Assessment of a novel continuous cleaning device using metatranscriptomics in diverse hospital environments.

Introduction: Despite routine implementation of cleaning and disinfection practices in clinical healthcare settings, high-touch environmental surfaces and contaminated equipment often serve as reservoirs for the transmission of pathogens associated with healthcare-associated infections (HAIs). Methods: The current study involved the analysis of high-touch surface swabs using a metatranscriptomic sequencing workflow (CSI-Dx™) to assess the efficacy of cleanSURFACES® technology in decreasing microbial burden by limiting re-contamination. This is a non-human single center study conducted in the Emergency Department (ED) and on an inpatient Oncology Ward of Walter Reed National Military Medical Center that have followed hygienic practices during the COVID-19 pandemic environment. Results: Although there was no difference in observed microbial richness (two-tailed Wilcoxon test with Holm correction, P > 0.05), beta diversity findings identified shifts in microbial community structure between surfaces from baseline and post-intervention timepoints (Day 1, Day 7, Day 14, and Day 28). Biomarker and regression analyses identified significant reductions in annotated transcripts for various clinically relevant microorganisms' post-intervention, coagulase-negative staphylococci and Malassezia restricta, at ED and Oncology ward, respectively. Additionally, post-intervention samples predominantly consisted of Proteobacteria and to a lesser extent skin commensals and endogenous environmental microorganisms in both departments. Discussion: Findings support the value of cleanSURFACES®, when coupled with routine disinfection practices, to effectively impact on the composition of active microbial communities found on high-touch surfaces in two different patient care areas of the hospital (one outpatient and one inpatient) with unique demands and patient-centered practices.

cleanSURFACES® intervention reduces microbial activity on surfaces in a senior care facility.

As one of the top public health challenges outlined by the Centers for Disease Control (CDC), estimates report that hospital acquired infections (HAIs) claim the lives of 99,000 Americans and cost healthcare providers over $28 billion each year. In addition to underlying conditions related to age, elderly patients in long-term care facilities are at an elevated risk of acquiring HAIs. A large percentage of HAIs is attributable to contaminated surfaces and medical devices. To that end, this study utilized a metatranscriptomic sequencing workflow (CSI-Dx™) to profile active microbial communities from surfaces in the HJ Heinz Community Living Center, a long-term care facility in the Veterans Affairs Pittsburgh Health Care System. Swabs were collected from high-touch surfaces (Keyboard, Ledge, Workstation on Wheels, Worksurfaces) before (Baseline) and after cleanSURFACES® were installed at 4 timepoints (Day 1, Day 7, Day 14, and Day 30). Microbial richness was significantly reduced after cleanSURFACES® intervention (Wilcoxon test with Holm correction, p=0.000179). Beta diversity results revealed distinct clustering between Baseline and Post-intervention samples (Adonis, p<0.001). Reduction in bacterial (Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis) and fungal (Malassezia restricta, Candida albicans, Candida glabrata, and Candida orthopsilosis) expression of opportunistic pathogens was observed. Additionally, a subset of taxa (Corynebacterium, Cutibacterium acnes, and Ralstonia pickettii) was present in specific Post-intervention timepoints and surface types. This study revealed decreased microbial activity, highlighting the potential for the combinatorial application of cleanSURFACES® and regular decontamination practices to reduce the prevalence of microbes causing HAIs.

Pharmacokinetics and tolerability of sumatriptan after single-dose administration of a fixed-dose combination tablet of sumatriptan/naproxen sodium 85/500 mg followed two hours later by subcutaneous sumatriptan 4- or 6-mg injection: a randomized, open-label, three-period crossover study in healthy volunteers.

