Pneumocystis jirovecii: a review with a focus on prevention and treatment

Weyant, Robert B.; Kabbani, Dima; Doucette, Karen; Lau, Cecilia; Cervera, Carlos

doi:10.1080/14656566.2021.1915989

Cited by 59 publications

(42 citation statements)

References 114 publications

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“…After the 12th day of hospitalization, the patient recovered, which can be attributed to the following factors: There are three options to treat PCP: co-trimoxazole, clindamycin-primaquine, and pentamidine ( 14 ). Interestingly, the patient showed hypersensitivity to the first two, and pentamidine was not available.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Pneumonia in a Patient With Combined Variable Immunodeficiency: COVID-19 or Pneumocystis Pneumonia?

et al. 2022

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Combined variable immunodeficiency (CVID) is a primary immunodeficiency, characterized by impairment in immune system function. These patients are susceptible to opportunistic infections, which may mimic COVID-19 manifestations. Also, misdiagnosis or delayed diagnosis of opportunistic infections can lead to perilous consequences. We report a 28-year-old woman with a history of combined variable immunodeficiency disorder (CVID) and ulcerative colitis (UC) complained of fever, cough, and dyspnea. According to the clinical and radiological manifestations and the COVID-19 epidemic, she was admitted with a primary diagnosis of COVID-19 pneumonia. After a week, the patient did not respond to treatment, so she underwent bronchoscopy. Using polymerase chain reaction (PCR) methodology, we detected DNA of Pneumocystis jirovecii, the causative agent of a life-threatening pneumonia (PCP), in respiratory specimens. The patient was hypersensitive to common PCP treatments, so she was treated with high-dose clindamycin. However, the patient's clinical condition aggravated. Besides, we found evidence of pneumothorax, pneumomediastinum, and pneumopericardium in chest CT scan. We inserted a catheter for the patient to evacuate the air inside the mediastinum. Also, we added caspofungin to the treatment. The patient eventually recovered and was discharged from the hospital about a week later. Thus, during the COVID-19 epidemic, in febrile patients with respiratory symptoms, physicians should not think only of COVID-19. They must consider opportunistic infections such as PCP, especially in immunocompromised patients.

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Section: Discussionmentioning

confidence: 99%

Case Report: Pneumonia in a Patient With Combined Variable Immunodeficiency: COVID-19 or Pneumocystis Pneumonia?

et al. 2022

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“…In non-HIV patients, data on adjuvant corticosteroids is less clear and no consensus has been determined. Although corticosteroids may be beneficial to patients in these settings, there are still both short-term (co-infections, hyperglycemia) and long-term (myopathy and osteoporosis) factors that need to be considered [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Preclinical and Toxicology Studies of BRD5529, a Selective Inhibitor of CARD9

et al. 2022

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Background The caspase recruitment domain-containing protein 9 (CARD9) inhibitor BRD5529 has been shown to be an effective in vitro inhibitor of Pneumocystis β-glucan-induced proinflammatory signaling, suggesting its viability as a candidate for preliminary anti- Pneumocystis drug testing in the rodent Pneumocystis pneumonia (PCP) model. Methods Mice were injected intraperitoneally (IP) daily with either vehicle or BRD5529 at 0.1 or 1.0 mg/kg for 2 weeks. Mouse weights were taken daily. At day 14, mice were euthanized, weighed, and analyzed by flexiVent™ for lung stiffness. Lungs, liver, and kidney were then harvested for hematoxylin and eosin (H&E) staining and pathology scoring. Lung samples were further analyzed for proinflammatory cytokines via enzyme-linked immunosorbent assay (ELISA) and extracellular matrix generation via quantitative polymerase chain reaction (qPCR). Blood collection postmortem was performed for blood chemistry analysis. Furthermore, administration of BRD5529 prior to the intratracheal inoculation of fungal β-glucans, which are known proinflammatory mediators via the Dectin-1-CARD9 pathway, resulted in significant reductions in lung tissue interleukin-6 and tumor necrosis factor-α, suggesting the exciting possibility of the use of this CARD9 inhibitor as an additional therapeutic tool in fungal infections. Results BRD5529 at both IP doses resulted in no significant changes in daily or final weight gain, and analysis of lung stiffness by flexiVent™ showed no significant differences between the groups. Furthermore, ELISA results of proinflammatory cytokines showed no major differences in the respective groups. qPCR analysis of extracellular matrix transcripts were statistically similar. Examination and pathology scoring of H&E slides from lung, liver, and kidney in all groups, as well as subsequent pathology scoring, showed no significant change. Blood chemistry analysis revealed similar, non-significant patterns. Conclusions In our initial general safety and toxicology assessments, BRD5529 displayed no inherent safety concerns in the analyzed parameters. These data support broader in vivo testing of the inhibitor as a timed adjunct therapy to the deleterious proinflammatory host immune response often associated with anti- Pneumocystis therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s40268-022-00389-0.

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“…Nowadays it is used in a fixed-dose combination with Proguanil (Malarone) for the treatment of uncomplicated malaria or for prophylaxis in travelers [ 143 ]. It is also indicated for the treatment of severe pneumonia due to Pneumocystis jirovecii in immunocompromised patients [ 144 ]. In silico molecular docking studies have identified different proteins of SARS-CoV-2: the main protease [ 145 ], the B chain of the RBM [ 146 ], the NTD of the N protein [ 147 ] and the papain-like proteinase [ 148 ] as the most promising targets showing the lowest binding energies with atovaquone.…”

Section: Antimalarial Drugsmentioning

confidence: 99%

Antiparasitic Drugs against SARS-CoV-2: A Comprehensive Literature Survey

et al. 2022

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More than two years have passed since the viral outbreak that led to the novel infectious respiratory disease COVID-19, caused by the SARS-CoV-2 coronavirus. Since then, the urgency for effective treatments resulted in unprecedented efforts to develop new vaccines and to accelerate the drug discovery pipeline, mainly through the repurposing of well-known compounds with broad antiviral effects. In particular, antiparasitic drugs historically used against human infections due to protozoa or helminth parasites have entered the main stage as a miracle cure in the fight against SARS-CoV-2. Despite having demonstrated promising anti-SARS-CoV-2 activities in vitro, conflicting results have made their translation into clinical practice more difficult than expected. Since many studies involving antiparasitic drugs are currently under investigation, the window of opportunity might be not closed yet. Here, we will review the (controversial) journey of these old antiparasitic drugs to combat the human infection caused by the novel coronavirus SARS-CoV-2.

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Pneumocystis jirovecii: a review with a focus on prevention and treatment

Cited by 59 publications

References 114 publications

Case Report: Pneumonia in a Patient With Combined Variable Immunodeficiency: COVID-19 or Pneumocystis Pneumonia?

Case Report: Pneumonia in a Patient With Combined Variable Immunodeficiency: COVID-19 or Pneumocystis Pneumonia?

Preclinical and Toxicology Studies of BRD5529, a Selective Inhibitor of CARD9

Antiparasitic Drugs against SARS-CoV-2: A Comprehensive Literature Survey

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