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Journal For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can...
Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient's immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend-as first line treatment-(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.
Topics: Humans; Abatacept; Adrenal Cortex Hormones; Colitis; Hepatitis; Immunoglobulins, Intravenous; Infliximab; Mycophenolic Acid; Myocarditis; Neoplasms; Nitriles; Pneumonia; Pyrazoles; Pyrimidines
PubMed: 38233099
DOI: 10.1136/jitc-2023-007409 -
Environmental Research Apr 2024The Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) have effectively kept lower antibiotic-resistant bacterial (ARB) pathogen rates than many other... (Review)
Review
The Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) have effectively kept lower antibiotic-resistant bacterial (ARB) pathogen rates than many other countries. However, in recent years, these five countries have encountered a rise in ARB cases and challenges in treating infections due to the growing prevalence of ARB pathogens. Wastewater-based surveillance (WBS) is a valuable supplement to clinical methods for ARB surveillance, but there is a lack of comprehensive understanding of WBS application for ARB in the Nordic countries. This review aims to compile the latest state-of-the-art developments in WBS for ARB monitoring in the Nordic countries and compare them with clinical surveillance practices. After reviewing 1480 papers from the primary search, 54 were found relevant, and 15 additional WBS-related papers were included. Among 69 studies analyzed, 42 dedicated clinical epidemiology, while 27 focused on wastewater monitoring. The PRISMA review of the literature revealed that Nordic countries focus on four major WBS objectives of ARB: assessing ARB in the human population, identifying ARB evading wastewater treatment, quantifying removal rates, and evaluating potential ARB evolution during the treatment process. In both clinical and wastewater contexts, the most studied targets were pathogens producing carbapenemase and extended-spectrum beta-lactamase (ESBL), primarily Escherichia coli and Klebsiella spp. However, vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) have received more attention in clinical epidemiology than in wastewater studies, probably due to their lower detection rates in wastewater. Clinical surveillance has mostly used culturing, antibiotic susceptibility testing, and genotyping, but WBS employed PCR-based and metagenomics alongside culture-based techniques. Imported cases resulting from international travel and hospitalization abroad appear to have frequently contributed to the rise in ARB pathogen cases in these countries. The many similarities between the Nordic countries (e.g., knowledge exchange practices, antibiotic usage patterns, and the current ARB landscape) could facilitate collaborative efforts in developing and implementing WBS for ARB in population-level screening.
Topics: Humans; Wastewater; Methicillin-Resistant Staphylococcus aureus; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Drug Resistance, Microbial; beta-Lactamases; Escherichia coli; Scandinavian and Nordic Countries
PubMed: 38163547
DOI: 10.1016/j.envres.2023.118052 -
EClinicalMedicine May 2024The escalating resistance of to macrolides has become a significant global health concern, particularly in low-income and middle-income countries (LMICs). Although...
BACKGROUND
The escalating resistance of to macrolides has become a significant global health concern, particularly in low-income and middle-income countries (LMICs). Although tetracyclines and quinolones have been proposed as alternative therapeutic options, concerns regarding age-specific safety issues and the lack of consensus in recommendations across various national guidelines prevail. Thus, the primary objective of this study is to ascertain the most efficacious interventions for second-line treatment of . infection while considering the age-specific safety issues associated with these interventions.
METHODS
In this systematic review and network meta-analysis we searched PubMed, Embase, CNKI, and WanFang Data, from inception up to November 11th, 2023. Studies of quinolones or tetracyclines for the treatment of people with infection were collected and screened by reading published reports, with any type of study included, and no individual patient-level data requested. A systematic review and direct meta-analysis compared the efficacy of tetracyclines and quinolones regarding time to defervescence (TTD) and the rates of fever disappearance within 24 h and 48 h of antibiotic administration, for managing . infection. Bayesian network meta-analysis (NMA) was employed to indirectly assess the relative effectiveness of different interventions in people with . infection and the safety profile of medication in paediatric patients. This study is registered with PROSPERO, CRD42023478383.
