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1.
  • Ahmed, S, et al. (författare)
  • Host-Directed Therapy as a Novel Treatment Strategy to Overcome Tuberculosis: Targeting Immune Modulation
  • 2020
  • Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Tuberculosis (TB) is one of the leading causes of mortality and morbidity, particularly in developing countries, presenting a major threat to the public health. The currently recommended long term treatment regimen with multiple antibiotics is associated with poor patient compliance, which in turn, may contribute to the emergence of multi-drug resistant TB (MDR-TB). The low global treatment efficacy of MDR-TB has highlighted the necessity to develop novel treatment options. Host-directed therapy (HDT) together with current standard anti-TB treatments, has gained considerable interest, as HDT targets novel host immune mechanisms. These immune mechanisms would otherwise bypass the antibiotic bactericidal targets to kill Mycobacterium tuberculosis (Mtb), which may be mutated to cause antibiotic resistance. Additionally, host-directed therapies against TB have been shown to be associated with reduced lung pathology and improved disease outcome, most likely via the modulation of host immune responses. This review will provide an update of host-directed therapies and their mechanism(s) of action against Mycobacterium tuberculosis.
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2.
  • Al-Kass, Ziyad, et al. (författare)
  • Sperm Quality during Storage Is Not Affected by the Presence of Antibiotics in EquiPlus Semen Extender but Is Improved by Single Layer Centrifugation
  • 2018
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Contamination of semen with bacteria arises during semen collection and handling. This bacterial contamination is typically controlled by adding antibiotics to semen extenders but intensive usage of antibiotics can lead to the development of bacterial resistance and may be detrimental to sperm quality. The objective of this study was to determine the effects of antibiotics in a semen extender on sperm quality and to investigate the effects of removal of bacteria by modified Single Layer Centrifugation (MSLC) through a colloid. Semen was collected from six adult pony stallions (three ejaculates per male). Aliquots of extended semen were used for MSLC with Equicoll, resulting in four treatment groups: control and MSLC in extender with antibiotics (CA and SA, respectively); control and MSLC in extender without antibiotics (CW and SW, respectively). Sperm motility, membrane integrity, mitochondrial membrane potential and chromatin integrity were evaluated daily by computer-assisted sperm analysis (CASA) and flow cytometry. There were no differences in sperm quality between CA and CW, or between SA and SW, although progressive motility was negatively correlated to total bacterial counts at 0 h. However, MSLC groups showed higher mean total motility (P < 0.001), progressive motility (P < 0.05), membrane integrity (P < 0.0001) and mitochondrial membrane potential (P < 0.05), as well as better chromatin integrity (P < 0.05), than controls. Sperm quality remained higher in the MSLC groups than controls throughout storage. These results indicate that sperm quality was not adversely affected by the presence of antibiotics but was improved considerably by MSLC.
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3.
  • Alshammari, Hatem, et al. (författare)
  • Antimicrobial Potential of Strontium Hydroxide on Bacteria Associated with Peri-Implantitis
  • 2021
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Peri-implantitis due to infection of dental implants is a common complication that may cause significant patient morbidity. In this study, we investigated the antimicrobial potential of Sr(OH)2 against different bacteria associated with peri-implantitis. Methods: The antimicrobial potential of five concentrations of Sr(OH)2 (100, 10, 1, 0.1, and 0.01 mM) was assessed with agar diffusion test, minimal inhibitory concentration (MIC), and biofilm viability assays against six bacteria commonly associated with biomaterial infections: Streptococcus mitis, Staphylococcus epidermidis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Escherichia coli, and Fusobacterium nucleatum. Results: Zones of inhibition were only observed for, 0.01, 0.1, and 1 mM of Sr(OH)2 tested against P. gingivalis, in the agar diffusion test. Growth inhibition in planktonic cultures was achieved at 10 mM for all species tested (p < 0.001). In biofilm viability assay, 10 and 100 mM Sr(OH)2 showed potent bactericidal affect against S. mitis, S. epidermidis, A. actinomycetemcomitans, E. coli, and P. gingivalis. Conclusions: The findings of this study indicate that Sr(OH)2 has antimicrobial properties against bacteria associated with peri-implantitis. 
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4.
  • Bak, Søren Alex, et al. (författare)
  • Occurrence of ionophores in the Danish environment
  • 2014
  • Ingår i: Antibiotics. - 2079-6382. ; 3:4, s. 564-571
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibiotics in the environment are a potential threat to environmental ecosystems as well as human health and safety. Antibiotics are designed to have a biological effect at low doses, and the low levels detected in the environment have turned focus on the need for more research on environmental occurrence and fate, to assess the risk and requirement for future regulation. This article describes the first occurrence study of the antibiotic polyether ionophores (lasalocid, monensin, narasin, and salinomycin) in the Danish environment. Various environmental matrices (river water, sediment, and soil) have been evaluated during two different sampling campaigns carried out in July 2011 and October 2012 in an agricultural area of Zealand, Denmark. Lasalocid was not detected in any of the samples. Monensin was measured at a concentration up to 20 ng·L−1 in river water and 13 µg·kg−1 dry weight in the sediment as well as being the most frequently detected ionophore in the soil samples with concentrations up to 8 µg·kg−1 dry weight. Narasin was measured in sediment samples at 2 µg·kg−1 dry weight and in soil between 1 and 18 µg·kg−1 dry weight. Salinomycin was detected in a single soil sample at a concentration of 30 µg·kg−1 dry weight.
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5.
  • Bak, Søren Alex, et al. (författare)
  • Occurrence of ionophores in the Danish environment
  • 2014
  • Ingår i: Antibiotics. - : MDPI Multidisciplinary Digital Publishing Institute. - 2079-6382. ; 3:4, s. 564-571
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibiotics in the environment are a potential threat to environmental ecosystems as well as human health and safety. Antibiotics are designed to have a biological effect at low doses, and the low levels detected in the environment have turned focus on the need for more research on environmental occurrence and fate, to assess the risk and requirement for future regulation. This article describes the first occurrence study of the antibiotic polyether ionophores (lasalocid, monensin, narasin, and salinomycin) in the Danish environment. Various environmental matrices (river water, sediment, and soil) have been evaluated during two different sampling campaigns carried out in July 2011 and October 2012 in an agricultural area of Zealand, Denmark. Lasalocid was not detected in any of the samples. Monensin was measured at a concentration up to 20 ng·L−1 in river water and 13 µg·kg−1 dry weight in the sediment as well as being the most frequently detected ionophore in the soil samples with concentrations up to 8 µg·kg−1 dry weight. Narasin was measured in sediment samples at 2 µg·kg−1 dry weight and in soil between 1 and 18 µg·kg−1 dry weight. Salinomycin was detected in a single soil sample at a concentration of 30 µg·kg−1 dry weight.
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6.
  • Böhm, Maria-Elisabeth, et al. (författare)
  • A novel, integron-regulated, class c β-lactamase
  • 2020
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 9:3
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2020 by the authors. Licensee MDPI, Basel, Switzerland. AmpC-type β-lactamases severely impair treatment of many bacterial infections, due to their broad spectrum (they hydrolyze virtually all β-lactams, except fourth-generation cephalosporins and carbapenems) and the increasing incidence of plasmid-mediated versions. The original chromosomal AmpCs are often tightly regulated, and their expression is induced in response to exposure to β-lactams. Regulation of mobile ampC expression is in many cases less controlled, giving rise to constitutively resistant strains with increased potential for development or acquisition of additional resistances. We present here the identification of two integron-encoded ampC genes, blaIDC-1 and blaIDC-2 (integron-derived cephalosporinase), with less than 85% amino acid sequence identity to any previously annotated AmpC. While their resistance pattern identifies them as class C β-lactamases, their low isoelectric point (pI) values make differentiation from other β-lactamases by isoelectric focusing impossible. To the best of our knowledge, this is the first evidence of an ampC gene cassette within a class 1 integron, providing a mobile context with profound potential for transfer and spread into clinics. It also allows bacteria to adapt expression levels, and thus reduce fitness costs, e.g., by cassette-reshuffling. Analyses of public metagenomes, including sewage metagenomes, show that the discovered ampCs are primarily found in Asian countries.
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7.
  • Chigome, AK, et al. (författare)
  • Availability and Use of Therapeutic Interchange Policies in Managing Antimicrobial Shortages among South African Public Sector Hospitals; Findings and Implications
  • 2020
  • Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Therapeutic interchange policies in hospitals are useful in dealing with antimicrobial shortages and minimising resistance rates. The extent of antimicrobial shortages and availability of therapeutic interchange policies is unknown among public sector hospitals in South Africa. This study aimed to ascertain the extent of and rationale for dealing with antimicrobial shortages, describe policies or guidelines available, and the role of pharmacists in the process. Methods: A quantitative and descriptive study was conducted with a target population of 403 public sector hospitals. Data were collected from hospital pharmacists using an electronic questionnaire via SurveyMonkeyTM. Results: The response rate was 33.5% and most (83.3%) hospitals had experienced shortages in the previous six months. Antimicrobials commonly reported as out of stock included cloxacillin (54.3%), benzathine benzylpenicillin (54.2%), and erythromycin (39.6%). Reasons for shortages included pharmaceutical companies with supply constraints (85.3%) and an inefficient supply system. Only 42.4% had therapeutic interchange policies, and 88.9% contacted the prescriber, when present, for substitution. Conclusions: Antimicrobial shortages are prevalent in South African public sector hospitals with the most affected being penicillins and cephalosporins. Therapeutic interchange policies are not available at most hospitals. Effective strategies are required to improve communication between pharmacists and prescribers to ensure that safe, appropriate, and therapeutically equivalent alternatives are available.
