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Antibiotics, Volume 10, Issue 3 (March 2021) – 117 articles

Cover Story (view full-size image): While self‐medication with antibiotics is a major contributing factor to AMR, the role of psychological distress associated with perceived health risks in explaining antibiotic self‐medication is less understood. This study addresses this knowledge gap in the context of the COVID‐19 pandemic. An online survey conducted at the height of the initial outbreak in Australia revealed that 19.5% of participants took antibiotics to protect themselves from COVID‐19. Survey results illustrated potential pathways and facilitating factors that contribute to prophylactic self‐medication with antibiotics, highlighting the significant key role of COVID‐19-induced psychological distress. The findings suggest that, to combat AMR, interventions need to focus on interrupting entrenched behavioural responses and address emotional reactions to perceived health risks. View this paper.
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Article
Reduced Susceptibility to Chlorhexidine among Staphylococcus aureus Isolates in Israel: Phenotypic and Genotypic Tolerance
Antibiotics 2021, 10(3), 342; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030342 - 23 Mar 2021
Viewed by 622
Abstract
Antiseptic use for body decolonization is the main activity applied to prevent healthcare-associated infections, including those caused by S. aureus. Consequentially, tolerance to several antiseptics such as chlorhexidine gluconate (CHG) has developed. This study aimed to estimate the prevalence of CHG tolerance [...] Read more.
Antiseptic use for body decolonization is the main activity applied to prevent healthcare-associated infections, including those caused by S. aureus. Consequentially, tolerance to several antiseptics such as chlorhexidine gluconate (CHG) has developed. This study aimed to estimate the prevalence of CHG tolerance among S. aureus strains in Israel and to evaluate factors that may affect this tolerance. Furthermore, it tested the associations between phenotypic and genotypic CHG tolerance. S. aureus strains (n = 190) were isolated from clinical samples of patients admitted to various medical institutions in Israel. Phenotypic susceptibility to CHG was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Genotypic tolerance was detected using real-time PCR for detection of qac A/B genes. MIC for the antibiotic mupirocin was determined using the Etest method. Presence of the Panton–Valentine Leucocidin (pvl) toxin, mecA and mecC genes was detected using an eazyplex® MRSAplus kit (AmplexDiagnostics GmbH, Gars, Germany). CHG tolerance was observed in 13.15% of the isolates. An association between phenotypic and genotypic tolerance to CHG was observed. Phenotypic tolerance to CHG was associated with methicillin resistance but not with mupirocin resistance. Additionally, most of the CHG-tolerant strains were isolated from blood cultures. In conclusion, this work shed light on the prevalence of reduced susceptibility to CHG among S. aureus strains in Israel and on the characteristics of tolerant strains. CHG-tolerant strains were more common than methicillin-resistant ones in samples from invasive infections. Further research should be performed to evaluate risk factors for the development of CHG tolerance. Full article
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Article
Microbial Photoinactivation by Visible Light Results in Limited Loss of Membrane Integrity
Antibiotics 2021, 10(3), 341; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030341 - 23 Mar 2021
Viewed by 517
Abstract
Interest in visible light irradiation as a microbial inactivation method has widely increased due to multiple possible applications. Resistance development is considered unlikely, because of the multi-target mechanism, based on the induction of reactive oxygen species by wavelength specific photosensitizers. However, the affected [...] Read more.
Interest in visible light irradiation as a microbial inactivation method has widely increased due to multiple possible applications. Resistance development is considered unlikely, because of the multi-target mechanism, based on the induction of reactive oxygen species by wavelength specific photosensitizers. However, the affected targets are still not completely identified. We investigated membrane integrity with the fluorescence staining kit LIVE/DEAD® BacLight™ on a Gram positive and a Gram negative bacterial species, irradiating Staphylococcus carnosus and Pseudomonas fluorescens with 405 nm and 450 nm. To exclude the generation of viable but nonculturable (VBNC) bacterial cells, we applied an ATP test, measuring the loss of vitality. Pronounced uptake of propidium iodide was only observed in Pseudomonas fluorescens at 405 nm. Transmission electron micrographs revealed no obvious differences between irradiated samples and controls, especially no indication of an increased bacterial cell lysis could be observed. Based on our results and previous literature, we suggest that visible light photoinactivation does not lead to rapid bacterial cell lysis or disruption. However, functional loss of membrane integrity due to depolarization or inactivation of membrane proteins may occur. Decomposition of the bacterial envelope following cell death might be responsible for observations of intracellular component leakage. Full article
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Article
Outcomes and Risk Factors in Prosthetic Joint Infections by multidrug-resistant Gram-negative Bacteria: A Retrospective Cohort Study
Antibiotics 2021, 10(3), 340; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030340 - 23 Mar 2021
Viewed by 665
Abstract
Gram-negative bacteria (GNB), including multidrug-resistant (MDR) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). This retrospective observational study identified independent risk factors (RFs) associated with MDR-GNB PJI and their influence on treatment outcomes. We assessed MDR bacteria causing hip [...] Read more.
Gram-negative bacteria (GNB), including multidrug-resistant (MDR) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). This retrospective observational study identified independent risk factors (RFs) associated with MDR-GNB PJI and their influence on treatment outcomes. We assessed MDR bacteria causing hip and knee PJIs diagnosed at a Brazilian tertiary hospital from January 2014 to July 2018. RFs associated with MDR-GNB PJI were estimated by bivariate and multivariate analyses using prevalence ratios (PRs) with significance at p < 0.05. Kaplan–Meier analysis was performed to evaluate treatment outcomes. Overall, 98 PJI patients were analysed, including 56 with MDR-GNB and 42 with other bacteria. Independent RFs associated with MDR-GNB PJI were revision arthroplasty (p = 0.002), postoperative hematoma (p < 0.001), previous orthopaedic infection (p = 0.002) and early infection (p = 0.001). Extensively drug-resistant GNB (p = 0.044) and comorbidities (p = 0.044) were independently associated with MDR-GNB PJI treatment failure. In sum, MDR-GNB PJI was independently associated with previous orthopaedic surgery, postoperative local complications and pre-existing infections and was possibly related to selective pressure on bacterial skin colonisation by antibiotics prescribed for early PJI. Infections due to MDR-GNB and comorbidities were associated with higher treatment failure rates. Full article
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Article
Clonal Clusters, Molecular Resistance Mechanisms and Virulence Factors of Gram-Negative Bacteria Isolated from Chronic Wounds in Ghana
Antibiotics 2021, 10(3), 339; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030339 - 22 Mar 2021
Viewed by 506
Abstract
Wound infections are common medical problems in sub-Saharan Africa but data on the molecular epidemiology are rare. Within this study we assessed the clonal lineages, resistance genes and virulence factors of Gram-negative bacteria isolated from Ghanaian patients with chronic wounds. From a previous [...] Read more.
