Features and global impact of invasive fungal infections caused by Pneumocystis jirovecii: A systematic review to inform the World Health Organization fungal priority pathogens list.

This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%. Risk factors for disease principally include immunosuppression from HIV, but other types of immunosuppression are increasingly recognised, including solid organ and haematopoietic stem cell transplantation, autoimmune and inflammatory disease, and chemotherapy for cancer. Although prophylaxis is available and generally effective, burdensome side effects may lead to discontinuation. After a period of decline associated with improvement in access to HIV treatment, new risk groups of immunosuppressed patients with PJP are increasingly identified, including solid organ transplant patients.

A combined immune and inflammatory indicator predict the prognosis of severe Pneumocystis jirovecii pneumonia patients: a 12-year, retrospective, observational cohort.

Persistent inflammatory damage and suppressed immune function play a crucial role in the pathogenesis and progression of the pneumocystis jirovecii pneumonia (PjP). Therefore, we aimed to investigate the correlation between the combined immune and inflammatory indicator: the neutrophil-to-lymphocyte ratio (NLR) and prognosis of non-human immunodeficiency virus (non-HIV) PjP.In the retrospective analysis conducted in ICUs at Beijing Chao-Yang Hospital, we examined data from 157 patients diagnosed with non-HIV PjP. Our findings reveal a concerning hospital mortality rate of 43.3%, with the 28-day mortality rate reaching 47.8%.Through multivariable logistic and Cox regression analyses, we established a significant association between elevated NLR levels and hospital mortality (adjusted odd ratio, 1.025; 95% CI, 1.008-1.043; p = 0.004) or 28-day mortality (adjusted hazard ratio, 1.026; 95% CI, 1.008-1.045; p = 0.005). Specifically, patients with an NLR exceeding 20.3 demonstrated markedly lower overall survival rates, underscoring the biomarker's predictive value for both hospital and 28-day mortality.In conclusion, non-HIV PjP patients in the ICU still have a high rate of mortality and a poor short-term prognosis after discharge. A high level of NLR was associated with an increased risk of hospital mortality and 28-day mortality.

Prone positioning does not improve outcomes of intubated patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome: a single-center, retrospective, observational, cohort study.

BACKGROUND: Pneumocystis pneumonia is an uncommon precipitant of acute respiratory distress syndrome and is associated with high mortality. Prone positioning ventilation has been proven to reduce mortality in patients with moderate-severe acute respiratory distress syndrome. We investigated the effect of prone positioning on oxygenation and mortality in intubated patients with pneumocystis pneumonia comorbid with moderate-severe acute respiratory distress syndrome. METHODS: In this single-center, retrospective, observational, cohort study, eligible patients were enrolled at West China Hospital of Sichuan University from January 1, 2017, to December 31, 2021. Data on demographics, clinical features, ventilation parameters, arterial blood gas, and outcomes were collected. Patients were assigned to the prone cohort or supine cohort according to whether they received prone positioning ventilation. The main outcome was 28-day mortality. FINDINGS: A total of 79 patients were included in the study. Sixty-three patients were enrolled in the prone cohort, and 16 patients were enrolled in the supine cohort. The 28-day mortality was 61.9% in the prone cohort and 68.8% in the supine cohort (P = 0.26), and 90-day mortality was 66.7% in the prone cohort and 68.8% in the supine cohort (P = 0.55). Patients in the supine cohort had fewer invasive mechanical ventilation days and more ventilator-free days. The incidence of complications was higher in the prone cohort than in the supine cohort. CONCLUSIONS: In patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome, prone positioning did not decrease 28-day or 90-day mortality. Trial registration ClinicalTrials.gov number, ChiCTR2200063889. Registered on 20 September 2022, https://www.chictr.org.cn/showproj.html?proj=174886 .

Elevated serum lactate dehydrogenase aids prediction of mortality in Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection - Derivation of a clinical risk score.

