scholarly journals Pneumocystis jirovecii Pneumonia in Children with Hematological Malignancies: Diagnosis and Approaches to Management

2020 ◽  
Vol 6 (4) ◽  
pp. 331
Author(s):  
Elpis Mantadakis

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that mostly affects children with suppressed cellular immunity. PJP was the most common cause of infectious death in children with acute lymphoblastic leukemia prior to the inclusion of cotrimoxazole prophylaxis as part of the standard medical care in the late 1980s. Children with acute leukemia, lymphomas, and those undergoing hematopoietic stem cell transplantation, especially allogeneic transplantation, are also at high risk of PJP. Persistent lymphopenia, graft versus host disease, poor immune reconstitution, and lengthy use of corticosteroids are significant risk factors for PJP. Active infection may be due to reactivation of latent infection or recent acquisition from environmental exposure. Intense hypoxemia and impaired diffusing capacity of the lungs are hallmarks of PJP, while computerized tomography of the lungs is the diagnostic technique of choice. Immunofluorescence testing with monoclonal antibodies followed by fluorescent microscopy and polymerase chain reaction testing of respiratory specimens have emerged as the best diagnostic methods. Measurement of (1-3)-β-D-glucan in the serum has a high negative predictive value in ruling out PJP. Oral cotrimoxazole is effective for prophylaxis, but in intolerant patients, intravenous and aerosolized pentamidine, dapsone, and atovaquone are effective alternatives. Ιntravenous cotrimoxazole is the treatment of choice, but PJP has a high mortality even with appropriate therapy.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4876-4876
Author(s):  
Mukta Kumar ◽  
William Keough

Abstract Abstract 4876 Pneumocystis jirovecii is an opportunistic pathogen responsible for severe pneumonia in immunocompromised patients. Management of this pneumonia remains a major challenge for all physicians caring for immunosuppressed patients. The prognosis of Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure is traditionally known to be poor. We report a case of PCP in a child with recently diagnosed childhood Precursor B cell Acute Lymphoblastic Leukemia (ALL). Course was complicated with acute respiratory failure showing hypoxemia, respiratory failure requiring intubation and reduced compliance resembling ARDS. Our Patient, 8 weeks into chemotherapy for newly diagnosed ALL, presented with high grade fevers and poor activity. Patient was admitted 3 weeks prior for Bacillus cereus bacteremia. Additionally the patient had been on broad spectrum antibiotics on 2 occasions for febrile neutropenia episodes within the past 2 weeks. Patient had minimal respiratory symptoms at this presentation and recovered from pancytopenia at the time of this presentation. CT scans and chest x-ray (Figures 1 and 2) showed diffuse marked ground glass opacities with dependent consolidation in the lungs. On day 3 of admission, bronchoalveolar lavage (BAL) was preformed and empiric trimethoprim-sulfamethoxazole was initiated in addition to broad spectrum antibacterial, antifungal and antiviral medications. Within 24 hours, patient rapidly deteriorated with significant respiratory distress and hypoxemia requiring intubation. Clinical and radiologic findings were suggestive of ARDS. Patient required significant ventilatory support, fluid restriction, diuretics, and steroids. PCR testing of BAL fluid was reported as positive for Pneumocystis jirovecii. By hospital day 6 the patient was still requiring a fair amount of respiratory support. Corticosteroids had been added but concern amongst some members of the team surrounded possible lack of efficacy of trimethoprim-sulfamethoxazole. Review of published case reports suggested that addition of caspofungin provided salvage therapy in cases where trimethoprim-sulfamethoxazole was believed to be suboptimal. Caspofungin was added to this patient's treatment. However, liver trans-aminases experienced a 2–3 fold increase within 72 hours after initiating caspofungin. Caspofungin was withdrawn but the patient's condition gradually improved and was extubated 7 days later. Also of note, there have been wide spread regional and national shortages of intravenous trimethoprim-sulfamethoxazole preparations. We were forced to convert to oral therapy several days after extubation. The patient continued to improve and had no signs of complications or increased morbidity from this conversion; however, this was a continued concern during his treatment. A Pub Med review of the literature reveals very little failure of trimethoprim-sulfamethoxazole prophylaxis in the non-HIV immunocompromised population. Further, studies in Denmark, Italy, and the UK reveal that trimethoprim-sulfamethoxazole prophylaxis in children with ALL also decreases the number of febrile and bacteremic incidents. Trimethoprim-sulfamethoxazole also has advantages over other prophylactic choices against Pneumocystis jirovecii with fewer side effects such as methemoglobinemia induced by dapsone for example. Other studies from the UK, US, and Denmark stress that the early diagnosis and treatment with appropriate antimicrobials and possibly corticosteroids has a better outcome in this frequently fatal complication of immunosupressed patients. This case stresses the need for continued patient education regarding adherence to prophylactic regimens, early diagnosis and suspicion of opportunistic organisms such as Pneumocystis jirovecii, and prompt diagnosis and treatment of the same.Figure 1.Ground Glass Opacities on CT ChestFigure 1. Ground Glass Opacities on CT ChestFigure 2.Chest x-ray infiltratesFigure 2. Chest x-ray infiltrates Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Arezoo BOZORGOMID ◽  
Yazdan HAMZAVI ◽  
Sahar HEIDARI KHAYAT ◽  
Behzad MAHDAVIAN ◽  
Homayoon BASHIRI

