non-HIV Pneumocystis Jirovecii Pneumonia Research Articles

Outcomes of low-dose trimethoprim-sulfamethoxazole treatment in patients with non-HIV pneumocystis pneumonia: A nationwide Japanese retrospective cohort study

ObjectivesLow-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be a treatment option for patients with Pneumocystis jirovecii pneumonia (PCP). However, its effectiveness in patients without human immunodeficiency virus (HIV) infection has yet to be thoroughly investigated. MethodsThis retrospective cohort study used data extracted from the Japanese Diagnosis Procedure Combination inpatient database. We included immunocompromised patients without HIV having been diagnosed with PCP and had started TMP-SMX treatment between July 2010 and March 2022. We divided eligible patients into conventional-dose (15.0–20.0 mg/kg/d) and low-dose (7.5–15.0 mg/kg/d) groups and performed propensity-score overlap-weighting analysis. The primary outcome was in-hospital mortality rate. Secondary outcomes were completion of the initial treatment and use of alternatives to TMP-SMX for PCP treatment during hospitalization. ResultsAmong 4449 eligible patients, 1682 (37.8 %) and 2767 (62.2 %) received conventional- and low-dose TMP-SMX treatments, respectively. No significant difference was observed in in-hospital mortality (risk difference, −1.4 %; 95 % CI, −4.5–1.7 %; P = 0.388). Low-dose TMP-SMX was associated with increased completion of initial treatment (risk difference, 4.6 %; 95 % CI, 2.3–6.9 %; P < 0.001), and reduced use of alternative agents (risk difference, −4.0 %; 95 % CI, −7.4 to −0.6 %; P = 0.020). ConclusionLow-dose TMP-SMX may be a treatment option for patients with non-HIV PCP.

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.

Low-Dose vs Conventional-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia in Patients Not Infected With HIV: A Multicenter, Retrospective Observational Cohort Study

Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics? In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP< 12.5mg/kg/d) and conventional-dose (TMP 12.5-20mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores. Fifty-five patients in the low-dose group and 81 in the conventional-dose group were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of women was 55.1%. The average dose of TMP-SMX was 8.71mg/kg/d in the low-dose group and 17.78mg/kg/d in the conventional-dose group. There was no significant difference in 30-day mortality (6.7%vs18.4%, respectively; P= .080) or 180-day mortality (14.6%vs26.1%, respectively; P= .141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8%vs59.0%, respectively; P= .005). The initial treatment completion rates were 43.3%and 29.6%in the low-dose and conventional-dose groups (P= .158), respectively. Survival was similar between the low-dose and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP.

Pathophysiological mechanism of non-HIV Pneumocystis jirovecii pneumonia.

While Pneumocystis jirovecii pneumonia (PCP) can occur in immunocompromised patients with HIV infection, the prognosis of non-HIV PCP is still poor, showing a high mortality rate of 30%-75%. The pathophysiological mechanism of non-HIV PCP is quite different from that of HIV-PCP. Aging, underlying disease, dysbiotic gut microbiome, and Th1 predominance, leads to macrophagic polarization shifting from M2 to M1. These cause dysregulation in the host immunity against P. jirovecii, resulting in severe lung injury and a high mortality rate among non-HIV PCP patients. This review describes poor prognostic factors, an issue of predictive values used for general pneumonia practice, and new aspects, including the dysbiosis of the gut microbiome and macrophagic polarization in the treatment of non-HIV PCP.

Pneumocystis Jirovecii Pneumonia Diagnosis via Metagenomic Next-Generation Sequencing.

