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Evidence of Greater Immune Aging among Untreated HIV Slow Progressors than Antiretroviral-controlled People Living with HIV
Authors: Anthony Y.Y. Hsieh
Abstract
Background: Uncontrolled HIV viremia results in the progression to AIDS, however this can be stopped with antiretroviral therapy (ART). Slow progressors are rare individuals who can prevent or delay HIV disease progression without ART. It is unknown whether they experience immune aging akin to normal progressors on ART.
Methods: We investigated persons living with HIV (PWH) who were either HIV slow progressors (n=58), PWH on ART with undetectable HIV viremia (n=58), PWH not on ART with detectable viremia (n=56), and 56 controls without HIV. The groups were well matched for age and sex. A panel of T-cell differentiation and immune aging markers were measured, along with T and B cell subset telomere length, adjusting for major confounders.
Results: Relative to the ART-suppressed HIV group, slow progressors showed immune aging markers indicative of more advanced aging, including lower CD8 naïve:effector memory ratio (standardized effect size -0.41 [95% CI -0.74,-0.07]), and shorter telomere length in B cells (-0.52 [-0.97,-0.07]), CD4 T cells (-0.58 [-0.94,-0.23]), and proliferative CD8 cells (-0.41 [-0.80,-0.01]). Comparison of slow progressors with the control group without HIV showed the same effects. Further, within the slow progressor group, immune aging patterns for the subgroup of elite controllers were not different.
Conclusions: Our findings indicate that despite natural host control of HIV replication, slow progressors show evidence of disproportionately advanced immune aging. This reinforces the potential benefit of ART and emphasizes the need to both diagnose slow progressors, and study their potential age-related comorbidities.
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Faecal microbiota transplant to ERadicate gastrointestinal carriage of Antibiotic-Resistant Organisms (FERARO): a feasibility randomised controlled trial
Authors: Blair Merrick
Abstract
Objectives: The gastrointestinal tract (GIT) is a reservoir of multidrug-resistant organisms (MDRO). Colonisation with MDRO precedes invasive infections which can be challenging to treat with excess morbidity and mortality compared to antimicrobial susceptible infections. Currently, there are no effective GIT decolonisation strategies. Whilst Faecal Microbiota Transplant (FMT) has emerged as a potential therapeutic, there remains uncertainty about its feasibility, safety and efficacy.
Methods: Population: Patients with invasive infection with Extended-spectrum Beta-Lactamase (ESBL-) or Carbapenem-resistant Enterobacterales (CRE) and persistent GIT carriage.
Intervention: Three doses of encapsulated lyophilised FMT.
Comparator: Matched placebo capsules.
Outcomes: Primary outcome was participant consent rate as a proportion of those approached to be screened for GIT carriage of ESBL-E/CRE. Secondary outcomes were additional feasibility, safety and tolerability, and efficacy metrics. Exploratory outcomes included stool metagenomic analysis.
Results: Of 460 approached individuals, 124 (27%) consented. 53/124 participants (43%) fulfilled all eligibility criteria. 44/53 (83%) of those eligible were randomised and 41/44 (93%) received investigational medicinal product (IMP): 20 FMT and 21 placebo. 39/41 (95%) completed IMP dosing. Abdominal bloating and skin and subcutaneous tissue disorders were more common following FMT but there were no unanticipated harms. MDRO carriage decreased over time across arms but was lower at all time points in the FMT arm. FMT increased microbiome diversity and microbiome-based health measures. FMT recipients’ samples clustered into two groups with those with more dissimilar community composition to donors more likely to decolonise post-FMT (3/5 vs. 0/12, p=0.01). Patients that decolonised exhibited a trend towards increased proportional representation of donor-derived strains in their post-FMT samples (p=0.05) and change in strain dominance within MDRO at species-level.
Conclusions: Progression to a substantive trial is feasible with modifications to the existing FERARO protocol. FMT was safe, well tolerated, and acceptable to patients colonised with MDRO. Microbiome analysis infers that greater donor-recipient microbiome dissimilarity at baseline and higher rates of donor-derived strain engraftment favour MDRO decolonisation, which in turn maybe facilitated by conspecific strain replacement.
