Background Antibiotic Resistance Research Articles

Genome-centric metagenomes unveiling the hidden resistome in an anchialine cave

BackgroundAntibiotic resistance is a critical global concern, posing significant challenges to human health and medical treatments. Studying antibiotic resistance genes (ARGs) is essential not only in clinical settings but also in diverse environmental contexts. However, ARGs in unique environments such as anchialine caves, which connect both fresh and marine water, remain largely unexplored despite their intriguing ecological characteristics.ResultsWe present the first study that comprehensively explores the occurrence and distribution of ARGs and mobile genetic elements (MGEs) within an anchialine cave. Utilizing metagenomic sequencing we uncovered a wide array of ARGs with the bacitracin resistance gene, bacA and multidrug resistance genes, being the most dominant. The cave’s microbial community and associated resistome were significantly influenced by the salinity gradient. The discovery of novel β-lactamase variants revealed the cave’s potential as a reservoir for previously undetected resistance genes. ARGs in the cave demonstrated horizontal transfer potential via plasmids, unveiling ecological implications.ConclusionsThese findings highlight the need for further exploration of the resistome in unique environments like anchialine caves. The interconnected dynamics of ARGs and MGEs within anchialine caves offer valuable insights into potential reservoirs and mechanisms of antibiotic resistance in natural ecosystems. This study not only advances our fundamental understanding but also highlights the need for a comprehensive approach to address antibiotic resistance in diverse ecological settings.

Predicting early appropriate therapy for patients infected by carbapenem-resistant Gram-negative pathogens in intensive care units in Italy

BackgroundAntibiotic resistance among Gram-negative bacteria in intensive care units (ICUs) is linked with high morbidity and mortality in patients. In this study, we estimated the therapeutic coverage of various antibiotics, focusing on cefiderocol and comparators, administered empirically against an infection of unknown origin in the ICU.MethodsIn the ARTEMIS surveillance study, susceptibilities of 624 Italian Gram-negative isolates to amikacin, aztreonam-avibactam, cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, colistin, imipenem-relebactam, meropenem, and meropenem-vaborbactam were tested by broth microdilution, and results were interpreted by European Committee on Antimicrobial Susceptibility Testing breakpoints. The susceptibility rates from the ARTEMIS study were extrapolated to Gram-negative isolates obtained from 5,774 patients in Italian ICUs in 2021. The sum of the predicted susceptibilities of individual pathogens represented the overall likelihood of in vitro activity of each antibiotic as early targeted therapy for ICU patients.ResultsA total of 624 Italian Gram-negative isolates included 206 Pseudomonas aeruginosa, 138 Acinetobacter baumannii, 187 Klebsiella pneumoniae, and 93 Escherichia coli. Against A. baumannii, K. pneumoniae, P. aeruginosa, and E. coli, the overall susceptibility rates for cefiderocol were 87.7%, 96.8%, 99%, and 100%, respectively; and for comparator agents, 8.7–96.4%, 25.7–100%, 73.3–100%, and 89.2–100%, respectively. Among the subset of meropenem-resistant isolates, susceptibility rates of A. baumannii, K. pneumoniae, and P. aeruginosa to cefiderocol were 86.4%, 96.2% and 100%, respectively. Corresponding susceptibility rates to comparator agents were 0–96.8%, 0–100%, and 6.4–100%, respectively. There were no meropenem-resistant isolates of E. coli. The extrapolation of data to isolates from Italian ICUs showed that the highest likelihood of therapeutic coverage, both overall and among meropenem-resistant isolates, was reported for colistin (96.8% and 72.2%, respectively) and cefiderocol (95.7% and 71.4%, respectively). All other antibiotics were associated with a likelihood below 73% overall and between 0% and 41.4% for meropenem-resistant isolates.ConclusionsBased on confirmed susceptibility rates and reported ICU prevalence of multiple Gram-negative species, cefiderocol showed a higher predicted therapeutic coverage and utility in ICUs compared with comparator beta-lactam–beta-lactamase inhibitor antibiotics. Cefiderocol may be a promising early treatment option for patients at high risk of carbapenem-resistant Gram-negative bacterial infections in the ICU.

Antibiotic Resistance Profiles of Escherichia coli and Salmonella spp. Isolated From Dairy Farms and Surroundings in a Rural Area of Western Anatolia, Turkey.

