A Case of Severe Pneumocystis Pneumonia in a Thyroid Cancer Patient Receiving Lenvatinib

Lenvatinib is a multitargeted tyrosine kinase inhibitor approved for use in patients with iodine-131–refractory thyroid cancer. The common adverse events of lenvatinib include hypertension, proteinuria, fatigue, and diarrhea. To date, no report on Pneumocystis pneumonia (PCP) in patients receiving lenvatinib has been published. Here, we present a case of severe PCP that led to the death of a 79-year-old woman who was diagnosed with poorly differentiated thyroid cancer and received lenvatinib. The development of PCP should be considered when patients taking lenvatinib show clinical symptoms of pneumonia, and regular chest X-ray follow-up is needed for patients receiving lenvatinib.

Pneumocystis Pneumonia Developing during Treatment of Recurrent Renal Cell Cancer with Nivolumab / 대한내과학회지

Nivolumab is an immune checkpoint inhibitor approved for the treatment of metastatic cancers. Here, we report the case of a 65-year-old male with recurrent renal cell carcinoma. After six cycles of nivolumab treatment, positron emission tomography/computed tomography (PET/CT) was performed to evaluate the response. PET/CT revealed diffuse ground glass opacities in both lungs. He developed a cough, sputum, chills, and a febrile sense. After bronchoscopic bronchoalveolar lavage, pneumocystis pneumonia was finally diagnosed.

Proposal of a Selective Prophylaxis Strategy Based on Risk Factors to Prevent Early and Late Pneumocystis jirovecii Pneumonia after Renal Transplantation / 대한이식학회지

BACKGROUND: Currently, trimethoprim-sulfamethoxazole is used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis, but it is associated with frequent adverse effects. This study evaluated the efficacy and safety of the current protocol and proposes an individualized risk-based prophylaxis protocol. METHODS: The PJP incidence and risk factors during the first 6 months (early PJP) and afterwards (late PJP) was assessed in renal transplant recipients with (prophylaxis group) and without (no-prophylaxis group) 6-month PJP prophylaxis. RESULTS: In 578 patients, there were 39 cases of PJP during a median follow-up of 51 months. Renal adverse events were encountered frequently during trimethoprim-sulfamethoxazole prophylaxis, leading to premature discontinuation. Patients without the prophylaxis had a significantly higher incidence of early PJP (n=27, 6.6%) compared to patients with the prophylaxis (n=0). The incidence of late PJP was 2.2%, without between-group differences. The factors associated with early PJP were preoperative desensitization and acute rejection within 1 month, whereas late PJP was associated with age, deceased donor transplant, and acute rejection requiring antithymocyte globulin treatment. CONCLUSIONS: Based on the simulation results of several risk-based scenarios, the authors recommend universal prophylaxis up to 6 months post-transplant and extended selective prophylaxis in patients aged ≥57 years and those with a transplant from deceased donors.

Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole used as First-Line Treatment for Pneumocystis jirovecii Pneumonia

BACKGROUND: Trimethoprim/sufamethoxazole (TMP/SMX) is the recommended treatment for Pneumocystis jirovecii pneumonia (PCP). However, the efficacy and the safety of alternative salvage treatments are less guarauteed especially when patient experiences treatment failure and/or an adverse drug reactions (ADR). The purpose of this study is to recognize potential risk factors imitating successful treatment with TMP/SMX among PCP patients. MATERIALS AND METHODS: Ninety one adult patients diagnosed with PCP were included after searching electronical medical records from January 2013 through July 2015 at Asan Medical Center Seoul, Korea. We compared clinical characteristics and laboratory findings including bronchoalveolar lavage (BAL) fluid analysis in patients who experienced TMP/SMX treatment failure or ADR (the case group) versus those who did not (the control group). RESULTS: Among the enrolled PCP patients, 39 (42.9%) required salvage treatment owing to either treatment failure (28, 28.6%) and/or ADR (17, 18.7%). The BAL lymphocyte percentage (25% [IQR, 8–40%] vs. 47% [IQR, 15–62%]; P = 0.005) was lower in the case group. Diabetes mellitus (adjusted odds ratio [aOR] 4.98, 95% confidence interval [95% CI] 1.20–18.58), glomerular filtration rate ≤50 mL/min (aOR 4.48, 95% CI 1.08–18.66), and BAL lymphocyte percentage ≤45% (aOR 9.25, 95% CI 2.47–34.58) were independently associated with the case group in multivariate analysis. CONCLUSION: This study suggests that BAL lymphocyte count may play some role during PCP treatment. Further studies should be followed to reveal what the role of BAL lymphocyte is in the PCP treatment.

