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Antibiotics, Volume 10, Issue 6 (June 2021) – 139 articles

Cover Story (view full-size image): Modern dosing regimens of antibiotics have abandoned the notion of “one-size-fits-all”. Antibiotics have a clear exposure–effect relationship that is causally linked to treatment efficacy. According to their pharmacokinetic (PK) properties, maximizing the ß-lactam exposure can be achieved by increasing the time (T) that the unbound fraction of the drug (f) remains above the pathogen-specific minimal inhibitory concentration (MIC). Extending the ß-lactam infusions is a feasible approach for extending the fT>MIC without a need for regular therapeutic drug monitoring (TDM) of serum concentrations. Recent national and international guidelines favor extended infusions of ß-lactams over intermittent bolus application in critically ill patients. View this paper
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Article
National Facilitators and Barriers to the Implementation of Incentives for Antibiotic Access and Innovation
Antibiotics 2021, 10(6), 749; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060749 - 21 Jun 2021
Viewed by 792
Abstract
Prominent reports have assessed the challenges to antibiotic innovation and recommended implementing “pull” incentives, i.e., mechanisms that give increased and predictable revenues for important, marketed antibiotics. We set out to understand countries’ perceptions of these recommendations, through frank and anonymous dialogue. In 2019 [...] Read more.
Prominent reports have assessed the challenges to antibiotic innovation and recommended implementing “pull” incentives, i.e., mechanisms that give increased and predictable revenues for important, marketed antibiotics. We set out to understand countries’ perceptions of these recommendations, through frank and anonymous dialogue. In 2019 and 2020, we performed in-depth interviews with national policymakers and antibiotic resistance experts in 13 countries (ten European countries and three non-European) for a total of 73 individuals in 27 separate interviews. Interviewees expressed high-level support for antibiotic incentives in 11 of 13 countries. There is recognition that new economic incentives are needed to maintain a reliable supply to essential antibiotics. However, most countries are uncertain which incentives may be appropriate for their country, which antibiotics should be included, how to implement incentives, and how much it will cost. There is a preference for a multinational incentive, so long as it is independent of national pricing, procurement, and reimbursement processes. Nine countries indicated a preference for a model that ensures access to both existing and new antibiotics, with the highest priority for existing antibiotics. Twelve of thirteen countries indicated that shortages of existing antibiotics is a serious problem. Since countries are skeptical about the public health value of many recently approved antibiotics, there is a mismatch regarding revenue expectations between policymakers and antibiotic innovators. This paper presents important considerations for the design and implementation of antibiotic pull mechanisms. We also propose a multinational model that appears to match the needs of both countries and innovators. Full article
(This article belongs to the Section The Global Need for Effective Antibiotics)
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Article
Molecular and Anti-Microbial Resistance (AMR) Profiling of Methicillin-Resistant Staphylococcus aureus (MRSA) from Hospital and Long-Term Care Facilities (LTCF) Environment
Antibiotics 2021, 10(6), 748; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060748 - 21 Jun 2021
Cited by 1 | Viewed by 641
Abstract
To provide evidence of the cross-contamination of emerging pathogenic microbes in a local network between long-term care facilities (LTCFs) and hospitals, this study emphasizes the molecular typing, the prevalence of virulence genes, and the antibiotic resistance pattern of methicillin-resistant Staphylococcus aureus. MRSA [...] Read more.
To provide evidence of the cross-contamination of emerging pathogenic microbes in a local network between long-term care facilities (LTCFs) and hospitals, this study emphasizes the molecular typing, the prevalence of virulence genes, and the antibiotic resistance pattern of methicillin-resistant Staphylococcus aureus. MRSA isolates were characterized from 246 samples collected from LTCFs, medical tubes of LTCF residents, and hospital environments of two cities, Chiayi and Changhua. Species identification, molecular characterization, and drug resistance analysis were performed. Hospital environments had a higher MRSA detection rate than that of LTCF environments, where moist samples are a hotspot of MRSA habitats, including tube samples from LTCF residents. All MRSA isolates in this study carried the exfoliative toxin eta gene (100%). The majority of MRSA isolates were resistant to erythromycin (76.7%), gentamicin (60%), and ciprofloxacin (55%). The percentage of multidrug-resistant MRSA isolates was approximately 50%. The enterobacterial repetitive intergenic consensus polymerase chain reaction results showed that 18 MRSA isolates belonged to a specific cluster. This implied that genetically similar isolates were spread between hospitals and LTCFs in Changhua city. This study highlights the threat to the health of LTCFs’ residents posed by hospital contact with MRSA. Full article
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Article
Fecal Carriage and Epidemiology of Extended-Spectrum Beta-Lactamase/Carbapenemases Producing Enterobacterales Isolates in Bulgarian Hospitals
Antibiotics 2021, 10(6), 747; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060747 - 20 Jun 2021
Viewed by 562
Abstract
The gastrointestinal tract is an important reservoir of extended spectrum beta-lactamase (ESBL)/carbapenemase-producing Enterobacterales isolates. This study included patients from two Bulgarian hospitals. Overall, 98 ESBL producers (including 68 Escherichia coli and 20 Klebsiella pneumoniae isolates) were detected among 99 hospitalized patients, 212 patients [...] Read more.
The gastrointestinal tract is an important reservoir of extended spectrum beta-lactamase (ESBL)/carbapenemase-producing Enterobacterales isolates. This study included patients from two Bulgarian hospitals. Overall, 98 ESBL producers (including 68 Escherichia coli and 20 Klebsiella pneumoniae isolates) were detected among 99 hospitalized patients, 212 patients at admission, and 92 hospital staff in 42.4%, 24.5%, and 4%, respectively. We observed blaCTX-M-15 in 47% of isolates, blaCTX-M-3 in 39% and blaCTX-M-14 in 11%. Three blaCTX-M-15 positive isolates were also blaKPC-2 positive. High transferability was detected for blaCTX-M-3 carrying plasmids (55%) with L/M and I1 replicon plasmids, followed by CTX-M-14 (36.4%) and CTX-M-15 (27.9%) with IncF plasmids. BlaKPC-2 was carried by FIIAs plasmids. Epidemiology typing revealed 8 K. pneumoniae ST types—ST15(8/20), ST17(4/20), ST37(2/20) and 9 E. coli ST types—ST131 (30.9%, 21/68), ST38 (8/68), ST95(7/68) and ST316(7/68). All ST131 isolates but one was from the highly virulent epidemic clone O25bST131. This is the first report in Bulgaria about ESBL/carbapenemase faecal carriage. We observed high ESBL/carbapenemases prevalence. A predominant number of isolates were members of highly epidemic and virulent PanEuropean clones ST15 K. pneumoniae and O25bST131 E. coli. High antibiotics usage during the COVID pandemic will worsen the situation. Routine screenings and strict infection control measures should be widely implemented. Full article
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Review
Evaluation of Microalgae Antiviral Activity and Their Bioactive Compounds
Antibiotics 2021, 10(6), 746; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060746 - 20 Jun 2021
Cited by 1 | Viewed by 1070
Abstract
During the last year, science has been focusing on the research of antivirally active compounds overall after the SARS-CoV-2 pandemic, which caused a great amount of deaths and the downfall of the economy in 2020. Photosynthetic organisms such as microalgae are known to [...] Read more.
