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Antibiotics, Volume 12, Issue 5 (May 2023) – 150 articles

Cover Story (view full-size image): Aspects of recent approaches to countering antimicrobial resistance through the design and development of antibacterial drug combinations, multiple action-based small molecule antibacterials, and prodrugs are discussed in this review, together with some suggestions for future work. The areas covered, amongst others, include nanoparticulates in drug combinations, single-molecule non-cleavable hybrids, and selective activation mechanisms for prodrugs. Many opportunities exist for innovative developments in the general multi-targeting area for antibacterials to help address antimicrobial resistance challenges. View this paper
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12 pages, 1918 KiB  
Article
Genome-Based Retrospective Analysis of a Providencia stuartii Outbreak in Rome, Italy: Broad Spectrum IncC Plasmids Spread the NDM Carbapenemase within the Hospital
by Valerio Capitani, Gabriele Arcari, Alessandra Oliva, Federica Sacco, Gaia Menichincheri, Linda Fenske, Riccardo Polani, Giammarco Raponi, Guido Antonelli and Alessandra Carattoli
Antibiotics 2023, 12(5), 943; https://doi.org/10.3390/antibiotics12050943 - 22 May 2023
Cited by 2 | Viewed by 1720
Abstract
Providencia stuartii is a member of the Morganellaceae family, notorious for its intrinsic resistance to several antibiotics, including last-resort drugs such as colistin and tigecycline. Between February and March 2022, a four-patient outbreak sustained by P. stuartii occurred in a hospital in Rome. [...] Read more.
Providencia stuartii is a member of the Morganellaceae family, notorious for its intrinsic resistance to several antibiotics, including last-resort drugs such as colistin and tigecycline. Between February and March 2022, a four-patient outbreak sustained by P. stuartii occurred in a hospital in Rome. Phenotypic analyses defined these strains as eXtensively Drug-Resistant (XDR). Whole-genome sequencing was performed on the representative P. stuartii strains and resulted in fully closed genomes and plasmids. The genomes were highly related phylogenetically and encoded various virulence factors, including fimbrial clusters. The XDR phenotype was primarily driven by the presence of the blaNDM-1 metallo-β-lactamase alongside the rmtC 16S rRNA methyltransferase, conferring resistance to most β-lactams and every aminoglycoside, respectively. These genes were found on an IncC plasmid that was highly related to an NDM-IncC plasmid retrieved from a ST15 Klebsiella pneumoniae strain circulating in the same hospital two years earlier. Given its ability to acquire resistance plasmids and its intrinsic resistance mechanisms, P. stuartii is a formidable pathogen. The emergence of XDR P. stuartii strains poses a significant public health threat. It is essential to monitor the spread of these strains and develop new strategies for their control and treatment. Full article
(This article belongs to the Special Issue Advances in Plasmid Mediated Antimicrobial Resistance)
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16 pages, 1357 KiB  
Article
Anaerobic Gram-Negative Bacteria: Role as a Reservoir of Antibiotic Resistance
by Anshul Sood, Pallab Ray and Archana Angrup
Antibiotics 2023, 12(5), 942; https://doi.org/10.3390/antibiotics12050942 - 22 May 2023
Cited by 2 | Viewed by 1880
Abstract
Background: Anaerobic Gram-negative bacteria (AGNB) play a significant role as both pathogens and essential members of the human microbiota. Despite their clinical importance, there remains limited understanding regarding their antimicrobial resistance (AMR) patterns. This knowledge gap poses challenges in effectively managing AGNB-associated infections, [...] Read more.
Background: Anaerobic Gram-negative bacteria (AGNB) play a significant role as both pathogens and essential members of the human microbiota. Despite their clinical importance, there remains limited understanding regarding their antimicrobial resistance (AMR) patterns. This knowledge gap poses challenges in effectively managing AGNB-associated infections, as empirical treatment approaches may not adequately address the evolving resistance landscape. To bridge this research gap, we conducted a comprehensive study aimed at exploring the role of human AGNB as a reservoir of AMR. This can provide valuable insights for the prevention and management of anaerobic infections. Methods: We studied the prevalence of AMR and AMR determinants conferring resistance to metronidazole (nimE), imipenem (cfiA), piperacillin–tazobactam (cepA), cefoxitin (cfxA), clindamycin (ermF), chloramphenicol (cat) and mobile genetic elements (MGEs) such as cfiAIS and IS1186 associated with the cfiA and nim gene expression. These parameters were studied in Bacteroides spp., Fusobacterium spp., Prevotella spp., Veillonella spp., Sutterella spp., and other clinical AGNB. Results: Resistance to metronidazole, clindamycin, imipenem, piperacillin–tazobactam, cefoxitin and chloramphenicol was 29%, 33.5%, 0.5%, 27.5%, 26.5% and 0%, respectively. The presence of resistance genes, viz., nim, ermF, cfiA, cepA, cfxA, was detected in 24%, 33.5%, 10%, 9.5%, 21.5% isolates, respectively. None of the tested isolates showed the presence of a cat gene and MGEs, viz., cfiAIS and IS1186. The highest resistance to all antimicrobial agents was exhibited by Bacteroides spp. The association between resistant phenotypes and genotypes was complete in clindamycin, as all clindamycin-resistant isolates showed the presence of ermF gene, and none of the susceptible strains harbored this gene; similarly, all isolates were chloramphenicol-susceptible and also lacked the cat gene, whereas the association was low among imipenem and piperacillin–tazobactam. Metronidazole and imipenem resistance was seen to be dependent on insertion sequences for the expression of AMR genes. A constrained co-existence of cepA and cfiA gene in B. fragilis species was seen. Based on the absence and presence of the cfiA gene, we divided B. fragilis into two categories, Division I (72.6%) and Division II (27.3%), respectively. Conclusion: AGNB acts as a reservoir of specific AMR genes, which may pose a threat to other anaerobes due to functional compatibility and acquisition of these genes. Thus, AST-complying standard guidelines must be performed periodically to monitor the local and institutional susceptibility trends, and rational therapeutic strategies must be adopted to direct empirical management. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria, 2nd Edition)
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15 pages, 309 KiB  
Article
Antimicrobial Resistance of Escherichia coli Isolates from Livestock and the Environment in Extensive Smallholder Livestock Production Systems in Ethiopia
by Biruk Alemu Gemeda, Barbara Wieland, Gezahegn Alemayehu, Theodore J. D. Knight-Jones, Hiwot Desta Wodajo, Misgana Tefera, Adem Kumbe, Abebe Olani, Shubisa Abera and Kebede Amenu
Antibiotics 2023, 12(5), 941; https://doi.org/10.3390/antibiotics12050941 - 22 May 2023
Cited by 3 | Viewed by 1832
Abstract
The objective of this study was to characterize the distribution of antimicrobial resistance (AMR) of Escherichia coli (E. coli) isolated from livestock feces and soil in smallholder livestock systems. A cross-sectional study was carried out sampling 77 randomly selected households in [...] Read more.
The objective of this study was to characterize the distribution of antimicrobial resistance (AMR) of Escherichia coli (E. coli) isolated from livestock feces and soil in smallholder livestock systems. A cross-sectional study was carried out sampling 77 randomly selected households in four districts representing two agroecologies and production systems. E. coli was isolated and the susceptibility to 15 antimicrobials was assessed. Of 462 E. coli isolates tested, resistance to at least one antimicrobial was detected in 52% (43.7–60.8) of isolates from cattle fecal samples, 34% (95% CI, 26.2–41.8) from sheep samples, 58% (95% CI, 47.9–68.2) from goat samples and 53% (95% CI, 43.2–62.4) from soil samples. AMR patterns for E. coli from livestock and soil showed some similarities, with the highest prevalence of resistance detected against streptomycin (33%), followed by amoxycillin/clavulanate (23%) and tetracycline (8%). The odds of detecting E. coli resistance to ≥2 antimicrobials in livestock fecal samples were nearly three times (Odd Ratio—OR: 2.9; 95% CI, 1.72–5.17; p = 0.000) higher in lowland pastoral than in highland mixed crop–livestock production systems. These findings provide insights into the status of resistance in livestock and soil, and associated risk factors in low-resource settings in Ethiopia. Full article
(This article belongs to the Special Issue Antimicrobial Use and Resistance in Food-Producing Animals)
11 pages, 509 KiB  
Article
Chemical Composition of the Cinnamomum malabatrum Leaf Essential Oil and Analysis of Its Antioxidant, Enzyme Inhibitory and Antibacterial Activities
by Aswathi Moothakoottil Kuttithodi, Arunaksharan Narayanankutty, Naduvilthara U. Visakh, Joice Tom Job, Berin Pathrose, Opeyemi Joshua Olatunji, Ahmed Alfarhan and Varsha Ramesh
Antibiotics 2023, 12(5), 940; https://doi.org/10.3390/antibiotics12050940 - 22 May 2023
Cited by 5 | Viewed by 1590
Abstract
Cinnamomum species are a group of plants belonging to the Lauraceae family. These plants are predominantly used as spices in various food preparations and other culinary purposes. Furthermore, these plants are attributed to having cosmetic and pharmacological potential. Cinnamomum malabatrum (Burm. f.) J. [...] Read more.
