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Antibiotics
Volume 11
Issue 1
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Antibiotics, Volume 11, Issue 1 (January 2022) – 121 articles

Cover Story (view full-size image): Nosocomial and medical-device-induced biofilm infections affect millions of lives and urgently require innovative preventive approaches. Antimicrobial peptides (AMPs) are ideal candidates for this fight. Surfaces functionalized with AMPs to prevent bacterial attachment/biofilms formation have experienced tremendous development over the last decade. We describe the different mechanisms of action by which AMPs act in this prevention. We also analyze AMP immobilization techniques on a variety of materials, with a focus on biomedical applications. Then, we summarize the advances made to date regarding the immobilization strategies of AMPs on various surfaces and their ability to prevent the adhesion of various microorganisms. Progress toward the clinical approval of AMPs in antibiotherapy is also reviewed. View this paper.
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7 pages, 1347 KiB  
Article
A New Antimicrobial Phenylpropanol from the Leaves of Tabernaemontana inconspicua Stapf. (Apocynaceae) Inhibits Pathogenic Gram-Negative Bacteria
by Lidwine Ngah, Willifred Dongmo Tékapi Tsopgni, Judith Caroline Ngo Nyobe, Alain Tadjong Tcho, Moses K. Langat, Jean Claude Ndom, Eduard Mas-Claret, Nicholas John Sadgrove, Alain François Kamdem Waffo and Methee Phumthum
Antibiotics 2022, 11(1), 121; https://doi.org/10.3390/antibiotics11010121 - 17 Jan 2022
Cited by 1 | Viewed by 2661
Abstract
A chemical investigation of the leaves of Tabernaemontana inconspicua Stapf. led to the isolation of a new phenylpropanol derivative, namely irisdichototin G (1), together with nine known compounds, including one polyol derivative, dambonitol (2); three alkaloids, 10-hydroxycoronaridine (3 [...] Read more.
A chemical investigation of the leaves of Tabernaemontana inconspicua Stapf. led to the isolation of a new phenylpropanol derivative, namely irisdichototin G (1), together with nine known compounds, including one polyol derivative, dambonitol (2); three alkaloids, 10-hydroxycoronaridine (3), voacristine (4) and vobasine (5); two triterpenes lupeol (6), betulinic acid (7) and three sterols, sitosterol (8), sitosterol-3-O-β-D-glucopyranoside (9) and stigmasterol (10). The structure of the new compound, as well as those of the known ones, was established by means of spectroscopic methods: NMR analysis (1H and 13C NMR, 1H-1H-COSY, HSQC, HMBC and NOESY), high-resolution mass spectrometry (HR-ESI-MS) and comparisons with previously reported data. Among the known compounds, compound 2 was firstly reported from the family Apocynaceae. Compounds 1–5 were tested for their antimicrobial effects against three Gram-negative organisms associated with human wound and systemic infections, namely Haemophilus influenzae 9435337A, Klebsiella pneumoniae 17102005 and Pseudomonas aeruginosa 2137659B. Compounds 1, 3, and 5 showed significant antimicrobial effects with minimum inhibitory concentrations (MIC) of 62.5 μg/mL, 62.5 μg/mL and 7.81 μg/mL, respectively, against Haemophilus influenzae, whereas compounds 1 and 5 showed significant antimicrobial effects, with a MIC value of 31.25 μg/mL against Pseudomonas aeruginosa. In addition, compound 3 showed significant antimicrobial activity, with a MIC value of 31.25 μg/mL against Klebsiella pneumoniae. Full article
(This article belongs to the Special Issue Phytocompounds with Antimicrobial Activity: From Discovery to Application)
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10 pages, 249 KiB  
Article
Retrospective Cohort Analysis of the Effect of Antimicrobial Stewardship on Postoperative Antibiotic Therapy in Complicated Intra-Abdominal Infections: Short-Course Therapy Does Not Compromise Patients’ Safety
by Güzin Surat, Pascal Meyer-Sautter, Jan Rüsch, Johannes Braun-Feldweg, Christoph-Thomas Germer and Johan Friso Lock
Antibiotics 2022, 11(1), 120; https://doi.org/10.3390/antibiotics11010120 - 17 Jan 2022
Cited by 5 | Viewed by 3022
Abstract
Background: Recent evidence suggests that short-course postoperative antibiotic therapy (PAT) of intra-abdominal infections is non-inferior considering clinical outcomes. The aim of this study was to compare the outcome of short vs. long PAT in complicated intra-abdominal infections (cIAIs) without sepsis. Methods: We performed [...] Read more.
Background: Recent evidence suggests that short-course postoperative antibiotic therapy (PAT) of intra-abdominal infections is non-inferior considering clinical outcomes. The aim of this study was to compare the outcome of short vs. long PAT in complicated intra-abdominal infections (cIAIs) without sepsis. Methods: We performed a single center-quality improvement study at a 1500 bed sized university hospital in Bavaria, Germany, with evaluation of the length of antibiotic therapy after emergency surgery on cIAIs with adequate source control during 2016 to 2018. We reviewed a total of 260 cases (160 short duration vs. 100 long duration). The antibiotic prescribing quality was assessed by our in-house antimicrobial stewardship team (AMS). Results: No significant differences of patient characteristics were observed between short and long PAT. The frequency of long PAT declined during the observation period from 48.1% to 26.3%. Prolongation of PAT was not linked with any clinical benefits, on the contrary clinical outcome of patients receiving longer regimes were associated with higher postoperative morbidity. AMS identified additional educational targets to improve antibiotic prescribing quality on general wards like unnecessary postoperative switches of antibiotic regimes, e.g., unrequired switches to oral antibiotics as well as prolongation of PAT due to elevated CRP. Conclusion: Short-course antibiotic therapy after successful surgical source control in cIAIs is safe, and long-duration PAT has no beneficial effects. Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Stewardship, 2nd Volume)
12 pages, 2157 KiB  
Article
Reservoir of Antibiotic Residues and Resistant Coagulase Negative Staphylococci in a Healthy Population in the Greater Accra Region, Ghana
by Samuel Oppong Bekoe, Sophie Hane-Weijman, Sofie Louise Trads, Emmanuel Orman, Japheth Opintan, Martin Hansen, Niels Frimodt-Møller and Bjarne Styrishave
Antibiotics 2022, 11(1), 119; https://doi.org/10.3390/antibiotics11010119 - 17 Jan 2022
Cited by 3 | Viewed by 1973
Abstract
Antimicrobial resistance threatens infectious disease management outcomes, especially in developing countries. In this study, the occurrence of resistant coagulase-negative staphylococci (rCoNS) and antibiotic residues in urine samples of 401 healthy individuals from Korle-Gonno (KG) and Dodowa (DDW) in Ghana was investigated. MALDI-ToF/MS with [...] Read more.
Antimicrobial resistance threatens infectious disease management outcomes, especially in developing countries. In this study, the occurrence of resistant coagulase-negative staphylococci (rCoNS) and antibiotic residues in urine samples of 401 healthy individuals from Korle-Gonno (KG) and Dodowa (DDW) in Ghana was investigated. MALDI-ToF/MS with gram-staining techniques detected and identified the CoNS. SPE-LC-MS/MS detected and quantified nine commonly used antibiotics in the samples. The results showed 63 CoNS isolates detected in 47 (12%) samples, with S. haemolyticus (78%) and S. epidermidis (8%) being predominant. Most of the isolates (95%) were resistant to at least one antibiotic, with the highest resistance observed against sulphamethoxazole (87%). Resistance profiles in samples from DDW and KG were largely comparable, but with some differences. For instance, DDW isolates were more resistant to gentamicin (p = 0.0244), trimethoprim (p = 0.0045), and cefoxitin (p = 0.0078), whereas KG isolates were more resistant to erythromycin (p = 0.0356). Although the volunteers had not knowingly consumed antibiotics two weeks before sampling, antibiotic residues, ranging between 1.44–17000 ng mL−1 were identified in 22% of urine samples. Samples with antibiotic residues were likely to also contain rCoNS (89%). The most frequent antibiotics detected were tetracycline (63%) and ciprofloxacin (54%). Healthy individuals could thus be reservoirs of antibiotic residues and rCoNS at the community level. Full article
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13 pages, 682 KiB  
Article
Home Oral Care of Periodontal Patients Using Antimicrobial Gel with Postbiotics, Lactoferrin, and Aloe Barbadensis Leaf Juice Powder vs. Conventional Chlorhexidine Gel: A Split-Mouth Randomized Clinical Trial
by Andrea Butera, Simone Gallo, Maurizio Pascadopoli, Damiano Taccardi and Andrea Scribante
Antibiotics 2022, 11(1), 118; https://doi.org/10.3390/antibiotics11010118 - 17 Jan 2022
Cited by 64 | Viewed by 4751
Abstract
Periodontitis is a progressive destruction of both soft and hard tooth-supporting tissues. In the last years, probiotics have been proposed as a support to the gold standard treatment scaling and root planing (SRP), but no extensive literature is present as regards the effect [...] Read more.
