Pneumocystis jiroveci pneumonia with cytomegalovirus infection diagnosed by metagenomic next-generation sequencing in a patient with nephrotic syndrome: A case report.

INTRODUCTION: Opportunistic infection with multiple pathogens currently has become less uncommon since the application of immunosuppressant or corticosteroid in non- Human immunodeficiency virus patients. However, the clinical diagnosis of the co-infection remains difficult since the uncertainty and deficiency of the microbiologic testing methods. PATIENT CONCERNS: A 66-year-old male patient was admitted to our hospital with chest stuffiness, shortness of breath and elevated body temperature. DIAGNOSIS: He was diagnosed with the co-infection of Pneumocystis jiroveci and cytomegalovirus by metagenomic next-generation sequencing of bronchoalveolar lavage fluid after bronchoscopy. INTERVENTIONS: The patient was empirically treated with broad-spectrum antibiotics, trimethoprim/ sulfamethoxazole and ganciclovir in the beginning of the admission. OUTCOMES: The condition of this patient was not improved even with the intervention at the early stage of the disease. His family requested discharge after 24 inpatient days. LESSONS: This case highlights the application of metagenomic next-generation sequencing in the clinical diagnosis of pulmonary co-infection. Suitable prophylaxis, necessary clinical awareness and accurate diagnosis are indispensable for immunocompromised patients with pulmonary infection.

Characteristics and risk factors for Pneumocystis jirovecii pneumonia in patients with idiopathic membranous nephropathy.

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection in idiopathic membranous nephropathy (IMN) patients, who are treated with immunosuppressive drugs. However, the risk factors of infection and their prognosis are rarely investigated. We aimed to characterize the clinical manifestations of PCP in patients with IMN, and to understand their risk factors, so that we can provide early warnings to patients with high risk and potential poor prognosis. We conducted a retrospective observational study of IMN patients in a referral center in China, from Jan 2012 to Dec 2018. Clinical and laboratory data were collected separately at the time of IMN and PCP diagnosis. Patients with PCP were matched to those without by gender and age at a ratio of 1:4. The risk factors and prognostic factors were determined by univariate and multivariate logistic regression analysis. A total of 879 patients with IMN were included, with a median follow-up of 267 (interquartile range (IQR) 64,842) days. In total, 26 (2.96%) of them were diagnosed with PCP. The infection rate increased to 3.87% among patients who received corticosteroids, and it further increased to 5.49% in those received over 0.5mg/kg prednisone. Univariate analysis indicated that initial usage of corticosteroids, use of cyclophosphamide, reduced estimated glomerular filtration rate (eGFR), and higher 24-h proteinuria were related to the PCP susceptibility. Multivariate analysis revealed that corticosteroid treatment and reduced eGFR increased the risk of the Pneumocystis jirovecii infection. The case fatality rate of the PCP patients was 23.08%, and increased to 75% among patients requiring invasive ventilation. Univariate analysis indicated that pulmonary insufficiency, invasive ventilation, decreased eGFR, and increased lactate dehydrogenase at presentation were linked to poor prognosis. PCP is not rare in patients with IMN, especially those on corticosteroids, and presented with decreased eGFR. Considering the high case fatality rate, further studies are in need for prevention and management of these patients.

Clinical characteristics and prognosis of patients with Pneumocystis jirovecii pneumonia without a compromised illness.

OBJECTIVE: Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP. METHODS: We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC). RESULTS: The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015-1.153; P = 0.016). CONCLUSIONS: Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.

Pneumocystis pneumonia, a COVID-19 mimic, reminds us of the importance of HIV testing in COVID-19.

While clinical environments are highly focused on COVID-19, reports of missed or delayed treatment for conditions that imitate COVID-19, such as pneumonia caused by the fungus Pneumocystis jirovecii, are emerging. Given the uncertain spectrum of COVID-19 presentations and variable sensitivity of laboratory tests for SARS-CoV-2, there is a risk that, without a high index of suspicion, alternative aetiologies may be overlooked while pursuing a diagnosis of COVID-19. The British HIV Association has been calling for the inclusion of HIV testing in all patients admitted to hospital with suspected COVID-19. In this article we reflect on the importance of including HIV testing to prevent avoidable morbidity and mortality in our patients.

Pulmonary tuberculosis and pneumocystis jirovecii concurrent pneumonia in HIV infected patients at a resource limited setting in Eastern India: A case series.