Cinnamomum species are a group of plants belonging to the Lauraceae family. These plants are predominantly used as spices in various food preparations and other culinary purposes. Furthermore, these plants are attributed to having cosmetic and pharmacological potential. Cinnamomum malabatrum (Burm. f.) J. Presl is an underexplored plant in the Cinnamomum genus. The present study evaluated the chemical composition by a GC-MS analysis and antioxidant properties of the essential oil from C. malabatrum (CMEO). Further, the pharmacological effects were determined as radical quenching, enzyme inhibition and antibacterial activity. The results of the GC-MS analysis indicated the presence of 38.26 % of linalool and 12.43% of caryophyllene in the essential oil. Furthermore, the benzyl benzoate (9.60%), eugenol (8.75%), cinnamaldehyde (7.01%) and humulene (5.32%) were also present in the essential oil. The antioxidant activity was indicated by radical quenching properties, ferric-reducing potential and lipid peroxidation inhibition ex vivo. Further, the enzyme-inhibitory potential was confirmed against the enzymes involved in diabetes and diabetic complications. The results also indicated the antibacterial activity of these essential oils against different Gram-positive and Gram-negative bacteria. The disc diffusion method and minimum inhibitory concentration analysis revealed a higher antibacterial potential for C. malabatrum essential oil. Overall, the results identified the predominant chemical compounds of C. malabatrum essential oil and its biological and pharmacological effects. Full article
(This article belongs to the Special Issue Antioxidant and Antibacterial Activity of Plant Extracts)
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25 pages, 7985 KiB  
Review
From Gene to Transcript and Peptide: A Deep Overview on Non-Specific Lipid Transfer Proteins (nsLTPs)
by Carlos André dos Santos-Silva, José Ribamar Costa Ferreira-Neto, Vinícius Costa Amador, João Pacífico Bezerra-Neto, Lívia Maria Batista Vilela, Eliseu Binneck, Mireli de Santana Rêgo, Manassés Daniel da Silva, Ana Luiza Trajano Mangueira de Melo, Rahisa Helena da Silva and Ana Maria Benko-Iseppon
Antibiotics 2023, 12(5), 939; https://doi.org/10.3390/antibiotics12050939 - 21 May 2023
Cited by 1 | Viewed by 1807
Abstract
Non-specific lipid transfer proteins (nsLTPs) stand out among plant-specific peptide superfamilies due to their multifaceted roles in plant molecular physiology and development, including their protective functions against pathogens. These antimicrobial agents have demonstrated remarkable efficacy against bacterial and fungal pathogens. The discovery of [...] Read more.
Non-specific lipid transfer proteins (nsLTPs) stand out among plant-specific peptide superfamilies due to their multifaceted roles in plant molecular physiology and development, including their protective functions against pathogens. These antimicrobial agents have demonstrated remarkable efficacy against bacterial and fungal pathogens. The discovery of plant-originated, cysteine-rich antimicrobial peptides such as nsLTPs has paved the way for exploring the mentioned organisms as potential biofactories for synthesizing antimicrobial compounds. Recently, nsLTPs have been the focus of a plethora of research and reviews, providing a functional overview of their potential activity. The present work compiles relevant information on nsLTP omics and evolution, and it adds meta-analysis of nsLTPs, including: (1) genome-wide mining in 12 plant genomes not studied before; (2) latest common ancestor analysis (LCA) and expansion mechanisms; (3) structural proteomics, scrutinizing nsLTPs’ three-dimensional structure/physicochemical characteristics in the context of nsLTP classification; and (4) broad nsLTP spatiotemporal transcriptional analysis using soybean as a study case. Combining a critical review with original results, we aim to integrate high-quality information in a single source to clarify unexplored aspects of this important gene/peptide family. Full article
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10 pages, 676 KiB  
Article
Outcome of Irrigation and Debridement with Topical Antibiotic Delivery Using Antibiotic-Impregnated Calcium Hydroxyapatite for the Management of Periprosthetic Hip Joint Infection
by Hiroki Wakabayashi, Masahiro Hasegawa, Yohei Naito, Shine Tone and Akihiro Sudo
Antibiotics 2023, 12(5), 938; https://doi.org/10.3390/antibiotics12050938 - 21 May 2023
Cited by 1 | Viewed by 1177
Abstract
We assessed the clinical results of irrigation and debridement (I&D) with antibiotic-impregnated calcium hydroxyapatite (CHA) as a novel antibiotic delivery system for the treatment of prosthetic-joint-associated infection (PJI) after total hip arthroplasty (THA). Thirteen patients (14 hips) treated with I&D for PJI after [...] Read more.
We assessed the clinical results of irrigation and debridement (I&D) with antibiotic-impregnated calcium hydroxyapatite (CHA) as a novel antibiotic delivery system for the treatment of prosthetic-joint-associated infection (PJI) after total hip arthroplasty (THA). Thirteen patients (14 hips) treated with I&D for PJI after THA at our institution between 1997 and 2017 were retrospectively evaluated. The study group included four men (five hips) and nine women, with an average age of 66.3 years. Four patients (five hips) had symptoms of infection within less than 3 weeks; however, nine patients had symptoms of infection over 3 weeks. All patients received I&D with antibiotic-impregnated CHA in the surrounding bone. In two hips (two cups and one stem), cup and/or stem revision were performed with re-implantation because of implant loosening. In ten patients (11 hips), vancomycin hydrochloride was impregnated in the CHA. The average duration of follow-up was 8.1 years. Four patients included in this study died of other causes, with an average follow-up of 6.7 years. Eleven of thirteen patients (12 of 14 hips) were successfully treated, and no signs of infection were observed at the latest follow-up. In two patients (two hips) for whom treatment failed, infection was successfully treated with two-stage re-implantation. Both patients had diabetes mellitus and symptoms of infection over 3 weeks. Eighty-six percent of patients were successfully treated. No complications were observed with this antibiotic-impregnated CHA. I&D treatment with antibiotic-impregnated CHA produced a higher rate of success in patients with PJI after THA. Full article
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12 pages, 1182 KiB  
Article
Chronic Suppressive Antibiotic Treatment for Staphylococcal Bone and Joint Implant–Related Infections
by Giancarlo Ceccarelli, Beatrice Perciballi, Alessandro Russo, Paolo Martini, Francesco Marchetti, Marco Rivano Capparuccia, Giancarlo Iaiani, Silvia Fabris, Massimo Ciccozzi, Ciro Villani, Mario Venditti, Gabriella D’Ettorre and Daniele De Meo
Antibiotics 2023, 12(5), 937; https://doi.org/10.3390/antibiotics12050937 - 21 May 2023
Cited by 1 | Viewed by 1659
Abstract
Prosthetic joint infection (PJI) and fracture-related infection (FRI) are difficult-to-treat conditions in patients with severe comorbidity or significant surgical risk. In cases not eligible for standard strategy, debridement procedures with the retention of prosthesis or internal fixation device, combined with long-term antibiotic treatment [...] Read more.
Prosthetic joint infection (PJI) and fracture-related infection (FRI) are difficult-to-treat conditions in patients with severe comorbidity or significant surgical risk. In cases not eligible for standard strategy, debridement procedures with the retention of prosthesis or internal fixation device, combined with long-term antibiotic treatment and subsequent indefinite chronic oral antimicrobial suppression (COAS), can be the only reasonable choice. The aim of this study was to investigate the role of COAS and its follow-up in the management of these cases. We retrospectively analyzed a cohort of 16 patients with a follow-up of at least 6 months (mean age 75 yo, 9F, 7M, 11 PJI, 5 FRI). All microbiological isolates were tetracycline-susceptible staphylococci and for this reason a minocycline-based COAS was adopted after debridement and 3 months of antibiogram-guided antibiotic treatment. Patient monitoring was carried out on a clinical basis, with bimonthly execution of the inflammation indices and serial radiolabeled leukocyte scintigraphy (LS). The overall median time of COAS follow-up was 15 months (min 6–max 30). Moreover, 62.5% of patients were still taking COAS with no relapse after cure at the last evaluation available. Clinical failure with a relapse of the infection was observed in 37.5% of patients; interestingly, 50% of them had previously stopped COAS due to side effects of the antibiotic used. In the COAS follow-up, a combination of clinical, laboratory and LS evaluation seems to monitor the infection properly. COAS can be considered as an interesting approach in patients not suitable for standard treatments of PJI or FRI but it requires careful monitoring. Full article
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9 pages, 223 KiB  
Communication
Clinical Outcome of Cefiderocol for Infections with Carbapenem-Resistant Organisms
by Monirul I. Sajib, Melinda Monteforte and Roderick Go
Antibiotics 2023, 12(5), 936; https://doi.org/10.3390/antibiotics12050936 - 21 May 2023
Cited by 1 | Viewed by 1572
Abstract
Cefiderocol is a novel cephalosporin recently approved by the FDA to aid clinicians in the fight against multidrug-resistant (including carbapenem-resistant) gram-negative organisms. The primary objective of this study is to evaluate the 14- and 28-day mortality associated with cefiderocol. We performed a retrospective [...] Read more.