Periodontitis is a progressive destruction of both soft and hard tooth-supporting tissues. In the last years, probiotics have been proposed as a support to the gold standard treatment scaling and root planing (SRP), but no extensive literature is present as regards the effect of the more recent postbiotics. Thirty patients subjected to SRP were randomly assigned to two domiciliary hygiene treatments based on the following oral gels: the postbiotics-based Biorepair Parodontgel Intensive (Group 1) and the chlorhexidine-based Curasept Periodontal Gel (Group 2). At baseline (T0) and after 3 and 6 months (T1–T2), the following periodontal clinical parameters were recorded: Probing Pocket Depth (PPD), recession, dental mobility, Bleeding on Probing (BoP), and Plaque Control Record (PCR). A significant intragroup reduction was assessed in both groups for PPD, BoP, and PCR; conversely, recession significantly increased in both groups, whereas dental mobility did not vary. As regards intergroup comparisons, no statistically significant differences were assessed. Both gels, respectively, containing antioxidant natural ingredients and chlorhexidine, are effective for the domiciliary treatment of periodontitis. Further studies are required to evaluate the singular chemical compounds of the gels expected to exert the beneficial action assessed in this preliminary study. Full article
(This article belongs to the Special Issue Antibacterial Treatment in Periodontal and Endodontic Therapy)
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13 pages, 2835 KiB  
Brief Report
Effect of Cephalosporin Treatment on the Microbiota and Antibiotic Resistance Genes in Feces of Dairy Cows with Clinical Mastitis
by Lei Dong, Lu Meng, Huimin Liu, Haoming Wu, Martine Schroyen, Nan Zheng and Jiaqi Wang
Antibiotics 2022, 11(1), 117; https://doi.org/10.3390/antibiotics11010117 - 17 Jan 2022
Cited by 11 | Viewed by 2578
Abstract
Antibiotics are frequently used to treat dairy cows with mastitis. However, the potential effects of β-lactam antibiotics, such as cephalosporins, on the fecal microbiome is unknown. The objective was to investigate the effects of ceftiofur and cefquinome on the fecal microbiota and antibiotic [...] Read more.
Antibiotics are frequently used to treat dairy cows with mastitis. However, the potential effects of β-lactam antibiotics, such as cephalosporins, on the fecal microbiome is unknown. The objective was to investigate the effects of ceftiofur and cefquinome on the fecal microbiota and antibiotic resistance genes of dairy cows with mastitis. The fecal samples were collected from 8 dairy cows at the following periods: the start day (Day 0), medication (Days 1, 2, and 3), withdrawal (Days 4, 6, 7, and 8), and recovery (Days 9, 11, 13, and 15). 16S rRNA gene sequencing was applied to explore the changes in microbiota, and qPCR was used to investigate the antibiotic resistance genes. The cephalosporin treatment significantly decreased the microbial diversity and richness, indicated by the decreased Shannon and Chao 1 indexes, respectively (p < 0.05). The relative abundance of Bacteroides, Bacteroidaceae, Bacteroidales, and Bacteroidia increased, and the relative abundance of Clostridia, Clostridiales, Ethanoligenens, and Clostridium IV decreased at the withdrawal period. The cephalosporin treatment increased the relative abundance of β-lactam resistance genes (blaTEM and cfxA) at the withdrawal period (p < 0.05). In conclusion, the cephalosporin treatment decreased the microbial diversity and richness at the medication period, and increased the relative abundance of two β-lactam resistance genes at the withdrawal period. Full article
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12 pages, 2529 KiB  
Article
Effect of Doxycycline in Decreasing the Severity of Clostridioides difficile Infection in Mice
by Bo-Yang Tsai, Yi-Hsin Lai, Chun-Wei Chiu, Chih-Yu Hsu, Yi-Hsuan Chen, Yueh-Lin Chen, Pei-Jane Tsai, Yuan-Pin Hung and Wen-Chien Ko
Antibiotics 2022, 11(1), 116; https://doi.org/10.3390/antibiotics11010116 - 17 Jan 2022
Viewed by 3598
Abstract
Background: Doxycycline possesses antibacterial activity against Clostridioides difficile and anti-inflammatory effects. Materials and Methods: The influence of doxycycline on the development of CDI was studied in an established animal model of CDI using C57BL/6 mice. Results: Mice intraperitoneally administered doxycycline had higher cecum [...] Read more.
Background: Doxycycline possesses antibacterial activity against Clostridioides difficile and anti-inflammatory effects. Materials and Methods: The influence of doxycycline on the development of CDI was studied in an established animal model of CDI using C57BL/6 mice. Results: Mice intraperitoneally administered doxycycline had higher cecum weight (1.3 ± 0.1 vs. 0.5 ± 0.1 g; p < 0.001) and less body weight reduction (0.7 ± 0.5 g vs. −17.4 ± 0.2 g; p < 0.001) than untreated mice infected with C. difficile. Oral doxycycline, metronidazole, or vancomycin therapy resulted in less body weight reduction in mice with CDI than in untreated mice (1.1 ± 0.1 g, 1.3 ± 0.2 g, 1.2 ± 0.1 g, vs. 2.9 ± 0.3 g; p < 0.001). Doxycycline therapy led to lower expression levels of inflammatory cytokines, such as macrophage inflammatory protein-2 (0.4 ± 0.1 vs. 2.9 ± 1.3, p = 0.02), and higher levels of zonula occludens-1 (1.2 ± 0.1 vs. 0.8 ± 0.1, p = 0.02) in colonic tissues than in untreated mice. Conclusions: Concurrent intraperitoneal administration of doxycycline and oral C. difficile challenge does not aggravate the disease severity of CDI, and oral doxycycline may be a potential therapeutic option for CDI. Full article
(This article belongs to the Special Issue Next-Generation Interventions for Clostridioides difficile Infections to Minimize Microbiota Disturbance, Increase Efficacy, and Decrease Recurrence)
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13 pages, 270 KiB  
Article
Antimicrobial and Antibiotic Resistance from the Perspective of Polish Veterinary Students: An Inter-University Study
by Tomasz Sobierajski, Beata Mazińska, Wioleta Chajęcka-Wierzchowska, Marcin Śmiałek and Waleria Hryniewicz
Antibiotics 2022, 11(1), 115; https://doi.org/10.3390/antibiotics11010115 - 17 Jan 2022
Cited by 9 | Viewed by 2376
Abstract
The phenomenon of antibiotic resistance is a global problem that affects the use of antibiotics by humans and animal husbandry. One of the primary reasons for the growing phenomenon of antibiotic resistance is the over-prescription of antibiotics by doctors in human medicine and [...] Read more.