Pneumocytis jirovecii pneumonia (PJP) and Pulmonary TB (PTB) both are common opportunistic infections among HIV infected individuals. But concurrent infections pose a diagnostic challenge owing to similar clinical features. Data suggests a high prevalence of such concurrent infections in developing countries but limited diagnostic modalities especially in resource constraint setup limits accurate diagnosis. At our centre we came across 6 newly diagnosed PTB patients among HIV infected ones had persistent shortness of breath (SOB) and hypoxia despite starting anti-tuberculous treatment (ATT). We excluded concomitant bacterial pneumonia by imaging, sputum examination and blood culture. Serum lactate dehydrogenase (LDH) was estimated and hypoxia by arterial blood gas (ABG). We found all 6 patients had elevated serum LDH, hypoxia and imaging suggestive of PJP were offered sputum for Geisma stain and standard treatment for PJP in form of Bactrim-double strength and steroid. 1 patient had PJ cysts in sputum. 5 patient's classical radiologic findings in form of ground glass opacities in lower lobes along with bilateral infiltrates and 1 had honeycombing. Serum LDH was elevated all 6 subjects. 5 were newly diagnosed HIV and 4 had CD4 count below 50 cells/mm3 and 2 had below 200 cells/mm3.1 patient had developed bilateral pneumothorax as complication. 4 patients responded to treatment and 2 (33.3%) died of respiratory failure during treatment. We were able to diagnose only severe PJP cases as concurrent infection with PTB as there was no availability of broncho alveolar lavage (BAL) as well as direct fluorescent antigen (DFA) test for PJ detection. A high index of suspicion for PJP even in PTB patients with low CD4 count will guide to appropriate therapy for both infections and eventually reduces morbidity and mortality.

The many faces of interstitial pneumonia: a case of presumed SARS-CoV-2 infection.

We present the case of an oncology patient admitted to our hospital during the current COVID-19 pandemic with clinical and radiological features strongly suggestive of interstitial pneumonia. Multiple laboratory tests were negative for SARS-CoV-2 (polymerase chain reaction testing of nasopharyngeal swabs, and of induced sputum and stool samples, investigation of serum immunoglobulins G and M). In the setting of an immunocompromised status due to recent chemotherapy cycles for lung adenocarcinoma and prolonged corticosteroid therapy (due to frequent exacerbations of chronic obstructive pulmonary disease in recent months), we actively searched for the pathological agent and found it to be Pneumocystis jirovecii. The patient started specific antibiotic treatment but finally had a negative outcome due to the progression of the lung adenocarcinoma. The importance of differential diagnostics in clinical practice should be a given, especially during times of pandemic. The novel coronavirus infection introduced new guidelines for and approaches to the investigation of immunocompromised patients, so it is especially important not to forget the basis of differential diagnosis, to and adopt a thorough approach when assessing these complex patients. We want to stress the importance of thorough investigation to avoid misdiagnosis of atypical pathogens in the current setting of SARS-CoV-2 pandemic.

Clinical Characteristics and Risk Factors for Pneumocystis Jirovecii Pneumonia during Immunosuppressive Treatment in Patients with Ulcerative Colitis: A Retrospective Study.

AIMS: This study aimed to clarify the clinical characteristics of Pneumocystis jirovecii pneumonia (PJP) infection in patients with ulcerative colitis (UC) and to identify risk factors for PJP using a retrospective case-control study. METHODS: Of 4,525 patients with UC treated between 2007 and 2019, we identified those who satisfied the criteria for PJP. The Lichtiger clinical activity index (LCI) was compared between the initiation of immunosuppressive drug treatment and the onset of PJP. A retrospective case-control study was conducted using a PJP group and a non-PJP group. RESULTS: Nine patients experienced PJP, of whom two died. Since October 2014, there were no cases of PJP among UC patients aged ≥50 years who were prescribed three or more immunosuppressive agents given prophylactic sulfamethoxazole-trimethoprim (TPM-SMX). The median LCI (range) was 13 (8-17) at the initiation of treatment versus 2 (1-8) at PJP onset (p = 0.016). The median time to PJP onset was 83 days after treatment initiation. In the PJP group the median age was significantly greater (p = 0.022), three immunosuppressants were used significantly more frequently (p = 0.004), and the lymphocyte counts during treatment were significantly lower (p < 0.01) than in the non-PJP group. The cut-off lymphocyte count that distinguished PJP patients from non-PJP patients was 570/µL according to a receiver-operating curve analysis. CONCLUSIONS: Prophylactic administration of TPM-SMX prevented further cases of PJP. The onset of PJP occurred at the same time as the symptoms of UC were stabilizing and the immunosuppressive drugs were being reduced. Greater age, lower lymphocyte count, and treatment with three immunosuppressive drugs were risk factors for PJP.