Cefiderocol is a novel cephalosporin recently approved by the FDA to aid clinicians in the fight against multidrug-resistant (including carbapenem-resistant) gram-negative organisms. The primary objective of this study is to evaluate the 14- and 28-day mortality associated with cefiderocol. We performed a retrospective chart review of all adult patients admitted at Stony Brook University Hospital between October 2020 and December 2021 and received cefiderocol for at least 3 days. Patients were excluded if they received more than one course of cefiderocol therapy or remained hospitalized at the time of this study. A total of 22 patients met the inclusion criteria. The all-cause mortality on day 28 for all patients was 13.6%, whereas this rate for patients with BSI was 0%, with cUTI was 0% and with LRTI was 16.7%. The all-cause mortality on day 28 for patients who received the dual antibiotics (in conjunction with cefiderocol) was 0%, compared to 25% for patients who only received cefiderocol (p = 0.25). We noted treatment failure in two patients (9.1%). Our findings suggest that cefiderocol could possibly be associated with lower all-cause mortality than previously thought. In our study, we did not find any significant difference between cefiderocol’s use in combination with another antibacterial agent and its use as a monotherapy. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
16 pages, 2674 KiB  
Systematic Review
Clinical Equivalence between Generic Versus Branded Antibiotics: Systematic Review and Meta-Analysis
by André Cotia, Haliton Alves Oliveira Junior, Jessica Y. Matuoka and Ícaro Boszczowski
Antibiotics 2023, 12(5), 935; https://doi.org/10.3390/antibiotics12050935 - 21 May 2023
Viewed by 1561
Abstract
Regulatory authorities authorize the clinical use of generic drugs (GD) based on bioequivalence studies, which consist of the evaluation of pharmacokinetics after a single dose in vitro or in healthy individuals. There are few data on clinical equivalence between generic and branded antibiotics. [...] Read more.
Regulatory authorities authorize the clinical use of generic drugs (GD) based on bioequivalence studies, which consist of the evaluation of pharmacokinetics after a single dose in vitro or in healthy individuals. There are few data on clinical equivalence between generic and branded antibiotics. Our aim was to synthesize and analyze the available evidence on the clinical efficacy and safety of generic antibiotics compared to their original formulations. A systematic review was performed on Medline (PubMed) and Embase and validated through Epistemonikos and Google Scholar. The last search was conducted on 30 June 2022. Meta-analyses of clinical cure and mortality outcomes were performed. One randomized clinical trial (RCT) and 10 non-randomized intervention studies were included. No differences in clinical cure were observed between groups in the meta-analysis (OR = 0.89, 95% CI [0.61–1.28]; I2 = 70%, p = 0.005). No difference was observed between groups when considering the use of carbapenems for overall mortality (OR = 0.99, 95% CI [0.63–1.55]; I2 = 78%) or death associated with infections (OR = 0.79, 95% CI [0.48–1.29], I2 = 67%). Most of the studies were observational, and the duration of follow-up, the characteristics of the participants, and the sites of infections were heterogeneous. Due to the uncertainty of the evidence, it is not possible to contraindicate the use of generics, which is an important strategy to expand access. Full article
(This article belongs to the Special Issue Diagnostics, Treatment and Prevention of Bacterial Infections)
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15 pages, 930 KiB  
Article
Cross-Sectional Study for Detection and Risk Factor Analysis of ESBL-Producing Avian Pathogenic Escherichia coli Associated with Backyard Chickens in Pakistan
by Muhammad Adnan Saeed, Muhammad Saqlain, Usman Waheed, Syed Ehtisham-ul-Haque, Aman Ullah Khan, Aziz ur Rehman, Muhammad Sajid, Farhan Ahmad Atif, Heinrich Neubauer and Hosny El-Adawy
Antibiotics 2023, 12(5), 934; https://doi.org/10.3390/antibiotics12050934 - 20 May 2023
Cited by 4 | Viewed by 2102
Abstract
The increasing incidence of extended-spectrum β-lactamase (ESBL)-producing Escherichia (E.) coli in backyard chicken farming in Pakistan is of serious concern. This study aimed to assess the prevalence, antimicrobial resistance patterns and risk factors associated with ESBL avian pathogenic E. coli (APEC) [...] Read more.
The increasing incidence of extended-spectrum β-lactamase (ESBL)-producing Escherichia (E.) coli in backyard chicken farming in Pakistan is of serious concern. This study aimed to assess the prevalence, antimicrobial resistance patterns and risk factors associated with ESBL avian pathogenic E. coli (APEC) isolated from backyard chickens in the Jhang district, Punjab, Pakistan. In total, 320 cloacal swabs were collected from four breeds of backyard chicken (Aseel, Golden, Misri and Necked Neck). ESBL E. coli were phenotypically identified using double disc synergy test (DDST) and corresponding genes were confirmed by multiplex polymerase chain reaction (mPCR). Out of the 320 samples, 164 (51.3%) were confirmed as E. coli, while 74 (45.1%) were characterized as ESBL E. coli. The frequency of isolation of ESBL E. coli was highest in Aseel chickens (35.1%). Of the 164 confirmed E. coli, 95.1%, 78.6%, 76.8%, 71.3%, 70.1%, 68.9%, 60.4% and 57.3% were resistant against tylosin, doxycycline, cefotaxime, enrofloxacin, colistin, trimethoprim/sulfamethoxazole, chloramphenicol and gentamicin, respectively. The ESBL gene types detected and their corresponding proportions were blaCTX-M (54.1 %, 40/74), blaTEM, (12.2%, 9/74) and co-existence (blaCTX-M and blaTEM) were shown in 33.8% (25/74). The blaCTX-M gene sequence showed homology to blaCTX-M-15 from clinical isolates. The mean multiple antibiotic resistance index (MARI) was found to be higher among ESBL E. coli (0.25) when compared to non-ESBL E. coli (0.17). Both free-range husbandry management system (p = 0.02, OR: 30.00, 95% CI = 1.47–611.79) and high antimicrobial usage in the last 6 months (p = 0.01, OR: 25.17, 95% CI = 1.81–348.71) were found significantly associated with isolation of ESBL-producing E. coli in the tested samples using binary logistic regression analysis. This study confirmed the potential of backyard chickens as a reservoir for ESBL E. coli in the Jhang district, Punjab, Pakistan. Full article
(This article belongs to the Special Issue Antibiotics Used in Animals Disease Control)
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14 pages, 2082 KiB  
Article
Cold Atmospheric Plasma Exerts Antimicrobial Effects in a 3D Skin Model of Cutaneous Candidiasis
by Sarah Fink, Michael Fischer, Sebastian Spange, Oliver Beier, Kerstin Horn, Jörg Tittelbach and Cornelia Wiegand
Antibiotics 2023, 12(5), 933; https://doi.org/10.3390/antibiotics12050933 - 19 May 2023
Viewed by 1175
Abstract
Cutaneous candidiasis is characterized by an overgrowth of Candida leading to skin inflammation and infection. Similar to bacteria, Candida can develop tolerance to common antifungal drugs. Cold atmospheric plasma (CAP), with its proven antimicrobial properties, offers a promising alternative to the prevailing methods. [...] Read more.
Cutaneous candidiasis is characterized by an overgrowth of Candida leading to skin inflammation and infection. Similar to bacteria, Candida can develop tolerance to common antifungal drugs. Cold atmospheric plasma (CAP), with its proven antimicrobial properties, offers a promising alternative to the prevailing methods. Because of plasma heterogeneity each new device must be tested individually for its effectiveness. Antimicrobial activity is usually studied using planktonic microorganisms or animal models, making it difficult to extrapolate the results to the human system. Therefore, a 3D skin model of cutaneous candidiasis for the antimicrobial testing of CAP was established. First, the reaction of the 3D-skin model to Candida infection was examined using various histological and molecular–biological methods. Infection with C. albicans resulted in increased expression and secretion of pro-inflammatory cytokines and augmented expression of antimicrobial peptides. Within 48 h, hyphal growth spread throughout the model and caused tissue damage. Second, the CAP treatment was employed. It was shown that CAP significantly reduced the spread of the yeast in the infected skin models as well as decreased the expression and secretion of the infection markers. The plasma device exhibited a high antifungal activity by completely inhibiting hyphal growth and reducing inflammation at the highest treatment duration. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
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17 pages, 2735 KiB  
Article
Performance of a Pilot-Scale Continuous Flow Ozone-Based Hospital Wastewater Treatment System
by Takashi Azuma, Miwa Katagiri, Naobumi Sasaki, Makoto Kuroda and Manabu Watanabe
Antibiotics 2023, 12(5), 932; https://doi.org/10.3390/antibiotics12050932 - 19 May 2023
Cited by 2 | Viewed by 1816
Abstract
Antimicrobial resistance (AMR) is becoming a global concern. Recently, research has emerged to evaluate the human and environmental health implications of wastewater from medical facilities and to identify acceptable wastewater treatment methods. In this study, a disinfection wastewater treatment system using an ozone-based [...] Read more.
