Next Issue
Volume 10, May
Previous Issue
Volume 10, March

Antibiotics, Volume 10, Issue 4 (April 2021) – 127 articles

Cover Story (view full-size image): Infections caused by nontuberculous mycobacteria (NTM) are increasing worldwide, resulting in a new neglected global health concern. NTM treatment is complex and requires combinations of several drugs for extended periods (months to years). In spite of this, NTM disease is associated with poor treatment outcomes, highlighting an urgent need for new therapeutic alternatives. However, NTM drug discovery and development is costly and lengthy with little interest from pharmaceutical companies. In this work, authors aimed to bridge this gap by applying a one-health drug repurposing strategy. They characterized the in vitro activity of anti-parasitic avermectins (and milbemycins) against a wide panel of NTM species and identified candidates for further development. The extensive pharmacological and safety data available in veterinary and human medicines could facilitate a repurposing [...] Read more.
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
Order results
Result details
Select all
Export citation of selected articles as:
Article
Clinical Impact of Revised Ciprofloxacin Breakpoint in Patients with Urinary Tract Infections by Enterobacteriaceae
Antibiotics 2021, 10(4), 469; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040469 - 20 Apr 2021
Viewed by 442
Abstract
In 2018, the Clinical and Laboratory Standards Institute (CLSI) revised ciprofloxacin (CIP)-susceptible breakpoint for Enterobacteriaceae from ≤1 μg/mL to ≤0.25 μg/mL, based on pharmacokinetic-pharmacodynamic (PK-PD) analysis. However, clinical data supporting the lowered CIP breakpoint are insufficient. This retrospective cohort study evaluated the clinical [...] Read more.
In 2018, the Clinical and Laboratory Standards Institute (CLSI) revised ciprofloxacin (CIP)-susceptible breakpoint for Enterobacteriaceae from ≤1 μg/mL to ≤0.25 μg/mL, based on pharmacokinetic-pharmacodynamic (PK-PD) analysis. However, clinical data supporting the lowered CIP breakpoint are insufficient. This retrospective cohort study evaluated the clinical outcomes of patients with bacteremic urinary tract infections (UTIs) caused by Enterobacteriaceae, which were previously CIP-susceptible and changed to non-susceptible. Bacteremic UTIs caused by Enterobacteriaceae with CIP minimal inhibitory concentration (MIC) ≤ 1 μg/mL were screened, and then patients treated with CIP as a definitive treatment were finally included. Patients in CIP-non-susceptible group (MIC = 0.5 or 1 μg/mL) were compared with patients in CIP-susceptible group (MIC ≤ 0.25 μg/mL). Primary endpoints were recurrence of UTIs within 4 weeks and 90 days. A total of 334 patients were evaluated, including 282 of CIP-susceptible and 52 of CIP-non-susceptible. There were no significant differences in clinical outcomes between two groups. In multivariate analysis, CIP non-susceptibility was not associated with recurrence of UTIs. CIP non-susceptibility based on a revised CIP breakpoint, which was formerly susceptible, was not associated with poor clinical outcomes in bacteremic UTI patients were treated with CIP, similar to those of the susceptible group. Further evaluation is needed to guide the selection of definitive antibiotics for UTIs. Full article
Show Figures

Figure 1

Article
Evaluation of the MeroRisk Calculator, A User-Friendly Tool to Predict the Risk of Meropenem Target Non-Attainment in Critically Ill Patients
Antibiotics 2021, 10(4), 468; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040468 - 20 Apr 2021
Viewed by 520
Abstract
Background: The MeroRisk-calculator, an easy-to-use tool to determine the risk of meropenem target non-attainment after standard dosing (1000 mg; q8h), uses a patient’s creatinine clearance and the minimum inhibitory concentration (MIC) of the pathogen. In clinical practice, however, the MIC is rarely available. [...] Read more.
Background: The MeroRisk-calculator, an easy-to-use tool to determine the risk of meropenem target non-attainment after standard dosing (1000 mg; q8h), uses a patient’s creatinine clearance and the minimum inhibitory concentration (MIC) of the pathogen. In clinical practice, however, the MIC is rarely available. The objectives were to evaluate the MeroRisk-calculator and to extend risk assessment by including general pathogen sensitivity data. Methods: Using a clinical routine dataset (155 patients, 891 samples), a direct data-based evaluation was not feasible. Thus, in step 1, the performance of a pharmacokinetic model was determined for predicting the measured concentrations. In step 2, the PK model was used for a model-based evaluation of the MeroRisk-calculator: risk of target non-attainment was calculated using the PK model and agreement with the MeroRisk-calculator was determined by a visual and statistical (Lin’s concordance correlation coefficient (CCC)) analysis for MIC values 0.125–16 mg/L. The MeroRisk-calculator was extended to include risk assessment based on EUCAST-MIC distributions and cumulative-fraction-of-response analysis. Results: Step 1 showed a negligible bias of the PK model to underpredict concentrations (−0.84 mg/L). Step 2 revealed a high level of agreement between risk of target non-attainment predictions for creatinine clearances >50 mL/min (CCC = 0.990), but considerable deviations for patients <50 mL/min. For 27% of EUCAST-listed pathogens the median cumulative-fraction-of-response for the observed patients receiving standard dosing was < 90%. Conclusions: The MeroRisk-calculator was successfully evaluated: For patients with maintained renal function it allows a reliable and user-friendly risk assessment. The integration of pathogen-based risk assessment substantially increases the applicability of the tool. Full article
Show Figures

Figure 1

Article
Molecular Epidemiology of Extensively Drug-Resistant mcr Encoded Colistin-Resistant Bacterial Strains Co-Expressing Multifarious β-Lactamases
Antibiotics 2021, 10(4), 467; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040467 - 20 Apr 2021
Viewed by 440
Abstract
Plasmid-mediated colistin resistance (Col-R) conferred by mcr genes endangers the last therapeutic option for multifarious β-lactamase-producing bacteria. The current study aimed to explore the mcr gene molecular epidemiology in extensively drug-resistant (XDR) bacteria. Col-R gram-negative bacterial strains were screened using a minimum inhibitory [...] Read more.
Plasmid-mediated colistin resistance (Col-R) conferred by mcr genes endangers the last therapeutic option for multifarious β-lactamase-producing bacteria. The current study aimed to explore the mcr gene molecular epidemiology in extensively drug-resistant (XDR) bacteria. Col-R gram-negative bacterial strains were screened using a minimum inhibitory concentration (MIC) breakpoint ≥4 µg/mL. Resistant isolates were examined for mcr variants, extended-spectrum β-lactamase, AmpC, and carbapenemase genes using polymerase chain reaction (PCR). The MIC breakpoints for mcr-positive strains were determined using broth microdilution and E-test strips. Overall, 19/718 (2.6%) gram-negative rods (GNRs) harboring mcr were identified, particularly in pus (p = 0.01) and tracheal secretions (p = 0.03). Molecular epidemiology data confirmed 18/19 (95%) mcr-1 and 1/19 (5%) mcr-2 genes. Integron detection revealed 15/17 (88%) Int-1 and 2/17 (12%) Int-2. Common co-expressing drug-resistant β-lactamase genes included 8/16 (50%) blaCTM-1, 3/16 (19%) blaCTM-15, 3/3 (100%) blaCMY-2, 2/8 (25%) blaNDM-1, and 2/8 (25%) blaNDM-5. The MIC50 and MIC90 values (µg/mL) were as follows: Escherichia coli, 12 and 24; Klebsiella pneumoniae, 12 and 32; Acinetobacter baumannii, 8 and 12; and Pseudomonas aeruginosa, 32 and 64, respectively. Treatment of XDR strains has become challenging owing to the co-expression of mcr-1, mcr-2, multifarious β-lactamase genes, and integrons. Full article
Show Figures