Preadmission Corticosteroid Therapy and the Risk of Respiratory Failure in Adults Without HIV Presenting With Pneumocystis Pneumonia.

BACKGROUND: Corticosteroid therapy is a well-recognized risk factor for Pneumocystis pneumonia (PCP); however, it has also been proposed as an adjunct to decrease inflammation and respiratory failure. OBJECTIVE: To determine the association between preadmission corticosteroid use and risk of moderate-to-severe respiratory failure at the time of PCP presentation. METHODS: This retrospective cohort study evaluated HIV-negative immunosuppressed adults diagnosed with PCP at Mayo Clinic from 2006 to 2016. Multivariable regression models were used to evaluate the association between preadmission corticosteroid exposure and moderate-to-severe respiratory failure at presentation. RESULTS: Of the 323 patients included, 174 (54%) used preadmission corticosteroids with a median daily dosage of 20 (interquartile range: 10-40) mg of prednisone or equivalent. After adjustment for baseline demographics, preadmission corticosteroid therapy did not decrease respiratory failure at the time of PCP presentation (odds ratio: 1.23, 95% confidence interval: 0.73-2.09, P = .38). Additionally, after adjusting for inpatient corticosteroid administration, preadmission corticosteroid use did not impact the need for intensive care unit admission (P = .98), mechanical ventilation (P = .92), or 30-day mortality (P = .11). CONCLUSIONS: Corticosteroid exposure before PCP presentation in immunosuppressed HIV-negative adults was not associated with a reduced risk of moderate-to-severe respiratory failure.

Dyspnea in homosexual male patients: throwback to an occasionally forgotten but severe clinical presentation of HIV/AIDS.

Pneumocystis jirovecii pneumonia (PJP) can be a severe indicator disease of acquired immunodeficiency syndrome (AIDS). We present two cases of homosexual male patients who came to the emergency unit of a Belgian hospital because of shortness of breath. Both men had been sent back home, initially diagnosed with a benign viral infection. Because of worsening symptoms and gradually evolving hypoxemia, both patients came back and were admitted to the hospital with a diagnosis of (microbiology proven) Pneumocystis jirovecii pneumonia. HIV serology in both men was tested and was clearly positive, indicating a new diagnosis of HIV infection. In this article, we provide an overview of this possibly severe AIDS defining condition. First, we give an introduction of the history of HIV/AIDS and its occurrence in homosexual males in Europe. Secondly, we provide an overview of the diagnosis and treatment of Pneumocystis jirovecii pneumonia. Finally, since the first case reports of Pneumocystis jirovecii pneumonia at the beginning of the AIDS epidemic also included homosexual men, we emphasize the potential importance of a sexual anamnesis in young male patients with an initial complaint of dyspnea.

Pneumocystis jirovecii Pneumonia in a Patient with Breast Cancer Receiving Neoadjuvant Dose-dense Chemotherapy.

We herein report a 38-year-old woman with breast cancer who developed Pneumocystis jirovecii pneumonia (PCP) during neoadjuvant dose-dense chemotherapy combined with dexamethasone as antiemetic therapy. Chest computed tomography showed bilateral ground-glass opacities and consolidation. The serum ß-D-glucan levels were elevated, and P. jirovecii DNA was detected from the bronchoalveolar lavage fluid by polymerase chain reaction. Her clinical findings improved with trimethoprim/sulfamethoxazole and adjunctive steroid therapy. Clinicians must be mindful of the manifestations of PCP in non-human immunodeficiency virus (HIV)-infected immunocompromised patients and include the possibility of PCP in the differential diagnosis when confronted with breast cancer on dose-dense chemotherapy showing diffuse lung disease.

Hypercalcemia Heralding Pneumocystis jirovecii Pneumonia in an HIV-Seronegative Patient with Diffuse Cutaneous Systemic Sclerosis.