The incidence of non-HIV-infected Pneumocystis Jirovecii Pneumonia (PJP) is increasing. The prognosis for non-HIV PJP is poor and diagnostic tests are of lower sensitivity in non-HIV patients. Metagenomic next-generation sequencing (mNGS) was compared with routine detection assays, including Gomori methenamine silver (GMS) stain and polymerase chain reaction (PCR) technique. Specimens of 4 bronchoalveolar lavages (BAL) and 1 lung tissue samples were obtained from 4 non-HIV patients from our hospitals. Although both GMS and mNGS were positive for P. jirovecii with PCR as positive control, the testing time of mNGS was obviously shorter than GMS. Compared with the traditional GMS method, mNGS has absolute advantages. However, the issue with PJP presentations having atypical symptoms and ambiguous imaging features persists. Hence, the disease can easily be ignored. Secondly, PJP progresses rapidly in non-HIV-infected patients and can cause severe respiratory failure with unfavorable prognosis. This study affirms that mNGS can be used to quickly and accurately diagnose PJP, but a combination of clinical judgement of symptoms, laboratory testing, and imaging examination is required to make a comprehensive judgment along with mNGS test results.

Pneumocystis jirovecii Pneumonia in Neurologic Disorders: Is Prophylaxis Necessary?

The incidence of Pneumocystis jirovecii pneumonia (PJP) in patients with underlying neurologic conditions is not well established, and the necessity of PJP prophylaxis for immunocompromised patients with neurologic disorders is uncertain. Single-center retrospective analysis of non-HIV PJP patients at a tertiary referral center from 2007 to 2016 to determine the incidence of PJP in patients with primary neurologic disorders. The study included 142 patients with PJP without HIV. Twenty patients had primary neurologic diagnoses, and 122 had non-neurologic conditions. Associated neurologic diagnoses included brain malignancies (N = 14), myasthenia gravis (MG) (N = 2), myopathy (N = 2), neuromyelitis optica (NMO) (N = 1), and CNS vasculitis (N = 1). Estimated incidences of PJP were 0.7% for patients with NMO and 0.3% for patients with MG for the 10-year study period, whereas 4.6% of patients with NMO and 3.8% of patients with MG were placed on PJP prophylaxis. A survey of 24 neurologists who prescribe immunotherapy or chemotherapy confirmed an infrequent occurrence of PJP in their practice. Malignancy or parenchymal organ failure was present in 90% of neurologic patients with PJP, and coexisting infections occurred in 45%. The overall incidence of PJP in patients with non-neoplastic neurologic disorders is exceedingly low, raising doubt about the value of routine PJP prophylaxis in neurologic patients outside neuro-oncology. PJP infection occurs frequently in patients with malignancy or parenchymal organ failure, indicating that overall health status may serve as a predisposing factor for PJP.

Pneumocystis jirovecii pneumonia in patients treated for systemic autoimmune disorders: a retrospective analysis of patient characteristics and outcome

Objectives: Pneumocystis jirovecii is an opportunistic fungus. Pneumocystis jirovecii pneumonia (PJP) is well known in the human immunodeficiency virus (HIV)-infected population, but in non-HIV-related immunosuppressed patients, risk factors are largely unknown. We studied the characteristics and outcome of patients treated for systemic autoimmune disorders infected with P. jirovecii, aiming to clarify risk stratification to guide prophylaxis. Method: Clinical charts collected between 2010 and 2016 at the University Hospital of Leuven (Belgium) were reviewed. Information on type of systemic disorder, organ involvement, immunosuppressant use, and comorbidity was collected, and laboratory results were consulted. Results: In total, 39 cases of non-HIV PJP were retrieved, 24 of whom had pre-existing pulmonary disease. All were on immunosuppressant medication at the time of infection, the majority (36/39) taking glucocorticoids, with a median dose of 16 mg methylprednisolone over the past 3 months. Of the 39 cases, 21 were admitted to the intensive care unit and mortality reached 35%. Age and pulmonary disease correlated positively and methotrexate use negatively with mortality. When applying current prophylactic strategies to our cohort, 50% of infections could theoretically have been prevented. Conclusion: PJP is a rare but relevant clinical problem when caring for immunosuppressed patients with autoimmune systemic disorders. Pulmonary disease and age are risk factors for acquiring the infection and carry a worse prognosis. More studies are needed to further define prophylactic criteria.