Figure 1

Article
Multiresistant Bacteria Isolated from Intestinal Faeces of Farm Animals in Austria
Antibiotics 2021, 10(4), 466; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040466 - 20 Apr 2021
Viewed by 416
Abstract
In recent years, antibiotic-resistant bacteria with an impact on human health, such as extended spectrum β-lactamase (ESBL)-containing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), have become more common in food. This is due to the use of antibiotics in animal [...] Read more.
In recent years, antibiotic-resistant bacteria with an impact on human health, such as extended spectrum β-lactamase (ESBL)-containing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), have become more common in food. This is due to the use of antibiotics in animal husbandry, which leads to the promotion of antibiotic resistance and thus also makes food a source of such resistant bacteria. Most studies dealing with this issue usually focus on the animals or processed food products to examine the antibiotic resistant bacteria. This study investigated the intestine as another main habitat besides the skin for multiresistant bacteria. For this purpose, faeces samples were taken directly from the intestines of swine (n = 71) and broiler (n = 100) during the slaughter process and analysed. All samples were from animals fed in Austria and slaughtered in Austrian slaughterhouses for food production. The samples were examined for the presence of ESBL-producing Enterobacteriaceae, MRSA, MRCoNS and VRE. The resistance genes of the isolated bacteria were detected and sequenced by PCR. Phenotypic ESBL-producing Escherichia coli could be isolated in 10% of broiler casings (10 out of 100) and 43.6% of swine casings (31 out of 71). In line with previous studies, the results of this study showed that CTX-M-1 was the dominant ESBL produced by E. coli from swine (n = 25, 83.3%) and SHV-12 from broilers (n = 13, 81.3%). Overall, the frequency of positive samples with multidrug-resistant bacteria was lower than in most comparable studies focusing on meat products. Full article
(This article belongs to the Special Issue Usage of Antibiotic in Agriculture and Animal Farming)
Show Figures

Figure 1

Article
The Effect of Colistin Treatment on the Selection of Colistin-Resistant Escherichia coli in Weaner Pigs
Antibiotics 2021, 10(4), 465; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040465 - 20 Apr 2021
Cited by 1 | Viewed by 441
Abstract
The treatment of diarrhea in the postweaning period is a common reason for the use of antimicrobials in pig production, and Escherichia coli is the single most important causative agent for this condition. Colistin has recently been classified as a critically important antimicrobial [...] Read more.
The treatment of diarrhea in the postweaning period is a common reason for the use of antimicrobials in pig production, and Escherichia coli is the single most important causative agent for this condition. Colistin has recently been classified as a critically important antimicrobial for human health, as it is a last-resort drug against certain multi-drug-resistant Gram-negative bacteria. Therefore, the use of colistin has been significantly reduced in some countries, including Denmark. Despite this, the drug is still commonly used to treat diarrhea in pigs in many countries, and there is a need to understand the risks associated with this practice. We performed a prospective cohort study to investigate the effect of colistin treatment on the changes in the average minimum inhibitory concentration (MIC) in commensal E. coli in a pig herd where no colistin-resistant bacteria were detectable before treatment. One group of pigs was batch treated with colistin after the clinical observation of diarrhea, one group was batch treated with colistin approximately 10 days before the expected onset of diarrhea, and a control group was not treated with colistin but provided with nonantimicrobial antidiarrheal feed supplement. Treatment with colistin in the dose and time combinations used did not result in a significant increase in the average colistin MIC values in E. coli. Moreover, no E. coli strains showed a MIC above the breakpoint of >2 mg/L against colistin. Co-selection of resistance to other antimicrobials was not observed. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
Show Figures

Figure 1

Perspective
Should the Increased Awareness of the One Health Approach Brought by the COVID-19 Pandemic Be Used to Further Tackle the Challenge of Antimicrobial Resistance?
Antibiotics 2021, 10(4), 464; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040464 - 20 Apr 2021
Cited by 1 | Viewed by 807
Abstract
Several experts have expressed their concerns regarding the potential increase in antimicrobial resistance (AMR) during the COVID-19 pandemic as a consequence of the increase in antimicrobial and biocide use in humans globally. However, the impact of the pandemic on antimicrobial use (AMU) and [...] Read more.
Several experts have expressed their concerns regarding the potential increase in antimicrobial resistance (AMR) during the COVID-19 pandemic as a consequence of the increase in antimicrobial and biocide use in humans globally. However, the impact of the pandemic on antimicrobial use (AMU) and AMR in animals has yet to be discussed and evaluated. Indeed, veterinary practices have been hugely impacted by the pandemic and its restrictive measures around the world. In this perspective, we call for more research to estimate the impact of COVID-19 on AMU and AMR in both humans and animals, as well as on the environment, in coherence with the One Health approach. In addition, we argue that the current pandemic is an opportunity to accelerate the implementation of a One Health approach to tackle the AMR crisis at the global scale. Indeed, the momentum created by the increased general awareness of both the public and decision-makers for the development and maintenance of effective drugs to treat human infections, as well as for the importance of a One Health approach to prevent the emergence of infectious diseases, should be used as a lever to implement global collaborative and sustainable solutions to the complex challenges of AMR. Full article
(This article belongs to the Special Issue Antibiotic Resistance: A One-Health Approach)
Article
Rapid Screening of Essential Oils as Substances Which Enhance Antibiotic Activity Using a Modified Well Diffusion Method
Antibiotics 2021, 10(4), 463; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040463 - 20 Apr 2021
Viewed by 488
Abstract
Antimicrobial resistance is recognized as one of the major global health challenges of the 21st century. Synergistic combinations for antimicrobial therapies can be a good strategy for the treatment of multidrug resistant infections. We examined the ability of a group of 29 plant [...] Read more.
Antimicrobial resistance is recognized as one of the major global health challenges of the 21st century. Synergistic combinations for antimicrobial therapies can be a good strategy for the treatment of multidrug resistant infections. We examined the ability of a group of 29 plant essential oils as substances which enhance the antibiotic activity. We used a modified well diffusion method to establish a high-throughput screening method for easy and rapid identification of high-level enhancement combinations against bacteria. We found that 25 essential oils possessed antibacterial activity against Escherichia Coli ATCC 25922 and methicillin-resistant Staphylococcus aureus (MRSA) 43300 with MICs that ranged from 0.01% to 2.5% v/v. We examined 319 (11 × 29) combinations in a checkerboard assay with E. Coli ATCC 25922 and MRSA 43300, and the result showed that high-level enhancement combinations were 48 and 44, low-level enhancement combinations were 214 and 211, and no effects combinations were 57 and 64, respectively. For further verification we randomly chose six combinations that included orange and Petitgrain essential oils in a standard time-killing assay. The results are in great agreement with those of the well diffusion assays. Therefore, the modified diffusion method was a rapid and effective method to screen high-level enhancement combinations of antibiotics and essential oils. Full article
(This article belongs to the Special Issue Development and Application of Plant Antimicrobial Substance)
Show Figures