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Long term outcomes in drug resistant tuberculosis with Bedaquiline, Pretomanid and varying doses of Linezolid
Authors: Bella Devaleenal Daniel
Abstract
Objectives: Assess the effectiveness of bedaquiline, pretomanid and linezolid (BPaL) regimens with varying doses and duration of linezolid at the end of 48 weeks post treatment among drug resistant tuberculosis (DR TB) patients.
Methods: Multicentric pragmatic randomized clinical trial in which BPaL regimens were given for 26 weeks for pulmonary pre extensively drug resistant tuberculosis (PreXDR TB); bedaquiline, pretomanid and linezolid 600mg for 26 weeks (arm1), structured dose reduction arms with linezolid dose reduction from 600 to 300mg after nine weeks (arm2) and 13 weeks (arm3). Participants were followed up for recurrence free cure up to 48 weeks post treatment. Whole genome sequencing in sputum samples at baseline and recurrence differentiated relapse and reinfection.
Results: Of 403 enrolled, 378 were included for the modified intent to treat analysis based on baseline sputum culture positivity and sensitivity to medications in the study regimen. Among them, 331(88%) had recurrence free cure at the end of 48 weeks of post treatment follow-up; arm1:112(87%), arm2:110(88%), arm3:109(88%). Overall, 14 (12 bacteriological and 2 clinical) recurrences (arm1-four, 2-six and 3-four) occurred; 11 recurrences occurred within 24 weeks after treatment completion; four out of 11 within the first 12 weeks. Of the 10 paired sputum samples available at baseline and recurrence for comparison of lineages, there were two reinfections and eight relapses.
Conclusion: Structured dose reduction arms had comparable recurrence free cure rates as linezolid 600mg arm when given along with bedaquiline and pretomanid for 26 weeks in PreXDR TB. Most of the recurrences occurred within the first six months.
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High dose, subcutaneous injections of benzathine penicillin G (SCIP) to prevent rheumatic fever: a single arm, phase IIa trial of safety and pharmacokinetics
Authors: Julie Bennett
Abstract
Objectives: This Phase-IIa trial evaluates the safety and pharmacokinetics of high-dose, 10 weekly subcutaneous injections of penicillin (SCIP) in young people with a history of acute rheumatic fever (ARF).
Methods: Participants received 7.2-10.8 MU (13.8-20.7mL) of Bicillin-LA® via subcutaneous injection in Wellington, New Zealand. A subset underwent intensive safety monitoring and serial dried blood spot collection for penicillin assay. Penicillin concentrations informed a population pharmacokinetic model based on 169 data points from 31 participants. The proportion of time penicillin concentrations remained above a range of plausible pharmacological correlates of protection was estimated for SCIP and compared with estimates for intramuscular benzathine penicillin G (BPG).
Results: Fifty-five participants received SCIP at least once, totalling 182 doses. No recurrent ARF or breakthrough streptococcal throat infections were reported. Model-based simulations indicated that SCIP outperformed intramuscular BPG in maintaining protective concentrations across nearly all plausible pharmacological target correlates of protection (10-20ng/mL). SCIP performed even more favourably when considering modified weight-based dosing or missed BPG injections.
Conclusions: SCIP is safe and well tolerated, demonstrating favourable penicillin exposure for most individuals. Future research should explore the effectiveness of SCIP over longer periods and in diverse populations and settings.
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Impact of an antimicrobial time-out program on antimicrobial consumption rate in hospitalized patients: a quasi-experimental study on the national antimicrobial stewardship program in Iran : Iranian antimicrobial stewardship program.
Authors: Salehi M et al
Abstract
Background: This study evaluated the impact of the national antimicrobial stewardship program (NASP) on the consumption of antimicrobial agents.
Methods: A quasi-experimental study was conducted on hospitalized patients at a referral hospital in Tehran, Iran where the antimicrobial-defined daily dose (DDD) and antimicrobial consumption index (ACI) between the third quarter of 2022 (before the implementation of NASP after the COVID-19 pandemic in October 2022) and the same timeframe in 2023, following the NASP implementation were compared. The NASP was based on antimicrobial time-out assessment. Within 72 h of prescribing meropenem, imipenem, linezolid, vancomycin, voriconazole, caspofungin, and amphotericin B liposomal, infectious disease specialists audited the clinical and microbiological evidence of patients to assess whether it was consistent with the correct prescription.
