Pneumocystis Jirovecii Pneumonia In Patients Research Articles

Clinical features and death risk factors of pneumocystis jirovecii pneumonia in kidney disease patients with immunosuppressive therapy

To investigate the clinical features and death risk factors of pneumocystis jirovecii pneumonia (PJP) in kidney disease patients with immunosuppressive patients. A Retrospective case series study was performed in 52 PJP patients with kidney disease who received immunosuppressive therapy in Nephrology or Respiratory department of Peking University First Hospital from January 1, 2006 to August 31, 2021. Patients were divided into survival group (36 cases) and death group (16 cases) according to their clinical outcomes. Univariate analysis was performed to compare the differences of clinical features between the two groups. Multivariate logistic regression model was used to analyze the death risk factors. The results showed that the median serum creatinine was 192.5 (109.8, 293.7) μmol/L, and the incidence of acute kidney injury was 63.5% (33/52). Univariate analysis showed that age (t=1.197,P=0.030), C-reactive protein level (t=2.378,P=0.022), time from onset to diagnosis (χ2=6.62,P=0.010), PJP severity (χ2=5.482,P=0.019), complicated with septic shock (χ2=3.997,P=0.046), mechanical ventilation (χ2=11.755,P=0.001), and blood purification therapy (χ2=4.748,P=0.029) were statistically significant. There were no statistically significant differences between the two groups in gender, duration and dosage of hormone therapy before PJP onset, intravenous methylprednisolone pulse therapy, immunosuppressant use, and serum creatinine level before and after hospitalization for anti-PJP treatment (all P>0.05). Multivariate analysis showed that the time from onset to diagnosis of PJP was >10 days (OR=40.945, 95%CI: 1.738-451.214; P=0.021) and severe PJP (OR=25.502, 95%CI: 1.426-74.806; P=0.028) was an independent death risk factor for kidney disease complicated with PJP of immunosuppressive therapy. In conclusion, the time from onset to diagnosis of PJP and PJP severity are independent death risk factors in patients with kidney disease complicated with PJP of immunosuppressive therapy. Close attention should be paid to oxygenation condition and early diagnosis can prevent the aggravation of PJP and improve the prognosis.

The Clinical Value of Metagenomic Next-Generation Sequencing in Pneumocystis jirovecii Pneumonia.

The incidence of Pneumocystis jirovecii pneumonia (PJP) is increasing. 108 patients were analysed retrospectively at the Wuhan Union Hospital. The patients were classified into the PJP group or the P. jirovecii colonisation (PJC) group based on clinical diagnosis. Clinical data included demographics, laboratory examinations, treatment, and outcomes. A notable difference in the fungal load was seen between two groups, with median reads of 3215.79 vs. 5.61 in two groups, respectively (P<0.001). The optimal threshold value for discriminating P. jirovecii infection between colonisation for mNGS was six, and serum (1,3)-β-D-glucan (BDG) was 47.6 pg/mL. Besides, the positive detection rate of mNGS for co-pathogens in PJP patients was significantly higher than that of culture (88.16% vs. 22.37%, P<0.0001). Epstein-Barr virus and cytomegalovirus were the most common pathogens of co-infection in PJP patients. The antibiotic therapy in PJP patients was adjusted according to the mNGS results, of which seventeen (22.37%) were downgraded, 38 (50.0%) patients were upgraded, and 21 (27.63%) were unchanged. And almost all patients showed significant improvement in C-reactive protein. mNGS is a promising and valuable technique with good performance for differentiating P. jirovecii infection and colonisation, the detection of pathogens, and antibiotic treatment.