Figure 1

Article
Barriers and Facilitators in Perioperative Antibiotic Prophylaxis: A Mixed-Methods Study in a Small Island Setting
Antibiotics 2021, 10(4), 462; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040462 - 19 Apr 2021
Viewed by 510
Abstract
Few studies have addressed antibiotic guideline adherence in small island settings, such as Aruba. This study aimed to evaluate the appropriateness of perioperative antibiotic prophylaxis (PAP) and identify barriers for PAP guideline adherence. A mixed-methods study was carried out at the operating theatre [...] Read more.
Few studies have addressed antibiotic guideline adherence in small island settings, such as Aruba. This study aimed to evaluate the appropriateness of perioperative antibiotic prophylaxis (PAP) and identify barriers for PAP guideline adherence. A mixed-methods study was carried out at the operating theatre (OT) in the Dr. Horacio E. Oduber Hospital (HOH) in Aruba. First, a prospective audit was performed on the appropriateness of guideline-derived quality indicators (QIs). Then, interviews based on the Flottorp framework were conducted to identify barriers for guideline adherence. Finally, a survey was distributed to verify the outcomes of the interviews. The appropriateness of QIs was measured: correct indication (50.6%); antimicrobial agent (30.8%); dose (94.4%); timing (55.0%); route of administration (100%); duration (89.5%); and redosing (95.7%). The overall appropriateness was 34.9%. The main barriers discovered were poor knowledge about PAP and the guidelines and professional interactions regarding PAP, specifically poor communication and lack of clarity about responsibilities regarding PAP. This study was the first to evaluate the appropriateness and to identify barriers for PAP guideline adherence in a small island hospital. The overall appropriateness of PAP was poor with just 34.9%. Future interventions should be focused on communication, education and awareness of the possibility to consult an ID physician or microbiologist. Full article
Show Figures

Figure 1

Article
A Highly Active Chimeric Lysin with a Calcium-Enhanced Bactericidal Activity against Staphylococcus aureus In Vitro and In Vivo
Antibiotics 2021, 10(4), 461; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040461 - 19 Apr 2021
Viewed by 495
Abstract
Lysins, including chimeric lysins, have recently been explored as novel promising alternatives to failing antibiotics in treating multi-drug resistant (MDR) pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Herein, by fusing the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain from the Ply187 lysin with the non-SH3b [...] Read more.
Lysins, including chimeric lysins, have recently been explored as novel promising alternatives to failing antibiotics in treating multi-drug resistant (MDR) pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Herein, by fusing the CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) catalytic domain from the Ply187 lysin with the non-SH3b cell-wall binding domain from the LysSA97 lysin, a new chimeric lysin ClyC was constructed with Ca2+-enhanced bactericidal activity against all S. aureus strains tested, including MRSA. Notably, treating S. aureus with 50 μg/mL of ClyC in the presence of 100 μM Ca2+ lead to a reduction of 9 Log10 (CFU/mL) in viable bacterial number, which was the first time to observe a lysin showing such a high activity. In addition, the effective concentration of ClyC could be decreased dramatically from 12 to 1 μg/mL by combination with 0.3 μg/mL of penicillin G. In a mouse model of S. aureus bacteremia, a single intraperitoneal administration of 0.1 mg/mouse of ClyC significantly improved the survival rates and reduced 2 Log10 (CFU/mL) of the bacterial burdens in the organs of the infected mice. ClyC was also found stable after lyophilization without cryoprotectants. Based on the above observations, ClyC could be a promising candidate against S. aureus infections. Full article
(This article belongs to the Special Issue Bacteriophage Lysins in the Era of Antibiotic Resistance)
Show Figures

Figure 1

Article
Performance Evaluation of the Newly Developed In Vitro Rapid Diagnostic Test for Detecting OXA-48-Like, KPC-, NDM-, VIM- and IMP-Type Carbapenemases: The RESIST-5 O.K.N.V.I. Multiplex Lateral Flow Assay
Antibiotics 2021, 10(4), 460; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040460 - 19 Apr 2021
Viewed by 340
Abstract
The objective of this study was to evaluate the performance of the RESIST-5 O.K.N.V.I. assay for identifying these five common domestic carbapenemases among a large number of clinical isolates in South Korea. A total of 268 non-duplicated clinical isolates of gram-negative bacilli were [...] Read more.
The objective of this study was to evaluate the performance of the RESIST-5 O.K.N.V.I. assay for identifying these five common domestic carbapenemases among a large number of clinical isolates in South Korea. A total of 268 non-duplicated clinical isolates of gram-negative bacilli were included in this study as follows: 258 carbapenemase-producing (CP) strains (OXA-48-like, KPC, NDM, VIM, IMP, GES, OXA-23 and two or more carbapenemase producers) and 10 non-CP carbapenem-resistant Enterobacterales (non-CP CREs). Overall sensitivity and specificity were 98.4% and 100%, respectively. In addition, all non-targeted carbapenemase producers including GES and OXA-23 producers and non-CP CREs were correctly identified as negative results. There were only four discrepant cases in which three VIM carbapenemase producers and one NDM carbapenemase producer were not detected. The RESIST-5 O.K.N.V.I. assay as an in vitro diagnostic test for detecting five common carbapenemases provided rapid and accurate results in a short time, indicating that this method could provide an innovative solution for early detection, resulting in appropriate antimicrobial treatment in the clinical field. Full article
(This article belongs to the Special Issue Rapid Diagnostics of the Antimicrobial Resistance)
Show Figures

