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Understanding antimicrobial resistance (AMR) mechanisms and advancements in AMR diagnostics.
Authors: Sinha S et al
Abstract
The overuse and abuse of antibiotics, which results in the evolution of resistant microorganisms, is the primary cause of the global health catastrophe known as antimicrobial resistance (AMR). The enzymatic breakdown of antibiotics, target site modification, efflux pump overexpression, and the formation of biofilm are some of the mechanisms responsible for acquiring antimicrobial resistance (AMR). These mechanisms enable bacteria to evade or neutralize the effects of antimicrobial agents, complicating treatment options and increasing mortality rates. The rapid dissemination of resistance genes via horizontal gene transfer further exacerbates the problem, necessitating urgent intervention. Advanced AMR diagnostics are transforming the fight against antimicrobial resistance. Biosensors enable rapid, point-of-care detection; Cluster regularly interspaced short palindromic repeat (CRISPR) technologies offer precise identification of resistance genes; and mass spectrometry provides fast, accurate profiling. Automated systems streamline workflows and boost throughput, while flow cytometry delivers real-time, single-cell analysis of phenotypic resistance. Together, these innovations accelerate detection and support targeted antimicrobial stewardship, essential for combating the global AMR threat. This review covers the mechanisms underlying antimicrobial resistance (AMR) and recent advancements in AMR diagnostic technologies.
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Estimating Global Antibiotic Needs for Chronic Obstructive Pulmonary Disease and Community- and Hospital- acquired Pneumonia in 20 Countries: A Modelling Analysis.
Authors: Summan A et al
Abstract
Introduction: Antibiotic stewardship advocates for prudent antibiotic use. However, estimates of ‘appropriate’ antibiotic use remain limited.
Methods: The total antibiotics required to treat chronic obstructive pulmonary disease (COPD) exacerbations and pneumonia in 2019 across the 20 most populous countries were estimated. Antibiotic needs were determined according to World Health Organization AWaRe guidelines. The proportion of cases requiring antibiotics was based on bacterial etiology averages. Patients not responding to first-line treatment were assumed to either recover after second-line treatment, discontinue further care, or die during treatment. Where two treatment options were available, patients were assumed to be evenly split.
Results: Penicillins (76.1%) and cephalosporins (22.6%) were the most frequently needed antibiotics, for treatment of community-acquired pneumonia, followed by hospital-acquired pneumonia, and COPD exacerbations. India and China were estimated as the greatest consumers of penicillins (37% and 21% of total use, respectively), followed by the U.S., Brazil, and Indonesia (15% combined). Per capita penicillin consumption was highest in India, Brazil, and Germany. In total, 2,276,046 and 676,098 million mg of penicillins and cephalosporins, respectively, were needed.
Conclusions: Prudent antibiotic use is essential to curb antimicrobial resistance. This framework offers a method for estimating needs and informing global planning.
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Improved diagnostic stewardship in carbapenem-resistant Enterobacterales gene detection helps in early initiation of targeted therapy.
DOI: 10.1099/jmm.0.002029
Authors: Guchhait P et al
Abstract
Introduction. Antimicrobial resistance (AMR) is an escalating global health crisis, leading to ~700,000 deaths annually. Without significant containment efforts, this number could surge to 10 million by 2050. Carbapenem-resistant organisms, particularly carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii, present a critical challenge due to their ability to evade potent carbapenem antibiotics.
Hypothesis and Aim. This study aimed to determine the prevalence of CRE among 1,317 culture-positive patients and to assess the impact of advanced diagnostic techniques, such as RT-PCR, modified carbapenem inactivation method (mCIM), EDTA carbapenem inactivation method (eCIM) and Vitek susceptibility testing, on improving diagnostic stewardship and patient outcomes.
Methodology. A retrospective cross-sectional study was conducted at Peerless Hospitex Hospital and Research Centre Limited, Kolkata, from June 2023 to May 2024. CRE isolates were identified from various clinical samples and subjected to phenotypic (Vitek 2, mCIM and eCIM) and genotypic real time polymerase chain reaction (RT-PCR) testing for carbapenemase genes. Data on demographics, specimen types, bacterial isolates, comorbidities, etc. were analysed.