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8.
  • Destoumieux-Garzón, Delphine, et al. (författare)
  • Resistance to antimicrobial peptides in vibrios
  • 2010
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 3:4, s. 540-563
  • Forskningsöversikt (refereegranskat)abstract
    • Vibrios are associated with a broad diversity of hosts that produce antimicrobial peptides (AMPs) as part of their defense against microbial infections. In particular, vibrios colonize epithelia, which function as protective barriers and express AMPs as a first line of chemical defense against pathogens. Recent studies have shown they can also colonize phagocytes, key components of the animal immune system. Phagocytes infiltrate infected tissues and use AMPs to kill the phagocytosed microorganisms intracellularly, or deliver their antimicrobial content extracellularly to circumvent tissue infection. We review here the mechanisms by which vibrios have evolved the capacity to evade or resist the potent antimicrobial defenses of the immune cells or tissues they colonize. Among their strategies to resist killing by AMPs, primarily vibrios use membrane remodeling mechanisms. In particular, some highly resistant strains substitute hexaacylated Lipid A with a diglycine residue to reduce their negative surface charge, thereby lowering their electrostatic interactions with cationic AMPs. As a response to envelope stress, which can be induced by membrane-active agents including AMPs, vibrios also release outer membrane vesicles to create a protective membranous shield that traps extracellular AMPs and prevents interaction of the peptides with their own membranes. Finally, once AMPs have breached the bacterial membrane barriers, vibrios use RND efflux pumps, similar to those of other species, to transport AMPs out of their cytoplasmic space.
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9.
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10.
  • Eriksen, Jaran, et al. (författare)
  • Exploring the One Health Perspective in Sweden's Policies for Containing Antibiotic Resistance
  • 2021
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibiotic resistance is considered to be a major threat to global health. The main driver of antibiotic resistance is antibiotic use. Antibiotics are used in humans, animals, and food production and are released into the environment. Therefore, it is imperative to include all relevant sectors in the work to contain antibiotic resistance, i.e., a One Health approach. In this study, we aimed to describe and analyse Sweden's policies related to containing antibiotic resistance, from a One Health perspective. Twenty-three key policy documents related to containment of antibiotic resistance in Sweden were selected and analysed according to the policy triangle framework. Sweden started early to introduce policies for containing antibiotic resistance from an international perspective. Systematic measures against antibiotic resistance were implemented in the 1980s, strengthened by the creation of Strama in 1995. The policies involve agencies and organisations from human and veterinary medicine, the environment, and food production. All actors have clear responsibilities in the work to contain antibiotic resistance with a focus on international collaboration, research, and innovation. Sweden aims to be a model country in the work to contain antibiotic resistance and has a strategy for achieving this through international cooperation through various fora, such as the EU, the UN system, and OECD.
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11.
  • Espinosa-Gongora, C, et al. (författare)
  • Towards a Better and Harmonized Education in Antimicrobial Stewardship in European Veterinary Curricula
  • 2021
  • Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Education in antimicrobial stewardship (AMS) in veterinary medicine is essential to foster responsible antimicrobial use and control of antimicrobial resistance (AMR) in animals. AMS is listed by the EU and international organizations among the basic ‘Day One Competences’ required of veterinary students upon graduation. Our aim was to evaluate the quality of education of European veterinary students in AMS. We distributed a 27-item survey addressing the perceptions of preparedness and acquired skills on key topics related to AMS to final-year veterinary students in Europe. We collected 3423 complete answers from 89 veterinary schools in 30 countries. Selection of treatment strategies and awareness of emerging AMR problems were markedly different between countries. Overall, only one in four students was familiar with guidelines for antimicrobial use. The students perceived a medium-high impact of veterinary antimicrobial use on AMR in humans. Notably, 75% of the students felt the need for improved teaching on AMS, half of which also demanded more teaching on general antimicrobial therapy. Our results highlight several possible strategies to improve the quality of education, ranging from a better link between clinical rotations and the theory taught in pre-clinical modules, to a more effective introduction into best practices for antimicrobial use.
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12.
  • Gijsen, Matthias, et al. (författare)
  • Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia : An Observational Cohort Study
  • 2021
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in >= 90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.
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13.
  • Granlund, Margareta, et al. (författare)
  • Discrepancies in Antimicrobial Susceptibility between the JP2 and the Non-JP2 Genotype of Aggregatibacter actinomycetemcomitans
  • 2022
  • Ingår i: Antibiotics. - Basel : MDPI. - 2079-6382. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The Aggregatibacter actinomycetemcomitans JP2 genotype is associated with high leukotoxin production and severe (aggressive) periodontitis. The aim of this study was to compare the antimicrobial susceptibility of JP2 and non-JP2 genotype strains. Minimal inhibitory concentrations (MICs) of 11 antimicrobials were determined for 160 A. actinomycetemcomitans of serotype a, b, or c, mostly isolated in Sweden or Ghana. MIC distributions for benzylpenicillin and fusidic acid revealed a more susceptible subpopulation for 38 serotype b strains, including the 32 of the JP2 genotype, with a benzylpenicillin MIC range of 0.125–0.5 mg/L. In contrast, benzylpenicillin MIC ≤ 16 mg/L was the estimated 99.5% epidemiological cutoff (ECOFF) of all strains. Beta-lactamase production was not detected. The fusidic acid MIC distribution of 11 strains of Aggregatibacter aphrophilus agreed with that found in non-JP2 strains. Cefotaxime, meropenem, levofloxacin, and trimethoprim–sulfamethoxazole MICs were all ≤0.25 mg/L, while MIC90 values for amoxicillin, azithromycin and tetracycline were 1 mg/L. Metronidazole MICs varied between 0.5 and >256 mg/L. The discrepant findings indicate that A. actinomycetemcomitans may be divided into two separate wild types, with a suggested intrinsic reduced susceptibility for benzylpenicillin in the majority of non-JP2 genotype strains. Possible implications for the treatment of A. actinomycetemcomitans infections are discussed.
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14.
  • Gray, Declan Alan, et al. (författare)
  • More than a pore: A current perspective on the in vivo mode of action of the lipopeptide antibiotic daptomycin
  • 2020
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 9:1
  • Forskningsöversikt (refereegranskat)abstract
    • Daptomycin is a cyclic lipopeptide antibiotic, which was discovered in 1987 and entered the market in 2003. To date, it serves as last resort antibiotic to treat complicated skin infections, bacteremia, and right-sided endocarditis caused by Gram-positive pathogens, most prominently methicillin-resistant Staphylococcus aureus. Daptomycin was the last representative of a novel antibiotic class that was introduced to the clinic. It is also one of the few membrane-active compounds that can be applied systemically. While membrane-active antibiotics have long been limited to topical applications and were generally excluded from systemic drug development, they promise slower resistance development than many classical drugs that target single proteins. The success of daptomycin together with the emergence of more and more multi-resistant superbugs attracted renewed interest in this compound class. Studying daptomycin as a pioneering systemic membrane-active compound might help to pave the way for future membrane-targeting antibiotics. However, more than 30 years after its discovery, the exact mechanism of action of daptomycin is still debated. In particular, there is a prominent discrepancy between in vivo and in vitro studies. In this review, we discuss the current knowledge on the mechanism of daptomycin against Gram-positive bacteria and try to offer explanations for these conflicting observations.
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15.
  • Hughes, Diarmaid, 1956-, et al. (författare)
  • Rifampicin Resistance : Fitness Costs and the Significance of Compensatory Evolution
  • 2013
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 2:2, s. 206-216
  • Forskningsöversikt (refereegranskat)abstract
    • Seventy years after the introduction of antibiotic chemotherapy to treat tuberculosis, problems caused by drug-resistance in Mycobacterium tuberculosis have become greater than ever. The discovery and development of novel drugs and drug combination therapies will be critical to managing these problematic infections. However, to maintain effective therapy in the long-term and to avoid repeating the mistakes of the past, it is essential that we understand how resistance to antibiotics evolves in M. tuberculosis. Recent studies in genomics and genetics, employing both clinical isolates and model organisms, have revealed that resistance to the frontline anti-tuberculosis drug, rifampicin, is very strongly associated with the selection of fitness compensatory mutations in the different subunits of RNA polymerase. This mode of resistance evolution may also apply to other drugs, and knowledge of the rates and mechanisms could be used to design improved diagnostics and by tracking the evolution of infectious strains, to inform the optimization of therapies.
