Clinical course and prognostic factors of Pneumocystis pneumonia with respiratory failure in non-HIV patients.

Background: Compared with Human Immunodeficiency Virus (HIV) patients, non-HIV patients with Pneumocystis pneumonia (PCP) have more rapid onset, more rapid progression, and higher mortality. Objectives: To investigate the predictive value of variables obtained upon hospital admission for in-hospital death and 90-day outcomes in non-HIV-PCP patients with respiratory failure (RF). Methods: This was a single center retrospective study in a tertiary care institution over 15 years. It included all adults inpatients (≥18 years old) with laboratory confirmed non-HIV-PCP with RF who were discharged or died from Peking University First Hospital between April 1st, 2007 and November 1st, 2022. Epidemiological, clinical, laboratory, imaging and outcome data were collected from patient records. Results: In this study, a total of 146 non-HIV-PCP patients with RF were included. There were 57 patients (39%) died during hospitalization, 44 patients (53%) died in Intensive care unit (ICU). A total of 137 patients completed 90 days of follow-up, of which 58 (42.3%) died. The multivariable regression analysis revealed that a CD8+ T cell count <115/µl (P=0.009), bronchoalveolar lavage fluid (BALF)-neutrophil percentage ≥50% (P=0.047), the time from corticosteroids withdrawal to symptom onset ≤5 days (P=0.012), and the time from visit to initiation of sulfonamides ≥2 days (P=0.011) were independent risk factors for in-hospital death. Furthermore, a CD8+ T cell count < 115/µl (P=0.001) and the time from visit to initiation of sulfonamides therapy ≥2 days (P=0.033) was independently associated with 90-day all-cause death. Conclusions: A low CD8+ T cell count in peripheral blood, a high percentage of BALF-neutrophils, a short time from corticosteroids withdrawal to symptom onset, and a long time from visit to initiation of sulfonamides are associated with poor prognosis in non-HIV-PCP patients with RF.

Herpes zoster in the context of immune reconstitution inflammatory syndrome in patients with rheumatic diseases: a single-center retrospective study.

Immune reconstitution inflammatory syndrome (IRIS) experienced in rheumatology practice is diverse and includes opportunistic infections such as herpes zoster (HZ). This study aimed to explore the risk of HZ in patients with rheumatic diseases in the perspective of IRIS. The study retrospectively reviewed the clinical courses of 20 patients with HZ and investigated the IRIS triggers such as the reduction or discontinuation of immunosuppressive drugs within 3 months and coronavirus disease 2019 (COVID-19) vaccination within 4 weeks prior to HZ development. Disease activity of the underlying rheumatic disease at HZ onset was evaluated using the physician's global assessment. Thirteen patients developed HZ after reducing or discontinuing immunosuppressive drugs, with mild and stable disease activity. In four of these cases, disease activity increased after dose reduction or discontinuation, and HZ subsequently developed. Two of the seven patients who did not reduce or discontinue immunosuppressive drugs received the COVID-19 vaccination. Fifteen patients (75%) had at least one of the two IRIS triggers. Four of the five patients who developed HZ without any IRIS triggers were at HZ risk. To conclude, IRIS, caused by the reduction or discontinuation of immunosuppressive drugs, may be involved in the development of HZ in rheumatology practice.

Multiple systemic infections caused by Rhodococcus equi: a case report.

Background: Rhodococcus equi is one of the most important causes of zoonotic infections from grazing animals. It poses a particular risk to immunocompromised individuals, including those who are undergoing long-term immunosuppressive therapy. Case presentation: We report a case of Rhodococcus equi infection in a 65-year-old man with a medical history of diabetes, hypertension, and Adult Still's Disease, currently taking long-term hormone therapy. The non-human immunodeficiency virus (HIV)-infected patient had blood, lung tissue, and sputum samples infected with Rhodococcus equi. His condition initially failed to improve despite multiple therapies, including vancomycin and meropenem. Although his symptoms improved after shifting his antibiotics to cover for the causative agent, he did not completely recover upon hospital discharge. Conclusions: In recent years, the number of Rhodococcus equi cases has increased. This report describes a lethal case of Rhodococcus equi infection in a patient without HIV.