Results: The antimicrobial consumption rate was assessed in 13,794 and 15,030 hospitalized patients during the third quarter of 2022 and the third quarter of 2023, respectively. The mean length of hospital stay and mortality rate showed no significant differences. The consumption of all restricted antimicrobials decreased. This reduction was significant for imipenem, caspofungin, vancomycin, and linezolid. The total cost of antimicrobial agents had a 22.24% reduction after the NASP implementation (P = 0.01).
Conclusions: The antimicrobial time-out program was associated with a reduction in the use of antimicrobials, including imipenem, linezolid, and vancomycin and antifungals, such as caspofungin without increasing the length of stay and mortality rate. The NASP implementation can be recommended as a beneficial method for reducing the use of broad-spectrum antimicrobials.
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Contribution of weekly ward rounds led by pediatric infectious diseases specialists in a pediatric intensive care unit.
Authors: de Gregorio M et al
Abstract
Community or healthcare-associated infectious diseases are common in Pediatric Intensive Care Units (PICUs). The main objectives of this study were 1/to describe the clinical recommendations given during weekly round of infectious disease team into a PICU and 2/to assess its compliance. An observational prospective single-center study conducted over a one-year period in a PICU of a tertiary university hospital. All clinical recommendations provided by an infectious disease team during a weekly round were collected. There were a total of 234 clinical recommendations on 148 patients (median age 34 months [IQR 2,5 months -126 months], 52% males). Infections occurred in patients with comorbidity in 73 (49%) of them. Ninety-three patients (40%) had pulmonary infections and patients presented with septic shock in 27 cases (12%). Clinical recommendations were categorized as diagnosis, therapeutic, preventive and monitoring in 98 (42%), 205 (88%), 41 (18%), 34 (15%) respectively. There were many therapeutic modifications after round, including treatment discontinuation (n = 82, 35%), spectrum modification (n = 54, 23%) and dosage adjustment (n = 15, 7%). The duration of treatment was also optimized in 144 situations (62%). Overall, it was found that there is a complete compliance with recommendations in most cases (n = 212, 90%). Conclusion: It was found that there is a very good compliance of clinical recommendations provided on a weekly basis by an infectious disease team in a PICU. Larger pediatric studies are warranted to assess a potential benefit on patients’ outcome.
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Antimicrobial prophylaxis for endourological procedures in Jordanian hospitals: a multi-centre qualitative study.
Authors: Abdalijaleel S et al
Abstract
Objectives: To explore urologists’ perceptions of barriers to, and facilitators of, adherence to international antimicrobial prophylaxis (AP) guidelines for endourological procedures in Jordan and to identify strategies to optimise guideline-concordant AP prescribing.
Design: The present study is a qualitative study undertaken through semi-structured interviews and inductive thematic analysis. Study results are reported per Consolidated Criteria for Reporting Qualitative Research.
Setting: Secondary and tertiary care across multiple public, private and academic hospitals in Jordan.
Participants: Nineteen practising urologists (all male; median age 32 years, IQR 8; nine residents, 10 specialists) who routinely prescribe AP for endourological procedures. Participants were recruited via convenience snowball sampling and interviewed until thematic saturation was reached.
Interventions: Not applicable.
Primary and secondary outcome measures: The main outcomes were themes describing perceived barriers to guideline adherence and potential facilitators to support appropriate AP use.
Results: Participants identified several barriers: (1) patient level, strong expectations for antibiotics post-procedure and concerns about procedure-site hygiene; (2) clinician level, fear of postoperative infections and litigation, lack of familiarity with updated guidance and doubts about applying international guidelines locally; (3) system level, hierarchical prescribing dynamics, referral communication gaps, high workloads and time pressures, and concerns over sterilisation practices. Facilitators included targeted professional training and regular guideline updates for urologists, development of local AP guidelines informed by local resistance data, enhanced patient education campaigns and active involvement of clinical pharmacists in preoperative antibiotic review and auditing.
Conclusions: Urologists in Jordan face multifaceted barriers to AP guideline adherence. Future stewardship programmes can use insights from this study to develop locally tailored guidelines, targeted clinician training and pharmacist-led audits. Pilot testing with metrics such as prescribing rates, guideline concordance, antibiotic consumption and postoperative infection incidence will be essential to validate their impact before wider implementation.
