Three new phenazine-type compounds, named phenazines SA-SC (1-3), together with four new natural products (4-7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1-5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.
Animals ; Anti-Bacterial Agents ; chemistry ; metabolism ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Crystallography, X-Ray ; Insecta ; microbiology ; Magnetic Resonance Spectroscopy ; Microbial Sensitivity Tests ; Micrococcus luteus ; drug effects ; Molecular Structure ; Multigene Family ; Phenazines ; chemistry ; metabolism ; pharmacology ; Streptomyces ; chemistry ; genetics ; metabolism

Infections with Pseudomonas aeruginosa are difficult to treat not only because it is often associated with multidrug-resistant infections but also it is able to form biofilm. The aim of this study was to evaluate the antibiofilm and anti-Quorum Sensing (QS) activities of Thymbra capitata essential oils (EOs) against Beta Lactamase (BL) producing P. aeruginosa and the reference strain P. aeruginosa 10145. GC/MS analysis showed that thymol (23.25%) is the most dominant compound in T. capitata EOs. The MICs of T. capitata EOs against P. aeruginosa (BL) and P. aeruginosa 10145 were 1.11%. At sub MIC (0.041, 0.014 and 0.0046%), the EOs of T. capitata remarkably inhibited the biofilm formation of both strains tested and complete inhibition of the biofilm formation was reported at 0.041%. The EOs of T. capitata were found to inhibit the swarming motility, aggregation ability and hydrophobic ability of P. aeruginosa (BL) and P. aeruginosa 10145. Interestingly, the EOs of T. capitata reduce the production of three secreted virulence factors that regulated by QS system including pyocyanin, rhamnolipids and LasA protease. The potent antibiofilm and anti-QS activities of T. capitata EOs can propose it as a new antibacterial agent to control pseudomonas infections.
beta-Lactamases ; Biofilms ; Oils, Volatile ; Pseudomonas aeruginosa ; Pseudomonas Infections ; Pseudomonas ; Pyocyanine ; Quorum Sensing ; Thymol ; Virulence Factors ; Virulence

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.
Amikacin ; Body Mass Index ; Clofazimine ; Consensus ; Disease Progression ; Ethambutol ; Humans ; Lung ; Lung Diseases ; Macrolides ; Mycobacterium avium Complex* ; Mycobacterium avium* ; Mycobacterium* ; Nontuberculous Mycobacteria ; Nutritional Status ; Recurrence ; Rifampin ; Sputum ; Treatment Failure ; Treatment Outcome

Mycobacterium abscessus is the second most important pathogen in pulmonary disease caused by nontuberculous mycobacteria (NTM), following Mycobacterium avium. Mycobacterium abscessus is classified into three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. Mycobacterium abscessus is the most difficult to treat NTM due to its resistance to many antibiotics. Treatment should include an initial regimen of 2–3 injectable and oral antibiotics for several weeks or months, followed by inhaled amikacin and 1–3 oral antibiotics, depending on the subspecies and drug susceptibility patterns, including macrolide susceptibility. The continuation phase should be continued for a minimum of 12 months after culture conversion. Suitable injectable antibiotics include amikacin, imipenem, cefoxitin, and tigecycline, while oral antibiotics include macrolides (azithromycin or clarithromycin), clofazimine, linezolid, and moxifloxacin. Surgery can be a useful adjunctive therapy for some patients with refractory disease. However, the overall treatment prognosis is still unsatisfactory. Therefore, novel and more effective interventions are required for the treatment of M. abscessus pulmonary disease.
Amikacin ; Anti-Bacterial Agents ; Cefoxitin ; Clofazimine ; Humans ; Imipenem ; Linezolid ; Lung Diseases ; Macrolides ; Mycobacterium avium ; Mycobacterium ; Nontuberculous Mycobacteria ; Prognosis

BACKGROUND: Bacterial vaginosis (BV) is the most prevalent cause of symptomatic vaginitis. In the Philippines, prevalence of BV is at 28.16%. The mainstay for the treatment of BV is Metronidazole. Although antibiotic therapy has been shown to eliminate BV associated organisms, there is extremely high recurrence rate.

OBJECTIVE: To compare the efficacy of metronidazole and metronidazole plus lactobacilli tablet in the treatment of bacterial vaginosis among non-pregnant patients seen at the outpatient department of a tertiary medical center.

METHODOLOGY: The population included non-pregnant women ages 15 t0 44 years old, with bacterial vaginosis diagnosed by Amsel's criteria and Nugent's scoring. The participants were randomly assigned to their treatment group, one is Metronidazole only and other received Metronidazole plus Lactobacillus tablet. All participants followed up on day 8,15,22 and 56 from initiation of treatment resolution or persistence of symptoms and collection of vaginal specimen for gram stain and inquire on adverse effects.