Dismal prognosis of Pneumocystis jirovecii pneumonia in patients with multiple myeloma

Patients with multiple myeloma (MM) are at high risk for infections, including opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP). We conducted a retrospective analysis of patients with MM developing PJP over a 6-year period between January 2016 and December 2021 at the University Hospital of Würzburg by screening cases of microbiologically documented PJP. A total of 201 positive results for P. jirovecii in respiratory specimens were retrospectively retrieved through our microbiology database. Of these cases, 13 patients with MM fulfilled the definition of probable PJP according to EORTC fungal disease definitions. We observed two peaks in PJP incidence, one after stem cell transplantation during first-line treatment (n = 5) and the other in heavily pretreated patients with six or more prior lines of therapy (n = 6). There was high morbidity with nine (69%) patients admitted to the ICU, seven of whom (78%) required mechanical ventilation, and high mortality (62%, n = 8). Notably, only two of the 13 patients (15%) had received PJP prophylaxis. The main reason for discontinuation of prophylaxis with trimethoprim-sulfamethoxazole was grade IV neutropenia. The observed morbidity and mortality of PJP in MM patients are significant and even higher than reported for patients with other hematologic malignancies. According to most current guidelines, the use of prophylaxis would have been clearly recommended in no more than three (23%) of the 13 patients. This illustrates the need to critically reconsider the indications for PJP prophylaxis, which remain incompletely defined.

Diagnostic challenge of Pneumocystis jirovecii pneumonia infection mimicking interstitial lung disease in initially HIV negative patient

Background: Pneumocystis jirovecii pneumonia (PJP) infections are common in immunocompromised patients and are rarely found in immunocompetent patients. Lung radiology in PJP patients could mimic the appearance of interstitial lung disease (ILD) and could be used to diagnose HIV-negative patients. Clinicians should rule out false negatives in patients with patterns suggestive of opportunistic infections and risk factors for HIV infection. Case illustration: A 34-year-old man presented with a chief complaint of shortness of breath, had history of 15 years of smoking, and daily chlorine exposure. The radiology pattern and initial HIV-negative test results suggested an ILD diagnosis. Owing to persistent symptoms despite initial management and the presence of risk factors, repeat HIV testing was initiated and was positive. The patient was treated with cotrimoxazole and showed rapid clinical improvement. Discussion: The diagnosis of PJP in our patient was based on radiology and an HIV-positive status. In patients who are not immunocompromised, the diagnosis of PJP is unlikely, and other diagnoses, such as ILD, should be considered. However, in the HIV testing window period of infection, a poor advanced state of HIV could cause a false negative result. Therefore, clinical judgement is essential in suspecting such a result. The empirical treatment course of cotrimoxazole has been shown to provide better clinical outcomes in PJP. Conclusion: The possibility of PJP must be considered in patients with initially HIV-negative results, especially in patients with risk factors and clinical symptoms suggestive of immunocompromise. While some ILD showed similar PJP, the risk factors for ILD and PCP could be distinguishing factors. Retesting for HIV infection can confirm the diagnosis and rule out false-negative results.

Prevalence of Pneumocystis jirovecii Colonization in Non-Critical Immunocompetent COVID-19 Patients: A Single-Center Prospective Study (JiroCOVID Study).

Pneumocystis jirovecii pneumonia (PJP) is an invasive fungal infection (IFI) that occurs mainly in immunocompromised hosts. After observing a high prevalence of PJP as a complication of COVID-19 in immunocompetent patients, we conducted a study to evaluate the prevalence of P. jirovecii colonization with PCR on oral washing samples (OWS) among non-immunocompromised and non-critical patients admitted with COVID-19 pneumonia at our university hospital. All patients over 18 years of age admitted to the Infectious Diseases Unit for SARS-CoV-2 pneumonia between July 2021 and December 2022 were included. Patients undergoing invasive mechanical ventilation or ECMO, those with risk factors for developing PJP, and those receiving prophylaxis for P. jirovecii were excluded. Samples were collected by gargling with 10 mL of 0.9% NaCl on day 14 of the hospital stay or at discharge. Of 290 screened patients, 59 (20%) met the inclusion criteria and were enrolled. Only 1 of 59 patients (1.7%) tested positive for P. jirovecii detection with PCR, and the same patient was the only one to develop PJP in the follow-up period. Our results are in line with the previous findings of other studies that confirmed a very low prevalence of P. jirovecii colonization on OWS in the immunocompetent population. Despite the limitations of the study, the fact that the only patient who tested positive for P. jirovecii was the only one in our cohort to develop PJP leads us to reflect on the role of this non-invasive sample in predicting the risk of PJP in patients with COVID-19.