The phenomenon of antibiotic resistance is a global problem that affects the use of antibiotics by humans and animal husbandry. One of the primary reasons for the growing phenomenon of antibiotic resistance is the over-prescription of antibiotics by doctors in human medicine and the overuse of antibiotics in industrial animal farming. Adequate education of veterinary medical students on the use of antibiotics in animal husbandry may reduce antibiotic resistance. For this reason, a survey was conducted among students at four primary research and didactic centers teaching veterinary medicine in Poland. The survey aimed to find out the knowledge and attitude of students towards the use of antibiotics and antibiotic resistance. The survey was conducted in May/June 2021. Four hundred and sixty-seven students participated in the study. The study positively verified that antibiotics and antibiotic resistance knowledge increase with successive years of veterinary studies/education. For most students (82.2%), antibiotic resistance is a significant problem, but only 58.7% believe it is global, and one in three respondents heard about the One Health approach. Full article
26 pages, 2024 KiB  
Review
Performance Efficiency of Conventional Treatment Plants and Constructed Wetlands towards Reduction of Antibiotic Resistance
by Moushumi Hazra and Lisa M. Durso
Antibiotics 2022, 11(1), 114; https://doi.org/10.3390/antibiotics11010114 - 16 Jan 2022
Cited by 18 | Viewed by 3583
Abstract
Domestic and industrial wastewater discharges harbor rich bacterial communities, including both pathogenic and commensal organisms that are antibiotic-resistant (AR). AR pathogens pose a potential threat to human and animal health. In wastewater treatment plants (WWTP), bacteria encounter environments suitable for horizontal gene transfer, [...] Read more.
Domestic and industrial wastewater discharges harbor rich bacterial communities, including both pathogenic and commensal organisms that are antibiotic-resistant (AR). AR pathogens pose a potential threat to human and animal health. In wastewater treatment plants (WWTP), bacteria encounter environments suitable for horizontal gene transfer, providing an opportunity for bacterial cells to acquire new antibiotic-resistant genes. With many entry points to environmental components, especially water and soil, WWTPs are considered a critical control point for antibiotic resistance. The primary and secondary units of conventional WWTPs are not designed for the reduction of resistant microbes. Constructed wetlands (CWs) are viable wastewater treatment options with the potential for mitigating AR bacteria, their genes, pathogens, and general pollutants. Encouraging performance for the removal of AR (2–4 logs) has highlighted the applicability of CW on fields. Their low cost of construction, operation and maintenance makes them well suited for applications across the globe, especially in developing and low-income countries. The present review highlights a better understanding of the performance efficiency of conventional treatment plants and CWs for the elimination/reduction of AR from wastewater. They are viable alternatives that can be used for secondary/tertiary treatment or effluent polishing in combination with WWTP or in a decentralized manner. Full article
(This article belongs to the Special Issue The Distribution of Antibiotic Resistance in Terrestrial Ecosystems)
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10 pages, 2389 KiB  
Article
An In Vitro Evaluation of Denture Cleansing Regimens against a Polymicrobial Denture Biofilm Model
by Jason L. Brown, Tracy Young, Emily McKloud, Mark C. Butcher, David Bradshaw, Jonathan R. Pratten and Gordon Ramage
Antibiotics 2022, 11(1), 113; https://doi.org/10.3390/antibiotics11010113 - 16 Jan 2022
Cited by 6 | Viewed by 2685
Abstract
Denture stomatitis (DS) is an inflammatory disease resulting from a polymicrobial biofilm perturbation at the denture surface–palatal mucosa interface. Recommendations made by dental health care professionals often lack clarity for appropriate denture cleaning. This study investigated the efficacy of brushing with off-the-shelf denture [...] Read more.
Denture stomatitis (DS) is an inflammatory disease resulting from a polymicrobial biofilm perturbation at the denture surface–palatal mucosa interface. Recommendations made by dental health care professionals often lack clarity for appropriate denture cleaning. This study investigated the efficacy of brushing with off-the-shelf denture cleanser (DC) tablets (Poligrip®) vs. two toothpastes (Colgate® and Crest®) in alleviating the viable microorganisms (bacteria and fungi) in an in vitro denture biofilm model. Biofilms were grown on poly(methyl)methacrylate (PMMA) discs, then treated daily for 7 days with mechanical disruption (brushing), plus Poligrip® DC, Colgate® or Crest® toothpastes. Weekly treatment with Poligrip® DC on day 7 only was compared to daily modalities. All treatment parameters were processed to determine viable colony forming units for bacteria and fungi using the Miles and Misra technique, and imaged by confocal laser scanning microscopy (CLSM). Brushing with daily DC therapy was the most effective treatment in reducing the viable biofilm over 7 days of treatment. Brushing only was ineffective in controlling the viable bioburden, which was confirmed by CLSM imaging. This data indicates that regular cleansing of PMMA with DC was best for polymicrobial biofilms. Full article
(This article belongs to the Special Issue In the Race against Polymicrobial Biofilms: Current Research and New Breakthroughs for the Clinic)
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10 pages, 965 KiB  
Article
The Serum Concentration of Vancomycin as a Diagnostic Predictor of Nephrotoxic Acute Kidney Injury in Critically Ill Patients
by Welder Zamoner, Karina Zanchetta Cardoso Eid, Lais Maria Bellaver de Almeida, Isabella Gonçalves Pierri, Adriano dos Santos, André Luis Balbi and Daniela Ponce
Antibiotics 2022, 11(1), 112; https://doi.org/10.3390/antibiotics11010112 - 15 Jan 2022
Cited by 2 | Viewed by 1916
Abstract
The impact of serum concentrations of vancomycin is a controversial topic. Results: 182 critically ill patients were evaluated using vancomycin and 63 patients were included in the study. AKI occurred in 44.4% of patients on the sixth day of vancomycin use. Vancomycin higher [...] Read more.
The impact of serum concentrations of vancomycin is a controversial topic. Results: 182 critically ill patients were evaluated using vancomycin and 63 patients were included in the study. AKI occurred in 44.4% of patients on the sixth day of vancomycin use. Vancomycin higher than 17.53 mg/L between the second and the fourth days of use was a predictor of AKI, preceding AKI diagnosis for at least two days, with an area under the curve of 0.806 (IC 95% 0.624–0.987, p = 0.011). Altogether, 46.03% of patients died, and in the Cox analysis, the associated factors were age, estimated GFR, CPR, and vancomycin between the second and the fourth days. Discussion: The current 2020 guidelines recommend using Bayesian-derived AUC monitoring rather than trough concentrations. However, due to the higher number of laboratory analyses and the need for an application to calculate the AUC, many centers still use therapeutic trough levels between 15 and 20 mg/L. Conclusion: The results of this study suggest that a narrower range of serum concentration of vancomycin was a predictor of AKI in critically ill septic patients, preceding the diagnosis of AKI by at least 48 h, and it can be a useful monitoring tool when AUC cannot be used. Full article
(This article belongs to the Special Issue TDM, Individual Dosing and Application of Antibiotics/Antiinfectives in Critically Ill Patients)
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18 pages, 2047 KiB  
Article
Optimization of Propidium Monoazide qPCR (Viability-qPCR) to Quantify the Killing by the Gardnerella-Specific Endolysin PM-477, Directly in Vaginal Samples from Women with Bacterial Vaginosis
by Agnieszka Latka, Leen Van Simaey, Marijke Reynders, Piet Cools, Tess Rogier, Barbara Lebbe, Lorenzo Corsini, Christine Landlinger and Mario Vaneechoutte
Antibiotics 2022, 11(1), 111; https://doi.org/10.3390/antibiotics11010111 - 15 Jan 2022
Cited by 3 | Viewed by 2485
Abstract
Quantification of the number of living cells in biofilm or after eradication treatments of biofilm, is problematic for different reasons. We assessed the performance of pre-treatment of DNA, planktonic cells and ex vivo vaginal biofilms of Gardnerella with propidium monoazide (PMAxx) to prevent [...] Read more.