Results. Out of 20,129 inpatient samples sent for culture during this 1-year period, 3,124 (15.51%) had culture-proven infections. A total of 1,317 Enterobacterales isolates were processed for carbapenem resistance (CR) detection PCR, with 354 (26.88%) identified as CRE. Klebsiella pneumoniae was the predominant isolate (60.17%), followed by Escherichia coli (26.55%). New Delhi metallo-β-lactamase (MBL) (NDM) and OXA-48-like co-production (33.75%) were most commonly seen, followed by NDM gene alone (32.50%). The concordance between phenotypic susceptibility and genotypic PCR method for CRE was 85.88%. Targeted antibiotic therapy could be initiated based on PCR results, in 70.90% of cases. Synergy test guided effective combination therapy of ceftazidime-avibactam and aztreonam for MBL-producing CRE isolates.
Conclusion. The study highlights a significant prevalence of CRE, particularly among older adults. Advanced diagnostic techniques improved diagnostic stewardship, allowing timely and accurate detection of CR. However, discrepancies between phenotypic and genotypic methods and the high cost of certain therapies are notable limitations. Enhanced infection control and early initiation of targeted therapy are crucial to combat AMR.
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Empiric and targeted antibiotic therapy for bloodstream infections in internal medicine patients in Poland: a three-year analysis in a single centre using the AWaRe classification.
Authors: Piekiełko P et al
Abstract
Background: Bloodstream infection (BSI), defined as bacteraemia accompanied by sepsis or septic shock, is a frequent cause of hospitalization in departments of internal medicine (DIM). This study aimed to characterize the epidemiology, microbiological profile, and antibiotic treatment patterns of BSIs in a DIM setting in 2021-2023 in Polish hospital.
Methods: A three-year, single-centre retrospective analysis was conducted at a DIM in Southern Poland. Medical records from 2021 to 2023 were reviewed for patients diagnosed with sepsis (ICD-10 codes A40-A41) with microbiological confirmation. Antibiotic use was assessed using Days of Therapy (DOT) and Length of Therapy (LOT). Empiric and targeted therapies were classified according to the WHO AWaRe (Access, Watch, Reserve) framework.
Results: A total of 124 BSI cases were identified, with an incidence rate of 5.8%. Community-acquired BSIs accounted for 84.3% of cases, while 15.7% were hospital-acquired. The predominant pathogens were Escherichia coli and Staphylococcus aureus. The median LOT for empiric therapy was 3 days (IQR 2-4), with third-generation cephalosporins being the most frequently used agents (78 patients; 43.3%, 228 DOTs; 43.9%). Targeted therapy had a median LOT of 8 days (IQR 5-10), most commonly involving penicillins (33 patients; 28.4%, 291 DOTs; 34.5%). Access group antibiotics were significantly more prevalent in targeted therapy compared to empiric therapy (p < 0.001).
Conclusions: Microbiological confirmation of BSI facilitates a safe de-escalation from broad-spectrum empiric antibiotics to narrow-spectrum targeted therapy, supporting antimicrobial stewardship in internal medicine settings.
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Superbug Surge-A Tale of Seven-Year Battle Against Escalating Antimicrobial Resistance in North India.
