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Current Fungal Infection Reports 2023Corticosteroids have a complex relationship with fungal disease - risk for many, benefit for others. This systematic review aims to address the effect of corticosteroids... (Review)
Review
PURPOSE OF REVIEW
Corticosteroids have a complex relationship with fungal disease - risk for many, benefit for others. This systematic review aims to address the effect of corticosteroids on mortality and visual outcome in different fungal diseases.
RECENT FINDINGS
Corticosteroids are a risk factor of aspergillosis for patients who have COVID-19, and they also led to a worse outcome. Similarity, corticosteroids are a risk factor for candidemia and mucormycosis. Some researchers reported that using topical corticosteroid in keratitis was associated with worse visual outcome if fungal keratitis. Some studies showed that corticosteroids are linked to a negative outcome for non-HIV patients with pneumonia (PCP), in contrast to those with HIV and PCP.
SUMMARY
In 59 references, we found that corticosteroid therapy showed a worse clinical outcome in invasive aspergillosis (IA) (HR: 2.50, 95%CI: 1.89-3.31, < 0.001) and chronic pulmonary aspergillosis (CPA) (HR: 2.74, 95%CI: 1.48-5.06, = 0.001), PCP without HIV infection (OR: 1.29, 95%CI: 1.09-1.53, = 0.003), invasive candidiasis and candidaemia (OR: 2.13, 95%CI: 1.85-2.46, < 0.001), mucormycosis (OR: 4.19, 95%CI: 1.74-10.05, = 0.001) and early in the course of fungal keratitis (OR: 2.99, 95%CI: 1.14-7.84, = 0.026). There was equivocal outcome in cryptococcal meningoencephalitis in AIDS and primary coccidioidomycosis, while corticosteroid therapy showed a better outcome in PCP in HIV-infected patients (RR: 0.62, 95%CI: 0.46-0.83, =0.001) and fungal keratitis patients after keratoplasty surgery (OR: 0.01, 95%CI: 0.00-0.41, = 0.041) and probably in cryptococcal meningoencephalitis in non-immunocompromised patients. A sub-analysis in invasive aspergillosis and CPA showed that use of more than 2 mg/kg/day of prednisolone equivalents per day is a significant factor in increasing mortality (HR: 2.94, 95%CI: 2.13-4.05, < 0.001). Corticosteroid therapy during invasive fungal disease was usually associated with a slightly or greatly increased mortality or worse visual outcome (in fungal keratitis), with two disease exceptions. Avoiding the addition of corticosteroids, or minimising dose and duration in those who require them, is likely to improve the outcome of most life- and vision-threatening fungal diseases. This review provides a cornerstone for further research in exploring the accuracy of suitable dose and duration of corticosteroids treatment in fungal diseases.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s12281-023-00456-2.
PubMed: 36852004
DOI: 10.1007/s12281-023-00456-2 -
Frontiers in Endocrinology 2023Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical...
OBJECTIVE
Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical characteristics, risk factors, treatment, and prognosis of TMP-SMX-induced hypoglycemia.
METHODS
Case reports and series of TMP-SMX-induced hypoglycemia were systematically searched using Chinese and English databases. Primary patient and clinical information were extracted for analysis.
RESULTS
A total of 34 patients were reported from 31 studies (16 males and 18 females). The patients had a median age of 64 years (range 0.4-91), and 75.8% had renal dysfunction. The median duration of a hypoglycemic episode was six days (range 1-20), and the median minimum glucose was 28.8 mg/dL (range 12-60). Thirty-two patients (97.0%) showed neuroglycopenic symptoms, with consciousness disturbance (30.3%) and seizure (24.2%), sweating (18.2%), confusion (15.2%), asthenia (12.1%) being the most common symptoms. Fifteen patients (44.1%) had elevated serum insulin levels, with a median of 31.8 μU/mL (range 3-115.3). C-peptide increased in 13 patients (38.2%), with a median of 7.7 ng/mL (range 2.2-20). Complete recovery from symptoms occurred in 88.2% of patients without sequelae. The duration of hypoglycemia symptoms was 8 hours to 47 days after the intervention. Interventions included discontinuation of TMP-SMX, intravenous glucose, glucagon, and octreotide.