Clinical significance of mutations in dihydropteroate synthase in Pneumocystis jirovecii pneumonia among non-HIV-infected patients.

BACKGROUND: Dihydropteroate synthase (DHPS) mutations may be associated with trimethoprim-sulfamethoxazole resistance in Pneumocystis jirovecii pneumonia (PCP) and worse clinical outcomes. However, the clinical significance of DHPS mutations in PCP among non-human immunodeficiency virus (HIV)-infected patients remains unclear. METHODS: Patients with PCP in three tertiary referral hospitals in Taiwan between 2016 and 2020 were retrospectively enrolled. Two point mutations, Thr55Ala and Pro57Ser, in the DHPS protein were analysed. Patients with invalid DHPS mutations in the respiratory specimen, chronic respiratory failure, receiving endotracheal intubation for surgical intervention, HIV infection, Pneumocystis jirovecii colonisation, and no lactate dehydrogenase (LDH) data were excluded. The primary outcome was 30-day survival. RESULTS: A total of 215 patients were analysed. Mutants inside DHPS were found in 78 patients (36.3%) and 68 patients (31.6%) died within 30 days. A total of 214 patients (99.5%) received trimethoprim-sulfamethoxazole as the first-line treatment. The rates of mechanical ventilation, 30-day, and in-hospital mortality were similar between wild-type and mutant DHPS PCP. After adjusting for important confounders, LDH > 500 µ/L (adjusted hazard ratio [aHR] = 2.448, P = 0.001), pneumonia severity index > 135 mg/dL (aHR = 1.689, P = 0.049), and having solid tumours (aHR = 1.832, P = 0.034) were independently associated with higher mortality. In subgroup analysis, mutant DHPS PCP patients had less 30-day mortality among patients aged > 65 years (P = 0.049), with lymphopenia (P = 0.040), and those without solid tumour (P = 0.045). CONCLUSIONS: In non-HIV-infected PCP, point mutants inside DHPS may not be associated with trimethoprim-sulfamethoxazole treatment outcomes. Further prospective large-scale studies are warranted.

Treatment of Pneumocystis jirovecii pneumonia in non-human immunodeficiency virus-infected patients using a combination of trimethoprim-sulfamethoxazole and caspofungin.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an infectious disease common in immunocompromised hosts. However, the currently, the clinical characteristics of non-HIV patients with PJP infection have not been fully elucidated. AIM: To explore efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) and caspofungin for treatment of non-human immunodeficiency virus (HIV)-infected PJP patients. METHODS: A retrospective study enrolled 22 patients with non-HIV-infected PJP treated with TMP-SMX and caspofungin from 2019 to 2021. Clinical manifestations, treatment and prognosis of the patients were analyzed. RESULTS: Five patients presented with comorbidity of autoimmune diseases, seven with lung cancer, four with lymphoma, two with organ transplantation and four with membranous nephropathy associated with use of immunosuppressive agents. The main clinical manifestations of patients were fever, dry cough, and progressive dyspnea. All patients presented with acute onset and respiratory failure. The most common imaging manifestation was ground glass opacity around the hilar, mainly in the upper lobe. All patients were diagnosed using next-generation sequencing, and were treated with a combination of TMP-SMX and caspofungin. Among them, 17 patients received short-term adjuvant glucocorticoid therapy. All patients recovered well and were discharged from hospital. CONCLUSION: Non-HIV-infected PJP have rapid disease progression, high risk of respiratory failure, and high mortality. Combination of TMP-SMX and caspofungin can effectively treat severe non-HIV-infected PJP patients with respiratory failure.