During the last year, science has been focusing on the research of antivirally active compounds overall after the SARS-CoV-2 pandemic, which caused a great amount of deaths and the downfall of the economy in 2020. Photosynthetic organisms such as microalgae are known to be a reservoir of bioactive secondary metabolites; this feature, coupled with the possibility of achieving very high biomass levels without excessive energetic expenses, make microalgae worthy of attention in the search for new molecules with antiviral effects. In this work, the antiviral effects of microalgae against some common human or animal viruses were considered, focusing our attention on some possible effects against SARS-CoV-2. We summed up the data from the literature on microalgae antiviral compounds, from the most common ones, such as lectins, polysaccharides and photosynthetic pigments, to the less known ones, such as unidentified proteins. We have discussed the effects of a microalgae-based genetic engineering approach against some viral diseases. We have illustrated the potential antiviral benefits of a diet enriched in microalgae. Full article
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Review
Antimicrobial Use in COVID-19 Patients in the First Phase of the SARS-CoV-2 Pandemic: A Scoping Review
Antibiotics 2021, 10(6), 745; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060745 - 19 Jun 2021
Viewed by 820
Abstract
This scoping review provides new evidence on the prevalence and patterns of global antimicrobial use in the treatment of COVID-19 patients; identifies the most commonly used antibiotics and clinical scenarios associated with antibiotic prescribing in the first phase of the pandemic; and explores [...] Read more.
This scoping review provides new evidence on the prevalence and patterns of global antimicrobial use in the treatment of COVID-19 patients; identifies the most commonly used antibiotics and clinical scenarios associated with antibiotic prescribing in the first phase of the pandemic; and explores the impact of documented antibiotic prescribing on treatment outcomes in COVID-19 patients. The review complies with PRISMA guidelines for Scoping Reviews and the protocol is registered with the Open Science Framework. In the first six months of the pandemic, there was a similar mean antibiotic prescribing rate between patients with severe or critical illness (75.4%) and patients with mild or moderate illness (75.1%). The proportion of patients prescribed antibiotics without clinical justification was 51.5% vs. 41.9% for patients with mild or moderate illness and those with severe or critical illness. Comparison of patients who were provided antibiotics with a clinical justification with those who were given antibiotics without clinical justification showed lower mortality rates (9.5% vs. 13.1%), higher discharge rates (80.9% vs. 69.3%), and shorter length of hospital stay (9.3 days vs. 12.2 days). In the first 6 months of the pandemic, antibiotics were prescribed for COVID-19 patients regardless of severity of illness. A large proportion of antibiotic prescribing for mild and moderate COVID-19 patients did not have clinical evidence of a bacterial co-infection. Antibiotics may not be beneficial to COVID-19 patients without clinical evidence of a bacterial co-infection. Full article
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Article
ESBL Activity, MDR, and Carbapenem Resistance among Predominant Enterobacterales Isolated in 2019
Antibiotics 2021, 10(6), 744; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060744 - 19 Jun 2021
Cited by 2 | Viewed by 666
Abstract
Antimicrobial-resistance in Enterobacterales is a serious concern in Saudi Arabia. The present study retrospectively analyzed the antibiograms of Enterobacterales identified from 1 January 2019 to 31 December 2019 from a referral hospital in the Aljouf region of Saudi Arabia. The revised document of [...] Read more.
Antimicrobial-resistance in Enterobacterales is a serious concern in Saudi Arabia. The present study retrospectively analyzed the antibiograms of Enterobacterales identified from 1 January 2019 to 31 December 2019 from a referral hospital in the Aljouf region of Saudi Arabia. The revised document of the Centers for Disease Control (CDC) CR-2015 and Magiorakos et al.’s document were used to define carbapenem resistance and classify resistant bacteria, respectively. The association of carbapenem resistance, MDR, and ESBL with various sociodemographic characteristics was assessed by the chi-square test and odds ratios. In total, 617 Enterobacterales were identified. The predominant (n = 533 (86.4%)) isolates consisted of 232 (37.6%), 200 (32.4%), and 101 (16.4%) Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, respectively. In general, 432 (81.0%) and 128 (24.0%) isolates were of MDR and ESBL, respectively. The MDR strains were recovered in higher frequency from intensive care units (OR = 3.24 (1.78–5.91); p < 0.01). E. coli and K. pneumoniae resistance rates to imipenem (2.55 (1.21–5.37); p < 0.01) and meropenem (2.18 (1.01–4.67); p < 0.04), respectively, were significantly higher in winter. The data emphasize that MDR isolates among Enterobacterales are highly prevalent. The studied Enterobacterales exhibited seasonal variation in antimicrobial resistance rates towards carbapenems and ESBL activity. Full article
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Review
Suppressive Antibiotic Treatment in Prosthetic Joint Infections: A Perspective
Antibiotics 2021, 10(6), 743; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060743 - 19 Jun 2021
Viewed by 686
Abstract
The treatment of prosthetic joint infections (PJIs) is a complex matter in which surgical, microbiological and pharmacological aspects must be integrated and, above all, placed in the context of each patient to make the best decision. Sometimes it is not possible to offer [...] Read more.
The treatment of prosthetic joint infections (PJIs) is a complex matter in which surgical, microbiological and pharmacological aspects must be integrated and, above all, placed in the context of each patient to make the best decision. Sometimes it is not possible to offer curative treatment of the infection, and in other cases, the probability that the surgery performed will be successful is considered very low. Therefore, indefinite administration of antibiotics with the intention of “suppressing” the course of the infection becomes useful. For decades, we had little information about suppressive antibiotic treatment (SAT). However, due to the longer life expectancy and increase in orthopaedic surgeries, an increasing number of patients with infected joint prostheses experience complex situations in which SAT should be considered as an alternative. In the last 5 years, several studies attempting to answer the many questions that arise on this issue have been published. The aim of this publication is to review the latest published evidence on SAT. Full article
Article
A New Dermal Substitute Containing Polyvinyl Alcohol with Silver Nanoparticles and Collagen with Hyaluronic Acid: In Vitro and In Vivo Approaches
Antibiotics 2021, 10(6), 742; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060742 - 19 Jun 2021
Viewed by 677
Abstract
The experimental use of poly (alcohol-vinyl) (PVA) as a skin curative is increasing widely. However, the use of this hydrogel is challenging due to its favorable properties for microbiota growth. The association with silver nanoparticles (AgNPs) as an antimicrobial agent turns the match [...] Read more.