Figure 1

Article
Multidrug-Resistant Healthcare-Associated Infections in Neonates with Severe Respiratory Failure and the Impacts of Inappropriate Initial Antibiotic Therap
Antibiotics 2021, 10(4), 459; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040459 - 18 Apr 2021
Viewed by 486
Abstract
Background: Multidrug-resistant (MDR) pathogens have emerged as an important issue in neonatal intensive care units (NICUs), especially in critically ill neonates with severe respiratory failure. We aimed to investigate neonatal healthcare-associated infections (HAIs) caused by MDR pathogens and the impacts of inappropriate initial [...] Read more.
Background: Multidrug-resistant (MDR) pathogens have emerged as an important issue in neonatal intensive care units (NICUs), especially in critically ill neonates with severe respiratory failure. We aimed to investigate neonatal healthcare-associated infections (HAIs) caused by MDR pathogens and the impacts of inappropriate initial antibiotic therapy on the outcomes. Methods: We retrospectively analyzed all cases of HAIs in neonates with severe respiratory failure in a tertiary-level NICU in Taiwan between January 2014 and May 2020. All clinical features, microbiology, therapeutic interventions, and outcomes were compared between the MDR-HAI and non-MDR HAI groups. Multivariate regression analyses were used to investigate independent risk factors for sepsis-attributable mortality. Results: A total of 275 critically ill neonates with severe respiratory failure who had HAIs were enrolled. Ninety-five cases (34.5%) were caused by MDR pathogens, and 141 (51.3%) cases had positive bacterial cultures from multiple sterile sites. In this cohort, the MDR-HAI group was more likely to receive inappropriate initial antibiotic therapy (51.0% versus 4.7%, respectively; p < 0.001) and exhibit delayed control of the infectious focus (52.6% versus 37.8%, respectively; p = 0.021) compared with the non-MDR HAI group. The sepsis-attributable and final in-hospital rates were 21.8% and 37.1%, respectively, and they were comparable between the MDR-HAI and non-MDR HAI groups. Empirically broad-spectrum antibiotics were prescribed in 76.7% of cases, and inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. Independent risk factors for sepsis-attributable mortality in neonates with severe respiratory failure included the presence of septic shock (OR: 3.61; 95% CI: 1.54–8.46; p = 0.003), higher illness severity (OR: 1.33; 95% CI: 1.04–1.72; p = 0.026), and neonates with bronchopulmonary dysplasia (OR: 2.99; 95% CI: 1.47–6.09; p = 0.003). Conclusions: MDR pathogens accounted for 34.5% of all neonatal HAIs in the NICU, but neither MDR pathogens nor inappropriate initial antibiotics were associated with final adverse outcomes. Because the overuse of broad-spectrum antibiotics has emerged as an important issue in critically ill neonates, the implementation of antimicrobial stewardship to promote the appropriate use of antimicrobials is urgently needed. Full article
Perspective
Candida Periprosthetic Joint Infection: Is It Curable?
Antibiotics 2021, 10(4), 458; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040458 - 17 Apr 2021
Viewed by 415
Abstract
Candida periprosthetic joint infection (CPJI) is a rare and very difficult to treat infection, and high-quality evidence regarding the best management is scarce. Candida spp. adhere to medical devices and grow forming biofilms, which contribute to the persistence and relapse of this infection. [...] Read more.
Candida periprosthetic joint infection (CPJI) is a rare and very difficult to treat infection, and high-quality evidence regarding the best management is scarce. Candida spp. adhere to medical devices and grow forming biofilms, which contribute to the persistence and relapse of this infection. Typically, CPJI presents as a chronic infection in a patient with multiple previous surgeries and long courses of antibiotic therapy. In a retrospective series of cases, the surgical approach with higher rates of success consists of a two-stage exchange surgery, but the best antifungal treatment and duration of antifungal treatment are still unclear, and the efficacy of using an antifungal agent-loaded cement spacer is still controversial. Until more evidence is available, focusing on prevention and identifying patients at risk of CPJI seems more than reasonable. Full article
Show Figures

Figure 1

Review
Comparative Studies on Different Extraction Methods of Centella asiatica and Extracts Bioactive Compounds Effects on Antimicrobial Activities
Antibiotics 2021, 10(4), 457; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040457 - 17 Apr 2021
Viewed by 575
Abstract
The interest of consumers in using products containing phytochemicals derived from plants is growing day by day due to the shift of consumers’ preferences from convenience to environmental sustainability. One plant utilized in many products is Centella asiatica, a herb commonly used [...] Read more.
The interest of consumers in using products containing phytochemicals derived from plants is growing day by day due to the shift of consumers’ preferences from convenience to environmental sustainability. One plant utilized in many products is Centella asiatica, a herb commonly used in folk medicine, health supplements, and beauty products. Extraction of bioactive compounds from C. asiatica was performed using conventional methods and modern methods (e.g., microwave or ultrasound-assisted and subcritical water extraction). This review summarizes the variety of methods used to extract active compounds from C. asiatica, their influence on the bioactive compounds and antimicrobial activity in vitro and in vivo, and the safety and toxicology of C. asiatica extract. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Natural Products and Plants)
Show Figures

Figure 1

Article
Pharmacist-Driven Antibiotic Stewardship Program in Febrile Neutropenic Patients: A Single Site Prospective Study in Thailand
Antibiotics 2021, 10(4), 456; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040456 - 17 Apr 2021
Viewed by 517
Abstract
The antibiotic stewardship program (ASP) is a necessary part of febrile neutropenia (FN) treatment. Pharmacist-driven ASP is one of the meaningful approaches to improve the appropriateness of antibiotic usage. Our study aimed to determine role of the pharmacist in ASPs for FN patients. [...] Read more.
The antibiotic stewardship program (ASP) is a necessary part of febrile neutropenia (FN) treatment. Pharmacist-driven ASP is one of the meaningful approaches to improve the appropriateness of antibiotic usage. Our study aimed to determine role of the pharmacist in ASPs for FN patients. We prospectively studied at Thammasat University Hospital between August 2019 and April 2020. Our primary outcome was to compare the appropriate use of target antibiotics between the pharmacist-driven ASP group and the control group. The results showed 90 FN events in 66 patients. The choice of an appropriate antibiotic was significantly higher in the pharmacist-driven ASP group than the control group (88.9% vs. 51.1%, p < 0.001). Furthermore, there was greater appropriateness of the dosage regimen chosen as empirical therapy in the pharmacist-driven ASP group than in the control group (97.8% vs. 88.7%, p = 0.049) and proper duration of target antibiotics in documentation therapy (91.1% vs. 75.6%, p = 0.039). The multivariate analysis showed a pharmacist-driven ASP and infectious diseases consultation had a favorable impact on 30-day infectious diseases-related mortality in chemotherapy-induced FN patients (OR 0.058, 95%CI:0.005–0.655, p = 0.021). Our study demonstrated that pharmacist-driven ASPs could be a great opportunity to improve antibiotic appropriateness in FN patients. Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Stewardship, 2nd Volume)
Article
Prevalence of and Factors Associated with Antibiotic Prescriptions in Patients with Acute Lower and Upper Respiratory Tract Infections—A Case-Control Study
Antibiotics 2021, 10(4), 455; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040455 - 16 Apr 2021
Viewed by 451
Abstract
Background: The goal of the present study was to estimate the prevalence of patient and physician related variables associated with antibiotic prescriptions in patients diagnosed with acute lower and upper respiratory tract infections (ALURTI), treated in general practices (GP) and pediatric practices, in [...] Read more.
Background: The goal of the present study was to estimate the prevalence of patient and physician related variables associated with antibiotic prescriptions in patients diagnosed with acute lower and upper respiratory tract infections (ALURTI), treated in general practices (GP) and pediatric practices, in Germany. Methods: The analysis included 1,140,095 adult individuals in 1237 general practices and 309,059 children and adolescents in 236 pediatric practices, from the Disease Analyzer database (IQVIA), who had received at least one diagnosis of an ALURTI between 1 January 2015 and 31 March 2019. We estimated the association between 35 predefined variables and antibiotic prescription using multivariate logistic regression models, separately for general and pediatric practices. The variables included the proportion (as a percentage) of antibiotics or phytopharmaceuticals on all prescriptions per practice, as an indicator of physician prescription preference. Results: The prevalence of antibiotic prescription was higher in patients treated in GP (31.2%) than in pediatric practices (9.1%). In GP, the strongest association with antibiotic prescription was seen in the practice preference for antibiotic use, followed by specific diagnoses (acute bronchitis, sinusitis, pharyngitis, laryngitis, and tracheitis), and higher patient age. In pediatric practices, acute sinusitis and bronchitis were the variables with the strongest association, followed by practice preference for antibiotic prescription. The strongest association with the non-prescription of antibiotics was practice preference for phytopharmaceuticals and the specific diagnosis of a viral infection. Conclusion: This study shows a high prevalence of antibiotic prescribing for patients with ALURTI in a primary care setting, especially in adult patients; physician related factors play an important role that should be addressed in interventions to reduce potentially inappropriate antibiotic prescribing. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
Show Figures