FINDINGS
The systematic review and direct meta-analysis included a total of 4 articles involving 246 patients, while the NMA encompassed 85 articles involving a substantial cohort of 7095 patients. The NMA measured the effectiveness across all ages and included 7043 patients, with a mean age of 37.80 ± 3.91 years. Of the 85 included studies, 14 (16.5%) were at low risk of bias, 71 (83.5%) were at moderate risk, and no studies were rated as having a high risk of bias. In the direct meta-analysis, no statistically significant differences were found between tetracyclines and quinolones concerning TTD (mean difference: -0.40, 95% CI: -1.43 to 0.63; = 0%), fever disappearance rate within 24 h of antibiotic administration (OR: 0.37, 95% CI: 0.08-1.79; = 58%), and fever disappearance rate within 48 h of antibiotic administration (OR: 1.10, 95% CI: 0.30-3.98; = 59%). However, the comprehensive NMA analysis of clinical response (in 70 studies; n = 6143 patients), shortening of TTD (in 52 studies; n = 4363 patients), shortening length of cough relief or disappearance (in 39 studies; n = 3235 patients), fever disappearance rate at 48 h (in four studies; n = 418 patients) revealed that minocycline exhibited the most favourable outcomes across these various parameters, and the analysis of fever disappearance rate at 24 h (in three studies; n = 145 patients) revealed that levofloxacin may be the most effective, as indicated by the rank probabilities and surface under the cumulative ranking area (SUCRA) value. Moxifloxacin ranked second in clinical response and in shortening the length of cough relief or disappearance, and third in shortening TTD. Notably, when evaluating the occurrence of adverse reactions in paediatric patients (in four studies; n = 239 children), levofloxacin was associated with the highest SUCRA value rankings for the rate of adverse events.
INTERPRETATION
Our findings suggest that tetracyclines and quinolones may be equally effective. Based on the age of participants in the included studies, minocycline may be the most effective intervention for children over eight years of age when all preventive measures are considered, whereas moxifloxacin may benefit people under eight years of age. However, these results should be interpreted with caution, given the limited number of studies and patients included, and the heterogeneity between included studies. Based on a limited number of studies in children, levofloxacin is likely to have one of the highest rates of adverse reactions. The majority of the studies included in the NMA were from the Asian region, and more randomised controlled trials comparing different therapeutic strategies in patients with . are warranted. This comparative study provides clinical pharmacists and clinicians with important information to enable them to make informed decisions about treatment options, considering drug efficacy and safety.
FUNDING
The Natural Science Foundation of Fujian Province, China.
PubMed: 38596615
DOI: 10.1016/j.eclinm.2024.102589 -
BMJ Open Respiratory Research Feb 2024Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.
DESIGN
Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.
DATA SYNTHESIS
The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.
RESULTS
A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI -4.00 to 9.88, I=79.3%; %DLco -2.03, 95% CI -4.38 to 0.32, I=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DL (95% CI 2.05 to 6.79, I=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.
CONCLUSIONS
There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.
PROSPERO REGISTRATION NUMBER
CRD42023423223.
Topics: Humans; Azathioprine; Immunosuppressive Agents; Lung Diseases, Interstitial; Lung; Mycophenolic Acid; Enzyme Inhibitors; Observational Studies as Topic
PubMed: 38413120
DOI: 10.1136/bmjresp-2023-002163 -
Iranian Journal of Public Health Dec 2023Meat and meat products are introduced as one of the frequent sources of . We aimed to determine the prevalence and antibiotic resistance of isolates in meat and meat... (Review)
Review
BACKGROUND
Meat and meat products are introduced as one of the frequent sources of . We aimed to determine the prevalence and antibiotic resistance of isolates in meat and meat products using a systematic review and meta-analysis.
METHODS
A literature search was performed in the primary international and bibliographic databases such as MEDLINE (PubMed), Cochrane Library, Embase, Scopus, and Web of Science to achieve all articles related to the prevalence and antibiotic resistance rates from 2007 to 2022.
