Antibiotics

21 pages, 5831 KiB

Open AccessArticle

Synthesis of Novel Quinazolinone Analogues for Quorum Sensing Inhibition

by Sahil Shandil, Tsz Tin Yu, Shekh Sabir, David StC. Black and Naresh Kumar

Antibiotics 2023, 12(7), 1227; https://doi.org/10.3390/antibiotics12071227 - 24 Jul 2023

Cited by 1 | Viewed by 1213

As bacteria continue to develop resistance mechanisms against antimicrobials, an alternative method to tackle this global concern must be developed. As the pqs system is the most well-known and responsible for biofilm and pyocyanin production, quinazolinone inhibitors of the pqs system in P. [...] Read more.

As bacteria continue to develop resistance mechanisms against antimicrobials, an alternative method to tackle this global concern must be developed. As the pqs system is the most well-known and responsible for biofilm and pyocyanin production, quinazolinone inhibitors of the pqs system in P. aeruginosa were developed. Molecular docking following a rationalised medicinal chemistry approach was adopted to design these analogues. An analysis of docking data suggested that compound 6b could bind with the key residues in the ligand binding domain of PqsR in a similar fashion to the known antagonist M64. The modification of cyclic groups at the 3-position of the quinazolinone core, the introduction of a halogen at the aromatic core and the modification of the terminal group with aromatic and aliphatic chains were investigated to guide the synthesis of a library of 16 quinazolinone analogues. All quinazolinone analogues were tested in vitro for pqs inhibition, with the most active compounds 6b and 6e being tested for biofilm and growth inhibition in P. aeruginosa (PAO1). Compound 6b displayed the highest pqs inhibitory activity (73.4%, 72.1% and 53.7% at 100, 50 and 25 µM, respectively) with no bacterial growth inhibition. However, compounds 6b and 6e only inhibited biofilm formation by 10% and 5%, respectively. Full article

(This article belongs to the Special Issue Novel Antimicrobial Agents: Design, Synthesis and Biological Evaluation)

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11 pages, 1540 KiB

Open AccessFeature PaperArticle

Screening for Antimicrobial Resistance and Genes of Exotoxins in Pseudomonas aeruginosa Isolates from Infected Dogs and Cats in Poland

by Daria Płókarz, Karolina Bierowiec and Krzysztof Rypuła

Antibiotics 2023, 12(7), 1226; https://doi.org/10.3390/antibiotics12071226 - 24 Jul 2023

Viewed by 1301

Abstract

Pseudomonas aeruginosa has assumed an increasingly prominent role as the aetiological agent in serious hard-to-treat infections in animals and humans. In this study, 271 P. aeruginosa strains collected from dogs and cats were investigated. The aim of the research was to screen these [...] Read more.

Pseudomonas aeruginosa has assumed an increasingly prominent role as the aetiological agent in serious hard-to-treat infections in animals and humans. In this study, 271 P. aeruginosa strains collected from dogs and cats were investigated. The aim of the research was to screen these P. aeruginosa strains for antibiotic resistance and the presence of selected virulence factor genes. Antibiotic resistance was determined using the Kirby–Bauer method, while virulence genes were detected by polymerase chain reaction (PCR). The most frequently detected resistance was to fluoroquinolones, ranging in prevalence from 17.3% for ciprofloxacin up to 83% for enrofloxacin. The resistance to carbapenems was 14% and 4.8% for imipenem and meropenem, respectively. Almost all P. aeruginosa strains harboured the exoT (97.8%) and lasB (93.4%) genes, while the lowest prevalence was found for exoU (17.3%) and plcH (17.3%). P. aeruginosa strains isolated from dogs that harboured the toxA gene were more frequently resistant to ceftazidime (p = 0.012), while the presence of the exoU gene was found to be connected with resistance to marbofloxacin (p = 0.025) and amikacin (p = 0.056). In strains originating from cats, only the connection between the presence of the exoU gene and resistance to enrofloxacin (p = 0.054) was observed. The confirmation of associations between virulence-factor-encoding genes and antibiotic resistance indicates that problems of antibiotic resistance may not only cause complications at the level of antibiotic dosage but also lead to changes in the virulence of the bacteria; thus, further studies in this area are required. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Zoonoses)

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13 pages, 1275 KiB

Open AccessArticle

Epidemiology of Antimicrobial Resistance Genes in Staphyloccocus aureus Isolates from a Public Database in a One Health Perspective—Sample Characteristics and Isolates’ Sources

by Francesca Zaghen, Valerio Massimo Sora, Gabriele Meroni, Giulia Laterza, Piera Anna Martino, Alessio Soggiu, Luigi Bonizzi and Alfonso Zecconi

Antibiotics 2023, 12(7), 1225; https://doi.org/10.3390/antibiotics12071225 - 24 Jul 2023

Cited by 5 | Viewed by 1358

Abstract

Staphylococcus aureus is considered one of the most widespread bacterial pathogens for both animals and humans, being the causative agent of various diseases like food poisoning, respiratory tract infections, nosocomial bacteremia, and surgical site and cardiovascular infections in humans, as well as clinical [...] Read more.