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Effectiveness of biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: the BATCH RCT.
DOI: 10.3310/mbva3675
Authors: Waldron CA et al
Abstract
Background: Procalcitonin is a biomarker specific for bacterial infection, with a more rapid response than other commonly used biomarkers, such as C-reactive protein, but it is not routinely used in the National Health Service.
Objective: To determine if using a procalcitonin-guided algorithm may safely reduce duration of antibiotic therapy compared to standard of care in hospitalised children with suspected or confirmed infection.
Design: A pragmatic, multicentre, open-label, parallel two-arm, individually randomised controlled trial with internal pilot phase, qualitative study and health economic evaluations.
Setting: Paediatric wards or paediatric intensive care units within children’s hospitals (n = 6) and district general hospitals (n = 9) in the United Kingdom.
Participants: Children aged between 72 hours and 18 years admitted to hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection.
Interventions: Procalcitonin-guided algorithm versus usual standard care alone.
Main outcome measures: Coprimary outcomes were duration of intravenous antibiotic use and a composite safety measure.
Results: Between 11 June 2018 and 12 October 2022, 1949 children were recruited: 977 to the procalcitonin group [427 female (43.7%), 550 male (56.3%)], and 972 to the usual care group [478 female (49.2%), 494 male (50.8%)]. Duration of intravenous antibiotics was not significantly different between the procalcitonin group (median 96.0 hours) and the usual care group (median 99.7 hours) [hazard ratio = 0.96 (0.87, 1.05)], and the procalcitonin-guided algorithm was non-inferior to usual care [risk difference = -0.81% (95% confidence interval upper bound 1.11%)]. At clinical review, a procalcitonin result was available for 81.8% of the time, which was considered as part of clinical decision-making 66.6% of the time, and the algorithm was adhered to 57.2% of the time. Incremental cost-effectiveness ratio per duration of intravenous antibiotics hour avoided from bootstrapped samples was £467.62 per intravenous antibiotic hour avoided. Cost analysis of complete cases was also higher in the procalcitonin arm for all age groups, and for children aged 5 years and over. The intervention is not cost-effective as it is more expensive with no significant improvement in intravenous antibiotic duration.
Limitations: Robust antimicrobial stewardship programmes were already implemented in the lead recruiting sites, and adherence to the algorithm was poor. Clinicians may be reluctant to adhere to biomarker-guided algorithms, due to unfamiliarity with interpreting the test result.
Conclusions: In children hospitalised with confirmed or suspected bacterial infection, the addition of a procalcitonin-guided algorithm to usual care is non-inferior in terms of safety, but does not reduce duration of intravenous antibiotics, and is not cost-effective. In the presence of robust antimicrobial stewardship programmes to reduce antibiotic use, a procalcitonin-guided algorithm may offer little added value.
Future work: Future trials must include an implementation framework to improve trial intervention fidelity, and repeated cycles of education and training to facilitate implementation of biomarker-guided algorithms into routine clinical care.
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Antimicrobial resistance in northern Australia: the HOTspots surveillance and response program annual epidemiology report 2022.
Authors: Wozniak TM et al
Abstract
Background: The HOTspots surveillance and response program monitors antimicrobial resistance (AMR) in selected bacterial pathogens across three jurisdictions in northern Australia. In 2022, the program collected data from 164 community healthcare clinics and 50 hospitals to assess AMR trends and geographic variations.
Methods: Data on resistance rates for methicillin-resistant Staphylococcus aureus (MRSA) and for Escherichia coli (E. coli) were analysed. Geographic regions were compared to identify variations in AMR across the Northern Territory, northern Western Australia and northern Queensland. Resistance rates were compared between community clinics and hospitals.
Findings: In 2022, there were 56,003 clinical isolates submitted to HOTspots. Geographic variation was evident in S. aureus methicillin resistance, with MRSA accounting for 14.4% of S. aureus isolates in the east, 53.1% in central northern Australia and 46.3% in western northern Australia. Clindamycin-resistant MRSA was highest in the Northern Territory (21.7%) compared to Western Australia (16.1%) and Queensland (5.9%), limiting treatment options for community-acquired MRSA. Ceftriaxone-resistant E. coli also varied geographically, with resistance rates ranging from 3.9% in the east to 23.4% in central and 10.1% in the west. High rates of ceftriaxone resistance were observed in both community clinics (10.6%) and hospitals (16.3%). Nitrofurantoin-resistant E. coli remained low (0.2%) and stable over the past five years.