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16.
  • Ishchuk, Olena P., et al. (författare)
  • Simple carbohydrate derivatives diminish the formation of biofilm of the pathogenic yeast candida albicans
  • 2020
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The opportunistic human fungal pathogen Candida albicans relies on cell morphological transitions to develop biofilm and invade the host. In the current study, we developed new regulatory molecules, which inhibit the morphological transition of C. albicans from yeast-form cells to cells forming hyphae. These compounds, benzyl α-l-fucopyranoside and benzyl β-d-xylopyranoside, inhibit the hyphae formation and adhesion of C. albicans to a polystyrene surface, resulting in a reduced biofilm formation. The addition of cAMP to cells treated with α-l-fucopyranoside restored the yeast-hyphae switch and the biofilm level to that of the untreated control. In the β-d-xylopyranoside treated cells, the biofilm level was only partially restored by the addition of cAMP, and these cells remained mainly as yeast-form cells.
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17.
  • Jamil, Z, et al. (författare)
  • Beneficial Effects of Anticoagulants on the Clinical Outcomes of COVID-19 Patients
  • 2021
  • Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • (1) Background: Severe coronavirus disease can be complicated by a hypercoagulable state in conjunction with sepsis, increasing the risk of venous thromboembolism. This study aimed to observe the effect of anticoagulants on 30-day high-dependency unit (HDU) outcomes of moderate to severe coronavirus disease 2019 (COVID-19) patients of a tertiary care hospital at Rawalpindi, Pakistan. (2) Methods: A retrospective propensity-based case–control study was carried out to examine COVID-19 patients admitted to the HDU. Patient groups who did and did not receive anticoagulants were labeled as “anticoagulant” and “non-anticoagulant”, respectively. Case–control matching (1:1) was performed via propensity scores (calculated by a regression model). Kaplan–Meier and logrank analyses were used to study survival probability. Single predictors of outcomes were determined by Cox regression analysis. (3) Results: The anticoagulant group had elevated D-dimers, advanced age, more comorbidities and a higher frequency of severe disease compared to the non-anticoagulant group (p < 0.05). Therefore, 47 cases and 47 matched controls were selected based on their propensity scores. The primary endpoint was outcome (survived vs. died). The 30-day in-HDU mortality was 25.5% for cases and 61.7% for controls (p = 0.0004). The median time from admission to death was 16 days for the case group and 7 days for the control group (p < 0.0001). The 30-day mortality was 19.1% for the enoxaparin group and 16.4% for the heparin group (p > 0.05). Enoxaparin (therapeutic and prophylactic doses) and heparin (prophylactic dose) were found to be independent factors affecting the outcomes of these patients (p < 0.001). (4) Conclusions: Anticoagulants play a beneficial role in reducing mortality among COVID-19 patients. Both anticoagulant formulations, enoxaparin (therapeutic and prophylactic doses) and heparin (prophylactic dose), were associated with improving survival among these patients.
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18.
  • Jamil, Z, et al. (författare)
  • Comparison of Low-Versus High-Dose Steroids in the Clinical Outcome of Hospitalized COVID-19 Patients
  • 2021
  • Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • (1) Objectives: Patients with COVID-19 infection have been given various formulations and dosages of steroids over the last year and a half. This study aims to compare the effects of different formulations and doses of steroids on the 30 day in-hospital clinical outcome of patients with severe COVID-19 infection. (2) Material and Methods: An analysis of a retrospective cohort was carried out on patients with severe COVID-19 infection in a high-dependency unit (HDU) between February and July 2021. In total, 557 patients were included in this study. Patients who did not receive steroids (124) were excluded. Patients were divided into three groups based on dosages of steroids (Dexamethasone = 6 mg/day, Dexamethasone > 6 mg/day, and Methylprednisolone = 500 mg/day), given for 10 days. First, clinical outcome was evaluated on the 10th day of steroid administration in relation to mode of oxygen delivery. Then, Kaplan–Meier analysis was employed to determine 30 day in-hospital survival in relation to the use of steroid. (3) Results: Three groups were statistically equal according to biochemical characteristics. After 10 days of Methylprednisolone = 500 mg/day vs. Dexamethasone = 6 mg/day, 10.9% vs. 6.2% of patients required invasive ventilation (p = 0.01). The 30 day in-hospital mortality was lowest, 3%, in individuals receiving Dexamethasone = 6 mg/day, compared to 3.9% in individuals receiving Dexamethasone > 6 mg/day and 9.9% in individuals receiving Methylprednisolone = 500 mg/day, respectively. The median elapsed time was longer than 28 days between admission and outcome for Dexamethasone = 6 mg/day, compared to 18 days for Dexamethasone > 6 mg/day and 17 days for Methylprednisolone = 500 mg/day (p = < 0.0001). Dexamethasone = 6 mg/day was found to be a positive predictor of clinical outcome in COVID-19 patients on regression analysis. (4) Conclusions: Low-dose Dexamethasone (6 mg/day) is more effective than high-dose Dexamethasone and Methylprednisolone in improving the survival outcome of severe COVID-19 cases.
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19.
  • Jansåker, Filip, et al. (författare)
  • The effect of sociodemographic factors, parity and cervical cancer on antibiotic treatment for uncomplicated cystitis in women : A nationwide cohort study
  • 2021
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Uncomplicated cystitis is one of the most common reasons for antibiotic treatment in otherwise healthy women. Nationwide studies on antibiotic treatment for this infection and in relation to factors beyond the infection itself have hitherto not been available. Methods: This was a nationwide open cohort study consisting of 352,507 women aged 15–50 years with uncomplicated cystitis (2006–2018). The outcome was a redeemed antibiotic prescription within five days from the cystitis diagnosis. Logistic regression models were used to examine the relationship between the outcome and the predictor variables. Results: This study identified 192,065 redeemed treatments (54.5%). Several sociodemographic variables were associated with antibiotic treatment. For example, women with the lowest income had an odds ratio (OR) of 1.26 (95% CI 1.23–1.28) compared to those with the highest income. History of cervical cancer and high parity were also associated with lower treatment rates. Conclusion: This study presents novel factors beyond the infection which seem to affect the antibiotic treatment for uncomplicated cystitis in women. Future studies to investigate possible mechanisms are warranted in order to properly use our findings. This may help healthcare workers and planners to provide a more equal treatment plan for this common infection, which may reduce misuse of antibiotics, decrease costs and improve efforts against antibiotic resistance.
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20.
  • Karlsen, Eskil, et al. (författare)
  • Anti-colonization effect of au surfaces with self-assembled molecular monolayers functionalized with antimicrobial peptides on s. Epidermidis
  • 2021
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Medical devices with an effective anti-colonization surface are important tools for com-batting healthcare-associated infections. Here, we investigated the anti-colonization efficacy of antimicrobial peptides covalently attached to a gold model surface. The gold surface was modified by a self-assembled polyethylene glycol monolayer with an acetylene terminus. The peptides were covalently connected to the surface through a copper-catalyzed [3 + 2] azide-acetylene coupling (CuAAC). The anti-colonization efficacy of the surfaces varied as a function of the antimicrobial activity of the peptides, and very effective surfaces could be prepared with a 6 log unit reduction in bacterial colonization. © 2021 by the authors. 
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21.
  • Kesarimangalam, Sriram, 1983, et al. (författare)
  • Optical dna mapping of plasmids reveals clonal spread of carbapenem-resistant klebsiella pneumoniae in a large thai hospital
  • 2021
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 10:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbapenem-resistant Klebsiella pneumoniae (CR-KP) in patients admitted to hospitals pose a great challenge to treatment. The genes causing resistance to carbapenems are mostly found in plasmids, mobile genetic elements that can spread easily to other bacterial strains, thus exacerbating the problem. Here, we studied 27 CR-KP isolates collected from different types of samples from 16 patients admitted to the medical ward at Siriraj Hospital in Bangkok, Thailand, using next generation sequencing (NGS) and optical DNA mapping (ODM). The majority of the isolates belonged to sequence type (ST) 16 and are described in detail herein. Using ODM, we identified the plasmid carrying the blaNDM-1 gene in the ST16 isolates and the plasmids were very similar, highlighting the possibility of using ODM of plasmids as a surrogate marker of nosocomial spread of bacteria. We also demonstrated that ODM could identify that the blaCTX-M-15 and blaOXA-232 genes in the ST16 isolates were encoded on separate plasmids from the blaNDM-1 gene and from each other. The other three isolates belonged to ST147 and each of them had distinct plasmids encoding blaNDM-1 .
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22.