Pneumocystis jirovecii pneumonia (PCP) is associated with significant mortality amongst patients without underlying human immunodeficiency virus infection (HIV). We sought to develop a risk score to predict mortality in this population. We reviewed patients with a presumed or confirmed PCP and a negative HIV test from 2006-2023. We constructed a multivariable model to identify parameters independently associated with mortality and the adjusted odds ratios were converted to weights to derive a risk score. Subsequently, we compared the performance of our score to the CURB-65 score by means of area under receiver operating characteristic curve (AUC). In total, we examined 93 patients with PCP without HIV. Mortality was 31.2%. Risk factors for mortality included older age, male sex and high serum lactate dehydrogenase levels (LDH) and C-reactive protein levels. A risk score was derived comprising age> 65 years (2 points), male sex (2 points) and LDH> 770 U/L (3 points). Our risk score (AUC 0.71, 95%CI 0.60-0.82) performed better than the CURB-65 score (AUC 0.53, 95%CI 0.41-0.66). A low-risk score of 0-1 had excellent negative predictive value for mortality (97.5%). In conclusion, a risk score comprising age, sex and LDH can predict mortality in PCP without underlying HIV and help with prognostication.

MiR-150 levels are related to in-hospital mortality in non-HIV Pneumocystis pneumonia patients.

Pneumocystis pneumonia (PCP) is a common opportunistic infection that occurs in immunocompromised patients. Compared with HIV patients, PCP in non-HIV patients tends to follow up a more urgent course and poorer prognosis. Therefore, markers that could predict survival of PCP patients in non-HIV population are of great value. MiRNA-150 has been widely studied in many diseases since it has been identified as a vital regulator of immune cell differentiation and activation. We thus conduct this study aiming to evaluate the prognostic value of miR-150 level in non-HIV PCP. First, the expression levels of miR-150 were compared between PCP patients and healthy volunteers. The miR-150 levels in immune cells were also detected in PCP mouse models. Then the prognostic value of miR-150 was further assessed in another PCP population (n = 72). The expression levels of miR-150 were measured by reverse transcription real-time PCR (RT-PCR) technique. Our data demonstrated significantly decreased miR-150 expression levels in PCP patients and mouse models compared to controls. The miR-150 levels also decreased in various immune cells of PCP mouse models. With a cut-off value of 3.48, the area under the curve, sensitivity, specificity of miR-150 to predicate PCP mortality were 0.845, 68.2% and 96.0%, respectively. In conclusion, miR-150 expression value might serve as a potential biomarker to identify PCP patients at high risk of death.

Pneumocystis pneumonia (PCP) remains a fatal risk for immunosuppressed patients. MiR-150 takes part in immune regulation, and thus is involved in infection control. Our study indicated that the miR-150 expression may act as a potential biomarker for predicting mortality of PCP patients.

Characteristics and Prognosis Factors of Pneumocystis jirovecii Pneumonia According to Underlying Disease: A Retrospective Multicenter Study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PcP) remains associated with high rates of mortality, and the impact of immunocompromising underlying disease on the clinical presentation, severity, and mortality of PcP has not been adequately evaluated. RESEARCH QUESTION: Does the underlying disease and immunosuppression causing PcP impact the outcome and clinical presentation of the disease? STUDY DESIGN AND METHODS: In this multicenter retrospective observational study, conducted from January 2011 to December 2021, all consecutive patients admitted with a proven or probable diagnosis of PcP according to the European Organisation for Research and Treatment of Cancer consensus definitions were included to assess the epidemiology and impact of underlying immunosuppressive diseases on overall and 90-day mortality. RESULTS: Overall, 481 patients were included in the study; 180 (37.4%) were defined as proven PcP and 301 (62.6%) were defined as probable PcP. Patients with immune-mediated inflammatory diseases (IMIDs) or solid tumors had a statistically poorer prognosis than other patients with PcP at day 90. In multivariate analysis, among the HIV-negative population, solid tumor underlying disease (OR, 5.47; 95% CI, 2.16-14.1; P < .001), IMIDs (OR, 2.19; 95% CI, 1.05-4.60; P = .037), long-term corticosteroid exposure (OR, 2.07; 95% CI, 1.03-4.31; P = .045), cysts in sputum/BAL smears (OR, 1.92; 95% CI, 1.02-3.62; P = .043), and SOFA score at admission (OR, 1.58; 95% CI, 1.39-1.82; P < .001) were independently associated with 90-day mortality. Prior corticotherapy was the only immunosuppressant associated with 90-day mortality (OR, 1.67; 95% CI, 1.03-2.71; P = .035), especially for a prednisone daily dose ≥ 10 mg (OR, 1.80; 95% CI, 1.14-2.85; P = .010). INTERPRETATION: Among patients who were HIV-negative, long-term corticosteroid prior to PcP diagnosis was independently associated with increased 90-day mortality, specifically in patients with IMIDs. These results highlight both the needs for PcP prophylaxis in patients with IMIDs and to early consider PcP curative treatment in severe pneumonia among patients with IMIDs.