Seven cases of severe pneumocystis jirovecii pneumonia in children with non-human immunodeficiency virus infection and a literature review / 中国小儿急救医学

Objective:To summarize the clinical features and treatment of pneumocystis jirovecii pneumonia(PCP) in children with non-human immunodeficiency virus(HIV) infection.Methods:A retrospective study was performed on seven cases of severe PCP children with non-HIV infection who were admitted to PICU of The University of Hong Kong-Shenzhen Hospital and PICU of Xianyang Rainbow Hospital from May 1, 2015 to May 1, 2021.The risk factors, clinical manifestations, laboratory results, pulmonary radiological features, treatment and outcomes were observed.Results:Seven children with PCP, including four males and three females, aged from 13 months to 85 months[(42.4±26.8) months], were all associated with underlying diseases, and most of which was hematological malignancies.Six children had a history of using TMP-SMX for PCP prevention, but four of them stopped by themselves and infected PCP in 2 to 4 weeks.All children had hypoxic respiratory failure, whose OI was 30.6±3.4, and presented with fever, dry cough, progressive dyspnea but no lung rales in the early stage.LDH[(745.7±317.0) U/L] and β-D-glucan[(513.8±225.0) pg/mL] increased in all patients.Chest CT showed diffused interstitial changes in bilateral lung fields associated with multiple exudative lesions.Among the anti-Pneumocystis Jirovecii treatment regimens, all cases began the treatment in the first three days during the admission, five cases were treated with intravenous TMP-SMX, and two cases were treated with oral TMP-SMX + caspofungin, with a course of 21 days.All children were also treated with glucocorticoid at the same time.Three days after the treatment of PCP, two children were worsened and one of them died, while another one started to recover on the 6th day of the regimen.The remaining five cases began to show clinical improvement after 3~7 days of PCP treatment.Finally six children were cured and one was died.Conclusion:PCP infection of children without HIV has high risk of destruction in immune system.TMP-SMX can prevent PCP effectively.In the severe PCP cases, early commencement of intravenous TMP-SMX can reduce the mortality rate.In the absence of intravenous TMP-SMX, oral TMP-SMX can be used with caspofungin.

Advance in potential immunodeficiency in opportunistic infection among non-human immunodeficiency virus hosts / 中华微生物学和免疫学杂志

Opportunistic infections often occur in immunocompetent hosts. Human immunodeficiency virus (HIV) infection and underlying diseases that can cause immunodeficiency or immune disorders are the main susceptibility factors. In recent years, it has been found that there are some new potential immunodeficiency mechanisms such as anti-cytokine antibody diseases and primary immunodeficiency diseases that are closely related to various opportunistic infections such as Talaromyces marneffei, non- Tuberculous mycobacteria and Aspergillus infections in non-HIV hosts. Moreover, many problems including clinical infection phenotype, immunodeficiency regulation mechanisms and treatment strategies have drawn increasing attention. This review summarized the potential mechanisms of immunodeficiency and opportunistic infections in non-HIV hosts.

Clinical characteristics of pneumocystis carinii pneumonia in children without human immunodeficiency virus infection / 中国小儿急救医学

Objective:To investigate the clinical characteristics and prognosis factors in children with pneumocystis carinii pneumonia (PCP) without human immunodeficiency virus (HIV) infected.Methods:From January 2017 to December 2020, 35 non-HIV infected patients with PCP were admitted to Hunan Children′s Hospital.According to the prognosis at discharge, they were divided into survival group and death group.The clinical characteristics of two groups were compared, and the prognostic factors were analyzed.Results:The age of 35 patients ranged from 1 month to 15 years, including 24 males and 11 females.Seven patients(20.0%) had primary immunodeficiency, 5 patients(14.2%) had autoimmune disease, and 4 patients(11.4%) had renal disease.Eighteen patients were treated with long-term hormone and 13 patients were treated with immunosuppressive agents before the onset of the disease.Clinical symptoms included shortness of breath or dyspnea, cough, fever and so on, while with few pulmonary signs.Peripheral blood lymphocyte count was less than 1.5×10 9/L in 18 cases.The median LDH was(654.94±57.66)U/L; Fungal D-glucan increased in 13 cases.The median P/F was(121.29±23.25)mmHg, and P/F was less than 200 mmHg in 16 cases.CD4 cells were less than 500/μL in 15 cases and less than 200/μL in 8 cases.The imaging findings were mainly consolidation or patellar shadow, diffuse ground glass shadow, 3 cases with pleural effusion, and 1 case with pneumothorax.Twenty-two cases survived and 13 died, with a mortality rate of 37.1%.There were statistically significant differences in hospitalization days, CD4 cell count, Fungal D-glucan, P/F, ICU admission and invasive mechanical ventilation between two groups( P<0.05). Logistic multivariate analysis showed that decreased P/F value was an independent risk factor affecting the prognosis of non-HIV infected children with PCP ( OR=0.006, 95% CI 0.975-1.000). Conclusion:The clinical manifestations, laboratory examinations and imaging examinations of non-HIV infected patients with PCP lack specificity.When a diagnosis is suspected, high-resolution CT should be performed based on the results of peripheral blood lymphocyte count, CD4 cell count, fungal D, LDH, and blood gas analysis results as soon as possible, compound sulfamethoxazole should be used timely.Decreased P/F value is an independent factor affecting the prognosis of non-HIV children with PCP.