Quantification of the number of living cells in biofilm or after eradication treatments of biofilm, is problematic for different reasons. We assessed the performance of pre-treatment of DNA, planktonic cells and ex vivo vaginal biofilms of Gardnerella with propidium monoazide (PMAxx) to prevent qPCR-based amplification of DNA from killed cells (viability-qPCR). Standard PMAxx treatment did not completely inactivate free DNA and did not affect living cells. While culture indicated that killing of planktonic cells by heat or by endolysin was complete, viability-qPCR assessed only log reductions of 1.73 and 0.32, respectively. Therefore, we improved the standard protocol by comparing different (combinations of) parameters, such as concentration of PMAxx, and repetition, duration and incubation conditions of treatment. The optimized PMAxx treatment condition for further experiments consisted of three cycles, each of: 15 min incubation on ice with 50 µM PMAxx, followed by 15 min-long light exposure. This protocol was validated for use in vaginal samples from women with bacterial vaginosis. Up to log2.2 reduction of Gardnerella cells after treatment with PM-477 was documented, despite the complex composition of the samples, which might have hampered the activity of PM-477 as well as the quantification of low loads by viability-qPCR. Full article
(This article belongs to the Special Issue Bacteriophage Lysins in the Era of Antibiotic Resistance)
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14 pages, 1376 KiB  
Article
Protective Effects of Grape Seed Oligomeric Proanthocyanidins in IPEC-J2–Escherichia coli/Salmonella Typhimurium Co-Culture
by Dóra Kovács, Nikolett Palkovicsné Pézsa, Ákos Jerzsele, Miklós Süth and Orsolya Farkas
Antibiotics 2022, 11(1), 110; https://doi.org/10.3390/antibiotics11010110 - 15 Jan 2022
Cited by 11 | Viewed by 2289
Abstract
Intestinal epithelium provides the largest barrier protecting mammalian species from harmful external factors; however, it can be severely compromised by the presence of bacteria in the gastrointestinal (GI) tract. Antibiotics have been widely used for the prevention and treatment of GI bacterial infections, [...] Read more.
Intestinal epithelium provides the largest barrier protecting mammalian species from harmful external factors; however, it can be severely compromised by the presence of bacteria in the gastrointestinal (GI) tract. Antibiotics have been widely used for the prevention and treatment of GI bacterial infections, leading to antimicrobial resistance in human and veterinary medicine alike. In order to decrease antibiotic usage, natural substances, such as flavonoids, are investigated to be used as antibiotic alternatives. Proanthocyanidins (PAs) are potential candidates for this purpose owing to their various beneficial effects in humans and animals. In this study, protective effects of grape seed oligomeric proanthocyanidins (GSOPs) were tested in IPEC-J2 porcine intestinal epithelial cells infected with Escherichia coli and Salmonella enterica ser. Typhimurium of swine origin. GSOPs were able to alleviate oxidative stress, inflammation and barrier integrity disruption inflicted by bacteria in the co-culture. Furthermore, GSOPs could decrease the adhesion of both bacteria to IPEC-J2 cells. Based on these observations, GSOPs seem to be promising candidates for the prevention and treatment of gastrointestinal bacterial infections. Full article
(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals, 2nd Volume)
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10 pages, 935 KiB  
Article
Antimicrobial Stewardship from Health Professionals’ Perspective: Awareness, Barriers, and Level of Implementation of the Program
by Haya Nassar, Rana Abu-Farha, Muna Barakat and Eman Alefishat
Antibiotics 2022, 11(1), 99; https://doi.org/10.3390/antibiotics11010099 - 14 Jan 2022
Cited by 4 | Viewed by 2496
Abstract
This study aimed to evaluate health professionals’ perceptions regarding the level of implementation of the Antimicrobials Stewardship (AMS) programs in Jordanian tertiary hospitals and to assess the perceived barriers to its implementation. During this cross-sectional study, a total of 157 healthcare providers agreed [...] Read more.
This study aimed to evaluate health professionals’ perceptions regarding the level of implementation of the Antimicrobials Stewardship (AMS) programs in Jordanian tertiary hospitals and to assess the perceived barriers to its implementation. During this cross-sectional study, a total of 157 healthcare providers agreed to participate (response rate 96.3%). Participants were asked to complete an electronic survey after meeting them at their working sites. Only 43.9% of the healthcare providers (n = 69) reported having an AMS committee in their hospital settings. The results suggested that private hospitals have significantly better AMS implementation compared to public hospitals among four areas (p ≤ 0.05). Moreover, the results showed that the most widely available strategies to implement AMS were infectious disease/microbiology advice (n = 112, 71.3%), and treatment guidelines (n = 111, 70.7%). Additionally, the study revealed that the main barrier to AMS implementation was the lack of information technology support (n = 125, 79.6%). These findings could draw managers’ attention to the importance of AMS and support the health care provider’s practice of AMS in Jordanian tertiary hospitals by making the right decisions and the required modifications regarding the strategies needed for the implementation of AMS programs. Full article
(This article belongs to the Special Issue Antibiotics Use and Stewardship in Hospitals and Outpatients Care Facilities)
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15 pages, 1624 KiB  
Review
Air Ambulance: Antimicrobial Power of Bacterial Volatiles
by Alexander Lammers, Michael Lalk and Paolina Garbeva
Antibiotics 2022, 11(1), 109; https://doi.org/10.3390/antibiotics11010109 - 14 Jan 2022
Cited by 13 | Viewed by 3100
Abstract
We are currently facing an antimicrobial resistance crisis, which means that a lot of bacterial pathogens have developed resistance to common antibiotics. Hence, novel and innovative solutions are urgently needed to combat resistant human pathogens. A new source of antimicrobial compounds could be [...] Read more.
We are currently facing an antimicrobial resistance crisis, which means that a lot of bacterial pathogens have developed resistance to common antibiotics. Hence, novel and innovative solutions are urgently needed to combat resistant human pathogens. A new source of antimicrobial compounds could be bacterial volatiles. Volatiles are ubiquitous produced, chemically divers and playing essential roles in intra- and interspecies interactions like communication and antimicrobial defense. In the last years, an increasing number of studies showed bioactivities of bacterial volatiles, including antibacterial, antifungal and anti-oomycete activities, indicating bacterial volatiles as an exciting source for novel antimicrobial compounds. In this review we introduce the chemical diversity of bacterial volatiles, their antimicrobial activities and methods for testing this activity. Concluding, we discuss the possibility of using antimicrobial volatiles to antagonize the antimicrobial resistance crisis. Full article
(This article belongs to the Special Issue The Ecological Role of Antibiotic Production in Bacteria)
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45 pages, 1689 KiB  
Review
Nanoparticles—Attractive Carriers of Antimicrobial Essential Oils
by Arya Nair, Rashmi Mallya, Vasanti Suvarna, Tabassum Asif Khan, Munira Momin and Abdelwahab Omri
Antibiotics 2022, 11(1), 108; https://doi.org/10.3390/antibiotics11010108 - 14 Jan 2022
Cited by 48 | Viewed by 7891
Abstract
Microbial pathogens are the most prevalent cause of chronic infections and fatalities around the world. Antimicrobial agents including antibiotics have been frequently utilized in the treatment of infections due to their exceptional outcomes. However, their widespread use has resulted in the emergence of [...] Read more.