Antimicrobial resistance (AMR) is becoming a global concern. Recently, research has emerged to evaluate the human and environmental health implications of wastewater from medical facilities and to identify acceptable wastewater treatment methods. In this study, a disinfection wastewater treatment system using an ozone-based continuous flow system was installed in a general hospital located in Japan. The effectiveness of antimicrobial-resistant bacteria (ARB) and antimicrobials in mitigating the environmental impact of hospital wastewater was evaluated. Metagenomic analysis was conducted to characterize the microorganisms in the wastewater before and after treatment. The results demonstrated that ozone treatment enables effective inactivation of general gut bacteria, including Bacteroides, Prevotella, Escherichia coli, Klebsiella, DNA molecules, and ARGs, as well as antimicrobials. Azithromycin and doxycycline removal rates were >99% immediately after treatment, and levofloxacin and vancomycin removal rates remained between 90% and 97% for approximately one month. Clarithromycin was more readily removed than the other antimicrobials (81–91%), and no clear removal trend was observed for ampicillin. Our findings provide a better understanding of the environmental management of hospital wastewater and enhance the effectiveness of disinfection wastewater treatment systems at medical facilities for mitigating the discharge of pollutants into aquatic environments. Full article
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11 pages, 379 KiB  
Article
Evaluating the Counseling Standards and Ability of Pharmacy Staff to Detect Antibiotic-Drugs Interactions: A Simulated Client Study from Pakistan
by Muhammad Majid Aziz, Muhammad Fawad Rasool, Muteb Alanazi, Tareq Nafea Alharby, Jowaher Alanazi and Bader Huwaimel
Antibiotics 2023, 12(5), 931; https://doi.org/10.3390/antibiotics12050931 - 19 May 2023
Cited by 2 | Viewed by 1340
Abstract
Effective and safe medication use can be maximized by providing medication counseling, which aims to optimize therapeutic results. This approach improves the effectiveness of antibacterial treatment, reduces treatment expenses, and mitigates the emergence of antimicrobial resistance. No research from Pakistan has been previously [...] Read more.
Effective and safe medication use can be maximized by providing medication counseling, which aims to optimize therapeutic results. This approach improves the effectiveness of antibacterial treatment, reduces treatment expenses, and mitigates the emergence of antimicrobial resistance. No research from Pakistan has been previously documented. The purpose of this research was to evaluate both the quality of antibiotic counseling provided and the level of understanding exhibited by pharmacy employees with regard to interactions involving antibiotic medications. Using a simulated client method, two scenarios were used to assess 562 pharmacies that were systematically selected. Scenario 1 focused the counseling for use of prescribed medicines with non-prescribed antibiotics. Scenario2 indicated counseling provision for prescribed antibiotics that have possible antibiotic–drug interactions. The evaluation of counseling skills was also conducted. The analysis involved the use of descriptive statistics and chi-square tests. Only 34.1% of simulated clients received medication counseling directly; 45% received it on request. About 31.2% of clients were referred to a physician without counseling. The most frequently provided information was therapy dose (81.6%) and duration (57.4%). More than half (54.0%) of clients were asked about disease duration, but drug storage was ignored. Insufficient information was provided about side effects (1.1%) and antibiotic–drug interactions (1.4%). Most (54.3%) clients were instructed about dietary or lifestyle modifications. Only 1.9% of clients received information about drug administration route. No information was provided about other medication during therapy, effect of medicine withdrawal, and compliance to medication. The current level of antibiotic counseling within Pakistani community pharmacies is inadequate and requires the attention of medical authorities. Professional training of staff could improve counseling. Full article
(This article belongs to the Special Issue Antibiotics in Health and Diseases)
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15 pages, 3413 KiB  
Article
Exploring Alternative Pathways to Target Bacterial Type II Topoisomerases Using NBTI Antibacterials: Beyond Halogen-Bonding Interactions
by Maja Kokot, Doroteja Novak, Irena Zdovc, Marko Anderluh, Martina Hrast and Nikola Minovski
Antibiotics 2023, 12(5), 930; https://doi.org/10.3390/antibiotics12050930 - 18 May 2023
Cited by 2 | Viewed by 1254
Abstract
Novel bacterial topoisomerase inhibitors (NBTIs) are a new class of antibacterial agents that target bacterial type II topoisomerases (DNA gyrase and topoisomerase IV). Our recently disclosed crystal structure of an NBTI ligand in complex with DNA gyrase and DNA revealed that the halogen [...] Read more.
Novel bacterial topoisomerase inhibitors (NBTIs) are a new class of antibacterial agents that target bacterial type II topoisomerases (DNA gyrase and topoisomerase IV). Our recently disclosed crystal structure of an NBTI ligand in complex with DNA gyrase and DNA revealed that the halogen atom in the para position of the phenyl right hand side (RHS) moiety is able to establish strong symmetrical bifurcated halogen bonds with the enzyme; these are responsible for the excellent enzyme inhibitory potency and antibacterial activity of these NBTIs. To further assess the possibility of any alternative interactions (e.g., hydrogen-bonding and/or hydrophobic interactions), we introduced various non-halogen groups at the p-position of the phenyl RHS moiety. Considering the hydrophobic nature of amino acid residues delineating the NBTI’s binding pocket in bacterial topoisomerases, we demonstrated that designed NBTIs cannot establish any hydrogen-bonding interactions with the enzyme; hydrophobic interactions are feasible in all respects, while halogen-bonding interactions are apparently the most preferred. Full article
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13 pages, 1576 KiB  
Article
Prevalence and Antibiotic Resistance Pattern of Streptococcus, Staphylococcus, Neisseria meningitidis and Enterobacteriaceae in Two Reference Hospitals of Yaoundé: An Overview before and during COVID-19 Pandemic Era
by Cecile Ingrid Djuikoue, Willy Yamdeu Djonkouh, Cavin Epie Bekolo, Rodrigue Kamga Wouambo, Raspail Carrel Founou, Paule Dana Djouela Djoulako, Gilder Tonfak Temgoua, Benjamin D. Thumamo Pokam, Nicolas Antoine-Moussiaux and Teke R. Apalata
Antibiotics 2023, 12(5), 929; https://doi.org/10.3390/antibiotics12050929 - 18 May 2023
Cited by 1 | Viewed by 1905
Abstract
The COVID-19 pandemic led to tremendously use of antimicrobial due to the lack of proper treatment strategies, raising concerns about emergence of antimicrobial resistance (AMR). This study aimed at determining the prevalence and antibiotic resistance pattern of selected bacteria isolates in 02 referral [...] Read more.