Staphylococcus aureus is considered one of the most widespread bacterial pathogens for both animals and humans, being the causative agent of various diseases like food poisoning, respiratory tract infections, nosocomial bacteremia, and surgical site and cardiovascular infections in humans, as well as clinical and subclinical mastitis, dermatitis, and suppurative infections in animals. Thanks to their genetic flexibility, several virulent and drug-resistant strains have evolved mainly due to horizontal gene transfer and insurgence of point mutations. Infections caused by the colonization of such strains are particularly problematic due to frequently occurring antibiotic resistance, particulary methicillin-resistant S. aureus (MRSA), and are characterized by increased mortality, morbidity, and hospitalization rates compared to those caused by methicillin-sensitive S. aureus (MSSA). S. aureus infections in humans and animals are a prime example of a disease that may be managed by a One Health strategy. In fact, S. aureus is a significant target for control efforts due to its zoonotic potential, the frequency of its illnesses in both humans and animals, and the threat posed by S. aureus antibiotic resistance globally. The results of an epidemiological analysis on a worldwide public database (NCBI Pathogen Detection Isolate Browser; NPDIB) of 35,026 S. aureus isolates were described. We considered the diffusion of antibiotic resistance genes (ARGs), in both human and animal setting, and the results may be considered alarming. The result of this study allowed us to identify the presence of clusters with specific ARG patterns, and that these clusters are associated with different sources of isolation (e.g., human, non-human). Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Veterinary Science)

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9 pages, 815 KiB

Open AccessFeature PaperArticle

by Agata Pruss, Paweł Kwiatkowski, Monika Sienkiewicz, Helena Masiuk, Agnieszka Łapińska, Barbara Kot, Zuzanna Kilczewska, Stefania Giedrys-Kalemba and Barbara Dołęgowska

Antibiotics 2023, 12(7), 1224; https://doi.org/10.3390/antibiotics12071224 - 24 Jul 2023

Cited by 1 | Viewed by 1254

Abstract

Klebsiella pneumoniae is an important opportunistic pathogen responsible for severe infections, mainly urinary tract infections (UTIs) and pneumonia. Hospital epidemic infections caused by multiresistant strains of carbapenemase-producing K. pneumoniae are the most concerning. NDM-producing strains are resistant to a wide range of antibiotics [...] Read more.

Klebsiella pneumoniae is an important opportunistic pathogen responsible for severe infections, mainly urinary tract infections (UTIs) and pneumonia. Hospital epidemic infections caused by multiresistant strains of carbapenemase-producing K. pneumoniae are the most concerning. NDM-producing strains are resistant to a wide range of antibiotics and have become the most significant threat. Determining the natural reservoirs and routes of infections is essential to end hospital outbreaks. Understanding the relatedness of K. pneumoniae strains is essential to determine the range and nature of the infection. The study compared phylogenetic relatedness between multiresistant K. pneumoniae strains isolated from hospitalized patients. Susceptibility to drugs and mechanisms of resistance were confirmed using phenotypic methods. PFGE was used to analyze the relatedness between strains. We analyzed 69 K. pneumoniae strains from various healthcare units. The isolates were mainly identified from urine. Strains were resistant to β-lactam antibiotics with β-lactamase inhibitors, cephalosporins, and quinolones. Their susceptibility to aminoglycosides and carbapenem antibiotics was diverse. Most of the isolated strains produced New Delhi metallo-ß-lactamase (NDM). Although K. pneumoniae strains were classified into several genotype clusters, closely related isolates were confirmed in the same hospital’s wards, and in two hospitals in the same province. Full article

(This article belongs to the Special Issue Uropathogens—Antibiotic Resistance and Alternative Therapies, 2nd Edition)

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19 pages, 4340 KiB

Open AccessSystematic Review

A Systematic Review and Meta-Analysis of Systemic and Local Antibiotic Therapy in the Surgical Treatment of Peri-Implantitis

by María Baus-Domínguez, Sara Bakkali, Paula Hermida-Cabrera, María-Angeles Serrera-Figallo, José-Luis Gutiérrez-Pérez and Daniel Torres-Lagares

Antibiotics 2023, 12(7), 1223; https://doi.org/10.3390/antibiotics12071223 - 24 Jul 2023

Cited by 1 | Viewed by 1420

Abstract

(1) Background: Given the existing controversy regarding the use of antibiotics in the treatment of peri-implantitis, this systematic review and meta-analysis aim to ascertain how beneficial the role of systemic and local antibiotics is in peri-implant surgical therapy, considering the harmful effects that [...] Read more.