Wound infections are common medical problems in sub-Saharan Africa but data on the molecular epidemiology are rare. Within this study we assessed the clonal lineages, resistance genes and virulence factors of Gram-negative bacteria isolated from Ghanaian patients with chronic wounds. From a previous study, 49 Pseudomonas aeruginosa, 21 Klebsiellapneumoniae complex members and 12 Escherichia coli were subjected to whole genome sequencing. Sequence analysis indicated high clonal diversity with only nine P. aeruginosa clusters comprising two strains each and one E. coli cluster comprising three strains with high phylogenetic relationship suggesting nosocomial transmission. Acquired beta-lactamase genes were observed in some isolates next to a broad spectrum of additional genetic resistance determinants. Phenotypical expression of extended-spectrum beta-lactamase activity in the Enterobacterales was associated with blaCTX-M-15 genes, which are frequent in Ghana. Frequently recorded virulence genes comprised genes related to invasion and iron-uptake in E. coli, genes related to adherence, iron-uptake, secretion systems and antiphagocytosis in P. aeruginosa and genes related to adherence, biofilm formation, immune evasion, iron-uptake and secretion systems in K. pneumonia complex. In summary, the study provides a piece in the puzzle of the molecular epidemiology of Gram-negative bacteria in chronic wounds in rural Ghana. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Virulence Mechanisms)
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Review
Cystic Fibrosis: Recent Insights into Inhaled Antibiotic Treatment and Future Perspectives
Antibiotics 2021, 10(3), 338; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030338 - 22 Mar 2021
Cited by 1 | Viewed by 748
Abstract
Although new inhaled antibiotics have profoundly improved respiratory diseases in cystic fibrosis (CF) patients, lung infections are still the leading cause of death. Inhaled antibiotics, i.e., colistin, tobramycin, aztreonam lysine and levofloxacin, are used as maintenance treatment for CF patients after the development [...] Read more.
Although new inhaled antibiotics have profoundly improved respiratory diseases in cystic fibrosis (CF) patients, lung infections are still the leading cause of death. Inhaled antibiotics, i.e., colistin, tobramycin, aztreonam lysine and levofloxacin, are used as maintenance treatment for CF patients after the development of chronic Pseudomonas aeruginosa (P. aeruginosa) infection. Their use offers advantages over systemic therapy since a relatively high concentration of the drug is delivered directly to the lung, thus, enhancing the pharmacokinetic/pharmacodynamic parameters and decreasing toxicity. Notably, alternating treatment with inhaled antibiotics represents an important strategy for improving patient outcomes. The prevalence of CF patients receiving continuous inhaled antibiotic regimens with different combinations of the anti-P. aeruginosa antibiotic class has been increasing over time. Moreover, these antimicrobial agents are also used for preventing acute pulmonary exacerbations in CF. In this review, the efficacy and safety of the currently available inhaled antibiotics for lung infection treatment in CF patients are discussed, with a particular focus on strategies for eradicating P. aeruginosa and other pathogens. Moreover, the effects of long-term inhaled antibiotic therapy for chronic P. aeruginosa infection and for the prevention of pulmonary exacerbations is reviewed. Finally, how the mucus environment and microbial community richness can influence the efficacy of aerosolized antimicrobial agents is discussed. Full article
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Article
Identification of Bioactive Compounds from Marine Natural Products and Exploration of Structure-Activity Relationships (SAR)
Antibiotics 2021, 10(3), 337; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030337 - 22 Mar 2021
Viewed by 591
Abstract
Marine natural products (MNPs) have been an important and rich source for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein, we report bioassay guided fractionation of marine extracts from sponges Lendenfeldia, Ircinia and Dysidea that led us [...] Read more.
Marine natural products (MNPs) have been an important and rich source for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein, we report bioassay guided fractionation of marine extracts from sponges Lendenfeldia, Ircinia and Dysidea that led us to identify novel compounds with antimicrobial properties. Tertiary amines or quaternary amine salts: aniline 1, benzylamine 2, tertiary amine 3 and 4, and quaternary amine salt 5, along with three known compounds (6–8) were isolated from a crude extract and MeOH eluent marine extracts. The antibiotic activities of the compounds, and their isolation as natural products have not been reported before. Using tandem mass spectrometry (MS) analysis, potential structures of the bioactive fractions were assigned, leading to the hit validation of potential compounds through synthesis, and commercially available compounds. This method is a novel strategy to overcome insufficient quantities of pure material (NPs) for drug discovery and development which is a big challenge for pharmaceutical companies. The antibacterial screening of the marine extracts has shown several of the compounds exhibited potent in-vitro antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values between 15.6 to 62.5 microg mL−1. Herein, we also report structure activity relationships of a diverse range of commercial structurally similar compounds. The structure-activity relationships (SAR) results demonstrate that modification of the amines through linear chain length, and inclusion of aromatic rings, modifies the observed antimicrobial activity. Several commercially available compounds, which are structurally related to the discovered molecules, showed broad-spectrum antimicrobial activity against different test pathogens with a MIC range of 50 to 0.01 µM. The results of cross-referencing antimicrobial activity and cytotoxicity establish that these compounds are promising potential molecules, with a favourable therapeutic index for antimicrobial drug development. Additionally, the SAR studies show that simplified analogues of the isolated compounds have increased bioactivity. Full article
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Article
Repurposing of the Tamoxifen Metabolites to Combat Infections by Multidrug-Resistant Gram-Negative Bacilli
Antibiotics 2021, 10(3), 336; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030336 - 22 Mar 2021
Cited by 1 | Viewed by 858
Abstract
The development of new strategic antimicrobial therapeutic approaches, such as drug repurposing, has become an urgent need. Previously, we reported that tamoxifen presents therapeutic efficacy against multidrug-resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli in experimental infection models by modulating [...] Read more.