The experimental use of poly (alcohol-vinyl) (PVA) as a skin curative is increasing widely. However, the use of this hydrogel is challenging due to its favorable properties for microbiota growth. The association with silver nanoparticles (AgNPs) as an antimicrobial agent turns the match for PVA as a dressing, as it focuses on creating a physical barrier to avoid wound dehydration. When associated with extracellular components, such as the collagen matrix, the device obtained can create the desired biological conditions to act as a skin substitute. This study aimed to analyze the anti-microbiological activity and the in vitro and in vivo responses of a bilaminar device of PVA containing AgNPs associated with a membrane of collagen–hyaluronic acid (col-HA). Additionally, mesenchymal stem cells were cultured in the device to evaluate in vitro responses and in vivo immunomodulatory and healing behavior. The device morphology revealed a porous pattern that favored water retention and in vitro cell adhesion. Controlled wounds in the dorsal back of rat skins revealed a striking skin remodeling with new epidermis fulfilling all previously injured areas after 14 and 28 days. No infections or significant inflammations were observed, despite increased angiogenesis, and no fibrosis-markers were identified as compared to controls. Although few antibacterial activities were obtained, the addition of AgNPs prevented fungal growth. All results demonstrated that the combination of the components used here as a dermal device, chosen according to previous miscellany studies of low/mid-cost biomaterials, can promote skin protection avoiding infections and dehydration, minimize the typical wound inflammatory responses, and favor the cellular healing responses, features that give rise to further clinical trials of the device here developed Full article
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Article
Effect of Antibacterial Root Canal Sealer on Persistent Apical Periodontitis
Antibiotics 2021, 10(6), 741; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060741 - 18 Jun 2021
Viewed by 488
Abstract
The infection of Enterococcus faecalis and its interacting microorganisms in the root canal could cause persistent apical periodontitis (AP). Antibacterial root canal sealer has favorable prospects to inhibit biofilms. The purpose of this study was to investigated the antibacterial effect of root canal [...] Read more.
The infection of Enterococcus faecalis and its interacting microorganisms in the root canal could cause persistent apical periodontitis (AP). Antibacterial root canal sealer has favorable prospects to inhibit biofilms. The purpose of this study was to investigated the antibacterial effect of root canal sealer containing dimethylaminododecyl methacrylate (DMADDM) on persistent AP in beagle dogs for the first time. Persistent AP was established by a two-step infection with Enterococcus faecalis and multi-bacteria (Enterococcus faecalis, Lactobacillus acidophilus, Actinomycesnaeslundii, Streptococcus gordonii). Root canal sealer containing DMADDM (0%, 1.25%, 2.5%) was used to complete root canal filling. The volume of lesions and inflammatory grade in the apical area were evaluated by cone beam computer tomography (CBCT) and hematoxylin-eosin staining. Both Enterococcus-faecalis- and multi-bacteria-induced persistent AP caused severe apical destruction, and there were no significant differences in pathogenicity between them. DMADDM-modified sealer significantly reduced the volume of periapical lesion and inflammatory grade compared with the control group, among them, the therapeutic effect of the 2.5% group was better than the 1.25% group. In addition, E.faecalis-induced reinfection was more sensitive to the 2.5% group than multi-bacteria reinfection. This study shows that root canal sealer containing DMADDM had a remarkable therapeutic effect on persistent AP, especially on E. faecalis-induced reinfection. Full article
(This article belongs to the Special Issue Antimicrobial Material in Dentistry)
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Article
Comparative Genomics of 42 Arcanobacterium phocae Strains
Antibiotics 2021, 10(6), 740; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060740 - 18 Jun 2021
Viewed by 536
Abstract
For the last 13 years, the fur industry in Europe has suffered from epidemic spouts of a severe necrotizing pyoderma. It affects all species currently farmed for fur and causes animal welfare problems and significant losses to the farmers. The causative agent of [...] Read more.
For the last 13 years, the fur industry in Europe has suffered from epidemic spouts of a severe necrotizing pyoderma. It affects all species currently farmed for fur and causes animal welfare problems and significant losses to the farmers. The causative agent of this disease was identified as Arcanobacterium phocae. Previously, this bacterium has been isolated from seals and other marine mammals, apparently causing wound and lung infections. Attempts at antibiotic treatment have been unsuccessful and the current advice on preventing the disease is to cull all animals with clinical signs. This poses an urgent question regarding possible vaccine development, as well as the need for further understanding of the pathogenicity of this organism. This study compared the whole genomes of 42 A. phocae strains isolated from seals, blue foxes, finnraccoons, mink and otter. The sequences were created using the Illumina technology and annotations were done using the RAST pipeline. A phylogenetic analysis identified a clear separation between the seal strains and the fur-animal-derived isolates, but also indicated that the bacterium readily adapts to new environments and host species with reasonable diversity. A pan- and core-genome was created and analyzed for proteins. A further analysis identified several virulence factors as well as multiple putative and secreted proteins of special interest for vaccine development. Full article
(This article belongs to the Special Issue The Genomics of Pathogens)
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Article
Population Pharmacokinetics and Significant Under-Dosing of Anti-Tuberculosis Medications in People with HIV and Critical Illness
Antibiotics 2021, 10(6), 739; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060739 - 18 Jun 2021
Viewed by 673
Abstract
Critical illness from tuberculosis (TB) bloodstream infection results in a high case fatality rate for people living with human immunodeficiency virus (HIV). Critical illness can lead to altered pharmacokinetics and suboptimal drug exposures. We enrolled adults living with HIV and hospitalized with sepsis, [...] Read more.
Critical illness from tuberculosis (TB) bloodstream infection results in a high case fatality rate for people living with human immunodeficiency virus (HIV). Critical illness can lead to altered pharmacokinetics and suboptimal drug exposures. We enrolled adults living with HIV and hospitalized with sepsis, with and without meningitis, in Mbarara, Uganda that were starting first-line anti-TB therapy. Serum was collected two weeks after enrollment at 1-, 2-, 4-, and 6-h post-dose and drug concentrations quantified by validated LC-MS/MS methods. Non-compartmental analyses were used to determine total drug exposure, and population pharmacokinetic modeling and simulations were performed to determine optimal dosages. Eighty-one participants were enrolled. Forty-nine completed pharmacokinetic testing: 18 (22%) died prior to testing, 13 (16%) were lost to follow-up and one had incomplete testing. Isoniazid had the lowest serum attainment, with only 4.1% achieving a target exposure over 24 h (AUC0–24) of 52 mg·h/L despite appropriate weight-based dosing. Simulations to reach target AUC0–24 found necessary doses of rifampin of 1800 mg, pyrazinamide of 2500–3000 mg, and for isoniazid 900 mg or higher. Given the high case fatality ratio of TB-related critical illness in this population, an early higher dose anti-TB therapy should be trialed. Full article
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Article
Use of Antimicrobials among Suspected COVID-19 Patients at Selected Hospitals, Bangladesh: Findings from the First Wave of COVID-19 Pandemic
Antibiotics 2021, 10(6), 738; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060738 - 18 Jun 2021
Cited by 2 | Viewed by 1108
Abstract
Antimicrobials are empirically used in COVID-19 patients resulting in increased antimicrobial resistance. Our objective was to assess antimicrobial use among suspected COVID-19 in-patients. From March to August 2020, we collected data from in-patients of 12 tertiary-level hospitals across Bangladesh. We identified suspected COVID-19 [...] Read more.
