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Cureus Mar 2022pneumonia (PCP) is an opportunistic fungal infection associated with human immunodeficiency virus (HIV) infection as an acquired immunodeficiency syndrome...
pneumonia (PCP) is an opportunistic fungal infection associated with human immunodeficiency virus (HIV) infection as an acquired immunodeficiency syndrome (AIDS)-defining illness. The PCP incidence in patients with HIV has declined over the last few decades due to effective antiretroviral therapy and prophylaxis. The PCP incidence in HIV-negative patients has increased due to the increasing use of a wide array of immunosuppressants in cancer and autoimmune disease. PCP clinical course varies from patients with HIV in their clinical features, the severity of clinical presentation, and mortality. PCP in autoimmune diseases is rare, especially in rheumatoid arthritis (RA) in the United States of America (USA). Here, we describe an elderly Caucasian female with rheumatoid arthritis and left lung mucinous adenocarcinoma status post recent resection with no chemotherapy on a low dose of methotrexate (MTX) and prednisone presenting with acute hypoxic respiratory failure due to PCP from absolute lymphopenia.
PubMed: 35371839
DOI: 10.7759/cureus.22768 -
Clinical Rheumatology Sep 2020Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid... (Review)
Review
Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition.
Topics: Aged; Anti-Bacterial Agents; Antifungal Agents; Antirheumatic Agents; Antiviral Agents; Arthritis, Rheumatoid; Aspergillosis; Aspergillus fumigatus; Betacoronavirus; COVID-19; Coronavirus Infections; Cough; Cytokine Release Syndrome; Deprescriptions; Disease Progression; Dyspnea; Female; Glucocorticoids; Humans; Hydroxychloroquine; Immunocompromised Host; Immunosuppressive Agents; Interleukin-6; Leflunomide; Lung; Lymphohistiocytosis, Hemophagocytic; Methylprednisolone; Oxygen Inhalation Therapy; Pandemics; Pneumocystis carinii; Pneumonia, Pneumocystis; Pneumonia, Viral; Pulmonary Aspergillosis; Recurrence; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 32562070
DOI: 10.1007/s10067-020-05234-w -
Medicine Jan 2021Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junctions that leads to fluctuating weakness and disabling fatigability. Due to difficulty in...
RATIONALE
Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junctions that leads to fluctuating weakness and disabling fatigability. Due to difficulty in breathing caused by weakness of the respiratory muscles, patients with MG are more susceptible to pneumonia and other respiratory infections. As many patients with MG are given immunosuppressive therapy, this makes them more prone to infections. However, coinfection with 3 pathogens is very rare.
PATIENT CONCERNS
Here, we report the case of a 41-year-old gentleman with MG who was receiving long-term steroid therapy. He presented with a cough with pale brown expectoration that occurred without obvious inducement, severe pain in the scapula, as well as swelling and weakness of both legs. Despite undergoing treatment, but his symptoms did not improve, prompting two additional hospital admissions over a period of several months.
DIAGNOSIS
Bronchoscopy and bronchoalveolar lavage (BAL) were performed, revealing the presence of Pneumocystis jirovecii , Nocardia brasiliensis, and Mycobacterium tuberculosis (MTB). N brasiliensis was identified by positive modified acid-fast Kinyoun staining as well as a positive colony culture identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry from the BAL sample. MTB was confirmed using GeneXpert, and due to the limitations of the culture conditions, methenamine silver stain was used to confirm Pneumocystis jirovecii. Next-generation sequencing (NGS) assay of the BAL samples also confirmed these pathogens.
INTERVENTIONS
The patient was transferred to a designated tuberculosis hospital and received anti-infective and anti-TB treatment.
OUTCOMES
During treatment at the designated hospital, the patient developed gastrointestinal bleeding and impaired liver function. One month later, he developed multiple organ failure, consolidation of the left lower lung, and pan-drug resistant bacteremia. He refused further treatment and was discharged.
CONCLUSION
In conclusion, physicians should be aware of the predisposition of MG patients to co-infections, especially patients with metabolic disorders, to avoid inadequate treatment and poor patient outcomes. Due to the limitations of culture conditions, NGS should be considered as a new technique for identifying pathogens.