Epidemiology, mortality and effectiveness of prophylaxis for Pneumocystis jiroveci pneumonia among rheumatic patients: a territory-wide study.

BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) is an opportunistic infection affecting immunocompromised individuals. However, evidence regarding the burden and effectiveness of prophylaxis among rheumatic patients remains limited. Delineating the epidemiology and efficacy of prophylaxis among rheumatic patients is urgently needed. METHODS: We performed a territory-wide cohort study of rheumatic patients in Hong Kong. All patients with a diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), immune-mediated myositis (IMM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or spondyloarthritis (SpA) between 2015 and 2019 were included. Prevalence, frequency of prophylaxis and mortality of PJP were calculated. Number needed to treat (NNT) analysis was also performed. RESULTS: Out of 21,587 patients (54% RA, 25% SLE, 13% SpA, 5% IMM, 2% AAV and 1% SSc), 1141 (5.3%) patients were prescribed PJP prophylaxis. 48/21,587 (0.2%) developed PJP. No patients who developed PJP received prophylaxis prior to infection. The incidence of PJP was highest among SSc, AAV, and IMM patients. Among these diseases, the majority of PJP occurred while patients were on glucocorticoids at daily prednisolone-equivalent doses of 15 mg/day (P15) or above. PJP prophylaxis was effective with NNT for SSc, AAV and IIM being 36, 48 and 114 respectively. There were 19 PJP-related mortalities and the mortality rate was 39.6%. CONCLUSION: PJP is an uncommon but important infection among rheumatic patients, PJP prophylaxis is effective and should be considered in patients with SSc, AAV and IMM, especially those receiving glucocorticoid doses above P15.

COVID-19-Associated Pulmonary Aspergillosis, Fungemia, and Pneumocystosis in the Intensive Care Unit: a Retrospective Multicenter Observational Cohort during the First French Pandemic Wave.

The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) (P < 10-4). For CAPA, the presence of several mycological criteria was associated with death (P < 10-4). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients (P = 0.001). Antimold treatment did not alter prognosis (P = 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses. IMPORTANCE To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.

Epidemiological and clinical characteristics of immunocompromised patients infected with Pneumocystis jirovecii in a twelve-year retrospective study from Norway.

BACKGROUND: Pneumocystis pneumonia (PCP) severely menaces modern chemotherapy and immunosuppression. Detailed description of the epidemiology of Pneumocystis jirovecii today is needed to identify candidates for PCP-prophylaxis. METHODS: We performed a 12-year retrospective study of patients with P. jirovecii detected by polymerase chain reaction in Central Norway. In total, 297 patients were included. Comprehensive biological, clinical and epidemiological data were abstracted from patients' medical records. Regional incidence rates and testing trends were also assessed. RESULTS: From 2007 to 2017 we found a 3.3-fold increase in testing for P. jirovecii accompanied by a 1.8-fold increase in positive results. Simultaneously, regional incidence rates doubled from 5.0 cases per 100,000 person years to 10.8. A majority of the study population had predisposing conditions other than human immunodeficiency virus (HIV). Hematological (36.0%) and solid cancers (25.3%) dominated. Preceding corticosteroids were a common denominator for 72.1%. Most patients (74.4%) presented with at least two cardinal symptoms; cough, dyspnea or fever. Main clinical findings were hypoxia, cytopenias and radiological features consistent with PCP. A total of 88 (29.6%) patients required intensive care and 121 (40.7%) suffered at least one complication. In-hospital mortality was 21.5%. Three patients (1.0%) had received prophylaxis. CONCLUSIONS: P. jirovecii is re-emerging; likely due to increasing immunosuppressants use. This opportunistic pathogen threatens the life of heterogenous non-HIV immunosuppressed populations currently at growth. Corticosteroids seem to be a major risk factor. A strategy to increase prophylaxis is called for.