Adjunctive corticosteroids may be associated with better outcome for non-HIV Pneumocystis pneumonia with respiratory failure: a systemic review and meta-analysis of observational studies

BackgroundEvidence supporting corticosteroids adjunctive treatment (CAT) for Pneumocystis jirovecii pneumonia (PCP) in non-HIV patients is highly controversial. We aimed to systematically review the literature and perform a meta-analysis of available data relating to the effect of CAT on mortality of PCP in non-HIV patients.MethodsWe searched Pubmed, Medline, Embase, and Cochrane database from 1989 through 2019. Data on clinical outcomes from non-HIV PCP were extracted with a standardized instrument. Heterogeneity was assessed with the I2 index. Pooled odds ratios and 95% confidence interval were calculated using a fixed effects model. We analyzed the impact of CAT on mortality of non-HIV PCP in the whole PCP population, those who had hypoxemia (PaO2 < 70 mmHg) and who had respiratory failure (PaO2 < 60 mmHg).ResultsIn total, 259 articles were identified, and 2518 cases from 16 retrospective observational studies were included. In all non-HIV PCP cases included, there was an association between CAT and increased mortality (odds ratio, 1.37; 95% confidence interval 1.07–1.75; P = 0.01). CAT showed a probable benefit of decreasing mortality in hypoxemic non-HIV PCP patients (odds ratio, 0.69; 95% confidence interval 0.47–1.01; P = 0.05). Furthermore, in a subgroup analysis, CAT showed a significantly lower mortality in non-HIV PCP patients with respiratory failure compared to no CAT (odds ratio, 0.63; 95% confidence interval 0.41–0.95; P = 0.03).ConclusionsOur meta-analysis suggests that among non-HIV PCP patients with respiratory failure, CAT use may be associated with better clinical outcomes, and it may be associated with increased mortality in unselected non-HIV PCP population. Clinical trials are needed to compare CAT vs no-CAT in non-HIV PCP patients with respiratory failure. Furthermore, CAT use should be withheld in non-HIV PCP patients without hypoxemia.

Prognostic significance of crazy paving ground grass opacities in non-HIV Pneumocystis jirovecii pneumonia: an observational cohort study

BackgroundIn patients with non-HIV Pneumocystis jirovecii pneumonia (PjP), computed tomography imaging reveals ground grass opacities (GGO). Previous reports show that some patients with non-HIV PjP exhibit GGO with crazy paving. However, there have been no studies on the association between crazy paving GGO and non-HIV PjP clinical outcomes. Here, at the diagnosis of non-HIV PjP, we reviewed high-resolution computed tomography (HRCT) findings that included GGO types and evaluated the prognostic impact of crazy paving GGO on the clinical outcomes of non-HIV PjP immunocompromised patients.MethodsWe retrospectively reviewed the clinical information including the HRCT findings of patients diagnosed with non-HIV PjP from five institutions between 2006 and 2015. The GGO types included those with or without crazy paving. The associations between clinical factors such as HRCT findings and in-hospital mortality were assessed using the Cox regression model.ResultsSixty-one patients were included in our study. Nineteen patients died at a hospital. All patients exhibited GGO on HRCT imaging at diagnosis of non-HIV PjP. The HRCT findings included crazy paving GGO (29 patients, 47.5%), consolidations (23 patients, 37.7%), bronchiectasis (14 patients, 23.0%), and centrilobular small nodules (30 patients, 49.2%). Cysts were not observed in any patient. Multivariate analysis revealed that crazy paving GGO and low serum albumin levels were independent risk factors for mortality.ConclusionsAt the diagnosis of non-HIV PjP, patients with crazy paving GGO on HRCT imaging and low serum albumin levels may have a poor prognosis.

Pneumocystis jirovecii pneumonia (PCP) PCR-negative conversion predicts prognosis of HIV-negative patients with PCP and acute respiratory failure.

