Dapsone for Pneumocystis jirovecii pneumonia prophylaxis – applying theory to clinical practice with a focus on drug interactions

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Carmela Emma Corallo ◽  
John Coutsouvelis ◽  
Susan Morgan ◽  
Orla Morrissey ◽  
Sharon Avery
Keyword(s):  
Organ Transplant ◽  
Cost Effective ◽  
Chemotherapeutic Agents ◽  
Pneumocystis Jirovecii ◽  
Haematopoietic Stem Cell ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Solid Organ ◽  
Immunosuppressed Patients ◽  
Life Threatening ◽  
Substantial Risk

AbstractPneumocystis jirovecii pneumonia (PJP) is a potentially life-threatening infection that occurs in immunocompromised individuals. The incidence can be as high as 80% in some groups but can be reduced to less than 1% with appropriate prophylaxis. HIV-infected patients with a low CD4 count are at the highest risk of PJP. Others at substantial risk include haematopoietic stem cell and solid organ transplant recipients, those with cancer (particularly haematologic malignancies), and those receiving glucocorticoids, chemotherapeutic agents, and other immunosuppressive medications. Trimethoprim-sulfamethoxazole is an established first-line line agent for prevention and treatment of PJP. However, in some situations, this medication cannot be used and dapsone is considered a suitable cost-effective second line agent. However, information on potential interactions with drugs commonly used in immunosuppressed patients is lacking or contradictory. In this this article we review the metabolic pathway of dapsone with a focus on interactions and clinical significance particularly in patients with haematological malignancies. An understanding of this process should optimise the use of this agent.

scholarly journals JC Polyomavirus and Transplantation: Implications for Virus Reactivation after Immunosuppression in Transplant Patients and the Occurrence of PML Disease

2021 ◽  
Vol 2 (1) ◽  
pp. 37-48
Author(s):  
James E. K. Hildreth ◽  
Donald J. Alcendor
Keyword(s):  
Inflammatory Responses ◽  
Rare Complication ◽  
Organ Transplant ◽  
Solid Organ ◽  
Virus Reactivation ◽  
Jc Polyomavirus ◽  
Hematological Disorders ◽  
Transplant Patients ◽  
Immunosuppressed Patients ◽  
Life Threatening

The JC polyomavirus (JCPyV/JCV) is a member of the Polyomaviridae family and is ubiquitious in the general population, infecting 50–80% of individuals globally. A primary infection with JCV usally results in an asymptomatic, persistent infection that establishes latency in the renourinary tract. Reactivation from latency via iatrogenic immununosuppression for allograft transplantation may result in organ pathology and a potential life-threatening neuropathological disease in the form of progressive multifocal leukoencephalopathy (PML). Currently, no treatment exists for PML, a rare complication that occurs after transplantation, with an incidence of 1.24 per 1000 persons a year among solid organ transplant patients. PML is also observed in HIV patients who are immununosuppressed and are not receiving antiretroviral therapy, as well as individuals treated with biologics to suppress chronic inflammatory responses due to multiple sclerosis, Crohn’s disease, non-Hodgkin’s lymphoma, rheumatoid arthritis, and other autoimmune-mediated hematological disorders. Here, we describe the proposed mechanisms of JCV reactivation as it relates to iatrogenic immunosuppression for graft survival and the treatment of proinflammatory disease, such as biologics, proposed trafficking of JCV from the renourinary tract, JCV central nervous system dissemination and the pathology of PML in immunosuppressed patients, and potential novel therapeutics for PML disease.

scholarly journals Pneumocystis Jirovecii Pneumonia in a Kidney Transplant Recipient 13 Months after Transplantation: A Case Report and Literature Review

2021 ◽  
Vol 28 (1) ◽  
pp. 5
Author(s):  
Dominykas Varnas ◽  
Augustina Jankauskienė
Keyword(s):  
Kidney Function ◽  
Kidney Transplant Recipient ◽  
Organ Transplant ◽  
Clinical Signs ◽  
Risk Groups ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Solid Organ ◽  
Respiratory Compromise ◽  
Effective Prophylaxis

