Clinical treatment and management of invasive fungal disease in recipients of solid organ transplantation / 器官移植

With widespread application of solid organ transplantation (SOT), the incidence of postoperative invasive fungal disease (IFD) in SOT recipients has been increased year by year. In recent years, the awareness of preventive antifungal therapy for SOT recipients has been gradually strengthened. However, the problem of fungal resistance has also emerged, leading to unsatisfactory efficacy of original standardized antifungal regimens. Drug-drug interaction and hepatorenal toxicity induced by drugs are also challenges facing clinicians. In this article, the characteristics of drug-drug interaction and hepatorenal toxicity among triazole, echinocandin and polyene antifungal drugs and immunosuppressants were reviewed, and postoperative preventive strategies for IFD in different types of SOT recipients and treatment strategies for IFD caused by infection of different pathogens were summarized, aiming to provide reference for physicians in organ transplantation and related disciplines.

Neumonía por Pneumocystis jirovecii asociada a hemorragia alveolar difusa en un paciente con trasplante renal

La neumonía por Pneumocystis jirovecii es una enfermedad fúngica oportunista descrita principalmente en pacientes con VIH, sin embargo, tras la introducción de la TARV, ha incrementado su incidencia en pacientes con inmunosupresión no asociada a VIH, como neoplasias hematológicas y trasplantes de órganos sólidos. Presentamos el caso de un varón de 17 años, receptor de un trasplante renal, con inmunosupresión prolongada con corticoesteroides, con cuadro clínico de tos, disnea y fiebre. La TC mostró micronódulos pulmonares centrolobulillares y vidrio esmerilado. El LBA fue compatible con hemorragia alveolar difusa (HAD), con RPC positiva para P. jirovecii. Se descartaron otras infecciones y enfermedades autoinmunes. Recibió tratamiento con cotrimoxazol con buena evolución clínica y mejoría radiológica. Si bien las causas más frecuentes de HAD son etiologías autoinmunes como enfermedades reumatológicas o vasculitis, es prioritario descartar causas infecciosas, incluyendo P. jirovecii, ya que el tratamiento dirigido puede tener un impacto significativo en la mortalidad en este grupo de pacientes.

Pneumocystis jirovecii pneumonia is an opportunistic fungal infection, described mainly in HIV patients, however, after the introduction of ART, its presentation has increased in patients with non-HIV immunosuppression, such as hematological cancers, solid or hematopoietic stem cell transplantation. We report the case of a 17-year-old male, kidney transplant patient, with prolonged immunosuppression with corticoesteroids, with history of cough, dyspnea, and fever. Chest CT evidences centrilobular pulmonary micronodules with ground glass. BAL was performed compatible with diffuse alveolar hemorrhage, with positive PCR for P. jirovecii. Other infections and autoimmune disease were ruled out. He received treatment with cotrimoxazole with clinical improvement of the patient, and follow up chest CT at the end of treatment showed decrease of pulmonary infiltrates. Although the most frequent causes of DAH are autoimmune etiologies such as rheumatic diseases or vasculitis, it is a priority to rule out infectious causes, including P. jirovecii, since targeted treatment could have a significant impact on mortality outcomes in this group of patients.

The conventional diagnosis challenge: Real-time PCR and nested PCR correlation with the scoring system for individuals at high-risk of Pneumocystis jirovecii pneumonia

Introduction. Pneumocystis jirovecii is an opportunistic fungus that affects mainly people living with HIV (CD4 cell count lower than 200 cells/ml) and other immunosuppressed patients. Since P. jirovecii does not grow on routine mycological media, diagnosis of P. jirovecii pneumonia relies on indirect evidence of its presence in respiratory samples. Objectives. To associate the results of direct immunofluorescence and two molecular methods with a score to predict P. jirovecii pneumonia in patients with AIDS. Materials and methods. A prospective study was conducted with 40 patients. A respiratory sample collected before treatment was subjected to direct immunofluorescence using the Merifluor kit, to nested PCR targeting the mitochondrial large subunit ribosomal RNA, and to the VIASURE real-time PCR kit. Results. These three techniques revealed P. jirovecii in 6, 12, and 15 samples, respectively. All positive samples by direct immunofluorescence were positive by nested PCR, and all positive samples by nested PCR amplified by real-time PCR. There was a statistically significant association between the P. jirovecii pneumonia score and the molecular methods. Two patients were early diagnosed and responded well to treatment. Conclusion. Molecular methods, especially real-time PCR, are recommended for early diagnosis of P. jirovecii pneumonia in AIDS patients.