BackgroundPneumocystis jirovecii pneumonia (PCP) is often fatal in human immunodeficiency (HIV)-negative patients and typically presents with respiratory insufficiency. Predicting treatment failure is challenging. This study aimed to identify prognostic factors and examine PCP polymerase chain reaction (PCR)-negative conversion in non-HIV PCP patients with respiratory failure.MethodWe retrospectively enrolled 81 non-HIV patients diagnosed with and treated for PCP with respiratory failure in the intensive care unit at a tertiary hospital over a 3-year period. PCP was diagnosed via nested PCR-mediated detection of Pneumocystis jirovecii in induced sputum samples, endotracheal aspirates, and bronchoalveolar lavage fluids. PCP PCR was performed weekly to check for negative conversion.ResultsThe overall survival rate was 35.8%. Seventy-four patients (91.3%) required mechanical ventilation, and 6 (7.4%) required high-flow nasal oxygen treatment. The PCP PCR-negative conversion rate was 70.5% (survivors, 97%; non-survivors, 63.5%); the median time to conversion was 10 (7.0–14.0) days. On univariate analysis, the APACHE II score (p < 0.001), renal failure requiring renal replacement therapy (p = 0.04), PCP PCR-negative conversion (p = 0.003), and the PaO2/FiO2 ratio (first 24 hours) (p < 0.001) significantly correlated with mortality. On multivariate analysis, PCP PCR-negative conversion (hazard ratio, 0.433; 95% confidence interval, 0.203–0.928; p = 0.031) and the PaO2/FiO2 ratio (first 24 hours) (hazard ratio, 0.988; 95% confidence interval, 0.983–0.993; p < 0.001) independently predicted prognosis.ConclusionsDetermination of PCP PCR-negative conversion and PaO2/FiO2 ratios may help physicians predict treatment failure and mortality in non-HIV PCP patients with respiratory failure.

Clinical Manifestations and Prognostic Factors of Pneumocystis jirovecii Pneumonia without HIV

Introduction:Pneumocystis jirovecii pneumonia (PCP) can occur in HIV patients but also in those without HIV (non-HIV PCP) but with other causes of immunodeficiency including malignancy or rheumatic diseases. Objective and Methods: To evaluate the clinical presentation and prognostic factors of non-HIV PCP, we retrospectively reviewed all patients diagnosed as having PCP without HIV at Kameda Medical Center, Chiba, Japan, from January 2005 until June 2012. For the purpose of examining a prognostic factor for non-HIV PCP with 30-day mortality, we compared the characteristics of patients, clinical symptoms, radiological images, Eastern Cooperative Oncology Group performance status (PS), and the time from the onset of respiratory symptoms to the start of therapy, in both survival and fatality groups. Results: A total of 38 patients were eligible in this study. Twenty-five survived and 13 had died. The non-HIV PCP patients in the survivor group had a better PS and received anti-PCP therapy earlier than those in the nonsurvivor group. Rales upon auscultation and respiratory failure at initial visits were seen more frequently in the nonsurvivor group than in the survivor group. Lactate dehydrogenase and C-reactive protein values tended to be higher in the nonsurvivor group, but this was not statistically significant. Multivariate analyses using 5 variables showed that a poor PS of 2-4 was an independent risk factor for non-HIV PCP patients and resulted in death (odds ratio 15.24; 95% confidence interval 1.72-135.21). Conclusion: We suggest that poor PS is an independent risk factor in non-HIV PCP, and a patient's PS and disease activity may correlate with outcome.

