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BMC Infectious Diseases Oct 2023Pneumocystis jirovecii pneumonia (PCP) and SARS-CoV2 share some similarities in their effects on the respiratory system, clinical presentation, and management. The... (Observational Study)
Observational Study
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) and SARS-CoV2 share some similarities in their effects on the respiratory system, clinical presentation, and management. The COVID-19 pandemic required rapid action to curb transmission and mitigate its lethiferous impact. Non-pharmaceutical interventions (NPIs) were globally adopted. We hypothesized that these measures reduced the transmission and acquisition of P. jirovecii in both hospital and community settings.
METHODS
We conducted a retrospective observational study on 2950 respiratory specimens from patients with suspected pulmonary infection, analyzed at the Laboratory of Parasitology Unit of the Policlinico Tor Vergata of Rome, Italy, from January 2014 to December 2022.
RESULTS
We show a significant reduction in the frequency of PCP in the COVID-19 pandemic era compared to the previous period. Among the four sequence types of P. jirovecii identified, genotype 1 was the most prevalent (37%). We observed a non-significant trend of decreasing cases with genotype 1 and increasing cases with genotype 3 over the study period.
CONCLUSIONS
The nationwide implementation of NPIs against COVID-19 may have changed the microbiological landscape of exposure, thereby decreasing the exposure to P. jirovecii and consequently reducing the incidence of PCP.
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; Pneumocystis carinii; Pandemics; RNA, Viral; COVID-19; SARS-CoV-2
PubMed: 37848811
DOI: 10.1186/s12879-023-08545-w -
Mycoses Jan 2024Pneumocystis jirovecii pneumonia (PJP) is a common and troublesome complication of kidney transplantation. In the era of prophylaxis, the peak incidence of PJP after...
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) is a common and troublesome complication of kidney transplantation. In the era of prophylaxis, the peak incidence of PJP after kidney transplantation and specific characteristics of late-onset PJP have always been debated.
METHODS
We performed a retrospective study by analysing the data of post-transplantation pneumonia in adult kidney transplantation recipients between March 2014 and December 2021 in The Affiliated First Hospital of University of Science and Technology of China (USTC). A total of 361 patients were included and divided into early-onset PJP, late-onset PJP and non-PJP groups. The characteristics of each group and related risk factors for the late-onset patients were investigated.
RESULTS
Some patients developed PJP 9 months later with a second higher occurrence between month 10 and 15 after transplantation. Compared with non-PJP, ABO-incompatible and cytomegalovirus (CMV) viremia were significantly associated with late onset of PJP in multivariate analysis. The use of tacrolimus, CMV viremia, elevated CD8(+) T cell percent and hypoalbuminemia were risk factors for late PJP. Receiver operating characteristic curve analysis demonstrated that a combination of those factors could increase the sensitivity of prediction remarkably, with an area under the curve of 0.82, a sensitivity of 80% and a specificity of 83%.
CONCLUSIONS
PJP could occur months after kidney transplantation. ABO-incompatible transplant recipients are at high risk of PJP. In the later stages of transplantation, CMV viremia, T lymphocyte subsets percentage and serum albumin levels should be monitored in patients using tacrolimus.
Topics: Adult; Humans; Pneumonia, Pneumocystis; Kidney Transplantation; Retrospective Studies; Transplant Recipients; Tacrolimus; Viremia; Pneumocystis carinii; Risk Factors; Cytomegalovirus Infections
PubMed: 38214337
DOI: 10.1111/myc.13688 -
International Journal of Clinical... Nov 2023To investigate drug concentration of trimethoprim-sulfamethoxazole (TMP-SMX) using therapeutic drug monitoring (TDM) for severe (PJP) infection in a critically ill...
Sub-therapeutic trimethoprim and sulfamethoxazole plasma concentrations during continuous venovenous hemofiltration in a patient with COVID-19 and pulmonary co-infection: A case report.
