SASPI Ltd.
Guideline based on systematic review
WHO guideline on the prevention and diagnosis of rheumatic fever and rheumatic heart disease
Reference No:- https://www.who.int/publications/i/item/9789240100077
Guideline, WHO
Abstract
Rheumatic fever (RF) and Rheumatic heart disease (RHD) are a preventable public health problem in low- and middle-income countries and in marginalized communities in middle- and high-income countries. RF is an autoimmune inflammatory reaction to throat infections (pharyngitis) or possibly to superficial skin and skin structure infections caused by Streptococcus pyogenes, a group A beta‐haemolytic Streptococcus (GAS) bacterium. The first episode of RF is commonly seen in children aged 5 to 14 years. Recurrent episodes are most common within 1 year of the first episode but can occur throughout the life course. RHD is characterized by chronic structural and/or functional changes in the heart, most commonly in the valves, caused by one or more episodes of rheumatic fever (RF). RHD most commonly starts in childhood with a diagnostic peak in young adults aged 20 to 39 years. RHD can lead to death or lifelong disability, however, effective early intervention can prevent premature morbidity and mortality.
The WHO guideline on the prevention and diagnosis of rheumatic fever (RF) and rheumatic heart disease (RHD) provides evidence-informed recommendations for the prevention and management of RF and RHD. It encompasses three areas; 1) primary prevention of rheumatic fever and rheumatic heart disease, specifically the identification and treatment of suspected group A (beta-haemolytic) Streptococcus (GAS) pharyngitis and skin infections; 2) secondary prevention of recurrent rheumatic fever and of rheumatic heart disease, specifically use of long-term antibiotic prophylaxis, interventions to increase adherence to antibiotic prophylaxis, and screening for early rheumatic heart disease; and 3) management of rheumatic fever, specifically the treatment with anti-inflammatory drugs.
The recommendations are intended for wide audience involved in the prevention and management of RF and RHD.
Guideline based on systematic review
WHO recommendation on screening of pregnant women for intrapartum antibiotic prophylaxis for the prevention of early onset group B streptococcus disease in newborns
Reference No:- https://www.who.int/publications/i/item/9789240099128
Guideline, WHO
Abstract
The primary audience for this recommendation includes health professionals who are responsible for developing national and local health-care guidelines and protocols (particularly those related to the prevention and treatment of peripartum infections) and those involved in the provision of care to women and their newborns during labour and childbirth, including midwives, nurses, general medical practitioners and obstetricians, as well as managers of maternal and child health programmes, and relevant staff in ministries of health and training institutions, in all settings.
Epidemiological update
Global leishmaniasis surveillance updates 2023: 3 years of the NTD road map
Reference NO :- https://www.who.int/publications/i/item/who-wer-9945-653-669
Weekly epidemiological record, WHO
Abstract
Leishmaniasis continues to be a major health problem in 4 eco-epidemiological regions of the world: the Americas, East Africa, North Africa and West and South-East Asia.
This report on global leishmaniasis surveillance follows those published in 2016–2023.2–6 Six indicators of leishmaniasis are publicly available from the Global Health Observatory (GHO).7 In addition to the GHO, country profiles with up to 30 indicators are published, with detailed data received from 45 Member States.
The aims of this report are to update the description of the GHO leishmaniasis indicators reported by Member States to WHO up to 2023, to describe specific indicators of gender and age distribution, relapse, treatment for cutaneous leishmaniasis (CL), visceral leishmaniasis (VL) and VL treatment outcomes, VL case fatality rates (CFRs) and the burden of post kala-azar dermal leishmaniasis (PKDL). The report also contains a brief section on HIV–VL coinfection, the kala-azar elimination programme in South-East Asia and the VL elimination initiative in eastern Africa. Leishmaniasis fact sheet. Geneva: World Health Organ.
Guideline based on systematic review, Position Statement based on review/RCTs
Guidelines for the Prevention, Diagnosis, and Management of Urinary Tract Infections in Pediatrics and Adults, A WikiGuidelines Group Consensus Statement
Authors: Zachary Nelson et al.,
Abstract
Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence.
Objective: To create a clinical guideline for the diagnosis and management of urinary tract infections that addresses the gap between the evidence and recommendation strength.
Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In May 2023, new and existing members were solicited for questions on urinary tract infection prevention, diagnosis, and management. For each topic, literature searches were conducted up until early 2024 in any language. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were developed discussing the available literature and associated risks and benefits of various approaches.
Findings: A total of 54 members representing 12 countries reviewed 914 articles and submitted information relevant to 5 sections: prophylaxis and prevention (7 questions), diagnosis and diagnostic stewardship (7 questions), empirical treatment (3 questions), definitive treatment and antimicrobial stewardship (10 questions), and special populations and genitourinary syndromes (10 questions). Of 37 unique questions, a clear recommendation could be provided for 6 questions. In 3 of the remaining questions, a clear recommendation could only be provided for certain aspects of the question. Clinical reviews were generated for the remaining questions and aspects of questions not meeting criteria for a clear recommendation.
Conclusions and Relevance: In this consensus statement that applied the WikiGuidelines method for clinical guideline development, the majority of topics relating to prevention, diagnosis, and treatment of urinary tract infections lack high-quality prospective data and clear recommendations could not be made. Randomized clinical trials are underway to address some of these gaps; however further research is of utmost importance to inform true evidence-based, rather than eminence-based practice.
RCTs having large positive / negative effect
Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine versus a quadrivalent meningococcal conjugate vaccine in adults in India: an observer-blind, randomised, active-controlled, phase 2/3 study
Authors: Prasad S Kulkarni et al.,
Abstract
Background: Meningococcal disease remains an important public health problem globally. We assessed the non-inferiority and the lot-to-lot consistency of a pentavalent meningococcal ACYWX conjugate vaccine (NmCV-5; Serum Institute of India, Pune, India) versus a quadrivalent meningococcal ACWY conjugate vaccine (MenACWY-D) in healthy adults.
Methods: In this observer-blind, randomised, active-controlled, phase 2/3 study, healthy adults aged 18–85 years were recruited from nine hospitals across seven cities in India. Participants were grouped by age (age 18–29, 30–60, and 61–85 years), and within each age group they were randomly assigned (3:1) to receive either NmCV-5 or MenACWY-D (Sanofi Pasteur). In the age 18–29 years group, participants were additionally randomly assigned (1:1:1:1) to either lot A, lot B, or lot C of NmCV-5 or MenACWY-D. Block randomisation was used (block sizes of 4, 8, and 12). Study participants and study personnel were masked to treatment assignment. Participants received either a 0·5 mL dose of NmCV-5, containing 5 μg each of conjugated A, C, W, Y, and X polysaccharides, or 0·5 mL MenACWY-D, containing 4 μg of each of conjugated A, C, W, and Y polysaccharides. Vaccinations were administered intramuscularly in the deltoid muscle. The primary outcomes were seroresponse (non-inferiority margin of –10%) and geometric mean titres (GMTs; non-inferiority margin of 0·5) in all participants, and lot-to-lot consistency of NmCV-5 (in participants aged 18–29 years; consistency was shown if the geometric mean ratio [GMR] 95% CIs were within the limit interval of 0·5 to 2). For non-inferiority, serogroup X immune response in the NmCV-5 group was compared with the lowest immune response among serogroups A, C, W, and Y in the MenACWY-D group. Immunogenicity was assessed with a serum bactericidal activity assay that used baby rabbit serum as the complement (rSBA) on days 1 and 29 in the modified per-protocol population (including all participants who were randomly assigned, received vaccine, had a post-vaccination rSBA measurement up to 121 days after vaccination, and no major protocol violations). Solicited events were collected for 7 days and serious adverse events were collected for 180 days, and assessed in the safety population (all participants who received vaccination). This study is registered with ClinicalTrials.gov, NCT04358731, and CTRI, CTRI/2019/12/022436, and is now complete.
