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How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "The Global Need for Effective Antibiotics".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 40918

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Prof. Dr. Mohammad Amjad Kamal

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Guest Editor

1. Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
2. King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
3. Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
4. Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770, Australia
5. Novel Global Community Educational Foundation, Hebersham, Australia
Interests: biochemistry; neuroscience; enzymology; toxicology; metabolomics; nanomedicines; manual lymph drainage and miRNA; leadership in managing staff performance and chaplaincy
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Firoz Anwar

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Guest Editor

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
Interests: antibiotics; resistance pattern; metabolic toxicity; gut microbiota; fungal infection; non antibiotic role

Special Issue Information

Dear Colleagues,

Antibiotics are drugs to prevent and treat bacterial infections. Recent trends have shown increased resistance to these drugs by different classes of bacteria. This causes increased mortality, high medical costs, and prolonged hospital stays. Even if newer antibiotics are developed, the development of resistance will undoubtedly always be a threat.

Health scientists are also concerned by the growing list of infections—such as tuberculosis, pneumonia, gonorrhea, food-borne disease, and even blood poisoning—which are not only difficult to treat or cure but will become next to impossible to eradicate.

The present theme of this Special Issue “How to Optimize the Use of Antibiotics in Human and Animal Healthcare: Time to Take Action” is in line with the guidelines of the WHO. We aim to provide a platform to present the valuable results of your research into aspects of this important issue.

Prof. Dr. Mohammad Amjad Kamal
Prof. Dr. Firoz Anwar
Guest Editors

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Keywords

Resistance pattern
Antibiotics
Cost
Health care

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Research

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13 pages, 451 KiB

Open AccessArticle

Increase and Change in the Pattern of Antibiotic Use in Serbia (2010–2019)

by Ana Tomas, Nebojša Pavlović, Nebojša Stilinović, Olga Horvat, Milica Paut-Kusturica, Tihomir Dugandžija, Zdenko Tomić and Ana Sabo

Antibiotics 2021, 10(4), 397; https://doi.org/10.3390/antibiotics10040397 - 7 Apr 2021

Cited by 21 | Viewed by 3930

Abstract

The aim of this study was to determine and describe trends in antibiotics utilization in Serbia over a ten-year period. Data were retrieved from publicly available annual reports (2010–2019). The results were expressed as Defined Daily Dose (DDD) per 1000 inhabitants per day (DID). All calculations were performed using the DDD values for the 2020 Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) version for each year of the study, to account for the DDD changes during the study period. Antibiotics were classified using the WHO Access, Watch, Reserve (AWaRe) classification. Total utilization of antibacterials for systemic use increased from 17.25 DID in 2010 to 28.65 DID in 2019. A statistically significant increasing trend in the use of the Watch category antibiotics was observed. A tendency towards use of broad-spectrum antibiotics, apparent by a statistically significant increase in the rate of utilization of broad-spectrum macrolides, quinolones and third-generation cephalosporins vs. narrow-spectrum ones, as well as a significant increasing trend in the use of quinolones was identified. Total antibiotic utilization was found to be well above the European average. Several specific problem areas were identified, which requires further efforts to improve antibiotic prescribing. The present study provides the information needed to facilitate antibiotic stewardship in Serbia further and proposes specific interventions to optimize antibiotic use in Serbia. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

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12 pages, 1823 KiB

Open AccessArticle

Influence of Human Eating Habits on Antimicrobial Resistance Phenomenon: Aspects of Clinical Resistome of Gut Microbiota in Omnivores, Ovolactovegetarians, and Strict Vegetarians

by Suzane Fernandes da Silva, Isabela Brito Reis, Melina Gabriela Monteiro, Vanessa Cordeiro Dias, Alessandra Barbosa Ferreira Machado, Vânia Lúcia da Silva and Cláudio Galuppo Diniz

Antibiotics 2021, 10(3), 276; https://doi.org/10.3390/antibiotics10030276 - 9 Mar 2021