RESULTS
The 278 retrieved articles were reduced to 54 worldwide eligible studies after screening and matching inclusion/exclusion criteria. was examined in different types of samples and its resistance to 10 antibiotics. The pooled prevalence of was 3.4% in all samples. pooled prevalence was detected in fish, poultry, and red meat groups with 6.9%, 5.2%, and 3.2%, respectively. Regarding antibiotic resistance, the highest pooled prevalence was for ciprofloxacin (86.6%), followed by clindamycin (42.6%) and erythromycin (34%). The lowest pooled prevalence was observed in metronidazole (7.6%), vancomycin (6.6%), and chloramphenicol (6%).
CONCLUSION
Low resistance was found to commonly used drugs for infection (CDI) treatment. Since each antibiotic can be predisposing cause for CDI development, this finding possibly will be warning from a One Health viewpoint about the misuse of antibiotics in the chain of farm to fork including agriculture, animal husbandry and the food industry and also their injudicious use in medicine.
PubMed: 38435778
DOI: 10.18502/ijph.v52i12.14313 -
BMC Infectious Diseases Aug 2023Neonatal sepsis, particularly gram-negative (GN) bacteria-induced, is a significant cause of morbidity and mortality in newborns. Healthcare professionals find this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Neonatal sepsis, particularly gram-negative (GN) bacteria-induced, is a significant cause of morbidity and mortality in newborns. Healthcare professionals find this issue challenging because of antibiotic resistance. This study aims to combine findings to identify the prevalence of GN bacteria and their antibiotic resistance in Iranian neonates with sepsis.
METHODS
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The literature search was performed through international databases, including (PubMed/MEDLINE, EMBASE, Scopus, and Web of Science), Iranian local databases (Magiran, Iranmedex, Irandoc, Scimed, and SID), and the first 100 records of Google Scholar. Analytical cross-sectional study checklist from the Joanna Briggs Institute (JBI) was used for the quality assessment of included studies. Comprehensive Meta-Analysis Software Version 2 was used to conduct the meta-analysis. The between-study heterogeneity was investigated by I statistics.
RESULTS
The prevalence of GN bacteria was estimated to be 53.6% [95% CI: 45.9- 61.1: P = 0.362] in Iranian neonates with sepsis, based on 31 studies with a sample size of 104,566. klebsiella pneumoniae (K.pneumonia) (23.2% [95% CI: 17.5-30.0, P < 0.001]) followed by Escherichia coli (E.coli) (13.5% [95% CI: 9.4-18.9, P < 0.001]) were more prevalent among GN bacteria. The highest resistance in K.pneumoniae was observed in Cefixime (80.6%, [95% CI: 56.3-93.1, P = 0.018]). E.coli showed greater resistance to Ampicillin (61.8%, [95% CI: 44.2-76.5, P = 0.188]. The prevalence of GN bacteria in Iranian neonates with sepsis has a decreasing trend based on the year, as shown by a meta-regression model (P < 0.0004).
CONCLUSION
GN pathogens, particularly K.pneumoniae, and E.coli, are the leading cause of neonatal sepsis in Iran. GN bacteria showed the highest resistance to Third-generation cephalosporin and Aminoglycosides.
Topics: Humans; Infant, Newborn; Iran; Neonatal Sepsis; Prevalence; Cross-Sectional Studies; Gram-Negative Bacteria; Drug Resistance, Microbial; Klebsiella pneumoniae; Escherichia coli
PubMed: 37582726
DOI: 10.1186/s12879-023-08508-1 -
EBioMedicine Dec 2023Antibiotic consumption can lead to antimicrobial resistance and microbiome imbalance. We sought to estimate global antibiotic consumption for sore throat, and the...
BACKGROUND
Antibiotic consumption can lead to antimicrobial resistance and microbiome imbalance. We sought to estimate global antibiotic consumption for sore throat, and the potential reduction in consumption due to effective vaccination against group A Streptococcus (Strep A).
