Benjamin W. Teh

Consensus guidelines for diagnosis, prophylaxis and management of Pneumocystis jirovecii pneumonia in patients with haematological and solid malignancies, 2014.

Pneumocystis jirovecii infection (PJP) is a common cause of pneumonia in patients with cancer-related immunosuppression. There are well-defined patients who are at risk of PJP due to the status of their underlying malignancy, treatment-related immunosuppression and/or concomitant use of corticosteroids. Prophylaxis is highly effective and should be given to all patients at moderate to high risk of PJP. Trimethoprim-sulfamethoxazole is the drug of choice for prophylaxis and treatment, although several alternative agents are available.

Risks, severity and timing of infections in patients with multiple myeloma: a longitudinal cohort study in the era of immunomodulatory drug therapy

We defined the epidemiology and clinical predictors of infection in patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and autologous haematopoietic stem cell transplant (ASCT) in a large longitudinal cohort study. Clinical and microbiology records of patients with MM diagnosed between January 2008 and December 2012 were reviewed to capture patient demographics, characteristics of myeloma and infections (type, severity, outcomes). Conditional risk set modelling was used to determine clinical predictors of infection. One hundred and ninety‐nine patients with MM with 771 episodes of infection were identified. 44·6% of infections were clinically defined, 35·5% were microbiologically defined and 19·9% were fever of unknown focus. There was a bimodal peak in incidence of bacterial (4–6 and 70–72 months) and viral infections (7–9 and 52–54 months) following disease diagnosis. Chemotherapy regimens high‐dose melphalan [hazard ratio (HR) = 2·07], intravenous cyclophosphamide (HR = 1·96) and intensive combination systemic chemotherapy (HR = 1·86) and cumulative doses of corticosteroid (HR = 3·06 at highest dose) were independently associated with increased risk of infection overall (P < 0·05). IMiDs and PI and other clinical factors were not independently associated with increased risk of infection. New approaches to prevention and treatment of infection should focus upon identified periods of risk and treatment‐related risk factors.

Changing treatment paradigms for patients with plasma cell myeloma: impact upon immune determinants of infection.

Plasma cell myeloma (PCM) is increasing in prevalence in older age groups and infective complications are a leading cause of mortality. Patients with PCM are at increased risk of severe infections, having deficits in many arms of the immune system due to disease and treatment-related factors. Treatment of PCM has evolved over time with significant impacts on immune function resulting in changing rates and pattern of infection. Recently, there has been a paradigm shift in the treatment of PCM with the use of immunomodulatory drugs and proteasome inhibitors becoming the standard of care. These drugs have wide-ranging effects on the immune system but their impact on infection risk and aetiology remain unclear. The aims of this review are to discuss the impact of patient, disease and treatment factors on immune function over time for patients with PCM and to correlate immune deficits with the incidence and aetiology of infections seen clinically in these patients. Preventative measures and the need for clinically relevant tools to enable infective profiling of patients with PCM are discussed.

Late‐onset Pneumocystis jirovecii pneumonia post–fludarabine, cyclophosphamide and rituximab: implications for prophylaxis

Fludarabine, cyclophosphamide and rituximab (FCR) therapy for lymphoid malignancies has historically been associated with a low reported incidence of Pneumocystis jirovecii pneumonia (PJP). However, prophylaxis was routinely used in early studies, and molecular diagnostic tools were not employed. The objective of this study was to review the incidence of PJP during and post‐FCR in the era of highly sensitive molecular diagnostics and 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET)–computerised tomography (CT).

Invasive fungal infections in patients with multiple myeloma: a multi-center study in the era of novel myeloma therapies

Multiple myeloma (MM) is a hematologic malignancy with increasing prevalence in older populations.1 Infections, particularly pyogenic infections and reactivation of latent viral infections,2 are a leading cause of morbidity and mortality in patients with MM. Previously, invasive aspergillosis (IA) had been found to be a significant opportunistic infection in patients with myeloma managed with intensive conventional combination chemotherapeutic regimens with nearly 50% attributable mortality. IA tended to occur early in the treatment course in patients with higher disease stage.3 However, the treatment of myeloma has undergone a paradigm shift with the use of immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and autologous hematopoietic stem cell transplant (ASCT) as the new standard of care.