Correspondence Regarding the Article Titled “Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole Used as First-Line Treatment for Pneumocystis jirovecii Pneumonia”

No abstract available.

Reply: Correspondence Regarding the Article Titled “Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole Used as First-Line Treatment for Pneumocystis jirovecii Pneumoni

No abstract available.

Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole used as First-Line Treatment for Pneumocystis jirovecii Pneumonia

BACKGROUND: Trimethoprim/sufamethoxazole (TMP/SMX) is the recommended treatment for Pneumocystis jirovecii pneumonia (PCP). However, the efficacy and the safety of alternative salvage treatments are less guarauteed especially when patient experiences treatment failure and/or an adverse drug reactions (ADR). The purpose of this study is to recognize potential risk factors imitating successful treatment with TMP/SMX among PCP patients. MATERIALS AND METHODS: Ninety one adult patients diagnosed with PCP were included after searching electronical medical records from January 2013 through July 2015 at Asan Medical Center Seoul, Korea. We compared clinical characteristics and laboratory findings including bronchoalveolar lavage (BAL) fluid analysis in patients who experienced TMP/SMX treatment failure or ADR (the case group) versus those who did not (the control group). RESULTS: Among the enrolled PCP patients, 39 (42.9%) required salvage treatment owing to either treatment failure (28, 28.6%) and/or ADR (17, 18.7%). The BAL lymphocyte percentage (25% [IQR, 8–40%] vs. 47% [IQR, 15–62%]; P = 0.005) was lower in the case group. Diabetes mellitus (adjusted odds ratio [aOR] 4.98, 95% confidence interval [95% CI] 1.20–18.58), glomerular filtration rate ≤50 mL/min (aOR 4.48, 95% CI 1.08–18.66), and BAL lymphocyte percentage ≤45% (aOR 9.25, 95% CI 2.47–34.58) were independently associated with the case group in multivariate analysis. CONCLUSION: This study suggests that BAL lymphocyte count may play some role during PCP treatment. Further studies should be followed to reveal what the role of BAL lymphocyte is in the PCP treatment.

Correspondence Regarding the Article Titled “Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole Used as First-Line Treatment for Pneumocystis jirovecii Pneumonia”

No abstract available.

Reply: Correspondence Regarding the Article Titled “Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole Used as First-Line Treatment for Pneumocystis jirovecii Pneumoni

No abstract available.

Characteristic Features of Pneumocystis Pneumonia in Pediatric Acute Lymphoblastic Leukemia / 임상소아혈액종양

BACKGROUND: Pneumocystis is difficult to culture or detect in laboratory environments. Its ecology including the timing and method of transmission as well as environmental sources and communicability remain unclear. METHODS: We retrospectively evaluated the pattern and treatment outcome of Pneumocystis jirovecii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL) who received chemotherapy. RESULTS: A total of 56 patients with ALL were evaluated. While on chemotherapy, all patients received PCP prophylaxis. PCP were found in a total of 6 patients, including definite PCP in 2, probable PCP in 2, and possible PCP in 2 patients. There were no significant differences in sex, age group, National Cancer Institute risk group, or pneumocystis prophylaxis type between PCP and non-PCP groups. However, there was a significant statistical difference in the times of ALL diagnosis. Regarding recent chemotherapy at the time of PCP diagnosis, there were one induction, one consolidation, and four maintenance cases. All PCP patients were treated with high-dose sulfamethoxazole (100 mg/kg/day) and trimethoprim (20 mg/kg/day) intravenously. Five patients survived, while one patient with endotracheal mechanical ventilation therapy died due to respiratory failure in spite of aggressive treatment. CONCLUSION: Pediatric PCP became extremely rare due to routine prophylaxis in clinical practice of pediatric malignancy. Nevertheless, we analyzed patients with acute lymphoblastic leukemia who had received PCP prophylaxis for 14 years, and analyzed the clustered outbreaks of PCP. It is still important to emphasize the need for prophylaxis and to increase the level of attention and isolation under environmental and personal risk factors.