(1) Background: Given the existing controversy regarding the use of antibiotics in the treatment of peri-implantitis, this systematic review and meta-analysis aim to ascertain how beneficial the role of systemic and local antibiotics is in peri-implant surgical therapy, considering the harmful effects that they represent and the abuse of antibiotics in terms of global health. (2) Methods: To determine the therapeutic efficacy of the administration of antibiotics in the surgical treatment of peri-implantitis in terms of probing pocket depth (PPD) and bleeding on probing (BoP), electronic and manual bibliographic searches were carried out in the Embase and PubMed databases, collecting data that related to before and after treatment. (3) Results: The adjunctive use of local antibiotics provides significant improvements in PPD (MD = 1.29; 95% CI: 0.56 to 2.02; p ≤ 0.0006; I² = 0%) when compared with surgical treatment alone. No significant differences were found in the other subgroup; that is, the use of systemic antibiotics did not significantly improve PPD changes in the surgical treatment of peri-implantitis (MD = 0.40; 95% CI: −0.15 to 0.95; p = 0.15; I² = 0). (4) Conclusions: The use of local antibiotics in the surgical treatment of peri-implantitis seems to offer treatment improvements in terms of PPD and BoP, unlike that observed with the use of systemic antibiotics. However, these results should be taken with caution as they also depend on the type of surgical technique used, whether regenerative or resective. More research is needed on this topic to understand the role of local and systemic antibiotics in the treatment of peri-implantitis. Full article

(This article belongs to the Special Issue The Application of Antibiotic Therapy in Oral Surgery and Dental Implant Procedures)

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14 pages, 3492 KiB

Open AccessSystematic Review

Streptococcus mitis as a New Emerging Pathogen in Pediatric Age: Case Report and Systematic Review

by Claudia Colomba, Valeria Garbo, Giovanni Boncori, Chiara Albano, Sara Bagarello, Anna Condemi, Salvatore Giordano, Laura A. Canduscio, Cristina Gallo, Gaspare Parrinello and Antonio Cascio

Antibiotics 2023, 12(7), 1222; https://doi.org/10.3390/antibiotics12071222 - 23 Jul 2023

Viewed by 5573

Abstract

Streptococcus mitis, a normal inhabitant of the oral cavity, is a member of Viridans Group Streptococci (VGS). Generally recognized as a causative agent of invasive diseases in immunocompromised patients, S. mitis is considered to have low pathogenic potential in immunocompetent individuals. We [...] Read more.

Streptococcus mitis, a normal inhabitant of the oral cavity, is a member of Viridans Group Streptococci (VGS). Generally recognized as a causative agent of invasive diseases in immunocompromised patients, S. mitis is considered to have low pathogenic potential in immunocompetent individuals. We present a rare case of sinusitis complicated by meningitis and cerebral sino-venous thrombosis (CSVT) caused by S. mitis in a previously healthy 12-year-old boy with poor oral health status. With the aim of understanding the real pathogenic role of this microorganism, an extensive review of the literature about invasive diseases due to S. mitis in pediatric patients was performed. Our data define the critical role of this microorganism in invasive infections, especially in immunocompetent children and in the presence of apparently harmful conditions such as sinusitis and caries. Attention should be paid to the choice of therapy because of VGS’s emerging antimicrobial resistance patterns. Full article

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20 pages, 769 KiB

Open AccessFeature PaperArticle

The Prevalence of the Virulence Genes of Staphylococcus aureus in Sickle Cell Disease Patients at KSUMC, Riyadh, Saudi Arabia

by Adel A. Abdulmanea, Naiyf S. Alharbi, Ali M. Somily, Jamal M. Khaled and Farjah H. Algahtani

Antibiotics 2023, 12(7), 1221; https://doi.org/10.3390/antibiotics12071221 - 22 Jul 2023

Cited by 1 | Viewed by 1581

Abstract

Staphylococcus aureus in the blood of sickle cell disease (SCD) patients may result in a significant increase in morbidity and mortality. S. aureus strains contain various virulence characteristics, including the ability to create a variety of toxins and develop drug resistance. The current [...] Read more.