Background Antibiotic resistance is a significant public health issue worldwide. Antibiotic-resistant zoonotic bacteria such as Escherichia coli (E. coli), Campylobacter, Salmonella, Listeria, Coxiella, and Mycobacterium can be particularly isolated from biofertilizers. Epidemiological studies have shown that cases of foodborne infections and intoxications are significantly related to animal-derived foods. The presence of these species in aquatic environments indicates areas or organisms contaminated with animal or human feces. Especially, the presence of E. coli in aquatic environments has become a serious problem worldwide. Pathogenic strains of E. coli cause waterborne and foodborne diseases. Materials and methods This study included a total of 290 samples collected from five different dairy farms between April and September 2023 which comprised 20 samples of cow manure, 20 samples of milk, three samples of dairy workers' hand washing water, five samples ofsoil, five samples of water, and five samples of vegetables. The samples taken from the farms were homogenized with 0.1% peptone water at a ratio of 1/10. They were then cultured on xylose lysine deoxycholate (XLD), eosin methylene blue agar (EMB), and blood agar media, and gram-negative colonies were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and the VITEK2 automated system (BioMerieux Inc., Durham, NC). Amplification of the isolated DNA extracts was performed with A.B.T.™ 2X HS-PCR MasterMix (A.B.T Laboratory Industry, Arnavutköy, Turkey) in the SimpliAmp™ thermal cycler (Thermo Fischer Scientific Inc., Waltham, MA) and visualized by agarose gel electrophoresis. Results Among the 52E. coli strains isolated in our study, the highest antibiotic sensitivity rate was observed in meropenem, while the lowest sensitivity rates were determined in cefazolin and cefuroxime. While two of the Salmonella spp. (n = 2) isolates were found to be resistant to tetracycline, and one was found to be resistant to penicillin and ampicillin. No resistance to trimethoprim/sulfamethoxazole was detected in either isolate. Extended-spectrum beta-lactamases (ESBLs) were detected in only four (7.7%) E. coli strains. While tetA, tetB, and TEM genes were seen in almost all E. coli strains, they were not found in Salmonella spp. Conclusion In conclusion, our study revealed the presence of antimicrobial resistance genes in E. coli and Salmonella spp. isolates collected from various farms and environmental samples, which render the antimicrobials used for disease treatment ineffective. Consequently, research should be undertaken to prevent the development of new resistance genes in our country, as creating new medications and treatment strategies for these diseases is costly and time-intensive.

Surface enhanced Raman spectroscopy and machine learning for identification of beta-lactam antibiotics resistance gene fragment in bacterial plasmid

BackgroundAntibiotic resistance stands as a critical medical concern, notably evident in commonly prescribed beta-lactam antibiotics. The imperative need for expeditious and precise early detection methods underscores their role in facilitating timely intervention, curbing the propagation of antibiotic resistance, and enhancing patient outcomes. ResultsThis study introduces the utilization of surface-enhanced Raman spectroscopy (SERS) in tandem with machine learning (ML) for the sensitive detection of characteristic gene fragments responsible for antibiotic resistance appearance and spreading. To make the detection procedure close to the real case, we used bacterial plasmids as starting biological objects, containing or not the characteristic gene fragment (up to 1:10 ratio), encoding beta-lactam antibiotics resistance. The plasmids were subjected to enzymatic digestion and without preliminary purification or isolation the created fragments were captured by functional SERS substrates. Based on subsequent SERS measurements, a database was created for the training and validation of ML. Method validation was performed using separately measured spectra, which did not overlap with the database used for ML training. To check the efficiency of recognising the target fragment, control experiments involved bacterial plasmids containing different resistance genes, the use of inappropriate enzymes, or the absence of plasmid. SignificanceSERS-ML allowed express detection of bacterial plasmids containing a characteristic gene fragment up to the 10−7 concentration of the initial plasmid, despite the complex composition of the biological sample, including the presence of interfering plasmids. Our approach offers a promising alternative to existing methods for monitoring antibiotic-resistant bacteria, characterized by its simplicity, low detection limit, and the potential for rapid and straightforward analysis.

The effect of silver nanoparticles on the antimicrobial activity of cloned nisin against extensively drug-resistant Acinetobacter baumannii”

BackgroundAntibiotic resistance is a global threat to human health that leads to disasters. Acinetobacter baumannii cannot be controlled by the existing antibiotics, and it became challenging. Therefore, novel antibacterial agents are required to combat such threats. The aim of this project is to find a novel antimicrobial agent to treat this multi-drug resistant bacterium. MethodsThe NisA gene was isolated from Lactococcus lactis spp. lactis and cloned into the pET-3a plasmid using Gibson cloning assembly. Purified Nisin from cloning was conjugated with silver nanoparticles. Finally, an assessment of antibacterial activity for each of the purified Nisin, Silver nanoparticles, and Nisin-Silver nanoparticles conjugate against the extensively drug-resistant A. baumannii was performed. ResultsNisin was successfully purified from cloned bacteria, and the concentration was 416 µg/ml. The conjugation of nisin and silver nanoparticles was analyzed by electron microscopy. The minimum inhibitory concentration of Nisin and silver nanoparticles against A. baumannii were 104 µg/ml and 125 µg/ml, respectively. While Nisin-silver nanoparticle conjugates showed potent antimicrobial activity with MIC 125–52 µg/ml in which silver nanoparticles increased the antimicrobial activity of nisin beyond its optimum concentration (104 µg/ml). ‎ ConclusionThe development of new antibacterial agents is necessary to control extensively drug-resistant bacteria. Nisin-silver conjugates showed more potent antimicrobial activity than when applied separately and gave hope to combat the multi-drug resistant A. baumannii.

