Evaluation of three alternatives cost-effective culture media for Mycobacterium tuberculosis detection and drug susceptibility determination using the microscopic observation drug susceptibility (MODS) assay.

Tuberculosis phenotypic detection assays are commonly used in low-resource countries. Therefore, reliable detection methods are crucial for early diagnosis and treatment. The microscopic observation drug susceptibility (MODS) assay is a culture-based test to detect Mycobacterium tuberculosis and characterize drug resistance in 7-10 days directly from sputum. The use of MODS is limited by the availability of supplies necessary for preparing the enriched culture. In this study, we evaluated three dry culture media that are easier to produce and cheaper than the standard one used in MODS [1]: an unsterilized powder-based mixed (Boldú et al., 2007) [2], a sterile-lyophilized medium, and (Sengstake et al., 2017) [3] an irradiated powder-based mixed. Mycobacterial growth and drug susceptibility were evaluated for rifampin, isoniazid, and pyrazinamide (PZA). The alternative cultures were evaluated using 282 sputum samples with positive acid-fast smears. No significant differences were observed in the positivity test rates. The positivity time showed high correlations (Rho) of 0.925, 0.889, and 0.866 between each of the three alternative media and the standard. Susceptibility testing for MDR and PZA showed an excellent concordance of 1 compared to the reference test. These results demonstrate that dry culture media are appropriate and advantageous for use in MODS in low-resource settings.

Phytochemical screening, cytotoxicity assessment and evaluation of in vitro antiplasmodial and in vivo antimalarial activities of Mentha spicata L. methanolic leaf extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria causes extensive morbidity and mortality, and the decreasing efficacy of artemisinin and its partner drugs has posed a serious concern. Therefore, it is important to identify new antimalarials, and the natural compounds from plants provide a promising platform. Mentha spicata L. representing the Lamiaceae family has been used in traditional medicine for various diseases including malaria. AIM OF THE STUDY: This study was aimed at evaluating the antiplasmodial activity of M. spicata methanolic leaf extract using Plasmodium falciparum (Pf) cultures (Pf3D7 and artemisinin (ART)-resistant PfCam3.IR539T strains) and antimalarial activity using Plasmodium berghei (Pb)-infected mice. Dry leaf powder and methanolic leaf extract were examined for in vivo antimalarial activity and the efficacy of oral versus parenteral administration was compared. MATERIALS AND METHODS: Leaves of M. spicata were collected and extracted using 70% methanol in water (v/v). [3H]-hypoxanthine incorporation assays and Giemsa-stained smears were used to assess the in vitro antiplasmodial activity of M. spicata methanolic extract against Pf3D7 and ART-resistant PfCam3.IR539T strains. Cytotoxicity was evaluated in HeLa and HEK-293T cell lines using MTT assays. Hemolysis assays were performed using red blood cells (RBCs). In vivo antimalarial activities of M. spicata dry leaf powder and methanolic leaf extract were examined in P. berghei-infected mice by Rane's curative test and Peters' 4-day suppressive test. RESULTS: Phytochemical screening of M. spicata methanolic leaf extract indicated the presence of reducing sugars, phenolic compounds, flavonoids, glycosides, sterols, saponins, alkaloids, coumarins, tannins, carbohydrates, and proteins. In vitro studies carried out using Pf cultures showed that M. spicata methanolic leaf extract had significant antiplasmodial activity against Pf3D7 cultures with a 50% inhibitory concentration (IC50) of 57.99 ± 2.82 µg/ml. The extract was also effective against ART-resistant PfCam3.IR539T strain with an IC50 of 71.23 ± 3.85 µg/ml. The extract did not show significant in vitro cytotoxicity, hemolysis, and in vivo toxicity. In vivo studies performed using Pb-infected mice treated with M. spicata dry leaf powder and methanolic leaf extract showed ∼50% inhibition in parasite growth at 1500 mg/kg and 1000 mg/kg doses, respectively. There was also a significant delay in the mortality of treated mice. Parenteral administration was found to be appropriate for the in vivo treatment. CONCLUSIONS: Our in vitro and in vivo findings from Pf and Pb parasites suggested the therapeutic potential of M. spicata leaf extract as an antimalarial. M. spicata leaf extract could also inhibit the growth of ART-resistant Pf strain. Further studies on fractionation and active component analysis of M. spicata leaf extract would be required to identify the bioactive phytochemicals having pharmaceutical and therapeutic values. Such efforts would help us in developing new antimalarials to combat malaria.

An observational assessment of the safety of mass drug administration for trachoma in Ethiopian children.