Microbial pathogens are the most prevalent cause of chronic infections and fatalities around the world. Antimicrobial agents including antibiotics have been frequently utilized in the treatment of infections due to their exceptional outcomes. However, their widespread use has resulted in the emergence of multidrug-resistant strains of bacteria, fungi, viruses, and parasites. Furthermore, due to inherent resistance to antimicrobial drugs and the host defence system, the advent of new infectious diseases, chronic infections, and the occurrence of biofilms pose a tougher challenge to the current treatment line. Essential oils (EOs) and their biologically and structurally diverse constituents provide a distinctive, inexhaustible, and novel source of antibacterial, antiviral, antifungal, and antiparasitic agents. However, due to their volatile nature, chemical susceptibility, and poor solubility, their development as antimicrobials is limited. Nanoparticles composed of biodegradable polymeric and inorganic materials have been studied extensively to overcome these limitations. Nanoparticles are being investigated as nanocarriers for antimicrobial delivery, antimicrobial coatings for food products, implantable devices, and medicinal materials in dressings and packaging materials due to their intrinsic capacity to overcome microbial resistance. Essential oil-loaded nanoparticles may offer the potential benefits of synergism in antimicrobial activity, high loading capacity, increased solubility, decreased volatility, chemical stability, and enhancement of the bioavailability and shelf life of EOs and their constituents. This review focuses on the potentiation of the antimicrobial activity of essential oils and their constituents in nanoparticulate delivery systems for a wide range of applications, such as food preservation, packaging, and alternative treatments for infectious diseases. Full article
(This article belongs to the Special Issue The Antimicrobial and Antivirulent Effects of Natural Products and Their Nanoparticles)
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16 pages, 2244 KiB  
Article
Characterization of the Antibacterial Activity of an SiO2 Nanoparticular Coating to Prevent Bacterial Contamination in Blood Products
by Sahra Fonseca, Marie-Pierre Cayer, K. M. Tanvir Ahmmed, Nima Khadem-Mohtaram, Steve J. Charette and Danny Brouard
Antibiotics 2022, 11(1), 107; https://doi.org/10.3390/antibiotics11010107 - 14 Jan 2022
Cited by 11 | Viewed by 2342
Abstract
Technological innovations and quality control processes within blood supply organizations have significantly improved blood safety for both donors and recipients. Nevertheless, the risk of transfusion-transmitted infection remains non-negligible. Applying a nanoparticular, antibacterial coating at the surface of medical devices is a promising strategy [...] Read more.
Technological innovations and quality control processes within blood supply organizations have significantly improved blood safety for both donors and recipients. Nevertheless, the risk of transfusion-transmitted infection remains non-negligible. Applying a nanoparticular, antibacterial coating at the surface of medical devices is a promising strategy to prevent the spread of infections. In this study, we characterized the antibacterial activity of an SiO2 nanoparticular coating (i.e., the “Medical Antibacterial and Antiadhesive Coating” [MAAC]) applied on relevant polymeric materials (PM) used in the biomedical field. Electron microscopy revealed a smoother surface for the MAAC-treated PM compared to the reference, suggesting antiadhesive properties. The antibacterial activity was tested against selected Gram-positive and Gram-negative bacteria in accordance with ISO 22196. Bacterial growth was significantly reduced for the MAAC-treated PVC, plasticized PVC, polyurethane and silicone (90–99.999%) in which antibacterial activity of ≥1 log reduction was reached for all bacterial strains tested. Cytotoxicity was evaluated following ISO 10993-5 guidelines and L929 cell viability was calculated at ≥90% in the presence of MAAC. This study demonstrates that the MAAC could prevent bacterial contamination as demonstrated by the ISO 22196 tests, while further work needs to be done to improve the coating processability and effectiveness of more complex matrices. Full article
(This article belongs to the Special Issue Antimicrobial Materials and Surface)
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14 pages, 2724 KiB  
Article
Effects of Tylosin, a Direct-Fed Microbial and Feedlot Pen Environment on Phenotypic Resistance among Enterococci Isolated from Beef Cattle Feces
by Sarah A. Murray, Ashlyn C. Holbert, Keri N. Norman, Sara D. Lawhon, Jason E. Sawyer and Harvey M. Scott
Antibiotics 2022, 11(1), 106; https://doi.org/10.3390/antibiotics11010106 - 14 Jan 2022
Cited by 4 | Viewed by 2112
Abstract
In two sequential replicates (n = 90 and n = 96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, [...] Read more.
In two sequential replicates (n = 90 and n = 96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, not fed) the macrolide tylosin. Diluted fecal samples were spiral-plated on plain and antibiotic-supplemented m-Enterococcus agar. In the first replicate, tylosin significantly (p < 0.05) increased the relative quantity of erythromycin-resistant enterococci. This effect was diminished in cattle fed the DFM in conjunction with tylosin, indicating a macrolide susceptible probiotic may help mitigate resistance. A similar observed effect was not statistically significant (p > 0.05) in the second replicate. Isolates were speciated and resistance phenotypes were obtained for E. faecium and E. hirae. Susceptible strains of bacteria fed as DFM may prove useful for mitigating the selective effects of antibiotic use; however, the longer-term sustainability of such an approach remains unclear. Full article
(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)
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18 pages, 567 KiB  
Article
Management of Children Admitted to Hospitals across Bangladesh with Suspected or Confirmed COVID-19 and the Implications for the Future: A Nationwide Cross-Sectional Study
by Kona Chowdhury, Mainul Haque, Nadia Nusrat, Nihad Adnan, Salequl Islam, Afzalunnessa Binte Lutfor, Dilara Begum, Arif Rabbany, Enamul Karim, Abdul Malek, Nasim Jahan, Jesmine Akter, Sumala Ashraf, Mohammad Nazmul Hasan, Mahmuda Hassan, Najnin Akhter, Monika Mazumder, Nazmus Sihan, Nurun Naher, Shaheen Akter, Sifat Uz Zaman, Tanjina Chowdhury, Jebun Nesa, Susmita Biswas, Mohammod Didarul Islam, Al Mamun Hossain, Habibur Rahman, Palash Kumar Biswas, Mohammed Shaheen, Farah Chowdhury, Santosh Kumar, Amanj Kurdi, Zia Ul Mustafa, Natalie Schellack, Marshall Gowere, Johanna C. Meyer, Sylvia Opanga and Brian Godmanadd Show full author list remove Hide full author list
Antibiotics 2022, 11(1), 105; https://doi.org/10.3390/antibiotics11010105 - 14 Jan 2022
Cited by 23 | Viewed by 3209
Abstract
There is an increasing focus on researching children admitted to hospital with new variants of COVID-19, combined with concerns with hyperinflammatory syndromes and the overuse of antimicrobials. Paediatric guidelines have been produced in Bangladesh to improve their care. Consequently, the objective is to [...] Read more.
There is an increasing focus on researching children admitted to hospital with new variants of COVID-19, combined with concerns with hyperinflammatory syndromes and the overuse of antimicrobials. Paediatric guidelines have been produced in Bangladesh to improve their care. Consequently, the objective is to document the management of children with COVID-19 among 24 hospitals in Bangladesh. Key outcome measures included the percentage prescribed different antimicrobials, adherence to paediatric guidelines and mortality rates using purposely developed report forms. The majority of 146 admitted children were aged 5 years or under (62.3%) and were boys (58.9%). Reasons for admission included fever, respiratory distress and coughing; 86.3% were prescribed antibiotics, typically parenterally, on the WHO ‘Watch’ list, and empirically (98.4%). There were no differences in antibiotic use whether hospitals followed paediatric guidance or not. There was no prescribing of antimalarials and limited prescribing of antivirals (5.5% of children) and antiparasitic medicines (0.7%). The majority of children (92.5%) made a full recovery. It was encouraging to see the low hospitalisation rates and limited use of antimalarials, antivirals and antiparasitic medicines. However, the high empiric use of antibiotics, alongside limited switching to oral formulations, is a concern that can be addressed by instigating the appropriate programmes. Full article
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13 pages, 1760 KiB  
Perspective
Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance
by James V. Rogers, Veronica L. Hall and Charles C. McOsker
Antibiotics 2022, 11(1), 104; https://doi.org/10.3390/antibiotics11010104 - 14 Jan 2022
Cited by 10 | Viewed by 2747
Abstract
Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, [...] Read more.
Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship. Full article
(This article belongs to the Special Issue Nontraditional Antibiotics—Challenges and Triumphs, 2nd Volume)
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16 pages, 1318 KiB  
Article
Methicillin-Resistant Staphylococcus aureus from Peninsular Malaysian Animal Handlers: Molecular Profile, Antimicrobial Resistance, Immune Evasion Cluster and Genotypic Categorization
by Minhian Chai, Muhammad Zikree Sukiman, Amirah Huda Kamarun Baharin, Insyirah Ramlan, Lennard Zhunhoong Lai, Yeewen Liew, Pavitra Malayandy, Noor Muzamil Mohamad, Siewshean Choong, Siti Mariam Zainal Ariffin and Mohd Faizal Ghazali
Antibiotics 2022, 11(1), 103; https://doi.org/10.3390/antibiotics11010103 - 14 Jan 2022
Cited by 5 | Viewed by 2704
Abstract
Staphylococcus aureus (S. aureus) infections, particularly methicillin-resistant Staphylococcus aureus (MRSA) in humans and animals, have become a significant concern globally. The present study aimed to determine the prevalence and antibiogram of S. aureus isolated from animal handlers in Peninsular Malaysia. Furthermore, [...] Read more.
