioedema: A Case Report].

Hereditary angioedema (HAE) is a very rare disease that occurs in about 1 in 50,000 to 150,000 people. HAE is caused by low levels or inproper function of the plasma protein C1 inhibitor (C1-INH) which regulates activation of the complement system and the coagulation system. The typical symptom of HAE is regional swellings without pain nor itching, usually triggered by physical trauma or emotional stress. Unlike allergic edema, HAE attacks do not respond to antihistamines, corticosteroids noradrenaline. The swelling attacks against face and throat are potentially life-threatening, and should be treated as a medical emergency. We report a patient with HAE who underwent radical cystectomy of the upper gum under general anesthesia. Because the oral surgery with tracheal intubation is known to be a risk factor of laryngeal edema in a patient with HAE, she was given C1-INH before operation to prevent laryngeal edema according to HAE Guideline 2010 by the Japanese Association for Complement Research. Her pharynx and larynx were checked with Airwayscope before intubation and with bronchofiberscope before extubation, but no edema was recognized. Postoperatively, she was given C1-INH on the next morning again. She was discharged seven days after operation without any complications.

[Retrospective analysis of perioperative cardiovascular complications in patients with low left ventricular function undergoing noncardiac surgery].

BACKGROUND: Regarding patients for noncardiac surgery with low left ventricular function, we have little information about perioperative cardiovascular complications, making it difficult to evaluate such patients preoperatively and to inform them of their perioperative course. METHODS: We retrospectively investigated the patients undergoing noncardiac surgery under general anesthesia in our hospital from January 2008 to December 2011. The subjects were 52 patients with low left ventricular function defined as left ventricular ejection fraction under 40%. Patients with perioperative complications were compared with those without them in about 14 factors which might influence their perioperative course. RESULTS: Only one patient had severe hypotension intraoperatively. Postoperatively, five patients had cardiovascular complications in a week and three more in a month. Compared with those with complications and those without them, significant differences were found in 3 of 14 factors : type of surgery (P = 0.006), operation time (P = 0.013), and amount of intraoperative transfusion (P = 0.039). CONCLUSIONS: Regarding patients for noncardiac surgery with low left ventricular function, high risk of perioperative cardiovascular complications was found in a surgery which is highly invasive, long lasting, or requiring massive transfusion.