Cited by 7 | Viewed by 3170

Abstract

The use of xenobiotics in food production and how food intake is carried out in different cultures, along with different eating habits (omnivorism (ON), ovolactovegetarianism (VT), and strict vegetarianism (VG)) seem to have implications for antimicrobial resistance, especially in the human gut microbiota. Thus, the aim of this study was to evaluate aspects of the clinical resistome of the human gut microbiota among healthy individuals with different eating habits. Volunteers were divided into 3 groups: n = 19 omnivores (ON), n = 20 ovolactovegetarians (VT), and n = 19 strict vegetarians (VG), and nutritional and anthropometric parameters were measured. Metagenomic DNA from fecal samples was used as a template for PCR screening of 37 antimicrobial resistance genes (ARG) representative of commonly used agents in human medicine. The correlation between eating habits and ARG was evaluated. There were no significant differences in mean caloric intake. Mean protein intake was significantly higher in ON, and fiber and carbohydrate consumption was higher in VG. From the screened ARG, 22 were detected. No clear relationship between diets and the occurrence of ARG was observed. Resistance genes against tetracyclines, β-lactams, and the MLS group (macrolides, lincosamides, and streptogramins) were the most frequent, followed by resistance genes against sulfonamides and aminoglycosides. Vegetables and minimally processed foods seem to be the main source of ARG for the human gut microbiota. Although eating habits vary among individuals, the open environment and the widespread ARG from different human activities draw attention to the complexity of the antimicrobial resistance phenomenon which should be addressed by a One Health approach. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

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12 pages, 282 KiB

Open AccessArticle

Complementary Medicine and Self-Care Strategies in Women with (Recurrent) Urinary Tract and Vaginal Infections: A Cross-Sectional Study on Use and Perceived Effectiveness in The Netherlands

by Louise Witteman, Herman A. van Wietmarschen and Esther T. van der Werf

Antibiotics 2021, 10(3), 250; https://doi.org/10.3390/antibiotics10030250 - 3 Mar 2021

Cited by 4 | Viewed by 3352

Abstract

Due to the excessive use of antibiotic and antimycotic treatments, the risk of resistant microbes and fungi is rapidly emerging. Previous studies have demonstrated that many women with (recurrent) urinary tract infection (UTI) and/or vaginal infections (VIs) welcome alternative management approaches to reduce the use of antibiotics and antifungals and avoid short- and long-term adverse effects. This study aims to determine which complementary medicine (CM) and self-care strategies are being used by women suffering from (recurrent) UTI and VI in The Netherlands and how they perceive their effectiveness in order to define directions for future research on safety, cost-effectiveness, and implementation of best practices. A cross-sectional online survey was performed among women, ≥18 years old, with a history of UTIs; 162 respondents were included in the data analysis, with most participants aged between 50 and 64 years (36.4%). The women reported having consulted a CM practitioner for UTI-specific symptoms (23.5%) and VI-specific symptoms (13.6%). Consultations of homeopaths, acupuncturists, and herbal physicians are most often reported. Overall, 81.7% of the women suffering from UTI used complementary or self-care strategies besides regular treatment, and 68.7% reported using CM/self-care strategies to treat vaginal symptoms. UTI- related use of cranberries (51.9%), vitamin C (43.8%), and D-mannose (32.7%) were most reported. Perceived effectiveness was mostly reported for homeopathic remedies and D-mannose. The results showed a substantial burden of UTI and VI on daily and sexual activities. Besides the frequency of use, the indication of perceived effectiveness seems to be an important parameter for further and rigorously designed research to encourage nonantibiotic/antifungal treatment implementation into daily clinical practice. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

15 pages, 989 KiB

Open AccessArticle

Tracking Reservoirs of Antimicrobial Resistance Genes in a Complex Microbial Community Using Metagenomic Hi-C: The Case of Bovine Digital Dermatitis

by Ashenafi F. Beyi, Alan Hassall, Gregory J. Phillips and Paul J. Plummer

Antibiotics 2021, 10(2), 221; https://doi.org/10.3390/antibiotics10020221 - 23 Feb 2021