Topics: Adult; Bronchoalveolar Lavage Fluid; Coinfection; Diagnosis, Differential; Humans; Male; Myasthenia Gravis; Mycobacterium tuberculosis; Nocardia; Pneumocystis carinii; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Tuberculosis, Pulmonary
PubMed: 33429828
DOI: 10.1097/MD.0000000000024245 -
Antimicrobial Agents and Chemotherapy Oct 2019
Topics: Caspofungin; Catalytic Domain; Glucosyltransferases; Humans; Mutagenesis, Site-Directed; Pneumocystis carinii; Pneumonia, Pneumocystis
PubMed: 31548211
DOI: 10.1128/AAC.01320-19 -
Journal de Mycologie Medicale Mar 2023To analyze clinical characteristics and risk factors for in-hospital mortality in patients coinfected with P. jirovecii and Aspergillus.
OBJECTIVE
To analyze clinical characteristics and risk factors for in-hospital mortality in patients coinfected with P. jirovecii and Aspergillus.
METHODS
This study included 53 patients with coinfection of P. jirovecii pneumonia (PJP) and invasive pulmonary aspergillosis (IPA) in our center from January 2011 to December 2021. All cases were divided into survivor (n=27) and non-survivor groups (n=26). Medical records, laboratory and radiology data were collected. Risk factors for in-hospital mortality were identified by multivariable analyses.
RESULTS
HIV-positive patients accounted for 3.8%. Fever (77.4%), dyspnea (69.8%) and wet cough (24.5%) were common symptoms. Ground-glass opacity (83.0%), consolidation (71.7%), septal thickening (66.0%), and nodules (54.7%) were the most common radiological signs. CD4+ T cell count and serum albumin (ALB) level were significantly lower in non-survival group than in the survival group. Conversely, serum lactate dehydrogenase (LDH) and procalcitonin (PCT) levels were higher in non-survival group than in survival group. Lactic acidosis [odds ratio (OR): 33.999,95% confidential interval (CI): 3.112-371.409; p=0.004], low CD4+ T cell count (<114 cell/µL) [OR: 19.343, 95% CI: 1.533-259.380; p=0.022] and high level of LDH (> 519 U/L) [OR: 11.422, 95% CI: 1.271-102.669; p=0.030] were independent risk factors for mortality.
CONCLUSION
PJP coinfected with IPA incurs high mortality with nonspecific clinical characteristics and is more likely to involve HIV-negative patients. Lactic acidosis, low CD4+ T cell count and high LDH level are independent risk factors for mortality, close monitoring of these parameters is necessary to help distinguish high-risk patients and make appropriate clinical decisions.
Topics: Humans; Pneumocystis carinii; Coinfection; Hospital Mortality; Acidosis, Lactic; HIV Infections; Risk Factors; Pneumonia, Pneumocystis; Aspergillus; Invasive Pulmonary Aspergillosis; Retrospective Studies
PubMed: 36265259
DOI: 10.1016/j.mycmed.2022.101330 -
Annals of Clinical Microbiology and... Jan 2024Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary...
BACKGROUND
Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.
METHODS
Our main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.
RESULTS
One hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection.
CONCLUSION
Our results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.
Topics: Humans; Pneumocystis carinii; Retrospective Studies; Pneumonia, Pneumocystis; Coinfection; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Herpesviridae; Cytomegalovirus Infections
PubMed: 38245721
DOI: 10.1186/s12941-023-00663-2 -
Infection and Drug Resistance 2023We report a case of pneumocystis jiroveci pneumonia (PJP) in a 46-year-old woman, who previously underwent kidney transplant for chronic renal failure. She did not...
Case Report: Comprehensive Management of Pneumocystis Jiroveci Pneumonia (PJP) and Secondary Infections of Multiple-Drug Resistant and in a Kidney Transplant Recipient with Sulfonamide Allergies.