BACKGROUND: Rescue medication options that are consistent with the product labeling for sumatriptan/naproxen sodium (S/N) and that have been permitted in >or=1 clinical trial include the use of a second tablet of S/N, sumatriptan tablets (to a total daily dose of 200 mg), and naproxen sodium tablets (within the maximum limits recommended in the labeling). Sumatriptan subcutaneous (SC) injection might be especially useful as rescue medication mostly because of its rapid onset of activity. OBJECTIVE: The aim of this study was to assess the pharmacokinetics and tolerability of sumatriptan SC used as rescue medication after the administration of oral S/N for the treatment of migraine. METHODS: This randomized, open-label, 3-period crossover study compared the exposure to sumatriptan (Cmax and AUC to 14 hours after the administration of the second dose [AUC(0-14)]) between 3 treatment regimens: an initial dose of S/N 85/500 mg followed 2 hours later by sumatriptan 4 or 6 mg SC (S/N + S4 and S/N + S6, respectively) (test), or sumatriptan 100 mg PO (2 tablets administered 2 hours apart) (S100 + S100) (reference). Healthy adults aged 18 to 55 years were randomly assigned to receive all 3 regimens in a randomized sequence. On day 1 of each treatment period, continuous cardiovascular monitoring (ECG telemetry), serial 12-lead ECG, and serial blood pressure (BP) measurements were conducted 1 hour before to 10 hours after the administration of the first dose. Blood samples for pharmacokinetic assessment were collected up to 14 hours after the administration of the first dose. Adverse events (AEs) were monitored from the time of consent until study completion. Participants returned to the clinic for pharmacokinetic blood sampling (for S/N + S4 and S/N + S6) and for tolerability assessment at 24, 48, and 72 hours after S/N administration. RESULTS: A total of 30 healthy adults were randomized. Five withdrew prematurely (3, withdrawn consent; 1, AE; and 1, protocol deviation). Half of the subjects were men, the mean age was 27.8 years, and the mean weight was 79.3 kg (range, 54.6-100.8 kg). With S/N + S4, sumatriptan Cmax and AUC(0-14) did not exceed those with S100 + S100. Sumatriptan Cmax was 1.26-fold higher with S/N + S6 than with S100 + S100. Sumatriptan AUC(0-14) with S/N + S6 was not significantly greater than that with S100 + S100. Differences in serial BP measurements between the SC and S100 + S100 regimens were not statistically significant. The numbers of subjects in whom any AE was reported were 10 (37%) with S/N + S4, 14 (54%) with S/N + S6, and 13 (48%) with S100 + S100. CONCLUSIONS: Sumatriptan 4 and 6 mg SC administered 2 hours after an S/N tablet yielded sumatriptan exposure that did not exceed that of S100 + S100. Cmax with the S/N + S6 regimen was 1.26-fold higher than reference values. Both regimens were reasonably well tolerated. Randomized controlled trials are needed to test the efficacy and tolerability of these SC regimens. ClinicalTrials.gov identifier: NCT00875784.

Distinct pharmacokinetic profile and safety of a fixed-dose tablet of sumatriptan and naproxen sodium for the acute treatment of migraine.