Clinical characteristics of pneumocystis carinii pneumonia in children without human immunodeficiency virus infection / 中国小儿急救医学

Objective:To investigate the clinical characteristics and prognosis factors in children with pneumocystis carinii pneumonia (PCP) without human immunodeficiency virus (HIV) infected.Methods:From January 2017 to December 2020, 35 non-HIV infected patients with PCP were admitted to Hunan Children′s Hospital.According to the prognosis at discharge, they were divided into survival group and death group.The clinical characteristics of two groups were compared, and the prognostic factors were analyzed.Results:The age of 35 patients ranged from 1 month to 15 years, including 24 males and 11 females.Seven patients(20.0%) had primary immunodeficiency, 5 patients(14.2%) had autoimmune disease, and 4 patients(11.4%) had renal disease.Eighteen patients were treated with long-term hormone and 13 patients were treated with immunosuppressive agents before the onset of the disease.Clinical symptoms included shortness of breath or dyspnea, cough, fever and so on, while with few pulmonary signs.Peripheral blood lymphocyte count was less than 1.5×10 9/L in 18 cases.The median LDH was(654.94±57.66)U/L; Fungal D-glucan increased in 13 cases.The median P/F was(121.29±23.25)mmHg, and P/F was less than 200 mmHg in 16 cases.CD4 cells were less than 500/μL in 15 cases and less than 200/μL in 8 cases.The imaging findings were mainly consolidation or patellar shadow, diffuse ground glass shadow, 3 cases with pleural effusion, and 1 case with pneumothorax.Twenty-two cases survived and 13 died, with a mortality rate of 37.1%.There were statistically significant differences in hospitalization days, CD4 cell count, Fungal D-glucan, P/F, ICU admission and invasive mechanical ventilation between two groups( P<0.05). Logistic multivariate analysis showed that decreased P/F value was an independent risk factor affecting the prognosis of non-HIV infected children with PCP ( OR=0.006, 95% CI 0.975-1.000). Conclusion:The clinical manifestations, laboratory examinations and imaging examinations of non-HIV infected patients with PCP lack specificity.When a diagnosis is suspected, high-resolution CT should be performed based on the results of peripheral blood lymphocyte count, CD4 cell count, fungal D, LDH, and blood gas analysis results as soon as possible, compound sulfamethoxazole should be used timely.Decreased P/F value is an independent factor affecting the prognosis of non-HIV children with PCP.

Comprehensive Analysis and Risk Identification of Pulmonary Cryptococcosis in Non-HIV Patients.