Epidemiology of Invasive Fungal Disease in Lymphoproliferative Disorders

Invasive fungal disease (IFD) in the immunocompromised host is associated with high mortality,[1][1] prolonged stays in hospital and significant healthcare costs.[2][2] The epidemiology of IFD within the heterogeneous group of patients with lymphoproliferative disorders is not well defined and

Disseminated Scedosporium prolificans infection in an ‘extensive metaboliser’: navigating the minefield of drug interactions and pharmacogenomics

We report a case of non‐fatal disseminated Scedosporium prolificans infection, including central nervous system disease and endophthalmitis, in a relapsed acute myeloid leukaemia patient with extensive CYP2C19 metabolism. Successful treatment required aggressive surgical debridement, three times daily voriconazole dosing and cimetidine CYP2C19 inhibition. In addition, the unique use of miltefosine was employed due to azole‐chemotherapeutic drug interactions. Prolonged survival following disseminated S. prolificans, adjunctive miltefosine and augmentation of voriconazole exposure with cimetidine CYP2C19 inhibition has not been reported.

A messenger at the door: cytomegalovirus retinitis in myeloma patients with progressive disease

Cytomegalovirus (CMV) retinitis is an uncommon manifestation of CMV disease and is a marker of severe and profound immunosuppression in human immunodeficiency virus‐positive patients. Here, we describe 2 cases of CMV retinitis in myeloma patients with progressive disease, following autologous stem cell transplantation and immunomodulatory therapy for myeloma. To our knowledge, this is the first report of CMV retinitis in this patient population. This report illustrates the need for close monitoring of relapsed and refractory myeloma patients for new presentations of opportunistic infections secondary to severe immunosuppression.

Molecular diagnosis of Pneumocystis jirovecii in patients with malignancy: Clinical significance of quantitative polymerase chain reaction

Pneumocystis jirovecii pneumonia (PJP) is increasingly seen in association with the use of new and potent immunosuppressive therapies in populations not infected with human immunodeficiency virus. Today, molecular methods are widely used to improve diagnostic yield; however, the relationship between clinical findings and quantitative polymerase chain reaction (qPCR) results is undefined. Our objective was to describe characteristics of PJP in patients with malignancies and determine if qPCR results were correlated with clinical findings. From 2007 to 2012, all patients at the Peter MacCallum Cancer Centre with positive Pneumocystis PCR were identified from a microbiology database. Clinical, radiological, and microbiological records were reviewed. PJP was defined as the presence of positive PCR for Pneumocystis on a respiratory specimen, radiological abnormalities consistent with a pneumonic process, and receipt of targeted PJP treatment. qPCR was performed on all diagnostic specimens, and values were reported according to clinical findings. Forty-five patients fulfilled inclusion criteria: 44.4% had underlying solid organ tumors and 55.6% had hematological malignancies. Nonsmall cell lung carcinoma and lymphoma were the most frequent predispositions. Shortness of breath, cough, and fever were reported in 64.4%, 48.9%, and 42.2% of the patients, respectively. Admission to the intensive care unit and mortality rates were lower than in previous reports. Overall, a relationship between other clinical features and qPCR results was not identified. In the era of routine molecular diagnostics, patients with malignancy and PJP have improved outcomes. However, there was no demonstrable relationship between qPCR results and clinical features or PCR data and outcomes.

Prevention of viral infections in patients with multiple myeloma: the role of antiviral prophylaxis and immunization.

Viral infections are a major cause of morbidity and mortality in patients with myeloma. Over the last decade, treatment of myeloma has undergone a paradigm shift with the use of immunomodulatory drugs, proteasome inhibitors and autologous stem cell transplantation, resulting in changes to risk periods and risk factors for viral infection. Viral infections affecting this patient group fall broadly into reactivation of latent viral infections (e.g., varicella zoster and hepatitis B) and acquisition of acute viral respiratory infections. The periods following autologous stem cell transplantation and progressive disease are identified as increased risk for viral infections. This review focuses on evidence-based prevention strategies for key viral infections, particularly approaches to prophylaxis and immunization. Recommended prevention strategies are summarized using a risk-stratified approach. Further studies evaluating preventative measures for newly identified risk periods are required.