METHODS
We reviewed and analysed articles published between January 2000 and February 2022, identified though Clarivate Analytics' Web of Science search platform, with reference to antibiotic prescribing or consumption, sore throat, pharyngitis, or tonsillitis. We then used those analyses, combined with assumptions for the effectiveness, duration of protection, and coverage of a vaccine, to calculate the estimated reduction in antibiotic prescribing due to the introduction of Strep A vaccines.
FINDINGS
We identified 101 studies covering 38 countries. The mean prescribing rate for sore throat was approximately 5 courses per 100 population per year, accounting for approximately 5% of all antibiotic consumption. Based on 2020 population estimates for countries with empiric prescribing rates, antibiotic consumption for sore throat was estimated to exceed 37 million courses annually, of which half could be attributable to treatment for Strep A. A vaccine that reduces rates of Strep A infection by 80%, with 80% coverage and 10 year's duration of protection, could avert 2.8 million courses of antibiotics prescribed for sore throat treatment among 5-14 year-olds in countries with observed prescribing rates, increasing to an estimated 7.5 million averted if an effective vaccination program also reduced precautionary prescribing.
INTERPRETATION
A vaccine that prevents Strep A throat infections in children may reduce antibiotic prescribing for sore throat by 32-87% depending on changes to prescribing and consumption behaviours.
FUNDING
The Wellcome Trust, grant agreement number 215490/Z/19/Z.
Topics: Child; Humans; Anti-Bacterial Agents; Pharyngitis; Streptococcus pyogenes; Streptococcal Infections; Vaccines
PubMed: 37950997
DOI: 10.1016/j.ebiom.2023.104864 -
BMC Pregnancy and Childbirth Nov 2023Given the physiological changes during pregnancy, pregnant women are likely to develop recurrent urinary tract infections (UTIs) and pyelonephritis, which may result in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Given the physiological changes during pregnancy, pregnant women are likely to develop recurrent urinary tract infections (UTIs) and pyelonephritis, which may result in adverse obstetric outcomes, including prematurity and low birth weight preeclampsia. However, data on UTI prevalence and bacterial profile in Latin American pregnant women remain scarce, necessitating the present systematic review to address this issue.
METHODS
To identify eligible observational studies published up to September 2022, keywords were systematically searched in Medline/PubMed, Cochrane Library, Embase, Web of Science, and Bireme/Lilacs electronic databases and Google Scholar. The systematic review with meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the quality of studies was classified according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. The meta-analysis employed a random-effects method with double-arcsine transformation in the R software.
RESULTS
Database and manual searches identified 253,550 citations published until September 2022. Among the identified citations, 67 met the inclusion criteria and were included in the systematic review, corresponding to a sample of 111,249 pregnant women from nine Latin American countries. Among Latin American pregnant women, the prevalence rates of asymptomatic bacteriuria, lower UTI, and pyelonephritis were estimated at 18.45% (95% confidence interval [CI]: 15.45-21.53), 7.54% (95% CI: 4.76-10.87), and 2.34% (95% CI: 0.68-4.85), respectively. Some regional differences were also detected. Among the included studies, Escherichia coli (70%) was identified as the most frequently isolated bacterial species, followed by Klebsiella sp. (6.8%).
CONCLUSION
Pregnant women in Latin America exhibit a higher prevalence of bacteriuria, UTI, and pyelonephritis than pregnant women globally. This scenario reinforces the importance of universal screening with urine culture during early prenatal care to ensure improved outcomes. Future investigations should assess the microbial susceptibility profiles of uropathogens isolated from pregnant women in Latin America.
TRIAL REGISTRATION
This research was registered at PROSPERO (No. CRD42020212601).