Cited by 5 | Viewed by 3571

Abstract

Bovine digital dermatitis (DD) is a contagious infectious cause of lameness in cattle with unknown definitive etiologies. Many of the bacterial species detected in metagenomic analyses of DD lesions are difficult to culture, and their antimicrobial resistance status is largely unknown. Recently, a novel proximity ligation-guided metagenomic approach (Hi-C ProxiMeta) has been used to identify bacterial reservoirs of antimicrobial resistance genes (ARGs) directly from microbial communities, without the need to culture individual bacteria. The objective of this study was to track tetracycline resistance determinants in bacteria involved in DD pathogenesis using Hi-C. A pooled sample of macerated tissues from clinical DD lesions was used for this purpose. Metagenome deconvolution using ProxiMeta resulted in the creation of 40 metagenome-assembled genomes with ≥80% complete genomes, classified into five phyla. Further, 1959 tetracycline resistance genes and ARGs conferring resistance to aminoglycoside, beta-lactams, sulfonamide, phenicol, lincosamide, and erythromycin were identified along with their bacterial hosts. In conclusion, the widespread distribution of genes conferring resistance against tetracycline and other antimicrobials in bacteria of DD lesions is reported for the first time. Use of proximity ligation to identify microorganisms hosting specific ARGs holds promise for tracking ARGs transmission in complex microbial communities. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

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14 pages, 3741 KiB

Open AccessArticle

Pangenome Analysis of Mycobacterium tuberculosis Reveals Core-Drug Targets and Screening of Promising Lead Compounds for Drug Discovery

by Hamza Arshad Dar, Tahreem Zaheer, Nimat Ullah, Syeda Marriam Bakhtiar, Tianyu Zhang, Muhammad Yasir, Esam I. Azhar and Amjad Ali

Antibiotics 2020, 9(11), 819; https://doi.org/10.3390/antibiotics9110819 - 17 Nov 2020

Cited by 16 | Viewed by 4446

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), is one of the leading causes of human deaths globally according to the WHO TB 2019 report. The continuous rise in multi- and extensive-drug resistance in M. tuberculosis broadens the challenges to control tuberculosis. The availability of a large number of completely sequenced genomes of M. tuberculosis has provided an opportunity to explore the pangenome of the species along with the pan-phylogeny and to identify potential novel drug targets leading to drug discovery. We attempt to calculate the pangenome of M. tuberculosis that comprises a total of 150 complete genomes and performed the phylo-genomic classification and analysis. Further, the conserved core genome (1251 proteins) is subjected to various sequential filters (non-human homology, essentiality, virulence, physicochemical parameters, and pathway analysis) resulted in identification of eight putative broad-spectrum drug targets. Upon molecular docking analyses of these targets with ligands available at the DrugBank database shortlisted a total of five promising ligands with projected inhibitory potential; namely, 2′deoxy-thymidine-5′-diphospho-alpha-d-glucose, uridine diphosphate glucose, 2′-deoxy-thymidine-beta-l-rhamnose, thymidine-5′-triphosphate, and citicoline. We are confident that with further lead optimization and experimental validation, these lead compounds may provide a sound basis to develop safe and effective drugs against tuberculosis disease in humans. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

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21 pages, 1850 KiB

Open AccessArticle

Prevalence of Antibiotic-Resistant Pulmonary Tuberculosis in Bangladesh: A Systematic Review and Meta-Analysis

by Shoumik Kundu, Mahfuza Marzan, Siew Hua Gan and Md Asiful Islam

Antibiotics 2020, 9(10), 710; https://doi.org/10.3390/antibiotics9100710 - 17 Oct 2020

Cited by 11 | Viewed by 6223

Abstract

Resistance to anti-tuberculosis (anti-TB) antibiotics is a major public health concern for many high-TB burden countries in Asia, including Bangladesh. Therefore, to represent the overall drug-resistance pattern against TB in Bangladesh, a systematic review and meta-analysis was conducted. Databases such as PubMed, Scopus, and Google Scholar were searched to identify studies related to antibiotic-resistant TB. A total of 24 studies covering 13,336 patients with TB were secured and included. The random-effects model was used to calculate the summary estimates. The pooled prevalence of any, mono, multi, poly, and extensive anti-TB antibiotic-resistances were 45.3% [95% CI: 33.5–57.1], 14.3% [95% CI: 11.4–17.2], 22.2% [95% CI: 18.8–25.7], 7.7% [95% CI: 5.6–9.7], and 0.3% [95% CI: 0.0–1.0], respectively. Among any first and second-line anti-TB drugs, isoniazid (35.0%) and cycloserine (44.6%) resistances were the highest, followed by ethambutol (16.2%) and gatifloxacin (0.2%). Any, multi, and poly drug-resistances were higher in retreatment cases compared to the newly diagnosed cases, although mono drug-resistance tended to be higher in newly diagnosed cases (15.7%) than that in retreatment cases (12.5%). The majority (82.6%) of the included studies were of high quality, with most not exhibiting publication bias. Sensitivity analyses confirmed that all outcomes are robust and reliable. It is concluded that resistance to anti-TB drugs in Bangladesh is rampant and fast growing. Therefore, the implementation of a nationwide surveillance system to detect suspected and drug-resistant TB cases, as well as to ensure a more encompassing treatment management by national TB control program, is highly recommended. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