The COVID-19 pandemic led to tremendously use of antimicrobial due to the lack of proper treatment strategies, raising concerns about emergence of antimicrobial resistance (AMR). This study aimed at determining the prevalence and antibiotic resistance pattern of selected bacteria isolates in 02 referral health facilities in Yaoundé before and during the COVID-19 pandemic era. We conducted a retrospective study over a period of 03 years (from 1 January 2019 to 31 December 2021) in the bacteriology units of the Central and General Hospitals of Yaoundé, Cameroon. Data on bacteria genera (Streptococcus, Staphylococcus, Neisseria meningitidis and Enterobacteriaceae) as well as their corresponding specifics antibiotics: Cefixime, azythromycin and erythromycin were obtained from laboratory records. The global resistance rate of bacteria as well as their correlation with antibiotics according to COVID-19 pandemic era was determined and compared. For p < 0.05, the difference was statistically significant. In all, 426 bacterial strains were included. It appeared that the highest number of bacteria isolates and lowest rate of bacterial resistance were recorded during the pre-COVID-19 period in 2019 (160 isolates vs. 58.8% resistance rate). Conversely, lower bacteria strains but greater resistance burden were recorded during the pandemic era (2020 and 2021) with the lowest bacteria amount and peak of bacteria resistance registered in 2020, the year of COVID-19 onset (120 isolates vs. 70% resistance in 2020 and 146 isolates vs. 58.9% resistance in 2021). In contrast to almost all others groups of bacteria where the resistance burden was quite constant or decreasing over years, the Enterobacteriaceae exhibited greater resistance rate during the pandemic period [60% (48/80) in 2019 to 86.9% (60/69) in 2020 and 64.5% (61/95) in 2021)]. Concerning antibiotics, unlike erythromycin, azythromycin related resitance increased during the pandemic period and the resistance to Cefixim tends to decrease the year of the pandemic onset (2020) and re-increase one year therafter. A significant association was found between resistant Enterobacteriaceae strains and cefixime (R = 0.7; p = 0.0001) and also, between resistant Staphylococcus strains and erythromycin (R = 0.8; p = 0.0001). These retrospective data showed a herogeneous MDR bacteria rate and antibiotic resistance pattern over time before and during the COVID-19 pandemic era suggesting that antimicrobial resistance needs to be more closely monitored. Full article
(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)
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16 pages, 3243 KiB  
Article
Adaptive Laboratory Evolution of Staphylococcus aureus Resistance to Vancomycin and Daptomycin: Mutation Patterns and Cross-Resistance
by Vladimir Gostev, Olga Kalinogorskaya, Julia Sopova, Ofelia Sulian, Polina Chulkova, Maria Velizhanina, Irina Tsvetkova, Irina Ageevets, Vladimir Ageevets and Sergey Sidorenko
Antibiotics 2023, 12(5), 928; https://doi.org/10.3390/antibiotics12050928 - 18 May 2023
Cited by 1 | Viewed by 1882
Abstract
Vancomycin and daptomycin are first-line drugs for the treatment of complicated methicillin-resistant Staphylococcus aureus (MRSA) infections, including bacteremia. However, their effectiveness is limited not only by their resistance to each antibiotic but also by their associated resistance to both drugs. It is unknown [...] Read more.
Vancomycin and daptomycin are first-line drugs for the treatment of complicated methicillin-resistant Staphylococcus aureus (MRSA) infections, including bacteremia. However, their effectiveness is limited not only by their resistance to each antibiotic but also by their associated resistance to both drugs. It is unknown whether novel lipoglycopeptides can overcome this associated resistance. Resistant derivatives from five S. aureus strains were obtained during adaptive laboratory evolution with vancomycin and daptomycin. Both parental and derivative strains were subjected to susceptibility testing, population analysis profiles, measurements of growth rate and autolytic activity, and whole-genome sequencing. Regardless of whether vancomycin or daptomycin was selected, most of the derivatives were characterized by a reduced susceptibility to daptomycin, vancomycin, telavancin, dalbavancin, and oritavancin. Resistance to induced autolysis was observed in all derivatives. Daptomycin resistance was associated with a significant reduction in growth rate. Resistance to vancomycin was mainly associated with mutations in the genes responsible for cell wall biosynthesis, and resistance to daptomycin was associated with mutations in the genes responsible for phospholipid biosynthesis and glycerol metabolism. However, mutations in walK and mprF were detected in derivatives selected for both antibiotics. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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10 pages, 2840 KiB  
Communication
The COVID-19 Pandemic Enhanced the Decade-Long Trend of the Decreasing Utilization of Antibiotics
by Christian Tanislav, Josef Rosenbauer and Karel Kostev
Antibiotics 2023, 12(5), 927; https://doi.org/10.3390/antibiotics12050927 - 18 May 2023
Viewed by 1317
Abstract
Purpose/Introduction: A decline in antibiotic (AB) prescriptions was reported during the coronavirus 2019 (COVID-19) pandemic. Therefore, we investigated AB utilization during the COVID-19 pandemic using data from a large database in Germany. Methods: AB prescriptions in the Disease Analyzer database (IQVIA) were analyzed [...] Read more.
Purpose/Introduction: A decline in antibiotic (AB) prescriptions was reported during the coronavirus 2019 (COVID-19) pandemic. Therefore, we investigated AB utilization during the COVID-19 pandemic using data from a large database in Germany. Methods: AB prescriptions in the Disease Analyzer database (IQVIA) were analyzed for each year between 2011 and 2021. Descriptive statistics were used to assess developments in relation to age group, sex, and antibacterial substances. Infection incidence rates were also investigated. Results: In total, 1,165,642 patients received antibiotic prescriptions during the entire study period (mean age: 51.8; SD: 18.4 years; 55.3% females). AB prescriptions started to decline in 2015 (505 patients per practice), and this development persisted until 2021 (2020: 300 patients per practice and 2021: 266 patients per practice). The sharpest drop was observed in 2020 and occurred in both women and men (27.4% and 30.1%). In the youngest age group (≤30), the decrease was −56%, while in the age group >70, it was −38%. The number of patients with prescriptions for fluoroquinolones dropped the most, falling from 117 in 2015 to 35 in 2021 (−70%), followed by macrolides (−56%) and tetracyclines (−56%). In 2021, 46% fewer patients were diagnosed with acute lower respiratory infections, 19% fewer with chronic lower respiratory diseases, and just 10% fewer with diseases of the urinary system. Conclusion: AB prescriptions decreased more in the first year (2020) of the COVID-19 pandemic than infectious diseases did. While the factor of older age influenced this trend negatively, it remained unaffected by the factor of sex and the selected antibacterial substance. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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15 pages, 1120 KiB  
Article
Characterization of blaKPC-2 and blaNDM-1 Plasmids of a K. pneumoniae ST11 Outbreak Clone
by Camila Maria dos Santos Boralli, Julian Andres Paganini, Rodrigo Silva Meneses, Camila Pacheco Silveira Martins da Mata, Edna Marilea Meireles Leite, Anita C. Schürch, Fernanda L. Paganelli, Rob J. L. Willems and Ilana Lopes Baratella Cunha Camargo
Antibiotics 2023, 12(5), 926; https://doi.org/10.3390/antibiotics12050926 - 18 May 2023
Cited by 3 | Viewed by 1800
Abstract
The most common resistance mechanism to carbapenems is the production of carbapenemases. In 2021, the Pan American Health Organization warned of the emergence and increase in new carbapenemase combinations in Enterobacterales in Latin America. In this study, we characterized four Klebsiella pneumoniae isolates [...] Read more.
The most common resistance mechanism to carbapenems is the production of carbapenemases. In 2021, the Pan American Health Organization warned of the emergence and increase in new carbapenemase combinations in Enterobacterales in Latin America. In this study, we characterized four Klebsiella pneumoniae isolates harboring blaKPC and blaNDM from an outbreak during the COVID-19 pandemic in a Brazilian hospital. We assessed their plasmids’ transference ability, fitness effects, and relative copy number in different hosts. The K. pneumoniae BHKPC93 and BHKPC104 strains were selected for whole genome sequencing (WGS) based on their pulsed-field gel electrophoresis profile. The WGS revealed that both isolates belong to ST11, and 20 resistance genes were identified in each isolate, including blaKPC-2 and blaNDM-1. The blaKPC gene was present on a ~56 Kbp IncN plasmid and the blaNDM-1 gene on a ~102 Kbp IncC plasmid, along with five other resistance genes. Although the blaNDM plasmid contained genes for conjugational transfer, only the blaKPC plasmid conjugated to E. coli J53, without apparent fitness effects. The minimum inhibitory concentrations (MICs) of meropenem/imipenem against BHKPC93 and BHKPC104 were 128/64 and 256/128 mg/L, respectively. Although the meropenem and imipenem MICs against E. coli J53 transconjugants carrying the blaKPC gene were 2 mg/L, this was a substantial increment in the MIC relative to the original J53 strain. The blaKPC plasmid copy number was higher in K. pneumoniae BHKPC93 and BHKPC104 than in E. coli and higher than that of the blaNDM plasmids. In conclusion, two ST11 K. pneumoniae isolates that were part of a hospital outbreak co-harbored blaKPC-2 and blaNDM-1. The blaKPC-harboring IncN plasmid has been circulating in this hospital since at least 2015, and its high copy number might have contributed to the conjugative transfer of this particular plasmid to an E. coli host. The observation that the blaKPC-containing plasmid had a lower copy number in this E. coli strain may explain why this plasmid did not confer phenotypic resistance against meropenem and imipenem. Full article
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15 pages, 980 KiB  
Article
Identifying Predictors Associated with Risk of Death or Admission to Intensive Care Unit in Internal Medicine Patients with Sepsis: A Comparison of Statistical Models and Machine Learning Algorithms
by Antonio Mirijello, Andrea Fontana, Antonio Pio Greco, Alberto Tosoni, Angelo D’Agruma, Maria Labonia, Massimiliano Copetti, Pamela Piscitelli, Salvatore De Cosmo and on behalf of the Internal Medicine Sepsis Study Group
Antibiotics 2023, 12(5), 925; https://doi.org/10.3390/antibiotics12050925 - 18 May 2023
Cited by 3 | Viewed by 1431
Abstract
Background: Sepsis is a time-dependent disease: the early recognition of patients at risk for poor outcome is mandatory. Aim: To identify prognostic predictors of the risk of death or admission to intensive care units in a consecutive sample of septic patients, comparing different [...] Read more.