BACKGROUND: The International Trachoma Initiative (ITI) provides azithromycin for mass drug administration (MDA) to eliminate trachoma as a public health problem. Azithromycin is given as tablets for adults and powder for oral suspension (POS) is recommended for children aged <7 y, children <120 cm in height (regardless of age) or anyone who reports difficulty in swallowing tablets. An observational assessment of MDA for trachoma was conducted to determine the frequency with which children aged 6 mo through 14 y received the recommended dose and form of azithromycin according to current dosing guidelines and to assess risk factors for choking and adverse swallowing events (ASEs). METHODS: MDA was observed in three regions of Ethiopia and data were collected on azithromycin administration and ASEs. RESULTS: A total of 6477 azithromycin administrations were observed; 97.9% of children received the exact recommended dose. Of children aged 6 mo to <7 y or <120 cm in height, 99.6% received POS. One child experienced choking and 132 (2%) experienced ≥1 ASEs. Factors significantly associated with ASEs included age 6-11 mo or 1-6 y, non-calm demeanor and requiring coaxing prior to drug administration. CONCLUSIONS: There is a high level of adherence to the revised azithromycin dosing guidelines and low incidence of choking and ASEs.

Clinical Response and Cost-Savings Associated With Generic Fluticasone Propionate/Salmeterol Multidose, Dry-Powder Inhaler in Asthma Patients Managed in an Ambulatory Care Practice Setting.

BACKGROUND: Fluticasone propionate/salmeterol multidose, dry powder inhaler (MDPI) was the first and only authorized generic inhaled corticosteroid/long-acting beta agonist (ICS/LABA) combination inhaler at the time of this study. This offers the potential for significant prescription cost-savings for both patients and accountable care organizations. The objective of the study was to demonstrate patients' clinical response to generic fluticasone propionate/salmeterol MDPI when switched from one of its brand name competitors. METHODS: The study was approved by the Institutional Review Board at MCPHS University. This was a prospective chart review of a large, multi-center ambulatory care organization in the Greater Boston area. Patients 12 years of age or older who were switched from a brand-name ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI were included in the study. The primary endpoint was worsened asthma control requiring a change in therapy, oral corticosteroid therapy, or hospitalization at or before 12 weeks after the inhaler was switched. RESULTS: In total, 203 patients met inclusion criteria. Of those 203 patients, 35 had a change in therapy due to worsened asthma control (17.2% of patients, 95% CI 12.0% to 22.4%) within 12 weeks. Total projected yearly prescription cost-savings for patients who were switched and remained on the generic inhaler was $581,628. CONCLUSION: Eighty-three percent of patients maintained appropriate asthma control after switching from a brand ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI for 12 weeks. Switching to the generic inhaler resulted in significant prescription cost-savings for the accountable care organization.

The Role of ICS/LABA Fixed-Dose Combinations in the Treatment of Asthma and COPD: Bioequivalence of a Generic Fluticasone Propionate-Salmeterol Device.

Both asthma and chronic obstructive pulmonary disease (COPD) are inflammatory chronic respiratory conditions with high rates of morbidity and mortality worldwide. The objectives of this review are to briefly describe the pathophysiology and epidemiology of asthma and COPD, discuss guideline recommendations for uncontrolled disease, and review a new generic option for the treatment of asthma and COPD. Although mild forms of these diseases may be controlled with as-needed pharmacotherapy, uncontrolled or persistent asthma and moderate or severe COPD uncontrolled by bronchodilators with elevated eosinophilia or frequent exacerbations may require intervention with combination therapy with inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), according to international guidelines. Fixed-dose combinations of ICS/LABA are commonly prescribed for both conditions, with fluticasone propionate (FP) and salmeterol forming a cornerstone of many treatment plans. An oral inhalation powder containing the combination of FP and salmeterol has been available as Advair Diskus® in the United States for almost 20 years, and the first and only substitutable generic version of this product has recently been approved for use: Wixela™ Inhub™. Bioequivalence of Wixela Inhub and Advair Diskus has been established. Furthermore, the Inhub inhaler was shown to be robust and easy to use, suggesting that Wixela Inhub may provide an alternative option to Advair Diskus for patients with asthma or COPD requiring intervention with an ICS/LABA.

Long-Term Nonclinical Pulmonary Safety Assessment of Afrezza, a Novel Insulin Inhalation Powder.