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11 pages, 618 KiB

Open AccessArticle

Effect of Antibiotic Susceptibility and CYP3A4/5 and CYP2C19 Genotype on the Outcome of Vonoprazan-Containing Helicobacter pylori Eradication Therapy

by Mitsushige Sugimoto, Daiki Hira, Masaki Murata, Takashi Kawai and Tomohiro Terada

Antibiotics 2020, 9(10), 645; https://doi.org/10.3390/antibiotics9100645 - 26 Sep 2020

Cited by 22 | Viewed by 3287

Abstract

Background: Helicobacter pylori eradication containing the potassium-competitive acid blocker, vonoprazan, achieves a higher eradication rate than therapy with proton pump inhibitors (PPIs). Because vonoprazan is mainly metabolized by CYP3A4/5, CYP genotype may affect the eradication rate. We investigated the influence of antibiotic susceptibility and CYP3A4/5 and CYP2C19 genotypes on the eradication rates. Methods: A total of 307 Japanese who were genotyped for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17, and investigated for susceptibility to antimicrobial agents, received vonoprazan-containing regimens: (1) With amoxicillin and clarithromycin as the first-line treatment; (2) with amoxicillin and metronidazole as the second-line treatment; or (3) with amoxicillin and sitafloxacin as the third-line treatment. Results: The eradication rate was 84.5% (95% confidence interval [CI]: 78.9–89.1%) using first-line, 92.6% (95% CI: 82.1–97.9%) using second-line and 87.5% (95% CI: 73.1–95.8%) using third-line treatment. Infection with clarithromycin-resistant strains was a predictive factor for failed eradication (odds ratio: 5.788, 95% CI: 1.916–17.485, p = 0.002) in multivariate analysis. No significant differences were observed in the eradication rate of regimens among CYP3A4, CYP3A5 and CYP2C19 genotypes. Conclusions: Genotyping for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17 before vonoprazan-containing eradication treatment may not be useful for predicting clinical outcomes. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

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9 pages, 213 KiB

Open AccessArticle

Gram-negative Organisms from Patients with Community-Acquired Urinary Tract Infections and Associated Risk Factors for Antimicrobial Resistance: A Single-Center Retrospective Observational Study in Japan

by Naoki Kanda, Hideki Hashimoto, Tomohiro Sonoo, Hiromu Naraba, Yuji Takahashi, Kensuke Nakamura and Shuji Hatakeyama

Antibiotics 2020, 9(8), 438; https://doi.org/10.3390/antibiotics9080438 - 23 Jul 2020

Cited by 11 | Viewed by 2921

Abstract

A specific antibiogram is necessary for the empiric antibiotic treatment of community-acquired urinary tract infections (UTI) because of the global spread of antimicrobial resistance. This study aimed to develop an antibiogram specific for community-acquired UTI and assess the risk factors associated with community-acquired UTI caused by antimicrobial-resistant organisms. This cross-sectional observational retrospective study included patients with community-acquired UTI caused by Gram-negative rods (GNR) who were admitted to the emergency department at a tertiary care hospital in Ibaraki, Japan, in 2017–2018. A total of 172 patients were enrolled (including 38 nursing home residents). Of the 181 GNR strains considered as causative agents, 135 (75%) were Escherichia coli, and 40 (22%) exhibited third-generation cephalosporin resistance. Extended-spectrum β-lactamase (ESBL)-producing E. coli accounted for 25/40 (63%) of resistant GNR. Overall susceptibility rate of Enterobacterales was 92%, 81%, 100%, 75%, and 89% for cefmetazole, ceftriaxone, meropenem, levofloxacin, and trimethoprim–sulfamethoxazole, respectively. Residence in a nursing home (odds ratio (OR), 2.83; 95% confidence interval (CI), 1.18–6.79) and recent antibiotic use (OR, 4.52; 95% CI, 1.02–19.97) were independent risk factors for UTI with resistant GNR. ESBL-producing E. coli was revealed to have a strong impact on antimicrobial resistance pattern. Therefore, an antibiotic strategy based on a disease-specific antibiogram is required. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