Clinical significance of positive Pneumocystis jirovecii polymerase chain reaction in non-human immunodeficiency virus immunocompromised patients in a real practice

BACKGROUND/AIMS: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. METHODS: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. RESULTS: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. CONCLUSIONS: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.

Clinical significance of positive Pneumocystis jirovecii polymerase chain reaction in non-human immunodeficiency virus immunocompromised patients in a real practice

BACKGROUND/AIMS: Pneumocystis jirovecii polymerase chain reaction (PCR) can be helpful in diagnosing Pneumocystis pneumonia (PCP); however it has limitations. We evaluated the prevalence of positive P. jirovecii PCR from non-human immunodeficiency virus (HIV) immunocompromised patients and tried to determine the risk of PCP development. METHODS: Between May 2009 and September 2012, P. jirovecii PCR was performed in bronchoscopic specimens from 1,231 adult non-HIV immunocompromised patients suspected of respiratory infection. Only 169 patients (13.7%) who were tested positive for P. jirovecii PCR were enrolled. Retrospective chart review was performed. PCP was defined in patients with positive P. jirovecii PCR who were treated for PCP based on the clinical decision. RESULTS: From 169 P. jirovecii PCR-positive patients, 90 patients were in the PCP group (53.3%) and 79 patients were in the non-PCP group (46.7%). In the PCP group, 38% of patients expired or aggravated after therapy, whereas the majority of patients (84%) in the non-PCP group recovered without treatment for PCP. Independent risk factors for PCP by binary logistic regression analysis were underlying conditions- hematological malignancies, solid tumors or solid organ transplantation, dyspnea, age < 60 years, and albumin < 2.9 g/dL. CONCLUSIONS: This study suggests that not all P. jirovecii PCR-positive patients need to be treated for PCP. Among P. jirovecii PCR-positive patients, those who are less than 60 years old, with hematological malignancies, solid tumors or solid organ transplantation, low albumin, and with symptoms of dyspnea, the possibility of PCP might be higher. Treatment should also be selected to these patients.

Pneumocystis jirovecii Pneumonia with Granulomatous Reaction in the Lung and the Liver Discovered at Autopsy / 대한법의학회지

We report the case of a 42-year-old woman who died in hospital from severe respiratory failure, 10 days after the onset of symptoms. Autopsy and microscopic examination identified features of diffuse alveolar damage in both lungs including hyaline membranes and intra-alveolar exudate. Gomori's methenamine silver stain of pink frothy materials in these exudates revealed thin-walled and cup-shaped microorganisms and a diagnosis of Pneumocystis jirovecii pneumonia was made. There were small granulomas in the pulmonary interstitium and hepatic lobules representing an unusual inflammatory reaction against Pneumocystis jirovecii. Extrapulmonary involvement with pneumocystis infection is a rare event occurring in 1% to 2% of all pneumocystis cases. Screening and confirmatory tests for human immunodeficiency virus (HIV) detection were positive. There was no information available regarding the patient's medical history or the possibility of HIV infection prior to the autopsy, because the patient was a foreign worker who arrived in Korea 2 months before her death. Medical examiners often perform autopsies with limited information regarding the deceased person, even when person is a Korean national. Therefore, an awareness of protection protocols during autopsy, as well as of the atypical patterns of critical diseases, is crucial.

