Predictors of mortality in chronic pulmonary aspergillosis.

Chronic pulmonary aspergillosis (CPA) is a chronic progressive infection that destroys lung tissue in non-immunocompromised patients. Contemporary series suggest 50-85% 5-year mortality, with few prognostic factors identified.A cohort of 387 CPA patients referred to the UK's National Aspergillosis Centre from 1992 to June 2012 was studied until June 2015. The impact of objective and subjective variables including age, sex, previous pulmonary conditions, dyspnoea score, quality of life, serum albumin and C-reactive protein and radiological appearances were assessed using Kaplan-Meier curves, log rank tests and Cox proportional hazards modelling. In samples of patients, retrospective review of time from likely onset of CPA to referral and cause of death were also investigated.Survival was 86%, 62% and 47% at 1, 5 and 10 years, respectively. Increased mortality was associated with nontuberculous mycobacterial infection (hazard ratio 2.07, 95% CI 1.22-3.52; p<0.001) and chronic obstructive pulmonary disease (1.57, 1.05-2.36; p=0.029) as well as higher age (1.053, 1.03-1.07 per year; p<0.001), lower albumin (0.92, 0.87-0.96 per g·L-1), lower activity (1.021, 1.01-1.03 per point increase in St George's Respiratory Questionnaire activity domain; p<0.001) and having one, and especially, bilateral aspergillomas (p<0.001).Several factors impact on mortality of CPA, and can be evaluated as tools to assess CPA prognosis.

Pharmacist-led feedback workshops increase appropriate prescribing of antimicrobials.

OBJECTIVES: To investigate whether and how structured feedback sessions can increase rates of appropriate antimicrobial prescribing by junior doctors. METHODS: This was a mixed-methods study, with a conceptual orientation towards complexity and systems thinking. Fourteen junior doctors, in their first year of training, were randomized to intervention (feedback) and 21 to control (routine practice) groups in a single UK teaching hospital. Feedback on their antimicrobial prescribing was given, in writing and via group sessions. Pharmacists assessed the appropriateness of all new antimicrobial prescriptions 2 days per week for 6 months (46 days). The mean normalized prescribing rates of suboptimal to all prescribing were compared between groups using the t-test. Thematic analysis of qualitative interviews with 10 participants investigated whether and how the intervention had impact. RESULTS: Data were collected on 204 prescriptions for 166 patients. For the intervention group, the mean normalized rate of suboptimal to all prescribing was 0.32 ±â€Š0.36; for the control group, it was 0.68 ±â€Š0.36. The normalized rates of suboptimal prescribing were significantly different between the groups (P = 0.0005). The qualitative data showed that individuals' prescribing behaviour was influenced by a complex series of dynamic interactions between individual and social variables, such as interplay between personal knowledge and the expectations of others. CONCLUSIONS: The feedback intervention increased appropriate prescribing by acting as a positive stimulus within a complex network of behavioural influences. Prescribing behaviour is adaptive and can be positively influenced by structured feedback. Changing doctors' perceptions of acceptable, typical and best practice could reduce suboptimal antimicrobial prescribing.

International expert opinion on the management of infection caused by azole-resistant Aspergillus fumigatus.

An international expert panel was convened to deliberate the management of azole-resistant aspergillosis. In culture-positive cases, in vitro susceptibility testing should always be performed if antifungal therapy is intended. Different patterns of resistance are seen, with multi-azole and pan-azole resistance more common than resistance to a single triazole. In confirmed invasive pulmonary aspergillosis due to an azole-resistant Aspergillus, the experts recommended a switch from voriconazole to liposomal amphotericin B (L-AmB; Ambisome(®)). In regions with environmental resistance rates of ≥10%, a voriconazole-echinocandin combination or L-AmB were favoured as initial therapy. All experts recommended L-AmB as core therapy for central nervous system aspergillosis suspected to be due to an azole-resistant Aspergillus, and considered the addition of a second agent with the majority favouring flucytosine. Intravenous therapy with either micafungin or L-AmB given as either intermittent or continuous therapy was recommended for chronic pulmonary aspergillosis due to a pan-azole-resistant Aspergillus. Local and national surveillance with identification of clinical and environmental resistance patterns, rapid diagnostics, better quality clinical outcome data, and a greater understanding of the factors driving or minimising environmental resistance are areas where research is urgently needed, as well as the development of new oral agents outside the azole drug class.