Findings: Between Dec 27, 2019, and Sept 19, 2020, 1712 individuals were screened, of whom 1640 were randomly assigned and received NmCV-5 (n=1233) or MenACWY-D (n=407; mean age 26·4 years [SD 12·2], 551 [33·6%] of 1640 were female, and 1089 [66·4%] were male). 1441 participants were aged 18–29 years (362 received lot A, 360 received lot B, and 361 received lot C of NmCV-5 and 357 received MenACWY-D, with one participant mis-randomised by age group and excluded from lot-to-lot consistency analysis). Non-inferiority of NmCV-5 against MenACWY-D was met in terms of seroresponse rates and GMT ratios for all five serogroups. The seroresponse rates were 84·3% (97·5% CI 81·7 to 86·7; serogroup A) or higher in the NmCV-5 group and 54·5% (48·5 to 60·3; serogroup A) or higher in the MenACWY-D group, with the difference in the seroresponse rate between vaccine groups ranging from 0·2 (97·5% CI –2·2 to 2·6) for serogroup W to 29·8 (24·4 to 35·2) for serogroup A. GMTs on day 29 were 7016·9 (97·5% CI 6475·7 to 7603·4; serogroup Y) or higher in the NmCV-5 group and 3646·8 (3188·2 to 4171·5; serogroup Y) or higher in the MenACWY-D group, with GMT ratios between vaccine groups for serogroups A, C, Y, and W ranging from 1·9 (97·5% CI 1·5–2·3) for serogroup W to 2·5 (2·2–2·8) for serogroup A. NmCV-5 induced robust immune responses against serogroup X. Lot-to-lot consistency of NmCV-5 was found for all five serogroups, with 95% CIs for the GMT ratio for each pair of lots being between 0·5 and 2: the lowest lower bound and the highest upper bound of the 95% CI for the GMR between NmCV-5 lot A and lot B were 0·6 and 1·4, between lot A and lot C were 0·7 and 1·6, and between lot B and lot C were 0·8 and 1·6, respectively, for any of the five serogroups. At least one solicited adverse event was reported by 527 (42·7%) of 1233 participants in the NmCV-5 group and 142 (34·9%) of 407 in the MenACWY-D group. No serious adverse events occurred that were determined to be causally related to vaccination.
Interpretation: NmCV-5 was non-inferior to MenACWY-D in terms of seroresponse and GMTs, was safe, and demonstrated lot-to-lot consistency. NmCV-5 is prequalified by WHO and was rolled out in the African meningitis belt in April, 2024.
Funding: Serum Institute of India.
RCTs having large positive / negative effect
Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial
Authors: Roisin Connon et al.,
Abstract
Background: African children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection.
Methods: We conducted a phase I/II trial in Ugandan children with severe malaria comparing a 5-day course of azithromycin: 10, 15 and 20 mg/kg of azithromycin (prescribed by weight bands) spanning the dose-range effective for other salmonellae infection. We generated relevant pharmacokinetic (PK) data by sparse sampling during dosing intervals and investigated associations between azithromycin exposure and potential mechanisms (PK-pharmacodynamics) using change in C-reactive protein (CRP), a putative marker of sepsis, at 72 h (continuous) and microbiological cure (7-day) (binary), alone and as a composite with 7-day and 90-day survival. To assess whether clinical or biomarkers could identify those at risk of sepsis, a non-severe malaria control was concurrently enrolled.
Results: Between January 2020 and January 2022, 105 cases were randomised azithromycin doses: 35 to 10 mg/kg, 35 to 15 mg/kg and 35 to 20 mg/kg. Fifty non-severe malaria controls were concurrently enrolled. CRP reduced in all arms by 72 h with a mean reduction of 65.8 mg/L (95% CI 57.1, 74.5) in the 10 mg/kg arm, 64.8 mg/L (95% CI 56.5, 73.1; p = 0.87) in the 20 mg/kg arm and a smaller reduction 51.2 mg/L (95% CI 42.9, 59.5; p = 0.02) in the 15 mg/kg arm. Microbiological cure alone outcome was not analysed as only one pathogen was found among cases. Three events contributed to the composite outcome of 7-day survival and microbiological cure, with no events in the 15 mg/kg arm. The odds ratio comparing 20 vs 10 mg/kg was 0.50 (95% CI 0.04, 5.79); p = 0.58. Due to the low number of pathogens identified, it was not possible to identify better methods for targeting antibiotics including both the cases and controls.
Conclusions: We found no evidence for an association between systemic azithromycin exposure and reduction in CRP. Further work is needed to better identify children at highest risk from bacterial co-infection.
Trial registration: ISRCTN49726849 (registered on 27th October 2017).
Systematic review/Scoping review with large effect size
Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial
Authors: Connor Prosty et al.,
Abstract
Background: The diagnosis of Pneumocystis jirovecii pneumonia (PCP) can be challenging because of diagnostic tests that are imperfect and/or invasive. The Fungitell serum (1→3)-β-D-glucan (BDG) assay is a non-invasive blood test studied for PCP; however, the manufacturer-recommended cut-off of 80pg/mL is not well validated for this disease.
Objectives: We conducted a systematic review and meta-analysis to determine the diagnostic test accuracy of the Fungitell BDG assay for the diagnosis of PCP.
Methods:
Data Sources: A search strategy of MEDLINE and Embase from a previous meta-analysis on BDG was updated to January 31, 2024.
Test: Fungitell BDG assay.
Reference Standard – One or more of: lung biopsy, bronchoalveolar lavage, induced sputum, or nasopharyngeal swab specimens tested for PCP by histopathology, microscopy using immunofluorescence or staining, or polymerase chain reaction.
Assessment of Risk of Bias: The QUADAS-2 tool.
Methods of Data Synthesis: Diagnostic test accuracy data of the Fungitell serum BDG assay across all reported cut-offs were pooled by meta-analysis. We then evaluated a categorical approach using <80pg/mL as a rule-out threshold and ≥400pg/mL as a rule-in threshold.
Results: 26 articles were included comprising 5111 patients and 1150 PCP cases. At the conventional cut-off of 80pg/mL, the overall pooled sensitivity and specificity were 83.5% (95% Confidence Interval [95%CI]=72.8-90.6) and 75.5% (95%CI=66.0-83.0), respectively. At a pre-test probability of <20% and a BDG <80pg/mL, the post-test probability would be <5% (negative predictive value >95%). At 400pg/mL, sensitivity was reduced to 63.5% (95%CI=45.8-78.1) with specificity increased to 93.6% (95%CI=88.6-96.5). At a pre-test probability of 47.5%, a BDG >400pg/mL would have a post-test probability of >90%.
Discussion: A categorical approach using <80pg/mL to rule-out and >400pg/mL to rule-in PCP may allow for a more nuanced interpretation based on pre-test probability. More accurate estimates of pre-test probability and further external validation is required.