The development of new strategic antimicrobial therapeutic approaches, such as drug repurposing, has become an urgent need. Previously, we reported that tamoxifen presents therapeutic efficacy against multidrug-resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli in experimental infection models by modulating innate immune system cell traffic. The main objective of this study was to analyze the activity of N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen, three major metabolites of tamoxifen, against these pathogens. We showed that immunosuppressed mice infected with A. baumannii, P. aeruginosa, or E. coli in peritoneal sepsis models and treated with tamoxifen at 80 mg/kg/d for three days still reduced the bacterial load in tissues and blood. Moreover, it increased mice survival to 66.7% (for A. baumannii and E. coli) and 16.7% (for P. aeruginosa) when compared with immunocompetent mice. Further, susceptibility and time-kill assays showed that N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen exhibited minimum inhibitory concentration of the 90% of the isolates (MIC90) values of 16 mg/L, and were bactericidal against clinical isolates of A. baumannii and E. coli. This antimicrobial activity of tamoxifen metabolites paralleled an increased membrane permeability of A. baumannii and E. coli without affecting their outer membrane proteins profiles. Together, these data showed that tamoxifen metabolites presented antibacterial activity against MDR A. baumannii and E. coli, and may be a potential alternative for the treatment of infections caused by these two pathogens. Full article
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Article
Quantity and Quality of Aquaculture Enrichments Influence Disease Epidemics and Provide Ecological Alternatives to Antibiotics
Antibiotics 2021, 10(3), 335; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030335 - 22 Mar 2021
Viewed by 832
Abstract
Environmental heterogeneity is a central component influencing the virulence and epidemiology of infectious diseases. The number and distribution of susceptible hosts determines disease transmission opportunities, shifting the epidemiological threshold between the spread and fadeout of a disease. Similarly, the presence and diversity of [...] Read more.
Environmental heterogeneity is a central component influencing the virulence and epidemiology of infectious diseases. The number and distribution of susceptible hosts determines disease transmission opportunities, shifting the epidemiological threshold between the spread and fadeout of a disease. Similarly, the presence and diversity of other hosts, pathogens and environmental microbes, may inhibit or accelerate an epidemic. This has important applied implications in farming environments, where high numbers of susceptible hosts are maintained in conditions of minimal environmental heterogeneity. We investigated how the quantity and quality of aquaculture enrichments (few vs. many stones; clean stones vs. stones conditioned in lake water) influenced the severity of infection of a pathogenic bacterium, Flavobacterium columnare, in salmonid fishes. We found that the conditioning of the stones significantly increased host survival in rearing tanks with few stones. A similar effect of increased host survival was also observed with a higher number of unconditioned stones. These results suggest that a simple increase in the heterogeneity of aquaculture environment can significantly reduce the impact of diseases, most likely operating through a reduction in pathogen transmission (stone quantity) and the formation of beneficial microbial communities (stone quality). This supports enriched rearing as an ecological and economic way to prevent bacterial infections with the minimal use of antimicrobials. Full article
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Article
Comparative Investigation of Composition, Antifungal, and Anti-Inflammatory Effects of the Essential Oil from Three Industrial Hemp Varieties from Italian Cultivation
Antibiotics 2021, 10(3), 334; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030334 - 22 Mar 2021
Cited by 3 | Viewed by 929
Abstract
Industrial hemp is characterized by a huge amount of by-products, such as inflorescences, that may represent high-quality sources of biomolecules with pharmaceutical interest. In the present study, we have evaluated the phytochemical profile, including terpene and terpenophenolic compounds, of the essential oils (EOs) [...] Read more.
Industrial hemp is characterized by a huge amount of by-products, such as inflorescences, that may represent high-quality sources of biomolecules with pharmaceutical interest. In the present study, we have evaluated the phytochemical profile, including terpene and terpenophenolic compounds, of the essential oils (EOs) of Futura 75, Carmagnola selezionata and Eletta campana hemp varieties. The EOs were also tested for antifungal properties toward Trichophyton mentagrophytes, Trichophyton rubrum, Arthroderma crocatum, Arthroderma quadrifidum, Arthroderma gypseum, Arthroderma curreyi, and Arthroderma insingulare. In parallel, we investigated the inhibitory effects of the EOs against tyrosinase, and the production of prostaglandin E2 in isolated mouse skin exposed to hydrogen peroxide. In human H1299 lung adenocarcinoma cells, we also evaluated the influence of the EOs on the gene expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), which are involved in SARS-CoV-2 entry in human host. E-caryophyllene and α-pinene were the prominent terpenes in the EOs, whereas the cannabidiolic acid was the terpenophenol present at higher concentration. The EOs inhibited the growth of all tested dermatophytes species. In isolated skin specimens, EOs prevented the hydrogen-peroxide-induced synthesis of prostaglandin E2, consistent with the intrinsic antityrosinase activity. Finally, in H1299 cells, all tested EOs reduced the gene expression of ACE-2 and TMPRSS2, as well. Therefore, the present findings highlight the rationale for the use of the present EOs against infectious diseases. Full article
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Article
Assessment and Antibiotic Resistance Profiling in Vibrio Species Isolated from Wild Birds Captured in Danube Delta Biosphere Reserve, Romania
Antibiotics 2021, 10(3), 333; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030333 - 22 Mar 2021
Viewed by 648
Abstract
Antimicrobial and multidrug-resistant bacteria are a major problem worldwide and, consequently, the surveillance of antibiotic-resistant bacteria and assessment of the dissemination routes are essential. We hypothesized that migratory birds, coming from various environments, would carry more numerous Vibrio strains than sedentary species, with [...] Read more.
Antimicrobial and multidrug-resistant bacteria are a major problem worldwide and, consequently, the surveillance of antibiotic-resistant bacteria and assessment of the dissemination routes are essential. We hypothesized that migratory birds, coming from various environments, would carry more numerous Vibrio strains than sedentary species, with increased risk to be passed to their contacts or environment in habitats they transit or nest in. Similarly, we presumed that strains from migratory birds will show multidrug resistance. A total of 170 oral and rectal swabs were collected from wild birds captured in different locations of the Danube Delta (Malic, Sfantu-Gheorghe, Letea Forest) and processed using standardized selective media. V. cholerae strains were confirmed by serology and molecular methods and, subsequently, their susceptibility was evaluated. The prevalence of Vibrio species by host species, habitat type, and location was interpreted. The isolated Vibrio species were identified as Vibrio cholerae 14.33%, V. fluvialis 13.33%, V. alginolyticus 12%, V. mimicus 17.33%, V. vulnificus 10.88%, with V. parahaemolyticus and V. metschnikovii (16%) also being prevalent. Of the 76 Vibrio spp. isolates, 18.42% were resistant towards at least three antimicrobials, and 81.57% demonstrated a multidrug resistance phenotype, including mainly penicillins, aminoglycosides, and macrolides. The results of the present study indicate higher numbers of Vibrio strains in migratory (74.66%) than in sedentary birds (25.33%), confirming our hypothesis. Furthermore, the increased pathogenicity of Vibrio spp. strains, isolated from wild migratory and sedentary birds, was confirmed by their increased multiple antibiotic resistance (MAR) index (0.09–0.81). Full article
(This article belongs to the Special Issue Antimicrobial Resistance and the Environment: One Health Approach)
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Article
Knowledge, Attitudes and Practices Regarding Antibiotic Use and Resistance among Veterinary Students in Bangladesh
Antibiotics 2021, 10(3), 332; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030332 - 22 Mar 2021
Viewed by 1424
Abstract
The use of antibiotics in animals for both therapeutic and non-therapeutic purposes is a major driver of the emergence and spread of antimicrobial resistance (AMR). While several studies have investigated prescription and consumption patterns in humans, little attention has been paid to the [...] Read more.