Negative serum (1,3) -β-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR

ObjectiveThe current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results.MethodsThis was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort.ResultsTwo hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG.ConclusionsSerum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

IMMU-54. PNEUMOCYSTIS JIROVECII PNEUMONIA INFECTION IN A PATIENT WITH ANAPLASTIC ASTROCYTOMA AND RADIATION NECROSIS IN THE SETTING OF CORTICOSTEROID AND PEMBROLIZUMAB USE

Abstract We present a case with anaplastic astrocytoma and radiation-induced brain necrosis, diagnosed with pneumocystis jirovecii pneumonia(PJP) while receiving corticosteroid and pembrolizumab, an immune checkpoint inhibitor(ICI). ICIs have significantly changed management of many cancer types and are known to be associated with immune related adverse events(irAEs). Recently, concerns have emerged regarding the potential relationship between ICI use and infection risks, and PJP, a rare opportunistic infection, has been reported in patients with ICI treatments with or without corticosteroid use. A 40-year-old man with anaplastic astrocytoma and radiation-induced brain necrosis on corticosteroid and pembrolizumab presented with high fever and tachycardia over three days, and the patient later developed hypoxia and cough. The patient was on dexamethasone for brain radiation necrosis for two months and he received one dose of pembrolizumab two weeks prior to his symptom onset, based on genetic information that showed hypermutated tumor and abnormal DNA mismatch repair protein expression. Chest CT showed abnormal findings from infectious or inflammatory process. Bronchoalveolar lavage sample confirmed positive pneumocystis jiroveci PCR test, confirmed PJP, and he was treated with clindamycin, primaquine, and prednisone. To the best of our knowledge, this is the first reported case of PJP in a patient with primary brain tumor receiving corticosteroid and pembrolizumab. ICIs are being investigated in patients with primary brain tumors and wildly used in patients with malignancies with frequent central nervous system involvements, such as malignant melanomas and non-small cell lung cancers. Awareness of risk for infectious conditions including PJP in patients on ICI treatment, especially with corticosteroid use is crucial for implementing appropriate prophylactic measures and prompt diagnosis and treatment interventions.

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

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

MO8-5 Pneumocystis jiroveci pneumonia in patients receiving ddAC for breast cancer: A single center retrospective study

MO8-5 Pneumocystis jiroveci pneumonia in patients receiving ddAC for breast cancer: A single center retrospective study

Incidence of Pneumocystis Jiroveci Pneumonia in Patients With ANCA-Associated Vasculitis Initiating Therapy With Rituximab or Cyclophosphamide.

This manuscript assesses the incidence of Pneumocystis jiroveci pneumonia (PJP) among patients receiving contemporary treatment regimens for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and adverse events associated with PJP prophylaxis. Incident users of rituximab or cyclophosphamide for AAV were identified in the TriNetX electronic health records database from 2011 to 2022. The incidence rates (IRs) of PJP in the first 6 months of induction therapy with rituximab and/or cyclophosphamide and during postinduction maintenance therapy with rituximab were calculated. Cox proportional hazard models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) for the risk of adverse events commonly associated with PJP prophylaxis. We identified 1,461 AAV cases who received induction therapy with rituximab (69.7%), cyclophosphamide (18.9%), or both (11.4%). Prophylaxis prescribed within 30 days of induction included trimethoprim-sulfamethoxazole (30.7%), atovaquone (5.4%), dapsone (3.8%), and pentamidine (0.8%). During induction therapy, 10 cases of PJP were identified (IR 15.0 cases per 1,000 patient-years); no deaths occurred. In adjusted analyses, those who received prophylaxis had a higher risk of leukopenia (HR 3.1; 95% CI 1.1-8.6), rash (HR 1.9; 95% CI 1.0-3.6), and nephropathy (HR 2.6; 95% CI 1.3-5.1) than those who did not.During rituximab maintenance therapy (n=709), five cases of PJP were identified (IR 2.1 cases per 1,000 person-years), one of whom died during the hospitalization associated with a PJP diagnosis. Rates of PJP in patients with AAV were lower than previously observed, and few cases occurred during rituximab maintenance therapy. PJP prophylaxis was associated with adverse events.