Interpretation: HOTspots data are critical for informing local antibiotic guidelines and aiding clinical decision-making. This detailed surveillance captures geographic and healthcare-setting-specific variations in AMR, which can improve regional treatment strategies across northern Australia, with a focus on the Northern Territory, which had previously lacked comprehensive surveillance.
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Impact of Glycemic Variability on Vaginal Flora Alterations and Concomitant Antimicrobial Resistance During Pregnancy: Implications for Fetomaternal Outcomes.
Authors: Rafat D et al
Abstract
Purpose: Vaginal flora alterations (AVF) have been implicated in both health and disease states. Few studies have looked at the connection between AVF and adverse fetomaternal outcomes(AFMOs), and even fewer have assessed their concurrent link with gestational diabetes mellitus (GDM). Therefore, this study investigated the association between AVF and GDM and their impact on AFMOs. In addition, we assessed the antimicrobial resistance(AMR) of isolated pathogens and sought to identify the associated risk factors.
Methods: This prospective, cross-sectional study was conducted among 640 pregnant women; divided into two groups, GDM and non-GDM. Standardized questionnaires were administered to collect data regarding sociodemographic and clinical characteristics; collected vaginal samples at 26-38 weeks for Nugent scoring and determination of bacterial and fungal species; assessed AMR of the isolated pathogens and followed up patients for assessment of AFMOs.
Results: It was found that AVF is in 47.5% of participants, with 36.6% having single AVF and 10.9% mixed AVF. There was a significantly higher occurrence of all studied AVF subtypes in GDM group. Also, high prevalence of AMR and MDR among isolated pathogens was noted. The association of AFMO with different AVF subtypes was also found, with higher prevalence of AFMOs among participants with mixed AVF.
Conclusion: The impact of AVF on AFMOs, along with their association with hyperglycemia; provides a potential avenue for working on minimizing AFMOs, which will eventually contribute toward improving the health of both the women and their offspring. The high prevalence of AVF and AMR in this study, calls for effective infection control and stewardship programmes.
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Effectiveness of biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: the BATCH RCT
DOI: 10.3310/MBVA3675
Authors: Cherry-Ann Waldron
Abstract
Background: Procalcitonin is a biomarker specific for bacterial infection, with a more rapid response than other commonly used biomarkers, such as C-reactive protein, but it is not routinely used in the National Health Service.
Objective: To determine if using a procalcitonin-guided algorithm may safely reduce duration of antibiotic therapy compared to standard of care in hospitalised children with suspected or confirmed infection.
Design: A pragmatic, multicentre, open-label, parallel two-arm, individually randomised controlled trial with internal pilot phase, qualitative study and health economic evaluations.
Setting: Paediatric wards or paediatric intensive care units within children’s hospitals (n = 6) and district general hospitals (n = 9) in the United Kingdom.
Participants: Children aged between 72 hours and 18 years admitted to hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection.
Interventions: Procalcitonin-guided algorithm versus usual standard care alone.
Main outcome measures: Coprimary outcomes were duration of intravenous antibiotic use and a composite safety measure.
Results: Between 11 June 2018 and 12 October 2022, 1949 children were recruited: 977 to the procalcitonin group [427 female (43.7%), 550 male (56.3%)], and 972 to the usual care group [478 female (49.2%), 494 male (50.8%)]. Duration of intravenous antibiotics was not significantly different between the procalcitonin group (median 96.0 hours) and the usual care group (median 99.7 hours) [hazard ratio = 0.96 (0.87, 1.05)], and the procalcitonin-guided algorithm was non-inferior to usual care [risk difference = -0.81% (95% confidence interval upper bound 1.11%)]. At clinical review, a procalcitonin result was available for 81.8% of the time, which was considered as part of clinical decision-making 66.6% of the time, and the algorithm was adhered to 57.2% of the time. Incremental cost-effectiveness ratio per duration of intravenous antibiotics hour avoided from bootstrapped samples was £467.62 per intravenous antibiotic hour avoided. Cost analysis of complete cases was also higher in the procalcitonin arm for all age groups, and for children aged 5 years and over. The intervention is not cost-effective as it is more expensive with no significant improvement in intravenous antibiotic duration.