Background: The human immunodeficiency virus (HIV) is one of the greatest health challenges facing worldwide. The virus suppresses the immune system of the patient. The purpose of this study was to describe the epidemiology of Pneumocystis jirovecii colonization, rarely found in normal people, in patients with stage 4 HIV infection in Kermanshah, Iran, from Mar 1995 to Feb 2016. Methods: In this retrospective study, we surveyed medical records of stage 4 HIV-positive patients with Pneumocystis admitted to Behavioral Counseling Center of Kermanshah. Several parameters were analyzed including demographic characteristics, body mass index (BMI), treatment regimen, diagnostic methods, presenting signs and symptoms, presence of co-pathogens (bacteria, viruses, or fungi), and nadir of CD4 T-cell count before and after treatment. Results: During the study period, 114 HIV-positive patients were analyzed, of whom 93 were male and 21 were female, respectively. Of 114 cases, 26 (22.8%) patients had Pneumocystis. All 26 colonized patients had CD4 cell counts below 200 cells/mm3 (range 9–186). The median CD4 count increased from 91 cells/mm3 pretrimethoprim/sulfamethoxazole (TMP/SMX) to an estimated 263 cells/mm3 after starting (TMP/SMX). BMI was normal in the majority of the patients (85%) and coughs, sputum, and chest pain (19; 73%) followed by dyspnea, weakness, and lethargy (7; 27%) were the most common presentations of fungal pneumonia. Conclusion: HIV/AIDS-infected patients are an environmental reservoir of P. jirovecii infection that might transmit the infection from one person to another via the airborne route. In addition, rapid identification of such individuals may reduce the morbidity and mortality rate of this disease.


2020 ◽  
Vol 58 (8) ◽  
pp. 1015-1028 ◽  
Author(s):  
Marjorie Bateman ◽  
Rita Oladele ◽  
Jay K Kolls

Abstract Pneumocystis jirovecii can cause life-threatening pneumonia in immunocompromised patients. Traditional diagnostic testing has relied on staining and direct visualization of the life-forms in bronchoalveolar lavage fluid. This method has proven insensitive, and invasive procedures may be needed to obtain adequate samples. Molecular methods of detection such as polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and antibody-antigen assays have been developed in an effort to solve these problems. These techniques are very sensitive and have the potential to detect Pneumocystis life-forms in noninvasive samples such as sputum, oral washes, nasopharyngeal aspirates, and serum. This review evaluates 100 studies that compare use of various diagnostic tests for Pneumocystis jirovecii pneumonia (PCP) in patient samples. Novel diagnostic methods have been widely used in the research setting but have faced barriers to clinical implementation including: interpretation of low fungal burdens, standardization of techniques, integration into resource-poor settings, poor understanding of the impact of host factors, geographic variations in the organism, heterogeneity of studies, and limited clinician recognition of PCP. Addressing these barriers will require identification of phenotypes that progress to PCP and diagnostic cut-offs for colonization, generation of life-form specific markers, comparison of commercial PCR assays, investigation of cost-effective point of care options, evaluation of host factors such as HIV status that may impact diagnosis, and identification of markers of genetic diversity that may be useful in diagnostic panels. Performing high-quality studies and educating physicians will be crucial to improve the rates of diagnosis of PCP and ultimately to improve patient outcomes.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3372-3372
Author(s):  
Kadee J Raser ◽  
Gregory A. Yanik ◽  
John M. Magenau ◽  
Steven C. Goldstein ◽  
Attaphol Pawarode ◽  
...  