Lymphocyte subset analysis to evaluate the prognosis of HIV-negative patients with pneumocystis pneumonia.

OBJECTIVES: We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. METHODS: We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. RESULTS: A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/µL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597-83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. CONCLUSION: The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.

Prognostic impact of early adjunctive corticosteroid therapy in non-HIV oncology or haematology patients with Pneumocystis jirovecii pneumonia: A propensity score analysis.

PURPOSE: While early adjunctive corticosteroid therapy (EACST) has been proven effective in HIV patients with Pneumocystis Jirovecii Pneumonia (PJP), data remains controversial concerning non-HIV oncology or haematology patients. METHODS: This retrospective study included cancer patients without HIV and with diagnosis of PJP admitted in a cancer referral centre, from January-1-2010 to March-31-2017. We compared 30-day and 1-year mortality rate, change in the respiratory item of the Sequential Organ Failure Assessment score(SOFA-resp worsening), use of tracheal intubation between day-1 and day-5 of anti-pneumocystis therapy and occurrence of coinfections between patients with EACST and those with no or late corticosteroid therapy, using an inverse probability weighting propensity score-based (IPW) analysis. RESULTS: 133 non-HIV oncology or haematology PJP patients were included (EACST n = 58, others n = 75). The main underlying conditions were haematological malignancies (n = 107, 80,5%), solid tumour (n = 27, 20,3%) and allogeneic stem cell transplantation (n = 17, 12,8%). Overall 30-day and 1-year mortality rate was 24,1% and 56,4%, respectively. IPW analysis found no difference on 30-day (HR = 1.45, 95% CI [0.7-3.04], p = 0.321) and 1-year (HR = 1.25, CI 95% [0.75-2.09], p = 0.39) mortality rate between groups. CONCLUSION: No difference in SOFA-resp worsening, tracheal intubation and coinfections was found between groups. Combination of EACST with anti-pneumocystis therapy in non-HIV onco-haematology PJP-patients was not associated with clinical improvement.

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.

UK paediatric oncology Pneumocystis jirovecii pneumonia surveillance study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a serious infective complication of immunosuppressive therapy. There are insufficient data concerning the incidence or mortality rate in children undergoing treatment for malignancies and how these may be influenced by prophylaxis. OBJECTIVE: Prospective collection of clinical information for all suspected and proven cases of PJP in children with cancer in the UK and Ireland. DESIGN: A surveillance survey was undertaken using a key contact at each paediatric oncology Principle Treatment Centre (PTC). MAIN OUTCOME MEASURES: To describe the mortality, outcomes and use of prophylaxis in this at-risk group. RESULTS: The study confirms that PJP is rare, with only 32 cases detected in the UK over a 2-year period reported from all 20 PTCs. No deaths were directly attributed to PJP, in contrast to previously reported high mortality rates. Breakthrough infection may occur despite prescription of ostensibly adequate prophylaxis with co-trimoxazole; 11 such cases were identified. Six infections occurred in patients for whom prophylaxis was not thought to be indicated. Two infections occurred in patients for whom prophylaxis was specifically omitted due to concerns about potential bone marrow suppression or delayed engraftment. CONCLUSION: PJP in children treated for malignant disease is rare. Breakthrough infection despite prophylaxis with co-trimoxazole may represent pathogen resistance or non-compliance. Further consideration of the use of PJP prophylaxis during acute myeloid leukaemia and non-Hodgkin's lymphoma treatment is warranted, alongside appraisal of the clinical implications of the possible marrow suppressive effects of co-trimoxazole and its interactions with methotrexate.

Risk factors associated with Pneumocystis jirovecii pneumonia in juvenile myositis in North America.