Introducción. Pneumocystis jirovecii es un hongo oportunista que afecta principalmente a personas con HIV (recuento de CD4 menor de 200 células/ml) y a otros pacientes inmunosuprimidos. Como P. jirovecii no crece en los medios micológicos de rutina, el diagnóstico de neumonía por P. jirovecii se basa en la evidencia presente en muestras respiratorias. Objetivos. Asociar los resultados de la inmunofluorescencia directa y los de dos métodos moleculares con un puntaje para predecir la neumonía causada por P. jirovecii en pacientes con sida. Materiales y métodos. Se realizó un estudio prospectivo de 40 pacientes. Se recolectó una muestra respiratoria antes del inicio de tratamiento y se sometió a una prueba de inmunofluorescencia directa con el kit Merifluor, una PCR anidada para la amplificación de la subunidad larga del ribosoma mitocondrial y una PCR en tiempo real usando el kit VIASURE. Resultados. Estas tres técnicas evidenciaron la presencia de P. jirovecii en 6, 12 y 15 muestras, respectivamente. Todas las muestras positivas por inmunofluorescencia directa fueron positivas en la PCR anidada y todas las muestras positivas en la PCR anidada amplificaron por PCR en tiempo real. Se encontró una asociación estadística entre los valores de la neumonía causada por P. jirovecii y los métodos moleculares. Dos pacientes con diagnóstico temprano respondieron satisfactoriamente al tratamiento. Conclusión. Se recomiendan los métodos moleculares, especialmente la PCR en tiempo real, para el diagnóstico temprano de neumonía causada por P. jirovecii en pacientes con sida.

Application of prone position in severe ARDS caused by pneumocystis jirovecii pneumonia after kidney transplantation / 器官移植

Objective To investigate the improvement of oxygenation after the treatment of prone position in patients with severe acute respiratory distress syndrome (ARDS) caused by pneumocystis jirovecii pneumonia (PJP) after kidney transplantation. Methods Clinical data of 5 cases of moderate and severe ARDS caused by PJP after kidney transplantation were analyzed retrospectively, and clinical characteristics, treatment regimen and prognosis were summarized. Results Clinical manifestations of 5 patients were fever, dry cough, chest tightness, shortness ofbreath,sweating and fatigue, and body temperature fluctuated between 38 ℃ and 39 ℃, percutaneous arterial oxygen saturation(SpO2) was gradually decreased, and respiratory distress symptoms were worsened. Pulmonary CT scan showed diffuse ground-glass shadow. After transfer to intensive care unit (ICU), immunosuppressive drugs were terminated, and all patients were given with compound sulfamethoxazole, caspofungin, low-dose glucocorticoids against pneumocystis jirovecii (PJ), oxygen therapy and other symptomatic supportive treatments. Four patients diagnosed with severe ARDS upon admission to ICU were treated in a prone position. One patient with moderate ARDS was not kept in a prone position. At 1 d after treatment in a prone position, partial pressure of arterial oxygen (PaO2) and oxygenation index were increased, whereas alveolar-arterial oxygen difference (A-aDO2) was decreased compared with before treatment (allP<0.05). Compared with 1 d after treatment, SpO2, PaO2 and oxygenation index were all increased, while A-aDO2 was decreased at 4 d after treatment (all P<0.05). Box diagram showed that oxygenation index showed an overall upward trend after prone-position treatment, whereas A-aDO2 showed an overall downward trend. The length of ICU stay of 5 patients was 14 (8, 29) d. All patients in a prone position did not develop complications, such as skin pressure sore, tube detachment and tube displacement, etc. Among 5 patients, 4 patients were mitigated, and 1 patient died of septic shock and multiple organ failure. Conclusions For both conscious and intubated patients, a prone position may significantly improve oxygenation and prognosis of patients with severe ARDS caused by PJP after kidney transplantation. Early diagnosis and accurate and standardized treatment play a pivotal role in enhancing cure rate.