Seeing an apocalyptic post-antibiotic future lowers antibiotics expectations and requests

BackgroundAntibiotic resistance is an ongoing pandemic which represents a global public health threat. To encourage the judicious use of antibiotics, public health discourse and campaigns often engage in threat-based messaging depicting an apocalyptic post-antibiotic future. We studied the effectiveness of the strategy because of mixed evidence for its success, and because it is unclear how experiencing the COVID-19 pandemic might have influenced it.MethodsWe conducted a randomised controlled trial with 378 participants in three waves (before and during the pandemic in 2021 and 2022). Participants were randomly allocated to either the baseline arm, featuring a control film, or the intervention arm featuring a short film, Catch, depicting a post-antibiotic future. Participants expressed expectations and intended requests for antibiotics for a hypothetical ear infection and their adherence to a prescribed antibiotic for a hypothetical kidney infection. In waves 2 and 3, they also reported any COVID-19-related changes to their antibiotic desires.ResultsShowing participants a film about a post-antibiotic future substantially lowers clinically inappropriate expectations for antibiotics and their intended requests. Participants report that the experience of the COVID-19 pandemic decreased their desire for antibiotics but only when they watched the intervention film. The intervention slightly decreases participants’ adherence intentions towards a prescribed antibiotic treatment.ConclusionsPresenting a film about an apocalyptic post-antibiotic future lowers expectations and intended requests for antibiotics and therefore has the potential to encourage judicious use of them. However, the adverse effects of such messaging on adherence to a course of antibiotics should be proactively managed.

Integrated surveillance systems for antibiotic resistance in a One Health context: a scoping review

BackgroundAntibiotic resistance (ABR) has emerged as a major threat to health. Properly informed decisions to mitigate this threat require surveillance systems that integrate information on resistant bacteria and antibiotic use in humans, animals, and the environment, in line with the One Health concept. Despite a strong call for the implementation of such integrated surveillance systems, we still lack a comprehensive overview of existing organizational models for integrated surveillance of ABR. To address this gap, we conducted a scoping review to characterize existing integrated surveillance systems for ABR.MethodsThe literature review was conducted using the PRISMA guidelines. The selected integrated surveillance systems were assessed according to 39 variables related to their organization and functioning, the socio-economic and political characteristics of their implementation context, and the levels of integration reached, together with their related outcomes. We conducted two distinct, complementary analyses on the data extracted: a descriptive analysis to summarize the characteristics of the integrated surveillance systems, and a multiple-correspondence analysis (MCA) followed by a hierarchical cluster analysis (HCA) to identify potential typology for surveillance systems.ResultsThe literature search identified a total of 1330 records. After the screening phase, 59 references were kept from which 14 integrated surveillance systems were identified. They all operate in high-income countries and vary in terms of integration, both at informational and structural levels. The different systems combine information from a wide range of populations and commodities -in the human, animal and environmental domains, collection points, drug-bacterium pairs, and rely on various diagnostic and surveillance strategies. A variable level of collaboration was found for the governance and/or operation of the surveillance activities. The outcomes of integration are poorly described and evidenced. The 14 surveillance systems can be grouped into four distinct clusters, characterized by integration level in the two dimensions. The level of resources and regulatory framework in place appeared to play a major role in the establishment and organization of integrated surveillance.ConclusionsThis study suggests that operationalization of integrated surveillance for ABR is still not well established at a global scale, especially in low and middle-income countries and that the surveillance scope is not broad enough to obtain a comprehensive understanding of the complex dynamics of ABR to appropriately inform mitigation measures. Further studies are needed to better characterize the various integration models for surveillance with regard to their implementation context and evaluate the outcome of these models.

A Study of Awareness, Knowledge, Attitudes, and Practices Regarding Antibiotic Resistance.