Figure 1

Article
Antimicrobial Use, Residues, Resistance and Governance in the Food and Agriculture Sectors, Tanzania
Antibiotics 2021, 10(4), 454; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040454 - 16 Apr 2021
Cited by 1 | Viewed by 720
Abstract
All infections are potentially curable as long as the etiological agents are susceptible to antimicrobials. The increased rate at which antimicrobials are becoming ineffective is a global health risk of increasing concern that threatens withdrawal of beneficial antimicrobials for disease control. The increased [...] Read more.
All infections are potentially curable as long as the etiological agents are susceptible to antimicrobials. The increased rate at which antimicrobials are becoming ineffective is a global health risk of increasing concern that threatens withdrawal of beneficial antimicrobials for disease control. The increased demand for food of animal origin, in particular eggs, meat and milk has led to intensification and commercial production systems where excessive use and misuse of antimicrobials may prevail. Antimicrobials, handled and used by farmers and animal attendants with no formal education, may be predisposed to incorrect dosages, misuse, incorrect applications and non-adherence to withdrawal periods. This study was conducted to assess the regulatory roles and governance of antimicrobials, establish the pattern and extent of their use, evaluate the antimicrobial residues and resistance in the food animals and crop agriculture value chains, and relate these findings to existing strategies in place for combating the emergence of antimicrobial resistance in Tanzania. A multimethod approach (desk review, field study and interviews) was used. Relevant establishments were also visited. High levels of resistance to penicillin G, chloramphenicol, streptomycin and oxytetracycline have been reported, especially for Actinobacter pyogenes, Staphylococcus hyicus, Staphylococcus intermedius and Staphylococcus aureus from dairy cattle with mastitis and in humans. Similar trends were found in poultry where eggs and meat are contaminated with Escherichia coli strains resistant to amoxicillin + clavulanate, sulphamethoxazole and neomycin. An increasing trend of emerging multidrug resistant E. coli, Klebsiella pneumoniae, Staphylococcus aureus and Salmonella was also found in food animals. An increase in methicillin resistant Staphlococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL) in the livestock sector in Tanzania have been reported. The pathogens isolated in animals were resistant to ampicillin, augmentin, gentamicin, co-trimoxazole, tetracycline, amoxicillin, streptomycin, nalidixic acid, azithromycin, chloramphenicol, tylosin, erythromycin, cefuroxime, norfloxacin and ciprofloxacin. An increased usage of antimicrobials for prophylaxis, and therapeutics against pathogens and for growth promotion in livestock, aquaculture and crop production were observed. A One Health strategic approach is advocated to combat antimicrobial resistance (AMR) in the food and agriculture sectors in Tanzania. Practical recommendations include (a) legislation review and implementation; (b) antimicrobial use (AMU), AMR and antimicrobial residue (AR) awareness and advocacy among stakeholders along the value chain; (c) strengthening of surveillance and monitoring programs for AMU, AMR and AR; (d) enhanced development and use of rapid and innovative diagnostic tests and the promotion of biosecurity principles; and (e) good husbandry practices. The utilization of this information to improve public health policies and reduce the burden of AMR will be beneficial. Full article
Show Figures

Figure 1

Article
Antimicrobial Resistance Patterns of Escherichia coli Isolated from Sheep and Beef Farms in England and Wales: A Comparison of Disk Diffusion Interpretation Methods
Antibiotics 2021, 10(4), 453; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040453 - 16 Apr 2021
Viewed by 607
Abstract
Little data exist on the levels of antimicrobial resistance from bacteria isolated from British sheep and beef cattle. The aim of this study was to investigate antimicrobial resistance patterns on sheep and beef farms in England and Wales using multiple interpretation methods. Fecal [...] Read more.
Little data exist on the levels of antimicrobial resistance from bacteria isolated from British sheep and beef cattle. The aim of this study was to investigate antimicrobial resistance patterns on sheep and beef farms in England and Wales using multiple interpretation methods. Fecal samples (n = 350) from sheep and beef cattle were collected from 35 farms. Disk diffusion antimicrobial susceptibility testing against ten antimicrobials was carried out for 1115 (699 sheep, 416 beef) β-glucuronidase-positive Escherichia coli isolates. Susceptibility was interpreted using clinical breakpoints, which determine clinically resistant bacteria, and epidemiological and livestock-specific cut-off values, which determine microbiological-resistant bacteria (non-wild type). Using livestock-specific cut-off values, a high frequency of wild type for all ten antimicrobials was observed in isolates from sheep (90%) and beef cattle (85%). Cluster analysis was performed to identify patterns in antimicrobial resistance. Interpretation of susceptibility using livestock-specific cut-off values showed a cluster of isolates that were non-wild type to cefotaxime and amoxicillin/clavulanic acid, whereas clinical breakpoints did not. A multilevel logistic regression model determined that tetracycline use on the farm and soil copper concentration were significantly associated with tetracycline non-wild type isolates. The results suggest that using human clinical breakpoints could lead to both the under-reporting and over-reporting of antimicrobial resistance in sheep and beef cattle. Full article
Show Figures

Figure 1

Article
Microbiological Profiles of Dental Implants in Metabolic Syndrome Patients: A Case-Control Study
Antibiotics 2021, 10(4), 452; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040452 - 16 Apr 2021
Viewed by 386
Abstract
There is a lack of knowledge on the possible influence of systemic conditions on peri-implantitis. The aim of this case-control study is to evaluate the difference in terms of oral pathogens’ concentrations in the peri-implant sulcus of a group of patients affected by [...] Read more.
There is a lack of knowledge on the possible influence of systemic conditions on peri-implantitis. The aim of this case-control study is to evaluate the difference in terms of oral pathogens’ concentrations in the peri-implant sulcus of a group of patients affected by metabolic syndrome (Mets) compared to healthy subjects. For each patient, peri-implant sulcular biofilm samples were obtained by inserting two sterile endodontic paper points in the deepest aspect of the peri-implant sulcus for 30 s. The quantitative real-time polymerase chain reaction was performed to evaluate total bacterial counts of six pathogens. Patients were screened for peri-implant diseases and clinical and radiographic parameters were recorded. A total of 50 patients was enrolled in the study, 25 affected by Mets and 25 healthy. Significantly higher bacterial counts were discovered for Aggregatibacter actinomycetemcomitans (p = 0.0008), Prevotella intermedia (p = 0.0477) and Staphylococcus aureus (p = 0.034) in MetS patients compared to healthy subjects. Performing a sub-group analysis, considering peri-implant status and dividing patients by MetS diagnosis, no statistically significant (p < 0.05) differences were found. For the first time, a correlation between MetS presence and a greater prevalence of some bacterial species in the peri-implant sulcus was reported, irrespectively from peri-implant status (health vs. disease). Full article
Article
Impact of Prior Antibiotic Use in Primary Care on Escherichia coli Resistance to Third Generation Cephalosporins: A Case-Control Study
Antibiotics 2021, 10(4), 451; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040451 - 16 Apr 2021
Viewed by 521
Abstract
Research is lacking on the reversibility of antimicrobial resistance (AMR). Thus, we aimed to determine the influence of previous antibiotic use on the development and decay over time of third generation cephalosporin (3GC)-resistance of E. coli. Using the database of hospital laboratories [...] Read more.
Research is lacking on the reversibility of antimicrobial resistance (AMR). Thus, we aimed to determine the influence of previous antibiotic use on the development and decay over time of third generation cephalosporin (3GC)-resistance of E. coli. Using the database of hospital laboratories of the Autonomous Province of Bolzano/Bozen (Italy), anonymously linked to the database of outpatient pharmaceutical prescriptions and the hospital discharge record database, this matched case-control study was conducted including as cases all those who have had a positive culture from any site for 3GC resistant E. coli (3GCREC) during a 2016 hospital stay. Data were analyzed by conditional logistic regression. 244 cases were matched to 1553 controls by the date of the first isolate. Male sex (OR 1.49, 95% CI 1.10–2.01), older age (OR 1.11, 95% CI 1.02–1.21), the number of different antibiotics taken in the previous five years (OR 1.20, 95% CI 1.08–1.33), at least one antibiotic prescription in the previous year (OR 1.92, 95% CI 1.36–2.71), and the diagnosis of diabetes (OR 1.57, 95% CI 1.08–2.30) were independent risk factors for 3GCREC colonization/infection. Patients who last received an antibiotic prescription two years or three to five years before hospitalization showed non-significant differences with controls (OR 0.97, 95% CI 0.68–1.38 and OR 0.85, 95% CI 0.59–1.24), compared to an OR of 1.92 (95% CI 1.36–2.71) in those receiving antibiotics in the year preceding hospitalization. The effect of previous antibiotic use on 3GC-resistance of E. coli is highest after greater cumulative exposure to any antibiotic as well as to 3GCs and in the first 12 months after antibiotics are taken and then decreases progressively. Full article
(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship)
Show Figures