The diagnostic value of metagenomic next-generation sequencing in AIDS patients complicated with Pneumocystis jirovecii infection / 中华检验医学杂志

Objective:To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) in AIDS patients complicated with Pneumocystis jirovecii ( P. jirovecii) infection. Methods:This is a retrospective study. From January 2019 to June 2021, the respiratory tract and other body fluid samples of 236 cases of AIDS co-infected patients diagnosed in the AIDS Department of Changsha First Hospital were collected, along with corresponding medical histories. Traditional etiological hexamine silver staining and serum 1,3-β-D glucan (BDG) were performed simultaneously with mNGS detection, and Fisher′s exact test was used to analyze the results and compare the diagnostic performances of mNGS with those of hexamine silver staining and serum G test.Results:A total of 236 cases of AIDS patients with pulmonary infection were collected and tested. Seventy-seven cases were clinically diagnosed with Pneumocystis jiroveci pneumonia and 159 cases with non- Pneumocystis jiroveci pneumonia. Among the 236 AIDS patients with pulmonary infection, mNGS detected 77 [32.63%(77/236)] positive cases of Pneumocystis jiroveci, while hexamine silver staining detected 10[4.24%(10/236)] and serum BDG detected 146 [61.86% (146/236). Based on these clinical diagnostic results, the sensitivity of mNGS detection was 100% (77/77) for the 77 patients with Pneumocystis pneumoniae, significantly higher than that of silver hexamine staining [12.99% (10/77), P=0.046] and serum BDG [58.44% (45/77), P=0.038]. The mNGS showed good specificity, which was the same as that of hexamine silver staining [100% (159/159)] and significantly higher than that of serum BDG [36.48% (58/159), P=0.026]. With therapeutic clinical diagnosis as the reference method, the accuracy of mNGS detection was 100% (236/236). Conclusions:This study evaluated the diagnostic value of mNGS detection in AIDS patients with Pneumocystis jirovecii infection. The results showed that the sensitivity and specificity of mNGS detection were high, and it had exceptional clinical application value in the pathogenic detection of infectious diseases.

Efficacy and safety of trimethoprim/sulfamethoxazole combined with caspofungin for the treatment of acquired immunodeficiency syndrome patients with moderate to severe pneumocystis pneumonia / 中华传染病杂志

Objective:To assess the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMZ) combined with caspofungin for the treatment of acquired immunodeficiency syndrome (AIDS)patients with moderate to severe pneumocystis pneumonia (PCP) requiring mechanical ventilation.Methods:The clinical data of AIDS patients who admitted to Chongqing Public Health Medical Center from March 1, 2019 to March 1, 2021 with moderate to severe PCP requiring mechanical ventilation were retrospectively analyzed. Clinical characteristics and outcomes were compared between two groups receiving either combination therapy with TMP/SMZ and caspofungin (combination therapy group) or TMP/SMZ monotherapy (monotherapy group). The patients were divided into two subgroups according to the baseline arterial partial pressure of oxygen (PaO 2), patients with arterial PaO 2≥50 mmHg (1 mmHg=0.133 kPa) and PaO 2 <50 mmHg. The clinical efficacies of combination therapy and monotherapy in each subgroup were further compared. Chi-square and Fisher exact test were used for statistical analysis. The three-month survival was estimated by the Kaplan-Meier method, and the three-month survival rates were compared by Log-rank method. Results:A total of 83 patients were enrolled, including 23 in the monotherapy group and 60 in the combination therapy group. There was no significant difference in all-cause hospital mortalities between these two groups (34.8%(8/23) vs 23.3%(14/60), χ2=1.12, P=0.290). Kaplan-Meier survival curves indicated no significant difference in the three-month survival rates between the two groups ( χ2=0.51, P=0.477). There ware no significant differences observed in the positive clinical response rates and the mechanical ventilation rates after seven days of anti-PCP treatment between the two groups ( χ2=0.02 and 0.01, respectively, both P>0.05). In the 52 patients with PaO 2≥50 mmHg, no significant difference in all-cause hospital mortalities was observed between the monotherapy group and the combination therapy group (2/13 vs 25.6%(10/39), χ2=0.14, P=0.704). There was no statistical significance in the three-month survival rates between the two groups ( χ2=0.69, P=0.407). No significant difference was observed either in the clinical positive response rates or the mechanical ventilation rates after seven days of anti-PCP treatment between the two group( χ2=1.02 and 0.69, respectively, both P>0.05). In the 31 patients with PaO 2<50 mmHg, the all-cause hospital mortality in the combination therapy group was 19.0%(4/21), while six of the 10 patients in the monotherapy group died, and the difference was statistically significant (Fisher exact test, P=0.040). The three-month survival rate in the combination therapy group was significantly higher than that in the monotherapy group ( χ2=4.09, P=0.043). There were no significant differences in clinical positive response rate and the mechanical ventilation rate after seven days of anti-PCP treatment between the two group (Fisher exact test, both P>0.05). The overall adverse event rate in the monotherapy group was 87.0%(20/23), with an incidence of 56.5%(13/23) for both electrolyte disturbances and bone marrow suppression. The above incidences in the combination therapy group were 78.3%(47/60), 35.0%(21/60) and 53.3%(32/60), respectively, and all differences were not statistically significant ( χ2=0.34, 3.18 and 0.07, respectively, all P>0.05). Conclusions:The efficacy of combination therapy with TMP/SMZ and caspofungin is comparable to that of TMP/SMZ monotherapy in AIDS patients with moderate to severe PCP requiring mechanical ventilation. However, in AIDS patients with PCP requiring mechanical ventilation with the baseline PaO 2<50 mmHg, the efficacy of combination therapy is statistically superior to that of TMP/SMZ monotherapy. Combination therapy does not increase the risk of adverse events.