OBJECTIVE
To investigate drug concentration of trimethoprim-sulfamethoxazole (TMP-SMX) using therapeutic drug monitoring (TDM) for severe (PJP) infection in a critically ill patient with COVID-19 receiving continuous venovenous hemofiltration treatment and regional citrate anticoagulation (RCA-CCVH).
MATERIALS AND METHODS
A 72-year-old man with hypoxemic respiratory failure due to COVID-19 infection was admitted to the intensive care unit for invasive mechanical ventilation. The patient developed acute renal failure that required RCA-CVVH. Pulmonary co-infection with PJP was diagnosed, and a high TMP-SMX dose was initiated according to (inter)national guidelines with dose reduction after 3 days because of renal failure. Population pharmacokinetics were assessed for TMP and SMX as well as clearance by RCA-CVVH, volume of distribution, and time above threshold levels for measured plasma concentrations.
RESULTS
During renal failure requiring RCA-CVVH, a corresponding dose reduction of TMP-SMX to 320/1,600 mg twice a day, according to current Dutch SWAB and Dutch Association of Hospital Pharmacists guidelines, resulted in unintended under-dosing with sub-therapeutic TMP-SMX concentrations. Pharmacokinetic modeling and dose adjustment of TMP-SMX to 640/3,200 mg 3 times daily resulted in steady-state TMP-SMX peak concentrations associated with efficacy against PJP. Hence, the patient was successfully weaned from the ventilator and discharged.
CONCLUSION
We hypothesize that our new dose recommendation of 640/3,200 mg TMP-SMX 3 times daily is associated with an increased probability of critical patients being successfully liberated from mechanical weaning following PJP pneumonia and COVID-19 infection.
Topics: Male; Humans; Aged; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; Pneumonia, Pneumocystis; Continuous Renal Replacement Therapy; Coinfection; COVID-19; Renal Insufficiency; Retrospective Studies
PubMed: 37489071
DOI: 10.5414/CP204407 -
BMJ Case Reports Jul 2023pneumonia typically presents with diffuse bilateral infiltrates or ground-glass opacities. However, the radiographic pattern may be atypical. We report a case of a...
pneumonia typically presents with diffuse bilateral infiltrates or ground-glass opacities. However, the radiographic pattern may be atypical. We report a case of a woman in her 40s who presented with multiple pulmonary masses and prolonged symptoms of non-productive cough, generalised weakness and fatigue. Serial chest CT performed prior to her presentation showed a large right lower lobe lung mass with multiple additional bilateral pulmonary nodules. Her workup revealed a new diagnosis of AIDS. Pathology of several CT-guided needle biopsies was consistent with which was confirmed by microbial DNA sequencing. No additional pathogens were identified. Her clinical symptoms and radiographs improved significantly with trimethoprim-sulfamethoxazole and treatment of her HIV infection. Clinicians should evaluate for underlying immunodeficiency and seek infectious disease and pulmonary consultation early for consideration of alternative diagnoses when patients present with cough, dyspnoea and atypical chest radiographs, and initial pathological examination is unrevealing.
Topics: Female; Humans; Pneumonia, Pneumocystis; HIV Infections; Acquired Immunodeficiency Syndrome; Cough; Pneumocystis carinii; Lung
PubMed: 37524509
DOI: 10.1136/bcr-2022-253563 -
Journal of Clinical Microbiology Apr 2024pneumonia (PJP) is a serious and sometimes fatal infection occurring in immunocompromised individuals. High-risk patients include those with low CD4 counts due to human...