Background. Pneumocystis jirovecii pneumonia (PCP) is an opportunistic and prevalent fungal infection in immunocompromised hosts, including patients after kidney transplantation (KTx). It is a life threatening infection. While with effective prophylaxis it became less common, it still remains an issue among solid organ transplant (SOT) recipients during the first year. There are no specific clinical signs for PCP. Computed tomography (CT) is a better method for detecting PCP, but definite diagnosis can only be made by identification of the microorganism either by a microscopy or by a polymerase chain reaction (PCR).Clinical case. We present a case of a 17 year old with severe PCP 13 months after KTx followed by reduction in kidney function and respiratory compromise. The pathogen was detected by PCR from bronchoalveolar lavage fluid (BALF) and patient was treated successfully with trimethoprim-sulfamethoxazole (TMP-SMX). Patient’s condition, respiratory status and kidney function gradually improved. Our presented case is unusual because patient had no known risk factors for PCP and he was more than one year after KTx, what is considered rare. In addition patient and his parents delayed in notifying the treating physician about ongoing symptoms because did not deem them important enough.Conclusions. Clinicians treating patients in risk groups for PCP must always remain vigilant even in era of effective prophylaxis. The vigilance should also extend to the patient and patient’s family.

scholarly journals 1171. Lower Mortality with Adjuvant Corticosteroid Therapy in non-HIV Infected Patients with pneumocystis jirovecii pneumonia: A Single US Cohort Study and a Proposed Novel Mechanism of Corticosteroids

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S610-S611
Author(s):  
William Mundo ◽  
Carlos Franco-Paredes ◽  
Steven C Johnson ◽  
Leland Shapiro ◽  
Andres Henao-Martinez
Keyword(s):  
Corticosteroid Therapy ◽  
Multivariable Analysis ◽  
Solid Organ Transplantation ◽  
Pneumocystis Jirovecii ◽  
Lower Mortality ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Solid Organ ◽  
Hiv Status ◽  
Predictors Of Mortality ◽  
Hiv Negative

Abstract Background Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids given at the time of PJP antimicrobial therapy in these patients is uncertain. This study aimed to determine if corticosteroids reduced mortality in a cohort of HIV-negative PJP patients, and to propose a novel mechanism explaining corticosteroid benefit in patients regardless of HIV status. Methods We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995-2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify predictors of mortality. Results Underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), or solid organ transplantation (10.7%). Compared to HIV-positive patients, HIV-negative patients had higher rates and duration of mechanical ventilation and ICU stay. Survival was significantly increased in HIV-negative patients receiving adjunct corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (p=0.034). In an adjusted multivariable model, corticosteroids were associated with lower mortality (OR 13.5, 95% CI: 1.1-158.5, p= 0.039) regardless of HIV status. In a novel model of adjunct corticosteroid benefit, we propose corticosteroids reduce immune-mediated lysis of Pneumocystis organisms that curtails the surfactant-disabling effect of PJP internal contents. Table 1. Multivariable Analysis of Predictors of Mortality in patients with PJP Figure 1. Mortality differences by HIV status and use of steroids in PJP Conclusion We found substantial mortality among HIV-negative patients with PJP and adjunct corticosteroid use was associated with decreased mortality. Adjunct corticosteroid mortality-lowering effect is best explained by suppressing pneumocystis lysis. This reduces surfactant disruption resulting from pneumocystis internal substances. Figure 2. Proposed mechanism of action for benefits of adjunct exogenous corticosteroid therapy during PJP Disclosures All Authors: No reported disclosures

Rashes associated with transplantations

2020 ◽  
pp. 535-538
Keyword(s):  
Fungal Infections ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Host Immunity ◽  
Solid Organ ◽  
Graft Versus Host ◽  
Gingival Hypertrophy ◽  
Life Threatening ◽  
Transplant Complications

Dermatological manifestations following transplantation are common but important to recognize and diagnose since they may be severe and life-threatening if not adequately and promptly treated. This chapter provides a systematic overview of the types of skin disease that may be encountered in children that have received a haematological or solid organ transplant. Complications relating to immunosuppression include an increased susceptibility to bacterial, viral, and fungal infections which may be significantly more virulent and hazardous in the context of reduced host immunity. Immune suppressant drugs may also cause drug rashes and aesthetic complications such as acne, hypertrichosis, or gingival hypertrophy, as well as longer-term risks from the development of malignancy. It is also important to recognize the range of mucocutaneous signs of acute and chronic graft versus host disease following bone marrow and solid organ transplantation which, again, may be severe and associated with significant morbidity and mortality.