CONCLUSION
Hypoglycemia is a rare and serious adverse effect of TMP-SMX. Physicians should be aware of this potential adverse effect, especially in patients with renal insufficiency, increased drug doses, and malnutrition.
Topics: Male; Female; Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Trimethoprim, Sulfamethoxazole Drug Combination; Risk Factors; Hypoglycemia; Renal Insufficiency; Glucose
PubMed: 36843590
DOI: 10.3389/fendo.2023.1059522 -
Tropical Medicine and Infectious Disease Feb 2023pneumonia (PCP) is a leading cause of death among patients with AIDS worldwide, but its burden is difficult to estimate in low- and middle-income countries, including... (Review)
Review
pneumonia (PCP) is a leading cause of death among patients with AIDS worldwide, but its burden is difficult to estimate in low- and middle-income countries, including Ethiopia. This systematic review aimed to estimate the pooled prevalence of PCP in Ethiopia, the second most densely populated African country. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to review published and unpublished studies conducted in Ethiopia. Studies that reported on the prevalence of PCP among HIV-infected patients were searched systematically. Variations between the studies were assessed by using forest plot and I-squared heterogeneity tests. Subgroup and sensitivity analyses were carried out when I2 > 50. The pooled estimate prevalence with 95% CI was computed using a random-effects model of analysis. Thirteen articles, comprising studies of 4847 individuals living with HIV, were included for analysis. The pooled prevalence of PCP was 5.65% (95% CI [3.74-7.56]) with high heterogeneity (I2 = 93.6%, < 0.01). To identify the source of heterogeneity, subgroup analyses were conducted by study design, geographical region, diagnosis methods, and year of publication. PCP prevalence differed significantly when biological diagnostic methods were used (32.25%), in studies published before 2010 (32.51%), in cross-sectional studies (8.08%), and in Addis Ababa (14.05%). PCP prevalence differences of 3.25%, 3.07%, 3.23%, and 2.29% were recorded in studies based on clinical records, published since 2017, follow-up studies, and north-west Ethiopian studies, respectively. The prevalence of PCP is probably underestimated, as the reports were mainly based on clinical records. An expansion of biological diagnostic methods could make it possible to estimate the exact burden of PCP in Ethiopia.
PubMed: 36828530
DOI: 10.3390/tropicalmed8020114 -
Journal of Global Health Feb 2023Knowledge of the risk factors for and causes of treatment failure and mortality in childhood pneumonia is important for prevention, diagnosis, and treatment at an...
BACKGROUND
Knowledge of the risk factors for and causes of treatment failure and mortality in childhood pneumonia is important for prevention, diagnosis, and treatment at an individual and population level. This review aimed to identify the most important risk factors for mortality among children aged under ten years with pneumonia.
METHODS
We systematically searched MEDLINE, EMBASE, and PubMed for observational and interventional studies reporting risk factors for mortality in children (aged two months to nine years) in low- and middle-income countries (LMICs). We screened articles according to specified inclusion and exclusion criteria, assessed risk of bias using the EPHPP framework, and extracted data on demographic, clinical, and laboratory risk factors for death. We synthesized data descriptively and using Forest plots and did not attempt meta-analysis due to the heterogeneity in study design, definitions, and populations.
FINDINGS
We included 143 studies in this review. Hypoxaemia (low blood oxygen level), decreased conscious state, severe acute malnutrition, and the presence of an underlying chronic condition were the risk factors most strongly and consistently associated with increased mortality in children with pneumonia. Additional important clinical factors that were associated with mortality in the majority of studies included particular clinical signs (cyanosis, pallor, tachypnoea, chest indrawing, convulsions, diarrhoea), chronic comorbidities (anaemia, HIV infection, congenital heart disease, heart failure), as well as other non-severe forms of malnutrition. Important demographic factors associated with mortality in the majority of studies included age <12 months and inadequate immunisation. Important laboratory and investigation findings associated with mortality in the majority of studies included: confirmed Pneumocystis jirovecii pneumonia (PJP), consolidation on chest x-ray, pleural effusion on chest x-ray, and leukopenia. Several other demographic, clinical and laboratory findings were associated with mortality less consistently or in a small numbers of studies.