Systematic review/Scoping review with large effect size
Timeline and outcomes of viral and fungal infections after Chimeric Antigen Receptor (CAR) T-cell therapy: A large database analysis
Authors: Joseph Sassine et al.,
Abstract
Objectives: This large database analysis aims to describe the incidence, timeline, and risk factors for viral and fungal infections after chimeric antigen receptor (CAR) T-cell therapy.
Methods: We queried a global research network database, TriNetX, for patients who received CAR T-cell therapy, who were identified and followed for the development of viral and fungal infections. Baseline demographic, oncologic history, laboratory data and medication histories were collected. We evaluated risk factors for respiratory viral infections (RVI), herpesvirus, fungal infections and mortality using Cox regression.
Results: A total of 2,256 patients who received CAR T-cell therapy were included, 1,867 (82.7%) were CD19-targeted and 400 (17.7%) were BCMA-targeted. Following CAR T-cell infusion, RVI were the most prevalent (23.3%) with a median onset of 160 days (IQR 52-348 days), while herpesvirus and fungal infections were less frequent, occurring in 13.6% and 11.4% of cases with median onsets of 71 (IQR 18-252) and 73 days (IQR 14-236 days), respectively. On multivariable Cox regression, independent predictors of RVI included acute lymphoblastic leukemia (ALL, HR 1.61), prior hematopoietic cell transplant (HCT, HR 1.29), cytokine release syndrome (CRS, HR 1.41), hemophagocytic lymphohistiocytosis (HLH, HR 1.96), and glucocorticoids (HR 3.37). Prior HCT (HR 2.00), hypogammaglobulinemia (HR 1.51), immune-effector cell-associated neurotoxicity syndrome (ICANS, HR 1.52), and HLH (HR 1.99) were associated with a higher risk of herpesviruses. Independent predictors of fungal infections included prior HCT (HR 1.59), CRS (HR 1.58) and hypogammaglobulinemia (HR 1.40). Idecabtagene vicleucel was associated with a lower risk of herpesvirus and fungal infections (HR 0.39 and 0.44, respectively).
Conclusions: In a large cohort of CAR T-cell therapy recipients, respiratory viral infections were the most common but occurred later, while herpesvirus and fungal infections were less frequent but occurred earlier. Prospective studies investigating prophylaxis and pre-emptive monitoring strategies are needed in this population.
Systematic review/Scoping review with large effect size
Antimicrobial resistance among refugees and asylum seekers: a global systematic review and meta-analysis
Authors: Elizabeth D Hermsen et al.,
Abstract
Refugees and asylum seekers might have an increased risk of antimicrobial resistance (AMR) carriage or infection due to several factors, with conflict and war known to accelerate the spread of AMR. However, data are scarce on prevalence and risk factors for AMR among refugees and asylum seekers and how they are affected globally; in addition, how their risk compares to that of the host-country population is unclear. We aimed to explore and assess global AMR data among refugees and asylum seekers. Ovid (MEDLINE and Embase) and PubMed were searched for peer-reviewed primary research articles from Jan 1, 2015, to Oct 23, 2023, and articles were included if they reported carriage or infection with laboratory-confirmed drug-resistant organisms in refugees or asylum seekers from any country. Of 884 articles identified, 41 reported prevalence of AMR among 16 970 refugees and asylum seekers and were included in the study. The most common phenotypes reported were multidrug-resistant Gram-negative bacteria (n=26; prevalence ranged from 4·2% to 60·8%), methicillin-resistant Staphylococcus aureus (n=24; 0·92% to 73%), and extended-spectrum β-lactamase-producing Gram-negative bacteria (n=20; 1·6% to 61·1%). Refugees and asylum seekers had a higher likelihood of carriage or infection with any AMR than the host-country population (n=7849 vs n=81 283, respectively; odds ratio 2·88, 95% CI 2·61–3·18; I2=94%). Refugees and asylum seekers are at an increased risk of AMR carriage and infection, with our data suggesting that refugees and asylum seekers might be exposed to conditions that support the emergence of drug resistance (including living in overcrowded camps and facing barriers to health and vaccine systems). Hence, more global and regional data on AMR are needed through strengthened surveillance programmes and health-care facilities, especially in low-income and middle-income countries. Increased efforts are needed to drive improvements in infection prevention and control (including vaccination), antimicrobial stewardship, treatment strategies tailored to groups at high risk, accessiblity to quality health care in these populations at risk globally, and address risk factors such as poor living and transit conditions.
Systematic review/Scoping review with large effect size
Evaluation of interventions led by pharmacists in antimicrobial stewardship programs in low- and middle-income countries: a systematic literature review
DOI:- 10.1017/ash.2024.342
Authors: Tatiana Aporta Marins et al.,
Abstract
Objective: We performed a systematic literature review to identify and describe pharmacist-led antimicrobial stewardship programs (ASPs) interventions in low- and middle-income countries (LMICs).
Design: Systematic literature review.
Methods: We searched PubMed for studies evaluating pharmacist-led ASP interventions in LMICs from January 1, 2012, to November 4, 2023. We evaluated the article’s country of origin, described ASP interventions, and analyzed their reported outcomes.
Results: Twenty-four studies were included; ten were conducted in China, two in India, two in Thailand, five in Africa, three in Latin America, and two in the Middle East. The predominant interventions in the studies were education and training followed by audit and feedback. The outcomes reported included reduction in antimicrobial consumption, cost reduction, shortening of the duration of antimicrobial therapy, and de-escalation.
Conclusions: Our findings reinforce the importance of clinical pharmacists leading interventions related to antimicrobial stewardship in LMCIs and the global importance of investing in Infectious Disease training.
Systematic review/Scoping review with large effect size
The effect of probiotic, prebiotic, and synbiotic supplements on anthropometric measures and respiratory infections in malnourished children: a systematic review and meta-analysis of randomized controlled trials
Authors: Masoumeh Paiandeh et al.,
Abstract
Background: Malnutrition remains a significant concern in many societies. This study systematically reviewed the effects of probiotics, prebiotics, and synbiotics on anthropometric measures in malnourished children, focusing on changes in weight, height, and respiratory infections (primary outcomes), and head circumference, hemoglobin, hematocrit, and body mass index (BMI) as secondary outcomes.
Methods: This systematic review and meta-analysis involved searching various databases in both Persian and English, including Scopus, Web of Science Core Collection, Cochrane Library, Science Direct, and PubMed up to October 5, 2024. Non-randomized controlled trials (RCTs) were excluded. The Cochrane Handbook Risk of Bias Version 2 tool was used to assess risk of bias, and RevMan 5.3 software was employed for analysis. Subgroup analyses were conducted based on the type of supplement received. Meta-regression was applied to identify factors influencing results, and the GRADE approach was used to evaluate evidence certainty.
Results: Twelve studies with a total of 3,086 children (aged up to 6 years, equally distributed between boys and girls) were included. All children were malnourished without underlying illnesses. Limitations of the study included variations in intervention type, dose, duration, and timing of outcome measurement. Meta-analysis revealed that probiotics, prebiotics, and synbiotics may increase weight (6 trials, mean difference: 0.33 kg, 95% CI: 0.15 to 0.50, low certainty of evidence), while probiotics and synbiotics may increase height compared to control groups (5 trials, mean difference: 0.44 cm, 95% CI: 0.02 to 0.85, low certainty of evidence). However, probiotics and synbiotics did not show a statistically significant effect on lower respiratory tract infections (5 trials, risk ratio: 0.84, 95% CI: 0.68 to 1.04, moderate certainty of evidence). Meta-regression indicated that intervention type, sample size, and follow-up duration were not significant moderators for outcomes related to weight, height, or respiratory infections.