The use of antibiotics in animals for both therapeutic and non-therapeutic purposes is a major driver of the emergence and spread of antimicrobial resistance (AMR). While several studies have investigated prescription and consumption patterns in humans, little attention has been paid to the veterinary sector. A cross-sectional study was conducted in 3002 veterinary students (VS) and non-medical students (NMS) from 12 universities in Bangladesh to explore their knowledge, attitudes and practices (KAP) about antibiotics and AMR using a self-administered questionnaire, and assess the influence of the veterinary curriculum. KAP regarding antibiotic use and AMR was significantly higher in veterinary than non-medical students, and in first-year than final-year students. However, gaps in knowledge and practices were highlighted, suggesting deficiencies in training. Moreover, final-year veterinary students were found to be more likely than first-year students to use antibiotics without instructions, which could indicate deficiencies in their curriculum. Although the study suggested a positive impact of the veterinary curriculum on KAP about antibiotics and AMR in Bangladesh, critical gaps remain that are likely to contribute to inadequate use in their future practice. Therefore, there is scope for improving educational programs on AMR in professional curricula. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship in Veterinary Medicine)
Article
Exploring Farmers’ Reasons for Antibiotic Use and Misuse in Pig Farms in Brazil
Antibiotics 2021, 10(3), 331; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030331 - 22 Mar 2021
Viewed by 683
Abstract
Stressful management that makes farmed pigs susceptible to infections is associated with high antibiotic use (AMU) and resistance (AMR). Pig farmers are key stakeholders to support the international agenda pushing AMU restrictions. We interviewed 58 pig farmers on AMU/AMR, biosecurity, veterinary assistance, disease [...] Read more.
Stressful management that makes farmed pigs susceptible to infections is associated with high antibiotic use (AMU) and resistance (AMR). Pig farmers are key stakeholders to support the international agenda pushing AMU restrictions. We interviewed 58 pig farmers on AMU/AMR, biosecurity, veterinary assistance, disease prevention and treatment, aiming to understand practices and attitudes towards the AMU/AMR problem. Farmers described a reliance on antibiotics to prevent and treat disease while neglecting biosecurity measures. We identified inappropriate AMU practices (high use of broad-spectrum antibiotics, incorrect dosage or treatment length) and unrestricted access to antibiotics, which encouraged imprudent AMU. Nevertheless, most farmers considered this AMU legitimate to guarantee herd productivity and showed unpreparedness and resistance to changing AMU practices, perceiving limitations (economic, sanitary and inspection) more easily than alternatives to reduce AMU. Agro-industries and foreign markets were mentioned, and internal consumers dismissed as potential motivators for behavioral changes. Importantly, farmers’ economic, technical and social factors may limit their autonomy to change practices. We conclude that the observed distancing of pig farmers from the AMU/AMR problem limits the efficiency of policies aiming for a prudent AMU. Our study indicates a need for education, training and behavior change nudging that should include other stakeholders beyond farmers. Full article
(This article belongs to the Special Issue Usage of Antibiotic in Agriculture and Animal Farming)
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Article
Intra-Articular Injections Prior to Total Knee Arthroplasty Do Not Increase the Risk of Periprosthetic Joint Infection: A Prospective Cohort Study
Antibiotics 2021, 10(3), 330; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030330 - 21 Mar 2021
Viewed by 584
Abstract
Periprosthetic joint infections (PJI) occur in 0.5 to 2.8% of total knee arthroplasties (TKA) and expose them to an increase of morbidity and mortality. TKA are mainly performed after failure of non-surgical management of knee osteoarthritis, which frequently includes intra-articular injections of corticosteroids [...] Read more.
Periprosthetic joint infections (PJI) occur in 0.5 to 2.8% of total knee arthroplasties (TKA) and expose them to an increase of morbidity and mortality. TKA are mainly performed after failure of non-surgical management of knee osteoarthritis, which frequently includes intra-articular injections of corticosteroids or hyaluronic acid. Concerning the potential impact of intra-articular injections on TKA infection, literature provides a low level of evidence because of the retrospective design of the studies and their contradictory results. In this prospective cohort study, we included patients after a total knee arthroplasty, at the time of their admission in a rehabilitation center, and we excluded patients with any prior knee surgery. 304 patients were included. Mean follow-up was 24.9 months, and incidence proportion of PJI was 2.6%. After multivariate logistic regression, male was the only significant risk factor of PJI (OR = 19.6; p = 0.006). The incidence of PJI did not differ between patients who received prior intra-articular injections and others, especially regarding injections in the last 6 months before surgery. The use of intra-articular injection remains a valid therapeutic option in the management of knee osteoarthritis, and a TKA could still be discussed. Full article
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Article
Determination of Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Parameters of Doxycycline against Edwardsiella ictaluri in Yellow Catfish (Pelteobagrus fulvidraco)
Antibiotics 2021, 10(3), 329; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030329 - 21 Mar 2021
Viewed by 543
Abstract
This study aimed to examine the pharmacokinetics of doxycycline (DC) in yellow catfish (Pelteobagrus fulvidraco) and to calculate related pharmacokinetic–pharmacodynamic (PK/PD) parameters of DC against Edwardsiella ictaluri. The minimum inhibitory concentration of DC against E. ictaluri was determined to be [...] Read more.
This study aimed to examine the pharmacokinetics of doxycycline (DC) in yellow catfish (Pelteobagrus fulvidraco) and to calculate related pharmacokinetic–pharmacodynamic (PK/PD) parameters of DC against Edwardsiella ictaluri. The minimum inhibitory concentration of DC against E. ictaluri was determined to be 500 µg/L. As the increase of oral dose from 10 to 40 mg/kg, the area under the concentration vs. time curve from 0 to 96 h (AUC0–96) values were considerably increased in gill, kidney, muscle and skin, and plasma, except in liver. Cmax values exhibited a similar dose-dependent increase trend in plasma and tissues except in liver, but other PK parameters had no apparent dose-dependence. The PK/PD parameter of the ratio of AUC0–96 to minimum inhibitory concentration (AUC0–96h/MIC) was markedly increased in plasma and tissues dose-dependently except in liver, but %T > MIC values were increased only moderately at some dose groups. After receiving the same dose with disparate time intervals from 96 to 12 h, the AUC0–96h/MIC was distinctly increased in plasma and tissues, but the %T > MIC had a decreasing trend. When administering 20 mg/kg with a time interval of 96 h, the AUC0–96h/MIC values were consistently >173.03 h and the %T > MIC values were above 99.47% in plasma and all tissues. These results suggest that administration of DC at 20 mg/kg every 96 h is a preferable regimen in yellow catfish. Full article
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Editorial
Implications of Antibiotic Use during the COVID-19 Pandemic: The Example of Associated Antimicrobial Resistance in Latin America
Antibiotics 2021, 10(3), 328; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030328 - 20 Mar 2021
Viewed by 1432
Abstract
Antimicrobials are essential for infection management [...] Full article
Perspective
Licensed Anti-Microbial Drugs Logical for Clinical Trials against Pathogens Currently Suspected in Alzheimer’s Disease
Antibiotics 2021, 10(3), 327; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030327 - 20 Mar 2021
Cited by 2 | Viewed by 689
Abstract
There is now considerable evidence that several infectious agents (viruses, bacteria, or parasites) may play a contributing role in the development of Alzheimer’s disease (AD). The six primary suspects are herpes viruses, spirochetal bacteria, Chlamydia pneumoniae, Porphyromonas gingivalis, mycobacteria, and toxoplasma [...] Read more.