Limitations: Robust antimicrobial stewardship programmes were already implemented in the lead recruiting sites, and adherence to the algorithm was poor. Clinicians may be reluctant to adhere to biomarker-guided algorithms, due to unfamiliarity with interpreting the test result.
Conclusions: In children hospitalised with confirmed or suspected bacterial infection, the addition of a procalcitonin-guided algorithm to usual care is non-inferior in terms of safety, but does not reduce duration of intravenous antibiotics, and is not cost-effective. In the presence of robust antimicrobial stewardship programmes to reduce antibiotic use, a procalcitonin-guided algorithm may offer little added value.
Future work: Future trials must include an implementation framework to improve trial intervention fidelity, and repeated cycles of education and training to facilitate implementation of biomarker-guided algorithms into routine clinical care.
Trial registration: This trial is registered as ISRCTN11369832.
Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/188/42) and is published in full in Health Technology Assessment; Vol. 29, No. 16. See the NIHR Funding and Awards website for further award information.
Keywords: ANTIBIOTIC DURATION; BACTERIAL INFECTION; BIOMARKER; COST-EFFECTIVENESS; HOSPITALISATION; PAEDIATRICS; PROCALCITONIN; QUALITY OF LIFE; RANDOMISED CONTROLLED TRIAL; SECONDARY CARE.
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Prevalence, trends, and molecular insights into colistin resistance among gram-negative bacteria in Egypt: a systematic review and meta-analysis
Authors: Ahmed Azzam
Abstract
Background: This study examines colistin resistance in Gram-negative bacteria in Egypt, analyzing prevalence, trends, geographic variations, colistin-carbapenem resistance correlation, and mcr-mediated plasmid resistance.
Methods: We conducted a systematic search of articles published between 2014 and 2024 that reported on colistin or mcr-mediated resistance in Gram-negative bacteria isolated from human infections in Egypt, with clearly defined susceptibility testing methods. A random-effects meta-analysis was conducted to estimate colistin resistance prevalence based on broth microdilution (BMD) findings, the gold standard method. To explore the influence of study-level factors-including alternative susceptibility testing methods-a multivariate meta-regression analysis was performed. The results of the meta-regression are reported as regression coefficients (β), representing the difference in colistin resistance, expressed in percentage points. All statistical analyses were conducted using R software.
Results: This analysis included 55 studies. Based on BMD susceptibility testing, colistin resistance was observed in 9% of all recovered Gram-negative isolates (95% CI: 6-14%) and was significantly higher among carbapenem-resistant isolates (31%, 95% CI: 25-38%), with p < 0.001. Multivariate meta-regression analysis further confirmed that colistin resistance was significantly higher in carbapenem-resistant isolates compared to the total recovered isolates (β = 9.8% points, p = 0.001). Additionally, colistin resistance has significantly increased over time, with a β = 1.8% points per year (p = 0.001). The use of the VITEK 2 system was associated with lower detected colistin resistance compared to BMD (β = -7.0, p = 0.02). Geographically, resistance rates were higher in Upper Egypt (β = 9.3, p = 0.04). Regarding mcr plasmid-mediated resistance, mcr-1 was the most prevalent resistance gene, particularly in E. coli. In contrast, mcr-2 was rare, detected sporadically in K. pneumoniae and P. aeruginosa.
Conclusion: In Egypt, BMD testing identified colistin resistance in 9% of Gram-negative bacteria, increasing to 31% in carbapenem-resistant isolates. This higher resistance in carbapenem-resistant strains suggests stronger selective pressure from frequent colistin use. Additionally, colistin resistance has shown a rising trend over time, likely driven by increased usage and the spread of plasmid-mediated resistance. These findings underscore the urgent need for strict antimicrobial stewardship and alternative therapies to curb resistance evolution.
Keywords: Mcr; Colistin; Egypt; Gram-negative bacteria; Meta-analysis; Resistance.