RESULTS: On day 8 treatment, there were significantly more participant in the metronidazole plus probiotic arm with an estimated lactobacilli count of more than 30/hpf as comapred to metronidazole alone. On day 15 post treatment, there was no statistically significant difference with the estimated Gardnerella vaginalis count, lactobacilli count, presence or absence of malodorous vaginal discharge between the metronidazole plus probiotic and the metronidazole alone arm. With metronidazole plus probiotic group, the proportion of women with less than 30 per hpf Gardnella vaginalis count and absent foul smelling vaginal discharge were accounted among 100% of the participants from day 8 to 56 post treatment. The early reduction in the causative agent and symptoms can be attributed to an increase in the estimated lactobacilli count sustained until 56 days post treatment metronidazole plus probiotic. However, from day 15 to 22 and 56 post- treatment, the proportion of participants who had a nugent's score of less than 4 were greater for both the metronidazole plus probiotic (100%) and metronidazole alone (95%) arm, when compared to day 8 post-treatment. This finding for the metronidazole plus probiotic group is due to sustained reduction in the Gardnella vaginalis count and increase in lactobacilli counts. Potentially , the metronidazole plus probiotic treatment was found to be more favorable in sustaining the normal flora and probiotic can be used as an adjunct may enhance the efficacy of metronidazole in the treatment of BV.

CONCLUSION: Metronidazole plus probiotic and metronidazole only treatment are comparable in treating bacterial vaginosis. In terms of restoring and maintaining the normal flora, metronidazole plus probiotic appears to be more significantly efficacious. Probiotic in the form of lactobacilli is a promising adjunct to enhance the efficacy of metronidazole in the treatment of bacterial vaginosis.

Human ; Female ; Adult (a Person 19-44 Years Of Age) ; Adolescent (a Person 13-18 Years Of Age) ; Gardnerella Vaginalis ; Vaginosis, Bacterial ; Metronidazole ; Lactobacillus ; Gardnerella ; Probiotics ; Vaginal Discharge ; Gentian Violet ; Phenazines ; Tablets ; Anti-bacterial Agents

BACKGROUND: Bacterial vaginosis (BV) is the most prevalent cause of symptomatic vaginitis. In the Philippines, prevalence of BV is at 28.16%. The mainstay for the treatment of BV is Metronidazole. Although antibiotic therapy has been shown to eliminate BV associated organisms, there is extremely high recurrence rate.
OBJECTIVE: To compare the efficacy of metronidazole and metronidazole plus lactobacilli tablet in the treatment of bacterial vaginosis among non-pregnant patients seen at the outpatient department of a tertiary medical center.
METHODOLOGY: The population included non-pregnant women ages 15 t0 44 years old, with bacterial vaginosis diagnosed by Amsel's criteria and Nugent's scoring. The participants were randomly assigned to their treatment group, one is Metronidazole only and other received Metronidazole plus Lactobacillus tablet. All participants followed up on day 8,15,22 and 56 from initiation of treatment resolution or persistence of symptoms and collection of vaginal specimen for gram stain and inquire on adverse effects.
RESULTS: On day 8 treatment, there were significantly more participant in the metronidazole plus probiotic arm with an estimated lactobacilli count of more than 30/hpf as comapred to metronidazole alone. On day 15 post treatment, there was no statistically significant difference with the estimated Gardnerella vaginalis count, lactobacilli count, presence or absence of malodorous vaginal discharge between the metronidazole plus probiotic and the metronidazole alone arm. With metronidazole plus probiotic group, the proportion of women with less than 30 per hpf Gardnella vaginalis count and absent foul smelling vaginal discharge were accounted among 100% of the participants from day 8 to 56 post treatment. The early reduction in the causative agent and symptoms can be attributed to an increase in the estimated lactobacilli count sustained until 56 days post treatment metronidazole plus probiotic. However, from day 15 to 22 and 56 post- treatment, the proportion of participants who had a nugent's score of less than 4 were greater for both the metronidazole plus probiotic (100%) and metronidazole alone (95%) arm, when compared to day 8 post-treatment. This finding for the metronidazole plus probiotic group is due to sustained reduction in the Gardnella vaginalis count and increase in lactobacilli counts. Potentially , the metronidazole plus probiotic treatment was found to be more favorable in sustaining the normal flora and probiotic can be used as an adjunct may enhance the efficacy of metronidazole in the treatment of BV.
CONCLUSION: Metronidazole plus probiotic and metronidazole only treatment are comparable in treating bacterial vaginosis. In terms of restoring and maintaining the normal flora, metronidazole plus probiotic appears to be more significantly efficacious. Probiotic in the form of lactobacilli is a promising adjunct to enhance the efficacy of metronidazole in the treatment of bacterial vaginosis.