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome following HAART Initiation in an HIV-infected Patient Being Treated for Severe Pneumocystis jirovecii Pneumonia: Case Report and Literature Review / 대한중환자의학회지

Pnuemocystis jirovecii pneumonia (PJP) is one of leading causes of acute respiratory failure in patients infected with human immunodeficiency virus (HIV), and the mortality rate remains high in mechanically ventilated HIV patients with PJP. There are several reported cases who received extracorporeal membrane oxygenation (ECMO) treatment for respiratory failure associated with severe PJP in HIV-infected patients. We report a patient who was newly diagnosed with HIV and PJP whose condition worsened after highly active antiretroviral therapy (HAART) initiation and progressed to acute respiratory distress syndrome requiring veno-venous ECMO. The patient recovered from PJP and is undergoing treatment with HAART. ECMO support can be an effective life-saving salvage therapy for acute respiratory failure refractory to mechanical ventilation following HAART in HIV-infected patients with severe PJP.

Pneumocystis jirovecii pneumonia in pediatric patients: an analysis of 15 confirmed consecutive cases during 14 years / 소아과

PURPOSE: Pneumocystis jirovecii pneumonia occurs in various immunocompromised patients. Despite the prophylaxis strategies in clinical practice, certain patients develop P. jirovecii pneumonia. This study was performed to investigate pediatric cases with P. jirovecii pneumonia in a single center. METHODS: We identified pediatric patients younger than 19 years with microbiologically confirmed P. jirovecii pneumonia from January 2000 to February 2014. A retrospective chart review was performed. RESULTS: Fifteen episodes of P. jirovecii pneumonia in 14 patients were identified with median age of 8.3 years (range, 0.4-18.6 years). Among these patients, 11 patients had hematology-oncology diseases, 2 had primary immunodeficiency disorders (one with severe combined immunodeficiency and the other with Wiskott Aldrich syndrome), 1 had systemic lupus erythematosus and 1 received kidney transplant. Four patients were transplant recipients; 1 allogeneic and 2 autologous hematopoietic cell transplant and 1 with kidney transplant. The median absolute lymphocyte count at the diagnosis of P. jirovecii pneumonia was 5,156 cells/mm³ (range, 20-5,111 cells/mm³). In 13 episodes (13 of 15, 86.7%), patients were not receiving prophylaxis at the onset of P. jirovecii pneumonia. For treatment, trimethoprim/sulfamethoxazole was given as a main therapeutic agent in all 15 episodes. Steroid was given in 9 episodes (60%). Median treatment duration was 15 days (range, 4-33 days). Overall mortality at 60 days was 35.7% (5 of 14). CONCLUSION: Majority of our patients developed P. jirovecii pneumonia while not on prophylaxis. Continuous efforts and more data are needed to identify high risk patients who may get benefit from P. jirovecii pneumonia prophylaxis.

Clinical Characteristics, Prognostic Factors and Influence of Prophylaxis in Children with Pneumocystis jirovecii Pneumonia

PURPOSE: The aim of this study was to investigate the prognostic factors for Pneumocystis jirovecii pneumonia (PCP) and to evaluate the influence of PCP prophylaxis in pediatric patients. METHODS: From January 2002 to April 2015, patients aged <18 years with a diagnosis of confirmed PCP at our institute were reviewed retrospectively. Clinical characteristics and outcomes were compared according to the groups with or without PCP prophylaxis. Risk factors associated with PCP-related death were analyzed by logistic regression analysis. RESULTS: During study period, a total of 24 patients were diagnosed with PCP by immunofluorescence assay and/or PCR. The median age of the patients was 5 years (range, 3 months-18 years) and 23 (96%) had immunocompromised conditions including hematologic disorders with or without hematopoietic stem cell transplantation (n=15), solid organ transplantation (n=4), and primary immune deficiency (n=4). Most common presenting symptoms were tachypnea and cough (92%, each). At the time of diagnosis, 79% (19/24) and 25% (6/24) suffered from respiratory failure and multi-organ dysfunction syndrome (MODS), respectively. Mechanical ventilation was required in 8 (33%) patients and 5 (21%) patients died of PCP. Multivariate analysis showed that MODS at initial presentation was an indicator of poor prognosis (OR, 17.1 [95% CI 1.13-257.67]; P=0.04). Compared to the patients without PCP prophylaxis, the frequency of MODS at diagnosis, need for mechanical ventilation and length of hospital days were significantly less common in the children who received PCP prophylaxis. CONCLUSIONS: MODS at presentation was a significant predictor for poor outcome and PCP prophylaxis could alleviate the clinical courses of pediatric PCP. Prospective study will be mandatory to determine the risk factors for development and deterioration of PCP in children.