Figure 1

Article
Comparative Analysis of Gradient Diffusion and Disk Diffusion with Agar Dilution for Susceptibility Testing of Elizabethkingia anophelis
Antibiotics 2021, 10(4), 450; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040450 - 16 Apr 2021
Cited by 1 | Viewed by 471
Abstract
Elizabethkingia anophelis has recently emerged as a cause of life-threatening infections. This study compared the results of antimicrobial susceptibility testing (AST) conducted for E. anophelis through different methods. E. anophelis isolates collected between January 2005 and June 2019 were examined for their susceptibility [...] Read more.
Elizabethkingia anophelis has recently emerged as a cause of life-threatening infections. This study compared the results of antimicrobial susceptibility testing (AST) conducted for E. anophelis through different methods. E. anophelis isolates collected between January 2005 and June 2019 were examined for their susceptibility to 14 antimicrobial agents by using disk diffusion, gradient diffusion (Etest; bioMérieux S.A., Marcy l’Etoile, France), and agar dilution methods. The agar dilution method was the reference assay. According to the agar dilution method, the isolates exhibited the highest susceptibility to minocycline (100%), doxycycline (97.6%), rifampin (95.2%), and levofloxacin (78.6%). A very major error rate of >1.5% was observed for nine antibiotics tested using the disk diffusion method. The overall categorical agreement rate between the disk diffusion and agar dilution methods was 74.8%, and ceftazidime, minocycline, levofloxacin, and rifampin met the minimum requirements for discrepancy and agreement rates. The Etest method tended to produce lower log2 minimum inhibitory concentrations for the antibiotics, except for trimethoprim–sulfamethoxazole and rifampin; the method resulted in very major errors for nine antibiotics. The overall essential and categorical agreement rates between the Etest and agar dilution methods were 67.3% and 76.1%, respectively. The Etest method demonstrated acceptable discrepancy and agreement rates for ceftazidime, minocycline, doxycycline, levofloxacin, and rifampin. AST results obtained through the disk diffusion and Etest methods for multiple antibiotics differed significantly from those obtained using the agar dilution method. These two assays should not be a routine alternative for AST for E. anophelis. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
Show Figures

Figure 1

Article
Meropenem Stability in Human Plasma at −20 °C: Detailed Assessment of Degradation
Antibiotics 2021, 10(4), 449; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040449 - 16 Apr 2021
Cited by 2 | Viewed by 465
Abstract
There are concerns about the stability of meropenem in plasma samples, even when frozen at −20 °C. Previous smaller studies suggested significant degradation of meropenem at −20 °C after 3–20 days. However, in several recent clinical studies, meropenem plasma samples were still stored [...] Read more.
There are concerns about the stability of meropenem in plasma samples, even when frozen at −20 °C. Previous smaller studies suggested significant degradation of meropenem at −20 °C after 3–20 days. However, in several recent clinical studies, meropenem plasma samples were still stored at −20 °C, or the storage temperature and/or time were not mentioned in the paper. The aim of this study was to describe and model meropenem degradation in human plasma at −20 °C over 1 year. Stability of meropenem in human plasma at −20 °C was investigated at seven concentrations (0.44, 4.38, 17.5, 35.1, 52.6, 70.1, and 87.6 mg/L) representative for the range of relevant concentrations encountered in clinical practice. For each concentration, samples were stored for 0, 7, 14, 21, 28, 42, 56, 70, 84, 112, 140, 168, 196, 224, 252, 280, 308, 336, and 364 days at −20 °C before being transferred to −80 °C until analysis. Degradation was modeled using polynomial regression analysis and artificial neural network (ANN). Meropenem showed significant degradation over time in human plasma when stored at −20 °C. Degradation was present over the whole concentration range and increased with higher concentrations until a concentration of 35.1 mg/L. Both models showed accurate prediction of meropenem degradation. In conclusion, this study provides detailed insights into the concentration-dependent degradation of meropenem in human plasma stored at −20 °C over 1 year. Meropenem in human plasma is shown to be stable at least up to approximately 80 days when stored at −20 °C. The polynomial model allows calculating original meropenem concentrations in samples stored for a known period of time at −20 °C. Full article
(This article belongs to the Special Issue Optimizing Antibiotic Treatment: Pharmacokinetics and Clinical Trials)
Show Figures

Figure 1

Article
Occurrence and Survival of Livestock-Associated MRSA in Pig Manure and on Agriculture Fields
Antibiotics 2021, 10(4), 448; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040448 - 16 Apr 2021
Viewed by 525
Abstract
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widespread in European pig production, and an increasing number of humans attract infections with this bacterium. Although most infections occur in humans with direct livestock contact, an increasing number of infections occur in humans without any established [...] Read more.
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) is widespread in European pig production, and an increasing number of humans attract infections with this bacterium. Although most infections occur in humans with direct livestock contact, an increasing number of infections occur in humans without any established livestock contact. There have been speculations that at least some of these infections may be connected to the exposure of liquid pig manure for example spread as fertilizers. The present study therefore undertook to measure the presence of LA-MRSA in liquid pig manure and on the surface of soils fertilized with liquid manure and investigate the survival of the bacterium in manure. The results showed that LA-MRSA could be detected in 7 out of 20 liquid manure samples and in 12 out of 186 soil samples. However, the bacterium was not more frequently detected in samples collected after compared to before the spreading of liquid manure on the fields, thus suggesting that other sources of LA-MRSA on agriculture fields likely exist. The decimation time in liquid manure was >32 days at 5 °C in vitro but decreased with increasing temperature. Based on these results, liquid manure does not appear to be an important risk factor for human exposure to LA-MRSA. Full article
(This article belongs to the Special Issue Usage of Antibiotic in Agriculture and Animal Farming)
Show Figures