CONCLUSIONS
Risk assessment for children with pneumonia should include routine evaluation for hypoxaemia (pulse oximetry), decreased conscious state (e.g. AVPU), malnutrition (severe, moderate, and stunting), and the presence of an underlying chronic condition as these are strongly and consistently associated with increased mortality. Other potentially useful risk factors include the presence of pallor or anaemia, chest indrawing, young age (<12 months), inadequate immunisation, and leukopenia.
Topics: Humans; Child; Infant; Developing Countries; HIV Infections; Pallor; Pneumonia; Risk Factors; Malnutrition; Hypoxia
PubMed: 36825608
DOI: 10.7189/jogh.13.05003 -
Frontiers in Pharmacology 2022Interstitial lung disease (ILD) is a common pulmonary disease often associated with significant morbidity and mortality in patients with connective tissue diseases...
Interstitial lung disease (ILD) is a common pulmonary disease often associated with significant morbidity and mortality in patients with connective tissue diseases (CTD). Currently, no gold-standard therapies are available for CTD-ILD. Recently, several studies have proposed that rituximab (RTX) may be effective for the treatment of CTD-ILD. This study aimed to systematically evaluate the efficacy and safety of RTX for the treatment of CTD-ILD. Studies were selected from PubMed, Embase, and Cochrane Library, up to 20 July 2022. Improvement and stable rates were extracted as the main outcomes and pooled using the weighted mean proportion with fixed or random-effects models, in case of significant heterogeneity ( > 50%). Safety analysis was performed based on the adverse events reported in all of the studies. Thirteen studies (312 patients) were included in the meta-analysis. The follow-up durations ranged from 6 to 36 months. The pooled improvement rate was 35.0% (95% CI: 0.277-0.442), while the pooled stable rate was 59.2% (95% CI: 0.534-0.656). Anti-synthetase syndrome associated with ILD [ASS-ILD, 48.1% (95% CI, 0.373-0.620)] and idiopathic inflammatory myopathies associated with ILD [IIM-ILD, non-ASS, 47.4% (95% CI, 0.266-0.846)] had higher improvement rates than the other types. A total of 106 adverse events associated with RTX or progressive ILD were reported among the 318 patients, 55.7% of which were mild. Among 19 deaths, 17 were due to ILD progression, one to severe pulmonary arterial hypertension, and one to infection. RTX, which exhibits a satisfactory safety profile, is an effective treatment option for CTD-ILD, even in patients who fail to respond to other therapies. Further randomized trials are needed to assess the efficacy of rituximab compared to other treatments for CTD-ILD. PROSPERO, identifier (CRD42022363403).
PubMed: 36386239
DOI: 10.3389/fphar.2022.1019915 -
RMD Open Nov 2022To conduct a systematic literature review (SLR) on the screening and prophylaxis of opportunistic and chronic infections in autoimmune inflammatory rheumatic diseases... (Review)
Review
Systematic literature review informing the 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases.
OBJECTIVE
To conduct a systematic literature review (SLR) on the screening and prophylaxis of opportunistic and chronic infections in autoimmune inflammatory rheumatic diseases (AIIRD).
METHODS
SLR (inception-12/2021) based on the following search domains: (1) infectious agents, (2) AIIRD, (3) immunosuppressives/immunomodulators used in rheumatology, (4) screening terms and (5) prophylaxis terms. Articles were retrieved having the terms from (1) AND (2) AND (3) plus terms from (4) OR(5). Databases searched: PubMed, Embase and Cochrane Library.
EXCLUSION CRITERIA
studies on postoperative infections, paediatric AIIRD, COVID-19, vaccinations and non-Εnglish literature. Study quality was assessed with Newcastle-Ottawa scale for non-randomised controlled trials (RCTs), RoB-Cochrane for RCTs, AMSTAR2 for SLRs.