Antimicrobials are empirically used in COVID-19 patients resulting in increased antimicrobial resistance. Our objective was to assess antimicrobial use among suspected COVID-19 in-patients. From March to August 2020, we collected data from in-patients of 12 tertiary-level hospitals across Bangladesh. We identified suspected COVID-19 patients; collected information on antimicrobial received within 24 h before and on hospitalization; tested nasopharyngeal swab for SARS-CoV-2 using rRT-PCR. We used descriptive statistics and a regression model for data analysis. Among 1188 suspected COVID-19 patients, 69% were male, 40% had comorbidities, and 53% required oxygen. Antibiotics were used in 92% of patients, 47% within 24 h before, and 89% on admission. Patients also received antiviral (1%) and antiparasitic drugs (3%). Third-generation cephalosporin use was the highest (708; 60%), followed by macrolide (481; 40%), and the majority (853; 78%) who took antibiotics were SARS-CoV-2 negative. On admission, 77% mild and 94% moderately ill patients received antibiotics. Antibiotic use on admission was higher among severely ill patients (AOR = 11.7; 95% CI: 4.5–30.1) and those who received antibiotics within 24 h before hospital admission (AOR = 1.6; 95% CI: 1.0–2.5). Antimicrobial use was highly prevalent among suspected COVID-19 in-patients in Bangladesh. Initiating treatment with third-generation cephalosporin among mild to moderately ill patients was common. Promoting antimicrobial stewardship with monitoring is essential to prevent blanket antibiotic use, thereby mitigating antimicrobial resistance. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Article
Polyhydroxyalkanoate/Antifungal Polyene Formulations with Monomeric Hydroxyalkanoic Acids for Improved Antifungal Efficiency
Antibiotics 2021, 10(6), 737; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060737 - 18 Jun 2021
Cited by 1 | Viewed by 643
Abstract
Novel biodegradable and biocompatible formulations of “old” but “gold” drugs such as nystatin (Nys) and amphotericin B (AmB) were made using a biopolymer as a matrix. Medium chain length polyhydroxyalkanoates (mcl-PHA) were used to formulate both polyenes (Nys and AmB) in the form [...] Read more.
Novel biodegradable and biocompatible formulations of “old” but “gold” drugs such as nystatin (Nys) and amphotericin B (AmB) were made using a biopolymer as a matrix. Medium chain length polyhydroxyalkanoates (mcl-PHA) were used to formulate both polyenes (Nys and AmB) in the form of films (~50 µm). Thermal properties and stability of the materials were not significantly altered by the incorporation of polyenes in mcl-PHA, but polyene containing materials were more hydrophobic. These formulations were tested in vitro against a panel of pathogenic fungi and for antibiofilm properties. The films containing 0.1 to 2 weight % polyenes showed good activity and sustained polyene release for up to 4 days. A PHA monomer, namely 3-hydroxydecanoic acid (C10-OH), was added to the films to achieve an enhanced synergistic effect with polyenes against fungal growth. Mcl-PHA based polyene formulations showed excellent growth inhibitory activity against both Candida yeasts (C. albicans ATCC 1023, C. albicans SC5314 (ATCC MYA-2876), C. parapsilosis ATCC 22019) and filamentous fungi (Aspergillus fumigatus ATCC 13073; Trichophyton mentagrophytes ATCC 9533, Microsporum gypseum ATCC 24102). All antifungal PHA film preparations prevented the formation of a C. albicans biofilm, while they were not efficient in eradication of mature biofilms, rendering them suitable for the transdermal application or as coatings of implants. Full article
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Article
The Synergistic Activity and Optimizing Doses of Tigecycline in Combination with Aminoglycosides against Clinical Carbapenem-Resistant Klebsiella pneumoniae Isolates
Antibiotics 2021, 10(6), 736; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060736 - 17 Jun 2021
Viewed by 655
Abstract
Carbapenem-resistant Enterobacteriaceae (CRE), especially carbapenem-resistant Klebsiella pneumoniae (CRKP), are among the largest pathogenic threats to humans. The available antibiotic treatment options for combating CRKP are limited. Colistin-resistant Enterobacteriaceae (CoRE) have also been reported worldwide, including in Thailand. Therefore, this study aimed (1) to [...] Read more.
Carbapenem-resistant Enterobacteriaceae (CRE), especially carbapenem-resistant Klebsiella pneumoniae (CRKP), are among the largest pathogenic threats to humans. The available antibiotic treatment options for combating CRKP are limited. Colistin-resistant Enterobacteriaceae (CoRE) have also been reported worldwide, including in Thailand. Therefore, this study aimed (1) to determine minimum inhibitory concentrations (MICs) and synergistic activities of antibiotics of CRKP, and (2) to determine the probability target of attainment (PTA) and cumulative fraction of response (CFR) using pharmacokinetic/pharmacodynamic (PK/PD) data. Clinical CRKP isolates were obtained from Phramongkutklao Hospital (June to November 2020). Broth microdilution and checkerboard techniques were used to determine the mono- and synergistic activities of antibiotics. Carbapenemase and mcr-1 genes were also identified by polymerase chain reaction (PCR). The optimal antibiotic regimens were evaluated using Monte Carlo simulations. Forty-nine CRKP isolates were collected, 40 of which were CoRKP strains. The MIC50 and MIC90 of tigecycline, amikacin, and gentamicin were 1 and 2 µg/mL, 4 and 16 µg/mL, and 0.25 and 4 µg/mL, respectively. None of any isolates expressed the mcr-1 gene, whereas blaOXA-48 (53.1%) and blaOXA-48 plus blaNDM (42.9%) were detected. The synergy of tigecycline combined with amikacin or gentamicin was 8.2%. Additive activity was observed in 75.5% of isolates for tigecycline-amikacin and 69.4% for tigecycline-gentamicin, and no antagonism was observed. High-dose antibiotic regimens achieved the PTA target. The general recommended dose of combination regimens began with 200 mg tigecycline and 25 mg/kg amikacin, or 7 mg/kg gentamicin, followed by 100 mg tigecycline every 12 h and 15 mg/kg amikacin or 5 mg/kg gentamicin every 24 h. In conclusion, tigecycline plus aminoglycosides might be a potential regimen against CRKP and CoRKP. The appropriate combination regimen based on MIC-based dose adjustment can improve optimal antibiotic dosing. Further research via clinical studies will be necessary to confirm these results. Full article
(This article belongs to the Section The Global Need for Effective Antibiotics)
Article
Perceptions of Antibiotic Use and Resistance: Are Antibiotics the Dentists’ Anxiolytics?