Afrezza delivers inhaled insulin using the Gen2 inhaler for the treatment of patients with type 1 and type 2 Diabetes. Afrezza was evaluated in long-term nonclinical pulmonary safety studies in 2 toxicology species. Chronic inhalation toxicology studies in rat (26 weeks) and dog (39 weeks) and an inhalation carcinogenicity study in rats were conducted with Technosphere insulin (Afrezza) and with Technosphere alone as a vehicle control. Respiratory tract tissues were evaluated by histopathology and cells expressing proliferating cell nuclear antigen (PCNA) were quantified in lungs of rats. Microscopic findings in rats exposed to Afrezza were attributed to the Technosphere particle component, were confined to nasal epithelia, and consisted of eosinophilic globules and nasal epithelial degeneration. There were no Afrezza-related changes in pulmonary PCNA labeling indices in alveoli, large bronchioles, or terminal bronchioles. Microscopic findings in rats exposed to Technosphere particles included eosinophilic globules, mucus cell hyperplasia, and epithelial degeneration in the nasal cavities. PCNA labeling indices were increased in large bronchioles and terminal bronchioles but not in alveoli. There were no Technosphere particle-related findings in the dog study. Afrezza did not exhibit carcinogenic potential in the 2-year study in rats. These nonclinical inhalation studies support the use of Afrezza in humans over extended periods.

Perianal Dermatitis, Its Incidence, and Patterns of Topical Therapies in a Level IV Neonatal Intensive Care Unit.

OBJECTIVE: To define the incidence of perianal dermatitis (PD) and determine the usage pattern and cost efficacy of diaper products among neonates admitted to a level IV neonatal intensive care unit (NICU) including those with a diagnosis of neonatal abstinence syndrome (NAS). METHODS: A retrospective cohort study to evaluate neonates with PD based on number of orders for Aquaphor, Bagbalm, Desitin, Flanders, or Nystatin. Various demographic and clinical parameters were recorded. Usage patterns of these five products were analyzed, and their costs estimated. Subgroup analysis was performed among infants with NAS. RESULTS: Of 1,241 admissions, 56.2% had at least one diaper product ordered during their NICU stay, while 52.6% had multiple products ordered. Only 23.0% of all neonates had appropriate documentation of PD. The most common product ordered first was Aquaphor (64.3%), followed by Desitin (19.2%). Note that 86% term NAS infants had PD compared with 28% term non-NAS infants. The estimated product cost was $14,139 over 2 years, averaging $20 per patient. CONCLUSION: Over half of NICU neonates were exposed to one or more diaper products, usually without documented PD diagnosis. Term NAS infants had three times higher incidence of PD than term non-NAS infants. The cost of diaper product use was significant, and possibly underestimated due to lack of documentation.

Local intrawound vancomycin powder decreases the risk of surgical site infections in complex adult deformity reconstruction: a cost analysis.

STUDY DESIGN: Retrospective cohort analysis. OBJECTIVE: To evaluate the rate of surgical site infections (SSIs) and cost-effectiveness of the use of intraoperative vancomycin powder in thoracolumbar adult deformity procedures. SUMMARY OF BACKGROUND DATA: The rates of SSI remain unacceptably high in adult spinal deformity surgery despite routine intravenous antibiotics. Vancomycin powder applied directly to the wound intraoperatively has shown promise for decreasing SSI in spine surgery. METHODS: Adults who underwent adult deformity reconstruction by 2 surgeons between 2008 and 2012 with a minimum of 3 months of clinical follow-up were retrospectively reviewed. The patients were subdivided into those who had received only routine perioperative intravenous antibiotics (control) and those who received intravenous antibiotics and 2 g of vancomycin powder applied into the surgical wound. The primary outcome was SSI within 90 days. Secondary outcomes included surgical/clinical parameters and SSI-related medical costs based on hospital billing records. RESULTS: Two hundred fifteen patients were evaluated-controls (n=64) and vancomycin powder group (n=151). The average number of levels fused was 10 (5-17, control) and 12 (5-19, vancomycin). The mean follow-up was 34 months (3-68 mo, control) and 18 months (3-35 mo, vancomycin) (P<0.05). There were significantly fewer hospital readmissions within 90 days for SSI in patients who received vancomycin powder (2.6%; 4/151) compared with controls (10.9%; 7/64) (P=0.01). There were no reported adverse events related to the intrawound vancomycin use. The average cost per patient of treating a postoperative SSI was higher in the control group ($34,388) than in the study group ($28,169). With the use of vancomycin powder, there was a cost saving of $244,402 per 100 complex spinal procedures. CONCLUSION: Local application of vancomycin powder significantly decreased SSI for adults undergoing spinal reconstructive surgery. This resulted in cost savings of $244,402 per 100 thoracolumbar adult deformity procedures. LEVEL OF EVIDENCE: 3.