  • Khare, Shweta, et al. (författare)
  • Antibiotic Prescribing by Informal Healthcare Providers for Common Illnesses : A Repeated Cross-Sectional Study in Rural India
  • 2019
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 8:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Informal healthcare providers (IHCPs) are predominant healthcare providers in rural India, who prescribe without formal training. Antibiotic prescription by IHCPs could provide crucial information for controlling antibiotic resistance. The aim of this study is to determine the practices and seasonal changes in antibiotic prescribing for common illnesses by IHCPs. A repeated cross-sectional study was conducted over 18 months, covering different seasons in the rural demographic surveillance site, at Ujjain, India. Prescriptions given to outpatients by 12 IHCPs were collected. In total, 15,322 prescriptions for 323 different complaint combinations were analyzed, of which 11,336 (74%) included antibiotics. The results showed that 14,620 (95%) of antibiotics prescribed were broad spectrum and the most commonly prescribed were fluoroquinolones (4771,31%), followed by penicillin with an extended spectrum (4119,27%) and third-generation cephalosporin (3069,20%). Antibiotics were prescribed more frequently in oral and dental problems (1126,88%), fever (3569,87%), and upper respiratory tract infections (3273, 81%); more during the monsoon season (2350,76%); and more frequently to children (3340,81%) than to adults (7996,71%). The study concludes that antibiotics were the more commonly prescribed drugs compared to other medications for common illnesses, most of which are broad-spectrum antibiotics, a situation that warrants further investigations followed by immediate and coordinated efforts to reduce unnecessary antibiotic prescriptions by IHCPs.
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23.
  • Kumar, Naresh, et al. (författare)
  • Understanding Antibiotic Usage on Small-Scale Dairy Farms in the Indian States of Assam and Haryana Using a Mixed-Methods Approach—Outcomes and Challenges
  • 2021
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:9, s. 1124-1124
  • Tidskriftsartikel (refereegranskat)abstract
    • The use and misuse of antibiotics in both humans and animals contributes to the global emergence of antimicrobial resistant (AMR) bacteria, a threat to public health and infection control. Currently, India is the world’s leading milk producer but antibiotic usage within the dairy sector is poorly regulated. Little data exists reflecting how antibiotics are used on dairy farms, especially on small-scale dairy farms in India. To address this lack of data, a study was carried out on 491 small-scale dairy farms in two Indian states, Assam and Haryana, using a mixed method approach where farmers were interviewed, farms inspected for the presence of antibiotics and milk samples taken to determine antibiotic usage. Usage of antibiotics on farms appeared low only 10% (95% CI 8–13%) of farmers surveyed confirmed using antibiotics in their dairy herds during the last 12 months. Of the farms surveyed, only 8% (6–11%) had milk samples positive for antibiotic residues, namely from the novobiocin, macrolides, and sulphonamide classes of antibiotics. Of the farmers surveyed, only 2% (0.8–3%) had heard of the term “withdrawal period” and 53% (40–65%) failed to describe the term “antibiotic”. While this study clearly highlights a lack of understanding of antibiotics among small-scale dairy farmers, a potential factor in the emergence of AMR bacteria, it also shows that antibiotic usage on these farms is low and that the possible role these farmers play in AMR emergence may be overestimated.
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24.
  • Legese, Melese Hailu, et al. (författare)
  • Molecular Epidemiology of Extended-Spectrum Beta-Lactamase and AmpC Producing Enterobacteriaceae among Sepsis Patients in Ethiopia : A Prospective Multicenter Study
  • 2022
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Extended-spectrum beta-lactamases (ESBLs) and AmpC producing Enterobacteriaceae are public health threats. This study aims to characterize ESBL and AmpC producing Enterobacteriaceae isolated from sepsis patients. A multicenter study was conducted at four hospitals located in central (Tikur Anbessa and Yekatit 12), southern (Hawassa) and northern (Dessie) parts of Ethiopia. Blood culture was performed among 1416 sepsis patients. Enterobacteriaceae (n = 301) were confirmed using MALDI-TOF and subjected for whole genome sequencing using the Illumina (HiSeq 2500) system. The overall genotypic frequencies of ESBL and AmpC producing Enterobacteriaceae were 75.5% and 14%, respectively. The detection of ESBL producing Enterobacteriaceae at Hawassa, Yekatit 12, Tikur Anbessa and Dessie was 95%, 90%, 82% and 55.8%, respectively. The detection frequency of bla(CTX-M), bla(TEM) and bla(SHV) genes was 73%, 63% and 33%, respectively. The most frequently detected ESBL gene was bla(CTX-M-15) (70.4%). The common AmpC genes were bla(ACT) (n = 22) and bla(CMY) (n = 13). Of Enterobacteriaceae that harbored AmpC (n = 42), 71% were ESBL co-producers. Both bla(TEM-1B) (61.5%) and bla(SHV-187) (27.6%) were the most frequently detected variants of bla(TEM) and bla(SHV), respectively. The molecular epidemiology of ESBL producing Enterobacteriaceae showed high frequencies and several variants of ESBL and AmpC genes. Good antimicrobial stewardship and standard bacteriological laboratory services are necessary for the effective treatment of ESBL producing Enterobacteriaceae.
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25.
  • Li, Xinjun, et al. (författare)
  • Fluoroquinolones and Other Antibiotics Redeemed for Cystitis—A Swedish Nationwide Cohort Follow-Up Study (2006–2018)
  • 2022
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Antibiotics are commonly prescribed for outpatient management of cystitis. Previous evidence suggests that certain factors likely beyond the infection seem to influence the choice of antimicrobial treatment. However, studies on the specific antibiotic treatments for cystitis are lacking. This study aimed to explore the antibiotic treatments for cystitis using nationwide primary healthcare data and investigate if factors beyond the infection could be associated with fluoroquinolone treatment. Methods: This nationwide follow-up cohort study consisted of 352,507 women with cystitis. The primary aim was to investigate what specific classes of antibiotics were redeemed by patients within five days from the cystitis diagnosis. Each patient could only be included once. Logistic regression models were also used to examine the relationship between fluoroquinolone (FQ) treatment, parity, and sociodemographic factors. Results: In total, 192,065 antibiotic prescriptions were redeemed. Pivmecillinam (58.4%) followed by nitrofurantoin (22.2%), trimethoprim (12.0%), fluoroquinolone (5.6%), and cephalosporins (1.5%) were the most redeemed antibiotics. Sociodemographic factors were weakly associated with fluoroquinolone treatment; young age was inversely associated with fluoroquinolone treatment. Parity and cervical cancer history were not associated with fluoroquinolone treatment. The proportion of fluoroquinolone and trimethoprim treatments decreased over time, while pivmecillinam and nitrofurantoin increased. Conclusions: The treatment trends of antibiotics redeemed within five days from a cystitis diagnosis were similar to the national surveillance program of these antibiotics (not diagnosis linked). Fluoroquinolones were weakly associated with sociodemographic factors, which likely is only of historical relevance.
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26.
  • Lindberg, Richard H, et al. (författare)
  • Occurrence and distribution of synthetic organic substances  in boreal coniferous forest soils fertilized with hygienized municipal sewage sludge
  • 2013
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 2:3, s. 352-366
  • Tidskriftsartikel (refereegranskat)abstract
    • The occurrence and distribution of synthetic organic substances following application of dried and granulated (hygienized) municipal sewage sludge in Swedish boreal coniferous forests were investigated. Elevated concentrations of triclosan (TCS), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) were detected in the humus layer. Concentrations of ethinyl estradiol (EE2), norfloxacin, ciprofloxacin, ofloxacin (FQs), and polyaromatic hydrocarbons (PAHs) were not significantly influenced. Maximum concentrations in humus were as follows (in ng/g dry matter): TCS; 778; PBDEs; 25; and PCB7; 16.7. Fertilization did not alter the levels of the substances in mineral soil, ground water, and various types of samples related to air. Further research within this area is needed, including ecotoxicological effects and fate, in order to improve the knowledge regarding the use of sludge as a fertilizing agent. Continuous annual monitoring, with respect to sampling and analysis, should be conducted on the already-fertilized fields.
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27.
  • Lundeheim, Nils (författare)
  • A Pilot Study in Sweden on Efficacy of Benzylpenicillin, Oxytetracycline, and Florfenicol in Treatment of Acute Undifferentiated Respiratory Disease in Calves
  • 2020
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Bovine respiratory disease (BRD) is a major indication for antibiotic treatment of cattle worldwide and some of the antibiotics used belong to classes of highest priority among those listed by WHO as critically important for human medicine. To preserve the efficacy of "newer" antibiotics, it has been suggested that "older" drugs should be revisited and used when possible. In this pilot study, we evaluated the efficacy of benzylpenicillin (PEN), oxytetracycline (OTC), and florfenicol (FLO) for treatment of naturally occurring BRD on two farms raising calves for slaughter. Farm personnel selected calves for enrolment, assigned calves to one of the three regimens in a systematically random manner, treated the calves, and registered the results. Overall, 117 calves were enrolled in the study. Nineteen calves relapsed in BRD before slaughter and were retreated (16.2%) and three died (2.6%). For PEN, treatment response rates after 30 days, 60 days, and until slaughter were 90.2%, 87.8%, and 80.5%, respectively; for OTC, 90.0%, 85.0%, and 85.0%, respectively; and for FLO, 86.1%, 83.3%, and 77.8%, respectively. There were no statistically significant differences in relapse, mortality, or response rates between the three treatment regimens. This indicates that PEN, OTC, and FLO were equally effective for treatment of BRD but the results need to be confirmed in a more elaborate study with a higher statistical power. The findings support the current recommendations from the Swedish Veterinary Association and the Medical Products Agency to use benzylpenicillin as a first line antibiotic for treatment of calves with undifferentiated respiratory disease in Sweden. Due to differences in the panorama of infectious agents and presence of acquired antibiotic resistance, the findings might not be applicable in other geographical areas.