Antibiotics 2021, 10(6), 735; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060735 - 17 Jun 2021
Cited by 1 | Viewed by 654
Abstract
Background: Antibiotic resistance is a global health crisis. The aim of this study was to explore dentists’ perceptions of antibiotic resistance. Methods: A qualitative method was used. Seventeen dentists practising in the Nancy (Lorraine, France) region were surveyed. They were general practitioners or [...] Read more.
Background: Antibiotic resistance is a global health crisis. The aim of this study was to explore dentists’ perceptions of antibiotic resistance. Methods: A qualitative method was used. Seventeen dentists practising in the Nancy (Lorraine, France) region were surveyed. They were general practitioners or specialised in oral surgery, implantology, or periodontology. The practitioners took part in semi-structured interviews between September 2019 and July 2020. All of the interviews were transcribed in full and analysed thematically. Results: Four major themes have been selected: attitudes of the dentists in regard to the guidelines, clinical factors that influence prescriptions, non-clinical factors that influence prescriptions, and the perception of antibiotic resistance. The dentists stated that they were very concerned regarding the public health issue of antibiotic resistance. However, they often prescribe according to their own interests and habits rather than according to the relevant guidelines. Conclusions: Although dentists are generally well aware of antibiotic resistance, they often do not adequately appreciate the link between their prescribing habits and the phenomenon of antibiotic resistance. Regular updating of practitioners’ knowledge in this regard is necessary, but patients and the general public should also be made more aware of the issue. Full article
(This article belongs to the Special Issue Antimicrobial Use, Resistance and Stewardship)
Article
Evolution of the Gram-Negative Antibiotic Resistance Spiral over Time: A Time-Series Analysis
Antibiotics 2021, 10(6), 734; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060734 - 17 Jun 2021
Viewed by 512
Abstract
We followed up the interplay between antibiotic use and resistance over time in a tertiary-care hospital in Hungary. Dynamic relationships between monthly time-series of antibiotic consumption data (defined daily doses per 100 bed-days) and of incidence densities of Gram-negative bacteria (Escherichia coli [...] Read more.
We followed up the interplay between antibiotic use and resistance over time in a tertiary-care hospital in Hungary. Dynamic relationships between monthly time-series of antibiotic consumption data (defined daily doses per 100 bed-days) and of incidence densities of Gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii) resistant to cephalosporins or carbapenems were followed using vector autoregressive models sequentially built of time-series ending in 2015, 2016, 2017, 2018, and 2019. Relationships with Gram-negative bacteria as a group were fairly stable across years. At species level, association of cephalosporin use and cephalosporin resistance of E. coli was shown in 2015–2017, leading to increased carbapenem use in these years. Association of carbapenem use and carbapenem resistance, as well as of carbapenem resistance and colistin use in case of A. baumannii, were consistent throughout; associations in case of Klebsiella spp. were rarely found; associations in case of P. aeruginosa varied highly across years. This highlights the importance of temporal variations in the interplay between changes in selection pressure and occurrence of competing resistant species. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Practices and Challenges of Veterinary Paraprofessionals in Regards to Antimicrobial Use and Resistance in Animals in Dar Es Salaam, Tanzania
Antibiotics 2021, 10(6), 733; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060733 - 17 Jun 2021
Viewed by 540
Abstract
We conducted a qualitative study to explore the practices and challenges of veterinary paraprofessionals (paravets) on antimicrobial use and resistance in domestic animals. Methods: This was a qualitative study, which involved semi-structured interviews with paravets from the Ilala, Ubungo, Kigamboni, Kinondoni, and Temeke [...] Read more.
We conducted a qualitative study to explore the practices and challenges of veterinary paraprofessionals (paravets) on antimicrobial use and resistance in domestic animals. Methods: This was a qualitative study, which involved semi-structured interviews with paravets from the Ilala, Ubungo, Kigamboni, Kinondoni, and Temeke districts in Dar es Salaam, Tanzania. Results: A total of 40 paravets participated in this study. The majority (72.5%) admitted to having not undergone any formal training on antimicrobial use and/or resistance. Paravets face several challenges, including poor working conditions and having no access to laboratory services to advise on antimicrobial choice and selection. They also face challenges from livestock farmers such as the inability to afford the recommended medicines, the self-prescription of antimicrobials, and poor record keeping. The presence of sub-standard medicine and the lack of guidelines on the appropriate disposal of medicines were also identified as affecting their services. Conclusion: Paravets should be trained in the judicious use of antimicrobials, and the same training should be used to refresh their knowledge on the diagnosis and prevention of infections. The Veterinary Council of Tanzania and other regulatory agencies should assist in addressing the challenges facing paravets that are related to animal health services and the quality of medicines. Full article
(This article belongs to the Special Issue Usage of Antibiotic in Agriculture and Animal Farming)
Article
Development of Bisphosphonate-Conjugated Antibiotics to Overcome Pharmacodynamic Limitations of Local Therapy: Initial Results with Carbamate Linked Sitafloxacin and Tedizolid
Antibiotics 2021, 10(6), 732; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060732 - 17 Jun 2021
Viewed by 746
Abstract
The use of local antibiotics to treat bone infections has been questioned due to a lack of clinical efficacy and emerging information about Staphylococcus aureus colonization of the osteocyte-lacuno canalicular network (OLCN). Here we propose bisphosphonate-conjugated antibiotics (BCA) using a “target and release” [...] Read more.
The use of local antibiotics to treat bone infections has been questioned due to a lack of clinical efficacy and emerging information about Staphylococcus aureus colonization of the osteocyte-lacuno canalicular network (OLCN). Here we propose bisphosphonate-conjugated antibiotics (BCA) using a “target and release” approach to deliver antibiotics to bone infection sites. A fluorescent bisphosphonate probe was used to demonstrate bone surface labeling adjacent to bacteria in a S. aureus infected mouse tibiae model. Bisphosphonate and hydroxybisphosphonate conjugates of sitafloxacin and tedizolid (BCA) were synthesized using hydroxyphenyl and aminophenyl carbamate linkers, respectively. The conjugates were adequately stable in serum. Their cytolytic activity versus parent drug on MSSA and MRSA static biofilms grown on hydroxyapatite discs was established by scanning electron microscopy. Sitafloxacin O-phenyl carbamate BCA was effective in eradicating static biofilm: no colony formation units (CFU) were recovered following treatment with 800 mg/L of either the bisphosphonate or α-hydroxybisphosphonate conjugated drug (p < 0.001). In contrast, the less labile tedizolid N-phenyl carbamate linked BCA had limited efficacy against MSSA, and MRSA. CFU were recovered from all tedizolid BCA treatments. These results demonstrate the feasibility of BCA eradication of S. aureus biofilm on OLCN bone surfaces and support in vivo drug development of a sitafloxacin BCA. Full article
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Article
Clostridioides difficile Infection among Cirrhotic Patients with Variceal Bleeding
Antibiotics 2021, 10(6), 731; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060731 - 17 Jun 2021
Cited by 2 | Viewed by 457
Abstract
Clostridioides difficile infection (CDI) stands as the leading cause of nosocomial infection with high morbidity and mortality rates, causing a major burden on the healthcare system. Driven by antibiotics, it usually affects older patients with chronic disease or immunosuppressed or oncologic management. Variceal [...] Read more.
