Mass spectrometric characterization of circulating and functional antigens derived from piperacillin in patients with cystic fibrosis.

A mechanistic understanding of the relationship between the chemistry of drug Ag formation and immune function is lacking. Thus, mass spectrometric methods were employed to detect and fully characterize circulating Ags derived from piperacillin in patients undergoing therapy and the nature of the drug-derived epitopes on protein that can function as an Ag to stimulate T cells. Albumin modification with piperacillin in vitro resulted in the formation of two distinct haptens, one formed directly from piperacillin and a second in which the dioxopiperazine ring had undergone hydrolysis. Modification was time and concentration dependent, with selective modification of Lys(541) observed at low concentrations, whereas at higher concentrations, up to 13 out of 59 lysine residues were modified, four of which (Lys(190), Lys(195), Lys(432), and Lys(541)) were detected in patients' plasma. Piperacillin-specific T lymphocyte responses (proliferation, cytokines, and granzyme B release) were detected ex vivo with cells from hypersensitive patients, and analysis of incubation medium showed that modification of the same lysine residues in albumin occurred in situ. The antigenicity of piperacillin-modified albumin was confirmed by stimulation of T cells with characterized synthetic conjugates. Analysis of minimally modified T cell-stimulatory albumin conjugates revealed peptide sequences incorporating Lys(190), Lys(432), and Lys(541) as principal functional epitopes for T cells. This study has characterized the multiple haptenic structures on albumin in patients and showed that they constitute functional antigenic determinants for T cells.

Drug metabolite-specific lymphocyte responses in sulfamethoxazole allergic patients with cystic fibrosis.

Sulfamethoxazole (SMX) is an important antibiotic in the management of patients with cystic fibrosis, but allergic reactions may develop thus restricting therapy. The aim of this study was to utilize drug (metabolite) antigens to diagnose SMX-mediated allergic reactions in patients with cystic fibrosis. Lymphocytes from 2/12 allergic patients were stimulated to proliferate strongly with the SMX metabolite nitroso SMX (SMX-NO). In contrast, responses to SMX were weak. The introduction of an antigen-driven T-cell enrichment step prior to the analysis of proliferation increased the sensitivity of the assay. SMX-NO responses were detected with lymphocytes from all patients with cutaneous signs.

Adherence to nebulised antibiotics in cystic fibrosis.

OBJECTIVE: To examine the adherence of patients with cystic fibrosis to nebulised antibiotics. METHODS: A longitudinal design with adherence data collected over 12 weeks. 38 patients (mean age 24.6 years, S.D. 5.3) were recruited from an adult cystic fibrosis (CF) clinic. Adherence was electronically monitored using a Prodose adaptive aerosol delivery (AAD) device. RESULTS: Three indices of adherence were calculated: mean percentage of times the nebuliser was used as prescribed was 50.0% (S.D.=39.7, range 1.1, 155.6); mean percentage of days fully adhered was 31.6% (S.D.=29.4, range 0, 97.2); mean percentage of days nebuliser used at least once was 57.1% (S.D.=34.2, range 3.3, 100). CONCLUSION: Rates of adherence were generally low. Adherence was not associated with any variables apart from age. There were wide variations between individuals, and differences in rates of adherence depending on how this was defined, with potentially important health consequences for the patients. PRACTICE IMPLICATIONS: Technology that improves medication administration may still be associated with low rates of adherence. Health professionals need to be mindful of the pattern of non-adherence for each individual, and factors which may be influencing this.

High Prevalence of Abandoned Needlesticks from Injecting Drug Users in Milton Keynes, UK: Analysing Access to Needle Exchange Centres and Drug Dependency Services.