OBJECTIVE: To describe the pharmacokinetic and safety profiles of sumatriptan 85 mg formulated with RT Technology (RT) and naproxen sodium 500 mg in a fixed-dose combination tablet (sumatriptan/naproxen sodium) that targets both serotonergic dysmodulation and inflammation in migraine. METHODS: Six open-label, crossover studies were conducted in healthy volunteers (Studies 1, 2, 3, 4, 5) or patients with migraine (Study 6). RESULTS: Consistently across studies, naproxen administered as a component of sumatriptan/naproxen sodium demonstrated a delayed-release profile similar to that of an enteric-coated product. Naproxen from the combination tablet showed a delayed time to peak plasma concentration and lower peak plasma concentration while exposures (area under the plasma concentration-time curve) were similar. The peak plasma concentration for naproxen was approximately 36% lower and the time to peak plasma concentration approximately 4 hours later when naproxen was administered as sumatriptan/naproxen sodium compared with a single naproxen sodium 550 mg tablet. Sumatriptan peak plasma concentration and area under the plasma concentration-time curve after administration of sumatriptan/naproxen sodium (containing sumatriptan 85 mg) were comparable to those after administration of a commercially available sumatriptan 100 mg (RT) tablet. Sumatriptan time to peak plasma concentration occurred, on average, 30 minutes earlier with sumatriptan/naproxen sodium compared with sumatriptan 100 mg (RT). No clinically significant differences between sumatriptan/naproxen sodium and sumatriptan tablets 100 mg (RT) were identified with respect to electrocardiograms, blood pressure, or heart rate. In addition, food had no significant effect on the bioavailability of naproxen or sumatriptan after administration of sumatriptan/naproxen sodium but slightly delayed the time to peak plasma concentration of sumatriptan by approximately 40 minutes. The pharmacokinetics of sumatriptan and naproxen did not differ according to whether sumatriptan/naproxen sodium was administered during a migraine attack or a migraine-free period. The pharmacokinetics of 2 sumatriptan/naproxen sodium tablets administered 2 hours apart were consistent with the pharmacokinetic predictions from a single dose of the combination tablet. The adverse-event profile of the sumatriptan/naproxen sodium combination tablet did not appear to differ from that of the individual components of the same or similar dosage strengths administered alone or in combination. In addition, the incidence of adverse events with 2 sumatriptan/naproxen sodium tablets administered 2 hours apart was lower than that with the single dose. CONCLUSION: The combination tablet of sumatriptan/naproxen sodium has unique pharmacokinetic properties. The rapid absorption of sumatriptan with the delayed-release properties of naproxen sodium from sumatriptan/naproxen sodium might contribute to its therapeutic advantage over monotherapy with either component. No clinically meaningful effects of food, administration during a migraine attack, or administration of a second tablet (2 hours after initial dose) on the pharmacokinetics or safety of sumatriptan/naproxen sodium were observed.

Effects of cilomilast, a selective phosphodiesterase 4 inhibitor, on esophageal motility and pH, and orocecal and colonic transit: two single-center, randomized, double-blind, placebo-controlled, two-part crossover studies in healthy volunteers.

BACKGROUND: Phase IIb studies have reported that cilomilast, a selective phosphodiesterase 4 inhibitor being developed for the treatment of chronic obstructive pulmonary disease, is associated with gastrointestinal (GI) adverse effects (AEs) in a small proportion (approximately 5%) of individuals. OBJECTIVES: The aims of these 2 studies were to investigate the effects of cilomilast 15 mg BID on: (1) lower esophageal sphincter pressure (LESP) and esophageal body motility and pH (study 1); and (2) orocecal and whole-gut transit times (OCTT and WGTT, respectively) (study 2) in healthy volunteers. METHODS: These 2 randomized, double-blind, placebo-controlled, 2-part crossover studies were conducted at the Neurogastroenterology Unit, Wythenshawe Hospital, Manchester, United Kingdom (study 1) and GlaxoSmithKline, Harlow, United Kingdom (study 2). In study 1, subjects were randomly assigned to receive either cilomilast (15 mg BID) or matched placebo (control) for 7 days (13 doses; subjects were not given the evening dose on day 7), and in study 2, cilomilast (15 mg BID) or matched placebo (control) for 9 days (18 doses) in each of 2 treatment periods. After study drug administration, combined esophageal motility and pH were recorded for 2 hours before and 4 hours after the administration of a standardized meal (2400 kJ [573 kcal]). Sequences of 6 consecutive 5-mL water swallows (separated by 20 seconds) were carried out 60 and 90 minutes (fasting) and 150, 180, 210, 240, 300, and 360 minutes (fed) after study drug administration. OCTT was determined from the increase in breath hydrogen after the meal. WGTT was determined from the time taken to excrete at least 16 of 20 ingested radiopaque markers, ingested as 2 capsules, each containing 10 radiopaque markers, with 240 mL of water. AEs were elicited at specified times throughout each session using nonleading questions, spontaneously reported AEs, and diary cards. RESULTS: Study 1 enrolled 20 subjects (11 men, 9 women; age range, 20-52 years). Study 2 enrolled 16 subjects (10 men, 6 women; age range, 19-48 years). No clinically significant differences in the amplitude (mean difference in postprandial-preprandial AUC0-t/t, 6.09 mm Hg; 95% CI, -10.66 to 22.84), duration (difference, -0.08 second; 95% CI, -0.54 to 0.37), or velocity of propagation (difference, 0.90 cm/s; 95% CI, -0.66 to 2.46) of esophageal contractions, LESP (difference, -0.39 mm Hg; 95% CI, -5.23 to 4.45), or preprandial or postprandial percentage time pH<4 (median differences: preprandial, 0.47% [95% CI, -0.45 to 1.27]; postprandial, -0.005% [95% CI, -1.30 to 6.27]) were found with cilomilast compared with placebo. No significant differences in OCTT (difference, -0.37 hour; 95% CI, -1.59 to 0.84) or WGTT (difference, -2.96 hours; 95% CI, -20.76 to 14.84) were found with cilomilast compared with controls. In both studies, the most frequently reported AEs with cilomilast use were nausea (8/18 in study 1 and 3/16 in study 2) and headache (8/18 in study 1 and 6/16 in study 2); however, these were generally of mild to moderate intensity. Overall, GI AEs did not correlate with changes in GI motility. CONCLUSION: The results of these 2 studies suggest that cilomilast was not associated with significant changes in esophageal motility and pH or GI transit in these healthy volunteers.