Human ; Female ; Adult ; Adolescent ; Gardnerella Vaginalis ; Vaginosis, Bacterial ; Metronidazole ; Lactobacillus ; Gardnerella ; Probiotics ; Vaginal Discharge ; Gentian Violet ; Phenazines ; Tablets ; Anti-bacterial Agents

PURPOSE: To report a case of secondary pigmentary glaucoma due to clofazimine treatment for extensive drug-resistant tuberculosis. CASE SUMMARY: A 23-year-old man presented with blurred vision in both eyes. The patient started to take clofazimine for extensive drug-resistant tuberculosis six months prior, after which his facial skin color changed to a dark-brown. Intraocular pressure (IOP) was 50 mm Hg in the right eye and 48 mm Hg in the left eye. Slit lamp examination revealed corneal edema, opacity, and flare in the anterior chamber in both eyes. A color vision test revealed a mild color defect in both eyes. Visual field (VF) test revealed superior temporal VF loss in the left eye. Gonioscopy revealed open angles with high pigmentation in the trabecular meshwork in both eyes. The patient was diagnosed with pigmentary glaucoma, and maximum tolerated medical therapy was performed. However, the IOP was uncontrolled. Trabeculectomy was performed in both eyes. Postoperative IOP was measured to be 12 mm Hg in both eyes without medication, and visual acuity measured 20/22 in the right eye and 20/17 in the left eye. CONCLUSIONS: To the best of our knowledge, this report is the first case of clofazimine being a possible cause of pigmentary glaucoma in a patient with extensive drug-resistant tuberculosis.
Anterior Chamber ; Clofazimine ; Color Vision ; Corneal Edema ; Glaucoma, Open-Angle* ; Gonioscopy ; Humans ; Intraocular Pressure ; Pigmentation ; Skin Pigmentation ; Slit Lamp ; Trabecular Meshwork ; Trabeculectomy ; Tuberculosis, Multidrug-Resistant* ; Visual Acuity ; Visual Fields ; Young Adult

Gentian Violet ; Humans ; Iatrogenic Disease ; Phenazines ; Pneumonia, Bacterial ; diagnosis ; Sputum ; microbiology

Anti-Bacterial Agents ; therapeutic use ; Gentian Violet ; Humans ; Phenazines ; Pneumonia, Bacterial ; diagnosis ; drug therapy ; microbiology

BACKGROUND: The extract and hemiterpene glycosides of Ilex Rotunda Thunb exert antioxidant and anti-inflammatory effects. The effect of rotundarpene on apoptosis in neuronal cells caused by the 1-methyl-4-phenylpyridinium (MPP⁺) has not been reported previously. METHODS: Using differentiated PC12 cells and human neuroblastoma SH-SY5Y cells, we investigated the effect of rotundarpene on MPP⁺-caused apoptosis in relation to the cell death process. RESULTS: MPP⁺-induced cell death was identified using the MTT and neutral red uptake tests. Apoptosis was induced by eliciting decreases in the cytosolic levels of Bid and Bcl-2 proteins, increases in the cytosolic levels of Bax and p53, disruption of the mitochondrial transmembrane potential, and the release of cytochrome c and the activation of caspase-8, -9, and -3 in differentiated PC12 cells and SH-SY5Y cells. Treatment with rotundarpene reduced the MPP⁺-induced changes in the levels of apoptosis-regulated proteins, formation of reactive oxygen species, depletion and oxidation of glutathione, and cell death in both PC12 and SH-SY5Y cells. CONCLUSIONS: Rotundarpene may reduce MPP⁺-induced apoptosis in neuronal cells by suppressing the activation of the mitochondria-mediated pathway and the caspase-8 and Bid pathways. Rotundarpene appears to act by inhibiting the production of reactive oxygen species and by the depletion and oxidation of glutathione.
1-Methyl-4-phenylpyridinium ; Animals ; Apoptosis ; Caspase 8 ; Cell Death* ; Cytochromes c ; Cytosol ; Glutathione ; Glycosides ; Humans ; Ilex ; Membrane Potentials ; Neuroblastoma ; Neurons ; Neutral Red ; PC12 Cells ; Reactive Oxygen Species