Clinical analysis of 5 children with lymphoma complicated with Pneumocystis jirovecii pneumonia / 白血病·淋巴瘤

Objective:To explore the clinical features of childhood lymphoma complicated with Pneumocystis jirovecii pneumonia (PJP).Methods:The clinical data, diagnosis and treatment of 5 children with lymphoma complicated with PJP admitted to Beijing Children's Hospital from January 2013 to April 2022 were retrospectively analyzed.Results:Among 5 patients, there were 3 males and 2 females, the median onset age was 7 years old; 4 cases were non-Hodgkin lymphoma and 1 case was Hodgkin lymphoma. Fever and cough occurred 5-18 months after chemotherapy; typical mosaic sign could be seen in 2 cases without pneumothorax and pleural effusion as well as other pathogenic infection; all 5 cases had hypoxemia; 4 cases were diagnosed by next-generation sequencing (NGS). The CD4/CD8 ratio decreased in all cases, and the median CD4 positive T-cell was 200/μl. Trimethoprim-sulfamethoxazole (TMP-SMZ) was irregularly used in 3 cases. During the treatment, all cases received mechanical ventilation, TMP-SMZ intravenously dripping combined with caspofungin, glucocorticoid and gamma globulin. All 5 cases of PJP were cured and there was no recurrent infection.Conclusions:Lymphoma children are susceptible to PJP due to immunocompromise caused by chemotherapy, and their condition progresses rapidly. When encountering fever, shortness of breath, severe lung symptoms and mild signs of children, it is necessary to improve the vigilance of PJP. NGS can help diagnosis, and TMP-SMZ should be actively treated and prevented. Early diagnosis and active treatment can achieve a good prognosis.

Clinical characteristics and CT findings of Pneumocystis Jirovecii pneumonia in 46 cases with hematological diseases / 中华血液学杂志

Objective: To summarize the original CT features of Pneumocystis Jirovecii pneumonia in patients with hematological diseases. Methods: A retrospective analysis was carried out in 46 patients with proven pneumocystis pneumonia (PJP) in the Hospital of Hematology, Chinese Academy of Medical Sciences between January 2014 and December 2021. All patients had multiple chests CT and related laboratory examinations, imaging typing were conducted based on the initial CT presentation, and the distinct imaging types were analyzed against the clinical data. Results: In the analysis, there were 46 patients with proven pathogenesis, 33 males, and 13 females, with a median age of 37.5 (2-65) years. The diagnosis was validated by bronchoalveolar lavage fluid (BALF) hexamine silver staining in 11 patients and clinically diagnosed in 35 cases. Of the 35 clinically diagnosed patients, 16 were diagnosed by alveolar lavage fluid macrogenomic sequencing (BALF-mNGS) and 19 by peripheral blood macrogenomic sequencing (PB-mNGS) . The initial chest CT presentation was categorized into 4 types, including ground glass (GGO) type in 25 cases (56.5%) , nodular type in 10 cases (21.7%) , fibrosis type in 4 cases (8.7%) , and mixed type in 5 cases (13.0%) . There was no substantial discrepancy in CT types among confirmed patients, BALF-mNGS diagnosed patients and PB-mNGS diagnosed patients (χ(2)=11.039, P=0.087) . The CT manifestations of confirmed patients and PB-mNGS diagnosed patients were primarily GGO type (67.6%, 73.7%) , while that of BALF-mNGS diagnosed patients were nodular type (37.5%) . Of the 46 patients, 63.0% (29/46) had lymphocytopenia in the peripheral blood, 25.6% (10/39) with positive serum G test, and 77.1% (27/35) with elevated serum lactate dehydrogenase (LDH) . There were no great discrepancies in the rates of lymphopenia in peripheral blood, positive G-test, and increased LDH among different CT types (all P>0.05) . Conclusion: The initial chest CT findings of PJP in patients with hematological diseases were relatively prevalent with multiple GGO in both lungs. Nodular and fibrosis types were also the initial imaging findings for PJP.