A case of Pneumocystis jiroveci pneumonia after bendamustine-based chemotherapy for refractory diffuse large B-cell lymphoma

No abstract available.

A Case of Pneumonia Caused by Pneumocystis jirovecii Resistant to Trimethoprim/Sulfamethoxazole in the Absence of Previous Drug Exposure

Pneumocystis jirovecii pneumonia is a common opportunistic infection seen in patients with human immunodeficiency virus (HIV) infection. Dihydropteroate synthase (DHPS) is a target of sulfa drugs, and mutations in DHPS gene are associated with failure in treatment and prophylaxis of P. jirovecii infections in HIV-infected patients. Here, we report a case of a patient with P. jirovecii infection, harboring DHPS gene mutations, who had not been previously treated with trimethoprim/sulfamethoxazole (TMP/SMX). A 50-yr-old man was admitted to the hospital with symptoms such as fever, cough, sputum, and sore throat. Chest computed tomography scanning revealed diffuse ground glass opacity in both the lungs, and the patient was diagnosed as having HIV infection with a CD4+ T cell count of 22/µL. Immunohistochemical test results were positive for P. jirovecii. He was treated with TMP/SMX; however, his symptoms and laboratory findings did not improve. The treatment was changed to clindamycin and primaquine, and his symptoms improved after 3 days. Molecular testing of the sample for the detection of DHPS gene mutations and the typing of mitochondrial large subunit rRNA (mtlsurRNA) revealed DHPS gene mutations at codon 55 and 57, respectively, and the case had type 3 mtlsurRNA. This case study illustrates that DHPS mutation test results can be positive even in patients without previous exposure to TMP/SMX.

Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome following HAART Initiation in an HIV-infected Patient Being Treated for Severe Pneumocystis jirovecii Pneumonia: Case Report and Literature Review / 대한구급학회지

Pnuemocystis jirovecii pneumonia (PJP) is one of leading causes of acute respiratory failure in patients infected with human immunodeficiency virus (HIV), and the mortality rate remains high in mechanically ventilated HIV patients with PJP. There are several reported cases who received extracorporeal membrane oxygenation (ECMO) treatment for respiratory failure associated with severe PJP in HIV-infected patients. We report a patient who was newly diagnosed with HIV and PJP whose condition worsened after highly active antiretroviral therapy (HAART) initiation and progressed to acute respiratory distress syndrome requiring veno-venous ECMO. The patient recovered from PJP and is undergoing treatment with HAART. ECMO support can be an effective life-saving salvage therapy for acute respiratory failure refractory to mechanical ventilation following HAART in HIV-infected patients with severe PJP.

Late Onset Infection of Pneumocystis jirovecii Infection in a Renal Transplant Recipient / 대한이식학회지

Pneumocystis jirovecii pneumonia (PCP) can be a life-threatening opportunistic infection after kidney transplantation, occurring most frequently in the first 12 months with the symptoms of dyspnea, cough, fever, and hypoxia. Prophylaxis for PCP is usually applied during the first 3 months to 1 year after transplantation, but late onset incidence of PCP can be detected. We report on a patient who developed PCP 9 years after renal transplantation. The patient showed indolent onset of acute respiratory distress and was treated with trimethoprim-sulfamethoxazole and corticosteroid therapy. Previous rescue treatment of acute cellular rejection with ongoing maintenance of an elevated level of immunosuppressants may have predisposed the patient to PCP.