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28.
  • Lunha, Kamonwan, et al. (författare)
  • Antimicrobial Resistance in Fecal Escherichia coli from Humans and Pigs at Farms at Different Levels of Intensification
  • 2020
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 9:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The overall aim of the current study was to test the hypotheses that (i) antibiotic resistance in bacteria were more frequent in clinically health pigs in intensified company owned, medium-scale farms (MSFs) (100-500 sows) than in pigs in family-owned, small-scale farms (SSFs) (1-50 sows) and (ii) that farmers working at the MSFs were more prone to attain antibiotic resistant bacteria than farmers working at SSFs. The study was conducted in North-Eastern Thailand, comprising fecal Escherichia coli isolates from pigs, farmers working with the pigs (contact humans) and persons living in the same household as the farmer (non-contact humans) at 51 MSFs and 113 SSFs. Samples from all farms were also screened for methicillin-resistant staphylococcus aureus (MRSA), which was not detected in pig samples, but was found in one human sample. Susceptibility was tested by disc-diffusion for seven antibiotics commonly used in the study area. Resistance in pig isolates from MSFs were more frequent for chloramphenicol which (P < 0.001), trimethoprim/sulfamethoxazole (P < 0.001) and gentamicin (P < 0.05) compared with isolates from SSFs, whereas the opposite was true for tetracycline (P < 0.01). Resistance in the human isolates was lower than those in the isolates from pigs for tetracycline, trimethoprim/sulfamethoxazole and chloramphenicol (P < 0.001). The frequency of resistance in the contact human samples from SSFs and MSFs did not differ. There was no difference between isolates from contact and non-contact humans for any of the tested antibiotics. Multidrug resistance in isolates from pigs was 26%, significantly higher (P < 0.01) than the 13% from humans. The data indicate that (i) resistance to antibiotics, including those critical and highly important for human medicine, were more common in fecal E. coli from pigs at the MSFs than at the SSFs, whereas (ii) the resistance in fecal E. coli from pig farmers seemed not to be influenced by the level of intensification of the farm they were working at.
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29.
  • Machowska, A, et al. (författare)
  • Antibiotic Prescribing to Patients with Infectious and Non-Infectious Indications Admitted to Obstetrics and Gynaecology Departments in Two Tertiary Care Hospitals in Central India
  • 2020
  • Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients admitted to obstetrics and gynaecology (OBGY) departments are at high risk of infections and subsequent antibiotic prescribing, which may contribute to antibiotic resistance (ABR). Although antibiotic surveillance is one of the cornerstones to combat ABR, it is rarely performed in low- and middle-income countries. Aim: To describe and compare antibiotic prescription patterns among the inpatients in OBGY departments of two tertiary care hospitals, one teaching (TH) and one nonteaching (NTH), in Central India. Methods: Data on patients’ demographics, diagnoses and prescribed antibiotics were collected prospectively for three years. Patients were divided into two categories- infectious and non-infectious diagnosis and were further divided into three groups: surgical, nonsurgical and possible-surgical indications. The data was coded based on the Anatomical Therapeutic Chemical classification system, and the International Classification of Disease system version-10 and Defined Daily Doses (DDDs) were calculated per 1000 patients. Results: In total, 5558 patients were included in the study, of those, 81% in the TH and 85% in the NTH received antibiotics (p < 0.001). Antibiotics were prescribed frequently to the inpatients in the nonsurgical group without any documented bacterial infection (TH-71%; NTH-75%). Prescribing of broad-spectrum, fixed-dose combinations (FDCs) of antibiotics was more common in both categories in the NTH than in the TH. Overall, higher DDD/1000 patients were prescribed in the TH in both categories. Conclusions: Antibiotics were frequently prescribed to the patients with no documented infectious indications. Misprescribing of the broad-spectrum FDCs of antibiotics and unindicated prescribing of antibiotics point towards threat of ABR and needs urgent action. Antibiotics prescribed to the inpatients having nonbacterial infection indications is another point of concern that requires action. Investigation of underlying reasons for prescribing antibiotics for unindicated diagnoses and the development and implementation of antibiotic stewardship programs are recommended measures to improve antibiotic prescribing practice.
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30.
  • Machowska, A, et al. (författare)
  • Impact of a Social Marketing Intervention on General Practitioners' Antibiotic Prescribing Practices for Acute Respiratory Tract Complaints in Malta
  • 2021
  • Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Antibiotics are commonly prescribed in primary care for acute respiratory tract complaints (aRTCs), often inappropriately. Social marketing interventions could improve prescribing in such settings. We evaluate the impact of a social marketing intervention on general practitioners’ (GPs’) antibiotic prescribing for aRTCs in Malta. Methods: Changes in GPs’ antibiotic prescribing were monitored over two surveillance periods between 2015 and 2018. Primary outcome: change in antibiotic prescription for aRTCs. Secondary outcomes: change in antibiotic prescription: (i) for immediate use, (ii) for delayed antibiotic prescription, (iii) by diagnosis, and (iv) by antibiotic class. Data were analysed using clustered analysis and interrupted time series analysis (ITSA). Results: Of 33 participating GPs, 18 successfully completed the study. Although clustered analyses showed a significant 3% decrease in overall antibiotic prescription (p = 0.024), ITSA showed no significant change overall (p = 0.264). Antibiotic prescription decreased significantly for the common cold (p < 0.001), otitis media (p = 0.044), and sinusitis (p = 0.004), but increased for pharyngitis (p = 0.015). Conclusions: The intervention resulted in modest improvements in GPs’ antibiotic prescribing. A more top-down approach will likely be required for future initiatives to be successful in this setting, focusing on diagnostic and prescribing support like rapid diagnostic testing, prescribing guidelines, and standardised delayed antibiotic prescriptions.
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31.
  • Maghembe, Reuben, et al. (författare)
  • Omics for bioprospecting and drug discovery from bacteria and microalgae
  • 2020
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 9:5
  • Forskningsöversikt (refereegranskat)abstract
    • “Omics” represent a combinatorial approach to high-throughput analysis of biological entities for various purposes. It broadly encompasses genomics, transcriptomics, proteomics, lipidomics, and metabolomics. Bacteria and microalgae exhibit a wide range of genetic, biochemical and concomitantly, physiological variations owing to their exposure to biotic and abiotic dynamics in their ecosystem conditions. Consequently, optimal conditions for adequate growth and production of useful bacterial or microalgal metabolites are critically unpredictable. Traditional methods employ microbe isolation and ‘blind’-culture optimization with numerous chemical analyses making the bioprospecting process laborious, strenuous, and costly. Advances in the next generation sequencing (NGS) technologies have offered a platform for the pan-genomic analysis of microbes from community and strain downstream to the gene level. Changing conditions in nature or laboratory accompany epigenetic modulation, variation in gene expression, and subsequent biochemical profiles defining an organism’s inherent metabolic repertoire. Proteome and metabolome analysis could further our understanding of the molecular and biochemical attributes of the microbes under research. This review provides an overview of recent studies that have employed omics as a robust, broad-spectrum approach for screening bacteria and microalgae to exploit their potential as sources of drug leads by focusing on their genomes, secondary metabolite biosynthetic pathway genes, transcriptomes, and metabolomes. We also highlight how recent studies have combined molecular biology with analytical chemistry methods, which further underscore the need for advances in bioinformatics and chemoinformatics as vital instruments in the discovery of novel bacterial and microalgal strains as well as new drug leads.
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32.