Diagnosis of Pneumocystis jirovecii pneumonia by cytological examination of bronchoalveolar lavage fluid combined with metagenomic next-generation sequencing / 中国热带医学

@#Abstract：Objective To investigate the morphological features of the Pneumocystis jirovecii, in order to facilitate early detection and rapid diagnosis of this rare pathogen from a morphology point of view by laboratory technicians. By analyzing the laboratory features and application value of different pathogen detection methods in the diagnosis of Pneumocystis jirovecii pneumonia, we aim to provide the most reliable diagnostic basis for rapid diagnosis of Pneumocystis jirovecii pneumonia.Methods A retrospective analysis was conducted on the test results of bronchoalveolar lavage fluid samples from a comprehensive hospital in Zhangqiu District, Jinan City, Shandong Province, and a hospital in Changde City from April 2022 to October 2022. Five confirmed cases of Pneumocystis jirovecii pneumonia were detected. Its clinical manifestations, laboratory results, and morphological characteristics of pathogens under different stains were analyzed to discuss the advantages and disadvantages of different detection methods. Results Cytological examination of bronchoalveolar lavage fluid found the trophozoites and cysts of Pneumocystis jirovecii by Wright's-Giemsa staining in 4 cases (80%), and the cysts of Pneumocystis jirovecii by Silver hexamine staining in 4 cases (80%), while the metagenomic next-generation sequencing confirmed all the 5 positive results. All 5 patients had different degrees of reduction in the absolute count of peripheral blood lymphocytes, and the serum lactic dehydrogenase and (1-3)-β-D-Glucan were increased. Among the 5 patients in this study, 4 were treated with sulfamethoxazole combined with caspofungin, and 1 was treated with sulfamethoxazole. Three patients were cured and discharged from hospital after treatment, but two died. Conclusions The method of Wright's-Giemsa staining for the cytological examination of bronchoalveolar lavage fluid to find Pneumocystis jirovecii has the unique and irreplaceable advantages as silver staining. Metagenomic next-generation sequencing can further increase the positive detection rate of Pneumocystis jirovecii. The combination of cytological examination of bronchoalveolar lavage fluid with metagenomic nextgeneration sequencing is a powerful diagnostic method for rapid diagnosis of Pneumocystis jirovecii pneumonia, which can diagnose accurately and reduce missed diagnosis.

Progress of researches on developmental processes and reproduction mode of Pneumocystis / 中国血吸虫病防治杂志

Pneumocystis, an important opportunistic fungal pathogen that parasitizes in multiple mammalian lungs, may cause life-threatening Pneumocystis pneumonia (PCP) and even death among immunocompromised individuals. With the rapid development of high-throughput sequencing and multi-omics technologies, systematic comparative analyses of genome, transcriptome, and whole-genome sequencing results demonstrate that Pneumocystis is a type of obligate biotrophic fungi, and requires obtaining nutrition from hosts. In addition, sexual reproduction is an essential process for Pneumocystis survival, production and transmission, and asexual reproduction facilitates Pneumocystis survival, which provides new insights into understanding of the whole developmental process of Pneumocystis in the host lung and inter-host transmission of Pneumocystis. This review summarizes the advances in the reproduction mode of Pneumocystis and underlying mechanisms, which provides insights into prevention and treatment of PCP, notably for the prophylaxis against nosocomial transmission of PCP.