13 pages, 984 KiB

Open AccessArticle

A Nationwide Survey of Australian General Practitioners on Antimicrobial Stewardship: Awareness, Uptake, Collaboration with Pharmacists and Improvement Strategies

by Sajal K. Saha, David C. M. Kong, Karin Thursky and Danielle Mazza

Antibiotics 2020, 9(6), 310; https://doi.org/10.3390/antibiotics9060310 - 8 Jun 2020

Cited by 20 | Viewed by 4612

Abstract

Implementing antimicrobial stewardship (AMS) programs is central to optimise antimicrobial use in primary care. This study aims to assess general practitioners’ (GPs’) awareness of AMS, uptake of AMS strategies, attitudes towards GP–pharmacist collaboration in AMS and future AMS improvement strategies. A paper-based survey of nationally representative GPs across Australia was conducted in 2019. Of 386 respondent GPs, 68.9% were familiar with AMS. Respondents most frequently used the Therapeutic Guidelines (TG) (83.2%, 321/385) and delayed antimicrobial prescribing (72.2%, 278/385) strategies, whereas few utilised point-of-care tests (18.4%, 71/382), patient information leaflets (20.2%, 78/384), peer prescribing reports (15.5%, 60/384) and audit and feedback (9.8%, 38/384). GPs were receptive to pharmacists’ recommendations on the choice (50.5%, 192/381) and dose (63%, 241/382) of antimicrobials, and more than 60% (235/381) supported a policy fostering increased GP–pharmacist collaboration. Most GPs agreed to have AMS training (72%, 278/386), integration of electronic TG (eTG) with prescribing software (88.3%, 341/386) and policies limiting the prescribing of selected antimicrobials (74.4%, 287/386) in the future. Conclusively, GPs are aware of the importance of judicious antimicrobial prescribing but inadequately uptake evidence-based AMS strategies. The majority of GPs support GP–pharmacist collaborative AMS approaches to optimise antimicrobial use. Developing a feasible GP–pharmacist collaborative AMS implementation model and facilitating stewardship resources and training could foster AMS activities in primary care. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

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22 pages, 502 KiB

Open AccessReview

Impact on Antibiotic Resistance, Therapeutic Success, and Control of Side Effects in Therapeutic Drug Monitoring (TDM) of Daptomycin: A Scoping Review

by Carolina Osorio, Laura Garzón, Diego Jaimes, Edwin Silva and Rosa-Helena Bustos

Antibiotics 2021, 10(3), 263; https://doi.org/10.3390/antibiotics10030263 - 5 Mar 2021

Cited by 20 | Viewed by 3784

Abstract

Antimicrobial resistance (AR) is a problem that threatens the search for adequate safe and effective antibiotic therapy against multi-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE) and Clostridium difficile, among others. Daptomycin is the treatment of choice for some infections caused by Gram-positive bacteria, indicated most of the time in patients with special clinical conditions where its high pharmacokinetic variability (PK) does not allow adequate plasma concentrations to be reached. The objective of this review is to describe the data available about the type of therapeutic drug monitoring (TDM) method used and described so far in hospitalized patients with daptomycin and to describe its impact on therapeutic success, suppression of bacterial resistance, and control of side effects. The need to create worldwide strategies for the appropriate use of antibiotics is clear, and one of these is the performance of therapeutic drug monitoring (TDM). TDM helps to achieve a dose adjustment and obtain a favorable clinical outcome for patients by measuring plasma concentrations of an administered drug, making a rational interpretation guided by a predefined concentration range, and, thus, adjusting dosages individually. Full article

(This article belongs to the Special Issue How to Optimize the Use of Antibiotics in Human and Animal Health Care? – A Time to Act)

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