There is now considerable evidence that several infectious agents (viruses, bacteria, or parasites) may play a contributing role in the development of Alzheimer’s disease (AD). The six primary suspects are herpes viruses, spirochetal bacteria, Chlamydia pneumoniae, Porphyromonas gingivalis, mycobacteria, and toxoplasma parasites. Also, some of the antimicrobial and antiviral agents that are used to treat them have shown promise for AD interventions. I describe this evidence and assert it is now time to accelerate clinical trials of these existing drugs, already federally approved, to determine if such treatments can delay, halt, or reverse AD. Full article
Review
Antimicrobial Resistance in Common Respiratory Pathogens of Chronic Bronchiectasis Patients: A Literature Review
Antibiotics 2021, 10(3), 326; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030326 - 20 Mar 2021
Viewed by 750
Abstract
Non-cystic fibrosis bronchiectasis is a chronic disorder in which immune system dysregulation and impaired airway clearance cause mucus accumulation and consequent increased susceptibility to lung infections. The presence of pathogens in the lower respiratory tract causes a vicious circle resulting in impaired mucociliary [...] Read more.
Non-cystic fibrosis bronchiectasis is a chronic disorder in which immune system dysregulation and impaired airway clearance cause mucus accumulation and consequent increased susceptibility to lung infections. The presence of pathogens in the lower respiratory tract causes a vicious circle resulting in impaired mucociliary function, bronchial inflammation, and progressive lung injury. In current guidelines, antibiotic therapy has a key role in bronchiectasis management to treat acute exacerbations and chronic infection and to eradicate bacterial colonization. Contrastingly, antimicrobial resistance, with the risk of multidrug-resistant pathogen development, causes nowadays great concern. The aim of this literature review was to assess the role of antibiotic therapy in bronchiectasis patient management and possible concerns regarding antimicrobial resistance based on current evidence. The authors of this review stress the need to expand research regarding bronchiectasis with the aim to assess measures to reduce the rate of antimicrobial resistance worldwide. Full article
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Article
The Phosin PptA Plays a Negative Role in the Regulation of Antibiotic Production in Streptomyces lividans
Antibiotics 2021, 10(3), 325; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030325 - 20 Mar 2021
Viewed by 621
Abstract
In Streptomyces, antibiotic biosynthesis is triggered in phosphate limitation that is usually correlated with energetic stress. Polyphosphates constitute an important reservoir of phosphate and energy and a better understanding of their role in the regulation of antibiotic biosynthesis is of crucial importance. [...] Read more.
In Streptomyces, antibiotic biosynthesis is triggered in phosphate limitation that is usually correlated with energetic stress. Polyphosphates constitute an important reservoir of phosphate and energy and a better understanding of their role in the regulation of antibiotic biosynthesis is of crucial importance. We previously characterized a gene, SLI_4384/ppk, encoding a polyphosphate kinase, whose disruption greatly enhanced the weak antibiotic production of Streptomyces lividans. In the condition of energetic stress, Ppk utilizes polyP as phosphate and energy donor, to generate ATP from ADP. In this paper, we established that ppk is co-transcribed with its two downstream genes, SLI_4383, encoding a phosin called PptA possessing a CHAD domain constituting a polyphosphate binding module and SLI_4382 encoding a nudix hydrolase. The expression of the ppk/pptA/SLI_4382 operon was shown to be under the positive control of the two-component system PhoR/PhoP and thus mainly expressed in condition of phosphate limitation. However, pptA and SLI_4382 can also be transcribed alone from their own promoter. The deletion of pptA resulted into earlier and stronger actinorhodin production and lower lipid content than the disruption of ppk, whereas the deletion of SLI_4382 had no obvious phenotypical consequences. The disruption of ppk was shown to have a polar effect on the expression of pptA, suggesting that the phenotype of the ppk mutant might be linked, at least in part, to the weak expression of pptA in this strain. Interestingly, the expression of phoR/phoP and that of the genes of the pho regulon involved in phosphate supply or saving were strongly up-regulated in pptA and ppk mutants, revealing that both mutants suffer from phosphate stress. Considering the presence of a polyphosphate binding module in PptA, but absence of similarities between PptA and known exo-polyphosphatases, we proposed that PptA constitutes an accessory factor for exopolyphosphatases or general phosphatases involved in the degradation of polyphosphates into phosphate. Full article
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Article
Salmonella spp. in Pet Reptiles in Portugal: Prevalence and Chlorhexidine Gluconate Antimicrobial Efficacy
Antibiotics 2021, 10(3), 324; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030324 - 19 Mar 2021
Viewed by 566
Abstract
A fraction of human Salmonella infections is associated with direct contact with reptiles, yet the number of reptile-associated Salmonellosis cases are believed to be underestimated. Existing data on Salmonella spp. transmission by reptiles in Portugal is extremely scarce. The aim of the present [...] Read more.