Clostridioides difficile infection (CDI) stands as the leading cause of nosocomial infection with high morbidity and mortality rates, causing a major burden on the healthcare system. Driven by antibiotics, it usually affects older patients with chronic disease or immunosuppressed or oncologic management. Variceal bleeding secondary to cirrhosis requires antibiotics to prevent bacterial translocation, and thus patients become susceptible to CDI. We aimed to investigate the risk factors for CDI in cirrhotic patients with variceal bleeding following ceftriaxone and the mortality risk in this patient’s population. We retrospectively screened 367 cirrhotic patients with variceal bleeding, from which 25 patients were confirmed with CDI, from 1 January 2017 to 31 December 2019. We found MELD to be the only multivariate predictor for mortality (odds ratio, OR = 1.281, 95% confidence interval, CI: 0.098–1.643, p = 0.042). A model of four predictors (age, days of admission, Charlson index, Child–Pugh score) was generated (area under the receiver operating characteristics curve, AUC = 0.840, 95% CI: 0.758–0.921, p < 0.0001) to assess the risk of CDI exposure. Determining the probability of getting CDI for cirrhotic patients with variceal bleeding could be a tool for doctors in taking decisions, which could be integrated in sustainable public health programs. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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Article
Efficacy of 0.05% Chlorhexidine and 0.05% Cetylpyridinium Chloride Mouthwash to Eliminate Living Bacteria on In Situ Collected Biofilms: An In Vitro Study
Antibiotics 2021, 10(6), 730; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060730 - 17 Jun 2021
Cited by 1 | Viewed by 657
Abstract
Chlorhexidine (CHX) mouthwashes are frequently used as an adjunctive measure for the treatment of periodontitis and peri-implantitis, as well as in patients on maintenance therapy. However, their prolonged use is associated with several side effects. This study aimed at evaluating if a mouthwash [...] Read more.
Chlorhexidine (CHX) mouthwashes are frequently used as an adjunctive measure for the treatment of periodontitis and peri-implantitis, as well as in patients on maintenance therapy. However, their prolonged use is associated with several side effects. This study aimed at evaluating if a mouthwash with a reduced concentration of CHX combined with cetylpyridnium chloride (CPC) was as effective as a conventional CHX mouthwash in the reduction in living cells in oral biofilms attached to hydroxyapatite (HA) and micro-rough titanium (Ti) surfaces. Four healthy volunteers wore a customized acrylic appliance containing HA and Ti discs for in situ plaque accumulation. Biofilms were grown on the discs for 24 or 48 h and then randomly exposed for 60 s to: 0.05% CHX + 0.05% CPC, 0.1% CHX (positive control) or sterile saline (negative control). Viability assay and live-dead staining were performed to quantify bacterial viability and to distinguish live and dead cells, respectively. At both time points, contrary to saline, CHX, both alone and in combination with CPC, exhibited high antibacterial properties and induced a significant reduction in biofilm viability. This study demonstrates the potential of mouthwashes containing a low concentration of CHX combined with CPC as effective antibacterial agents for long-term applications with reduced undesired side effects. Full article
(This article belongs to the Special Issue Oral Microorganisms and Inactivation of Oral Biofilms)
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Erratum
Erratum: Golding et al. 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, 445
Antibiotics 2021, 10(6), 729; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060729 - 17 Jun 2021
Viewed by 472
Abstract
The authors wish to make the following corrections to their published paper [...] Full article
Article
In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes
Antibiotics 2021, 10(6), 728; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060728 - 16 Jun 2021
Cited by 3 | Viewed by 969
Abstract
Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1 [...] Read more.
Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC® 25923, L. monocytogenes ATCC® 19115) and two Gram-negative strains (E. coli ATCC® 25922, P. aeruginosa ATCC® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S.aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study. Full article
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Article
Evaluation of Benzguinols as Next-Generation Antibiotics for the Treatment of Multidrug-Resistant Bacterial Infections
Antibiotics 2021, 10(6), 727; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060727 - 16 Jun 2021
Viewed by 900
Abstract
Our recent focus on the “lost antibiotic” unguinol and related nidulin-family fungal natural products identified two semisynthetic derivatives, benzguinols A and B, with unexpected in vitro activity against Staphylococcus aureus isolates either susceptible or resistant to methicillin. Here, we show further activity of [...] Read more.
Our recent focus on the “lost antibiotic” unguinol and related nidulin-family fungal natural products identified two semisynthetic derivatives, benzguinols A and B, with unexpected in vitro activity against Staphylococcus aureus isolates either susceptible or resistant to methicillin. Here, we show further activity of the benzguinols against methicillin-resistant isolates of the animal pathogen Staphylococcus pseudintermedius, with minimum inhibitory concentration (MIC) ranging 0.5–1 μg/mL. When combined with sub-inhibitory concentrations of colistin, the benzguinols demonstrated synergy against Gram-negative reference strains of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa (MICs of 1–2 μg/mL in the presence of colistin), whereas the benzguinols alone had no activity. Administration of three intraperitoneal (IP) doses of 20 mg/kg benzguinol A or B to mice did not result in any obvious adverse clinical or pathological evidence of acute toxicity. Importantly, mice that received three 20 mg/kg IP doses of benzguinol A or B at 4 h intervals exhibited significantly reduced bacterial loads and longer survival times than vehicle-only treated mice in a bioluminescent S. aureus murine sepsis challenge model. We conclude that the benzguinols are potential candidates for further development for specific treatment of serious bacterial infections as both stand-alone antibiotics and in combination with existing antibiotic classes. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
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Article
Molecular Detection of Carbapenemases in Enterobacterales: A Comparison of Real-Time Multiplex PCR and Whole-Genome Sequencing
Antibiotics 2021, 10(6), 726; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060726 - 16 Jun 2021
Viewed by 466
Abstract
Carbapenem-resistant Enterobacterales are a growing problem in healthcare systems worldwide. While whole-genome sequencing (WGS) has become a powerful tool for analyzing transmission and possible outbreaks, it remains laborious, and the limitations in diagnostic workflows are not well studied. The aim of this study [...] Read more.
