Early use of corticosteroids in infants with a clinical diagnosis of <i>Pneumocystis jiroveci</i> pneumonia in Malawi: a double-blind, randomised clinical trial

Newberry, Laura; O’Hare, Bernadette Ann-Marie; Selman, Andrew; Omar, Sofia; Dawson, Pamela; Stevenson, Kim; Nishihara, Yo; Lissauer, Samantha; Molyneux, Elizabeth

doi:10.1080/20469047.2016.1260891

Cited by 18 publications

(10 citation statements)

References 16 publications

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“…A recently published double-blind placebo-controlled trial performed in Malawi investigated whether early adjuvant prednisolone within 48 hours in addition to standard TMP-SMX treatment in HIV-exposed infants (including HIV exposed infected and HIV-exposed uninfected infants) with clinically diagnosed PCP in a setting where co-infection with CMV and other pathogens could not be excluded, reduces mortality. The infants receiving corticosteroids showed a statistically significant reduction in mortality in hospital and 6 months after hospital discharge [92].…”

Section: Pneumocystis Pneumoniamentioning

confidence: 86%

Current antimicrobial management of community-acquired pneumonia in HIV-infected children

Nuttall

2019

Expert Opinion on Pharmacotherapy

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Introduction: Community-acquired pneumonia is a leading cause of morbidity and mortality amongst HIV-infected infants and children. Polymicrobial infection is common and, due to the difficulties in confirming the etiology of pneumonia, empiric broad-spectrum antimicrobial therapy is frequently used. Areas covered: The author based this article on literature identified from PubMed. The author's search terms included: pneumonia, community-acquired pneumonia, HIV, children. The articles reviewed included original studies, recent review articles and current guidelines on the management of pneumonia in HIV-infected children. The microbiological etiology and the empiric and pathogen-specific antimicrobial therapy of community-acquired pneumonia in HIV-infected and HIV-exposed infants and children are also discussed. Expert opinion: There are many changing epidemiological factors impacting antimicrobial management of community-acquired pneumonia in the context of HIV infection in infants and children. These include vaccination strategies, antimicrobial prophylaxis, emerging drug-resistant pathogens, and recognition of the importance of viruses and tuberculosis in the etiology of community-acquired pneumonia. Further research is needed on optimal amtimicrobial management strategies in HIVexposed uninfected children, and HIV-infected children receiving antiretroviral therapy.

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Section: Pneumocystis Pneumoniamentioning

confidence: 86%

Current antimicrobial management of community-acquired pneumonia in HIV-infected children

Nuttall

2019

Expert Opinion on Pharmacotherapy

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“…Glucocorticoids can be added to HIV-induced PCP. Prophylactic treatment is recommended for immunocompromised patients, such as those taking glucocorticoids, bone marrow suppressive therapies, or antineoplastic therapies [10]. The patient outcome depends on age, comorbidities, degree of hypoxia at presentation, other opportunistic infections, and low CD4+ count, resulting in poor outcome and mortality.…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Pneumocystis Pneumonia in HIV Patient on Glucocorticoid

Rehman¹,

Farhan

Shahnawaz

et al. 2021

Cureus

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Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis jirovecii. PCP due to immunosuppressive drugs is rarely reported in the literature. Herein we present a case of PCP in a 49-yearold patient who presented with progressive shortness of breath, dry cough, and low-grade fever. History revealed that he was taking prednisolone daily for his hyperactive airway disease. His temperature was 99 o F, and he had bilateral crackles in the lungs with resonant wheezing. High-resolution computed tomography showed diffuse ground-glass haze and cystic lesions in the middle and upper zones of both lungs. He was commenced on intravenous ceftriaxone and methylprednisolone based on provisional diagnosis of interstitial pneumonia. However, his condition worsened. His human immunodeficiency virus (HIV) test was reactive, and his CD4+ count was 275 cells/mm 3 . Bronchoalveolar lavage revealed PCP by direct immunofluorescent assay. Additional serum testing revealed marked elevation of beta-D-glucan, consistent with PCP diagnosis due to glucocorticoid use. Trimethoprim-sulfamethoxazole and voriconazole were initiated, and his respiratory symptoms started improving. His respiratory condition improved on day 9, and he was discharged with follow-up.

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“…Despite signi cant progress, due to the Prevention of Mother-To-Child-Transmission (PMTCT) programs (estimated to have reduced by 66% reduction of perinatal HIV in this area), the number of children becoming newly infected with HIV remains unacceptably high (around 150,000) in sub-Saharan Africa. 27 The trial sites have been selected to provide a high number of infants with HIV infection with severe pneumonia in regions where TB rates are extremely high. Moreover, the selected sites have conducted previous studies of high public health relevance in the African continent: Mozambique, Malawi, Zambia, Zimbabwe, Uganda and Ivory Coast.…”

Section: Study Setting {9}mentioning

confidence: 99%

Empirical Treatment Against Cytomegalovirus and Tuberculosis in HIV-Infected Infants with Severe Pneumonia: Study Protocol for a Multicenter, an Open-Label Randomized Controlled Clinical Trial

Tagarro

Moraleda

Domínguez

et al. 2021

Preprint

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Background Pneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35-40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB) remain under-recognized and under-treated.The immune response elicited by CMV may be associated with the risk of developing TB and TB disease progression, and CMV may accelerate disease caused both by HIV and TB. Minimally invasive autopsies confirm that CMV and TB are unrecognized causes of death in children wit HIV. CMV and TB may also co-infect the same child. The aim of this study is to compare the impact on 15-day and 1-year mortality of empirical treatment against TB and CMV plus standard of care (SoC) versus SoC in HIV-infected infants with severe pneumonia. Methods This is a Phase II-III, open-label randomized factorial (2x2) clinical trial, conducted in six African countries. The trial has four arms. Infants from 28 to 365 days of age HIV-infected and hospitalized with severe pneumonia will be randomized (1:1:1:1) to i) SoC, ii) valganciclovir iii) TB-T and iv) TB-T plus valganciclovir. The primary endpoint of the study is all-cause mortality, focusing on the short term (up to 15-days) and long-term (up to 1-year) mortality. Secondary endpoints include repeat hospitalization, duration of oxygen therapy during initial admission, severe and notable adverse events, adverse reactions, CMV and TB prevalence at enrolment, TB incidence, CMV viral load reduction, and evaluation of diagnostic tests such as GeneXpert Ultra on fecal and nasopharyngeal aspirate samples and urine TB-LAM.Discussion Given the challenges in diagnosing CMV and TB in children and results from previous autopsy studies that show high rates of poly-infection in HIV-infected infants with respiratory disease, , this study aims to evaluate a new approach including empirical treatment of CMV and TB for this patient population. The potential downsides of empirical treatment of these conditions including toxicity, and medication interactions, which will be evaluated with pharmacokinetics substudies. Trial Registration: ClinicalTrials.gov, NCT03915366, Universal Trial Number U111-1231-4736, Pan African Clinical Trial Registry PACTR201994797961340.

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Early use of corticosteroids in infants with a clinical diagnosis of Pneumocystis jiroveci pneumonia in Malawi: a double-blind, randomised clinical trial

Cited by 18 publications

References 16 publications

Current antimicrobial management of community-acquired pneumonia in HIV-infected children

Current antimicrobial management of community-acquired pneumonia in HIV-infected children

A Rare Case of Pneumocystis Pneumonia in HIV Patient on Glucocorticoid

Empirical Treatment Against Cytomegalovirus and Tuberculosis in HIV-Infected Infants with Severe Pneumonia: Study Protocol for a Multicenter, an Open-Label Randomized Controlled Clinical Trial

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