Pulmonary cryptococcosis in the non-human immunodeficiency virus-infected population is uncommon. We aimed to explore the relevance between clinical presentations, radiological findings, and comorbidities and identify the outcome predictors. A total of 321 patients at Taichung Veterans General Hospital between 2005 and 2019 were included; of them, 204 (63.6%) had at least one comorbidity, while 67 (20.9%) had two or more. The most common comorbidities were diabetes mellitus (27.4%), malignant solid tumor (19.6%), autoimmune disease (15.6%), and chronic kidney disease (8.4%). Patients experiencing comorbidity, particularly those with multiple comorbidities, had a higher multilobar and extrapulmonary involvement, which could explain these patients being more symptomatic. In the overall population, extrapulmonary involvement independently predicted disease recurrence and death. Amongst patients with isolated pulmonary cryptococcosis, age, cryptococcal antigen (CrAg) titer in blood, and comorbidities not only predicted the extent of disease, but also its outcome. Of note, patients simultaneously with age ≥ 65 years, CrAg test ≥ 1:128, and multiple comorbidities had the lowest disease control of antifungal treatment (76.9%) and the highest rate of disease recurrence or death from any cause (40.0%). In conclusion, approximately two-thirds of patients had at least one underlying comorbidity. In addition to extrapulmonary involvement, old age, high CrAg titer in blood, and multiple comorbidities could act as risk factors for predicting the extent of disease and outcome.

Disseminated Talaromyces marneffei Infection in a Non-HIV Infant With a Homozygous Private Variant of RELB.

Objective: This study presents a relatively rare case of disseminated Talaromyces marneffei (T. marneffei) infection in an HIV-negative patient. Methods: An 8-month-old girl was hospitalized because of uncontrollable fever and cough for 6 days. Routine laboratory tests, biochemical detection, immunological tests, pathogenic examination, and imaging inspection were performed. Genetic tests of trio whole genome sequencing (Trio-WES), trio copy number sequencing (Trio-CNVseq), and Sanger sequencing were conducted to identify pathogenic variants. In silico analysis of the sequence alignment and structural modeling results was carried out to study the possible pathogenicity of the identified variant. Western blotting was performed to investigate the expression of the identified gene at the protein level. Results: Enhanced CT and MRI scanning demonstrated thymic dysplasia, diffuse pulmonary and liver nodules, and many balloon-like air sacs in both lungs. The white blood cell count, neutrophil count, and neutrophil ratio were normal or elevated. The patient was HIV-negative and bone marrow and blood culture showed T. marneffei infection. Total lymphocyte count, CD3+ T lymphocyte count, CD3+CD4+ T lymphocyte count, CD3+CD8+ T lymphocyte count, and NK cell count decreased, while the number of CD19 positive B cells increased. However, the ratio of CD3+CD4+:CD3+CD8+ T cells increased. Trio-WES identified a homozygous private variant of NM_006509: c.400_c.401insAGC/p.Lys134 delinsLysGln in RELB and Sanger sequencing validated the result. Structural modeling indicated that the variant may be pathogenic. Reverse transcription-polymerase chain reaction and Western blot analysis showed that the expression of RelB in the patient was lower than that in the healthy controls at mRNA and protein levels. Conclusion: This is the first report on disseminated T. marneffei infection in a patient with a homozygous private variant of RELB.

Veno-Venous Extracorporeal Membrane Oxygenation for Severe Pneumocystis jirovecii Pneumonia in an Immunocompromised Patient without HIV Infection.

Pneumocystis jirovecii pneumonia (PJP) occurs in immunocompromised hosts and is classified as PJP with human immunodeficiency virus (HIV) infection (HIV-PJP) and PJP without HIV infection (non-HIV PJP). Non-HIV PJP rapidly progresses to respiratory failure compared with HIV-PJP possibly due to the difference in immune conditions; namely, the prognosis of non-HIV PJP is worse than that of HIV PJP. However, the diagnosis of non-HIV PJP at the early stage is difficult. Herein, we report a case of severe non-HIV PJP successfully managed with veno-venous extracorporeal membrane oxygenation (V-V ECMO). A 54-year-old woman with neuromyelitis optica was treated with oral corticosteroid, azathioprine, and methotrexate. She admitted to our hospital for fever, dry cough, and dyspnea which developed a week ago. On admission, she required endotracheal intubation and invasive ventilation for hypoxia. A chest computed tomography (CT) scan revealed ground-glass opacity and consolidation in the both lungs. Grocott staining and PCR analysis of bronchoalveolar lavage fluid indicated the presence of fungi and Pneumocystis jirovecii, respectively, whereas serum HIV-antibody was negative. The patient was thus diagnosed with non-HIV PJP and was treated with intravenous pentamidine and corticosteroid pulse therapy for PJP. However, hypoxia was worsened; consequently, V-V ECMO assistance was initiated on day 7. The abnormal chest CT findings and hypoxia were gradually improved. The V-V ECMO support was successfully discontinued on day 14 and mechanical ventilation was discontinued on day 15. V-V ECMO could be a useful choice for respiratory assistance in severe cases of PJP among patients without HIV infection.