Background Antibiotic resistance is a critical global health concern, intensified by public misconceptions and inconsistent antibiotic use. Misunderstandings about antibiotics and their improper use contribute to the acceleration of resistance, making it harder to treat infections effectively. Previous research has identified knowledge gaps in the public, yet there is limited understanding of how these gaps translate into attitudes and practices across different demographic groups. This study aimed to assess the levels of knowledge, attitudes, and practices regarding antibiotic resistance among various demographic groups and to determine the influence of demographic factors on these variables. Methods A descriptive study was conducted using a structured online questionnaire distributed through social media and health forums. The questionnaire targeted adults aged 18 years and older from diverse socioeconomic backgrounds. Data were analyzed using SPSS version 26 (Armonk, NY: IBM Corp.) for descriptive statistics, chi-square tests, and logistic regression analysis. Results The study included responses from 1,561 participants, revealing that 75.72% had knowledge of antibiotic resistance, but only 68.23% understood its public health implications. Attitudes toward antibiotic use were generally positive, with 90.14% recognizing the importance of completing antibiotic courses. However, 32.16% admitted they would stop taking antibiotics once feeling better, even if the course was not finished, highlighting a significant gap between knowledge and practice. Regression analysis identified awareness of prevention measures (coefficient=2.06) and knowledge of antibiotic resistance (coefficient=1.38) as strong predictors of awareness. The chi-square test showed a significant association between gender and awareness of prevention measures (chi-square value=15.19, p-value=0.000097). Conclusions Despite a high level of knowledge about antibiotic resistance, gaps in attitudes and practices persist. These findings underscore the necessity for tailored educational campaigns that not only inform but also engage and alter behaviors across all demographic groups to combat antibiotic resistance effectively.

A cross-sectional analysis of antibiotic use: Attitudes and practices in the Albanian community

BackgroundAntibiotic resistance (AR) represents a global health challenge. Within the coordinated efforts to tackle AR, community education is a key strategy to enhance awareness and improve antibiotic use. The current study intends to investigate the Albanian community's attitude and practices regarding antibiotic use, including recent health related developments, like COVID-19. MethodsA cross sectional survey was conducted among Albanian residents between December 2022 and March 2023, using a standardized questionnaire which featured three sections covering demographic data, attitudes, and practices regarding antibiotic use. Statistical analysis included both descriptive statistics and the Chi-square test to assess relationships between categorical variables. ResultsThe questionnaire was effectively completed by 519 participants. The majority were females (70.1 %) within the 18–30 age range (55.5 %) and had a college/university degree (93.3 %). 53.4 % reported antibiotic use without a medical prescription, with amoxicillin and azithromycin being the most used antibiotics. Commonly cited reasons for antibiotic use were self-reported symptoms such as flu/common cold, sore throat, cough, and fever (82.3 %). 69.0 % reported following prescribed antibiotic courses, with higher adherence among females and those with higher education. Awareness of AR was considerable (78.0 %), with females evidencing more awareness compared to males. Only 34.3 % of participants reported antibiotic use for COVID-19, mostly after testing positive, with azithromycin being the most frequently used antibiotic. ConclusionsOur study highlights concerning trends in antibiotic self-medication and awareness gaps in prudent antibiotic use emphasizing the need for tailored educational programs, regulatory oversight, and robust surveillance systems in Albania's healthcare.

Upregulation of pmrA, pmrB, pmrC, phoQ, phoP, and arnT genes contributing to resistance to colistin in superbug Klebsiella pneumoniae isolates from human clinical samples in Tehran, Iran

BackgroundAntibiotic resistance in Klebsiella pneumoniae isolates, particularly resistance to colistin, has become a growing concern. This study seeks to investigate the upregulation of specific genes (pmrA, pmrB, pmrC, phoQ, phoP, and arnT) that contribute to colistin resistance in K. pneumoniae isolates collected from human clinical samples in Tehran, Iran. MethodsThirty eight K. pneumoniae isolates were obtained and subjected to antibiotic susceptibility testing, as well as evaluation for phenotypic AmpC and ESBL production according to CLSI guidelines. The investigation of antibiotic resistance genes was conducted using polymerase chain reaction (PCR), whereas the quantification of colistin resistance related genes expressions was performed via Real-Time PCR. ResultsThe highest and lowest antibiotics resistance were observed for cefotaxime 33 (86.8%) and minocycline 8 (21.1%), respectively. Twenty-four (63.2%) and 31 (81.6%) isolates carried AmpC and ESBLs, respectively. Also, antibiotic resistance genes containing blaNDM, blaIMP, blaVIM, blaSHV, blaTEM, blaCTXM, qnrA, qnrB, qnrS, and aac(6')-Ib were detected in K. pneumoniae isolates. Only 5 (13.1%) isolates were resistant to colistin and the MIC range of these isolates was between 4 and 64 μg ml−1. Upregulation of the pmrA, pmrB, pmrC, phoQ, phoP, and arnT genes was observed in colistin-resistant isolates. The colistin-resistant isolates were found to possess a simultaneous presence of ESBLs, AmpC, fluoroquinolone, aminoglycoside, and carbapenem resistant genes. ConclusionsThis study reveals escalating antibiotic resistance in K. pneumoniae, with notable coexistence of various resistance traits, emphasizing the need for vigilant surveillance and innovative interventions.