Figure 1

Article
Antibiotic Resistance of Uropathogens Isolated from Patients Hospitalized in District Hospital in Central Poland in 2020
Antibiotics 2021, 10(4), 447; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040447 - 16 Apr 2021
Viewed by 545
Abstract
The aim of this study was to determine antibiotic resistance patterns and the prevalence of uropathogenes causing urinary tract infections (UTIs) in patients hospitalized in January–June 2020 in central Poland. Antimicrobial susceptibility testing was performed using the disk-diffusion method. Escherichia coli (52.2%), Klebsiella [...] Read more.
The aim of this study was to determine antibiotic resistance patterns and the prevalence of uropathogenes causing urinary tract infections (UTIs) in patients hospitalized in January–June 2020 in central Poland. Antimicrobial susceptibility testing was performed using the disk-diffusion method. Escherichia coli (52.2%), Klebsiella pneumoniae (13.7%), Enterococcus faecalis (9.3%), E. faecium (6.2%), and Proteus mirabilis (4,3%) were most commonly isolated from urine samples. E. coli was significantly more frequent in women (58.6%) (p = 0.0089) and in the age group 0–18, while K. pneumoniae was more frequent in men (24.4%) (p = 0.0119) and in individuals aged 40–60 and >60. Gram-negative species showed resistance to ampicillin. K. pneumoniae were resistant to amoxicillin plus clavulanic acid (75.0%), piperacillin plus tazobactam (76.2%), cefotaxime (76.2%), cefuroxime (81.0%), ciprofloxacin (81.0%), and trimethoprim plus sulphamethoxazole (81.0%). Carbapenems were effective against all E. coli and P. mirabilis. Some K. pneumoniae (13.6%) produced metallo-β-lactamases (MBLs). E. coli (22.6%), K. pneumoniae (81.8%), and all E. faecium were multidrug-resistant (MDR). Some E. coli (26.2%), K. pneumoniae (63.6%), and P. mirabilis (14.3%) isolates produced extended-spectrum beta-lactamases (ESBL). Vancomycin-resistant E. faecium was also found. This study showed that the possibilities of UTIs therapy using available antibiotics become limited due to the increasing number of antibiotic-resistant uropathogens. Full article
(This article belongs to the Special Issue Uropathogens - Antibiotic Resistance and Alternative Therapies)
Communication
Risk Factors of Daptomycin-Induced Eosinophilic Pneumonia in a Population with Osteoarticular Infection
Antibiotics 2021, 10(4), 446; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040446 - 16 Apr 2021
Viewed by 449
Abstract
Background: Daptomycin-induced eosinophilic pneumonia (DEP) is a rare but severe adverse effect and the risk factors are unknown. The aim of this study was to determine risk factors for DEP. Methods: A retrospective cohort study was performed at the Bone and Joint Infection [...] Read more.
Background: Daptomycin-induced eosinophilic pneumonia (DEP) is a rare but severe adverse effect and the risk factors are unknown. The aim of this study was to determine risk factors for DEP. Methods: A retrospective cohort study was performed at the Bone and Joint Infection Unit of the Hospital Universitari Bellvitge (January 2014–December 2018). To identify risk factors for DEP, cases were divided into two groups: those who developed DEP and those without DEP. Results: Among the whole cohort (n = 229) we identified 11 DEP cases (4.8%) and this percentage almost doubled in the subgroup of patients ≥70 years (8.1%). The risk factors for DEP were age ≥70 years (HR 10.19, 95%CI 1.28–80.93), therapy >14 days (7.71, 1.98–30.09) and total cumulative dose of daptomycin ≥10 g (5.30, 1.14–24.66). Conclusions: Clinicians should monitor cumulative daptomycin dosage to minimize DEP risk, and be cautious particularly in older patients when the total dose of daptomycin exceeds 10 g. Full article
Show Figures

Figure 1

Article
Examining the Effect of Context, Beliefs, and Values on UK Farm Veterinarians’ Antimicrobial Prescribing: A Randomized Experimental Vignette and Cross-Sectional Survey
Antibiotics 2021, 10(4), 445; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040445 - 15 Apr 2021
Cited by 1 | Viewed by 500
Abstract
Antimicrobial resistance (AMR) is a pressing threat to public and animal health. There is evidence that antimicrobial prescribing and stewardship behaviors by veterinarians (vets) are influenced by non-clinical factors, such as psychological, social, and environmental factors. This study explored the role of context, [...] Read more.
Antimicrobial resistance (AMR) is a pressing threat to public and animal health. There is evidence that antimicrobial prescribing and stewardship behaviors by veterinarians (vets) are influenced by non-clinical factors, such as psychological, social, and environmental factors. This study explored the role of context, beliefs, and values on vets’ antimicrobial prescribing decisions. UK-based practicing farm vets (n = 97) were recruited to an online study. Using an experimental vignette methodology, vets were randomly assigned across four conditions, to examine the effects of different contexts (pressure on farm economics, the farmer, or the vet-farmer relationship, compared to a control condition) on vets’ likelihood of prescribing antibiotics. Vets’ beliefs about different groups’ responsibility for causing and preventing AMR and vets’ values were also measured. Key findings were that context alone, values, and beliefs about groups’ responsibilities for causing AMR were not predictive of vets’ likelihood of prescribing antibiotics. However, vets’ beliefs about groups’ responsibilities for preventing AMR were predictive of an increased likelihood of prescribing antibiotics, when vets were exposed to the experimental condition of the vignette in which the vet–farmer relationship was under pressure. Farm vets also believed that different groups have different levels of responsibility for causing and preventing AMR. Results should be interpreted cautiously, given the smaller than planned for sample size, and the possibility for both false negatives and false positives. Further research is needed to explore how these findings could inform antimicrobial stewardship interventions in veterinary medicine. Full article
(This article belongs to the Special Issue Antimicrobial Stewardship in Veterinary Medicine)
Show Figures