Conclusion: The current evidence suggests that probiotics, prebiotics, and synbiotics supplements may help manage malnutrition-related outcomes in malnourished children, but further research with stronger study designs is needed to confirm these findings due to the low certainty of evidence.
Systematic review/Scoping review with large effect size
Utility of preoperative prophylactic antibiotics for preventing surgical site infections in children with infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis
Authors: Annu Gulia et al.,
Abstract
Purpose: The aim of this study was to determine the utility of prophylactic antibiotics before pyloromyotomy for the prevention of Surgical Site Infections (SSI) among children with Infantile Hypertrophic Pyloric Stenosis (IHPS).
Methods: A systematic search of PubMed, Scopus, Embase, and Web of Science databases was performed to identify papers published till 30th July 2024. The main outcome of interest was the incidence of SSIs. The relative risk (RR) with 95% confidence interval (CI) was calculated using a random effects model. The I2 statistic was used to calculate the heterogeneity. The Newcastle–Ottawa-Scale (NOS) was used to assess the methodological quality of the included studies.
Results: Five studies, published between 1999 and 2024, were included in this systematic review and meta-analysis. The risk of developing SSI among those treated was RR = 0.97, 95% CI 0.53 to 1.78, with I2 = 0%, indicating no incremental benefit of administration of prophylactic antibiotics. A sensitivity analysis was performed by excluding the database studies. Results from this analysis (RR = 0.79, 95% CI 0.29 to 2.20, I2 = 0%) demonstrated that no significant difference was observed after excluding studies with large sample sizes. All included studies were of good methodological quality as assessed with the NOS.
Conclusion: The findings of this review demonstrate no incremental benefit of the administration of prophylactic antibiotics before pyloromyotomy in preventing SSIs in children with IHPS. However, randomized, double-blinded, placebo-controlled trials need to be conducted in the future before any definite conclusions are drawn in this regard.
Systematic review/Scoping review with large effect size
Usefulness of sonication in the microbiological diagnosis of cardiovascular implantable electronic device infections: systematic review, meta-analysis and meta-regression
Authors: Guillermo Martín-Gutiérrez et al.,
Abstract
Background: Multiple studies have demonstrated the utility of sonication to improve culture yield in patients with cardiovascular implantable electronic device (CIED) infections.
Objective: To analyze the usefulness of sonication in the microbiological diagnosis of CIED infections in comparison with traditional cultures.
Methods: Systematic database searches were performed to identify studies that provided enough data concerning both sensitivity and specificity of traditional (non-sonicated) and sonicated cultures from CIED samples. The diagnostic accuracy measures were obtained by three different statistical approaches: (i) The univariate model; (ii) The bivariate random; and (iii) The Bayesian bivariate hierarchical model. Heterogeneity was assessed using meta-regression.
Findings: Nine studies met the criteria for inclusion in the meta-analysis (1684 cultures). The summary estimates of sensitivity were higher for sonicated cultures (0.756) in comparison with non-sonicated cultures (0.446). On meta-regression, sonication of CIEDs significantly increased the sensitivity (p = 0.001) as well as the rates of false positive results (p = 0.003). The final model also showed that the studies that used a threshold for positivity were associated with lower rates of false positive results (p < 0.001).
Interpretation: Our results suggest that sonication improves the microbiological diagnosis of CIED infections in comparison with traditional cultures, but a standardization of processes is necessary.
Systematic review/Scoping review with large effect size
Antimicrobial efficacy and bonding properties of orthodontic bonding systems enhanced with silver nanoparticles: a systematic review with meta-analysis
Authors: Magdalena Sycińska-Dziarnowska et al.,
Abstract
The aim of this systematic review was to assess the antimicrobial effectiveness of silver nanoparticles (AgNPs) incorporated to different orthodontic bonding systems. Additionally, the review investigated the impact of AgNPs on the bonding properties of these materials. The hypothesis posed that the addition of AgNPs would enhance the antimicrobial efficacy of orthodontic bonding systems while maintaining their bonding properties. The systematic review employed a PICO-based search strategy, targeting in vitro studies focusing on the integration of nano silver particles into orthodontic bonding systems with potential antimicrobial activity. The intervention involved the use of nano silver in orthodontic bonding systems, with a comparison to systems lacking nano silver. The primary outcomes assessed were antimicrobial activity and shear bond strength (SBS). The search process, conducted without publication date restrictions, yielded 551 potential articles: 34 from PubMed, 360 from PubMed Central, 42 from Embase, 54 from Scopus, and 61 from Web of Science. Ultimately, a qualitative synthesis was conducted on 13 papers. The PRISMA diagram, visually represented the search strategy, screening process, and inclusion criteria. The study protocol was registered in PROSPERO CRD42023487656 to enhance transparency and adherence to systematic review guidelines. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale, revealing that the 13 articles meeting the inclusion criteria demonstrated a high level of evidence. Seven studies were included in the meta-analysis regarding shear bond strength. In summary, the synthesized findings from these studies strongly underscore the promising potential of orthodontic materials modified with AgNPs. These materials exhibit effective resistance against cariogenic bacteria without compromising bonding properties below clinical acceptability. Such innovative materials hold significant implications for advancing oral health within the realm of orthodontics.
Multi-centric observational study with large effect
Global trends in CD4 count measurement and distribution at first antiretroviral treatment initiation
DOI:- 10.1093/cid/ciae548
Authors: Reneé de Waal et al.,
Abstract
Background: While people with HIV (PWH) start antiretroviral treatment (ART) regardless of CD4 count, CD4 measurement remains crucial for detecting advanced HIV disease and evaluating ART programmes. We explored CD4 measurement (proportion of PWH with a CD4 result available) and prevalence of CD4 <200 cells/µL at ART initiation within the International epidemiology Databases to Evaluate AIDS (IeDEA) global collaboration.
Methods: We included PWH at participating ART programmes who first initiated ART at age 15–80 years during 2005–2019. We described proportions of PWH (i) with CD4 (measured within 6 months before to 2 weeks after ART initiation); and (ii) among those with a CD4, with CD4 <200; by year of ART initiation and region.
Results: We included 1,355,104 PWH from 42 countries in 7 regions; 63% were female. Median (interquartile range) age at ART initiation was 37 (31–44) in men and 32 (26–39) in women. CD4 measurement initially increased, or remained stable over time until around 2013, but then declined to low levels in some regions (Southern Africa, except South Africa: from 54 to 13%; East Africa 85 to 31%; Central Africa 72 to 20%; West Africa: 91 to 53%; and Latin America: 87 to 56%). Prevalence of CD4<200 declined over time in all regions, but plateaued after 2015 at ≥30%.
Conclusions: CD4 measurement has declined sharply in recent years, especially in sub-Saharan Africa. Among those with a CD4, the prevalence of CD4 <200 remains concerningly high. Scaling up CD4 testing and securing adequate funding are urgent priorities.