Factors Associated with Inappropriate Use of Antibiotics Among Animal Health Professionals in Selected Districts of Rwanda, 2021

BackgroundAntibiotic resistance is a global health concern. Humans can acquire antibiotic resistance through human-to-human transmission, from the environment, via the food chain, and through the contact with animals. The National Action Plan on antimicrobial resistance 2020–2024 highlights the prudent use of antibiotics in veterinary activities as the key element in keeping antibiotics effective. We determined the factors associated with misuse of antibiotics among animal health professionals in Rwanda.MethodsThis was a cross-sectional study that enrolled animal health field professionals from five districts, where stratified random sampling was used to select one district by each province of Rwanda. Structured questions were used during face-to-face interviews. The misuse of antibiotics was defined as the use of antibiotics for reasons other than treatment, the non-completion of required courses, or the use of a high dose (i.e., an overdose) of antibiotics. We collected socio-demographic data of respondents, as well as elementary knowledge and perceptions on veterinary antibiotics and antibiotic resistance. A backward stepwise logistic regression model was used to identify the factors that were predictive of the inappropriate use of antibiotics.ResultsThere were 256 respondents to the survey. Of those, 198 were male and 58 were female. Almost three quarters of respondents (n = 174/256; 68%) reported the misuse of antibiotics at least once in the previous 12 months. The final logistic regression analysis identified the following factors to be predictive of antibiotics misuse: aged ≤ 24 years (aOR 0.92; 95% CI [0.88, 0.96]; p < 0.001); low trust in veterinary antibiotics available in the local market (aOR 8.45; 95% CI [4.18, 17.07]; p < 0.01), insufficient knowledge about basic understanding of antibiotics and antibiotic resistance (aOR 2.78; 95% CI [1.38, 5.58], p < 0.01) and not acquiring any continuing education (aOR 1.97; 95% CI [1.02, 4.19]; p = 0.04).ConclusionsThis study identified inadequate perceptions of proper antibiotic use among animal health professionals. There is a need for continuous education on appropriate antibiotic use among animal health professionals to lessen the negative impact of antibiotic resistance on public health security.

Outcomes of antibiotic treatment for respiratory infections in children an observational study in primary care

Background Antibiotic resistance is an increasing global threat, accelerated by both misuse and overuse of antibiotics. Most antibiotics to humans are prescribed in primary care, commonly for respiratory symptoms, and there is a need for research on the usage of and outcomes after antibiotic treatment to counteract antibiotic resistance. Objective To evaluate symptom duration, treatment length, and adverse events of antibiotic treatment in children. Design and Setting Observational study at four out-of-hours services and one paediatric emergency clinic in Norwegian emergency primary care. Subjects 266 children aged 0 to 6 years with fever or respiratory symptoms. Main Outcome Measures Duration of symptoms and absenteeism from kindergarten/school, treatment length, and reported adverse events. Results There were no differences in duration of symptoms, fever or absenteeism when comparing the groups prescribed (30.8%) and not prescribed (69.2%) antibiotics. This lack of difference remained when analysing the subgroup with otitis media. In the group prescribed antibiotics, 84.5% of parents reported giving antibiotics for 5-7 days, and 50.7% reported no difficulties. Adverse events of antibiotics were reported in 42.3% of the cases, the vast majority being gastrointestinal disturbances. Conclusion Children with fever or respiratory symptoms experience similar duration of symptoms and absenteeism regardless of antibiotic treatment. A substantial number of parents reported adverse events when the child received antibiotics. Several parents experienced additional difficulties with the treatment, some ending treatment within day 4. Trial Registration Number NCT02496559; Results.

Molecular characterization of extended-spectrum β-lactamase-producing Escherichia coli isolated from lower respiratory tract samples between 2002 and 2019 in the Central Slovenia region

BackgroundAntibiotic resistance is one of the most serious global health problems and threatens the effective treatment of bacterial infections. Of greatest concern are infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC). The aim of our study was to evaluate the prevalence and molecular characteristics of ESBL-EC isolated over an 18-year pre-COVID period from lower respiratory tract (LRT) samples collected from selected Slovenian hospitals.Objectives and methodsAll isolates were identified by MALDI-TOF and phenotypically confirmed as ESBLs by a disk diffusion assay. Using a PCR approach, 487 non-repetitive isolates were assigned to phylogroups, sequence type groups, and clonal groups. Isolates were also screened for virulence-associated genes (VAGs) and antimicrobial resistance genes.ResultsThe prevalence of ESBL-EC isolates from LRT in a large university hospital was low (1.4%) in 2005 and increased to 10.8% by 2019. The resistance profile of 487 non-repetitive isolates included in the study showed a high frequency of group 1 blaCTX-M (77.4%; n = 377), blaTEM (54.4%; n = 265) and aac(6')-Ib-cr (52%; n = 253) genes and a low proportion of blaSHV and qnr genes. Isolates were predominantly assigned to phylogroup B2 (73.1%; n = 356), which was significantly associated with clonal group ST131. The ST131 group accounted for 67.6% (n = 329) of all isolates and had a higher number of virulence factor genes than the non-ST131 group. The virulence gene profile of ST131 was consistent with that of other extraintestinal pathogenic E. coli (ExPEC) strains and was significantly associated with ten of sixteen virulence factor genes tested. Using ERIC-PCR fingerprinting, isolates with the same ERIC-profile in samples from different patients, and at different locations and sampling dates were confirmed, indicating the presence of “hospital-adapted” strains.ConclusionOur results suggest that the ESBL-EC isolates from LRT do not represent a specific pathotype, but rather resemble other ExPEC isolates, and may be adapted to the hospital environment. To our knowledge, this is the first study of ESBL-EC isolated from LRT samples collected over a long period of time.