  • Mallavarpu Ambrose, Jenifer, et al. (författare)
  • Comparison of Immunological Profiles of SARS-CoV-2 Variants in the COVID-19 Pandemic Trends : An Immunoinformatics Approach
  • 2021
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The current dynamics of the COVID-19 pandemic have become a serious concern with the emergence of a series of mutant variants of the SARS-CoV-2 virus. Unlike the previous strain, it is reported that the descendants are associated with increased risk of transmission yet causing less impact in terms of hospital admission, the severity of illness, or mortality. Moreover, the vaccine efficacy is also not believed to vary among the population depending on the variants of the virus and ethnicity. It has been determined that the mutations recorded in the spike gene and protein of the newly evolved viruses are specificallyresponsible for this transformation in the behavior of the virus and its disease condition. Hence, this study aimed to compare the immunogenic profiles of the spike protein from the latest variants of the SARS-CoV-2 virus concerning the probability of COVID-19 severity. Genome sequences of the latest SARS-CoV-2 variants were obtained from GISAID and NCBI repositories. The translated protein sequences were run against T-cell and B-cell epitope prediction tools. Subsequently, antigenicity, immunogenicity, allergenicity, toxicity, and conservancy of the identified epitopes were ascertained using various prediction servers. Only the non-allergic and non-toxic potential epitopes were matched for population relevance by using the Human Leucocyte Antigen population registry in IEDB. Finally, the selected epitopes were validated by docking and simulation studies. The evaluated immunological parameters would concurrently reveal the severity of COVID-19, determining the infection rate of the pathogen. Our immunoinformatics approach disclosed that spike protein of the five variants was capable of forming potential T and B-cell epitopes with varying immune responses. Although the Wuhan strain showed a high number of epitope/HLA combinations, relatively less antigenicity and higher immunogenicity results in poor neutralizing capacity, which could be associated with increased disease severity. Our data demonstrate that increased viral antigenicity with moderate to high immunogenicity, and several potential epitope/HLA combinations in England strain, the USA, India, and South Africa variants, could possess a high neutralizing ability. Therefore, our findings reinforce that the newly circulating variants of SARS-CoV-2 might be associated with more infectiousness and less severe disease condition despite their greater viremia, as reported in the recent COVID-19 cases, whichconsequently determine their increased epidemiological fitness.
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33.
  • Mehta, Rishika, et al. (författare)
  • Emerging Chryseobacterium indologenes Infection in Indian Neonatal Intensive Care Units : A Case Report
  • 2018
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 7:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibiotic-resistant pathogens and nosocomial infections constitute common and serious problems for neonates admitted to neonatal intensive care units worldwide. Chryseobacterium indologenes is a non-lactose-fermenting, gram-negative, health care-associated pathogen (HCAP). It is ubiquitous and intrinsically resistant to several antibiotics. Despite its low virulence, C. indologenes has been widely reported to cause life-threatening infections. Patients on chronic immunosuppressant drugs, harboring invasive devices and indwelling catheters become the nidus for C. indologenes. Typically, C. indologenes causes major health care-associated infections such as pneumonia, empyema, pyelonephritis, cystitis, peritonitis, meningitis, and bacteremia in patients harboring central venous catheters. Management of C. indologenes infection in neonates is not adequately documented owing to underreporting, particularly in India. Because of its multidrug resistance and the scant availability of data from the literature, the effective empirical treatment of C. indologenes is challenging. We present an uncommon case of bacteremia caused by C. indologenes in a preterm newborn baby with moderate respiratory distress syndrome who was successfully treated. We also provide a review of infections in the neonatal age group. Henceforth, in neonates receiving treatments involving invasive equipment use and long-term antibiotic therapy, multidrug resistant C. indologenes should be considered an HCAP.
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34.
  • Meng, Qinglai, et al. (författare)
  • Rapid Detection of Multiple Classes of β-Lactam Antibiotics in Blood Using an NDM-1 Biosensing Assay
  • 2021
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 10:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Currently, assays for rapid therapeutic drug monitoring (TDM) of β-lactam antibiotics in blood, which might be of benefit in optimizing doses for treatment of critically ill patients, remain challenging. Previously, we developed an assay for determining the penicillin-class antibiotics in blood using a thermometric penicillinase biosensor. The assay eliminates sample pretreatment, which makes it possible to perform semicontinuous penicillin determinations in blood. However, penicillinase has a narrow substrate specificity, which makes it unsuitable for detecting other classes of β-lactam antibiotics, such as cephalosporins and carbapenems. In order to assay these classes of clinically useful antibiotics, a novel biosensor was developed using New Delhi metallo-β-lactamase-1 (NDM-1) as the biological recognition layer. NDM-1 has a broad specificity range and is capable of hydrolyzing all classes of β-lactam antibiotics in high efficacy with the exception of monobactams. In this study, we demonstrated that the NDM-1 biosensor was able to quantify multiple classes of β-lactam antibiotics in blood plasma at concentrations ranging from 6.25 mg/L or 12.5 mg/L to 200 mg/L, which covered the therapeutic concentration windows of the tested antibiotics used to treat critically ill patients. The detection of ceftazidime and meropenem was not affected by the presence of the β-lactamase inhibitors avibactam and vaborbactam, respectively. Furthermore, both free and protein-bound β-lactams present in the antibiotic-spiked plasma samples were detected by the NDM-1 biosensor. These results indicated that the NDM-1 biosensor is a promising technique for rapid TDM of total β-lactam antibiotics present in the blood of critically ill patients.
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35.
  • Mgbeahuruike, E. E., et al. (författare)
  • Antimicrobial and Synergistic Effects of Commercial Piperine and Piperlongumine in Combination with Conventional Antimicrobials
  • 2019
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbial resistance to currently available antibiotics is a public health problem in the fight against infectious diseases. Most antibiotics are characterized by numerous side effects that may be harmful to normal body cells. To improve the efficacy of these antibiotics and to find an alternative way to minimize the adverse effects associated with most conventional antibiotics, piperine and piperlongumine were screened in combination with conventional rifampicin, tetracycline, and itraconazole to evaluate their synergistic, additive, or antagonistic interactions against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The fractional inhibitory concentration index was used to estimate the synergistic effects of various combination ratios of the piperamides and antibiotics against the bacterial and fungal strains. Both piperine and piperlongumine showed synergistic effects against S. aureus when combined at various ratios with rifampicin. Synergistic interaction was also observed with piperine in combination with tetracycline against S. aureus, while antagonistic interaction was recorded for piperlongumine and tetracycline against S. aureus. All the piperamide/antibacterial combinations tested against P. aeruginosa showed antagonistic effects, with the exception of piperine and rifampicin, which recorded synergistic interaction at a ratio of 9:1 rifampicin/piperine. No synergistic interaction was observed when the commercial compounds were combined with itraconazole and tested against C. albicans. The results showed that piperine and piperlongumine are capable of improving the effectiveness of rifampicin and tetracycline. Dosage combinations of these bioactive compounds with the antibiotics used may be a better option for the treatment of bacterial infections that aims to minimize the adverse effects associated with the use of these conventional antibacterial drugs.
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36.
  • Muheim, Claudio, et al. (författare)
  • Identification of a Fragment-Based Scaffold that Inhibits the Glycosyltransferase WaaG from Escherichia coli
  • 2016
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • WaaG is a glycosyltransferase that is involved in the biosynthesis of lipopolysaccharide in Gram-negative bacteria. Inhibitors of WaaG are highly sought after as they could be used to inhibit the biosynthesis of the core region of lipopolysaccharide, which would improve the uptake of antibiotics. Herein, we establish an activity assay for WaaG using C-14-labeled UDP-glucose and LPS purified from a increment waaG strain of Escherichia coli. We noted that addition of the lipids phosphatidylglycerol (PG) and cardiolipin (CL), as well as the detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) increased activity. We then use the assay to determine if three molecular scaffolds, which bind to WaaG, could inhibit its activity in vitro. We show that 4-(2-amino-1,3-thiazol-4-yl)phenol inhibits WaaG (IC50 1.0 mM), but that the other scaffolds do not. This study represents an important step towards an inhibitor of WaaG by fragment-based lead discovery.
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37.
  • Nohrborg, Sandra, et al. (författare)
  • Geographic and Socioeconomic Influence on Knowledge and Practices Related to Antimicrobial Resistance among Smallholder Pig Farmers in Uganda
  • 2022
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • To mitigate the development of antimicrobial resistance (AMR), antibiotic use (ABU) in the livestock sector needs to be reduced. In low- and middle-income countries, regulations have shown to be less successful in reducing ABU. Here, a bottom-up approach can complement legal frameworks, which requires an understanding of the drivers for ABU. In this study, we investigated the influence of geographic and socioeconomic settings on determinants for ABU among pig farmers in Uganda. The data were collected through a questionnaire in two districts, Lira and Mukono, and comparative statistical analyses were performed. Farmers in Lira had less access to animal health services, applied disease prevention measures less and used antibiotics more. In Mukono, it was more common to consult a veterinarian in response to disease, while in Lira it was more common to consult an animal health worker. There was no difference in how many farmers followed treatment instructions from a veterinarian, but it was more common in Lira to follow instructions from pharmacies. The findings support the need for locally tailored AMR-reducing interventions to complement regulations. To accomplish this tailoring, systematic collection of knowledge of farm structures, farm practices and access to animal health services and veterinary drugs is necessary.
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38.
  • Olmos Antillón, Gabriela (författare)
  • Exploring Farmers’ Reasons for Antibiotic Use and Misuse in Pig Farms in Brazil
  • 2021
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 10
  • Tidskriftsartikel (refereegranskat)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 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.
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39.