RESULTS
From 5641 studies were retrieved, 568 full-text articles were assessed for eligibility, with 194 articles finally included. For tuberculosis, tuberculin skin test (TST) is affected by treatment with glucocorticoids and conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and its performance is inferior to interferon gamma release assay (IGRA). Agreement between TST and IGRA is moderate to low. For hepatitis B virus (HBV): risk of reactivation is increased in patients positive for hepatitis B surface antigen. Anti-HBcore positive patients are at low risk for reactivation but should be monitored periodically with liver function tests and/or HBV-viral load. Risk for Hepatitis C reactivation is existing but low in patients treated with biological DMARDs. For , prophylaxis treatment should be considered in patients treated with prednisolone ≥15-30 mg/day for >2-4 weeks.
CONCLUSIONS
Different screening and prophylaxis approaches are described in the literature, partly determined by individual patient and disease characteristics.
Topics: Adult; Child; Humans; Antirheumatic Agents; COVID-19; Hepatitis B virus; Opportunistic Infections; Rheumatic Diseases
PubMed: 36323488
DOI: 10.1136/rmdopen-2022-002726 -
Pharmacotherapy Nov 2022Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications... (Review)
Review
Patients with inflammatory bowel disease (IBD) are at increased risk of developing Pneumocystis jirovecii pneumonia (PJP) than the general population. Many medications utilized for the treatment of IBD affect the immune system, potentially further increasing the risk of PJP. Recommendations for prophylaxis against PJP in this patient population are based upon limited evidence, and risk factors for PJP development are not well-agreed upon. The purpose of this systematic review was to consolidate and evaluate the evidence for PJP prophylaxis in patients with IBD. An electronic literature search was performed, and 29 studies were included in the review, of which 24 were case reports or case series. Combined data from five cohort studies showed an absolute risk of developing PJP to be 0.07%. The majority of patients who developed PJP were receiving corticosteroids at the time of diagnosis (76%). The number of concomitant immunosuppressants received at time of PJP diagnosis varied from one to four. All studies reporting treatment of PJP utilized sulfamethoxazole-trimethoprim. Of the 27 studies reporting mortality data, 19% of patients died. Given the lack of conclusive data regarding risk factors for PJP development and the overall low incidence of PJP in patients with IBD, it is recommended to assess the patient's risk on a case-by-case basis to determine whether PJP prophylaxis is warranted.
Topics: Humans; Pneumonia, Pneumocystis; Pneumocystis carinii; Trimethoprim, Sulfamethoxazole Drug Combination; Inflammatory Bowel Diseases; Immunosuppressive Agents
PubMed: 36222368
DOI: 10.1002/phar.2733 -
Antibiotics (Basel, Switzerland) May 2022Although combination therapy using trimethoprim-sulfamethoxazole (TMP-SMX) plus echinocandins has been reported to reduce the mortality of patients with pneumocystis...
Efficacy of Trimethoprim-Sulfamethoxazole in Combination with an Echinocandin as a First-Line Treatment Option for Pneumocystis Pneumonia: A Systematic Review and Meta-Analysis.
Although combination therapy using trimethoprim-sulfamethoxazole (TMP-SMX) plus echinocandins has been reported to reduce the mortality of patients with pneumocystis pneumonia (PCP), it remains unclear whether it is more effective than TMP-SMX monotherapy, the current first-line treatment for this disease. Hence, we performed a systematic review and meta-analysis to compare the efficacies of these treatment options for PCP. The Scopus, EMBASE, PubMed, CINAHL, and Ichushi databases were searched for studies (up to January 2022) reporting the mortality and positive response rates (fewer clinical symptoms, improved partial pressure of arterial oxygen, and resolution of pneumonitis on chest imaging) of PCP patients receiving monotherapy or combination therapy. Four studies met the inclusion criteria. All four presented mortality data and one had positive response rates. Compared with the monotherapy, the combination therapy resulted in significantly lower mortality and higher positive response rates (mortality: odds ratio (OR) 2.20, 95% confidence interval (CI) 1.46-3.31; positive response rate: OR 2.13, 95%CI 1.41-3.23), suggesting it to be an effective and promising first-line therapy for PCP. However, further safety evaluations are needed to establish this as a fact.
