Linezolid-resistant ST36 methicillin-resistant Staphylococcus aureus associated with prolonged linezolid treatment in two paediatric cystic fibrosis patients.

OBJECTIVES: To describe the emergence of linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA) of sequence type (ST)36 lineage in two paediatric patients with cystic fibrosis, after long-term low-dose linezolid treatment. METHODS: Two paediatric males with cystic fibrosis had sputum samples quantitatively cultured during hospitalization. After the isolation of MRSA from both patients, oral treatment with 300 mg linezolid twice daily was initiated for periods of 1-2 months separated by up to 6 months. Isolates cultured 9 months after the start of treatment were tested for resistance to linezolid by agar dilution (BSAC). Resistant isolates were examined for 23S rDNA mutations, and typed by phage and macrorestriction with SmaI. Isolates from follow-up sputum samples were obtained until 44-51 months after treatment with linezolid. RESULTS: Colonization with MRSA was at a density of approximately 10(6) cfu/mL sputum for both subjects. Initial isolates were susceptible to linezolid, but, 9 months later, isolates from both patients were resistant (MICs > 16 mg/L). Both isolates were epidemic MRSA-16 variant A1 (ST36-MRSA-II), which is widespread in UK hospitals. Both isolates were heterozygous for a G2576T mutation in their 23S rDNA genes, but one was resistant to fusidic acid and tetracycline. In follow-up sampling, the younger patient yielded linezolid-resistant EMRSA-16 for a further 42 months, whilst the other lost the linezolid-resistant MRSA and had alternately Pseudomonas aeruginosa or linezolid-susceptible EMRSA-16 variant A1 isolated over 35 further months. CONCLUSIONS: Linezolid resistance emerged in two isolates of ST36 MRSA colonizing the lungs of two paediatric cystic fibrosis patients. Subtherapeutic levels of linezolid may have facilitated the selection of resistance.

Breathing pattern disorders (dysfunctional breathing) characteristics and outcomes of children and young people attending a secondary care respiratory clinic.

METHODS: We retrospectively audited the health records of 18 patients with breathing pattern disorders (BPDs), who were diagnosed in our respiratory clinic (2015-2018), and then referred onto our dysfunctional breathing care pathway to a specialist speech and language therapist. RESULTS: The age of the patients ranged from 11 to 16 years (median: 14 years, 14 female/4 male patients). Comorbidities included the following: 16 patients had asthma, 2 patients had a tracheoesophageal fistula and esophageal atresia repair, one patient suffered from chronic regional pain syndrome, and one patient had chronic fatigue syndrome. The commonest BPD was induced laryngeal obstruction (ILO) in 16 patients (exercise-induced laryngeal obstruction [EILO] in 15). Other types of BPDs included hyperventilation syndrome in seven patients, psychogenic cough in eight, and dysphonia in one. A single BPD was present in 6 patients (mainly EILO), and two or more BPDs were present in 10 patients. Inducers of BPD symptoms were as follows: exercise in 16 patients, bullying in 3, anxiety in 14, emotions and stress in 11, weather in 3, posture in 1, and odors in 3. Significant school absenteeism was observed in most of the patients (2 weeks to 24 months). Significant delays in diagnosing BPD were noted (range: 1-24 months and median: 6 months). Emergency calls occurred in 14 patients, with one patient presenting with ILO and comorbidity of asthma needing intubation and ventilation. A 1-year follow-up of patients showed that there was a complete resolution of BPD in two patients, 14 had good control of BPD with confidence in ability to control their symptoms, showing improved morbidity, two had no improvement, and one lost to follow-up. CONCLUSION: It is important to recognize and treat BPD early to limit the significant morbidity that adversely impacts the quality of life.

Identification of anomalous features of intravitreal injections using micro-computed tomography.

PURPOSE: To identify anomalous features that impact drug delivery in the eye as a result of intravitreal injections using micro-computed tomography imaging. METHODS: Three-dimensional micro-computed tomography images were acquired following an intravitreal injection of 0.03 mL of contrast agent into ex vivo porcine eyes (n = 24). A baseline scan was acquired prior to injection to detect any abnormalities in the eyes. Acquisition continued at various time intervals up to 230 min post-injection. RESULTS: Air bubbles were clearly visible within the vitreous of 21 eyes following injections. There was a total of 36 air bubbles in the 21 eyes and the volume of the air bubbles ranged from 0.01 µL to 1.50 µL. It was found the size of the air bubbles decreased over the scanning period. Furthermore, many of the injected boli in the eye specimens did not have the commonly assumed spherical shape; rather, a variety of other shapes resulted. CONCLUSION: The presence of air bubbles and inconsistent bolus shapes have indicated that intravitreal injections have high variability. It is only through the realization of these anomalous features that the efficacy of intravitreal drug delivery will be improved through a consistent and accurate injection technique.

A framework for modeling ocular drug transport and flow through the eye using micro-CT.

This study uses micro-computed tomography (micro-CT) imaging for assessment of concentration and transport mechanisms of ocular drug surrogates following intravitreal injection. Injections of an iodinated contrast agent were administered to enucleated porcine eyes prior to scanning over 192 min. Image analysis was performed using signal profiles and regions of interest that corresponded to specific iodine concentrations. Diffusion coefficients of the injected iodine solutions were calculated using nonlinear regression analysis with a diffusion model. There was a predominantly diffusive component in the movement of the contrast to the back of the eye in the horizontal (sagittal & coronal) directions, with ultimate retinal fate observed after 120 min. The diffusion coefficients were found to have a mean of 4.87 × 10(-4) mm(2) s(-1) and standard deviation of 8.39 × 10(-5) mm(2) s(-1) for 150 mg ml(-1) iodine concentration and 6.13 × 10(-4) ± 1.83 × 10(-4) mm(2) s(-1) for 37.5 mg ml(-1) concentration. However, it should be noted that these coefficients were time dependent and were found to decay as the diffusion front interacted with the retinal wall. A real-time, accurate, non-invasive method of tracking a bolus and its concentration is achieved using a high spatial resolution and fast scanning speed micro-CT system.