  • Pan, YY, et al. (författare)
  • Antimicrobial Resistance of Non-O157 Shiga Toxin-Producing Escherichia coli Isolated from Humans and Domestic Animals
  • 2021
  • Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-O157 Shiga toxin-producing Escherichia coli (STEC) is an important pathogen that can cause zoonotic diseases. To investigate the antimicrobial resistance of STEC in China, non-O157 STEC isolates, recovered from domestic animals and humans from 12 provinces, were analyzed using antimicrobial susceptibility testing and whole genome characterization. Out of the 298 isolates tested, 115 strains showed resistance to at least one antimicrobial and 85 strains showed multidrug resistance. The highest resistance rate was to tetracycline (32.6%), followed by nalidixic acid (25.2%) and chloramphenicol and azithromycin (both 18.8%). However, imipenem and meropenem were effective against all isolates. Antimicrobial resistance patterns varied among strains from different sources. Strains from pig, sheep, humans, and cattle showed resistance rates of 100.0%, 46.9%, 30.3%, and 6.3% to one or more antimicrobials, respectively. Forty-three genes related to 11 antimicrobial classes were identified among these strains. The colistin-resistance gene mcr was only carried by strains from pigs. A new fosfomycin-resistant gene, fosA7, was detected in strains from humans, cattle, and sheep. Whole genome phylogenetic analysis showed that strains from the four sources were genetically diverse and scattered throughout the phylogenetic tree; however, some strains from the same source had a tendency to cluster closely. These results provide a reference to monitor the emergence and spread of multidrug resistant STEC strains among animals and humans. Furthermore, with a better understanding of antimicrobial genotypes and phenotypes among the diverse STEC strains obtained, this study could guide the administration of antimicrobial drugs in STEC infections when necessary.
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40.
  • Ramaite, K., et al. (författare)
  • Human-Associated Methicillin-Resistant Staphylococcus aureus Clonal Complex 80 Isolated from Cattle and Aquatic Environments
  • 2021
  • Ingår i: Antibiotics-Basel. - : MDPI AG. - 2079-6382. ; 10:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Human-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) has mainly been reported in South African pig and chicken farms. The prevalence of antibiotic-resistant genes (ARGs), virulence factors (VFs), and multilocus sequence types (MLSTs) associated with HA-MRSA in cattle farms has not been reported. Consequently, this study characterised LA-MRSA and its spread from cattle farms into the environment. Method: Husbandry soil (HS), nearby river water (NRW), animal manure (AM) and animal drinking water (ADW) were collected on and around a cattle farm. Presumptive MRSA isolates were identified from these samples using CHROMagar media and genotyped as MRSA sequence types (STs), selected ARGs, and VFs, using polymerase chain reaction. An MLST-based dendrogram was generated to link the farm MRSA strains with those in a nearby river. Results: The prevalence of MRSA was 30.61% for HS, 28.57% for ADW, 22.44% for NRW, and 10.20% for AM. Isolates from HS harboured the highest number of resistant genes, with 100% for mecA, 91.66% for ermA, and 58.33% for blaZ. However, no ermC or tetM genes were detected. MRSA isolates from AM harboured the lowest number of resistant genes. Only sec and seq enterotoxins were found in all the assessed MRSA isolates. MRSA from the farm revealed six STs (ST80, ST728, ST1931, ST2030, ST3247, and ST5440); all of STs belonged to clonal complex 80 (CC80). An MLST-based dendrogram based on the concatenated sequences of MLST genes under the maximum likelihood criterion revealed four clades of amalgamated MRSA isolates from various livestock environmental matrices, including the NRW. Conclusion: The results suggest that livestock environmental matrices might be reservoirs of MRSA that could subsequently disseminate through runoff to pollute water resources. Therefore, continued surveillance of HA-MRSA in livestock environments is warranted.
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41.
  • Reda, Eman H., et al. (författare)
  • Comparative Study on the Essential Oils from Five Wild Egyptian Centaurea Species : Effective Extraction Techniques, Antimicrobial Activity and In-Silico Analyses
  • 2021
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The genus Centaurea is recognized in folk medicine for anti-inflammatory, anti-itch, antitussive, purgative, astringent, and tonic activities. To study the chemical determinant for antimicrobial activity essential oils (EOs), five Centaurea species were analyzed including: C. scoparia, C. calcitrapa, C. glomerata, C. lipii and C. alexandrina. Conventional hydro-distillation (HD) and microwave-assisted extraction (MAE), as new green technologies, were compared for the extraction of essential oils. GC/MS analysis identified 120 EOs including mostly terpenoid except from C. lipii and C. alexandrina in which nonterpenoids were the major constituents. Major terpenoids included spathulenol, caryophyllene oxide and alloaromadendrene oxide-2. To probe antibacterial activity, potential EO inhibitors of a bacterial type II DNA topoisomerase, DNA gyrase B were screened via an in silico molecular docking approach. Spathulenol and alloaromadendrene oxide-2 possessed the best binding affinity in the ATP- binding pocket of Gyrase B enzyme. Principal component analysis and agglomerative hierarchical clustering were used for sample classification and revealed that sesquiterpenes contributed the most for accessions classification. In vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli and Aspergillus niger for all EOs were also evaluated. EOs from C. lipii, C. glomerata and C. calcitrapa exhibited significant MIC against S. aureus with an MIC value of 31.25 µg/mL.
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42.
  • Sallam, Malik, et al. (författare)
  • Trends in Antimicrobial Drug Resistance of Streptococcus pneumoniae Isolates at Jordan University Hospital (2000–2018)
  • 2019
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Antimicrobial drug resistance (AMR) in pneumococci complicates the treatment of serious pneumococcal infections. Country-specific AMR patterns can help to establish guidelines for empiric therapy. The aim of the current study was to analyze the distribution of AMR among Streptococcus pneumoniae isolates at Jordan University Hospital (JUH) during 2000–2018. Paper-based and electronic clinical data registry records from 2000 to 2018 were retrospectively analyzed to study the AMR among pneumococcal isolates at JUH. Temporal trend analysis was done using two-tailed linear-by-linear test for association. The total number of unique pneumococcal isolates that were identified was 556, of which 544 isolates had antimicrobial susceptibility testing results. The most frequent specimens were eye (n = 117, 21.0%), bloodstream (n = 93, 16.7%) and sputum (n = 81, 14.6%). Invasive infections represented 23.6% of all unique isolates. The overall susceptibility of S. pneumoniae isolates during the study period to different antimicrobials was: 100% to vancomycin, 97.7% to ceftriaxone, 97.1% to cefotaxime, 94.9% to chloramphenicol, 89.7% to penicillin, 83.8% to levofloxacin, 67.7% to clindamycin and 52.1% to erythromycin. The prevalence of multi-drug resistance (MDR) was 8.6% (95% confidence interval: 6.4–11.5%). Trend analysis showed an increase in the prevalence of non-susceptibility to erythromycin, clindamycin and levofloxacin (p < 0.001). MDR prevalence increased from 1.6% in the first quarter to 14.6% in the fourth quarter (p < 0.001). The incidence of invasive infections declined over the study period (p < 0.001). The increase in the prevalence of AMR and MDR among pneumococcal isolates in Jordan demands judicious use of antimicrobials and regular surveillance of resistance.
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43.
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44.
  • Sid Ahmed, Mazen, 1970-, et al. (författare)
  • Association of blaVIM-2, blaPDC-35, blaOXA-10, blaOXA-488 and blaVEB-9 β-Lactamase Genes with Resistance to Ceftazidime-Avibactam and Ceftolozane-Tazobactam in Multidrug-Resistant Pseudomonas aeruginosa
  • 2022
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Ceftazidime-avibactam and ceftolozane-tazobactam are approved for the treatment of complicated Gram-negative bacterial infections including multidrug-resistant (MDR) Pseudomonas aeruginosa. Resistance to both agents has been reported, but the underlying mechanisms have not been fully explored. This study aimed to correlate β-lactamases with phenotypic resistance to ceftazidime-avibactam and/or ceftolozane-tazobactam in MDR-P. aeruginosa from Qatar. A total of 525 MDR-P. aeruginosa isolates were collected from clinical specimens between 2014 and 2017. Identification and antimicrobial susceptibility were performed by the BD PhoenixTM system and gradient MIC test strips. Of the 75 sequenced MDR isolates, 35 (47%) were considered as having difficult-to-treat resistance, and 42 were resistant to ceftazidime-avibactam (37, 49.3%), and/or ceftolozane-tazobactam (40, 53.3%). They belonged to 12 sequence types, with ST235 being predominant (38%). Most isolates (97.6%) carried one or more β-lactamase genes, with blaOXA-488 (19%) and blaVEB-9 (45.2%) being predominant. A strong association was detected between class B β-lactamase genes and both ceftazidime-avibactam and ceftolozane-tazobactam resistance, while class A genes were associated with ceftolozane-tazobactam resistance. Co-resistance to ceftazidime-avibactam and ceftolozane-tazobactam correlated with the presence of blaVEB-9, blaPDC-35, blaVIM-2, blaOXA-10 and blaOXA-488. MDR-P. aeruginosa isolates resistant to both combination drugs were associated with class B β-lactamases (blaVIM-2) and class D β-lactamases (blaOXA-10), while ceftolozane-tazobactam resistance was associated with class A (blaVEB-9), class C (blaVPDC-35), and class D β-lactamases (blaOXA-488).