UNLABELLED
pneumonia (PJP) is a serious and sometimes fatal infection occurring in immunocompromised individuals. High-risk patients include those with low CD4 counts due to human immunodeficiency virus infection and transplant recipients. The incidence of PJP is increasing, and rapid detection of PJP is needed to effectively target treatment and improve patient outcomes. A common method used is an immunofluorescent assay (IFA), which has limitations, including labor costs, low sensitivity, and requirement for expert interpretation. This study evaluates the performance of the DiaSorin Molecular analyte-specific reagent (ASR) in a laboratory-developed test (LDT) for the direct detection of DNA without prior nucleic acid extraction. Respiratory samples ( = 135) previously tested by IFA from 111 patients were included. Using a composite standard of in-house IFA and reference lab PJP PCR, the percent positive agreement for the LDT using the DiaSorin ASR was 97.8% (90/92). The negative percent agreement was 97.7% (42/43). The lower limit of detection of the assay was determined to be 1,200 copies/mL in bronchoalveolar lavage fluid. Analytical specificity was assessed using cultures of oropharyngeal flora and common respiratory bacterial and fungal pathogens. No cross-reactivity was observed. Our study suggests that the DiaSorin ASR accurately detects DNA and demonstrates improved sensitivity compared to the IFA method.
IMPORTANCE
Our study is unique compared to other previously published studies on the DiaSorin analyte-specific reagent (ASR) because we focused on microbiological diagnostic methods commonly used (immunofluorescent assay) as opposed to pathology findings or reference PCR. In addition, in our materials and methods, we describe the protocol for the use of the DiaSorin ASR as a singleplex assay, which will allow other users to evaluate the ASR for clinical use in their lab.
Topics: Humans; Pneumocystis carinii; Indicators and Reagents; Sensitivity and Specificity; Pneumonia, Pneumocystis; Bronchoalveolar Lavage Fluid; Immunocompromised Host; DNA
PubMed: 38477535
DOI: 10.1128/jcm.00045-24 -
Methods in Molecular Biology (Clifton,... 2024Atovaquone is an FDA-approved antiparasitic and antifungal therapeutic that is currently used as a prophylactic agent to prevent Pneumocystis carinii pneumonia (PCP)...
Atovaquone is an FDA-approved antiparasitic and antifungal therapeutic that is currently used as a prophylactic agent to prevent Pneumocystis carinii pneumonia (PCP) infections in acute myeloid leukemia (AML) patients after receiving hematopoietic stem cell transplantation (HSCT). Recent studies have shown that atovaquone has shown potential as an anticancer agent. The high variability in atovaquone bioavailability prompts the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients. Briefly, an organic-based solvent system is used to precipitate protein and extract the atovaquone content from each patient-derived plasma sample. After completing a second stage of sample dilution (5000-fold overall), a 2 μL volume of the plasma extract is analyzed using the liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based bioanalytical method described.
Topics: Humans; Child; Atovaquone; Pneumonia, Pneumocystis; Tandem Mass Spectrometry; Chromatography, Liquid; Antifungal Agents; Leukemia, Myeloid, Acute; Plant Extracts
PubMed: 38036811
DOI: 10.1007/978-1-0716-3541-4_7 -
Unique presentation of late-onset Pneumocystis pneumonia in a pediatric kidney transplant recipient.Pediatric Transplantation Sep 2023Restrictive lung disease leading to abnormal lung function in kidney transplant recipients is commonly associated with noninfectious complications or medications used...
BACKGROUND
Restrictive lung disease leading to abnormal lung function in kidney transplant recipients is commonly associated with noninfectious complications or medications used for post-transplant immunosuppression. Herein, we report an interesting case of pediatric kidney transplant recipient with weight loss and abnormal spirometry who was diagnosed to have late-onset Pneumocystis pneumonia.
CASE REPORT
A 17-year-old male patient with a history of allergic rhinitis, mild persistent asthma, and deceased donor kidney transplant, performed 18 months prior, presented for routine evaluation of his asthma to the pulmonology clinic. He was clinically asymptomatic except for a weight loss of 8 kg over 6-month period prior to presentation. Patient's spirometry was suggestive of a restrictive pattern and further investigation using a high-resolution computed tomography (HRCT) of the chest showed bilateral diffuse ground-glass reticulonodular opacities with subpleural sparing suggestive of interstitial pneumonitis. A bronchoscopy with bronchoalveolar lavage revealed organisms consistent with Pneumocystis jirovecii on gomori-methenamine-silver (GMS) staining. Beta-d-glucan testing in serum revealed a level of >500 pg/mL (normal 0-59 pg/mL) further supportive of Pneumocystis jirovecii infection. Patient was treated with a 6-week course of trimethoprim-sulfamethoxazole. His weight loss and beta-d-glucan levels improved over a course of 6 months, and he continues to be on trimethoprim-sulfamethoxazole prophylaxis.