Other specific ASP article suggested by Editorial Board
Antimicrobial resistance research – an IJID collection of selected articles 2020-2024
Authors: Shui-Shan Lee et al.,
Abstract
To mark the 2024 World Antimicrobial Resistance Awareness Week (WAAW), a selection of articles on antimicrobial resistance (AMR) published in International Journal of Infectious Diseases between 2020 to 2024 is highlighted as a Special Collection. Titled “Antimicrobial resistance research – an IJID collection of selected articles 2020-2024”, the updated Collection features 25 articles
Other specific ASP article suggested by Editorial Board
When antimicrobial stewardship begins with microbiological test requests: the case of asymptomatic bacteriuria
Authors: Imlay, Hannah et al.,
Abstract
Purpose of review : We aim to review the rationale, methods, and experiences with diagnostic stewardship targeted at urinary tract infection (UTI) and related urinary syndromes.
Recent findings : In the last 18 months, several articles have demonstrated the impact of diagnostic stewardship interventions at limiting inappropriate diagnosis of UTIs or inappropriate antibiotic-prescribing, targeting the urinary tract. Antimicrobial stewardship programs may create and implement interventions at the point of urine test ordering, urine test resulting, or at the point of prescribing antibiotics after results have returned. Specific design and implementation of stewardship interventions depends on context. To maximize their impact, interventions should be accompanied by education and garner buy-in from providers.
Summary : Diagnostic stewardship can decrease unnecessary antibiotics and inappropriate diagnosis of UTI with multifaceted interventions most likely to be effective. Remaining questions include how to reduce ASB treatment in new populations, such as those with immune compromise, and persistent unknowns regarding UTI diagnosis and diagnostics.
Other specific ASP article suggested by Editorial Board
Reassessment of the role of combination antifungal therapy in the current era
Authors: Neoh, Chin Fen et al.,
Abstract
Purpose of review : Given the high mortality and morbidity associated with invasive fungal diseases (IFDs), the use of combination antifungal therapies is often considered despite the dearth of data. This review aims to summarize the current state of literature of combination antifungal therapies, discussing the potential roles of newer antifungal combinations and key considerations for their clinical use.
Recent findings : In infections other than cryptococcal meningitis or in the setting of empirical treatment for suspected azole-resistant Aspergillus infections, the utility of the combination antifungal approaches remains controversial given the paucity of well designed randomized controlled trials. Data on potential combined antifungal treatments have been primarily limited to in-vitro studies, animal models, case reports and/or observational studies. With availability of novel antifungal agents (e.g. ibrexafungerp, fosmanogepix), combination therapy to treat mould infections should be re-visited. A phase 2 clinical trial of ibrexafungerp combined with voriconazole to treat invasive pulmonary aspergillosis is on-going.
Summary : There is a need to investigate the use of combination antifungal agents. This includes delineating the indication of these combined antifungal therapies and determining how to use them most appropriately in the clinical setting.
Other specific DSP article suggested by Editorial Board
American Society for Microbiology evidence-based laboratory medicine practice guidelines to reduce blood culture contamination rates: a systematic review and meta-analysis
DOI:- 10.1128/cmr.00087-24
Authors: Robert L. Sautter et al.,
Abstract
Blood cultures (BCs) are one of the critical tests used to detect bloodstream infections. BC results are not 100% specific. Interpretation of BC results is often complicated by detecting microbial contamination rather than true infection. False positives due to blood culture contamination (BCC) vary from 1% to as high as >10% of all BC results. False-positive BC results may result in patients undergoing unnecessary antimicrobial treatments, increased healthcare costs, and delay in detecting the true cause of infection or other non-infectious illness. Previous guidelines from the Clinical and Laboratory Standards Institute, College of American Pathologists, and others, based on expert opinion and surveys, promoted a limit of ≤3% as acceptable for BCC rates. However, the data supporting such recommendations are controversial. A previous systematic review of BCC examined three practices for reducing BCC rates (venipuncture, phlebotomy teams, and pre-packaged kits). Subsequently, numerous studies on different practices including using diversion devices, disinfectants, and education/training to lower BCC have been published. The goal of the current guideline is to identify beneficial intervention strategies to reduce BCC rates, including devices, practices, and education/training by providers in collaboration with the laboratory. We performed a systematic review of the literature between 2017 and 2022 using numerous databases. Of the 11,319 unique records identified, 311 articles were sought for full-text review, of which 177 were reviewed; 126 of the full-text articles were excluded based on pre-defined inclusion and exclusion criteria. Data were extracted from a total of 49 articles included in the final analysis. An evidenced-based committee’s expert panel reviewed all the references as mentioned in Data Collection and determined if the articles met the inclusion criteria. Data from extractions were captured within an extraction template in the US Agency for Healthcare Research and Quality’s Systematic Review Data Repository (https://srdr.ahrq.gov/). BCC rates were captured as the number of events (contaminated samples) per arm (standard practice versus improvement practice). Modified versions of the National Heart, Lung, and Blood Institute Study Quality Assessment Tools were used for risk of bias assessment (https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools). We used Grading of Recommendations, Assessment, Development and Evaluations to assess strength of evidence. There are several interventions that resulted in significant reduction in BCC rates: chlorhexidine as a disinfectant for skin preparation, using a diversion device prior to drawing BCs, using sterile technique practices, using a phlebotomy team to obtain BCs, and education/training programs. While there were no substantial differences between methods of decreasing BCC, our results indicate that the method of implementation can determine the success or failure of the intervention. Our evidence-based systematic review and meta-analysis support several interventions to effectively reduce BCC by approximately 40%–60%. However, devices alone without an education/training component and buy-in from key stakeholders to implement various interventions would not be as effective in reducing BCC rates.
Other specific DSP article suggested by Editorial Board
Progress on nonculture based diagnostic tests for invasive mould infection
Authors: White, P. Lewis
Abstract
Purpose of review : This review describes the current status of diagnosing invasive mould disease and Pneumocystis pneumonia using nonconventional diagnostics methods.
Recent findings : There has been significant development in the range of nonculture mycological tests. Lateral flow tests (LFTs) for diagnosing aspergillosis complement galactomannan ELISA testing, and LFTs for other fungal diseases are in development. Rapid and low through-put B-D-Glucan assays increase access to testing and there has been significant progress in the standardization/development of molecular tests. Despite this, no single perfect test exists and combining tests (e.g., antigen and molecular testing) is likely required for the optimal diagnosis of most fungal diseases.
Summary : Based on established clinical performance few mycological tests can be used alone for optimal diagnosis of fungal disease (FD) and combining tests, including classical approaches is the preferred route for confirming and excluding disease. Next-generation sequencing will likely play an increasing role in how we diagnose disease, but optimization, standardization and validation of the entire molecular process is needed and we must consider how host biomarkers can stratify risk. Given the burden of FD in low- and medium-income countries, improved access to novel but more so existing diagnostic testing is critical along with simplification of testing processes.
RCTs having large positive / negative effect
Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine versus a quadrivalent meningococcal conjugate vaccine in adults in India: an observer-blind, randomised, active-controlled, phase 2/3 study
Authors: Prasad S Kulkarni et al.,
Abstract
Background: Meningococcal disease remains an important public health problem globally. We assessed the non-inferiority and the lot-to-lot consistency of a pentavalent meningococcal ACYWX conjugate vaccine (NmCV-5; Serum Institute of India, Pune, India) versus a quadrivalent meningococcal ACWY conjugate vaccine (MenACWY-D) in healthy adults.