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45.
  • Sjöström, Karin, et al. (författare)
  • Antimicrobial Resistance Patterns in Organic and Conventional Dairy Herds in Sweden
  • 2020
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Monitoring antimicrobial resistance (AMR) and use (AMU) is important for control. We used Escherichia coli from healthy young calves as an indicator to evaluate whether AMR patterns differ between Swedish organic and conventional dairy herds and whether the patterns could be related to AMU data. Samples were taken twice, in 30 organic and 30 conventional dairy herds. Selective culturing for Escherichia coli, without antibiotics and with nalidixic acid or tetracycline, was used to estimate the proportions of resistant isolates. Microdilution was used to determine the minimum inhibitory concentrations (MICs) for thirteen antimicrobial substances. AMU data were based on collection of empty drug packages. Less than 8% of the bacterial growth on non-selective plates was also found on selective plates with tetracycline, and 1% on plates with nalidixic acid. Despite some MIC variations, resistance patterns were largely similar in both periods, and between organic and conventional herds. For most substances, only a few isolates were classified as resistant. The most common resistances were against ampicillin, streptomycin, sulfamethoxazole, and tetracycline. No clear association with AMU could be found. The lack of difference between organic and conventional herds is likely due to a generally good animal health status and consequent low AMU in both categories.
  •  
46.
  • Svebrant, Sofia, et al. (författare)
  • On-site pilot testing of hospital wastewater ozonation to reduce pharmaceutical residues and antibiotic-resistant bacteria
  • 2021
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Hospital sewage constitutes an important point source for antibiotics and antibiotic-resistant bacteria due to the high antibiotic use. Antibiotic resistance can develop and cause problems in sewage systems within hospitals and municipal wastewater treatment plants, thus, interventions to treat hospital sewage on-site are important. Ozonation has proven effective in treating relatively clean wastewater, but the effect on untreated wastewater is unclear. Therefore, we piloted implementation of ozonation to treat wastewater in a tertiary hospital in Uppsala, Sweden. We measured active pharmaceutical ingredients (APIs) using liquid chromatography-mass spectrometry and antibiotic-resistant Enterobacteriaceae using selective culturing pre-and post-ozonation. Comparing low (1 m3 /h) and high (2 m3 /h) flow, we obtained a 'dose-dependent' effect of API reduction (significant reduction of 12/29 APIs using low and 2/29 APIs using high flow, and a mean reduction of antibiotics of 41% using low vs. 6% using high flow, 25% vs. 6% for all APIs). There was no significant difference in the amount of antibiotic-resistant Enterobacteiaceae pre-and post-ozonation. Our results demonstrate that ozonation of untreated wastewater can reduce API content. However, due to the moderate API decrease and numerous practical challenges in the on-site setting, this specific ozonation system is not suitable to implement at full scale in our hospital.
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47.
  • Sychareun, V, et al. (författare)
  • Knowledge, Attitudes, Perception and Reported Practices of Healthcare Providers on Antibiotic Use and Resistance in Pregnancy, Childbirth and Children under Two in Lao PDR: A Mixed Methods Study
  • 2021
  • Ingår i: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Overuse and misuse of antibiotics contribute unnecessarily to antibiotic resistance (ABR), and are thereby global health threats. Inappropriate prescriptions of antibiotics during pregnancy, delivery and early childhood are widespread across the world. This study aimed to assess knowledge, attitudes, and reported practices of healthcare providers (HCPs) and to explore their perceptions regarding antibiotic use and ABR related to pregnancy, childbirth, and children under two in Lao PDR. Methods: This is a mixed methods study with data collection in 2019 via structured interviews among 217 HCPs (medical doctors/assistant doctors, midwives/nurses, pharmacists/assistant pharmacists and drug sellers), who prescribed/dispensed antibiotics in one rural and one urban district in Vientiane province and individual qualitative interviews with 30 HCPs and stakeholders. Results: Of the HCPs, 36% had below average knowledge regarding antibiotic use and ABR, and 67% reported prescribing antibiotics for uncomplicated vaginal delivery. Half of the HCPs did not believe that their prescribing contributed to ABR, and only 9% had participated in antibiotic education. Conclusion: A substantial number of HCPs had suboptimal knowledge and prescribed antibiotics unnecessarily, thereby contributing to ABR. Continuous education and regular supervision of HCPs is recommended to improve the use of antibiotics related to pregnancy, childbirth, and young children.
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48.
  • Tråven, Madeleine, et al. (författare)
  • Associations between Bovine Coronavirus and Bovine Respiratory Syncytial Virus Infections and Productivity, Health Status and Occurrence of Antimicrobial Resistance in Swedish Dairy Herds
  • 2021
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCoV) affect dairy herds worldwide. In this study, effects on herd health, morbidity, and antimicrobial resistance (AMR) were assessed. Herds were considered free of infection (FREE), recently infected (RI) or past steadily infected (PSI) based on antibody testing of milk from primiparous cows. Data from farm records, national databases, and AMR of fecal Escherichia coli from calves were used as outcome variables. Compared to BRSV FREE herds: BRSV PSI herds had significantly higher odds of cough in young stock, a higher proportion of quinolone-resistant E. coli (QREC), but a lower proportion of cows with fever. BRSV RI herds had significantly higher odds of diarrhea in calves and young stock, a higher proportion of QREC and higher odds of multidrug-resistant E. coli. Compared to BCoV FREE herds: BCoV PSI herds had significantly higher odds of cough in all ages, and of diarrhea in young stock and cows, and a higher proportion of cows with fever. BCoV RI herds had significantly higher odds of diarrhea in young stock and cows and of cough in all ages. The results support previous research that freedom from BRSV and BCoV is beneficial for animal welfare and farm economy and possibly also mitigates AMR.
  •  
49.
  • Uddin, Md Bashir, et al. (författare)
  • Molecular Detection of Colistin Resistance mcr-1 Gene in Multidrug-Resistant Escherichia coli Isolated from Chicken
  • 2022
  • Ingår i: Antibiotics. - : MDPI AG. - 2079-6382. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Zoonotic and antimicrobial-resistant Escherichia coli (hereafter, E. coli) is a global public health threat which can lead to detrimental effects on human health. Here, we aim to investigate the antimicrobial resistance and the presence of mcr-1 gene in E. coli isolated from chicken feces. Ninety-four E. coli isolates were obtained from samples collected from different locations in Bangladesh, and the isolates were identified using conventional microbiological tests. Phenotypic disk diffusion tests using 20 antimicrobial agents were performed according to CLSI-EUCAST guidelines, and minimum inhibitory concentrations (MICs) were determined for a subset of samples. E. coli isolates showed high resistance to colistin (88.30%), ciprofloxacin (77.66%), trimethoprim/sulfamethoxazole (76.60%), tigecycline (75.53%), and enrofloxacin (71.28%). Additionally, the pathotype eaeA gene was confirmed in ten randomly selected E. coli isolates using primer-specific polymerase chain reaction (PCR). The presence of mcr-1 gene was confirmed using PCR and sequencing analysis in six out of ten E. coli isolates. Furthermore, sequencing and phylogenetic analyses revealed a similarity between the catalytic domain of Neisseria meningitidis lipooligosaccharide phosphoethanolamine transferase A (LptA) and MCR proteins, indicating that the six tested isolates were colistin resistant. Finally, the findings of the present study showed that E. coli isolated from chicken harbored mcr-1 gene, and multidrug and colistin resistance. These findings accentuate the need to implement strict measures to limit the imprudent use of antibiotics, particularly colistin, in agriculture and poultry farms.
  •  
50.
  • Wang, Jinglan, et al. (författare)
  • Pbp4 is likely involved in cell division of the longitudinally dividing bacterium candidatus thiosymbion oneisti
  • 2021
  • Ingår i: Antibiotics. - : MDPI. - 2079-6382. ; 10:3, s. 1-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Peptidoglycan (PG) is essential for bacterial survival and maintaining cell shape. The rod-shaped model bacterium Escherichia coli has a set of seven endopeptidases that remodel the PG during cell growth. The gamma proteobacterium Candidatus Thiosymbion oneisti is also rod-shaped and attaches to the cuticle of its nematode host by one pole. It widens and divides by longitudinal fission using the canonical proteins MreB and FtsZ. The PG layer of Ca. T. oneisti has an unusually high peptide cross-linkage of 67% but relatively short glycan chains with an average length of 12 disaccharides. Curiously, it has only two predicted endopeptidases, MepA and PBP4. Cellular localization of symbiont PBP4 by fluorescently labeled antibodies reveals its polar localization and its accumulation at the constriction sites, suggesting that PBP4 is involved in PG biosynthesis during septum formation. Isolated symbiont PBP4 protein shows a different selectivity for β-lactams compared to its homologue from E. coli. Bocillin-FL binding by PBP4 is activated by some β-lactamssuggesting the presence of an allosteric binding site. Overall, our data point to a role of PBP4 in PG cleavage during the longitudinal cell division and to a PG that might have been adapted to the symbiotic lifestyle.
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