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Global knowledge, attitudes, and practices towards antimicrobial resistance among healthcare workers: a systematic review and meta-analysis
Authors: Abdolreza Sotoodeh Jahromi
Abstract
Background: The rising prevalence of antimicrobial resistance (AMR) poses a critical global health challenge. Healthcare workers (HCWs) play a pivotal role in combating AMR by implementing effective preventive strategies and adhering to good practices. This study aimed to evaluate the global knowledge, attitudes, and practices (KAP) of HCWs towards AMR.
Methods: A comprehensive search of PubMed/MEDLINE, ScienceDirect, Scopus, Web of Science, Cochrane Library, and Google Scholar was conducted for English-language articles published up to August 2024. Inclusion criteria were observational studies reporting KAP data among HCWs related to AMR. Study quality was assessed using the Joanna Briggs Institute critical appraisal checklist. Statistical analyses, including heterogeneity (I² statistic, Cochran Q), were conducted using STATA version 14. Random-effects models were applied for pooled estimates, and subgroup analyses, meta-regression, and sensitivity analyses were performed. Publication bias was assessed via Egger’s test and adjusted using the trim-and-fill method. Geographical distribution was analyzed with ArcGIS 10.3 software, and evidence certainty was evaluated using the GRADE framework.
Results: A meta-analysis of 108 studies involving 29,433 HCWs assessed their knowledge of AMR. Additionally, 51 studies with 13,660 HCWs evaluated attitudes, and 43 studies with 10,569 HCWs examined practices regarding AMR. The pooled proportion of HCWs with good knowledge of AMR was 56.5% (95% CI: 50.4-62.6%, I² = 99.5%), with the highest prevalence in Europe (70.3%) and the lowest in the Western Pacific (45.9%). Positive attitudes towards AMR were reported in 60.4% (95% CI: 48.5-72.3%, I² = 99.8%), with the highest prevalence in the Eastern Mediterranean Region (64.5%) and among those with less than five years of experience (77.8%). Good practices were observed in 48.5% (95% CI: 36.5-60.5%, I² = 99.7%), with the highest adherence in Europe (56.6%) and the lowest in Africa (39.1%). Subgroup analysis revealed that younger HCWs (under 30 years) showed better KAP scores across all domains.
Conclusion: The findings underscore the need for targeted interventions to enhance the knowledge, attitudes, and practices of HCWs regarding AMR. Priority should be given to designing and implementing robust training programs tailored to the specific needs of HCWs in resource-constrained settings. Strengthening AMR-related education and practice among HCWs is crucial for combating the global AMR crisis effectively.
Keywords: Antibiotic resistance; Antimicrobial stewardship; Global health; Health personnel.
© 2025. The Author(s).
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Pharmacodynamic Effect of Different Dosage Regimes of Oseltamivir in Severe Influenza Patients Requiring Mechanical Ventilation: A Multicentre Randomised Controlled Trial
DOI: 10.1111/irv.70109.
Authors: Wai-Tat Wong
Abstract
Background and objectives: This randomised controlled trial evaluated whether higher doses of oseltamivir would improve virological and clinical outcomes in severe influenza patients requiring invasive mechanical ventilation.
Methods: Forty intubated adult patients with severe influenza A or B from four intensive care units in Hong Kong were enrolled and randomised to receive either a double dose (300 mg/day) or a triple dose (450 mg/day) of oseltamivir for 10 days. Baseline data were collected, and outcomes were assessed daily using SOFA and Murray scores. Viral RNA was quantified from nasopharyngeal and tracheal aspirates. The primary outcome was the viral clearance rate after 5 days of treatment; secondary outcomes included 28-day and hospital mortality rates, changes in viral load, and serial SOFA and Murray scores.
Results: Viral clearance rates after 5 days of treatment were low and similar between the double (3/20, 15%) and triple-dose groups (2/20, 10%). No significant differences were observed in 28-day mortality, hospital mortality, ICU length of stay or duration of mechanical ventilation between the double and triple-dose groups. However, patients receiving triple doses exhibited a faster decline in influenza A viral load but had a longer hospital length of stay.
Conclusions: Triple doses of oseltamivir did not significantly improve virological or clinical outcomes compared with double doses in severe influenza.
Keywords: mechanical ventilation; oseltamivir; severe influenza.