A fraction of human Salmonella infections is associated with direct contact with reptiles, yet the number of reptile-associated Salmonellosis cases are believed to be underestimated. Existing data on Salmonella spp. transmission by reptiles in Portugal is extremely scarce. The aim of the present work was to evaluate the prevalence of Salmonella spp. in pet reptiles (snakes, turtles, and lizards), as well as evaluate the isolates’ antimicrobial resistance and virulence profiles, including their ability to form biofilm in the air-liquid interface. Additionally, the antimicrobial effect of chlorhexidine gluconate on the isolates was tested. Salmonella was isolated in 41% of the animals sampled and isolates revealed low levels of antimicrobial resistance. Hemolytic and lypolytic phenotypes were detected in all isolates. The majority (90.63%) of the Salmonella isolates were positive for the formation of pellicle in the air-liquid interface. Results indicate chlorhexidine gluconate is an effective antimicrobial agent, against the isolates in both their planktonic and biofilm forms, demonstrating a bactericidal effect in 84.37% of the Salmonella isolates. This study highlights the possible role of pet reptiles in the transmission of non-typhoidal Salmonella to humans, a serious and increasingly relevant route of exposure in the Salmonella public health framework. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Virulence Mechanisms)
Article
Antibiotic Resistance Patterns of Bacterial Isolates from Neonatal Sepsis Patients at University Hospital of Leipzig, Germany
Antibiotics 2021, 10(3), 323; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030323 - 19 Mar 2021
Viewed by 664
Abstract
Neonatal sepsis caused by resistant bacteria is a worldwide concern due to the associated high mortality and increased hospitals costs. Bacterial pathogens causing neonatal sepsis and their antibiotic resistance patterns vary among hospital settings and at different points in time. This study aimed [...] Read more.
Neonatal sepsis caused by resistant bacteria is a worldwide concern due to the associated high mortality and increased hospitals costs. Bacterial pathogens causing neonatal sepsis and their antibiotic resistance patterns vary among hospital settings and at different points in time. This study aimed to determine the antibiotic resistance patterns of pathogens causing neonatal sepsis and to assess trends in antibiotic resistance. The study was conducted among neonates with culture proven sepsis at the University Hospital of Leipzig between November 2012 and September 2020. Blood culture was performed by BacT/ALERT 3D system. Antimicrobial susceptibility testing was done with broth microdilution method based on ISO 20776-1 guideline. Data were analyzed by SPSS version 20 software. From 134 isolates, 99 (74%) were gram positive bacteria. The most common gram positive and gram negative bacteria were S. epidermidis, 51 (38%) and E. coli, 23 (17%), respectively. S. epidermidis showed the highest resistance to penicillin G and roxithromycin (90% each) followed by cefotaxime, cefuroxime, imipenem, oxacillin, and piperacillin-tazobactam (88% each), ampicillin-sulbactam (87%), meropenem (86%), and gentamicin (59%). Moreover, S. epidermidis showed raising levels of resistance to amikacin, gentamicin, ciprofloxacin, levofloxacin, moxifloxacin, and cotrimoxazol. Gram positive bacteria showed less or no resistance to daptomycin, linezolid, teicoplanin, and vancomycin. E. coli showed the highest resistance to ampicillin (74%) followed by ampicillin-sulbactam (52%) and piperacillin (48%). Furthermore, increasing levels in resistance to ampicillin, ampicillin-sulbactam, piperacillin, and cefuroxime were observed over the years. Encouragingly, E. coli showed significantly declining trends of resistance to ciprofloxacin and levofloxacin, and no resistance to amikacin, colistin, fosfomycin, gentamicin, imipenem, piperacillin-tazobactam, and tobramycin. In conclusion, this study demonstrates that gram positive bacteria were the leading causes of neonatal sepsis. Bacterial isolates were highly resistant to first and second-line empiric antibiotics used in this hospital. The high levels of antibiotic resistance patterns highlight the need for modifying empiric treatment regimens considering the most effective antibiotics. Periodic surveillance in hospital settings to monitor changes in pathogens, and antibiotic resistance patterns is crucial in order to implement optimal prevention and treatment strategies. Full article
(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship)
Review
Carbapenem-Resistant Enterobacteriaceae—Implications for Treating Acute Leukemias, a Subgroup of Hematological Malignancies
Antibiotics 2021, 10(3), 322; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030322 - 19 Mar 2021
Viewed by 577
Abstract
Acute leukemias (AL) are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. Patients with AL are highly susceptible to infectious diseases due to the disease itself, factors attributed to treatment, and specific individual risk factors. Enterobacteriaceae [...] Read more.
Acute leukemias (AL) are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. Patients with AL are highly susceptible to infectious diseases due to the disease itself, factors attributed to treatment, and specific individual risk factors. Enterobacteriaceae presence (e.g., Klebsiella pneumonia and Escherichia coli) is a frequent cause of bloodstream infections in AL patients. Carbapenem-resistant Enterobacteriaceae (CRE) is an emerging health problem worldwide; however, the incidence of CRE varies greatly between different regions. Carbapenem resistance in Enterobacteriaceae is caused by different mechanisms, and CRE may display various resistance profiles. Bacterial co-expression of genes conferring resistance to both broad-spectrum β-lactam antibiotics (including carbapenems) and other classes of antibiotics may give rise to multidrug-resistant organisms (MDROs). The spread of CRE represents a major treatment challenge for clinicians due to lack of randomized clinical trials (RCTs), a limited number of antibiotics available, and the side-effects associated with them. Most research concerning CRE infections in AL patients are limited to case reports and retrospective reviews. Current research recommends treatment with older antibiotics, such as polymyxins, fosfomycin, older aminoglycosides, and in some cases carbapenems. To prevent the spread of resistant microbes, it is of pivotal interest to implement antibiotic stewardship to reduce broad-spectrum antibiotic treatment, but without giving too narrow a treatment to neutropenic infected patients. Full article
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Article
Novel Seleno- and Thio-Urea Containing Dihydropyrrol-2-One Analogues as Antibacterial Agents
Antibiotics 2021, 10(3), 321; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030321 - 19 Mar 2021
Cited by 2 | Viewed by 922
Abstract
The quorum sensing (QS) system in multi-drug-resistant bacteria such as P. aeruginosa is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing [...] Read more.
The quorum sensing (QS) system in multi-drug-resistant bacteria such as P. aeruginosa is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing dihydropyrrol-2-one (DHP) analogues as LasR antagonists. The selenium DHP derivatives displayed significantly better quorum-sensing inhibition (QSI) activities than the corresponding sulphur analogues. The most potent analogue 3e efficiently inhibited the las QS system by 81% at 125 µM and 53% at 31 µM. Additionally, all the compounds were screened for their minimum inhibitory concentration (MIC) against the Gram-positive bacterium S. aureus, and interestingly, only the selenium analogues showed antibacterial activity, with 3c and 3e being the most potent with a MIC of 15.6 µM. Full article
(This article belongs to the Special Issue Selenium, Metals and Trace Elements in Novel Antimicrobial Compounds)
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Article
Methicillin-Resistant Staphylococcus aureus (MRSA) Clonal Replacement in a Malaysian Teaching Hospital: Findings from an Eight-Year Interval Molecular Surveillance
Antibiotics 2021, 10(3), 320; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030320 - 19 Mar 2021
Viewed by 767
Abstract
Periodical surveillance on nosocomial pathogens is important for antimicrobial stewardship and infection control. The first methicillin-resistant Staphylococcus aureus (MRSA) molecular surveillance in Hospital Canselor Tuanku Muhriz (HCTM), a Malaysian teaching hospital, was performed in 2009. The dominant clone was identified as an MRSA [...] Read more.