Authors: Fomda BA et al
Abstract
Antimicrobial resistance (AMR) is a global health concern, significantly impacting treatment outcomes. This prospective study, conducted from 2018 to 2024, under the Indian Council of Medical Research Antimicrobial Resistance Surveillance Network (ICMR-AMRSN), aims to assess bacterial prevalence and antimicrobial resistance patterns in a tertiary care hospital in North India. Clinical specimens were collected from outpatients, inpatients, and intensive care units (ICUs). Bacterial identification and antimicrobial susceptibility testing were done as per CLSI guidelines using conventional and automated methods. Phenotypic (Combined Disk test, CarbaNP, mCIM, eCIM, PBP2a latex agglutination test, D test, Penicillin Zone Edge test) and genotypic characterisation (like CTX-M, TEM, SHV, VIM, KPC, NDM1, mecA, van, erm gene detection) of the isolates was performed. All the data was recorded and analyzed using the online ICMR-AMRSN portal. Out of a total of 1,30,077 samples,20,509 (15.8%) were culture-positive, and positivity was high from urine samples (n = 6036, 29.4%), followed by respiratory samples (n = 3739, 18.2%), deep infections (13.2%, n = 2700) and blood samples (n = 1363, 6.6%). Gram-negative bacteria predominated (n = 16,477, 80.3%), with Escherichia coli (n = 6623, 32.3%) being the most common, followed by Klebsiella pneumoniae (n = 3381, 16.5%), Acinetobacter baumannii (n = 3017, 14.7%) and Pseudomonas aeruginosa (n = 2208, 10.8%). Among Gram-positive bacteria (n = 3950, 19.2%), Staphylococcus aureus (n = 1650, 8%) was most prevalent followed by Enterococcus faecalis (n = 786, 3.8%) and Enterococcus faecium (n = 673, 3.3%). Acinetobacter baumannii was the leading ICU pathogen (n = 869,41.9%). High resistance rates were observed, particularly in carbapenem-resistant A. baumannii and methicillin-resistant S. aureus (MRSA). Genotypic analysis confirmed the presence of beta-lactamase and carbapenemase genes in key pathogens. The study highlights the substantial burden of AMR, with rising resistance trends posing therapeutic challenges. Continuous surveillance, infection control measures, and antimicrobial stewardship are crucial for combating AMR and guiding regional antibiotic policies.
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Comparison of HANDOC and Chamat-Hedemand’s risk stratification systems for predicting infective endocarditis among patients with non-beta-hemolytic streptococci blood stream infections
Authors: Gustav Pernow
Abstract
Background: Non-β-hemolytic streptococci (NBHS) cause blood stream infections (BSI) which can be complicated by infective endocarditis (IE). To stratify the risk for IE in NBHS BSI and to guide the use of echocardiography in this condition, two risk stratification systems (RSSs), the HANDOC score (HANDOC), and the Chamat-Hedemand algorithm (CH-A) have been developed.
Objectives: To compare the sensitivity and the specificity of HANDOC and CH-A and to describe how the utilization of transesophageal echocardiography (TEE) would be affected using either HANDOC or CH-A.
Methods: A retrospective, population-based cohort study of patients with blood cultures positive for NBHS during 2018 was performed. Medical records of the included patients were studied for classification of the episodes according to HANDOC, CH-A, and the Duke-ISCVID criteria.
Results: Three hundred and twenty-five episodes of NBHS BSIs involving 308 patients were included. Twenty-one episodes (6.5%) met the Duke-ISCVID criteria for definite IE. TEE was performed in 26% of episodes. HANDOC had a sensitivity of 95% and a specificity of 73% for definite IE whereas CH-A had a sensitivity of 90% and a specificity of 63%. The CH-A outcome ‘any echocardiography’ had a sensitivity of 100% for definite IE, but the specificity was only 24%. In this cohort, implementation of the RSSs would lead to an increase in the utilization of TEE compared to the real-life use, both when using HANDOC (+22%) and CH-A (+60%).
Conclusion: HANDOC had the highest combined sensitivity and sensitivity for IE. The utilization of TEE would increase using these RSSs, especially the CH-A.”
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Outcomes of a paediatric antimicrobial stewardship program in the Emergency Department observation unit of a hospital in Spain
Authors: Paloma
Abstract
Background: In paediatric emergency departments the use of empirical antimicrobials is very common, even though most infections are caused by viruses, resulting in misuse of antimicrobials. We aimed to assess the impact of a comprehensive antimicrobial stewardship program (ASP) on the optimisation of antimicrobial prescribing and clinical outcomes in a paediatric Emergency Department Observation Unit (EDOU).
Methods : A quasi-experimental before-and-after longitudinal study was conducted at the EDOU of a paediatric hospital, over 24 quarters from January 2017 to December 2023, excluding 2020 due to the pandemic and the phase-in period. The ASP intervention included the development and implementation of clinical guidelines, rapid diagnostic tests (RDTs), and staff stabilisation. Data on antimicrobial use and clinical outcomes, such as revisits within 72 h and hospital admissions, were collected and analysed using Bayesian structural time series models.