Staphylococcus aureus (S. aureus) infections, particularly methicillin-resistant Staphylococcus aureus (MRSA) in humans and animals, have become a significant concern globally. The present study aimed to determine the prevalence and antibiogram of S. aureus isolated from animal handlers in Peninsular Malaysia. Furthermore, the genotypic characteristics of S. aureus isolates were also investigated. Nasal and oral swab samples were collected from 423 animal handlers in Peninsular Malaysia. The antibiogram profiles of S. aureus against 18 antibiotics were established using a Kirby–Bauer test. The genotypic profile of S. aureus, including the presence of antimicrobial resistance (AMR), virulence genes and spa genotypes, was investigated using molecular techniques. The overall carriage rate of S. aureus, MRSA and MDRSA was 30.5%, 1.2% and 19.4%, respectively. S. aureus was highly resistant against penicillin (72.3%) and amoxicillin (52.3%). Meanwhile, gentamicin and linezolid were fully effective against all the isolated S. aureus from animal handlers. It was observed that animal handlers with close exposure to poultry were more likely to carry S. aureus that is resistant to tetracycline and erythromycin. S. aureus isolates harboured tetracycline resistance (tetK, tetL and tetM), erythromycin resistance (ermA, ermB, ermC and msrA) and immune evasion cluster (IEC) genes (scn, chp, sak, sea and sep). Seventeen different spa types were detected among the 30 isolates of MDRSA, with t189 (16.7%) and t4171 (16.7%) being the predominant spa type, suggesting wide genetic diversity of the MDRSA isolates. The present study demonstrated the prevalence of S. aureus strains, including MRSA and MDRSA with various antimicrobial resistance and genetic profiles from animal handlers in Peninsular Malaysia. Full article
(This article belongs to the Special Issue Molecular Evolution and Pathogenicity of Methicillin-Resistant Staphylococcus aureus)
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11 pages, 481 KiB  
Article
Factors Affecting Antibiotic Prescription among Hospital Physicians in a Low-Antimicrobial-Resistance Country: A Qualitative Study
by Ingrid Christensen, Jon Birger Haug, Dag Berild, Jørgen Vildershøj Bjørnholt, Brita Skodvin and Lars-Petter Jelsness-Jørgensen
Antibiotics 2022, 11(1), 98; https://doi.org/10.3390/antibiotics11010098 - 13 Jan 2022
Cited by 8 | Viewed by 3372
Abstract
Antimicrobial resistance (AMR) is a threat to hospital patients. Antimicrobial stewardship programs (ASPs) can counteract AMR. To optimize ASPs, we need to understand what affects physicians’ antibiotic prescription from several contexts. In this study, we aimed to explore the factors affecting hospital physicians’ [...] Read more.
Antimicrobial resistance (AMR) is a threat to hospital patients. Antimicrobial stewardship programs (ASPs) can counteract AMR. To optimize ASPs, we need to understand what affects physicians’ antibiotic prescription from several contexts. In this study, we aimed to explore the factors affecting hospital physicians’ antibiotic choices in a low-resistance country to identify potential targets for future ASPs. We interviewed 14 physicians involved in antibiotic prescription in a Norwegian hospital. The interviews were audiotaped, transcribed verbatim, and analyzed using thematic analysis. The main factors affecting antibiotic prescription were a high work pressure, insufficient staff resources, and uncertainties regarding clinical decisions. Treatment expectations from patients and next of kin, benevolence towards the patients, suboptimal microbiological testing, and limited time for infectious disease specialists to offer advisory services also affected the antibiotic choices. Future ASP efforts should evaluate the system organization and prioritizations to address and manage potential time-pressure issues. To limit the use of broad-spectrum antibiotics, improving microbiology testing and the routines for consultations with infectious disease specialists seems beneficial. We also identified a need among the prescribing physicians for a debate on ethical antibiotic questions. Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Stewardship, 2nd Volume)
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20 pages, 6741 KiB  
Article
Molecular Detection of Colistin Resistance mcr-1 Gene in Multidrug-Resistant Escherichia coli Isolated from Chicken
by Md Bashir Uddin, Mohammad Nurul Alam, Mahmudul Hasan, S. M. Bayejed Hossain, Mita Debnath, Ruhena Begum, Mohammed A. Samad, Syeda Farjana Hoque, Md. Shahidur Rahman Chowdhury, Md. Mahfujur Rahman, Md. Mukter Hossain, Mohammad Mahmudul Hassan, Åke Lundkvist, Josef D. Järhult, Mohamed E. El Zowalaty and Syed Sayeem Uddin Ahmed
Antibiotics 2022, 11(1), 97; https://doi.org/10.3390/antibiotics11010097 - 13 Jan 2022
Cited by 8 | Viewed by 3655
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Antibiotic Resistance Genes: Spread and Evolution)
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10 pages, 711 KiB  
Article
Validation of Vancomycin Area under the Concentration—Time Curve Estimation by the Bayesian Approach Using One-Point Samples for Predicting Clinical Outcomes in Patients with Methicillin-Resistant Staphylococcus aureus Infections
by Takashi Ueda, Yoshio Takesue, Kazuhiko Nakajima, Kaoru Ichiki, Kaori Ishikawa, Kumiko Yamada, Toshie Tsuchida, Naruhito Otani, Yoshiko Takahashi, Mika Ishihara, Shingo Takubo, Hiroki Ikeuchi, Motoi Uchino, Toshimi Kimura, Kazuaki Matsumoto, Kazutaka Oda and Takeshi Kimura
Antibiotics 2022, 11(1), 96; https://doi.org/10.3390/antibiotics11010096 - 13 Jan 2022
Cited by 19 | Viewed by 2792
Abstract
Area under the concentration–time curve (AUC)-guided vancomycin treatment is associated with decreased nephrotoxicity. It is preferable to obtain two samples to estimate the AUC. This study examined the usefulness of AUC estimation via trough concentration (Cmin)-only sampling of 260 adults infected [...] Read more.
Area under the concentration–time curve (AUC)-guided vancomycin treatment is associated with decreased nephrotoxicity. It is preferable to obtain two samples to estimate the AUC. This study examined the usefulness of AUC estimation via trough concentration (Cmin)-only sampling of 260 adults infected with methicillin-resistant Staphylococcus aureus (MRSA) who received vancomycin. The exact Cmin sampling time was used for Bayesian estimation. A significantly higher early treatment response was observed in patients with a day 2 AUC ≥ 400 µg·h/mL than those with <400 µg·h/mL, and a significantly higher early nephrotoxicity rate was observed in patients with a day 2 AUC ≥ 600 µg·h/mL than those with <600 µg·h/mL. These AUC cutoff values constituted independent factors for each outcome. In sub-analysis, the discrimination ability for early clinical outcomes using these AUC cutoffs was confirmed only in patients with q12 vancomycin administration. A significant difference in early treatment response using the 400 µg·h/mL cutoff was obtained only in patients with low-risk infections. The usefulness of the vancomycin AUC target to decrease nephrotoxicity while assuring clinical efficacy was even confirmed with a single Cmin measurement. However, assessment with two samples might be required in patients with q24 administration or high/moderate-risk MRSA infections. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials)
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15 pages, 256 KiB  
Perspective
Marketing and Distribution System Foster Misuse of Antibiotics in the Community: Insights from Drugs Wholesalers in India
by Anita Kotwani, Arti Bhanot, Girdhari Lal Singal and Sumanth Gandra
Antibiotics 2022, 11(1), 95; https://doi.org/10.3390/antibiotics11010095 - 13 Jan 2022
Cited by 6 | Viewed by 2224
Abstract
Antibiotic misuse is one of the major drivers of antimicrobial resistance (AMR). In India, evidence of antibiotic misuse comes largely from retailers as well as formal and informal healthcare providers (IHCPs). This paper presents the practices and perspectives of drug wholesalers, a critical [...] Read more.