Methods: In this observer-blind, randomised, active-controlled, phase 2/3 study, healthy adults aged 18–85 years were recruited from nine hospitals across seven cities in India. Participants were grouped by age (age 18–29, 30–60, and 61–85 years), and within each age group they were randomly assigned (3:1) to receive either NmCV-5 or MenACWY-D (Sanofi Pasteur). In the age 18–29 years group, participants were additionally randomly assigned (1:1:1:1) to either lot A, lot B, or lot C of NmCV-5 or MenACWY-D. Block randomisation was used (block sizes of 4, 8, and 12). Study participants and study personnel were masked to treatment assignment. Participants received either a 0·5 mL dose of NmCV-5, containing 5 μg each of conjugated A, C, W, Y, and X polysaccharides, or 0·5 mL MenACWY-D, containing 4 μg of each of conjugated A, C, W, and Y polysaccharides. Vaccinations were administered intramuscularly in the deltoid muscle. The primary outcomes were seroresponse (non-inferiority margin of –10%) and geometric mean titres (GMTs; non-inferiority margin of 0·5) in all participants, and lot-to-lot consistency of NmCV-5 (in participants aged 18–29 years; consistency was shown if the geometric mean ratio [GMR] 95% CIs were within the limit interval of 0·5 to 2). For non-inferiority, serogroup X immune response in the NmCV-5 group was compared with the lowest immune response among serogroups A, C, W, and Y in the MenACWY-D group. Immunogenicity was assessed with a serum bactericidal activity assay that used baby rabbit serum as the complement (rSBA) on days 1 and 29 in the modified per-protocol population (including all participants who were randomly assigned, received vaccine, had a post-vaccination rSBA measurement up to 121 days after vaccination, and no major protocol violations). Solicited events were collected for 7 days and serious adverse events were collected for 180 days, and assessed in the safety population (all participants who received vaccination). This study is registered with ClinicalTrials.gov, NCT04358731, and CTRI, CTRI/2019/12/022436, and is now complete.
Findings: Between Dec 27, 2019, and Sept 19, 2020, 1712 individuals were screened, of whom 1640 were randomly assigned and received NmCV-5 (n=1233) or MenACWY-D (n=407; mean age 26·4 years [SD 12·2], 551 [33·6%] of 1640 were female, and 1089 [66·4%] were male). 1441 participants were aged 18–29 years (362 received lot A, 360 received lot B, and 361 received lot C of NmCV-5 and 357 received MenACWY-D, with one participant mis-randomised by age group and excluded from lot-to-lot consistency analysis). Non-inferiority of NmCV-5 against MenACWY-D was met in terms of seroresponse rates and GMT ratios for all five serogroups. The seroresponse rates were 84·3% (97·5% CI 81·7 to 86·7; serogroup A) or higher in the NmCV-5 group and 54·5% (48·5 to 60·3; serogroup A) or higher in the MenACWY-D group, with the difference in the seroresponse rate between vaccine groups ranging from 0·2 (97·5% CI –2·2 to 2·6) for serogroup W to 29·8 (24·4 to 35·2) for serogroup A. GMTs on day 29 were 7016·9 (97·5% CI 6475·7 to 7603·4; serogroup Y) or higher in the NmCV-5 group and 3646·8 (3188·2 to 4171·5; serogroup Y) or higher in the MenACWY-D group, with GMT ratios between vaccine groups for serogroups A, C, Y, and W ranging from 1·9 (97·5% CI 1·5–2·3) for serogroup W to 2·5 (2·2–2·8) for serogroup A. NmCV-5 induced robust immune responses against serogroup X. Lot-to-lot consistency of NmCV-5 was found for all five serogroups, with 95% CIs for the GMT ratio for each pair of lots being between 0·5 and 2: the lowest lower bound and the highest upper bound of the 95% CI for the GMR between NmCV-5 lot A and lot B were 0·6 and 1·4, between lot A and lot C were 0·7 and 1·6, and between lot B and lot C were 0·8 and 1·6, respectively, for any of the five serogroups. At least one solicited adverse event was reported by 527 (42·7%) of 1233 participants in the NmCV-5 group and 142 (34·9%) of 407 in the MenACWY-D group. No serious adverse events occurred that were determined to be causally related to vaccination.
Interpretation: NmCV-5 was non-inferior to MenACWY-D in terms of seroresponse and GMTs, was safe, and demonstrated lot-to-lot consistency. NmCV-5 is prequalified by WHO and was rolled out in the African meningitis belt in April, 2024.
Funding: Serum Institute of India.
RCTs having large positive / negative effect
Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial
Authors: Roisin Connon et al.,
Abstract
Background: African children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection.
Methods: We conducted a phase I/II trial in Ugandan children with severe malaria comparing a 5-day course of azithromycin: 10, 15 and 20 mg/kg of azithromycin (prescribed by weight bands) spanning the dose-range effective for other salmonellae infection. We generated relevant pharmacokinetic (PK) data by sparse sampling during dosing intervals and investigated associations between azithromycin exposure and potential mechanisms (PK-pharmacodynamics) using change in C-reactive protein (CRP), a putative marker of sepsis, at 72 h (continuous) and microbiological cure (7-day) (binary), alone and as a composite with 7-day and 90-day survival. To assess whether clinical or biomarkers could identify those at risk of sepsis, a non-severe malaria control was concurrently enrolled.
Results: Between January 2020 and January 2022, 105 cases were randomised azithromycin doses: 35 to 10 mg/kg, 35 to 15 mg/kg and 35 to 20 mg/kg. Fifty non-severe malaria controls were concurrently enrolled. CRP reduced in all arms by 72 h with a mean reduction of 65.8 mg/L (95% CI 57.1, 74.5) in the 10 mg/kg arm, 64.8 mg/L (95% CI 56.5, 73.1; p = 0.87) in the 20 mg/kg arm and a smaller reduction 51.2 mg/L (95% CI 42.9, 59.5; p = 0.02) in the 15 mg/kg arm. Microbiological cure alone outcome was not analysed as only one pathogen was found among cases. Three events contributed to the composite outcome of 7-day survival and microbiological cure, with no events in the 15 mg/kg arm. The odds ratio comparing 20 vs 10 mg/kg was 0.50 (95% CI 0.04, 5.79); p = 0.58. Due to the low number of pathogens identified, it was not possible to identify better methods for targeting antibiotics including both the cases and controls.
Conclusions: We found no evidence for an association between systemic azithromycin exposure and reduction in CRP. Further work is needed to better identify children at highest risk from bacterial co-infection.
Trial registration: ISRCTN49726849 (registered on 27th October 2017).
Systematic review/Scoping review with large effect size
Diagnostic Test Accuracy of the Fungitell Serum (1→3)-β-D-Glucan Assay for the Diagnosis of Pneumocystis jirovecii Pneumonia: A Systematic Review and Meta-Analysis
Authors: Connor Prosty et al.,
Abstract
Background: The diagnosis of Pneumocystis jirovecii pneumonia (PCP) can be challenging because of diagnostic tests that are imperfect and/or invasive. The Fungitell serum (1→3)-β-D-glucan (BDG) assay is a non-invasive blood test studied for PCP; however, the manufacturer-recommended cut-off of 80pg/mL is not well validated for this disease.