Background: Sepsis is a time-dependent disease: the early recognition of patients at risk for poor outcome is mandatory. Aim: To identify prognostic predictors of the risk of death or admission to intensive care units in a consecutive sample of septic patients, comparing different statistical models and machine learning algorithms. Methods: Retrospective study including 148 patients discharged from an Italian internal medicine unit with a diagnosis of sepsis/septic shock and microbiological identification. Results: Of the total, 37 (25.0%) patients reached the composite outcome. The sequential organ failure assessment (SOFA) score at admission (odds ratio (OR): 1.83; 95% confidence interval (CI): 1.41–2.39; p < 0.001), delta SOFA (OR: 1.64; 95% CI: 1.28–2.10; p < 0.001), and the alert, verbal, pain, unresponsive (AVPU) status (OR: 5.96; 95% CI: 2.13–16.67; p < 0.001) were identified through the multivariable logistic model as independent predictors of the composite outcome. The area under the receiver operating characteristic curve (AUC) was 0.894; 95% CI: 0.840–0.948. In addition, different statistical models and machine learning algorithms identified further predictive variables: delta quick-SOFA, delta-procalcitonin, mortality in emergency department sepsis, mean arterial pressure, and the Glasgow Coma Scale. The cross-validated multivariable logistic model with the least absolute shrinkage and selection operator (LASSO) penalty identified 5 predictors; and recursive partitioning and regression tree (RPART) identified 4 predictors with higher AUC (0.915 and 0.917, respectively); the random forest (RF) approach, including all evaluated variables, obtained the highest AUC (0.978). All models’ results were well calibrated. Conclusions: Although structurally different, each model identified similar predictive covariates. The classical multivariable logistic regression model was the most parsimonious and calibrated one, while RPART was the easiest to interpret clinically. Finally, LASSO and RF were the costliest in terms of number of variables identified. Full article
(This article belongs to the Special Issue Antibiotic Resistance and Antimicrobial Use in Elderly Patients)
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14 pages, 2894 KiB  
Article
Cytotoxicity and Antibiofilm Activity of Silver-Polypropylene Nanocomposites
by Denise Bellisario, Loredana Santo, Fabrizio Quadrini, Maryam Hassiba, Nour Bader, Shazeda H. Chowdhury, Mohammad K. Hassan and Susu M. Zughaier
Antibiotics 2023, 12(5), 924; https://doi.org/10.3390/antibiotics12050924 - 17 May 2023
Cited by 2 | Viewed by 1319
Abstract
The development of biocompatible nanomaterials that interface with human skin and tissue is critical for advancing prosthetics and other therapeutic medical needs. In this perspective, the development of nanoparticles with cytotoxicity and antibiofilm properties and biocompatibility characteristics are important. Metallic silver (Ag) exhibits [...] Read more.
The development of biocompatible nanomaterials that interface with human skin and tissue is critical for advancing prosthetics and other therapeutic medical needs. In this perspective, the development of nanoparticles with cytotoxicity and antibiofilm properties and biocompatibility characteristics are important. Metallic silver (Ag) exhibits good biocompatibility, but it is often challenging to integrate it into a nanocomposite without compromising its antibiofilm properties for optimal applications. In this study, new polymer nanocomposites (PNCs) with ultra-low filling content (0.0023–0.046 wt%) of Ag nanoplates were manufactured and tested. The cytotoxicity and antibiofilm activity of different composites with polypropylene (PP) matrix were examined. At first, PNCs surface were analyzed by means of AFM (atomic force microscopy) with phase contrast evaluation and FTIR (Fourier-transform infrared spectroscopy) to study the Ag nanoplates distribution. Subsequently, the cytotoxicity and growth properties of biofilms were assessed by MTT assay protocol and detection of nitric oxide radicals. Antibacterial and antibiofilm activities were measured against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (K. pneumoniae). The PNCs with silver exhibited antibiofilm activity although they did not inhibit regular planktonic bacterial growth. Moreover, the PNCs were not cytotoxic to mammalian cells and did not induce significant immune response. These features reveal the potential of the PNCs developed in this study for usage in fabrication of prosthetics and other smart structures for biomedical applications. Full article
(This article belongs to the Special Issue Nanoparticles as Antibacterial/Antibiofilm Agents)
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16 pages, 1139 KiB  
Article
Challenges in the Implementation of the NeoOBS Study, a Global Pragmatic Observational Cohort Study, to Investigate the Aetiology and Management of Neonatal Sepsis in the Hospital Setting
by Amy Riddell, Aislinn Cook, Nathalie Khavessian, Sally Ellis, Davide Bilardi, Erika Correia, Tomislav Kostyanev, Alessandra Nardone, Neal Russell, Tuba Vilken, Wolfgang Stohr, Bethou Adhisivam, Iana Rosa Alves de Moraes, Nawshad Uddin Ahmed, Adrie Bekker, Eitan Naaman Berezin, Suppawat Boonkasidecha, Cristina G. Carvalheiro, Prachi Chauhan, Sara Chiurchiù, Elisavet Chorafa, Angela Dramowski, Madhusudhan DS, Jinxing Feng, Shengnan Jia, Yuan Kong, Mary Kyohere, Angeliki Kontou, Sorasak Lochindarat, Maia De Luca, Aripfani Mphaphuli, Marisa M. Mussi-Pinhata, Sheila Murunga, Firdose Lambey Nakwa, Sushma Nangia, Erinah Nassolo, Ngoc Thi Bin Hoang, Christina W. Obiero, Linus Olson, Wang Ping, Nishad Plakkal, Priyanka Prasad, Kanchana Preedisripipat, Sheikh Wasik Rahman, Tiffany Seef, Pra-ornsuda Sukrakanchana, Reenu Thomas, Zhang Yu, Qiaoru Zhang, A. Sarah Walker, Julia Bielicki, Paul T. Heath, Michael Sharland and Tatiana Munera-Huertasadd Show full author list remove Hide full author list
Antibiotics 2023, 12(5), 923; https://doi.org/10.3390/antibiotics12050923 - 17 May 2023
Cited by 1 | Viewed by 2141
Abstract
Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that [...] Read more.
Neonatal sepsis is a significant cause of mortality and morbidity in low- and middle-income countries. To deliver high-quality data studies and inform future trials, it is crucial to understand the challenges encountered when managing global multi-centre research studies and to identify solutions that can feasibly be implemented in these settings. This paper provides an overview of the complexities faced by diverse research teams in different countries and regions, together with actions implemented to achieve pragmatic study management of a large multi-centre observational study of neonatal sepsis. We discuss specific considerations for enrolling sites with different approval processes and varied research experience, structures, and training. Implementing a flexible recruitment strategy and providing ongoing training were necessary to overcome these challenges. We emphasize the attention that must be given to designing the database and monitoring plans. Extensive data collection tools, complex databases, tight timelines, and stringent monitoring arrangements can be problematic and might put the study at risk. Finally, we discuss the complexities added when collecting and shipping isolates and the importance of having a robust central management team and interdisciplinary collaborators able to adapt easily and make swift decisions to deliver the study on time and to target. With pragmatic approaches, appropriate training, and good communication, these challenges can be overcome to deliver high-quality data from a complex study in challenging settings through a collaborative research network. Full article
(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)
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29 pages, 5844 KiB  
Article
Effect of Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones in the Virulence of Resistant Bacteria
by Mariana C. Almeida, Nikoletta Szemerédi, Fernando Durães, Solida Long, Diana I. S. P. Resende, Paulo Martins da Costa, Madalena Pinto, Gabriella Spengler and Emília Sousa
Antibiotics 2023, 12(5), 922; https://doi.org/10.3390/antibiotics12050922 - 17 May 2023
Viewed by 1701
Abstract
Drug resistance is rising to alarming levels, constituting one of the major threats to global health. The overexpression of efflux pumps and the formation of biofilms constitute two of the most common resistance mechanisms, favoring the virulence of bacteria. Therefore, the research and [...] Read more.