Acute subretinal abscess in Staphylococcus aureus septicaemia with endophthalmitis showcased by multimodal retinal imaging and with 2-year follow-up.

A middle-aged man presented to emergency services with central vision loss in the setting of flu-like illness with fever. A striking subfoveal abscess was observed in the right fundus. Focal acute chorioretinal inflammation was noted in the asymptomatic fellow eye. Staphylococcus aureus septicaemia was subsequently diagnosed. He presented with undiagnosed HIV infection and latent syphilis. Serial high-definition multimodal retinal imaging showcased resolution of the dome-shaped subretinal abscess following treatment with intravenous flucloxacillin. A chorioretinal scar swiftly replaced the subfoveal abscess. Peripheral right vision and full left vision was retained. Vision loss due to endogenous endophthalmitis in systemic sepsis is an emergency requiring prompt multidisciplinary care. Sight and life are at risk-thus this is not a diagnosis to miss! Early recognition is paramount to health and in retaining vision. We briefly review relevant literature and portray how multimodal imaging guided response to treatment of acute subretinal abscess.

Assessment of posaconazole salvage therapy in chronic pulmonary aspergillosis using predefined response criteria.

OBJECTIVES: Chronic pulmonary aspergillosis (CPA) is a progressive infection that destroys lung tissue in non-immunocompromised patients. First-line therapies for CPA (itraconazole and/or voriconazole) are often curtailed due to toxicity or the development of drug resistance. Posaconazole is a potential alternative for these patients. METHODS: Use of posaconazole was funded by the National Health Service Highly Specialised National Commissioners on an individual basis for patients who failed or did not tolerate first-line therapy; those who met predefined criteria for improvement at 4 and 6 months (weight gain and/or improvement in St George's Respiratory Questionnaire) continued posaconazole long-term. We recorded response, failure, discontinuation rates, and adverse events. RESULTS: Seventy-eight patients received posaconazole as salvage therapy. Thirty-four (44%) achieved targets for continuation of therapy. Fourteen (18%) failed therapy; five (36%) patients did not achieve clinical targets at 4 or 6 months of assessment and nine (64%) developed clinical and/or radiological failure. Twenty-eight (36%) discontinued their trial early; 8 (29%) died and 20 (71%) had significant side effects. One patient was non-compliant and another was lost to follow up. CONCLUSIONS: Establishing criteria for therapeutic success offered a clear, safe and sustainable method of identifying patients who benefit from additional therapy, and minimised continuation of ineffective therapy in those who did not.

Primary pyogenic ventriculitis caused by Neisseria meningitidis: case report and review of the literature.

Background. Pyogenic ventriculitis is a well-known complication of meningitis, brain abscesses and intraventricular drains. Primary pyogenic ventriculitis is a rare entity and few cases have been described so far. We report the first case of primary pyogenic ventriculitis in an adult caused by Neisseria meningitidis and present an overview of all reported adult primary pyogenic ventriculitis cases in the English literature. Methods. A PubMed search was performed using the terms ependymitis, ventricular empyema, pyocephalus and ventriculitis. Filter was set for adults and English. Articles in which pyogenic ventriculitis was a complication of well-known risk factors were excluded. A total of five cases of primary pyogenic ventriculitis were identified. Results. There were seven adult patients. Only one patient showed signs of meningeal irritation. Four patients had positive blood cultures with Escherichia coli (one patient), methicillin-resistant Staphylococcus aureus (one patient), one patient was bacteraemic with Enterococcus faecalis, Escherichia coli and Peptostreptococcus spp., and N. meningitidis (our patient). In four patients cerebrospinal fluid was sent for culture, which yielded methicillin-sensitive Staphylococcus aureus (one patient), Peptostreptococcus spp. (one patient), Streptococcus intermedius (one patient, identified via 16S PCR) and Listeria monocytogenes (one patient). Cerebrospinal fluid cell count was determined in four patients and showed pleocytosis in all four cases. Ventricular drainage was performed in four patients. Five patients survived. Discussion. We report the first case of pyogenic ventriculitis caused by N. meningitidis. Primary pyogenic ventriculitis is a rare entity with various clinical presentations caused by various bacterial species. Treatment consists of adequate antimicrobial therapy, and ventricular drainage may be necessary.