Carbapenem-resistant Enterobacterales are a growing problem in healthcare systems worldwide. While whole-genome sequencing (WGS) has become a powerful tool for analyzing transmission and possible outbreaks, it remains laborious, and the limitations in diagnostic workflows are not well studied. The aim of this study was to compare the performance of WGS and real-time multiplex PCR (RT-qPCR) for diagnosing carbapenem-resistant Enterobacterales. In this study, we analyzed 92 phenotypically carbapenem-resistant Enterobacterales, sent to the University Hospital Heidelberg in 2019, by the carbapenem inactivation method (CIM) and compared WGS and RT-qPCR as genotypic carbapenemase detection methods. In total, 80.4% of the collected isolates were identified as carbapenemase producers. For six isolates, discordant results were recorded for WGS, PCR and CIM, as the carbapenemase genes were initially not detected by WGS. A reanalysis using raw reads, rather than assembly, highlighted a coverage issue with failure to detect carbapenemases located in contigs with a coverage lower than 10×, which were then discarded. Our study shows that multiplex RT-qPCR and CIM can be a simple alternative to WGS for basic surveillance of carbapenemase-producing Enterobacterales. Using WGS in clinical workflow has some limitations, especially regarding coverage and sensitivity. We demonstrate that antimicrobial resistance gene detection should be performed on the raw reads or non-curated draft genome to increase sensitivity. Full article
(This article belongs to the Special Issue Carbapenemase-Producing Enterobacterales)
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Article
Counteraction of Biofilm Formation and Antimicrobial Potential of Terminalia catappa Functionalized Silver Nanoparticles against Candida albicans and Multidrug-Resistant Gram-Negative and Gram-Positive Bacteria
Antibiotics 2021, 10(6), 725; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060725 - 16 Jun 2021
Cited by 2 | Viewed by 675
Abstract
Biofilms not only protect bacteria and Candida species from antibiotics, but they also promote the emergence of drug-resistant strains, making eradication more challenging. As a result, novel antimicrobial agents to counteract biofilm formation are desperately needed. In this study, Terminalia catappa leaf extract [...] Read more.
Biofilms not only protect bacteria and Candida species from antibiotics, but they also promote the emergence of drug-resistant strains, making eradication more challenging. As a result, novel antimicrobial agents to counteract biofilm formation are desperately needed. In this study, Terminalia catappa leaf extract (TCE) was used to optimize the TCE-capped silver nanoparticles (TCE-AgNPs) via a one-pot single-step method. Varied concentrations of TCE have yielded different sized AgNPs. The physico-chemical characterization of TCE-AgNPs using UV-Vis, SEM, TEM, FTIR, and Raman spectroscopy have confirmed the formation of nanostructures, their shape and size and plausible role of TCE bio-active compounds, most likely involved in the synthesis as well as stabilization of NPs, respectively. TCE-AgNPs have been tested for antibiofilm and antimicrobial activity against multidrug-resistant Pseudomonas aeruginosa (MDR-PA), methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans using various microbiological protocols. TCE-Ag-NPs−3 significantly inhibits biofilm formation of MDR-PA, MRSA, and C. albicans by 73.7, 69.56, and 63.63%, respectively, at a concentration of 7.8 µg/mL, as determined by crystal violet microtiter assay. Furthermore, SEM micrograph shows that TCE-AgNPs significantly inhibit the colonization and adherence of biofilm forming cells; individual cells with loss of cell wall and membrane integrity were also observed, suggesting that the biofilm architecture and EPS matrix were severely damaged. Moreover, TEM and SEM images showed that TCE-AgNPs brutally damaged the cell wall and membranes of MDR-PA, MRSA, and C. albicans. Additionally, extreme ultrastructural changes such as deformation, disintegration, and separation of cell wall and membrane from the cells, have also been observed, indicating significant loss of membrane and cell wall integrity, which eventually led to cell death. Overall, the research revealed a simple, environmentally friendly, and low-cost method for producing colloidal TCE-AgNPs with promising applications in advanced clinical settings against broad-spectrum biofilm-forming antibiotic-resistant bacteria and candida strains. Full article
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Article
Alteration of Intestinal Microbiome of Clostridioides difficile-Infected Hamsters during the Treatment with Specific Cow Antibodies
Antibiotics 2021, 10(6), 724; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060724 - 16 Jun 2021
Cited by 1 | Viewed by 630
Abstract
Clostridioides difficile infection (CDI) often develops after pretreatment with antibiotics, which can lead to damage of the intestinal microbiome. The approach of this study was to use specific polyclonal antibodies isolated from the milk of immunized cows to treat CDI, in contrast to [...] Read more.
Clostridioides difficile infection (CDI) often develops after pretreatment with antibiotics, which can lead to damage of the intestinal microbiome. The approach of this study was to use specific polyclonal antibodies isolated from the milk of immunized cows to treat CDI, in contrast to the standard application of nonspecific antibiotics. To gain a deeper understanding of the role of the microbiome in the treatment of CDI with bovine antibodies, stool and intestinal fluid samples of hamsters were collected in large quantities from various treatments (>400 samples). The results show that the regeneration of the microbiome instantly begins with the start of the antibody treatment, in contrast to the Vancomycin-treated group where the diversity decreased significantly during the treatment duration. All antibody-treated hamsters that survived the initial phase also survived the entire study period. The results also show that the regeneration of the microbiome was not an antibody-induced regeneration, but a natural regeneration that occurred because no microbiota-inactivating substances were administered. In conclusion, the treatment with bovine antibodies is a functional therapy for both the acute treatment and the prevention of recurrence in hamsters and could meet the urgent need for CDI treatment alternatives in humans. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection)
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Perspective
Basics for Improved Use of Phages for Therapy
Antibiotics 2021, 10(6), 723; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060723 - 16 Jun 2021
Viewed by 693
Abstract
Blood-borne therapeutic phages and phage capsids increasingly reach therapeutic targets as they acquire more persistence, i.e., become more resistant to non-targeted removal from blood. Pathogenic bacteria are targets during classical phage therapy. Metastatic tumors are potential future targets, during use of drug delivery [...] Read more.