Figure 1

Article
Antibiotic Susceptibility of Staphylococcus aureus and Streptococcus pneumoniae Isolates from the Nasopharynx of Febrile Children under 5 Years in Nanoro, Burkina Faso
Antibiotics 2021, 10(4), 444; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040444 - 15 Apr 2021
Viewed by 373
Abstract
(1) Background: nasopharynx colonization by resistant Staphylococcus aureus and Streptococcus pneumoniae can lead to serious diseases. Emerging resistance to antibiotics commonly used to treat infections due to these pathogens poses a serious threat to the health system. The present study aimed to determine [...] Read more.
(1) Background: nasopharynx colonization by resistant Staphylococcus aureus and Streptococcus pneumoniae can lead to serious diseases. Emerging resistance to antibiotics commonly used to treat infections due to these pathogens poses a serious threat to the health system. The present study aimed to determine the antibiotic susceptibility of S. aureus and S. pneumoniae isolates from the febrile children’s nasopharynx under 5 years in Nanoro (Burkina Faso). (2) Methods: bacterial isolates were identified from nasopharyngeal swabs prospectively collected from 629 febrile children. Antibiotic susceptibility of S. aureus and S. pneumoniae isolates was assessed by Kirby–Bauer method and results were interpreted according to the Clinical and Laboratory Standard Institute guidelines. (3) Results: bacterial colonization was confirmed in 154 (24.5%) of children of whom 96.1% carried S. aureus, 3.2% had S. pneumoniae, and 0.6% carried both bacteria. S. aureus isolates showed alarming resistance to penicillin (96.0%) and S. pneumoniae was highly resistant to tetracycline (100%) and trimethoprim–sulfamethoxazole (83.3%), and moderately resistant to penicillin (50.0%). Furthermore, 4.0% of S. aureus identified were methicillin resistant. (4) Conclusion: this study showed concerning resistance rates to antibiotics to treat suspected bacterial respiratory tract infections. The work highlights the necessity to implement continuous antibiotic resistance surveillance. Full article
Article
Effects of On-Farm Dairy Manure Composting on Tetracycline Content and Nutrient Composition
Antibiotics 2021, 10(4), 443; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040443 - 15 Apr 2021
Viewed by 415
Abstract
This study quantified the potential of farm-scale composting to degrade antibiotics in dairy manure. The compost windrow, consisting of sick cow bedding from a 1000-cow US dairy farm, was managed using the dairy farm’s typical practices and monitored for tetracycline and nutrient composition. [...] Read more.
This study quantified the potential of farm-scale composting to degrade antibiotics in dairy manure. The compost windrow, consisting of sick cow bedding from a 1000-cow US dairy farm, was managed using the dairy farm’s typical practices and monitored for tetracycline and nutrient composition. Samples were collected over 33 days, which was the time from compost pile formation to land application as fertilizer, and analyzed for solids, antibiotics, and nutrient content. Average tetracycline concentrations at the beginning of the study (452 ng/g DW) were lower than at the end of composting (689 ng/g DW), illustrating that antibiotic degradation was not greater than degradation of the compost solids. Total Kjeldahl nitrogen (TKN) increased from 15.3 to 18.4 g/kg during the composting period due to decreases in solids and likely inhibition of N-mineralization due to the presence of antibiotics. The results indicated that antibiotics were not completely degraded when using the farm’s compost pile management techniques, with antibiotics possibly impacting nitrogen transformation in the compost, which should be considered in nutrient management when using sick cow bedding. Additionally, the results showed that antibiotic degradation during farm-scale composting can vary from reported laboratory-scale due to differences in management, composting duration, and temporal conditions, illustrating the need for more extensive on-farm research including common farm practices and real-world conditions. Full article
(This article belongs to the Special Issue Antimicrobial Substances and Nitrogen Cycle in Agro-Ecosystems)
Show Figures

Graphical abstract

Article
Computational Design and Development of Benzodioxane-Benzamides as Potent Inhibitors of FtsZ by Exploring the Hydrophobic Subpocket
Antibiotics 2021, 10(4), 442; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040442 - 15 Apr 2021
Viewed by 448
Abstract
Multidrug resistant Staphylococcus aureus is a severe threat, responsible for most of the nosocomial infections globally. This resistant strain is associated with a 64% increase in death compared to the antibiotic-susceptible strain. The prokaryotic protein FtsZ and the cell division cycle have been [...] Read more.
Multidrug resistant Staphylococcus aureus is a severe threat, responsible for most of the nosocomial infections globally. This resistant strain is associated with a 64% increase in death compared to the antibiotic-susceptible strain. The prokaryotic protein FtsZ and the cell division cycle have been validated as potential targets to exploit in the general battle against antibiotic resistance. Despite the discovery and development of several anti-FtsZ compounds, no FtsZ inhibitors are currently used in therapy. This work further develops benzodioxane-benzamide FtsZ inhibitors. We seek to find more potent compounds using computational studies, with encouraging predicted drug-like profiles. We report the synthesis and the characterization of novel promising derivatives that exhibit very low MICs towards both methicillin-susceptible and -resistant S. aureus, as well as another Gram positive species, Bacillus subtilis, while possessing good predicted physical-chemical properties in terms of solubility, permeability, and chemical and physical stability. In addition, we demonstrate by fluorescence microscopy that Z ring formation and FtsZ localization are strongly perturbed by our derivatives, thus validating the target. Full article
(This article belongs to the Special Issue FtsZ and RnpA as Valid Targets while Developing Novel Antimicrobials)
Show Figures

Figure 1

Article
Validation of a Questionnaire for Patient Awareness and the Need for a Community-Based Outpatient Antimicrobial Stewardship Program (O-ASP): A Pilot Study
Antibiotics 2021, 10(4), 441; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040441 - 15 Apr 2021
Viewed by 349
Abstract
An outpatient antimicrobial stewardship program (O-ASP) was developed and implemented to promote appropriate antibiotic therapy in outpatient settings. As active patient involvement is a critical component of an effective O-ASP, this study aimed to develop and validate a questionnaire addressing patient awareness for [...] Read more.
An outpatient antimicrobial stewardship program (O-ASP) was developed and implemented to promote appropriate antibiotic therapy in outpatient settings. As active patient involvement is a critical component of an effective O-ASP, this study aimed to develop and validate a questionnaire addressing patient awareness for appropriate antibiotic therapy and the need for pharmaceutical care services (PCS) in the O-ASP in Korea. The questionnaire was drafted based on ASPs and PCS guidelines and validated for content and construct validity using the item-content validity index (I-CVI) and Cronbach’s alpha, respectively. The estimated I-CVI and Cronbach’s alpha were considered excellent or adequate (≥0.8 and 0.70–0.90, respectively) for most of the survey items (17 out of 23 items). The validated questionnaire was utilized in a pilot survey study, including 112 individuals (37% male) with the mean ± SD age of 37 ± 13 years. Among the survey participants, 68% responded that antibiotics had been prescribed appropriately; however, ≥50% showed a lack of knowledge regarding their antibiotic therapy. The participants expressed the need for PCS as part of an O-ASP in the questionnaire (average Likert score ≥3.4/5). In conclusion, our newly validated questionnaire successfully measured patient awareness and knowledge of antimicrobial use and the need for PCS in the O-ASP. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
Article
Denture-Soaking Solution Containing Piper betle Extract-Loaded Polymeric Micelles; Inhibition of Candida albicans, Clinical Study, and Effects on Denture Base Resin
Antibiotics 2021, 10(4), 440; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040440 - 15 Apr 2021
Cited by 1 | Viewed by 362
Abstract
Candida albicans is a common overgrowth in people wearing dentures. Long-term use of antifungal chemicals carries a risk of toxic side effects. This study focused on the edible Piper betle extract because of its safety. The broth dilution method was applied for antifungal [...] Read more.
Candida albicans is a common overgrowth in people wearing dentures. Long-term use of antifungal chemicals carries a risk of toxic side effects. This study focused on the edible Piper betle extract because of its safety. The broth dilution method was applied for antifungal determination of the ethyl acetate fractionated extract (fEA) and fEA-loaded polymeric micelles (PMF). The PMF was prepared by thin-film hydration using poloxamer 407 as a polymer base. The results found that the weight ratio of fEA to polymer is the main factor to obtain PMF system as a clear solution, nanoparticle sizes, narrow size distribution, negative zeta potential, and high entrapment efficiency. The activity of PMF against C. albicans is significantly higher than fEA alone, with a minimum fungicidal concentration of 1.5 mg/mL. PMF from 1:3 ratio of fEA to polymer is used to develop a denture-soaking solution contained 1.5 mg fEA/mL (PMFS). A clinical study on dentures of 15 volunteers demonstrated an 86.1 ± 9.2% reduction of C. albicans after soaking the dentures in PMFS daily for 14 days. Interestingly, PMFS did not change the hardness and roughness of the denture base resins. The developed PMFS may serve as a potential natural denture-soaking solution against candidiasis in denture wearers. Full article
(This article belongs to the Special Issue Nanoparticles-Based Antimicrobials)
Show Figures

Figure 1

Previous Issue
Next Issue
Back to TopTop