Topics: Infant, Newborn; Pregnancy; Female; Humans; Bacteriuria; Latin America; Pregnant Women; Pregnancy Complications, Infectious; Prevalence; Urinary Tract Infections; Pyelonephritis; Anti-Bacterial Agents
PubMed: 37940852
DOI: 10.1186/s12884-023-06060-z -
Oral Surgery, Oral Medicine, Oral... Dec 2023We examined the range, nature, and extent of research conducted regarding the oral and dental implications of hereditary hemorrhagic telangiectasia (HHT) to identify... (Review)
Review
OBJECTIVE
We examined the range, nature, and extent of research conducted regarding the oral and dental implications of hereditary hemorrhagic telangiectasia (HHT) to identify gaps in the research and knowledge of the field.
STUDY DESIGN
We performed a scoping review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and 2017 Guidance for the Conduct of Joanna Briggs Institute Scoping Reviews. We searched the MEDLINE and Web of Science databases for all full-text articles published in English from December 1946 to October 2022.
RESULTS
We identified 103 articles describing oral and dental considerations of patients with HHT, primarily case reports. Most reported oral telangiectasias of the tongue, lips, and palate. Many reported management of bleeding and the use or recommendation of prophylactic antibiotics before dental procedures.
CONCLUSIONS
Oral telangiectasias are commonly found in patients with hereditary hemorrhagic telangiectasia, and dental professionals may be the first to diagnose it in their patients. Early detection and diagnosis are important to prevent potentially fatal outcomes, and prophylactic antibiotics before procedures may be warranted.
Topics: Humans; Telangiectasia, Hereditary Hemorrhagic; Telangiectasis; Hemorrhage; Anti-Bacterial Agents
PubMed: 37752017
DOI: 10.1016/j.oooo.2023.08.001 -
Annals of Clinical Microbiology and... Aug 2023The emergence of multidrug-resistant (MDR) strains of genital pathogens, notably Mycoplasma genitalium and Ureaplasma spp., constitutes a significant global threat... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The emergence of multidrug-resistant (MDR) strains of genital pathogens, notably Mycoplasma genitalium and Ureaplasma spp., constitutes a significant global threat today. The present study aimed to evaluate the prevalence and trend of changes in MDR mycoplasma and ureaplasma strains.
METHODS
An exhaustive search was performed across the ISI Web of Science, PubMed, Scopus, ScienceDirect, and Google Scholar databases to accumulate relevant studies without restrictions until April 2023. We used event rate and corresponding 95% confidence intervals to determine the frequency of resistance-related mutations and examine the trend of antibiotic resistance changes.
RESULTS
The data from 27 studies, including 24,662 patients across 14 countries, were evaluated. Out of the total studies, 20 focused on M. genitalium infections, and five on Ureaplasma spp. The frequency of resistance-associated mutations to macrolides, tetracyclines, and fluoroquinolones in clinical strains of M. genitalium was 43.5%, 13.1%, and 18.6%, respectively. The prevalence of M. genitalium strains with double resistance and MDR was 11.0% and 17.4%, respectively. The incidence of both double-drug-resistant and MDR strains was higher in the World Health Organization (WHO) Western Pacific Region than in European and American populations. For Ureaplasma strains, resistance-associated mutations to macrolides, tetracyclines, and fluoroquinolones were 40.8%, 25.7%, and 90.3%, respectively. The rate of antibiotic resistance was higher in the African population compared to the European and WHO Western Pacific Regions. The rate of MDR Ureaplasma infections was 13.2%, with a higher incidence in the African population compared to the WHO Western Pacific and European regions.
CONCLUSION
The proliferation and spread of MDR Mycoplasma and Ureaplasma strains present a significant public health challenge. The situation is indeed alarming, and the rising trend of MDR M. genitalium and MDR Ureaplasma infections suggests that therapies involving macrolides and fluoroquinolones may become less effective.
Topics: Humans; Mycoplasma; Mycoplasma Infections; Ureaplasma Infections; Mycoplasma hominis; Anti-Bacterial Agents; Ureaplasma; Fluoroquinolones; Tetracyclines; Macrolides; Mutation; Prevalence
PubMed: 37563660
DOI: 10.1186/s12941-023-00627-6