CONCLUSION
Late-onset Pneumocystis jirovecii infection in kidney transplant recipients can have an atypical presentation. Treating physicians should consider PJP in the differential diagnosis of unexplained weight loss in pediatric kidney transplant recipients, especially those receiving a large cumulative burden of immunosuppression.
Topics: Male; Humans; Child; Adolescent; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Kidney Transplantation; Pneumocystis carinii; Immunosuppression Therapy
PubMed: 37448256
DOI: 10.1111/petr.14576 -
Zhonghua Yi Xue Za Zhi Jul 2023To evaluate the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of pulmonary infection in immunocompromised patients....
To evaluate the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of pulmonary infection in immunocompromised patients. A total of 78 patients with immunocompromised pulmonary infection [55 males and 23 females, aged (50.3±16.9) years] and 61 patients with non-immunocompromised pulmonary infection [42 males and 19 females, aged (63.6±15.9) years] in the Intensive Care Unit of the First Medical Center of College of the Pulmonary & Critical Care Medicine, Chinese PLA General Hospital from November 2018 to May 2022 were retrospectively selected. Patients in both groups received bronchoalveolar lavage fluid (BALF) mNGS and conventional microbiological tests (CMTs) while clinically diagnosed with pulmonary infection. The diagnostic positive rate, pathogen detection rate and clinical coincidence rate of the two methods were compared. At the same time, the difference of adjustment rate of anti-infective treatment strategy based on the results of mNGS detection was compared between the two groups. The positive rates of mNGS in patients with pulmonary infection were 94.9% (74/78) and 82.0% (50/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of CMTs in patients with pulmonary infection were 64.1% (50/78) and 75.4% (46/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of mNGS and CMTs in patients with pulmonary infection in immunocompromised group showed a statistically significant difference (<0.001). The detection rates of mNGS in the immunocompromised group for pneumocystis jirovecii and cytomegalovirus were 41.0% (32/78) and 37.2% (29/78), respectively, and the detection rates of Klebsiella pneumoniae, chlamydia psittaci and Legionella pneumophila were 16.4% (10/61), 9.8% (6/61) and 8.2% (5/61) in the non-immunocompromised patients, respectively, which were higher than those of CMTs [1.3% (1/78), 7.7% (6/78), 4.9% (3/61), 0 and 0] (all <0.05). In the immunocompromised group, the clinical coincidence rates of mNGS and CMTs and were 89.7% (70/78) and 43.6% (34/78), respectively, with a statistically significant difference (<0.001). In the non-immunocompromised group, the clinical coincidence rates of mNGS and CMTs were 83.6% (51/61) and 62.3% (38/61), with a statistically significant difference (=0.008). In the immunocompromised group, according to the results of the etiology of mNGS, the adjustment rate of anti-infection treatment strategy was 87.2% (68/78), while in the non-immunocompromised group, the adjustment rate of anti-infective treatment strategy was 60.7% (37/61), with a statistically significant difference (<0.001). In patients with immunocompromised pulmonary infection, mNGS has more advantages than CMTs in diagnostic positive rate, diagnosis rate of mixed infection, pathogen detection rate and guidance of anti-infection treatment strategy adjustment, which is worthy of clinical promotion and application.