Risk Factors of Pneumocystis jirovecii Pneumonia in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Study.

: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD) patients. : This nationwide, population-based study was conducted in Korea using claims data. Cases of PJP were identified in patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 2010 and 2017, and the clinical data of each patient was analyzed. Dual and triple therapy was defined as the simultaneous prescription of two or three of the following drugs: steroids, calcineurin inhibitors, immunomodulators, and biologics. : During the mean follow-up period (4.6±2.3 years), 84 cases of PJP were identified in 39,462 IBD patients (31 CD and 53 UC). For CD patients, only age at diagnosis >40 years (hazard ratio [HR], 6.12; 95% confidence interval [CI], 1.58 to 23.80) was significantly associated with the risk of PJP, whereas in UC patients, diagnoses of diabetes (HR, 2.51; 95% CI, 1.19 to 5.31) and chronic obstructive pulmonary disease (HR, 3.41; 95% CI, 1.78 to 6.52) showed significant associations with PJP risk. Triple therapy increased PJP risk in both UC (HR, 3.90; 95% CI, 1.54 to 9.88) and CD patients (HR, 5.69; 95% CI, 2.32 to 14.48). However, dual therapy increased PJP risk only in UC patients (HR, 2.53; 95% CI, 1.36 to 4.70). Additionally, 23 patients (27%) received intensive care treatment, and 10 (12%) died within 30 days. : PJP risk factors differ in CD and UC patients. Considering the potential fatality of PJP, prophylaxis should be considered for at-risk IBD patients.

P-480 Outcome of pneumocystis jirovecii pneumonia in patients with multiple myeloma

P-480 Outcome of pneumocystis jirovecii pneumonia in patients with multiple myeloma

Prevention of pneumocystis pneumonia in patients with hematological diseases: Efficacy oflow-dose atovaquone.

At our institution, patients with hematological disease who require Pneumocystis jirovecii pneumonia (PJP) prophylaxis were administered atovaquone at a low dose (750 mg/day). However, there have been few reports on the efficacy of low-dose atovaquone administration, and the purpose of this study is, therefore, to investigate its effectiveness. We investigated the expression of PJP in patients with hematological disease who received atovaquone administration. Atovaquone was administered at a low dose of 750 mg once daily, and the follow-up time was the period of PJP prophylaxis that included atovaquone administration. 85 patients were included in the study. The median age of the study population was 72 years (range: 33-97). The duration of atovaquone treatment and follow-up time were 150 days (22-1,018) and 258 days (22-1,457), respectively. In hematologic diseases, multiple myeloma was high in 31 patients and malignant lymphoma in 28 patients. No patients exhibited PJP during the observation period. In hematological disease patients with relatively low risk of PJP, low-dose atovaquone may prevent the onset of PJP.

Risk-benefit analysis of primary prophylaxis against Pneumocystis jirovecii pneumonia in patients with rheumatic diseases receiving rituximab.

To identify a specific population of patients with rheumatic diseases receiving rituximab treatment for whom the benefit from primary prophylaxis against Pneumocystis jirovecii pneumonia (PJP) outweighs the risk of adverse events (AEs) METHODS: This study included 818 patients treated with rituximab for rheumatic diseases. Of these, 419 received prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) with rituximab while the remainder did not. Differences in 1-year PJP incidence between the groups were estimated using Cox regression. Risk-benefit assessment was performed in the subgroup stratified according to risk factors based on the number needed to treat (NNT) to prevent one case of PJP and the number needed to harm (NNH) due to severe AEs. Inverse probability of treatment weighting was applied to minimize the confounding by indication. During the 663.1 person-years, there were 11 PJP cases, with a mortality rate of 63.6%. Concomitant use of high-dose glucocorticoids (≥30mg/day of prednisone during 4 weeks after rituximab administration) was the most important risk factor. The PJP incidence (per 100 person-years) was 7.93 (2.91-17.25) in the subgroup receiving high-dose glucocorticoids, compared with 0.40 (0.01-2.25) in the subgroup without high-dose glucocorticoids. Although prophylactic TMP-SMX significantly reduced the overall PJP incidence (HR 0.11 [0.03-0.37]), the NNT to prevent one PJP was higher than the NNH (146 vs. 86). In contrast, the NNT fell to 20 (10.7-65.7) in patients receiving concomitant high-dose glucocorticoids. The benefit associated with primary PJP prophylaxis overweighs the risk of severe AEs in patients receiving rituximab and concomitant high-dose glucocorticoid treatment. This article is protected by copyright. All rights reserved.