scholarly journals Human cytomegalovirus seroprevalence and titres in solid organ transplant recipients and transplant donors in Seoul, South Korea

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yeonju La ◽  
Da Eun Kwon ◽  
Seul Gi Yoo ◽  
Kyoung Hwa Lee ◽  
Sang Hoon Han ◽  
...  
Keyword(s):  
South Korea ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Haematopoietic Stem Cell ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Seropositive Rate ◽  
Healthy Donors

Abstract Background Human cytomegalovirus (HCMV) can cause poor outcomes in solid organ transplant (SOT) recipients; moreover, it is associated with cardiovascular diseases (CVD) in the general population. Accordingly, anti-HCMV immunoglobulin G (IgG) seroepidemiology may be useful in identifying the risk of post-SOT HCMV infection or disease as well as immunosenescence or CVD. However, HCMV seroprevalence and titre have not been fully evaluated with regard to age distribution or compared between SOT recipients and healthy individuals in South Korea. Methods We retrospectively retrieved all unduplicated anti-HCMV IgG results of individuals aged > 1 year evaluated between July 2006 and November 2017 at Severance Hospital in Seoul. The cohort, excluding haematopoietic stem cell transplant recipients and subjects with equivocal values, included 2184 SOT recipients and 3015 healthy transplant donors. All IgG results in the SOT recipients were measured during the pre-transplant period. Results The overall IgG seroprevalence and titres were significantly higher among SOT recipients than among healthy donors (98.7% vs. 88.6%, p < 0.001, and 64.7 ± 44.3 vs. 49.8 ± 20.6 arbitrary units/mL, p < 0.001, respectively). The lowest seropositive rate in the SOT group was observed in recipients aged between 11 and 15 years (70.6%). The frequency of seropositivity among adults aged ≥41 years increased to ≥90% in SOT recipients and healthy donors. Age was independently associated with higher HCMV seroprevalence (41–60 years, OR, 76.4, 95% CI, 24.5–238.9, p < 0.001; ≥ 61 years, OR, 4.4, 95% CI, 1.3–14.9, p < 0.001, compared to ≤40 years). The healthy donor group had an independently low HCMV seropositive rate (OR, 0.1, 95% CI, 0.1–0.2, p < 0.001). Conclusions HCMV seropositivity was the lowest among school-aged children and adolescents. IgG testing revealed an intermediate serostatus risk of post-transplant HCMV infection and disease for most adult SOT recipients in South Korea.

Nocardia spp.: A Rare Cause of Pneumonia Globally

2020 ◽  
Vol 41 (04) ◽  
pp. 538-554
Author(s):  
Joseph P. Lynch ◽  
Gail Reid ◽  
Nina M. Clark
Keyword(s):  
Susceptibility Testing ◽  
Organ Transplant ◽  
Clinical Manifestations ◽  
Community Acquired Pneumonia ◽  
Solid Organ ◽  
In Vitro Susceptibility ◽  
Timely Initiation ◽  
Life Threatening ◽  
Initiation Of Therapy

AbstractMembers of the Nocardia genus are ubiquitous in the environment. These aerobic, gram-positive organisms can lead to life-threatening infection, typically in immunocompromised hosts such as solid organ transplant recipients or those receiving immunosuppressive medications for other reasons. This current review discusses the microbiology of nocardiosis, risk factors for infection, clinical manifestations, methods for diagnosis, and treatment. Nocardiosis primarily affects the lung but may also cause skin and soft tissue infection, cerebral abscess, bloodstream infection, or infection involving other organs. Although rare as a cause of community-acquired pneumonia, Nocardia can have severe morbidity and mortality, particularly in patients with comorbidities or compromised immunity. Early diagnosis and timely initiation of therapy are critical to optimizing patient outcomes. Species identification is important in determining treatment, as is in vitro susceptibility testing. Sulfonamide therapy is usually indicated, although a variety of other antimicrobials may be useful, depending on the species and susceptibility testing. Prolonged therapy is usually indicated, for 6 to 12 months, and in some cases surgical debridement may be required to resolve infection.

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