Drug resistance is rising to alarming levels, constituting one of the major threats to global health. The overexpression of efflux pumps and the formation of biofilms constitute two of the most common resistance mechanisms, favoring the virulence of bacteria. Therefore, the research and development of effective antimicrobial agents that can also counteract resistance mechanisms are extremely important. Pyrazino[2,1-b]quinazoline-3,6-diones, from marine and terrestrial organisms and simpler synthetic analogues, were recently disclosed by us as having relevant antimicrobial properties. In this study, using a multi-step approach, it was possible to synthesize new pyrazino[2,1-b]quinazoline-3,6-diones focusing on compounds with fluorine substituents since, to the best of our knowledge, the synthesis of fluorinated fumiquinazoline derivatives had not been attempted before. The new synthesized derivatives were screened for antibacterial activity and, along with previously synthetized pyrazino[2,1-b]quinazoline-3,6-diones, were characterized for their antibiofilm and efflux-pump-inhibiting effects against representative bacterial species and relevant resistant clinical strains. Several compounds showed relevant antibacterial activity against the tested Gram-positive bacterial species with MIC values in the range of 12.5–77 μM. Furthermore, some derivatives showed promising results as antibiofilm agents in a crystal violet assay. The results of the ethidium bromide accumulation assay suggested that some compounds could potentially inhibit bacterial efflux pumps. Full article
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14 pages, 2168 KiB  
Article
Evaluation of Five Host Inflammatory Biomarkers in Early Diagnosis of Ventilator-Associated Pneumonia in Critically Ill Children: A Prospective Single Center Cohort Study
by Maria Sdougka, Maria Simitsopoulou, Elena Volakli, Asimina Violaki, Vivian Georgopoulou, Argiro Ftergioti, Emmanuel Roilides and Elias Iosifidis
Antibiotics 2023, 12(5), 921; https://doi.org/10.3390/antibiotics12050921 - 17 May 2023
Cited by 1 | Viewed by 1376
Abstract
Background: Early diagnosis of ventilator-associated pneumonia (VAP) remains a challenge due to subjective clinical criteria and the low discriminative power of diagnostic tests. We assessed whether rapid molecular diagnostics in combination with Clinically Pulmonary Index Score (CPIS) scoring, microbiological surveillance and biomarker measurements [...] Read more.
Background: Early diagnosis of ventilator-associated pneumonia (VAP) remains a challenge due to subjective clinical criteria and the low discriminative power of diagnostic tests. We assessed whether rapid molecular diagnostics in combination with Clinically Pulmonary Index Score (CPIS) scoring, microbiological surveillance and biomarker measurements of PTX-3, SP-D, s-TREM, PTX-3, IL-1β and IL-8 in the blood or lung could improve the accuracy of VAP diagnosis and follow-up in critically ill children. Methods: A prospective pragmatic study in a Pediatric Intensive Care Unit (PICU) was conducted on ventilated critically ill children divided into two groups: high and low suspicion of VAP according to modified Clinically Pulmonary Index Score (mCPIS). Blood and bronchial samples were collected on days 1, 3, 6 and 12 after event onset. Rapid diagnostics were used for pathogen identification and ELISA for PTX-3, SP-D, s-TREM, IL-1β and IL-8 measurements. Results: Among 20 enrolled patients, 12 had a high suspicion (mCPIS > 6), and 8 had a low suspicion of VAP (mCPIS < 6); 65% were male; and 35% had chronic disease. IL-1β levels at day 1 correlated significantly with the number of mechanical ventilation days (rs = 0.67, p < 0.001) and the PICU stay (r = 0.66; p < 0.002). No significant differences were found in the levels of the other biomarkers between the two groups. Mortality was recorded in two patients with high VAP suspicion. Conclusions: PTX-3, SP-D, s-TREM, IL-1β and IL-8 biomarkers could not discriminate patients with a high or low suspicion of VAP diagnosis. Full article
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12 pages, 5848 KiB  
Article
Facile Implementation of Antimicrobial Coatings through Adhesive Films (Wraps) Demonstrated with Cuprous Oxide Coatings
by Saeed Behzadinasab, Myra D. Williams, Joseph O. Falkinham III and William A. Ducker
Antibiotics 2023, 12(5), 920; https://doi.org/10.3390/antibiotics12050920 - 17 May 2023
Cited by 1 | Viewed by 1130
Abstract
Antimicrobial coatings have a finite lifetime because of wear, depletion of the active ingredient, or surface contamination that produces a barrier between the pathogen and the active ingredient. The limited lifetime means that facile replacement is important. Here, we describe a generic method [...] Read more.
Antimicrobial coatings have a finite lifetime because of wear, depletion of the active ingredient, or surface contamination that produces a barrier between the pathogen and the active ingredient. The limited lifetime means that facile replacement is important. Here, we describe a generic method for rapidly applying and reapplying antimicrobial coatings to common-touch surfaces. The method is to deposit an antimicrobial coating on a generic adhesive film (wrap), and then to attach that modified wrap to the common-touch surface. In this scenario, the adhesion of the wrap and antimicrobial efficacy are separated and can be optimized independently. We demonstrate the fabrication of two antimicrobial wraps, both using cuprous oxide (Cu2O) as the active ingredient. The first uses polyurethane (PU) as the polymeric binder and the second uses polydopamine (PDA). Our antimicrobial PU/Cu2O and PDA/Cu2O wraps, respectively, kill >99.98% and >99.82% of the human pathogen, P. aeruginosa, in only 10 min, and each of them kill >99.99% of the bacterium in 20 min. These antimicrobial wraps can be removed and replaced on the same object in <1 min with no tools. Wraps are already frequently used by consumers to coat drawers or cars for aesthetic or protective purposes. Full article
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17 pages, 4389 KiB  
Article
Employing Gamma-Ray-Modified Carbon Quantum Dots to Combat a Wide Range of Bacteria
by Zoran M. Marković, Aleksandra S. Mišović, Danica Z. Zmejkoski, Nemanja M. Zdravković, Janez Kovač, Danica V. Bajuk-Bogdanović, Dušan D. Milivojević, Marija M. Mojsin, Milena J. Stevanović, Vladimir B. Pavlović and Biljana M. Todorović Marković
Antibiotics 2023, 12(5), 919; https://doi.org/10.3390/antibiotics12050919 - 17 May 2023
Cited by 3 | Viewed by 2056
Abstract
Nowadays, it is a great challenge to develop new medicines for treating various infectious diseases. The treatment of these diseases is of utmost interest to further prevent the development of multi-drug resistance in different pathogens. Carbon quantum dots, as a new member of [...] Read more.
Nowadays, it is a great challenge to develop new medicines for treating various infectious diseases. The treatment of these diseases is of utmost interest to further prevent the development of multi-drug resistance in different pathogens. Carbon quantum dots, as a new member of the carbon nanomaterials family, can potentially be used as a highly promising visible-light-triggered antibacterial agent. In this work, the results of antibacterial and cytotoxic activities of gamma-ray-irradiated carbon quantum dots are presented. Carbon quantum dots (CQDs) were synthesized from citric acid by a pyrolysis procedure and irradiated by gamma rays at different doses (25, 50, 100 and 200 kGy). Structure, chemical composition and optical properties were investigated by atomic force microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, UV-Vis spectrometry and photoluminescence. Structural analysis showed that CQDs have a spherical-like shape and dose-dependent average diameters and heights. Antibacterial tests showed that all irradiated dots had antibacterial activity but CQDs irradiated with dose of 100 kGy had antibacterial activity against all seven pathogen-reference bacterial strains. Gamma-ray-modified CQDs did not show any cytotoxicity toward human fetal-originated MRC-5 cells. Moreover, fluorescence microscopy showed excellent cellular uptake of CQDs irradiated with doses of 25 and 200 kGy into MRC-5 cells. Full article
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17 pages, 3638 KiB  
Article
Adverse Drug Reactions Relevant to Drug Resistance and Ineffectiveness Associated with Meropenem, Linezolid, and Colistin: An Analysis Based on Spontaneous Reports from the European Pharmacovigilance Database
by Bogdan Ioan Vintila, Anca Maria Arseniu, Anca Butuca, Mihai Sava, Victoria Bîrluțiu, Luca Liviu Rus, Dan Damian Axente, Claudiu Morgovan and Felicia Gabriela Gligor
Antibiotics 2023, 12(5), 918; https://doi.org/10.3390/antibiotics12050918 - 16 May 2023
Cited by 7 | Viewed by 1816
Abstract
Antimicrobial resistance is considered one of the major threats to public health and is an important factor that influences the patient’s outcome in the intensive care unit. Pharmacovigilance can help raise awareness of potential drug resistance (DR) or ineffectiveness (DI) through adverse drug [...] Read more.