Invasive fungal diseases in patients with autoimmune diseases: a case series from the French RESSIF network

ObjectivesWe aimed to describe patients with autoimmune diseases (AID) developing invasive fungal disease (IFD) and identify factors associated with short-term mortality.MethodsWe analysed cases of IFD associated with AID from the...

Diagnostic value of metagenomic next-generation sequencing of lower respiratory tract specimen for the diagnosis of suspected Pneumocystis jirovecii pneumonia

Aim To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori methenamine silver (GMS) staining and serum 1,3-β-d-Glucan (BG) assay. Methods 52 PCP patients and 103 patients with non-pneumocystic jirovecii pneumonia (non-PCP) were enrolled, and comparative analysis was conducted of different diagnostic tests. Clinical features and co-pathogen characteristics were reviewed. Results The diagnostic sensitivity (92.3%) and specificity (87.4%) of mNGS did not show significant differences compared with that of PCR while mNGS had the advantage over PCR in the detection of co-pathogens. Despite its excellent specificity, the sensitivity of GMS staining (9.3%) was inferior to that of mNGS (p < .001). The combination of mNGS with serum BG statistically outperformed mNGS or serum BG alone in the areas under the receiver operating characteristic curves (AUCs, p = .0013 and p = .0015, respectively). Notably, all the blood samples showing positive mNGS for Pneumocystis jirovecii came from PCP patients. The leading co-pathogens among patients with PCP were cytomegalovirus, Epstein-Barr virus and Torque teno virus. Conclusions mNGS shows superiority over several common clinical methods in the diagnosis of suspected PCP. Serum BG in conjunction with mNGS further improved the diagnostic efficacy of mNGS.

Metagenomic next‐generation sequencing for pneumocystis jirovecii pneumonia in patients with connective tissue disease

AbstractBackgroundAccurate diagnosis of Pneumocystis jirovecii pneumonia (PJP) is challenging, and the delayed diagnosis of PJP is associated with high mortality in patients with connective tissue disease (CTD). Metagenomic next‐generation sequencing (mNGS) technology facilitates etiological diagnosis of various infectious diseases, with promising application in diagnosing PJP. This study aimed to investigate the value of mNGS using bronchoalveolar lavage fluid (BALF) for diagnosing PJP infection.MethodsData from 55 patients with CTD and suspected pulmonary infection was retrospectively collected and analysed. A PJP group and non‐PJP group were formed. The clinical manifestations, laboratory test results, treatment methods, and outcomes were summarized. BALF mNGS results were compared with traditional pathogen tests (TPT) and serum 1,3‐beta‐D‐glucan (BDG) testing.ResultsThe mean age of PJP patients was 54 years, and 59% (10/17) of the patients were female. A significant difference was found between the average daily dose of prednisone administered to the PJP group and non‐PJP group (25 mg vs. 16 mg, P &lt; 0.001). The PJP group had a significantly higher incidence of dyspnoea (88% [15/17] vs. 16% [6/38], P &lt; 0.001) and elevated serum BDG level (167.73 vs. 30.67 pg/mL, P &lt; 0.001). BALF mNGS was more sensitive than both TPT (100% [95% confidence interval {CI}: 77.1%–100%] vs. 11.8% [95% CI: 2.1%–37.7%], P &lt; 0.001) and serum BDG (100% [95% CI: 77.1%–100%] vs. 85.7% [95% CI: 42%–99.2%], P &lt; 0.001). BALF mNGS was more specific than serum BDG (89.5% [95% CI: 74.3%–96.6%] vs. 46.7% [95% CI: 22.3%–72.6%], P = 0.493). Co‐infection with cytomegalovirus (CMV) was more common in the PJP patients than in the non‐PJP patients (59% [10/17] vs. 11% [4/38], respectively, P &lt; 0.001).ConclusionBALF mNGS technology is highly effective for diagnosing PJP in patients with CTD and identifying co‐infections.