Pneumocystis pneumonia (PCP) is a life-threatening fungal infection occurring in immunocompromised patients such as HIV-positive patients with low CD4 cell count or patients under heavy immunosuppressive therapy. We report the case of a 59-year-old male with severe diffuse cutaneous systemic sclerosis presenting with asthenia, dry cough and worsening shortness of breath for the last 15 days. Biological studies were remarkable for PTH-independent severe hypercalcemia with low 25-hydroxyvitamin D and a paradoxically elevated 1,25-dihydroxyvitamin D. Early bronchoalveolar lavage allowed for PCP diagnosis and targeted treatment. We discuss the underlying physiopathology and difficulties regarding prophylaxis and treatment.

Pneumocystis jirovecii pneumonia at chest High-resolution Computed Tomography (HRCT) in non-HIV immunocompromised patients: Spectrum of findings and mimickers.

Pneumocystis jirovecii pneumonia (PJP) has emerged as a main issue in non Human Immunodeficiency Virus (HIV) immunocompromised hosts, exposing patients to high mortality rates, especially when the diagnosis is delayed. Since microbiological confirmation is often unfeasible or difficult to obtain, High-resolution Computed Tomography (HRCT) represents a main tool for guiding the diagnosis in the appropriate clinical scenario. Nevertheless, radiologists must be aware that PJP at HRCT is a multifaceted process, with a variety of common and less frequent findings, along with a broad spectrum of infectious (e.g., viral and certain fungal and bacterial pneumonias) and non-infectious (e.g., pulmonary oedema, diffuse alveolar haemorrhage, and drug toxicity) differential diagnoses. In this review we resume background clinical information on PJP in non-HIV immunocompromised patients, illustrate both typical and less frequent HRCT findings, and present the spectrum of infectious and non-infectious mimickers at HRCT, highlighting the similarities with PJP and providing clues for the differential diagnosis.

Risk factors and clinical characteristics of Pneumocystis jirovecii pneumonia in lung cancer.

Solid malignancies are associated with the development of Pneumocystis jirovecii pneumonia (PJP). This study aimed to evaluate the risk factors for PJP among patients with lung cancer. This retrospective case-control study compared patients who had lung cancer with PJP (n = 112) or without PJP (n = 336) matched according to age, sex, histopathology, and stage. PJP definition was based on (i) positive PCR or direct immunofluorescence results for pneumocystis, (ii) clinical symptoms and radiological abnormalities that were consistent with a pneumonic process, and (iii) received targeted PJP treatment. The development of PJP was associated with radiotherapy (RTx), concurrent chemoradiotherapy (CCRTx), lymphopenia, and prolonged high-dose steroid therapy (20 mg of prednisolone equivalent per day for ≥3 weeks). Multivariate analysis revealed independent associations with prolonged high-dose steroid therapy (odds ratio [OR]: 1.96, 95% confidence interval [CI]: 1.06-3.63; p = 0.032) and CCRTx (OR: 2.09, 95% CI: 1.27-3.43; p = 0.004). Steroid use was frequently related to RTx pneumonitis or esophagitis (29 patients, 43.3%). Prolonged high-dose steroid therapy and CCRTx were risk factors for PJP development among patients with lung cancer. As these patients had a poor prognosis, clinicians should consider PJP prophylaxis for high-risk patients with lung cancer.

[Clinical Features of Pneumocystis Jiroveci Pneumonia in Patients with Inflammatory Bowel Disease].

Objective To investigate the clinical features of patients with inflammatory bowel disease (IBD) complicated with Pneumocystis Jiroveci Pneumonia (PJP). Methods We retrospectively analyzed the clinical data of 5 patients who were hospitalized in Peking Union Medical College Hospital from January 2012 to July 2017 for treatment of IBD complicated with PJP. Demographic characteristics,clinical manifestations,treatments,and outcomes were descriptively analyzed. Results Of these five patients,four had ulcerative colitis (UC) and one had Crohn's disease (CD). All patients were males,with an average age of (61.8±1.9) years. All patients were in active disease status and had symptoms including cough and suffocation. Three patients had hypoxemia,among whom two developed type 1 respiratory failure. Three patients were treated with immunosuppressive medications (corticosteroids and/or immunosuppressant drugs) before the diagnosis of PJP. Lymphocyte counts in three patients were less than 0.6×109/L. CD4+T cells in two patients were less than 200×106/L. Four patients had elevated serum cytomegalovirus DNA. The level of ß-D-glucan was elevated in four patients. Chest CT showed bilateral diffuse ground glass opacification. PJP-DNA was positive in sputum or bronchoalveolar lavage fluid in all patients. Two patients with type 1 respiratory failure required invasive mechanical ventilation. All patients received trimethoprim-sulfamethoxazole and methylprednisolone treatment. Four patients recovered completely and one died. Conclusion Elderly (aged>55 years) IBD patients who are receiving immune-suppressive therapy or with decreased peripheral blood lymphocyte count are at higher risk of PJP.