Abstract Background Pneumocystis jirovecii pneumonia (PJ), previously known as Pneumocystis carinii (PCP), is a potentially life-threatening disease in immunocompromised patients. The at-risk population includes patients with HIV infection and low CD4 counts, hematological malignancies, hematopoietic stem cell (HSC) and solid organ transplant recipients, and patients receiving glucocorticoids or other immunomodulatory agents. The highest-risk group of immunocompromised patients tends to be those with HIV (human immunodeficiency virus) infection, where PJ follows an indolent course. However, in non-HIV immunocompromised patients, such as HSC transplant recipients, the infection tends to present with respiratory failure. The incidence of Pneumocystic jirovecii pneumonia (PCP) in autologous BMT (bone marrow transplant) has not been clearly determined, and the indication for prophylaxis in this setting remains unclear. In this study we evaluate the incidence of PJ infection over a 10-year period in recipients of autologous transplants. Methods Retrospective analysis of 1191 consecutive autologous HSC transplants performed between 1/1/2000 and 6/30/2011 at the University of Michigan Blood and Marrow Transplantation Program. The data was obtained from the BMT Program Database at The University of Michigan Comprehensive Cancer Center. The diagnosis of PJ pneumonia was established by both bronchoscopy with brochoaveolar lavage (BAL) with polymerase chain reaction (PCR). We analyzed the following risk factors for the development of PJ pneumonia: diabetes, glucocorticoid use (in the setting of primary disease relapse, chemotherapy-induced pneumonitis, or idiopathic thrombocytopenic purpura), infections (Pseudomonal urinary tract infection, candidiasis, herpes simplex virus), cutaneous T-cell lymphoma, hypertension, and seizure disorder. Results A total number of 5 PJ infections were diagnosed during study period, resulting in a cumulative incidence incidence of 0.42% (95%CI [0.136449% -- 0.976969%]) over the 10 year period. All cases occurred between 2001 and 2006, and 3 months or later following transplantation. Most patients (n=4) were older than 50 years old, and all of them were on steroids. Diagnoses included non-Hodgkin’s lymphoma (n=3), Hodgkin’s lymphoma (n=1) and multiple myeloma (n=1). Conditioning regimen was BEAM (BCNU, etoposide, cytarabine, melphalan, n=4) and high dose melphalan (n=1). Only 2/5 patients were neutropenic at the time of the pneumonia, and this did not correlate with the CD34+ cell infused, which was ≥2.2x10E6/kg for all patients. Four patients were on corticosteroids for relapsed lymphoma (n=2), ITP (n=1), BCNU pneumonitis (n=1). The remainder patient was on florinef and was coinfected with candida and herpes virus. There were no particular comorbidities associated with the diagnosis of PJ pneumonia. One patient died of PJ, the remainder were treated successfully. Conclusion This is the largest cohort of patients undergoing autologous transplantation evaluated for PJ pneumonia over a long period of time. Our low incidence and successful therapy suggest that PJ prophylaxis is not routinely warranted in patients undergoing autologous HSCT. Special consideration may be given to patients with additional risk factors such as corticosteroids. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 55 (10) ◽  
pp. 1996-2007 ◽  
Author(s):  
Krzysztof Kalwak ◽  
Monika Mielcarek ◽  
Katharine Patrick ◽  
Jan Styczynski ◽  
Peter Bader ◽  
...  

Abstract Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m2/day (7.7%), 12 g/m2/day (35.4%), or 14 g/m2/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I–IV and 26.6% for grades II–IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2207-2207
Author(s):  
Jennifer Anderson ◽  
Scott Wirth ◽  
Pritesh R. Patel ◽  
John G. Quigley ◽  
Annie L. Oh ◽  
...  

