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Ginn A.N.,Center for Infectious Diseases and Microbiology | Ginn A.N.,University of Sydney | Ginn A.N.,Westmead Millennium Institute | Wiklendt A.M.,Center for Infectious Diseases and Microbiology | And 17 more authors.
PLoS ONE | Year: 2012

Background: Antibiotic homogeneity is thought to drive resistance but in vivo data are lacking. In this study, we determined the impact of antibiotic homogeneity per se, and of cefepime versus antipseudomonal penicillin/β-lactamase inhibitor combinations (APP-β), on the likelihood of infection or colonisation with antibiotic resistant bacteria and/or two commonly resistant nosocomial pathogens (methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa). A secondary question was whether antibiotic cycling was associated with adverse outcomes including mortality, length of stay, and antibiotic resistance. Methods: We evaluated clinical and microbiological outcomes in two similar metropolitan ICUs, which both alternated cefepime with APP-β in four-month cycles. All microbiological isolates and commensal samples were analysed for the presence of antibiotic-resistant bacteria including MRSA and P. aeruginosa. Results: Length of stay, mortality and overall antibiotic resistance were unchanged after sixteen months. However, increased colonisation and infection by antibiotic-resistant bacteria were observed in cefepime cycles, returning to baseline in APP-β cycles. Cefepime was the strongest risk factor for acquisition of antibiotic-resistant infection. Conclusions: Ecological effects of different β-lactam antibiotics may be more important than specific activity against the causative agents or the effect of antibiotic homogeneity in selection for antibiotic resistance. This has important implications for antibiotic policy. © 2012 Ginn et al.

Dentice R.L.,Royal Prince Alfred Hospital | Dentice R.L.,University of Sydney | Elkins M.R.,Royal Prince Alfred Hospital | Elkins M.R.,University of Sydney | And 9 more authors.
Thorax | Year: 2016

Background: The mucoactive effects of hypertonic saline should promote exacerbation resolution in people with cystic fibrosis (CF). Objectives: To determine the effects of hypertonic saline inhalation during hospitalisation for exacerbation of CF on length of stay, lung function, symptoms, oxygenation, exercise tolerance, quality of life, bacterial load and time to next hospitalisation. Methods: 132 adults with an exacerbation of CF were randomised to inhale three nebulised doses a day of either 4 mL 7% saline or a taste-masked control of 0.12% saline, throughout the hospital admission. The primary outcome measure was length of hospital stay. Results: All participants tolerated their allocated saline solution. There was no significant difference in length of stay, which was 12 days in the hypertonic saline group and 13 days in controls, with a mean between-group difference (MD) of 1 day (95% CI 0 to 2). The likelihood of regaining pre-exacerbation FEV1 by discharge was significantly higher in the hypertonic saline group (75% vs 57%), and the number needed to treat was 6 (95% CI 3 to 65). On a 0-100 scale, the hypertonic saline group had significantly greater reduction in symptom severity than the control group at discharge in sleep (MD=13, 95% CI 4 to 23), congestion (MD=10, 95% CI 3 to 18) and dyspnoea (MD=8, 95% CI 1 to 16). No significant difference in time to next hospitalisation for a pulmonary exacerbation was detected between groups (HR=0.86 (CI 0.57 to 1.30), p=0.13). Other outcomes did not significantly differ. Conclusions: Addition of hypertonic saline to the management of a CF exacerbation did not reduce the length of hospital stay. Hypertonic saline speeds the resolution of exacerbation symptoms and allows patients to leave hospital with greater symptom resolution.

Perri R.A.,Ludwig Engel Center for Respiratory Research | Perri R.A.,Westmead Millennium Institute | Kairaitis K.,Ludwig Engel Center for Respiratory Research | Kairaitis K.,Westmead Millennium Institute | And 9 more authors.
Sleep and Breathing | Year: 2014

Study objective: We used statistical modelling to probe the contributions of anthropometric and surface cephalometric variables to the OSA phenotype. Design: The design is prospective cohort study. Setting: The setting is community-based and sleep disorder laboratory. Patients or participants: Study #1 - Model development study: 147 healthy asymptomatic volunteers (62.6 % Caucasian; age, 18-76 years; 81 females; median multivariable apnea prediction index=0.15) and 140 diagnosed OSA patients (84.3 % Caucasian; age, 18-83 years; 41 females; polysomnography [PSG] determined apnea-hypopnea index >10 events/h). Study #2 - Model test study: 345 clinic patients (age, 18-86 years; 129 females) undergoing PSG for diagnosis of OSA. Intervention: We measured 10 anthropometric and 34 surface cephalometric dimensions (calipers) and calculated mandibular enclosure volumes for study #1 and recorded age and neck circumference for study #2. Statistical modelling included principal component (PC), logistic regression, and receiver-operator curve analyses. Measurements and results: Model development study: A regression model incorporating three identified PC predicted OSA with 88 % sensitivity and specificity. However, a simplified model based on age and NC alone was equally effective (87 % sensitivity and specificity). Model test study: The simplified model predicted OSA with high sensitivity (93 %) but poor specificity (21 %). Conclusion: We conclude that in our clinic-based cohort, craniofacial bony and soft tissue structures (excluding neck anatomy) do not play a substantial role in distinguishing patients with OSA from those without. This may be because craniofacial anatomy does not contribute greatly to the pathogenesis of OSA in this group or because referral bias has created a relatively homogeneous phenotypic population. © 2013 Springer-Verlag.

Narayan J.,Ludwig Engel Center for Respiratory Research | Narayan J.,Westmead Millennium Institute | Narayan J.,University of Sydney | Amatoury J.,Ludwig Engel Center for Respiratory Research | And 13 more authors.
Respiratory Physiology and Neurobiology | Year: 2013

Baroreflex sensitivity (BRS) is reduced during snoring in humans and animal models. We utilised our rabbit model to examine the contribution of increased upper airway resistance to baroreflex resetting during snoring, by comparing BRS and baroreflex operating point (OP) values during IS to those obtained during tracheostomised breathing through an external resistive load (RL) titrated to match IS levels of peak inspiratory pleural pressure (Ppl). During both IS and RL, BRS decreased by 45% and 49%. There was a linear relationship between the change in Ppl and the decrease in BRS, which was similar for IS and RL. During both RL and IS, there was a shift in OP driven by ∼16% increase in HR and no change in arterial pressure. Snoring related depression of BRS is likely mediated via a HR driven change in OP, which itself may be the outcome of negative intra-thoracic pressure mediated effects on right atrial wall stretch reflex control of heart rate. © 2012 Elsevier B.V.

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