Topics: Female; Male; Humans; Retrospective Studies; High-Throughput Nucleotide Sequencing; Pneumonia; Pneumocystis carinii; Hospitals, General; Sensitivity and Specificity
PubMed: 37402668
DOI: 10.3760/cma.j.cn112137-20221226-02703 -
Transplant International : Official... 2024pneumonia (PcP) remains life-threatening in kidney transplant recipients (KTR). Our study investigated risk factors one-year before PcP. We conducted a monocentric,...
pneumonia (PcP) remains life-threatening in kidney transplant recipients (KTR). Our study investigated risk factors one-year before PcP. We conducted a monocentric, case-control study including all KTR at the Dijon University Hospital (France) with a diagnosis of PcP between 2005 and 2022 (cases), and matched control KTR with no history of PcP (3 controls/case). Among all 1,135 KTR, 57 cases (5%) and 169 matched-controls were included. PcP was associated with 18% mortality. Compared to controls, cases were older, with a higher immunological risk, and CMV infection was more frequent in the year preceding the occurrence of PcP (23% vs. 4%; < 0.001). As early as 1 year before PcP, lymphocyte counts were lower and serum creatinine levels were higher in cases, but immunosuppressive regimens were not significantly different. Multivariable analysis identified lymphocyte count, serum creatinine level, being treated by immunosuppressive therapy other than anti-rejection drugs, and CMV infection in the year preceding the time PcP as independently associated with the occurrence of PcP. PcP was associated with an increased risk of subsequent chronic rejection (27% vs. 3%; = 0.001) and return to dialysis (20% vs. 3%; = 0.002). The occurrence of CMV infection and a low lymphocyte count could redefine the indications for continuation or reinitiation of anti- prophylaxis.
Topics: Humans; Pneumonia, Pneumocystis; Case-Control Studies; Kidney Transplantation; Pneumocystis carinii; Creatinine; Cytomegalovirus Infections; Risk Factors; Lymphopenia; Thrombocytopenia; Transplant Recipients; Retrospective Studies
PubMed: 38328616
DOI: 10.3389/ti.2024.12192 -
AIDS Research and Therapy Jan 2024Studies on antiretroviral therapy (ART) in children living with HIV (CLHIV) are limited due to the small population and low accession rate of ART.
BACKGROUND
Studies on antiretroviral therapy (ART) in children living with HIV (CLHIV) are limited due to the small population and low accession rate of ART.
METHODS
All 0-14-year-old CLHIV admitted to the Ganzhou Center for Disease Control and Prevention from January 2006 to June 2023 were included retrospectively. The information of treatment regimens, disease progression, and laboratory tests of the patients under ART were used to explore the outcomes and impacts of long-term ART. The normality of all the data was tested by the Shapiro-Wilk test.
RESULTS
From 2006 to 2023, 18 CLHIV were reported in Ganzhou. Among them, 11 received ART and were followed up for 60.0 ± 48.4 months. After receiving ART, the median viral load of them decreased from 89,600 copies/ml to 22 copies/ml (P = 0.007), the median CD4 T cell count increased from 380.7 cells/µL to 661.9 cells/µL (P = 0.028), and the median CD8 T cell count decreased from 1065.8 cells/µL to 983.3 cells/µL (P = 0.584). The laboratory test results regarding liver function, renal function, blood cell count, and glucolipid metabolism tended to be within normal reference ranges, and the mean height-for-age z-score and weight-for-age z-score increased. However, all the three CLHIV who received cotrimoxazole developed pneumocystis carinii pneumonia, upper respiratory infection, skin lesions, bacterial pneumonia and/or thrush; the mean body-mass-index-for-age z-score decreased from 0.52 to -0.63.
CONCLUSION
For CLHIV, ART could effectively inhibit the replication of HIV and improve the immune function of patients. More studies that focus on ART in CLHIV are urgently needed.
Topics: Child; Humans; Infant, Newborn; Infant; Child, Preschool; Adolescent; HIV Infections; Retrospective Studies; Anti-Retroviral Agents; Disease Progression; CD4 Lymphocyte Count; China; Viral Load; Anti-HIV Agents
PubMed: 38297382
DOI: 10.1186/s12981-024-00594-8