Abstract Prophylaxis for Pneumocystis jirovecii pneumonia (PJP) is routinely administered to patients undergoing hematopoietic stem cell transplantation (SCT) or intensive chemotherapy. There is continued risk of PJP particularly in SCT recipients when they require prolonged immunosuppression or high dose corticosteroids. Trimethoprim-sulfamethoxazole is the drug of choice but its use is limited by hematologic toxicities. Inhaled pentamidine is an alternative, but frequently causes bronchospasm, needs to be given by a respiratory therapist, and requires use of a private room during administration due to its teratogenicity. Intravenous (IV) pentamidine is FDA approved for PJP treatment, and overcomes these challenges. We conducted the first ever prospective study of IV pentamidine for PJP prophylaxis in adult patients undergoing SCT or intensive chemotherapy. Fifty patients were enrolled in a single-arm trial. Patients requiring PJP prophylaxis according to institutional guidelines received pentamidine 4 mg/kg (maximum 300 mg) intravenously with ondansetron pre-medication. Patients were followed for the occurrence of PJP pneumonia. Adverse events were recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4. Patient satisfaction was assessed by conducting the Treatment Satisfaction Questionnaire for Medication (TSQM Version 1.4) survey. Thirty-two (64%) patients were male, and the median age was 55 years (range: 19-72). Twenty-four patients (48%) were undergoing intensive chemotherapy while 26 (52%) were undergoing SCT. Of the latter group, 62% received autologous SCT and 38% allogeneic SCT. At the time of IV pentamidine administration, 58% of patients were neutropenic (absolute neutrophil count < 0.5 thous/µL) and 86% of patients were lymphopenic (absolute lymphocyte count < 1 thous/µL). All patients received at least one dose of IV pentamidine (range: 1-9). There were no cases of PJP documented during the 12 month study period. There were no NCI-CTCAE grade 3/4 events. Seventeen (34%) patients experienced a grade 1 or 2 adverse event. The most common adverse events were nausea (n=4) and hypotension (n=6). Hypotension typically occurred at the end of the infusion, was transient, and asymptomatic. Grade 1/2 acute kidney injury developing within one week of pentamidine occurred in 2 patients (4%). In both patients, serum creatinine increased within 3 days, peaked within 7 days, and normalized within 10 days. Two treatment-related interruptions of drug infusion occurred; one due to infusion-related perioral and facial numbness which resolved as soon as the drug was stopped and one due to nausea which resolved after intravenous ondansetron. IV infusion was resumed successfully in both cases. Engraftment was not adversely affected in patients undergoing SCT. The median time to neutrophil and platelet engraftment was 12 (range: 11-15) and 14 (range: 10-16) days in autologous SCT recipients and 13 (range: 13-31) and 14 (range: 14-31) days in allogeneic SCT recipients. Results from the TSQM questionnaire indicate that the majority of patients found that IV pentamidine was "not at all bothersome" (n=33, 69%), "did not interfere with physical health and ability to function" (n=37, 77%), and was "extremely easy to receive" (n=29, 60%). The most common adverse events reported in the TSQM questionnaire were nausea (n=6), nasal congestion (n=2), and mouth numbness (n=2). However, they had "minimal" or "no effect at all" on patient satisfaction with the drug. Overall patients were satisfied with the administration of IV pentamidine (n=43, 86%, p<0.01). Our study illustrates the safety and feasibility of using IV pentamidine for PJP prophylaxis in patients undergoing SCT or intensive chemotherapy. In SCT patients, IV pentamidine did not delay engraftment. The incorporation of patient centered outcomes showed a high degree of satisfaction with this method of prophylaxis. Thus, although comparative studies are required, IV pentamidine overcomes many of the respiratory and logistic challenges faced when administering inhaled pentamidine and appears to be better tolerated. In particular, patients undergoing SCT who require PJP prophylaxis over a prolonged period may derive benefit from the improved safety and patient satisfaction profile of IV pentamidine. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S947-S948
Author(s):  
Alexander Christian Drelick ◽  
Priya Kodiyanplakkal ◽  
Markus Plate ◽  
Michael J Satlin ◽  
Rosemary Soave ◽  
...  

Abstract Background Pneumocystis jirovecii pneumonia is an uncommon and life-threatening disease that can occur following hematopoietic stem cell transplantation (HSCT). Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis greatly reduces the incidence of PJP. We aim to determine what factors contribute to the development of PJP following HSCT where TMP-SMX prophylaxis is widely used. Methods We performed a single-center, retrospective case series of HSCT recipients from January 1, 2012 to December 31, 2018. Subjects had clinical symptoms and radiographic evidence for PJP along with at least one positive Pneumocystis test obtained from bronchoalveolar lavage (BAL) including direct fluorescence antibody (DFA), quantitative polymerase chain reaction (qPCR), cytology, and pathology. Results 1111 subjects underwent HSCT; of whom, 25 (2.2%) met inclusion criteria and were treated for PJP. 6 were autologous and 19 were allogeneic HSCT recipients (1.23% and 3.05% of total autologous and allogeneic HSCT, respectively). All allogeneic HSCT recipients received in-vivo T-cell depletion. Median duration from autologous and allogeneic HSCT to PJP diagnosis were 138 days (range 20 to 348) and 346 days (range 41 to 771), respectively. PJP qPCR was positive in all samples tested (n = 20, range < 84 to 14900). DFA was positive in 6 (28%). Death from pneumonia occurred in 2 subjects; 11 (44%) required ICU stay, and 7 (27%) required intubation. At diagnosis, 3 subjects had relapse of underlying disease and 10 were on immunosuppression. 12 were on PJP prophylaxis (autologous HSCT n = 3), the most common of which was atovaquone (n = 5); only 2 subjects were on TMP-SMX. Cytomegalovirus (CMV) viremia was detected in 9 subjects (36%) prior to PJP diagnosis; 4 had pulmonary CMV coinfection. In total, 17 subjects (68%) had one of the above risk factors for PJP. Median total lymphocyte count and % lymphocytes were 5.1 × 103 cells/μL (range 1.4 to 38.5 × 103 cells/μL) and 9.6% (range 1.1 to 29.5%), respectively. Conclusion PJP is an uncommon (2.2% of the study population) complication of HSCT while receiving PJP prophylaxis and in the absence of disease relapse, CMV reactivation, or ongoing immunosuppression. Presentation is often delayed in this population; a high degree of clinical suspicion should prompt diagnostic evaluation using a combination of laboratory tests on BAL fluid. Disclosures All authors: No reported disclosures.


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