Antibiotic misuse is one of the major drivers of antimicrobial resistance (AMR). In India, evidence of antibiotic misuse comes largely from retailers as well as formal and informal healthcare providers (IHCPs). This paper presents the practices and perspectives of drug wholesalers, a critical link between manufacturers and last-mile dispensers. Four experienced wholesalers and an ex-State Drug Controller (ex-SDC) were interviewed in depth, using semi-structured guides in the National Capital Region of Delhi, India, between November 2020 and January 2021. Four main findings were that wholesalers (i) have limited knowledge about wholesale licensing and practice regulations, as well as a limited understanding of AMR; (ii) directly supply and sell antibiotics to IHCPs; (iii) facilitate medical representatives (MRs) of pharmaceutical companies and manufacturers in their strategies to promote antibiotics use in the community; and (iv) blame other stakeholders for unlawful sale and overuse of antibiotics. Some of the potential solutions aimed at wholesalers include having a minimum education qualification for licensing and mandatory Good Distribution Practices certification programs. Decoupling incentives by pharmaceutical companies from sales targets to improve ethical sales practices for MRs and optimize antibiotic use by IHCPs could alleviate wholesalers’ indirect actions in promoting antibiotic misuse. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
17 pages, 598 KiB  
Article
Colistin Resistance Mechanisms in Human Salmonella enterica Strains Isolated by the National Surveillance Enter-Net Italia (2016–2018)
by Daniela Fortini, Slawomir Owczarek, Anna Maria Dionisi, Claudia Lucarelli, Sergio Arena, Alessandra Carattoli, Enter-Net Italia Colistin Resistance Study Group, Laura Villa and Aurora García-Fernández
Antibiotics 2022, 11(1), 102; https://doi.org/10.3390/antibiotics11010102 - 13 Jan 2022
Cited by 8 | Viewed by 2263
Abstract
Background: A collection of human-epidemiologically unrelated S. enterica strains collected over a 3-year period (2016 to 2018) in Italy by the national surveillance Enter-Net Italia was analysed. Methods: Antimicrobial susceptibility tests, including the determination of minimal inhibitory concentrations (MICs) for colistin, were performed. [...] Read more.
Background: A collection of human-epidemiologically unrelated S. enterica strains collected over a 3-year period (2016 to 2018) in Italy by the national surveillance Enter-Net Italia was analysed. Methods: Antimicrobial susceptibility tests, including the determination of minimal inhibitory concentrations (MICs) for colistin, were performed. Colistin resistant strains were analysed by PCR to detect mobile colistin resistance (mcr) genes. In mcr-negative S. enterica serovar Enteritidis strains, chromosomal mutations potentially involved in colistin resistance were identified by a genomic approach. Results: The prevalence of colistin-resistant S. enterica strains was 7.7%, the majority (87.5%) were S. Enteritidis. mcr genes were identified only in one strain, a S. Typhimurium monophasic variant, positive for both mcr-1.1 and mcr-5.1 genes in an IncHI2 ST4 plasmid. Several chromosomal mutations were identified in the colistin-resistant mcr-negative S. Enteritidis strains in proteins involved in lipopolysaccharide and outer membrane synthesis and modification (RfbN, LolB, ZraR) and in a component of a multidrug efflux pump (MdsC). These mutated proteins were defined as possible candidates for colistin resistance in mcr-negative S. Enteritidis of our collection. Conclusions: The colistin national surveillance in Salmonella spp. in humans, implemented with genomic-based surveillance, permitted to monitor colistin resistance, determining the prevalence of mcr determinants and the study of new candidate mechanisms for colistin resistance. Full article
(This article belongs to the Special Issue Epidemiology and Surveillance of Foodborne Pathogens and Antimicrobial Resistance)
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13 pages, 1325 KiB  
Article
Effect of Different Piperacillin-Tazobactam Dosage Regimens on Synergy of the Combination with Tobramycin against Pseudomonas aeruginosa for the Pharmacokinetics of Critically Ill Patients in a Dynamic Infection Model
by Jessica R. Tait, Hajira Bilal, Kate E. Rogers, Yinzhi Lang, Tae-Hwan Kim, Jieqiang Zhou, Steven C. Wallis, Jürgen B. Bulitta, Carl M. J. Kirkpatrick, David L. Paterson, Jeffrey Lipman, Phillip J. Bergen, Jason A. Roberts, Roger L. Nation and Cornelia B. Landersdorfer
Antibiotics 2022, 11(1), 101; https://doi.org/10.3390/antibiotics11010101 - 13 Jan 2022
Cited by 4 | Viewed by 3151
Abstract
We evaluated piperacillin-tazobactam and tobramycin regimens against Pseudomonas aeruginosa isolates from critically ill patients. Static-concentration time-kill studies (SCTK) assessed piperacillin-tazobactam and tobramycin monotherapies and combinations against four isolates over 72 h. A 120 h-dynamic in vitro infection model (IVM) investigated isolates Pa1281 (MIC [...] Read more.
We evaluated piperacillin-tazobactam and tobramycin regimens against Pseudomonas aeruginosa isolates from critically ill patients. Static-concentration time-kill studies (SCTK) assessed piperacillin-tazobactam and tobramycin monotherapies and combinations against four isolates over 72 h. A 120 h-dynamic in vitro infection model (IVM) investigated isolates Pa1281 (MICpiperacillin 4 mg/L, MICtobramycin 0.5 mg/L) and CR380 (MICpiperacillin 32 mg/L, MICtobramycin 1 mg/L), simulating the pharmacokinetics of: (A) tobramycin 7 mg/kg q24 h (0.5 h-infusions, t1/2 = 3.1 h); (B) piperacillin 4 g q4 h (0.5 h-infusions, t1/2 = 1.5 h); (C) piperacillin 24 g/day, continuous infusion; A + B; A + C. Total and less-susceptible bacteria were determined. SCTK demonstrated synergy of the combination for all isolates. In the IVM, regimens A and B provided initial killing, followed by extensive regrowth by 72 h for both isolates. C provided >4 log10 CFU/mL killing, followed by regrowth close to initial inoculum by 96 h for Pa1281, and suppressed growth to <4 log10 CFU/mL for CR380. A and A + B initially suppressed counts of both isolates to <1 log10 CFU/mL, before regrowth to control or starting inoculum and resistance emergence by 72 h. Overall, the combination including intermittent piperacillin-tazobactam did not provide a benefit over tobramycin monotherapy. A + C, the combination regimen with continuous infusion of piperacillin-tazobactam, provided synergistic killing (counts <1 log10 CFU/mL) of Pa1281 and CR380, and suppressed regrowth to <2 and <4 log10 CFU/mL, respectively, and resistance emergence over 120 h. The shape of the concentration–time curve was important for synergy of the combination. Full article
(This article belongs to the Special Issue 10th Anniversary of Antibiotics—Recent Advances in Pharmacodynamics of Antibiotics)
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7 pages, 244 KiB  
Communication
A Novel Method to Assess Antimicrobial Susceptibility in Commensal Oropharyngeal Neisseria—A Pilot Study
by Jolein Gyonne Elise Laumen, Saïd Abdellati, Christophe Van Dijck, Delphine Martiny, Irith De Baetselier, Sheeba Santhini Manoharan-Basil, Dorien Van den Bossche and Chris Kenyon
Antibiotics 2022, 11(1), 100; https://doi.org/10.3390/antibiotics11010100 - 13 Jan 2022
Cited by 2 | Viewed by 1538
Abstract
Commensal Neisseria provide a reservoir of resistance genes that can be transferred to the pathogens Neisseria gonorrhoeae and N. meningitidis in the human oropharynx. Surveillance programs are thus needed to monitor resistance in oropharyngeal commensal Neisseria, but currently the isolation and antimicrobial susceptibility [...] Read more.