Periodical surveillance on nosocomial pathogens is important for antimicrobial stewardship and infection control. The first methicillin-resistant Staphylococcus aureus (MRSA) molecular surveillance in Hospital Canselor Tuanku Muhriz (HCTM), a Malaysian teaching hospital, was performed in 2009. The dominant clone was identified as an MRSA carrying SCCmec type III-SCCmercury with ccrC and sea+cna toxin genes. In this study, we report the findings of the second HCTM MRSA surveillance carried out in 2017, after an interval of 8 years. Antibiotic susceptibility testing, SCCmec, toxin gene, and spa typing were performed for 222 MRSA strains isolated in 2017. Most strains were resistant to ciprofloxacin, erythromycin, clindamycin, cefoxitin, and penicillin (n = 126, 56.8%), belong to SCCmec type IV (n = 205, 92.3%), spa type t032 (n = 160, 72.1%) and harboured seg+sei toxin genes (n = 172, 77.5%). There was significant association between resistance of the aforementioned antibiotics with SCCmec type IV (p < 0.05), t032 (p < 0.001), and seg+sei carriage (p < 0.05). Results from this second MRSA surveillance revealed the occurrence of clonal replacement in HCTM during an interval of not more than 8 years. Investigation of the corresponding phenotype changes in this new dominant MRSA clone is currently on-going. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
Case Report
First Case of Bacteraemia Due to Carbapenem-Resistant Bacteroides faecis
Antibiotics 2021, 10(3), 319; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030319 - 19 Mar 2021
Viewed by 500
Abstract
Multidrug resistant (MDR) bacteria are increasingly observed in nosocomial and community-acquired settings. Anaerobes are no exception to this rule, but there are fewer reports of MDR in the scientific literature on anaerobes than there are for other bacteria. In this short case report, [...] Read more.
Multidrug resistant (MDR) bacteria are increasingly observed in nosocomial and community-acquired settings. Anaerobes are no exception to this rule, but there are fewer reports of MDR in the scientific literature on anaerobes than there are for other bacteria. In this short case report, we describe the first case of bacteraemia caused by a multidrug-resistant Bacteroides faecis, which produces a carbapenemase encoded by the blaCfiA gene. This bacteraemia followed a digestive surgery operation. Surprisingly, these findings did not lead to a change in antibiotic therapy, probably because the patient’s clinical state had improved. Nevertheless this report calls for better knowledge of anaerobic bacteria and for a systematic antimicrobial stewardship procedure following bacteraemia. Full article
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Review
Research Progress on Antibacterial Activities and Mechanisms of Natural Alkaloids: A Review
Antibiotics 2021, 10(3), 318; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030318 - 19 Mar 2021
Viewed by 754
Abstract
Alkaloids are nitrogen-containing heterocyclic compounds typically isolated from plants. They represent one of the most important types of natural products because of their large number and structural diversity and complexity. Based on their chemical core structures, alkaloids are classified as isoquinolines, quinolines, indoles, [...] Read more.
Alkaloids are nitrogen-containing heterocyclic compounds typically isolated from plants. They represent one of the most important types of natural products because of their large number and structural diversity and complexity. Based on their chemical core structures, alkaloids are classified as isoquinolines, quinolines, indoles, piperidine alkaloids, etc. In-depth analyses of alkaloids have revealed their antibacterial activities. To date, due to the widespread use of antibiotics, the problem of drug-resistant bacterial infections has been gradually increasing, which severely affects the clinical efficacy of antibacterial therapies and patient safety. Therefore, significant research efforts are focused on alkaloids because they represent a potentially new type of natural antibiotic with a wide antibacterial spectrum, rare adverse reactions, and a low tendency to produce drug resistance. Their main antibacterial mechanisms include inhibition of bacterial cell wall synthesis, change in cell membrane permeability, inhibition of bacterial metabolism, and inhibition of nucleic acid and protein synthesis. This article reviews recent reports about the chemical structures and the antibacterial activities and mechanisms of alkaloids. The purpose is to solve the problem of bacterial resistance and to provide a certain theoretical basis and research ideas for the development of new antibacterial drugs. Full article
(This article belongs to the Special Issue Search of New Natural Products with Antimicrobial Activity)
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Article
Barriers of Appropriate Antibiotic Prescription at PHCC in Qatar: Perspective of Physicians and Pharmacists
Antibiotics 2021, 10(3), 317; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030317 - 19 Mar 2021
Viewed by 659
Abstract
The Ministry of Public Health in Qatar developed the NAP (National Action Plan to combat Antimicrobial Resistance (AMR) in collaboration with WHO Regional Office for the Eastern Mediterranean (WHO/EMRO). Among the major factors shaping AMR is antimicrobial prescribing and use. Tailoring Antimicrobial Resistance [...] Read more.
The Ministry of Public Health in Qatar developed the NAP (National Action Plan to combat Antimicrobial Resistance (AMR) in collaboration with WHO Regional Office for the Eastern Mediterranean (WHO/EMRO). Among the major factors shaping AMR is antimicrobial prescribing and use. Tailoring Antimicrobial Resistance Program is a behavior change methodology that is utilized to adapt behavior change in relation to antimicrobial use. This study explores barriers of appropriate antibiotic (AB) prescription from the physicians’ and pharmacists’ perspectives at primary healthcare centers in Qatar. Data were collected from 50 participants across two PHCCs: 30 physicians and 20 pharmacists. Two different interview guides were constructed: One for physicians and one for pharmacists. In-depth, face-to-face, five focus groups were conducted and transcribed verbatim. Inductive qualitative analysis, involving discovering the themes in the interviews, was followed. Data were analyzed using constant comparative techniques. The Major themes arose from the analysis revealed that patients, practitioners mainly physicians, and the organization itself, played a role in shaping these barriers in the two primary healthcare centers. The findings would help develop and pilot behavior change interventions among patients, physicians and pharmacists with the aim of optimizing appropriate antibiotic prescription and use, which would support the implementation of the antibiotic stewardship program. Effective behavior change interventions should consider multiple factors including individual and organizational factors to optimize appropriate antibiotic prescription. Full article
(This article belongs to the Special Issue Antibiotics Use in Primary Care)
Article
Quality of the Diagnostic Process, Treatment Decision, and Predictors for Antibiotic Use in General Practice for Nursing Home Residents with Suspected Urinary Tract Infection
Antibiotics 2021, 10(3), 316; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030316 - 18 Mar 2021
Viewed by 556
Abstract
Urinary tract infections (UTIs) are common in nursing home (NH) residents and Denmark is one of the countries with the highest antibiotic use in NHs. The aim of this study was to assess the quality of the diagnostic process and treatment decision on [...] Read more.