Objectives: We conducted a systematic review and meta-analysis to determine the diagnostic test accuracy of the Fungitell BDG assay for the diagnosis of PCP.
Methods
Data Sources: A search strategy of MEDLINE and Embase from a previous meta-analysis on BDG was updated to January 31, 2024.
Test: Fungitell BDG assay.
Reference Standard – One or more of: lung biopsy, bronchoalveolar lavage, induced sputum, or nasopharyngeal swab specimens tested for PCP by histopathology, microscopy using immunofluorescence or staining, or polymerase chain reaction.
Assessment of Risk of Bias: The QUADAS-2 tool.
Methods of Data Synthesis: Diagnostic test accuracy data of the Fungitell serum BDG assay across all reported cut-offs were pooled by meta-analysis. We then evaluated a categorical approach using <80pg/mL as a rule-out threshold and ≥400pg/mL as a rule-in threshold.
Results: 26 articles were included comprising 5111 patients and 1150 PCP cases. At the conventional cut-off of 80pg/mL, the overall pooled sensitivity and specificity were 83.5% (95% Confidence Interval [95%CI]=72.8-90.6) and 75.5% (95%CI=66.0-83.0), respectively. At a pre-test probability of <20% and a BDG <80pg/mL, the post-test probability would be <5% (negative predictive value >95%). At 400pg/mL, sensitivity was reduced to 63.5% (95%CI=45.8-78.1) with specificity increased to 93.6% (95%CI=88.6-96.5). At a pre-test probability of 47.5%, a BDG >400pg/mL would have a post-test probability of >90%.
Discussion: A categorical approach using <80pg/mL to rule-out and >400pg/mL to rule-in PCP may allow for a more nuanced interpretation based on pre-test probability. More accurate estimates of pre-test probability and further external validation is required.
Systematic review/Scoping review with large effect size
Timeline and outcomes of viral and fungal infections after Chimeric Antigen Receptor (CAR) T-cell therapy: A large database analysis
Authors: Joseph Sassine et al.,
Abstract
Objectives: This large database analysis aims to describe the incidence, timeline, and risk factors for viral and fungal infections after chimeric antigen receptor (CAR) T-cell therapy.
Methods: We queried a global research network database, TriNetX, for patients who received CAR T-cell therapy, who were identified and followed for the development of viral and fungal infections. Baseline demographic, oncologic history, laboratory data and medication histories were collected. We evaluated risk factors for respiratory viral infections (RVI), herpesvirus, fungal infections and mortality using Cox regression.
Results: A total of 2,256 patients who received CAR T-cell therapy were included, 1,867 (82.7%) were CD19-targeted and 400 (17.7%) were BCMA-targeted. Following CAR T-cell infusion, RVI were the most prevalent (23.3%) with a median onset of 160 days (IQR 52-348 days), while herpesvirus and fungal infections were less frequent, occurring in 13.6% and 11.4% of cases with median onsets of 71 (IQR 18-252) and 73 days (IQR 14-236 days), respectively. On multivariable Cox regression, independent predictors of RVI included acute lymphoblastic leukemia (ALL, HR 1.61), prior hematopoietic cell transplant (HCT, HR 1.29), cytokine release syndrome (CRS, HR 1.41), hemophagocytic lymphohistiocytosis (HLH, HR 1.96), and glucocorticoids (HR 3.37). Prior HCT (HR 2.00), hypogammaglobulinemia (HR 1.51), immune-effector cell-associated neurotoxicity syndrome (ICANS, HR 1.52), and HLH (HR 1.99) were associated with a higher risk of herpesviruses. Independent predictors of fungal infections included prior HCT (HR 1.59), CRS (HR 1.58) and hypogammaglobulinemia (HR 1.40). Idecabtagene vicleucel was associated with a lower risk of herpesvirus and fungal infections (HR 0.39 and 0.44, respectively).
Conclusions: In a large cohort of CAR T-cell therapy recipients, respiratory viral infections were the most common but occurred later, while herpesvirus and fungal infections were less frequent but occurred earlier. Prospective studies investigating prophylaxis and pre-emptive monitoring strategies are needed in this population.
Systematic review/Scoping review with large effect size
Antimicrobial resistance among refugees and asylum seekers: a global systematic review and meta-analysis
Authors: Elizabeth D Hermsen et al.,
Abstract
Refugees and asylum seekers might have an increased risk of antimicrobial resistance (AMR) carriage or infection due to several factors, with conflict and war known to accelerate the spread of AMR. However, data are scarce on prevalence and risk factors for AMR among refugees and asylum seekers and how they are affected globally; in addition, how their risk compares to that of the host-country population is unclear. We aimed to explore and assess global AMR data among refugees and asylum seekers. Ovid (MEDLINE and Embase) and PubMed were searched for peer-reviewed primary research articles from Jan 1, 2015, to Oct 23, 2023, and articles were included if they reported carriage or infection with laboratory-confirmed drug-resistant organisms in refugees or asylum seekers from any country. Of 884 articles identified, 41 reported prevalence of AMR among 16 970 refugees and asylum seekers and were included in the study. The most common phenotypes reported were multidrug-resistant Gram-negative bacteria (n=26; prevalence ranged from 4·2% to 60·8%), methicillin-resistant Staphylococcus aureus (n=24; 0·92% to 73%), and extended-spectrum β-lactamase-producing Gram-negative bacteria (n=20; 1·6% to 61·1%). Refugees and asylum seekers had a higher likelihood of carriage or infection with any AMR than the host-country population (n=7849 vs n=81 283, respectively; odds ratio 2·88, 95% CI 2·61–3·18; I2=94%). Refugees and asylum seekers are at an increased risk of AMR carriage and infection, with our data suggesting that refugees and asylum seekers might be exposed to conditions that support the emergence of drug resistance (including living in overcrowded camps and facing barriers to health and vaccine systems). Hence, more global and regional data on AMR are needed through strengthened surveillance programmes and health-care facilities, especially in low-income and middle-income countries. Increased efforts are needed to drive improvements in infection prevention and control (including vaccination), antimicrobial stewardship, treatment strategies tailored to groups at high risk, accessiblity to quality health care in these populations at risk globally, and address risk factors such as poor living and transit conditions.
Systematic review/Scoping review with large effect size
Evaluation of interventions led by pharmacists in antimicrobial stewardship programs in low- and middle-income countries: a systematic literature review
DOI:- 10.1017/ash.2024.342
Authors: Tatiana Aporta Marins et al.,
Abstract
Objective: We performed a systematic literature review to identify and describe pharmacist-led antimicrobial stewardship programs (ASPs) interventions in low- and middle-income countries (LMICs).
Design: Systematic literature review.
Methods: We searched PubMed for studies evaluating pharmacist-led ASP interventions in LMICs from January 1, 2012, to November 4, 2023. We evaluated the article’s country of origin, described ASP interventions, and analyzed their reported outcomes.
Results: Twenty-four studies were included; ten were conducted in China, two in India, two in Thailand, five in Africa, three in Latin America, and two in the Middle East. The predominant interventions in the studies were education and training followed by audit and feedback. The outcomes reported included reduction in antimicrobial consumption, cost reduction, shortening of the duration of antimicrobial therapy, and de-escalation.