PubMed: 35740126
DOI: 10.3390/antibiotics11060719 -
Health Science Reports May 2022Bendamustine, a bifunctional mechlorethamine alkylating agent, is used in the treatment of patients with hematologic malignancies. Myelosuppression and cytotoxic effect... (Review)
Review
BACKGROUND
Bendamustine, a bifunctional mechlorethamine alkylating agent, is used in the treatment of patients with hematologic malignancies. Myelosuppression and cytotoxic effect arises quite often after bendamustine treatment. To date, there have been no recommendations for routine chemoprophylaxis for pneumonia (PCP) in patients under treatment with this agent. The present systematic review aimed to evaluate the existing data on bendamustine effects on pneumocystis pneumonia.
METHOD
English papers were systematically reviewed using Web of Science, Embase, Google Scholar, PubMed, and Cochrane library. There was no time constraint for the paper search. The used keywords included "Pneumonia, Pneumocystis"or "Pneumocystis Pneumonia"or "Pneumocystis jirovecii" and "Bendamustine hydrochloride or Bendamustine. "Through our search, 113 papers were found, 26 of which were chosen following a review of the titles and abstracts; ultimately, 10 were included in the research.
RESULT
A total of 10 studies (out of 113 studies) were retrieved. The papers were classified into seven case reports, two clinical trials, and one retrospective analysis study. The case reports included 14 patients diagnosed with PCP after bendamustine administration between 2003 and 2019. The patients' mean age was with a range of 66.8. Non-Hodgkin's lymphoma (including diffuse large B-cell lymphoma and mantle cell lymphoma) ( = 9, 60%), chronic lymphocytic leukemia ( = 4, 26.6%), and breast cancer ( = 2, 13.4%) were the most prevalent types of malignancy. Bendamustine, along with rituximab, were the most commonly prescribed chemotherapy regimens during the treatments. Finally, the mortality rate among the patients whose results were reported ( = 9) was 44.44% ( = 4).
CONCLUSION
The present review described PCP infection in patients with malignancies after the treatment with bendamustine, a chemotherapeutic agent associated with lymphopenia. Further research is required to determine the PCP risk in patients with bendamustine treatment and identify individuals who may benefit from prophylaxis.
PubMed: 35509412
DOI: 10.1002/hsr2.610 -
The Journal of International Medical... Mar 2022The aim of this study was to describe the clinical characteristics and prognostic factors of patients treated with rituximab (RTX) who developed severe pneumonia in the...
OBJECTIVE
The aim of this study was to describe the clinical characteristics and prognostic factors of patients treated with rituximab (RTX) who developed severe pneumonia in the intensive care unit (ICU).
METHODS
We systematically reviewed the medical records of 40 patients who received RTX and developed severe pneumonia in the ICU at our hospital from January 2009 to January 2019 to evaluate the underlying conditions, clinical course, and possible prognostic factors.
RESULTS
Most patients had underlying hematologic malignancies (n = 21, 52.5%), followed by rheumatologic diseases (n = 17, 42.5%). The most frequent causative pathogens were fungi (n = 11, 27.5%), followed by bacteria (n = 9, 22.5%) and pneumonia (n = 8, 20%). Thirty patients (75%) died, and the other 10 patients (25%) survived. Compared with survivors, patients who died were significantly older (60.6 ± 10.6 vs 44.4 ± 18.3 years) and had chronic lung disease (40% vs 0%).
CONCLUSION
Older age and chronic lung disease were significantly associated with mortality in patients treated with RTX.
Topics: Humans; Intensive Care Units; Pneumonia, Pneumocystis; Prognosis; Retrospective Studies; Rituximab
PubMed: 35350908
DOI: 10.1177/03000605211063281