Results : The study included 33,799 patients transferred to the EDOU. Mean antimicrobial consumption significantly decreased from 46.5 ± 12.9 pre-intervention defined daily doses (DDDs) per 100 patients transferred to the Observation Unit (TOs) to 20.1 ± 3.0 DDDs per 100 TOs in the intervention period (p < 0.0001). Significant reductions were observed for amoxicillin-clavulanic acid, amoxicillin, and azithromycin. The percentage of revisits and hospital admissions remained stable for the whole period.
Conclusion:
The implementation of ASP measures improved antimicrobial prescribing in the paediatric EDOU. These findings support the need for continued efforts in ASP, emphasising the development and implementation of guidelines, RDTs, and staff stabilisation.”
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The association of oral polio vaccine doses and severity of paralysis: an analysis of wild poliovirus type 1 cases in Pakistan
Authors: Soghaier, Mohammed
Abstract
Background: Wild poliovirus type 1 (WPV1) transmission persists in Pakistan, with cases increasing from 6 in 2023 to 56 by November 2024, highlighting critical challenges in polio eradication efforts. The aim of this study is to assess the relationship between bivalent oral polio vaccine (bOPV) doses and the severity of paralysis in the confirmed WPV1 cases in Pakistan.
Methods :We analysed all confirmed WPV1 cases reported in Pakistan from January 1, 2024, to November 15, 2024. Bivariate analyses were first conducted to explore initial associations. Firth, logistic regression models were then employed to evaluate the strength of these associations while adjusting for potential confounders.
Results: Higher bOPV doses were significantly associated with a lower risk of severe paralysis in both univariate analysis (OR = 0.75, 95% CI: 0.60–0.93, p = 0.009) and after adjustment for age and sex (OR = 0.76, 95% CI: 0.59–0.97, p = 0.026). For residual paralysis after 60 days of onset, univariate analysis showed a significant association (OR = 0.77, 95% CI: 0.61–0.97, p = 0.026); however, this association was no longer statistically significant after adjustment (OR = 0.82, 95% CI: 0.64–1.05, p = 0.115).
Conclusion: The study found a significant association between higher bOPV dose count and reduced paralysis severity in confirmed WPV1 cases. These findings suggest that bOPV may help to moderate the severity of paralysis, in addition to preventing WPV1 infection.”
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Epidemiology of acute undifferentiated febrile illness and acute encephalitis syndrome cases in Northern India: a prospective observational study
Authors:Bhardwaj, Pooja
Abstract
Purpose : Acute undifferentiated febrile illness (AUFI) and acute encephalitis syndrome (AES) continue to be major public health concerns, particularly in rural areas with limited healthcare facility. We investigated the aetiological agents responsible for seasonal sporadic AUFI and AES cases in Northern India.
Method : The study included 4200 patient samples (April 2022 to March 2024), fulfilling the AUFI or AES case definition. Clinical samples were tested for IgM antibodies against dengue, chikungunya, Japanese encephalitis, scrub typhus, and leptospirosis. Further, Leptospira IgM ELISA positives (n = 79) were also tested by microscopic agglutination test (MAT) assay.
Results : In AUFI cases, scrub typhus was the predominant bacterial aetiology (24.6%, 593/2407) followed by leptospirosis (12.4%, 266/2151). Dengue (23.0%, 321/1398) was the leading cause among viral aetiologies. Similarly, among AES cases, scrub typhus (36% in cerebrospinal fluid and 34.3% in serum) remained the most common bacterial aetiology followed by leptospirosis (5.42%, 11/203). Whereas, chikungunya was the predominant viral cause (5.4%, 17/314) behind AES cases. Further, using MAT assay, 7.6% (6/79) of the AUFI samples tested positive for leptospirosis. The prevalent serogroups identified included L. interrogans serovars Australis, Pomona, Hebdomadis, Pyrogenes and Djasiman, and L. borgpetersnii serovar Tarassovi. Housewives constituted the primary risk group for leptospirosis infection, followed by individuals engaged in various farming practices.
Conclusion: This study identifies scrub typhus as the predominant and leptospirosis as the second most common infection in sporadic cases of AUFI and AES. Therefore, continuous monitoring of changing aetiologies is crucial for the effective implementation of targeted control and preventive measures for neglected tropical diseases.”