Conclusions: Our findings reinforce the importance of clinical pharmacists leading interventions related to antimicrobial stewardship in LMCIs and the global importance of investing in Infectious Disease training.
Systematic review/Scoping review with large effect size
The effect of probiotic, prebiotic, and synbiotic supplements on anthropometric measures and respiratory infections in malnourished children: a systematic review and meta-analysis of randomized controlled trials
Authors: Masoumeh Paiandeh et al.,
Abstract
Background: Malnutrition remains a significant concern in many societies. This study systematically reviewed the effects of probiotics, prebiotics, and synbiotics on anthropometric measures in malnourished children, focusing on changes in weight, height, and respiratory infections (primary outcomes), and head circumference, hemoglobin, hematocrit, and body mass index (BMI) as secondary outcomes.
Methods: This systematic review and meta-analysis involved searching various databases in both Persian and English, including Scopus, Web of Science Core Collection, Cochrane Library, Science Direct, and PubMed up to October 5, 2024. Non-randomized controlled trials (RCTs) were excluded. The Cochrane Handbook Risk of Bias Version 2 tool was used to assess risk of bias, and RevMan 5.3 software was employed for analysis. Subgroup analyses were conducted based on the type of supplement received. Meta-regression was applied to identify factors influencing results, and the GRADE approach was used to evaluate evidence certainty.
Results: Twelve studies with a total of 3,086 children (aged up to 6 years, equally distributed between boys and girls) were included. All children were malnourished without underlying illnesses. Limitations of the study included variations in intervention type, dose, duration, and timing of outcome measurement. Meta-analysis revealed that probiotics, prebiotics, and synbiotics may increase weight (6 trials, mean difference: 0.33 kg, 95% CI: 0.15 to 0.50, low certainty of evidence), while probiotics and synbiotics may increase height compared to control groups (5 trials, mean difference: 0.44 cm, 95% CI: 0.02 to 0.85, low certainty of evidence). However, probiotics and synbiotics did not show a statistically significant effect on lower respiratory tract infections (5 trials, risk ratio: 0.84, 95% CI: 0.68 to 1.04, moderate certainty of evidence). Meta-regression indicated that intervention type, sample size, and follow-up duration were not significant moderators for outcomes related to weight, height, or respiratory infections.
Conclusion: The current evidence suggests that probiotics, prebiotics, and synbiotics supplements may help manage malnutrition-related outcomes in malnourished children, but further research with stronger study designs is needed to confirm these findings due to the low certainty of evidence.
Systematic review/Scoping review with large effect size
Utility of preoperative prophylactic antibiotics for preventing surgical site infections in children with infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis
Authors: Annu Gulia et al.,
Abstract
Purpose: The aim of this study was to determine the utility of prophylactic antibiotics before pyloromyotomy for the prevention of Surgical Site Infections (SSI) among children with Infantile Hypertrophic Pyloric Stenosis (IHPS).
Methods: A systematic search of PubMed, Scopus, Embase, and Web of Science databases was performed to identify papers published till 30th July 2024. The main outcome of interest was the incidence of SSIs. The relative risk (RR) with 95% confidence interval (CI) was calculated using a random effects model. The I2 statistic was used to calculate the heterogeneity. The Newcastle–Ottawa-Scale (NOS) was used to assess the methodological quality of the included studies.
Results: Five studies, published between 1999 and 2024, were included in this systematic review and meta-analysis. The risk of developing SSI among those treated was RR = 0.97, 95% CI 0.53 to 1.78, with I2 = 0%, indicating no incremental benefit of administration of prophylactic antibiotics. A sensitivity analysis was performed by excluding the database studies. Results from this analysis (RR = 0.79, 95% CI 0.29 to 2.20, I2 = 0%) demonstrated that no significant difference was observed after excluding studies with large sample sizes. All included studies were of good methodological quality as assessed with the NOS.
Conclusion: The findings of this review demonstrate no incremental benefit of the administration of prophylactic antibiotics before pyloromyotomy in preventing SSIs in children with IHPS. However, randomized, double-blinded, placebo-controlled trials need to be conducted in the future before any definite conclusions are drawn in this regard.
Systematic review/Scoping review with large effect size
Usefulness of sonication in the microbiological diagnosis of cardiovascular implantable electronic device infections: systematic review, meta-analysis and meta-regression
Authors: Guillermo Martín-Gutiérrez et al.,
Abstract
Background: Multiple studies have demonstrated the utility of sonication to improve culture yield in patients with cardiovascular implantable electronic device (CIED) infections.
Objective: To analyze the usefulness of sonication in the microbiological diagnosis of CIED infections in comparison with traditional cultures.
Methods: Systematic database searches were performed to identify studies that provided enough data concerning both sensitivity and specificity of traditional (non-sonicated) and sonicated cultures from CIED samples. The diagnostic accuracy measures were obtained by three different statistical approaches: (i) The univariate model; (ii) The bivariate random; and (iii) The Bayesian bivariate hierarchical model. Heterogeneity was assessed using meta-regression.
Findings: Nine studies met the criteria for inclusion in the meta-analysis (1684 cultures). The summary estimates of sensitivity were higher for sonicated cultures (0.756) in comparison with non-sonicated cultures (0.446). On meta-regression, sonication of CIEDs significantly increased the sensitivity (p = 0.001) as well as the rates of false positive results (p = 0.003). The final model also showed that the studies that used a threshold for positivity were associated with lower rates of false positive results (p < 0.001).
Interpretation: Our results suggest that sonication improves the microbiological diagnosis of CIED infections in comparison with traditional cultures, but a standardization of processes is necessary.
Systematic review/Scoping review with large effect size
Antimicrobial efficacy and bonding properties of orthodontic bonding systems enhanced with silver nanoparticles: a systematic review with meta-analysis
Authors: Magdalena Sycińska-Dziarnowska et al.,
Abstract
The aim of this systematic review was to assess the antimicrobial effectiveness of silver nanoparticles (AgNPs) incorporated to different orthodontic bonding systems. Additionally, the review investigated the impact of AgNPs on the bonding properties of these materials. The hypothesis posed that the addition of AgNPs would enhance the antimicrobial efficacy of orthodontic bonding systems while maintaining their bonding properties. The systematic review employed a PICO-based search strategy, targeting in vitro studies focusing on the integration of nano silver particles into orthodontic bonding systems with potential antimicrobial activity. The intervention involved the use of nano silver in orthodontic bonding systems, with a comparison to systems lacking nano silver. The primary outcomes assessed were antimicrobial activity and shear bond strength (SBS). The search process, conducted without publication date restrictions, yielded 551 potential articles: 34 from PubMed, 360 from PubMed Central, 42 from Embase, 54 from Scopus, and 61 from Web of Science. Ultimately, a qualitative synthesis was conducted on 13 papers. The PRISMA diagram, visually represented the search strategy, screening process, and inclusion criteria. The study protocol was registered in PROSPERO CRD42023487656 to enhance transparency and adherence to systematic review guidelines. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale, revealing that the 13 articles meeting the inclusion criteria demonstrated a high level of evidence. Seven studies were included in the meta-analysis regarding shear bond strength. In summary, the synthesized findings from these studies strongly underscore the promising potential of orthodontic materials modified with AgNPs. These materials exhibit effective resistance against cariogenic bacteria without compromising bonding properties below clinical acceptability. Such innovative materials hold significant implications for advancing oral health within the realm of orthodontics.