Factors contributing to the variation in antibiotic prescribing among primary health care physicians: a systematic review

BackgroundAntibiotic resistance is growing globally. The practice of health professionals when prescribing antibiotics in primary health care settings significantly impacts antibiotic resistance. Antibiotic prescription is a complex process influenced by various internal and external factors. This systematic review aims to summarize the available evidence regarding factors contributing to the variation in antibiotic prescribing among physicians in primary healthcare settings.MethodsThis systematic review was conducted based on PRISMA guidelines. We included qualitative, quantitative and mixed methods studies that examined factors influencing prescription practice and variability among primary healthcare physicians. We excluded editorials, opinions, systematic reviews and studies published in languages other than English. We searched studies from electronic databases: PubMed, ProQuest Health and Medicine, Web Science, and Scopus. The quality of the included studies was appraised using the Mixed Methods Appraisal Tool (Version 2018). Narrative synthesis was employed to synthesize the result and incorporate quantitative studies.ResultsOf the 1816 identified studies, 49 studies spanning 2000–2023 were eligible for review. The factors influencing antibiotic prescription practice and variability were grouped into physician-related, patient-related, and healthcare system-related factors. Clinical guidelines, previous patient experience, physician experience, colleagues’ prescribing practice, pharmaceutical pressure, time pressure, and financial considerations were found to be influencing factors of antibiotic prescribing practice. In addition, individual practice patterns, practice volume, and relationship with patients were also other factors for the variability of antibiotic prescription, especially for intra-physician prescription variability.ConclusionAntibiotic prescription practice in primary health care is a complex practice, influenced by a combination of different factors and this may account for the variation. To address the factors that influence the variability of antibiotic prescription (intra- and inter-physician), interventions should aim to reduce diagnostic uncertainty and provide continuous medical education and training to promote patient-centred care.

Effect of antibiotic medicines availability on adherence to standard treatment guidelines among hospitalized adult patients in southern Malawi.

Antibiotic resistance is a global public health problem. High and inappropriate use of antibiotic therapy exacerbate the risk of antibiotic resistance. We assessed the effect of availability of antibiotic medicines on adherence to standard treatment guidelines among hospitalized adult patients in Southern Malawi. A cross-sectional study was done to assess the availability of 16 antibiotics among the first-line recommended treatments for common bacterial infections in Malawi. Data for up to six-month duration was extracted from stock card records in Machinga and Nsanje District Hospitals and Zomba Central Hospital. This was complemented by a retrospective review of 322 patient management files from medical wards to assess adherence to the Malawi Standard Treatment Guidelines (MSTG). Investigators abstracted data such as patient demographics, diagnoses, and prescribed therapy using a data collection form that resulted in analyzing 304 patient files. Data was entered into Microsoft excel and analyzed using STATA 14.1. Point availability, stock-out duration and adherence to treatment guidelines were presented in terms of frequencies and percentages. Chi-square test or Fisher's exact test was applied to assess the association between variables and adherence to treatment guidelines. Point availability of antibiotics was 81.5%, 87.7%, and 42.8% for Zomba Central, Machinga and Nsanje District Hospitals respectively. Over a period of six months, 12.5% of antibiotic medicines were stocked out for at least one day at Zomba (Median stock out days = 0, (IQR 0-0 days), while 64.3% were stocked out at Machinga (Median stock out days = 21, IQR 0-31 days) and 85.7% were stocked out at Nsanje District Hospital (Median stock out days = 66.5, IQR 18-113 days). Overall, adherence to MSTG was 79.6%, (95% CI, 73.3-84.9%). By facilities, adherence to guidelines at Zomba Central Hospital was 95.9% (95% CI, 89.7-98.9%) while at Nsanje and Machinga District Hospitals was 73.2% (95% CI, 59.7-84.2%) and 54.2% (95% CI, 39.2-68.6%) respectively. Adherence to treatment guidelines was associated with health facility, presence of laboratory test results, antibiotic spectrum, and WHO-AWaRe category of the medicine, p<0.005. Adherence was lower for antibiotics that were stocked out than antibiotics that were not stocked out during the study period (63.8%, 95% CI 48.5-77.3% vs 84.4%, 95% CI 77.7-89.8%), p< 0.002. We found unstable availability of antibiotic medicines in hospitals which might contribute to the sub-optimal adherence to standard treatment guidelines. This is a setback to efforts aimed at curbing antibiotic resistance in Malawi.