Blood-borne therapeutic phages and phage capsids increasingly reach therapeutic targets as they acquire more persistence, i.e., become more resistant to non-targeted removal from blood. Pathogenic bacteria are targets during classical phage therapy. Metastatic tumors are potential future targets, during use of drug delivery vehicles (DDVs) that are phage derived. Phage therapy has, to date, only sometimes been successful. One cause of failure is low phage persistence. A three-step strategy for increasing persistence is to increase (1) the speed of lytic phage isolation, (2) the diversity of phages isolated, and (3) the effectiveness and speed of screening phages for high persistence. The importance of high persistence-screening is illustrated by our finding here of persistence dramatically higher for coliphage T3 than for its relative, coliphage T7, in murine blood. Coliphage T4 is more persistent, long-term than T3. Pseudomonas chlororaphis phage 201phi2-1 has relatively low persistence. These data are obtained with phages co-inoculated and separately assayed. In addition, highly persistent phage T3 undergoes dispersal to several murine organs and displays tumor tropism in epithelial tissue (xenografted human oral squamous cell carcinoma). Dispersal is an asset for phage therapy, but a liability for phage-based DDVs. We propose increased focus on phage persistence—and dispersal—screening. Full article
(This article belongs to the Special Issue Phage Therapy to Control Pathogenic Bacteria)
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Article
Engineering of the CHAPk Staphylococcal Phage Endolysin to Enhance Antibacterial Activity against Stationary-Phase Cells
Antibiotics 2021, 10(6), 722; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060722 - 16 Jun 2021
Cited by 1 | Viewed by 738
Abstract
Bacteriophage endolysins and their derivatives have strong potential as antibacterial agents considering the increasing prevalence of antibiotic resistance in common bacterial pathogens. The peptidoglycan degrading peptidase CHAPk, a truncated derivate of staphylococcal phage K endolysin (LysK), has proven efficacy in preventing and disrupting [...] Read more.
Bacteriophage endolysins and their derivatives have strong potential as antibacterial agents considering the increasing prevalence of antibiotic resistance in common bacterial pathogens. The peptidoglycan degrading peptidase CHAPk, a truncated derivate of staphylococcal phage K endolysin (LysK), has proven efficacy in preventing and disrupting staphylococcal biofilms. Nevertheless, the concentration of CHAPk required to eliminate populations of stationary-phase cells was previously found to be four-fold higher than that for log-phase cells. Moreover, CHAPk-mediated lysis of stationary-phase cells was observed to be slower than for log-phase cultures. In the present study, we report the fusion of a 165 amino acid fragment containing CHAPk with a 136 amino acid fragment containing the cell-binding domain of the bacteriocin lysostaphin to create a chimeric enzyme designated CHAPk-SH3blys in the vector pET28a. The chimeric protein was employed in concentrations as low as 5 μg/mL, producing a reduction in turbidity in 7-day-old cultures, whereas the original CHAPk required at least 20 μg/mL to achieve this. Where 7-day old liquid cultures were used, the chimeric enzyme exhibited a 16-fold lower MIC than CHAPk. In terms of biofilm prevention, a concentration of 1 μg/mL of the chimeric enzyme was sufficient, whereas for CHAPk, 125 μg/mL was needed. Moreover, the chimeric enzyme exhibited total biofilm disruption when 5 μg/mL was employed in 4-h assays, whereas CHAPk could only partially disrupt the biofilms at this concentration. This study demonstrates that the cell-binding domain from lysostaphin can make the phage endolysin CHAPk more effective against sessile staphylococcal cells. Full article
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Article
Speciation and Antibiotic Susceptibilities of Coagulase Negative Staphylococci Isolated from Ocular Infections
Antibiotics 2021, 10(6), 721; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060721 - 16 Jun 2021
Viewed by 521
Abstract
Coagulase-negative staphylococci (CoNS) are frequently occurring ocular opportunistic pathogens that are not easily identifiable to the species level. The goal of this study was to speciate CoNS and document antibiotic susceptibilities from cases of endophthalmitis (n = 50), keratitis (n = [...] Read more.
Coagulase-negative staphylococci (CoNS) are frequently occurring ocular opportunistic pathogens that are not easily identifiable to the species level. The goal of this study was to speciate CoNS and document antibiotic susceptibilities from cases of endophthalmitis (n = 50), keratitis (n = 50), and conjunctivitis/blepharitis (n = 50) for empiric therapy. All 150 isolates of CoNS were speciated using (1) API Staph (biochemical system), (2) Biolog GEN III Microplates (phenotypic substrate system), and (3) DNA sequencing of the sodA gene. Disk diffusion antibiotic susceptibilities for topical and intravitreal treatment were determined based on serum standards. CoNS identification to the species level by all three methods indicated that S. epidermidis was the predominant species of CoNS isolated from cases of endophthalmitis (84–90%), keratitis (80–86%), and conjunctivitis/blepharitis (62–68%). Identifications indicated different distributions of CoNS species among endophthalmitis (6), keratitis (10), and conjunctivitis/blepharitis (13). Antibiotic susceptibility profiles support empiric treatment of endophthalmitis with vancomycin, and keratitis treatment with cefazolin or vancomycin. There was no clear antibiotic choice for conjunctivitis/blepharitis. S. epidermidis was the most frequently found CoNS ocular pathogen, and infection by other CoNS appears to be less specific and random. Antibiotic resistance does not appear to be a serious problem associated with CoNS. Full article
(This article belongs to the Special Issue Ocular Surface Infection and Antimicrobials)
Article
Rapid and Accurate Detection of Escherichia coli and Klebsiella pneumoniae Strains Susceptible/Resistant to Cotrimoxazole through Evaluation of Cell Elongation
Antibiotics 2021, 10(6), 720; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060720 - 15 Jun 2021
Viewed by 441
Abstract
Trimethoprim-sulfamethoxazole is a well-known antibiotic that inhibits folic acid synthesis, a topic of renewed interest. Since resistant strains are increasingly more common, an early and accurate discrimination of susceptibility may assure confident therapy. Two morphological assays were performed in Escherichia coli (n [...] Read more.
Trimethoprim-sulfamethoxazole is a well-known antibiotic that inhibits folic acid synthesis, a topic of renewed interest. Since resistant strains are increasingly more common, an early and accurate discrimination of susceptibility may assure confident therapy. Two morphological assays were performed in Escherichia coli (n = 50; 27 non-susceptible) and Klebsiella pneumoniae (n = 52; 18 non-susceptible). First, the strains were incubated with the CLSI breakpoint of cotrimoxazole for 150 min, which induced cell lengthening in the susceptible strains. Second, the bacteria were incubated with mitomycin C (MMC) (0.5 mg/L) for 120 min to induce a SOS-linked cell enlargement higher than that obtained by cotrimoxazole alone. When cotrimoxazole was added 30 min before MMC, the inhibition of folic acid synthesis in the susceptible strain resulted in the suppression of MMC-induced extra elongation. In the non-susceptible strains, folic acid synthesis continued despite the antibiotic, so that the MMC-induced extra cell lengthening could not be impeded. Whereas the first assay resulted in five false negatives and four false positives of resistance, the results of the second assay matched those of the conventional antibiogram. This simple morphological procedure is performed in 2 h and 45 min and may allow a rapid selection of useful and relatively inexpensive therapy, thereby preserving the newer broad-spectrum antibiotics. Full article
(This article belongs to the Special Issue Rapid Diagnostics of the Antimicrobial Resistance)
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