We report a case of pneumocystis jiroveci pneumonia (PJP) in a 46-year-old woman, who previously underwent kidney transplant for chronic renal failure. She did not receive PJP prophylaxis treatment for the history of sulfonamide allergies. Four months after renal transplantation, the patient had cough, chest tightness, and shortness of breath. Procalcitonin (PCT) (0.06 ng/mL) and C-reactive protein (CRP) (5.33 mg/L) were normal, but the level of 1, 3-β-D-glucan test (G test, 193.89 pg/mL) were elevated. Metagenomics next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) rapidly and accurately identified . Through sulfonamide desensitization and sulfamethoxazole-trimethoprim (TMP-SMX) combined with caspofungin (CAS) treatment, PJP was controlled. However, the patients' conditions were worsen for the hospital-acquired secondary pulmonary infection. A second BALF mNGS identified and carrying carbapenem drug resistance genes, which were confirmed by subsequent culture and antimicrobial susceptibility test within 3 days. Finally, symptoms, such as chest tightness, cough, and shortness of breath, were improved and she was discharged after combined treatment with meropenem (MEM), polymyxin B (PMB), CAS, and TMP-SMX. In this case, mNGS, culture, and drug susceptibility testing were combined to monitor pathogenic microbial and adjust medication. At present, there are no case reports of mNGS use and sulfonamide desensitization in a kidney transplant recipient with sulfonamide allergies.
PubMed: 37724091
DOI: 10.2147/IDR.S428890 -
Frontiers in Microbiology 2022Infection is a severe complication of allo-HSCT in children, however, the accurate detection of the infection is hard. In this study, we traced the records of 101...
Metagenomic Next-Generation Sequencing vs. Traditional Pathogen Detection in the Diagnosis of Infection After Allogeneic Hematopoietic Stem Cell Transplantation in Children.
Infection is a severe complication of allo-HSCT in children, however, the accurate detection of the infection is hard. In this study, we traced the records of 101 pediatric recipients with allo-HSCT to investigate the pathogens of infection, and collected 54 bronchoalveolar lavage fluid, 32 blood, and 15 cerebrospinal fluid samples. In these samples, 87 was with post-transplant infection and 14 without infection. Using the metagenomic next-generation sequencing (mNGS) and traditional pathogen detection, we compared their sensitivity and specificity to detect pathogens of infection. Our results showed that mNGS was more sensitive (89.7%) than conventional pathogen detection (21.8%), with a difference of 67.9% ( < 0.001), However, mNGS was less specific (78.5%) than traditional methods (92.9%), with a difference of 14.4% ( = 0.596). The sensitivity of mNGS for diagnosing pulmonary infections, bloodstream infections or viremia, and CNS infections post-transplant were 91.7, 85.7, and 90.9%, respectively. In contrast, the sensitivity of conventional testing for diagnosing pulmonary infections, bloodstream infections or viremia, and CNS infections post-transplant were 22.9, 21.4, and 18.2%, respectively. There were significant differences in the sensitivity of mNGS and conventional testing in BALF, blood, and CSF samples, with values of 0.000, 0.000, and 0.002 respectively. Among the patients with pulmonary infection, 11 pathogens were both identified by mNGS and conventional testing, and 33 by mNGS only. The percentage with the mNGS-positive result was 44/48 (91.7%), including viruses ( = 12), bacteria ( = 17), fungi ( = 9) and mixed infections ( = 6). Among the patients diagnosed with fungal pneumonia ( = 9), the most prevalent pathogenic fungi were ( = 6), which were also detected in 4 patients with mixed infectious pneumonia. In the 28 blood specimens of patients with bloodstream infections or viremia, five patients were positive by both mNGS and conventional testing, 19 were positive by mNGS, and 1 was positive by traditional testing only. The percentage with the mNGS-positive results was 24/28 (85.7%), including viruses ( = 12), bacteria ( = 4), fungi ( = 3), and mixed infections ( = 5). Of the 15 CSF specimens enrolled, 11 patients were eventually diagnosed with CNS infections. Ten pathogens were identified by mNGS in the 11 patients, including viruses ( = 8), bacteria ( = 1), and fungi ( = 1). These results suggest that mNGS is more sensitive than conventional pathogen detection for diagnosing infections post HSCT in children which may help the clinic diagnosis. was the most frequent pathogen of pulmonary infections post-transplant, while viruses were the most common pathogens of CNS infections in allo-HSCT recipients.