Abstract #1407860: Rare Cause of Non-PTH Mediated Hypercalcemia Due to Pneumocystis Pneumonia in Renal Transplant Recipient

Hypercalcemia secondary to persistent hyperparathyroidism is common in kidney transplant recipients (KTR). We report a rare cause of non-PTH mediated hypercalcemia in KTR due to pneumocystis jirovecii pneumonia (PJP). The incidence of PJP in KTR is 5-15% in absence of antibiotic prophylaxis. Incidence of hypercalcemia in KTR with PJP is unclear, but scattered case reports are found in literature. The proposed mechanism for hypercalcemia is an infectious granulomatous reaction. PJP induced hypercalcemia needs to be considered in KTR patients with non-PTH mediated hypercalcemia. A 62-year-old male with kidney transplant for renal failure from glomerulosclerosis, three years prior to presentation was admitted for dyspnea and fever. Imaging showed bilateral lung infiltrates, concerning for multifocal infection. Considering his imaging findings and elevated Beta D glucan levels, he was empirically started on PJP treatment with atovaquone on day 4 of admission. Bactrim was not used due to acute renal failure. On day 1, calcium was 10 mg/dL (8.4-10.4), which then progressively increased from 10.7mg/dl on day 4 to a peak calcium level of 14.4 mg/dL on day 12. Further work up showed PTH: 4.7 pg/mL (12-88), PTHrP: 0.6 pMol/L (< /= 4.2), Vitamin D 1, 25: 198 pg/mL (18-72), Vitamin D 25: 79 ng/mL (20-100), SPEP: no M spike, UPEP: no M spike but had a lysozyme band suggestive of granulomatous infection, other fungal studies negative, normal thyroid levels, AFB culture negative. On day 12, he was started on prednisone 60mg presuming hypercalcemia from PJP. On day 13, calcium improved to 11.7 mg/ dL, but his renal function worsened requiring hemodialysis (HD). On day 14, he had respiratory failure requiring intubation and underwent bronchio-alveolar lavage (BAL) which was positive for pneumocystis PCR. He was started on bactrim on day 17 and continued on high dose steroid. By day 19, he was extubated, renal function stabilized without HD and calcium normalized to 8.9 mg/dL. Unfortunately, he had gastrointestinal bleed and refused further procedures eventually opting for hospice on day 23. PJP is a common opportunistic infection in immunosuppressed patients like KTR. The advent of prophylaxis has significantly decreased the incidence of PJP in KTR to 0.3%-2.6%. PJP in KTR is sometimes associated with hypercalcemia. Prevalence of hypercalcemia in KTR with PJP is unclear, but as per a hospital based retrospective study (Hamroun et al., 2019), 37% of PJP patients in KTR (18/49) had hypercalcemia that preceded pneumonia/findings on imaging. The proposed mechanism for hypercalcemia is granulomatous in nature, due to increased extra renal production of 1 alpha hydroxylase enzyme from increased macrophage recruitment in lungs to clear pneumocystis organisms. Hypercalcemia resolved after completion of treatment and resolution of PJP. High dose steroids can be used as hypercalcemia is mediated by a granulomatous reaction. It is crucial for physicians to have a high index of suspicion for PJP as the etiology of pneumonia in immunocompromised organ transplant recipients with non- PTH mediated hypercalcemia, thus ensuring timely diagnosis and treatment.

Retrospective analysis of risks and benefits of trimethoprim/sulfamethoxazole as prophylaxis for Pneumocystis jiroveci pneumonia in patients with dermatologic disease

Retrospective analysis of risks and benefits of trimethoprim/sulfamethoxazole as prophylaxis for Pneumocystis jiroveci pneumonia in patients with dermatologic disease

Clinical characteristics and CT findings of Pneumocystis Jirovecii pneumonia in 46 cases with hematological diseases

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.