OBJECTIVES: Pneumocystis jirovecii pneumonia (PJP) is associated with significant morbidity and mortality in adult myositis patients; however, there are few studies examining PJP in juvenile myositis [juvenile idiopathic inflammatory myopathy (JIIM)]. The purpose of this study was to determine the risk factors and clinical phenotypes associated with PJP in JIIM. METHODS: An research electronic data capture (REDCap) questionnaire regarding myositis features, disease course, medications and PJP infection characteristics was completed by treating physicians for 13 JIIM patients who developed PJP (PJP+) from the USA and Canada. Myositis features and medications were compared with 147 JIIM patients without PJP (PJP-) from similar geographic regions who enrolled in National Institutes of Health natural history studies. RESULTS: PJP+ patients were more often of Asian ancestry than PJP- patients [odds ratio (OR) 8.7; 95% CI 1.3, 57.9]. Anti- melanoma differentiation associated protein 5 (MDA5) autoantibodies (OR 12.5; 95% CI 3.0, 52.4), digital infarcts (OR 43.8; 95% CI 4.2, 460.2), skin ulcerations (OR 12.0; 95% CI 3.5, 41.2) and interstitial lung disease (OR 10.6; 95% CI 2.1, 53.9) were more frequent in PJP+ patients. Before PJP diagnosis, patients more frequently received pulse steroids, rituximab and more immunosuppressive therapy compared with PJP- patients. Seven PJP+ patients were admitted to the intensive care unit and four patients died due to PJP or its complications. CONCLUSIONS: PJP is a severe infection in JIIM that can be associated with mortality. Having PJP was associated with more immunosuppressive therapy, anti-MDA5 autoantibodies, Asian race and certain clinical features, including digital infarcts, cutaneous ulcerations and interstitial lung disease. Prophylaxis for PJP should be considered in juvenile myositis patients with these features.

Trends of Cause of Death among Human Immunodeficiency Virus Patients and the Impact of Low CD4 Counts on Diagnosis to Death: a Retrospective Cohort Study.

BACKGROUND: Monitoring the full spectrum of causes of death among human immunodeficiency virus (HIV) patients has become increasingly important as survival improves because of highly active antiretroviral therapy. However, there are no recently published data regarding the changes in the causes of death among HIV patients based on year of HIV diagnosis, and the impact of low CD4 count at the time of HIV diagnosis on the clinical outcome is still unclear in Korea. METHODS: A retrospective cohort study was conducted with 801 patients with HIV infection who were followed up at a tertiary university hospital and diagnosed with HIV between July 1984 and October 2019. The causes of death were analyzed by descriptive analysis based on CD4 count and the year of HIV diagnosis. Kaplan-Meier and log rank tests were performed to compare the prognosis between the CD4 < 200 cells/mm³ and CD4 ≥ 200 cells/mm³ groups. RESULTS: Among 801 patients, 67 patients were eligible for the death cause analysis. Infection-related death accounted for 44 patients (65.7%) and non-infection related death accounted for 23 patients (32.4%). Pneumocystis pneumonia (29.9%) was the single most common cause of death in both past and present cases, and tuberculosis (19.4%) was the second leading cause of death from infections, but the frequency has declined in recent years. Causes of infection-related death have decreased, whereas non-infection related causes of death have increased remarkably. Malignancy-related death was the most common cause of non-infection related death. Acquired immunodeficiency syndrome (AIDS) non-related malignancy accounted for 11.9%, whereas AIDS-related malignancy accounted for 6.0% of the total death among HIV patients. No significant statistical differences were found in mortality rate (P = 0.228), causes of death (P = 0.771), or survival analysis (P = 0.089) between the CD4 < 200 cells/mm³ and CD4 ≥ 200 cells/mm³ groups. CONCLUSION: Being diagnosed with CD4 < 200 cells/mm³ at the time of HIV diagnosis was not an indicator of greater risk of death compared with the CD4 ≥ 200 cells/mm³ group. Malignant tumors have become an important cause of death in recent years, and an increasing tendency of AIDS-non-related malignancy causes has been observed.

Pneumocystis pneumonia in HIV-negative adults: missed opportunities for prevention.