Urinary tract infections (UTIs) are common in nursing home (NH) residents and Denmark is one of the countries with the highest antibiotic use in NHs. The aim of this study was to assess the quality of the diagnostic process and treatment decision on the day of the first contact from NHs to general practice and assess predictors for prescription of antibiotics in NH residents without an indwelling urinary catheter. The study was a prospective observational study in general practice in the Capital Region of Denmark; 490 patients were included; 158 out of 394 (40.1%, 95% CI 35; 45) patients with suspected UTI had urinary tract symptoms; 270 out of 296 (91.2%, 95% CI 87; 94) patients without urinary tract symptoms had a urine culture performed. Performing urine culture in the general practice was inversely associated to prescription of antibiotics on day one (OR 0.27, 95% CI 0.13; 0.56). It is imperative to support the implementation of interventions aimed at improving the quality of the diagnostic process on day one, as less than half of the patients given the diagnosis “suspected UTI” had urinary tract symptoms, and most patients without urinary tract symptoms had a urine culture performed. Full article
(This article belongs to the Special Issue Antibiotics Use in Primary Care)
Article
A Cell-Free Screen for Bacterial Membrane Disruptors Identifies Mefloquine as a Novel Antibiotic Adjuvant
Antibiotics 2021, 10(3), 315; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030315 - 18 Mar 2021
Viewed by 603
Abstract
Antibacterial discovery efforts have lagged far behind the need for new antibiotics. An approach that has gained popularity recently is targeting bacterial phospholipid membranes. We leveraged the differences between bacterial and mammalian phospholipid compositions to develop a high-throughput screen that identifies agents that [...] Read more.
Antibacterial discovery efforts have lagged far behind the need for new antibiotics. An approach that has gained popularity recently is targeting bacterial phospholipid membranes. We leveraged the differences between bacterial and mammalian phospholipid compositions to develop a high-throughput screen that identifies agents that selectively disrupt bacterial membranes while leaving mammalian membranes intact. This approach was used to screen 4480 compounds representing a subset of the Maybridge HitFinderTM V.11 Collection and the Prestwick Chemical Drug Library®. The screen identified 35 “positives” (0.8% hit rate) that preferentially damage bacterial model membranes. Among these, an antimalarial compound, mefloquine, and an aminoglycoside, neomycin, were identified. Further investigation of mefloquine’s activity against Staphylococcus aureus showed that it has little antibiotic activity on its own but can alter membrane fluidity, thereby potentiating a β-lactam antibiotic, oxacillin, against both methicillin-susceptible and methicillin-resistant S. aureus. This study indicates that our cell-free screening approach is a promising platform for discovering bacterial membrane disruptors as antibacterials antibiotic adjuvants. Full article
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Article
Impact of an Education-Based Antimicrobial Stewardship Program on the Appropriateness of Antibiotic Prescribing: Results of a Multicenter Observational Study
Antibiotics 2021, 10(3), 314; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030314 - 17 Mar 2021
Cited by 1 | Viewed by 525
Abstract
To evaluate the effect that an education-based Antimicrobial stewardship program (ASP) implemented in two hospitals in southern Italy had on the quality and appropriateness of antibiotic prescription. We conducted a multicenter observational study in two hospitals in the Campania region. Only some departments [...] Read more.
To evaluate the effect that an education-based Antimicrobial stewardship program (ASP) implemented in two hospitals in southern Italy had on the quality and appropriateness of antibiotic prescription. We conducted a multicenter observational study in two hospitals in the Campania region. Only some departments of both hospitals were already participating in the ASP. We collected data on all patients admitted on the day of evaluation in antibiotic therapy or prophylaxis through a case report form. The primary outcome was to investigate the difference in the appropriateness of the antibiotic prescriptive practice in the departments that had joined the ASP and in those that had not participated in the project (non-ASP). The total number of patients assessed was 486. Of these, 78 (16.05%) were in antibiotic prophylaxis and 130 (26.7%) in antibiotic therapy. The prescriptive appropriateness was better in the units that had joined ASP than in those that had not, with respectively 65.8% versus 22.7% (p < 0.01). Patients in the non-ASP units more frequently received unnecessary antibiotics (44.9% versus 0%, p = 0.03) and, as surgical prophylaxis, the use of antibiotics not recommended by the guidelines (44.2% versus 0%, p = 0.036). Multivariable analysis of the factors associated with prescriptive appropriateness identified ASP units (p = 0.02) and bloodstream or cardiovascular infections (p = 0.03) as independent predictors of better prescriptive appropriateness. The findings of the present study reinforce the importance of adopting an educational ASP to improve the quality of antimicrobial prescription in clinical practice. Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Stewardship, 2nd Volume)
Article
Transmission of Similar Mcr-1 Carrying Plasmids among Different Escherichia coli Lineages Isolated from Livestock and the Farmer
Antibiotics 2021, 10(3), 313; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030313 - 17 Mar 2021
Viewed by 1281
Abstract
Colistin use has mostly been stopped in human medicine, due to its toxicity. However, nowadays, it still is used as a last-resort antibiotic to treat hospital infections caused by multi-drug resistant Enterobacteriaceae. On the contrary, colistin has been used in veterinary medicine until [...] Read more.
Colistin use has mostly been stopped in human medicine, due to its toxicity. However, nowadays, it still is used as a last-resort antibiotic to treat hospital infections caused by multi-drug resistant Enterobacteriaceae. On the contrary, colistin has been used in veterinary medicine until recently. In this study, 210 fecal samples from pigs (n = 57), calves (n = 152), and the farmer (n = 1) were collected from a farm where E. coli harboring mcr-1–mcr-3 was previously detected. Samples were plated, and mcr-genes presence was confirmed by multiplex-PCR. Hybrid sequencing which determined the presence and location of mcr-1, other antibiotic resistance genes, and virulence factors. Eighteen colistin resistant isolates (13 from calves, four from pigs, and one from the farmer) contained mcr-1 associated with plasmids (IncX4, IncI2, and IncHI2), except for two that yielded mcr-1 in the chromosome. Similar plasmids were distributed in different E. coli lineages. Transmission of mcr-1 to the farmer most likely occurred by horizontal gene transfer from E. coli of calf origin, since plasmids were highly similar (99% coverage, 99.97% identity). Moreover, 33 virulence factors, including stx2 for Shiga toxin E. coli (STEC) were detected, highlighting the role of livestock as a reservoir of pathotypes with zoonotic potential. Full article
(This article belongs to the Special Issue Multidrug-Resistant Bacteria in Animals)
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