Hypericin and Pheophorbide a Mediated Photodynamic Therapy Fighting MRSA Wound Infections: A Translational Study from In Vitro to In Vivo.

High prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625-10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log10 CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower (p < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted.

Clinical Manifestations and Prognostic Factors of Pulmonary Embolism in Adult Patients Visiting the Emergency Department: A Single Institute Experience.

BACKGROUND AND PURPOSE: To investigate the clinical manifestations of a pulmonary embolism (PE) in patients visiting the Emergency Department (ED) and to identify possible prognostic factors among the patients. METHODS: Patients who suspected as PE and presented to the ED with chest tightness, chest pain, or syncope were enrolled. Wells score, revised Geneva score, and PE severity Index (PESI) were all recorded for analysis. Twelve patients who were diagnosed with a PE after a serial work-up were further analyzed for possible prognostic factors. The demographic characteristics, serum lab data, clinical presentations, management strategies, computed tomography (CT) angiography findings, and final outcomes were analyzed retrospectively. Chi-squared tests with Fisher's exact tests, and t-test analyses were applied to evaluate the prognostic factors. RESULTS: Among the 763 patients enrolled, poor prediction effectiveness of Geneva score and Wells score were noticed, and PESI was also found with no significant predictive value in our study group. The initial vital signs, syncope, chest pain, leg edematous changes, dyspnea, D-dimer levels, CT angiography-measured thrombus diameter, the presence of a right atrium (RA) or right ventricular (RV) thrombus, and presence of lung consolidations all revealed no predictive values in this study (p > 0.05). Notably, the presence of a cardiac disease history showed possible prognostic factors for satisfactorily predicting patient outcomes (p = 0.02). The presence of left atrium (LA) thrombus showed a border significant differences in comparison (p = 0.05). CONCLUSIONS: Although the number of patients analyzed was relatively low, our findings suggest that a history of cardiac disease is predictive of a relatively lethal or severe condition in patients with a PE. The diagnosis and prediction of outcomes for patients with a PE remains a challenge and further study is necessary in the future.

Levofloxacin-resistant Helicobacter pylori in Hong Kong.

BACKGROUND: Fluoroquinolone-resistant Helicobacter pylori emerged in 1995 and the resistance was due to point mutation in the gyrA gene. In this study we investigate the resistance mechanism and the antimicrobial susceptibilities of clarithromycin, metronidazole, amoxicillin, tetracycline and telithromycin against levofloxacin-resistant H. pylori in Hong Kong. METHODS: One hundred and ninety-one nonduplicate H. pylori isolates were collected during 2004 and 2005, and 25 isolates with levofloxacin zone sizes less than 30 mm were selected for minimal inhibitory concentration determination by agar dilution, gyrA gene amplication and sequencing the amplified gyrA gene. RESULTS: The prevalence of levofloxacin-resistant H. pylori was 11.5% (22/191). Among these levofloxacin-resistant strains, 7 (31.8%) and 10 (45.5%) were resistant to clarithromycin and metronidazole, respectively, 17 (77.3%) had point mutations in gyrA gene at amino acids 87, 91 and 130 and the most frequent mutation point was at position 91. CONCLUSIONS: Amoxicillin, tetracycline and telithromycin were active against levofloxacin-resistant H. pylori and levofloxacin resistance was mainly due to point mutation in the gyrA gene, especially at amino acid position 91.

Multicenter antimicrobial susceptibility survey of gram-negative bacteria isolated from patients with community-acquired infections in the People's Republic of China.

A survey of 2,099 gram-negative bacilli from community infections at seven centers in the People's Republic of China is reported. The rates of resistance of 1,615 isolates of the family Enterobacteriaceae were as follows: 40.8% for ciprofloxacin, 32.2% for gentamicin, 0% for imipenem or ertapenem, and 14.7% for cefotaxime. The rates of extended-spectrum beta-lactamase production were 16% for Escherichia coli and 17% for Klebsiella.

Comparison of antimicrobial resistance of Acinetobacter baumannii clinical isolates from Shanghai and Hong Kong.

OBJECTIVE: To compare the antimicrobial resistance patterns of Acinetobacter baumannii isolates from Shanghai and Hong Kong. MATERIALS AND METHODS: A total of 212 A. baumannii strains of one isolate per patient were collected from Shanghai and Hong Kong from August 2002 to August 2003 that were tested against 15 commonly used antimicrobial agents by the agar dilution method according to the NCCLS guidelines. RESULTS: Most beta-lactams showed no significant increase in activity after adding beta-lactamase inhibitors. The resistance rates of the isolates against ticarcillin-clavulanate, piperacillin-tazobactam and ampicillin-sulbactam were for Shanghai 74.9, 70.9, 69.1% and Hong Kong 24.3, 18.9, 13.5%, respectively. Only cefoperazone-sulbactam showed a significant increase in activity against both Shanghai and Hong Kong strains, as the resistance rates dropped from 93.7 to 8.6% and 83.8 to 5.4%, respectively. The resistance rates of ceftazidime, cefepime, and gentamicin against Shanghai strains were 69.7, 72.0, 73.7% and Hong Kong strains 69.7, 29.7, 18.9%, respectively. About 65% of Shanghai strains were found to be amikacin-resistant, however, all Hong Kong strains were sensitive. Fluoroquinolones including ciprofloxacin and levofloxacin had resistance rates over 60% against Shanghai strains, but only 13.5% against Hong Kong strains. Shanghai strains had imipenem and meropenem resistance rate of 6.3%. Though 10.8% Hong Kong strains were resistant to meropenem, only 2.7% of them were resistant to imipenem. CONCLUSION: A. baumannii isolated from Shanghai were more resistant to all drugs except meropenem than Hong Kong isolates. The results indicate a need for measures to control the abuse of antibiotic usage in order to prevent the emergence of more multidrug-resistant isolates in both cities.

In vitro activity of telithromycin against respiratory tract pathogens in comparison with other antimicrobial agents.

This study was done to evaluate the in vitro activity of a new ketolide telithromycin in comparison with clarithromycin, erythromycin, moxifloxacin and levofloxacin against Streptococcus pneumoniae (n = 67), Haemophilus influenzae (n = 139), and Moraxella catarrhalis (n = 46)collected between January and June 2003 in Hong Kong. Among the H. influenzae isolates, 25.2% produced beta-lactamase, while 97.8% of M. catarrhalis isolates produced beta-lactamase. Half of the S. pneumoniae isolates were nonsusceptible to penicillin, and 90.9% of these strains were resistant to clarithromycin and erythromycin. One (1.5%) S. pneumoniae strain was resistant to levofloxacin (MIC = 8 mg/l) and all isolates were sensitive to moxifloxacin and telithromycin with MIC <1 mg/l. H. influenzae isolates were sensitive to all fluoroquinolones tested and 2.2% of H. influenzae were resistant to clarithromycin. M. catarrhalis isolates were sensitive except 1 strain which was resistant to levofloxacin (MIC = 4 mg/l) and moxifloxacin (8 mg/l). All M. catarrhalis strains were sensitive to telithromycin with MIC90 = 0.5 mg/l. Telithromycin demonstrated high activity and no resistance was found in all these major respiratory tract pathogens.