Public knowledge, attitudes, and practices (KAP) regarding antibiotics use and antimicrobial resistance (AMR) in Bangladesh

BackgroundAntibiotic resistance is a global public health concern that requires an understanding of public knowledge, attitudes, and practices (KAP) towards antibiotics. This study aimed to assess the KAP regarding antibiotic use and AMR among the general population in Bangladesh. MethodsA cross-sectional survey was conducted among 656 respondents in Bangladesh. Data on socio-demographic characteristics, knowledge, attitudes, and practices regarding antibiotics use and AMR were collected through a structured questionnaire. Descriptive statistics and ordered logit regression analysis were performed to analyze the data. ResultsThe study involved participants, with 52.44 % aged 18 to 30, 77.29 % males, and 92.53 % having primary education or higher. Urban residents were 80 %, and students formed the largest occupational group (29.57 %), followed by businessmen (25 %), service holders (24.7 %), housewives (10.52 %), and day laborers (8.84 %). The majority of respondents demonstrated average knowledge (52.29 %), moderate attitudes (67.84 %), and good practices (50.61 %) regarding antibiotic use and AMR. Socioeconomic factors such as education, media exposure, and urban residence significantly (1 % level of significance) influenced KAP. The findings revealed knowledge gaps and misconceptions among the respondents, including incorrect beliefs about antibiotic resistance (42%), and inadequate awareness of the importance of completing full antibiotic courses (54.88 %). ConclusionThis study sheds light on the existing KAP related to antibiotic use and AMR within the general population of Bangladesh. The findings reveal varying levels of knowledge, attitudes, and practices among the participants. The results underscore the importance of addressing knowledge gaps, and misconceptions for awareness building through educational campaigns utilizing social media platforms and newspapers. These insights provide a foundation for informed strategies to ensure the continued efficacy of antibiotics.

Influences on treatment-seeking and antibiotic use for common illnesses in eastern China

BackgroundAntibiotic resistance rates remain high in China where antibiotics are widely used for common illnesses. This study aimed to investigate the influences on people’s decisions on treatment and antibiotic use for common illnesses in eastern China.MethodsSemi-structured interviews were conducted with 29 patients recruited through convenience sampling between July 2020 and January 2021 in one hospital in County A in Zhejiang Province, and one hospital and one village clinic in County B in Jiangsu Province, respectively. All interviews were audio-recorded, transcribed verbatim and thematically analysed. This study is nested in a larger interdisciplinary mixed method project and we also compared our qualitative findings with quantitative results from a household survey conducted as part of this wider project.ResultsParticipants’ decisions about treatment-seeking and antibiotic use for common illnesses were found to be influenced by four interactive domains. (i) Self-evaluation of illness severity: Participants tend to self-treat minor conditions with ordinary medicines first and do not resort to antibiotics unless the condition worsens or is considered inflammation- related. Visiting healthcare facilities is seen as the final option. (ii) Access to and trust in care: These treatment-seeking practices are also associated with the perception, in contrast with retail pharmacies, hospitals provide professional and trustworthy care but are difficult to access, and hence require visiting only for severe illness. (iii) Prior experience: previous medical treatment and experiences of self-medication also influence participants’ treatment decisions including the use of antibiotics. (iv) Medication characteristics: Participants view antibiotics as powerful medicines with harms and risks, requiring consumers to carefully trade off benefits and harms before use.ConclusionsPeople’s treatment decisions in relation to antibiotic use in eastern China are influenced by an interplay of lay conceptual models of illnesses and antibiotics and broader organisational, social, and contextual factors. Interventions focusing on individual education to incorporate biomedical knowledge into lay understandings, and reducing situational and social incentives for self-medicating with antibiotics by strengthening access to quality professional care, would be helpful in promoting antibiotic stewardship.

The effect of sulfadiazine in manure on accumulation of sulfonamide resistance genes in freshly consumable plants