Clinical and epidemiological features analysis of pneumocystis jirovecii pneumonia in kidney transplant recipients / 器官移植

Objective To investigate clinical and epidemiological features of pneumocystis jirovecii pneumonia (PJP) in kidney transplant recipients. Methods Clinical data of 68 kidney transplant recipients admitted from July, 2021 to December, 2021 were collected. All patients were divided into the PJP group (n=11), common pulmonary infection group (n=24) and non-pneumonia group (n=33) according to the status of pulmonary infection. The incidence and treatment of PJP after kidney transplantation were analyzed. Basic characteristics and laboratory parameters of the recipients were compared among all groups. The genotyping and transmission map of PJP patients were evaluated. Results Among 64 kidney transplant recipients, 11 cases were definitely diagnosed with PJP. The most common clinical manifestations included elevated body temperature, and dry cough complicated with progressive dyspnea. Chest CT scan showed diffuse interstitial inflammation and ground glass-like lesions of bilateral lungs in all patients. After diagnosis, all patients were orally given with compound sulfamethoxazole for 3-4 weeks. Two patients received non-invasive ventilator-assisted ventilation due to severe lung infection and dyspnea, and the remaining patients were given with nasal cannula oxygenation. One patient experienced elevated serum creatinine level upon discharge, and developed renal allograft failure. The remaining 10 recipients with PJP obtained normal renal allograft function, and no recipient died. Compared with the non-pneumonia group, the rejection rate was higher, the length of hospital stay was longer, the lymphocyte count was less, the lymphocyte proportion was lower, the levels of C-reactive protein, serum creatinine and lactate dehydrogenase were higher, and the levels of serum albumin was lower and CD4+T cell count was less in the PJP group (all P < 0.05). Compared with common pulmonary infection group, the lymphocyte count was less, the lymphocyte proportion was lower, the CD4+T cell count was less and 1, 3-β-D- glucan (BDG) level was higher in the PJP group (all P < 0.05). No new genotype was detected in 10 of the 12 testing samples. It was considered that PJP mainly depended on two transmission chains and two independent transmission individuals. Conclusions Kidney transplant recipients are prone to pneumocystis jirovecii (PJ) infection due to impaired cellular immune function. The most common clinical manifestations consist of elevated body temperature and dry cough complicated with progressive dyspnea, accompanied by headache and fatigue in partial patients. Chest CT scan shows diffuse interstitial inflammation and ground glass-like lesion of bilateral lungs. PJ may be transmitted through respiratory tract. Small-scale PJP might occur in the follow-up outpatient of kidney transplant recipients. Preventive measures should be delivered in a timely manner.

PNEUMOCYSTIS JIROVECII AND CRYPTOCOCCUS NEOFORMANS CO- INFECTION IN AN HIV-INFECTED PATIENT : A CASE REPORT

Opportunistic fungal infections have a high morality rate, occurring most often in immunocompromised subjects. We report the case of a 19-year-old girl who presented with progressively worsening dyspnea, hypoxemia requiring oxygen supplementation with bilateral pulmonary cystic lesions, treated with antibiotics for a presumptive diagnosis of pneumonia. The patient did not improve clinically. A diagnostic bronchoscopy was performed, which revealed ?ndings consistent with pulmonary pneumocystis. The patient tested positive for HIV, and had a positive cryptococcal antigenemia. She was put on treatment adapted to each fungal infection with a favorable evolution.

Neumonía por Pneumocystis jirovecii posterior a COVID-19 en un paciente sin infección por VIH / Pneumonia by Pneumocystis jirovecii after COVID-19 in non-HIV patient

Resumen La neumonía oportunista por Pneumocystis jirovecii en pacientes con una infección respiratoria grave por SARS-CoV-2 es una entidad recién reconocida, asociada a la terapia con corticoesteroides junto a otros factores de riesgo predisponentes. Supone un reto diagnóstico y, tras el tratamiento, el pronóstico es favorable. Presentamos el caso de un varón con neumonía grave por SARS-CoV-2 que recibió tratamiento corticoidal, desarrollando posteriormente una neumonía por P. jirovecii.

Abstract Infection by Pneumocystis jirovecii in patients with severe respiratory infection caused by SARS-CoV-2 is a situation that we must take into account today. Corticotherapy along with other risk factors predisposes to it. It is a diagnostic challenge and, after treatment, the prognosis is favorable. We report the case of a male with severe pneumonia due to SARS-CoV-2 who received corticosteroid treatment, later developing pneumonia due to P. jiroveci.