PubMed: 35509305
DOI: 10.3389/fmicb.2022.868160 -
Medicine Feb 2023Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human... (Review)
Review
RATIONALE
Pneumocystis pneumonia (PCP) is an opportunistic infection of patients with congenital or acquired immunodeficiency. It is most frequently occurred in human immunodeficiency virus (HIV) infection, organ transplantation, leukemia, and immunosuppressive therapy. Here we describe the rare case of PCP in a non-HIV-infected diabetic patient and find possible reasons for the association through a literature review.
PATIENT CONCERNS
A 65-years-old male was admitted to our hospital due to a 10-year history of abnormal blood glucose levels and edema of both lower extremities for half a month. However, the patient developed a high fever and progressive dyspnea during hospitalization.
DIAGNOSES
The patient had elevated blood sugar levels, a low white blood cell count within normal limits, and severe lymphopenia. His blood G test and lactate dehydrogenase levels increased significantly. Multiple sputa and bronchoalveolar lavage fluid specimens for Pneumocystis jirovecii (PJ) nucleic acid detection were positive. Chest computed tomography scan demonstrated hazy patchy shadows in the lungs suspected to be pulmonary infections. No tumor, transplantation, or an autoimmune disease was found in the examinations. The patient was diagnosed with PCP finally.
INTERVENTIONS
A combination of oral trimethoprim-sulfamethoxazole and intravenous caspofungin was administered immediately against PJ. The patient was also treated with noninvasive ventilator-assisted ventilation, subcutaneous insulin, and hemodialysis therapy.
OUTCOMES
The patient was discharged home finally with a fair general condition and was followed up without respiratory symptoms.
LESSONS
The compromised immunity in HIV-negative patients with diabetes may be related to lymphocyte decrease and dysfunction, which may cause diabetic patients prone to PJ. Although PCP is rare in diabetes, it should be paid attention to the high rate of misdiagnosis and missed diagnosis.
Topics: Humans; Male; Aged; Pneumonia, Pneumocystis; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; HIV Infections; Diabetes Mellitus
PubMed: 36749248
DOI: 10.1097/MD.0000000000032290 -
Pharmaceutics Apr 2021Invasive Pulmonary Aspergillosis (IPA) and Pneumonia (PCP) are serious fungal pulmonary diseases for immunocompromised patients. The brand name drug CANCIDAS...
Invasive Pulmonary Aspergillosis (IPA) and Pneumonia (PCP) are serious fungal pulmonary diseases for immunocompromised patients. The brand name drug CANCIDAS (Caspofungin acetate for injection) is FDA approved to treat IPA, but is only 40% effective. Efficacious drug levels at the lung infection site are not achieved by systemic administration. Increasing the dose leads to toxicity. The objective, here, is to reformulate caspofungin for aerosolization to high drug concentration by lung targeted delivery and avoid systemic distribution. Described in this paper is a new, room temperature-stable formulation that meets these goals. The in vitro antifungal activity, solid state and reconstituted stability, and aerosol properties of the new formulation are presented. In addition, pharmacokinetic parameters and tissue distribution data are determined from nose-only inhalation studies in rats. Plasma and tissue samples were analyzed by High Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC-MS-MS). Inhaled drug concentrations for caspofungin Active Pharmaceutical Ingredient (API), and the new formulation, were compared at the same dose. In the lungs, the parameters C and Area Under Curve (AUC) showed a 70%, and 60%, respective increase in drug deposition for the new formulation without significant systemic distribution. Moreover, the calculated pharmacodynamic indices suggest an improvement in efficacy. These findings warrant further animal toxicology studies and human clinical trials, with inhaled caspofungin, for treating IPA.
PubMed: 33916988
DOI: 10.3390/pharmaceutics13040504