A Pneumocystis jirovecii pneumonia outbreak in a single kidney-transplant center: role of cytomegalovirus co-infection

Pneumocystis jirovecii pneumonia (PCP) and cytomegalovirus (CMV) infection represent possible complications of medical immunosuppression. Between 2005 and 2010, non-human immunodeficiency virus (HIV) PCP patients admitted to a nephrology unit were analyzed for outcome, CMV comorbidity, and patient-to-patient contacts prior to PCP. In contrast to 2002-2004 (no cases) and 2008-2010 (10 cases), a PCP outbreak of 29 kidney-transplant recipients and one patient with anti-glomerular basement membrane disease occurred between 2005 and 2007. None of the patients were on PCP chemoprophylaxis. In four PCP patients, the genotyping data of bronchoalveolar lavage specimen showed an identical Pneumocystis strain. PCP cases had a higher incidence of CMV infection (12 of 30 PCP patients) and CMV disease (four patients) when compared to matched PCP-free controls (p < 0.05). Cotrimoxazole and, if applicable, ganciclovir were started 2.0 ± 4.0days following admission, and immunosuppressive medication was reduced. In-hospital mortality was 10% and the three-year mortality was 20%. CMV co-infection did not affect mortality. CMV co-infection more frequently occurred during a cluster outbreak of non-HIV PCP in comparison to PCP-free controls. Here, CMV awareness and specific therapy of both CMV infection and PCP led to a comparatively favorable patient outcome. The role of patient isolation should be further investigated in incident non-HIV PCP.

Analysis of clinical features of non-HIV Pneumocystis jirovecii pneumonia

Pneumocystis jirovecii pneumonia (PCP) is classified as PCP with human immunodeficiency virus (HIV) and non-HIV PCP, and the two forms differ in progression and prognosis. Although early treatment is necessary, the diagnosis of non-HIV PCP is often difficult because of the underlying diseases. However, the outcome with treatment delay remains unclear because there are no concrete data indicating a worsened clinical situation or increased complications related to delayed therapy initiation. We retrospectively examined patients with non-HIV PCP admitted to Tokyo Women's Medical University Hospital from November 2008 to October 2010. The relationship between intubation with mechanical ventilation (within 1 week after starting treatment) and treatment delay was investigated. Treatment delay was defined as the period, in days, from onset to therapy initiation. In total, 24 confirmed non-HIV PCP cases were included. Median treatment delay was 7 ± 4.83 days (1-20 days). Twelve of 24 cases (50 %) were intubated, and 11 (45.8 %) died of their underlying diseases within 90 days. Treatment delay was more than 7 days in the intubation group, but was within 7 days in 9 of 12 nonintubation cases. The difference in treatment delay was significant (p = 0.0071) between the intubation and nonintubation groups, but there were no significant differences in survival rate at 90 days or other findings. We conclude that starting treatment within 7 days after onset is important because intubation and mechanical ventilation may be avoided in many cases.

Clinical Utility of Serum .BETA.-D-Glucan and KL-6 Levels in Pneumocystis jirovecii Pneumonia

New serum markers (1-->3) beta-D-glucan (beta-D-glucan) and KL-6 are reported to be useful for the clinical diagnosis of Pneumocystis jirovecii pneumonia (PCP). However, the utility of these markers in PCP with HIV infection (HIV PCP) and without HIV (non-HIV PCP) is unknown. This study was aimed to evaluate the utility of beta-D-glucan and KL-6 for the diagnosis of PCP in patients with HIV infection (HIV PCP) and non-HIV PCP. Retrospective study. We reviewed the medical records of consecutive 35 patients. The serum levels of beta-D-glucan and KL-6 in HIV PCP and non-HIV PCP were comparatively evaluated. We evaluated these markers in survivors and non survivors. The detection rates of serum beta-D-glucan and KL-6 levels in non-HIV PCP were lower than those in HIV PCP (88% vs. 100%, 66% vs. 88%, respectively). The false positive rates of these markers in both groups were similar (12%, 37%, respectively). Oxygenation index, serum albumin, and mechanical ventilation were the variables which were significantly associated with poor outcome in the univariate analysis. In conclusion, beta-D-glucan was a reliable diagnostic marker for PCP. However, the detection rate of beta-D-glucan and KL-6 in non-HIV PCP was lower than in HIV PCP. Neither beta-D-glucan nor KL-6 was associated with the outcome of PCP.