BackgroundAntibiotic resistance genes will spread via soil fertilized with animal manure to food products. Especially plants whose harvested products can be consumed freshly are of concern. The aim of this study was to assess the impact of sulfadiazine (SDZ)-manured soil on the occurrence of sulfonamide (SA) resistance genes in freshly consumable plants.MethodsSulfadiazine-containing manure was administered via soil to lettuce and leek plants. At harvest, the rhizosphere soil, roots and leaves were investigated on the presence of SDZ-resistant bacteria and sul1 and sul2 genes via qPCR. Further, the impact of SDZ in manure on bacterial community and antibiotic resistance gene composition via amplicon sequencing and shotgun metagenomics was investigated in rhizosphere soils.ResultsAmendment of SDZ to manure resulted in an increase in sul2 genes in manure. However, abundances of sul genes in rhizosphere soils was strongly determined by plant growth and not by soil treatments with SDZ-manure, which was also the case for the bacterial community composition. Effects of SDZ at low or undetectable levels in leek rhizosphere soil became evident by bacterial association network and resistome analyses, and also in roots and leaves by SDZ-selective bacterial cultivation.ConclusionsAntibiotic residues present in animal manure can lead to an increase in antibiotic resistances in food products. Plants play an important role in selection of antibiotic resistance genes present in manured soil. Transmission of antibiotic resistances via manure to the soil–plant ecosystem must be placed into the context of soils as vast reservoirs of ARGs.

BaPreS: a software tool for predicting bacteriocins using an optimal set of features

BackgroundAntibiotic resistance is a major public health concern around the globe. As a result, researchers always look for new compounds to develop new antibiotic drugs for combating antibiotic-resistant bacteria. Bacteriocin becomes a promising antimicrobial agent to fight against antibiotic resistance, due to cases of both broad and narrow killing spectra. Sequence matching methods are widely used to identify bacteriocins by comparing them with the known bacteriocin sequences; however, these methods often fail to detect new bacteriocin sequences due to their high diversity. The ability to use a machine learning approach can help find new highly dissimilar bacteriocins for developing highly effective antibiotic drugs. The aim of this work is to develop a machine learning-based software tool called BaPreS (Bacteriocin Prediction Software) using an optimal set of features for detecting bacteriocin protein sequences with high accuracy. We extracted potential features from known bacteriocin and non-bacteriocin sequences by considering the physicochemical and structural properties of the protein sequences. Then we reduced the feature set using statistical justifications and recursive feature elimination technique. Finally, we built support vector machine (SVM) and random forest (RF) models using the selected features and utilized the best machine learning model to implement the software tool.ResultsWe applied BaPreS to an established dataset and evaluated its prediction performance. Acquired results show that the software tool can achieve a prediction accuracy of 95.54% for testing protein sequences. This tool allows users to add new bacteriocin or non-bacteriocin sequences in the training dataset to further enhance the predictive power of the tool. We compared the prediction performance of the BaPreS with a popular sequence matching-based tool and a deep learning-based method, and our software tool outperformed both.ConclusionsBaPreS is a bacteriocin prediction tool that can be used to discover new highly dissimilar bacteriocins for developing highly effective antibiotic drugs. This software tool can be used with Windows, Linux and macOS operating systems. The open-source software package and its user manual are available at https://github.com/suraiya14/BaPreS.

“Handing out non-prescribed antibiotics is storing up trouble for the next generation!” Unpacking multistakeholder views of drivers and potential solutions in Ethiopia

BackgroundAntibiotic resistance is a global health crisis, with inappropriate antibiotic use often being linked to non-prescribed antibiotic dispensing practices. This study aimed to examine the perspectives of multiple stakeholders on the drivers and potential solutions for non-prescribed antibiotic dispensing in Ethiopian community drug retail outlets (CDROs). Despite the prescription only use policies, the practice remains prevalent in Ethiopia. Many factors are thought to contribute to this issue, although little research is available for non-urban settings.MethodsA phenomenological qualitative study was conducted. Pharmacy professionals (owners or employees) working in non-urban towns CDROs were selected through a simulated client study, which identified CDROs that had dispensed antibiotics without a prescription. Some high-level decision makers in the Ethiopian health system were also purposively selected. Interviews were conducted in-person and over the phone or via Zoom. The interview data were transcribed verbatim, translated to English, and thematically analysed. NVivo 12 software was used to assist with coding.ResultsCDRO pharmacy professionals (n = 18) and five decision makers were interviewed. Most professionals (61%) were pharmacists working in drug stores, with one to 11 years of work experience. Several contributing factors were identified at the level of patients, CDRO staff, and the healthcare system. These included economic interests, inadequate knowledge and inappropriate attitudes about antibiotic use or supply, and issues within the healthcare system included inaccessibility and insufficient capacity, absence of or a weak enforcement of prescription-only regulations or service supervision. Additionally, patient-related factors included a lack of knowledge and inappropriate attitudes about antibiotics use and their supply, previous successful treatment experience and a culture of seeking out antibiotics.ConclusionsA complex set of modifiable factors related to patients, CDRO staff and healthcare system were identified that contribute to the non-prescribed supply of antibiotics. Due to this complexity, a single solution will not resolve the issues. Therefore, a range of multifaceted solutions have been suggested, including stricter regulation, increasing availability and accessibility of healthcare services, collaboration, and local consensus-building among CDROs, regular training for CDRO staff, and using community social events to educate the public about responsible use of antibiotics.