Pneumocystis pneumonia in a patient treated with alemtuzumab for relapsing multiple sclerosis.

Pneumocystis jirovecii pneumonia (PJP) is a known risk in patients with chronic lymphocytic leukemia treated with alemtuzumab (Campath®). However, no recommendation for PJP prophylaxis for alemtuzumab use in multiple sclerosis (Lemtrada®) and no known associated PJP has been reported to date. We report a patient who developed PJP two months after receiving the first course of Lemtrada, and fully recovered after receiving cotrimoxazole treatment. We should remain vigilant of opportunistic infections in patients who develop pneumonitis and evaluate the need for PJP prophylaxis during Lemtrada treatment.

Clinical outcomes and management of patients with chronic hepatitis B and liver stiffness measurement in the grey zone.

BACKGROUND: A significant number of patients have liver stiffness measurements in the grey zone where liver biopsy is recommended. AIMS: To study chronic hepatitis B patients with initial liver stiffness measurements in the grey zone with regards to rates of liver biopsy, repeat liver stiffness measurements and outcomes. METHODS: Consecutive chronic hepatitis B patients who underwent transient elastography from August 2006 to July 2017 were retrospectively studied. Liver-related events were defined as hepatocellular carcinoma or cirrhotic complications. Grey zone was defined as liver stiffness measurements: 6.1-9.0 kPa (normal ALT) or 7.6-12.0 kPa (ALT 1-5 × upper limit of normal) on M-probe and 6.9-10.0 kPa on XL-probe. RESULTS: Of the 3212 patients analysed, 837 (26%) had initial liver stiffness measurements in grey zone. Only 3.6% of grey zone patients proceeded to liver biopsy within 6 months of transient elastography, of which 33% had METAVIR F3-4 fibrosis. Repeat liver stiffness measurements was performed in 44% of grey zone patients. Liver biopsy and repeat liver stiffness measurements prompted change in management in 47% and 31% of patients respectively. Independent predictors for liver-related events in grey zone patients included increased age, low albumin and low platelet count. Liver-related events rates were increased (9%-17%) in patients with METAVIR > F2 fibrosis on biopsy or repeat liver stiffness measurements which did not improve. CONCLUSIONS: Chronic hepatitis B patients with initial liver stiffness measurements in the grey zone rarely proceed to a clarifying liver biopsy which would reveal advanced fibrosis or cirrhosis in one-third of patients. Both liver biopsy and repeat liver stiffness measurements in grey zone patients have clinical utility in prompting changes in management and providing prognostic information.

Risk factors for drug-resistant bacterial pneumonia in older patients hospitalized with pneumonia in a Chinese population.

BACKGROUND: The relationship between healthcare-associated pneumonia (HCAP) and resistant bacteria is unclear. The aim of this study was to identify the risk factors for pneumonia caused by drug-resistant bacteria (DRB). METHODS: A prospective cohort study was conducted at a tertiary teaching hospital in Hong Kong. Consecutive older patients (aged ≥65 years) were hospitalized with pneumonia from January 2004 to June 2005. DRB comprised methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, extended-spectrum ß-lactamase (ESBL) producing Enterobacteriaceae and Acinetobacter baumannii. RESULTS: The entire cohort consisted of 1176 older patients. Of 472 (40.1%) patients with etiological diagnosis established, bacterial pneumonia was found in 354 (30.1%) cases. DRB were isolated in 48 patients: P. aeruginosa (41), MRSA (5) and ESBL producing enteric bacilli (3). Co-infection with P. aeruginosa and MRSA was found in one patient. The prevalence of DRB in culture-positive pneumonia was 20.1% (48/239). Patients with DRB were more likely to have limitation in activities of daily living, bronchiectasis, dementia, severe pneumonia, recent hospitalization and recent antibiotic use. Logistic regression revealed that bronchiectasis [relative risk (RR) 14.12, P = 0.002], recent hospitalization (RR 4.89, P < 0.001) and severe pneumonia (RR 2.42, P = 0.010) were independent predictors of drug-resistant bacterial pneumonia. CONCLUSION: Recent hospitalization is the only risk factor for HCAP which is shown to be associated with DRB. Nursing home residence is not a risk factor. The concept of HCAP may not be totally applicable in Hong Kong where the prevalence of drug-resistant pathogens in pneumonia is low.

Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia.

BACKGROUND: Little is known about the virological and inflammatory responses of severe pandemic 2009 influenza A(H1N1) virus pneumonia during antiviral treatment. METHODS: In a prospective observational study, we recruited consecutive adults hospitalized with confirmed pandemic 2009 H1N1 infection during a 16-week period. Nasopharyngeal aspirate and non-respiratory samples (blood, stool and urine) were collected at presentation, and serial nasopharyngeal flocked swabs (NPFS) and tracheal aspirates (TA) were collected after initiating oseltamivir treatment for quantitative viral RNA assay, using real-time reverse transcriptase-PCR. Serial plasma samples were collected for cytokine/chemokine assay using cytometric bead array. Patients with severe pneumonia (lung infiltrates and hypoxaemia) were compared to those with milder illnesses. RESULTS: A total of 66 patients were studied (mean age 43 ±20 years); 28 (42%) developed severe pneumonia, of whom 10 (15%) required intubation. Severe pneumonia was associated with older age, dyspnoea, delayed presentation >2 days from onset, extrapulmonary virus detection (13-28%) and higher viral concentration despite late-presentation (multiple linear regression, ß=0.94, 95% confidence interval 0.15-1.74; P=0.02). Patients with severe pneumonia exhibited slow viral clearance with oseltamivir treatment, particularly in the lower respiratory tract (median [interquartile range] durations of RNA positivity after antiviral initiation were NPFS 6.0 days [3.0-8.0], TA 11.0 days [7.8-14.3] versus milder illness group NPFS of 2.0 days [1.0-3.0] days; P<0.01). High viral load in lower respiratory tract despite upper-tract RNA negativity and viral rebound after stopping treatment were noted in some patients. H275Y mutation was absent. High plasma levels of interleukin (IL)-6, CXCL-8 (IL-8), CCL2 (monocyte chemoattractant protein-1) and soluble tumour necrosis factor receptor-1 were observed, which correlated with the extent and progression of pneumonia in hospital. CONCLUSIONS: In severe 2009 H1N1 pneumonia, viral clearance is slow with treatment, particularly in the lower respiratory tract. A more sustained antiviral regime appears warranted.