Clinical features of Pneumocystis jirovecii pneumonia / 中华检验医学杂志

Objective:The clinical features, laboratory indices, and imaging data of patients with Pneumocystis jirovecii pneumonia (PJP) were described and analyzed, aiming to provide helpful information for the diagnosis and treatment of PJP. Methods:A retrospective study were conducted with data from 154 PJP patients who visited China-Japan Friendship Hospital from May 2017 to August 2020. Their clinical characteristics, laboratory and imaging data, and clinical outcomes were collected for analysis. The patients were further divided into the death group (51 cases) and the survival group(103 cases). The differences between the groups were compared by using t-test, nonparametric test, and chi-square test. Results:Of the 154 PJP patients, there were 89 males and 65 females, with a mean age of (53.7±14.8) years. Among them, 85.7% (132/154) were on immunosuppressive/glucocorticoids agents within the past month. Besides, 27.9% (43/154) and 33.1% (51/154) had kidney diseases and connective tissue diseases, respectively. The major clinical manifestations in these patients involved fever 82.9% (126/154), cough 59.7% (92/154), and dyspnea 52.6% (81/154). For the laboratory data, the lactate dehydrogenase (LDH) was 561.0 (434.3, 749.0) IU/L and the value increased in 91.3% (95/104) of the patients. The CD4+T-cell lymphocytes in 88.0% (95/108) and 57.4% (62/108) of patients were lower than 400/μl and 200/μl, respectively. Furthermore, (1, 3)-β-D glucan (BG) increased in 74.4% (67/90) of PJP patients (≥100.0 ng/L). For the imaging results, chest computed tomography (CT) showed diffuse ground-glass shadows/grid shadows in 90% (117/130) patients. Compared with the survival group, higher LDH [690.5 (528.8, 932.3) IU/L vs 502.5 (381.8, 657.0) IU/L, Z=-3.375, P=0.001], white blood cell count (WBC) [9.8 (5.8, 12.6) ×10 9/L vs 7.3 (5.0, 10.1) ×10 9/L, Z=-2.392, P=0.017], and age [(69.8±14.5) years vs (50.6±14.0) years, t=-3.756, P=0.001] were found in the death group. Lower lymphocyte ratio [5.3 (3.2, 9.3) % vs 9.6 (5.6, 17.2) %, Z=?3.262, P=0.001] and oxygen partial pressure (PaO 2) levels [(73.2±20.5) mmHg vs (64.8±17.7) mmHg (1 mmHg=0.133 kPa), t=2.345, P=0.021] were also observed in the death group. Furthermore, in the death group, the bacterial and fungal infection rate was higher than the rates in the survival group [55.1% (27/51) vs 21.5% (22/103), χ 2=15.372, P=0.001]. Conclusions:Long-term use of immunosuppressive agents or glucocorticoids predispose to PJP. CD4+T-lymphocytes, LDH, and BG might be used as important auxiliary examinations for PJP patients. Age, LDH, WBC, lymphocyte ratio, PaO 2 and possible combinations with bacterial or fungal infections are more closely related to the prognostic of PJP patients.

Rapid detection of pneumocystis carinii infection in immunocompromised patients by loop mediated isothermal amplification technique / 中国小儿急救医学

Objective:To explore the value of detecting pneumocystis carini(PC)rapidly in immunocompromised patients by loop mediated isothermal amplification(LAMP).Methods:Respiratory tract specimens of immunocompromised children suspected of pneumocystis carinii pneumonia(PCP) at Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiao Tong University were collected from May 2020 to May 2021.PCR and LAMP methods were used to detect PC.Firstly, LAMP primers of PC were synthetized according to the conserved region of PC gene, and the LAMP reaction system and reaction conditions were optimized to evaluate the sensitivity and specificity.Then, the results of pathogens were compared with those of PCR detection.Results:The established LAMP detection technology for PC had high specificity and super sensitivity.The detection results could be obtained within 1 hour.In 12 clinical samples, 10 cases were positive and 2 cases were negative, the coincidence rate of LAMP and PCR technique was 100%.Conclusion:LAMP can detect PC more rapidly and sensitively than PCR, and it can provide a good support for clinical rapid diagnosis of PCP.