AIM: Pneumocystis pneumonia (PCP) has a high mortality rate in HIV-negative immunocompromised patients, but is preventable with antimicrobial prophylaxis. We aimed to determine the incidence of PCP in three hospitals in Auckland, New Zealand that would have been potentially preventable if patients had been prescribed prophylaxis according to commonly proposed indications. METHODS: We conducted a retrospective study of HIV-negative adults with PCP who were admitted to Middlemore, North Shore or Waitakere Hospitals between January 2011 and June 2017. We classified their PCP as potentially preventable if they had not been prescribed prophylaxis despite having a commonly proposed indication for this. RESULTS: Of the 108 patients with PCP, 33/108 (30.6%) had potentially preventable infection. Of these, 14/33 (42.4%) died within 30 days of diagnosis of PCP. Most potentially preventable infections occurred in patients with solid organ or haematologic malignancies who were receiving high-dose corticosteroids for >4 weeks. We estimate that 28 cases of PCP and 12 deaths could have been prevented over the study duration if prophylaxis was prescribed to those with commonly proposed indications. CONCLUSION: There is a substantial incidence of potentially preventable PCP and PCP-related mortality in the Auckland region. This could be reduced by greater clinician familiarity with commonly proposed indications for PCP prophylaxis, particularly for clinicians prescribing prolonged corticosteroid courses to patients with malignancies.

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.

Ability of quantitative PCR to discriminate Pneumocystis jirovecii pneumonia from colonization.

Introduction. Pneumocystis jirovecii pneumonia (PCP) is a severe disease affecting immunocompromised patients. Diagnosis is difficult due to the low sensitivity of direct examination and inability to grow the pathogen in culture. Quantitative PCR in bronchoalveolar lavage fluid (BAL) has high sensitivity, but limited specificity for distinguishing PCP from colonization.Aim. To assess the performance of an in-house quantitative PCR to discriminate between PCP and colonization.Methodology. This was a single-centre retrospective study including all patients with a positive PCR result for P. jirovecii in BAL between 2009 and 2017. Irrespective of PCR results, PCP was defined as the presence of host factors and clinical/radiological criteria consistent with PCP and (i) the presence of asci at direct examination of respiratory sample or (ii) anti-PCP treatment initiated with clinical response and absence of alternative diagnosis. Colonization was considered for cases who did not receive anti-PCP therapy with a favourable outcome or an alternative diagnosis. Cases who did not meet the above mentioned criteria were classified as 'undetermined'.Results. Seventy-one patients with positive P. jirovecii PCR were included (90 % non-HIV patients). Cases were classified as follows: 37 PCP, 22 colonization and 12 undetermined. Quantitative PCR values in BAL were significantly higher in patients with PCP versus colonization or undetermined (P<0.0001). The cut-off of 5×103 copies/ml was able to discriminate PCP cases from colonization with 97 % sensitivity, 82 % specificity, 90 % positive predictive value and 95 % negative predictive value.Conclusions. Our quantitative PCR for P. jirovecii in BAL was reliable to distinguish PCP cases from colonization in this predominantly non-HIV population.

HIV patients dying on anti-tuberculosis treatment: are undiagnosed infections still a problem in French Guiana?

OBJECTIVE: Despite scaling-up testing and antiretroviral treatment in Latin America, advanced HIV remains a significant public health problem. The objective of the present study was look for historical risk factors for death in French Guiana's HIV cohort taking into account the immunological status, the main opportunistic infections, and their treatment. A retrospective cohort study was conducted on data collected between 1992 and 2008 to identify factors associated with death in a cohort 2323 patients. RESULTS: There were 370 deaths for a total 9608 patient-years. Being on tuberculosis treatment was associated with a greater hazard of death. The diagnosis of confirmed tuberculosis, of histoplasmosis, of toxoplasmosis, and pneumocystosis were independently associated with death. Interactions terms between cotrimoxazole treatment and pneumocystosis, or between confirmed tuberculosis and tuberculosis treatment showed a protective treatment-effect. All patients having received anti-tuberculosis treatment (n = 347) did not have a final diagnosis of tuberculosis (n = 93). For histoplasmosis, 199 patients received antifungal treatment while 141 were diagnosed as having histoplasmosis. The number of patients on anti-tuberculosis drugs was far greater that the number of patients with confirmed tuberculosis, and these patients on treatment without confirmed tuberculosis had a twofold greater risk of dying.