BACKGROUND: In 2015, Milton Keynes (MK) Council waste management team shows an increase in the numbers of abandoned used needles being found across MK. MK is an area of high Human Immunodeficiency Virus (HIV) prevalence and high Hepatitis C (HCV) in People Who Inject Drugs (PWID), the overriding concern was for the safety of the public. METHODS: Analysis of data collection to understand the scale and spread of the problem, preventing/ reducing the incidence of abandoned needles and looking at access to the designated Drug Dependency Unit (DDU) and the Blood Borne Virus (BBV) service. Through data mapping, hotspot areas of used needles abandonment were analysed. RESULTS: Peak needle stick finds were in March and June 2015 mainly in areas of social deprivation and marginalisation where designated needle exchange points were identified. 174 reports of abandoned needles were reported between January 2015 and November 2015 with a total of 2379 individual needles. 87% of the total numbers of needles were found in just 8 estates. CONCLUSION: Tackling the issue of abandoned needles effectively should be done through a targeted, multi-agency approach. Reductions in needlestick abandonment can be strengthened through improving access to needle exchange points, DDU and BBV services, delivering high-quality harm reduction interventions and using data mapping in order to identify and target hot spot areas.

Sequential bronchoscopy in the management of lobar atelectasis secondary to allergic bronchopulmonary aspergillosis.

Lobar atelectasis is a common complication in patients with cystic fibrosis. Failure to reexpand the lung isassociated with poorer outcomes. We report sequential weekly flexible bronchoscopy, with instillation of recombinant human DNase, in 5 patients with cystic fibrosis who had lobar collapse secondary to allergic bronchopulmonary aspergillosis. The number of procedures ranged from 2 procedures in 3 patients, 3procedures in 1 patient, and 4 procedures in another patient. All the patients achieved full reexpansion radiologically and the procedures were well tolerated. We conclude that sequential bronchoscopy in patients who fail to show reexpansion of the lung is effective and should be considered as part of standard medical management.

Carbohydrate ingestion improves performance of a new reliable test of soccer performance.

The aim of the study was to investigate the reliability of a new test of soccer performance and evaluate the effect of carbohydrate (CHO) on soccer performance. Eleven university footballers were recruited and underwent 3 trials in a randomized order. Two of the trials involved ingesting a placebo beverage, and the other, a 7.5% maltodextrin solution. The protocol comprised a series of ten 6-min exercise blocks on an outdoor Astroturf pitch, separated by the performance of 2 of the 4 soccer-specific tests, making the protocol 90 min in duration. The intensity of the exercise was designed to be similar to the typical activity pattern during soccer match play. Participants performed skill tests of dribbling, agility, heading, and shooting throughout the protocol. The coefficients of variation for dribbling, agility, heading, and shooting were 2.2%, 1.2%, 7.0%, and 2.8%, respectively. The mean combined placebo scores were 42.4 +/- 2.7 s, 43.1 +/- 3.7 s, 210 +/- 34 cm, and 212 +/- 17 points for agility, dribbling, heading, and kicking, respectively. CHO ingestion led to a combined agility time of 41.5 +/- 0.8 s, for dribbling 41.7 +/- 3.5 s, 213 +/- 11 cm for heading, and 220 +/- 5 points for kicking accuracy. There was a significant improvement in performance for dribbling, agility, and shooting (p < .05) when CHO was ingested compared with placebo. In conclusion, the protocol is a reliable test of soccer performance, and ingesting CHO leads to an improvement in soccer performance.

Serum and sputum concentrations following the oral administration of linezolid in adult patients with cystic fibrosis.

OBJECTIVES: Linezolid is a new oxazolidinone antibiotic with efficacy against a broad range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we have determined the serum and sputum linezolid concentrations in adults with cystic fibrosis (CF) following oral drug administration. METHODS: Eleven adult patients with CF were recruited. Subjects received 600 mg of linezolid orally every 12 h for a total of six doses. Serum and sputum levels were measured just before and at 2 h after the final dose of linezolid. A further serum level was measured at 4 h. RESULTS: Ten adult patients completed the study. Mean (s.d.) serum linezolid concentrations were 2.3 mg/L (1.5) at 12 h following the fifth dose. At 2 and 4 h following the sixth dose, concentrations were 13.5 (4.3) and 8.1 (3.3). Mean (s.d.) linezolid sputum concentrations were 3.6 (2.1) and 17.4 (7.2) mg/L at 0 and 2 h following drug administration. CONCLUSIONS: The oral administration of linezolid results in good sputum penetration in patients with CF. Mean levels exceed the required MIC for the treatment of MRSA for >80% of the dosing period for serum and the majority of the dosing period for sputum.