Antimicrobial resistance is considered one of the major threats to public health and is an important factor that influences the patient’s outcome in the intensive care unit. Pharmacovigilance can help raise awareness of potential drug resistance (DR) or ineffectiveness (DI) through adverse drug reaction reports that are submitted to different spontaneous reporting systems. Based on spontaneous Individual Case Safety Reports from EudraVigilance, we conducted a descriptive analysis of adverse drug reactions associated with meropenem, colistin, and linezolid, with a focus on DR and DI. Of the total adverse drug reactions (ADRs) reported for each analyzed antibiotic by 31 December 2022, between 2.38–8.42% and 4.15–10.14% of the reports were related to DR and DI, respectively. A disproportionality analysis was conducted to evaluate the frequency of reporting adverse drug reactions relevant to the DR and DI of the analyzed antibiotics compared to other antimicrobials. Based on the analysis of the collected data, this study underlines the importance of post-marketing drug safety monitoring in raising a warning signal regarding antimicrobial resistance, thereby potentially contributing to the reduction in antibiotic treatment failure in an intensive care setting. Full article
(This article belongs to the Special Issue Hospital Infections and Antimicrobial Resistance)
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16 pages, 800 KiB  
Article
Genomic Characterization of Antibiotic-Resistant Campylobacterales Isolated from Chilean Poultry Meat
by Macarena Concha-Toloza, Mónica Lopez-Cantillo, Jose Arturo Molina-Mora and Luis Collado
Antibiotics 2023, 12(5), 917; https://doi.org/10.3390/antibiotics12050917 - 16 May 2023
Cited by 1 | Viewed by 1725
Abstract
Due to the lack of knowledge about Campylobacterales in the Chilean poultry industry, the objective of this research was to know the prevalence, resistance, and genotypes of Campylobacter, Arcobacter and Helicobacter in 382 samples of chicken meat purchased in Valdivia, Chile. The [...] Read more.
Due to the lack of knowledge about Campylobacterales in the Chilean poultry industry, the objective of this research was to know the prevalence, resistance, and genotypes of Campylobacter, Arcobacter and Helicobacter in 382 samples of chicken meat purchased in Valdivia, Chile. The samples were analyzed using three isolation protocols. Resistance to four antibiotics was evaluated by phenotypic methods. Genomic analyses were performed on selected resistant strains to detect resistance determinants and their genotypes. A total of 59.2% of the samples were positive. Arcobacter butzleri (37.4%) was the most prevalent species, followed by Campylobacter jejuni (19.6%), C. coli (11.3%), A. cryaerophilus (3.7%) and A. skirrowii (1.3%). Helicobacter pullorum (14%) was detected by PCR in a subset of samples. Campylobacter jejuni was resistant to ciprofloxacin (37.3%) and tetracycline (20%), while C. coli and A. butzleri were resistant to ciprofloxacin (55.8% and 2.8%), erythromycin (16.3% and 0.7%) and tetracycline (4.7% and 2.8%), respectively. Molecular determinants were consistent with phenotypic resistance. The genotypes of C. jejuni (CC-21, CC-48, CC-49, CC-257, CC-353, CC-443, CC-446 and CC-658) and C. coli (CC-828) coincided with genotypes of Chilean clinical strains. These findings suggest that besides C. jejuni and C. coli, chicken meat could play a role in the transmission of other pathogenic and antibiotic-resistant Campylobacterales. Full article
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12 pages, 5945 KiB  
Review
Regional Perspective of Antimicrobial Stewardship Programs in Latin American Pediatric Emergency Departments
by Adriana Yock-Corrales and Gabriela Naranjo-Zuñiga
Antibiotics 2023, 12(5), 916; https://doi.org/10.3390/antibiotics12050916 - 16 May 2023
Cited by 1 | Viewed by 1351
Abstract
Antibiotic stewardship (AS) programs have become a priority for health authorities to reduce the number of infections by super-resistant microorganisms. The need for these initiatives to minimize the inadequate use of antimicrobials is essential, and the election of the antibiotic in the emergency [...] Read more.
Antibiotic stewardship (AS) programs have become a priority for health authorities to reduce the number of infections by super-resistant microorganisms. The need for these initiatives to minimize the inadequate use of antimicrobials is essential, and the election of the antibiotic in the emergency department usually impacts the choice of treatment if the patients need hospital admission, becoming an opportunity for antibiotic stewardship. In the pediatric population, broad-spectrum antibiotics are more likely to be overprescribed without any evidence-based management, and most of the publications have focused on the prescription of antibiotics in ambulatory settings. Antibiotic stewardship efforts in pediatric emergency departments in Latin American settings are limited. The lack of literature on AS programs in the pediatric emergency departments in Latin America (LA) limits the information available. The aim of this review was to give a regional perspective on how pediatric emergency departments in LA are working towards antimicrobial stewardship. Full article
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10 pages, 606 KiB  
Article
The Real Practice Prescribing Antibiotics in Outpatients: A Failed Control Case Assessed through the Simulated Patient Method
by María Guadalupe Miranda-Novales, Karen Flores-Moreno, Mauricio Rodríguez-Álvarez, Yolanda López-Vidal, José Luis Soto-Hernández, Fortino Solórzano Santos and Samuel Ponce-de-León-Rosales
Antibiotics 2023, 12(5), 915; https://doi.org/10.3390/antibiotics12050915 - 16 May 2023
Viewed by 1461
Abstract
The first level of medical care provides the largest number of consultations for the most frequent diseases at the community level, including acute pharyngitis (AP), acute diarrhoea (AD) and uncomplicated acute urinary tract infections (UAUTIs). The inappropriate use of antibiotics in these diseases [...] Read more.
The first level of medical care provides the largest number of consultations for the most frequent diseases at the community level, including acute pharyngitis (AP), acute diarrhoea (AD) and uncomplicated acute urinary tract infections (UAUTIs). The inappropriate use of antibiotics in these diseases represents a high risk for the generation of antimicrobial resistance (AMR) in bacteria causing community infections. To evaluate the patterns of medical prescription for these diseases in medical offices adjacent to pharmacies, we used an adult simulated patient (SP) method representing the three diseases, AP, AD and UAUTI. Each person played a role in one of the three diseases, with the signs and symptoms described in the national clinical practice guidelines (CPGs). Diagnostic accuracy and therapeutic management were assessed. Information from 280 consultations in the Mexico City area was obtained. For the 101 AP consultations, in 90 cases (89.1%), one or more antibiotics or antivirals were prescribed; for the 127 AD, in 104 cases (81.8%), one or more antiparasitic drugs or intestinal antiseptics were prescribed; for the scenarios involving UAUTIs in adult women, in 51 of 52 cases (98.1%) one antibiotic was prescribed. The antibiotic group with the highest prescription pattern for AP, AD and UAUTIs was aminopenicillins and benzylpenicillins [27/90 (30%)], co-trimoxazole [35/104 (27.6%)] and quinolones [38/51 (73.1%)], respectively. Our findings reveal the highly inappropriate use of antibiotics for AP and AD in a sector of the first level of health care, which could be a widespread phenomenon at the regional and national level and highlights the urgent need to update antibiotic prescriptions for UAUTIs according to local resistance patterns. Supervision of adherence to the CPGs is needed, as well as raising awareness about the rational use of antibiotics and the threat posed by AMR at the first level of care. Full article
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18 pages, 3453 KiB  
Article
Evaluation of Alternative Doxycycline Antibiotic Regimes in an Inhalational Murine Model of Q Fever
by Kate A. Clay, M. Gill Hartley, Adam O. Whelan, Mark S. Bailey and Isobel H. Norville
Antibiotics 2023, 12(5), 914; https://doi.org/10.3390/antibiotics12050914 - 16 May 2023
Viewed by 1234
Abstract
The timing of the initiation of antibiotic treatment has been shown to impact the clinical outcome of many bacterial infections, including Q fever. Delayed, suboptimal or incorrect antibiotic treatment has been shown to result in poor prognosis, resulting in the progression of acute [...] Read more.
The timing of the initiation of antibiotic treatment has been shown to impact the clinical outcome of many bacterial infections, including Q fever. Delayed, suboptimal or incorrect antibiotic treatment has been shown to result in poor prognosis, resulting in the progression of acute disease to long-term chronic sequalae. Therefore, there is a requirement to identify an optimal, effective therapeutic regimen to treat acute Q fever. In the study, the efficacies of different doxycycline monohydrate regimens (pre-exposure prophylaxis, post-exposure prophylaxis or treatment at symptom onset or resolution) were evaluated in an inhalational murine model of Q fever. Different treatment lengths (7 or 14 days) were also evaluated. Clinical signs and weight loss were monitored during infection and mice were euthanized at different time points to characterize bacterial colonization in the lungs and the dissemination of bacteria to other tissues including the spleen, brain, testes, bone marrow and adipose. Post-exposure prophylaxis or doxycycline treatment starting at symptoms onset reduced clinical signs, and also delayed the systemic clearance of viable bacteria from key tissues. Effective clearance was dependent on the development of an adaptive immune response, but also driven by sufficient bacterial activity to maintain an active immune response. Pre-exposure prophylaxis or post-exposure treatment at the resolution of clinical signs did not improve outcomes. These are the first studies to experimentally evaluate different doxycycline treatment regimens for Q fever and illustrate the need to explore the efficacy of other novel antibiotics. Full article
(This article belongs to the Special Issue Animal Models of Biodefence Pathogens: Exploring Treatment)
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