Characteristics of pulmonary complications in non-Hodgkin's lymphoma patients treated with rituximab-containing chemotherapy and impact on survival.

Patients with non-Hodgkin's lymphoma (NHL) receiving rituximab-containing chemotherapy are at risk of developing respiratory complications, but comprehensive information on these complications and their impact on survival is lacking. We performed a retrospective cohort analysis on 123 NHL patients who received rituximab-containing chemotherapy between 2009 and 2016 in order to describe the incidence, etiologies and effect on survival of respiratory complications defined by new or worsening respiratory symptoms requiring diagnostic work-up or hospitalization. Thirty patients (24%) developed respiratory complications during a follow-up time of 825 (555-1338) days after chemotherapy. They had a higher prevalence of congestive heart failure and lung or pleural involvement at diagnosis as compared to patients who did not develop complications. Overall, 58 episodes of pulmonary complications were observed after median (interquartile) times from the first and last rituximab doses of 205 (75-580) days and 27 (14-163) days respectively. Infectious etiologies accounted for 75% of the respiratory complications, followed by heart failure exacerbation, lymphomatous involvement, and ARDS. Two Pneumocystis jirovecii pneumonias were observed, and no complication was ascribed to rituximab toxicity. Respiratory complications required ICU admission in 19 cases (33%) and invasive mechanical ventilation in 14 cases (24%). Using a time-dependent Cox regression analysis, we observed that the occurrence of respiratory complications was associated with a 170% increase in death hazard (hazard ratio 2.65, 95% CI 1.60-4.40, p = 0.001). In conclusion, respiratory complications in NHL patients receiving chemotherapy are relatively frequent, severe, and mostly infectious and are associated with increased mortality.

Nonopportunistic infection leading to rapidly progressive dementia in a patient with HIV/AIDS: A case report.

RATIONALE: Cognitive dysfunction is a common presenting symptom in patients with HIV/AIDS. It is usually directly associated with HIV infection or due to opportunistic infection. Rapidly progressive dementia, however, is rarely observed in acute HIV infection or during immune reconstitution. Recently, a case of Creutzfeld-Jakob disease (CJD) has been reported in a patient with chronic HIV infection. The incidence of CJD is not known to be increased among immunocompromised patients. PATIENT CONCERNS: We here report the case of a 59-year-old male patient with a recent diagnosis of HIV/AIDS and Pneumocystis jiroveci pneumonia presenting with secondary behavioral changes and disorientation. Over the course of several weeks, progressive dementia developed characterized by apraxia, gait ataxia, and mutism. DIAGNOSES: After the exclusion of common HIV-associated neurologic conditions, the clinical course as well as findings on electroencephalogram (EEG), magnetic resonance imaging (MRI), and a positive 14-3-3 assay converged into a probable diagnosis of CJD. The diagnosis was later confirmed histopathologically. OUTCOMES: Palliative care was provided, and the patient passed away within 2 months of symptom onset. LESSONS: HIV/AIDS is an important stratifying condition during the work-up of many clinical syndromes including encephalopathy but may prematurely exclude important differential diagnoses. Non-opportunistic etiologies have to be considered as part of a secondary workup as this case of concomitant AIDS and CJD demonstrates. Rapidly progressive dementia should be distinguished from delirium as early as possible in order to be able to choose the correct diagnostic pathway. Despite the common occurrence of neurologic syndromes in the setting of immunodeficiency, an analytical diagnostic approach is advisable to minimize diagnostic bias.

Animal models of polymicrobial pneumonia.

Pneumonia is one of the leading causes of severe and occasionally life-threatening infections. The physiopathology of pneumonia has been extensively studied, providing information for the development of new treatments for this condition. In addition to in vitro research, animal models have been largely used in the field of pneumonia. Several models have been described and have provided a better understanding of pneumonia under different settings and with various pathogens. However, the concept of one pathogen leading to one infection has been challenged, and recent flu epidemics suggest that some pathogens exhibit highly virulent potential. Although "two hits" animal models have been used to study infectious diseases, few of these models have been described in pneumonia. Therefore the aims of this review were to provide an overview of the available literature in this field, to describe well-studied and uncommon pathogen associations, and to summarize the major insights obtained from this information.