Commensal Neisseria provide a reservoir of resistance genes that can be transferred to the pathogens Neisseria gonorrhoeae and N. meningitidis in the human oropharynx. Surveillance programs are thus needed to monitor resistance in oropharyngeal commensal Neisseria, but currently the isolation and antimicrobial susceptibility testing of these commensals is laborious, complex and expensive. In addition, the posterior oropharyngeal/tonsillar swab, which is commonly used to sample oropharyngeal Neisseria, is poorly tolerated by many individuals. We evaluated an alternative non-invasive method to isolate oropharyngeal commensal Neisseria and to detect decreased susceptibility to azithromycin using selective media (LBVT.SNR) with and without azithromycin (2 µg/mL). In this pilot study, we compared paired posterior oropharyngeal/tonsillar swabs and oral rinse-and-gargle samples from 10 participants and demonstrated that a similar Neisseria species diversity and number of colonies were isolated from both sample types. Moreover, the proportion of Neisseria colonies that had a decreased susceptibility to azithromycin was similar in the rinse samples compared to the swabs. This pilot study has produced encouraging data that a simple protocol of oral rinse-and-gargle and culture on plates selective for commensal Neisseria with and without a target antimicrobial can be used as a surveillance tool to monitor antimicrobial susceptibility in commensal oropharyngeal Neisseria. Larger studies are required to validate these findings. Full article
(This article belongs to the Special Issue Rapid Diagnostics of the Antimicrobial Resistance)
15 pages, 872 KiB  
Article
Development of New Antimicrobial Oleanonic Acid Polyamine Conjugates
by Elmira F. Khusnutdinova, Véronique Sinou, Denis A. Babkov, Oxana Kazakova and Jean Michel Brunel
Antibiotics 2022, 11(1), 94; https://doi.org/10.3390/antibiotics11010094 - 12 Jan 2022
Cited by 8 | Viewed by 1890
Abstract
A series of oleanolic acid derivatives holding oxo- or 3-N-polyamino-3-deoxy-substituents at C3 as well as carboxamide function at C17 with different long chain polyamines have been synthesized and evaluated for antimicrobial activities. Almost all series presented good to moderate activity against [...] Read more.
A series of oleanolic acid derivatives holding oxo- or 3-N-polyamino-3-deoxy-substituents at C3 as well as carboxamide function at C17 with different long chain polyamines have been synthesized and evaluated for antimicrobial activities. Almost all series presented good to moderate activity against Gram-positive S. aureus, S. faecalis and B. cereus bacteria with minimum inhibitory concentration (MIC) values from 3.125 to 200 µg/mL. Moreover, compounds possess important antimicrobial activities against Gram-negative E. coli, P. aeruginosa, S. enterica, and EA289 bacteria with MICs ranging from 6.25 to 200 µg/mL. The testing of ability to restore antibiotic activity of doxycycline and erythromycin at a 2 µg/mL concentration in a synergistic assay showed that oleanonic acid conjugate with spermine spacered through propargylamide led to a moderate improvement in terms of antimicrobial activities of the different selected combinations against both P. aeruginosa and E. coli. The study of mechanism of action of the lead conjugate 2i presenting a N-methyl norspermidine moiety showed the effect of disruption of the outer bacterial membrane of P. aeruginosa PA01 cells. Computational ADMET profiling renders this compound as a suitable starting point for pharmacokinetic optimization. These results give confidence to the successful outcome of bioconjugation of polyamines and oleanane-type triterpenoids in the development of antimicrobial agents. Full article
(This article belongs to the Topic Novel Antimicrobial Agents: Discovery, Design and New Therapeutic Strategies)
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11 pages, 1844 KiB  
Review
Is Antibiotic Prophylaxis Necessary before Dental Implant Procedures in Patients with Orthopaedic Prostheses? A Systematic Review
by Angel-Orión Salgado-Peralvo, Juan-Francisco Peña-Cardelles, Naresh Kewalramani, Alvaro Garcia-Sanchez, María-Victoria Mateos-Moreno, Eugenio Velasco-Ortega, Iván Ortiz-García, Álvaro Jiménez-Guerra, Dániel Végh, Ignacio Pedrinaci and Loreto Monsalve-Guil
Antibiotics 2022, 11(1), 93; https://doi.org/10.3390/antibiotics11010093 - 12 Jan 2022
Cited by 2 | Viewed by 4621
Abstract
As the population ages, more and more patients with orthopaedic prostheses (OPs) require dental implant treatment. Surveys of dentists and orthopaedic surgeons show that prophylactic antibiotics (PAs) are routinely prescribed with a very high frequency in patients with OPs who are about to [...] Read more.
As the population ages, more and more patients with orthopaedic prostheses (OPs) require dental implant treatment. Surveys of dentists and orthopaedic surgeons show that prophylactic antibiotics (PAs) are routinely prescribed with a very high frequency in patients with OPs who are about to undergo dental procedures. The present study aims to determine the need to prescribe prophylactic antibiotic therapy in patients with OPs treated with dental implants to promote their responsible use and reduce the risk of antimicrobial resistance. An electronic search of the MEDLINE database (via PubMed), Web of Science, LILACS, Google Scholar, and OpenGrey was carried out. The criteria used were those described by the PRISMA® Statement. No study investigated the need to prescribe PAs in patients with OPs, so four studies were included on the risk of infections of OPs after dental treatments with varying degrees of invasiveness. There is no evidence to suggest a relationship between dental implant surgeries and an increased risk of OP infection; therefore, PAs in these patients are not justified. However, the recommended doses of PAs in dental implant procedures in healthy patients are the same as those recommended to avoid infections of OPs. Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Stewardship, 2nd Volume)
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Article
NDM-1 Introduction in Portugal through a ST11 KL105 Klebsiella pneumoniae Widespread in Europe
by Ângela Novais, Rita Veiga Ferraz, Mariana Viana, Paula Martins da Costa and Luísa Peixe
Antibiotics 2022, 11(1), 92; https://doi.org/10.3390/antibiotics11010092 - 12 Jan 2022
Cited by 14 | Viewed by 2225
Abstract
The changing epidemiology of carbapenem-resistant Klebsiella pneumoniae in Southern European countries is challenging for infection control, and it is critical to identify and track new genetic entities (genes, carbapenemases, clones) quickly and with high precision. We aimed to characterize the strain responsible for [...] Read more.
The changing epidemiology of carbapenem-resistant Klebsiella pneumoniae in Southern European countries is challenging for infection control, and it is critical to identify and track new genetic entities (genes, carbapenemases, clones) quickly and with high precision. We aimed to characterize the strain responsible for the first recognized outbreak by an NDM-1-producing K. pneumoniae in Portugal, and to elucidate its diffusion in an international context. NDM-1-producing multidrug-resistant K. pneumoniae isolates from hospitalized patients (2018–2019) were characterized using FTIR spectroscopy, molecular typing, whole-genome sequencing, and comparative genomics with available K. pneumoniae ST11 KL105 genomes. FT-IR spectroscopy allowed the rapid (ca. 4 h after incubation) identification of the outbreak strains as ST11 KL105, supporting outbreak control. Epidemiological information supports a community source but without linkage to endemic regions of NDM-1 producers. Whole-genome comparison with previous DHA-1-producing ST11 KL105 strains revealed the presence of different plasmid types and antibiotic resistance traits, suggesting the entry of a new strain. In fact, this ST11 KL105 clade has successfully disseminated in Europe with variable beta-lactamases, but essentially as ESBL or DHA-1 producers. We expand the distribution map of NDM-1-producing K. pneumoniae in Europe, at the expense of a successfully established ST11 KL105 K. pneumoniae clade circulating with variable plasmid backgrounds and beta-lactamases. Our work further supports the use of FT-IR as an asset to support quick infection control. Full article
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
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