Clinical characteristics and prognosis of severe pneumocystis carinii pneumonia in pediatric liver transplant recipients / 中国小儿急救医学

Objective:To analyze the clinical characteristics and risk factors for mortality of severe pneumocystis carinii pneumonia(PCP)in pediatric liver transplant(LT)recipients.Methods:The data of severe PCP in LT recipients diagnosed at Shanghai Children′s Medical Center from November 2019 to February 2021 were collected.The clinical characteristics and risk factors for 28-day mortality were analyzed.Results:Fifteen patients were enrolled in the study.Thirteen cases survived and 2 cases were non-survived.There was no routine anti-pneumocystis prophylaxis after LT.The median age of onset of PCP was 12(7, 26)months.The median time after LT was 3.00(0.33, 4.00)months.The onset clustered in November-December and June-August.All patients were mechanically ventilated, and some patients were given prone ventilation(11 cases), neuromuscular blocking agents(13 cases)and high concentration oxygen(more than 60%, nine cases). Fourteen cases were complicated with other infections.Two cases were complicated with pneumothorax and subcutaneous/mediastinal emphysema.There were 2 cases with septic shock-like manifestation, 1 case of right heart insufficiency, 1 case of right heart failure(death), and 1 case of multiple organ failure(death). Compared with the survived group, the non-survived group had higher pediatric risk of mortality Ⅲ score[3.5(0.0, 6.0)vs.8.5(5.0, 12.0), Z=1.993, P=0.046] and lactate dehydrogenase level[1 731.5(1 012.0, 3 270.0)U/L vs.4 387.5(3 606.0, 5 169.0)U/L, Z=2.148, P=0.032]. Conclusion:PCP in pediatric LT is critical and complicated.Pediatric risk of mortality Ⅲ scores and lactate dehydrogenase increase in 28-day hospitalized deaths.

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.

Rapid detection of pneumocystis carinii infection in immunocompromised patients by loop mediated isothermal amplification technique / 中国小儿急救医学

Objective:To explore the value of detecting pneumocystis carini(PC)rapidly in immunocompromised patients by loop mediated isothermal amplification(LAMP).Methods:Respiratory tract specimens of immunocompromised children suspected of pneumocystis carinii pneumonia(PCP) at Shanghai Children′s Medical Center, School of Medicine, Shanghai Jiao Tong University were collected from May 2020 to May 2021.PCR and LAMP methods were used to detect PC.Firstly, LAMP primers of PC were synthetized according to the conserved region of PC gene, and the LAMP reaction system and reaction conditions were optimized to evaluate the sensitivity and specificity.Then, the results of pathogens were compared with those of PCR detection.Results:The established LAMP detection technology for PC had high specificity and super sensitivity.The detection results could be obtained within 1 hour.In 12 clinical samples, 10 cases were positive and 2 cases were negative, the coincidence rate of LAMP and PCR technique was 100%.Conclusion:LAMP can detect PC more rapidly and sensitively than PCR, and it can provide a good support for clinical rapid diagnosis of PCP.

Clinical characteristics and prognosis of severe pneumocystis carinii pneumonia in pediatric liver transplant recipients / 中国小儿急救医学

Objective:To analyze the clinical characteristics and risk factors for mortality of severe pneumocystis carinii pneumonia(PCP)in pediatric liver transplant(LT)recipients.Methods:The data of severe PCP in LT recipients diagnosed at Shanghai Children′s Medical Center from November 2019 to February 2021 were collected.The clinical characteristics and risk factors for 28-day mortality were analyzed.Results:Fifteen patients were enrolled in the study.Thirteen cases survived and 2 cases were non-survived.There was no routine anti-pneumocystis prophylaxis after LT.The median age of onset of PCP was 12(7, 26)months.The median time after LT was 3.00(0.33, 4.00)months.The onset clustered in November-December and June-August.All patients were mechanically ventilated, and some patients were given prone ventilation(11 cases), neuromuscular blocking agents(13 cases)and high concentration oxygen(more than 60%, nine cases). Fourteen cases were complicated with other infections.Two cases were complicated with pneumothorax and subcutaneous/mediastinal emphysema.There were 2 cases with septic shock-like manifestation, 1 case of right heart insufficiency, 1 case of right heart failure(death), and 1 case of multiple organ failure(death). Compared with the survived group, the non-survived group had higher pediatric risk of mortality Ⅲ score[3.5(0.0, 6.0)vs.8.5(5.0, 12.0), Z=1.993, P=0.046] and lactate dehydrogenase level[1 731.5(1 012.0, 3 270.0)U/L vs.4 387.5(3 606.0, 5 169.0)U/L, Z=2.148, P=0.032]. Conclusion:PCP in pediatric LT is critical and complicated.Pediatric risk of mortality Ⅲ scores and lactate dehydrogenase increase in 28-day hospitalized deaths.

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.