Pharmacokinetic profile of a new form of sumatriptan tablets in healthy volunteers.

OBJECTIVE: Rapid delivery of migraine-specific medication to its site(s) of action is thought to be crucial in preventing or minimizing sensitization of central pain pathways and thereby in optimizing pain-free outcomes in patients with migraine. Sumatriptan has been developed as a new tablet formulation to enhance the rate of systemic drug delivery by improving tablet disintegration and drug dispersion relative to those of conventional tablets. These enhanced formulation characteristics may be beneficial during occurrences of the gastric stasis that can accompany migraine. METHODS: This randomized, open-label, 4-way crossover study (n = 32) was conducted to determine whether the new formulation of sumatriptan 50 and 100 mg is bioequivalent to sumatriptan conventional tablets and to compare the pharmacokinetic profiles of the new formulation and the conventional tablet during the early (0-2 h) postdose interval in healthy volunteers. Pharmacokinetics during the early post-dose interval are important in determining a drug's onset of action, an important parameter to patients with migraine. RESULTS: The results confirm that the new formulation of sumatriptan and sumatriptan conventional tablets are bioequivalent as demonstrated by the finding that the 90% confidence intervals for the sumatriptan area under the concentration time curve to infinity and to the last evaluable time point (AUC(0- infinity ) and AUC(0-t), respectively) and maximum plasma concentration (C(max)) fell within the predetermined bounds defining bioequivalence (0.80-1.25) for both doses. Pharmacokinetic parameters measured early (0-2 h) after dosing reveal slightly faster absorption, on average, of the new sumatriptan formulation than sumatriptan conventional tablets although high intersubject variability was observed. For the new sumatriptan formulation, AUC(0-2) (AUC up to 2 h post dose) was, on average, 1% greater (50 mg) and 8% greater (100 mg) and maximal sumatriptan levels were attained, on average, 10 min earlier (50 mg) and 15 min earlier (100 mg) compared with the conventional tablet. Other measures including AUC(0-0.5) (AUC to 30 min post-dose), times to achieve sumatriptan concentrations of 5 and 10 ng/mL, and mean percentage C(max) 15, 20 and 30 min post-dose demonstrate an observable improvement in rate of drug absorption for the new form of sumatriptan compared with conventional tablets. CONCLUSION: The new form of sumatriptan is bioequivalent to sumatriptan conventional tablets and is absorbed more quickly than conventional tablets.