Chronic fibrosing pulmonary aspergillosis: a cause of 'destroyed lung' syndrome.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) has substantial impact on quality of life. A subset of patients develops significant pulmonary fibrosis, identified either on biopsy or radiologically. The term chronic fibrosing pulmonary aspergillosis (CFPA) has been suggested. METHODS: We describe 11 patients with CFPA referred to our centre. RESULTS: Mean age was 58.5 years and five were male. In nine, fibrosis was already evident on presentation, while in two it developed 3 and 6 years later. The predominant radiological feature was extensive or complete involvement of the entire lung, with minimal contralateral involvement. All patients received prolonged antifungal treatment. Two patients had surgical treatment; both developed post-operative complications. The contralateral lung remained free of significant disease in all but three patients. CONCLUSIONS: CFPA is a rare complication of CPA that is usually evident on presentation, but may develop after years in patients not on antifungals. Fibrosis resembles the 'destroyed lung' syndrome described after treated tuberculosis.

Impact of liposomal amphotericin B therapy on chronic pulmonary aspergillosis.

OBJECTIVES: To assess the clinical response and renal toxicity observed in chronic pulmonary aspergillosis (CPA) patients receiving ≥1 short-courses of liposomal amphotericin (LAmB) (AmBisome®) therapy. METHODS: A retrospective audit of clinical response and renal function was undertaken in 71 CPA patients (41 male) treated with LAmB at the National Aspergillosis Centre, including 20 patients receiving repeated treatment courses or long-term therapy (n = 5). RESULTS: Median age was 64 years (range 29-86 years). Treatment indications included respiratory symptoms (n = 33; 46.5%), constitutional symptoms (n = 2; 2.8%) or both (n = 36; 50.7%). 48 patients (73.8%) responded to their first LAmB course. Quality of life (QOL) improvements occurred in 37 (92.5%) of 40 patients with sufficient data available. Response rates for repeated short-courses of LAmB were 76.6%; QOL improvements were observed in 91.7% of treatment courses. All patients on long-term therapy demonstrated a response. 34 (50%) and 17 (25%) patients respectively developed an increased risk of acute kidney injury (AKI) or actual AKI with their first treatment; a significant reduction in geometric mean eGFR was observed and a similar pattern occurred following their second treatment course. CONCLUSIONS: Whilst CPA is responsive to LAmB, caution should be exercised with repeated courses, if other treatments are available.

Should we consider patients with coexistent hepatitis B or C infection for orthotopic heart transplantation?

Heart transplantation (HTX) is the gold standard surgical treatment for patients with advanced heart failure. The prevalence of hepatitis B and hepatitis C infection in HTX recipients is over 10%. Despite its increased prevalence, the long-term outcome in this cohort is still not clear. There is a reluctance to place these patients on transplant waiting list given the increased incidence of viral reactivation and chronic liver disease after transplant. The emergence of new antiviral therapies to treat this cohort seems promising but their long-term outcome is yet to be established. The aim of this paper is to review the literature and explore whether it is justifiable to list advanced heart failure patients with coexistent hepatitis B/C infection for HTX.