Low-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in non-human immunodeficiency virus-infected immunocompromised patients: A single-center retrospective observational cohort study.

BACKGROUND/PURPOSE: The efficacy of low-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be acceptable for the treatment of pneumocystis pneumonia (PCP) in non-human immunodeficiency virus (HIV)-infected patients, with a low incidence of adverse reactions. This study is aimed to evaluate the efficacy and safety of such a regimen for the treatment of non-HIV PCP. METHODS: We retrospectively enrolled 24 consecutive patients diagnosed with non-HIV PCP who were treated with low-dose TMP-SMX (TMP, 4-10 mg/kg/day; SMX, 20-50 mg/kg/day). Data of the conventional-dose treatment were used as reference. The primary endpoints were the 30- and 180-day survival rates from the day of treatment, and secondary endpoints were the incidence of each adverse reaction and dropout rate from the initial TMP-SMX regimen. The survival rate was estimated using the Kaplan-Meier method with 95% confidence interval (CI). RESULTS: The median age of patients was 72 years (54.2% men), and connective tissue disease was the most frequent underlying disease (66.7%) in the low-dose group. The 30- and 180-day survival rates were 95.8% (95% CI: 88.2-100.0%) and 91.0% (95% CI: 79.9%-100.0%), respectively, in the low-dose group and 69.0% (95% CI: 54.0%-88.0%) and 51.5% (95% CI: 36.1%-73.4%), respectively, in the conventional-dose group. The total adverse reaction rate was 58.3% in the low-dose group and 72.4% in the conventional-dose group. A total of 75.0% of patients in the low-dose group and 31.0% in the conventional-dose group completed treatment with the initial regimen. CONCLUSION: Low-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

The risk factors for mortality in non-human immunodeficiency virus infected children with pneumocys-tis carinii pneumonia / 中国小儿急救医学

Objective To analyze the epidemiologic characteristics and risk factors for mortality in non-(human immunodeficiency virus,HIV) infected children with pneumocystis carinii pneumonia(PCP). Methods The data of non-HIV infected children with PCP diagnosed in Beijing Children′s Hospital from January 1,2006 to December 31,2012 were collected. They were divided into survival and non-survival group according to the prognosis. The epidemiologic characteristics and risk factors for mortality were analyzed. Results Sixteen patients were enrolled in this study. Ten of them survived and 6 of them were non-survived. The basic diseases included malignant tumor in 5 patients and non-malignancy diseases in 11 of them. Com-pared with the survival group,the non-survival group had a higher average age [(12. 00 ± 2. 00) years vs. (6. 65 ± 4. 32)years,P=0. 01],higher ratio to need mechanical ventilation (6/6 vs. 4/10,P=0. 04),lower PaO2/FiO2[(73. 88 ±26. 95) mmHg vs. (167. 50 ± 97. 17) mmHg,1 mmHg=0. 133 kPa,P=0. 01] and lower pediatric critical illness score(75. 67 ± 5. 72 vs. 86. 40 ± 8. 88,P=0. 02). There were no differences on sex ratio,kinds of basic diseases,whether with co-infections,the time of immunosuppressant administration, the time from onset to diagnosis,the time from onset to beginning trimethoprim-sulfamethoxazole therapy, PaCO2 ,white blood cell counts,lymphocyte counts,CD4+ cell counts,C-reactive protein,and hemoglobin con-centrations between the survival and non-survival group. Conclusion A higher age, need for mechanical ventilation,lower PaO2/FiO2 and lower pediatric critical illness score were risk factors for mortality in non-HIV infected children with PCP.