Staphylococcus aureus in the blood of sickle cell disease (SCD) patients may result in a significant increase in morbidity and mortality. S. aureus strains contain various virulence characteristics, including the ability to create a variety of toxins and develop drug resistance. The current study sought to assess the prevalence of S. aureus in SCD patients and to identify the pathogen’s virulence characteristics. Between 2017 and 2021, blood samples and data were collected at King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia. The Vitek system PCR and gene sequencing methods were used for identification, antibiotic resistance patterns, and genetic analysis. During the study period, 47 S. aureus blood isolates (methicillin-resistant S. aureus (MRSA) 41.6% and non-MRSA 58.4%) were isolated from 2406 SCD patients. The prevalence percentages of virulence genes (finbB, sdrC, sdrD, icaA, coa, nuc, hlg, hla, finbA, clfA, efb, pvl, agr, spa, seb, sea, sec, tst, and sed) among all the isolates from the SCD patients compared with non-SCD patients (control group) were as follows: (100% vs. 100%), (100% vs. 100%), (100% vs. 100%), (100% vs. 87.5%), (100% vs. 81.3%), (100% vs. 100%), (100% vs. 100%), (100% vs. 100%), (97.9% vs. 81.3%), (97.9% vs. 100%), (97.9% vs. 87.5%), (54.3% vs. 56.3%), (46.8% vs. 75%), (42.6% vs. 43.8%), (27.7% vs. 0%), (25.5% vs. 12.5%), (12.8% vs. 6.3%), (4.3% vs. 12.5%), and (4.3% vs. 0%). Regarding the resistance genes (plaZ, mecA, ermA, ermC, tetK, tetM, and ermB) of the S. aureus strains isolated from the SCD patients compared with non-SCD patients (control group), the prevalence percentages were as follows: (100% vs. 100%), (100% vs. 56.3%), (0% vs. 31.3%), (31.9% vs. 18.8%), (40.4% vs. 25%), (0% vs. 0%), and (0% vs. 0%). As for the antibiotic (ampicillin, penicillin, amoxicillin, cefazolin, imipenem, oxacillin, erythromycin, tetracycline, azithromycin, ciprofloxacin, moxifloxacin, and levofloxacin) resistance of the S. aureus strains isolated from the SCD patients compared with non-SCD patients (control group), the prevalence percentages were as follows: (100% vs. 100%), (97.9% vs. 100%), (72.3% vs. 25%), (68.1% vs. 37.5%), (68.1% vs. 25%), (66% vs. 25%), (36.2% vs. 18.8%), (23.4% vs. 12.5%), (19.1% vs. 12.5%), (17% vs. 12.5%), (14.9% vs. 25%), and (10.6% vs. 18.7%). This study concluded that several virulence genes were present in the S. aureus strains recovered from the SCD patients at KSUMC, with all the isolates containing the finbB, sdrC, sdrD, icaA, coa, nuc, hlg, and hla genes. Full article

(This article belongs to the Section Genetic and Biochemical Studies of Antibiotic Activity and Resistance)

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39 pages, 18739 KiB

Open AccessReview

Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review

by Maria Marinescu

Antibiotics 2023, 12(7), 1220; https://doi.org/10.3390/antibiotics12071220 - 22 Jul 2023

Cited by 8 | Viewed by 2150

Abstract

Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research to [...] Read more.

Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles, and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole-triazole hybrids with improved biological properties compared to the properties of simple mono-heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure–activity relationship reported in the literature. It was found that the presence of certain groups grafted onto the benzimidazole and/or triazole nuclei (-F, -Cl, -Br, -CF₃, -NO₂, -CN, -CHO, -OH, OCH₃, COOCH₃), as well as the presence of some heterocycles (pyridine, pyrimidine, thiazole, indole, isoxazole, thiadiazole, coumarin) increases the antimicrobial activity of benzimidazole-triazole hybrids. Also, the presence of the oxygen or sulfur atom in the bridge connecting the benzimidazole and triazole rings generally increases the antimicrobial activity of the hybrids. The literature mentions only benzimidazole-1,2,3-triazole hybrids with antiviral properties. Both for antimicrobial and antiviral hybrids, the presence of an additional triazole ring increases their biological activity, which is in agreement with the three-dimensional binding mode of compounds. This review summarizes the advances of benzimidazole triazole derivatives as potential antimicrobial and antiviral agents covering articles published from 2000 to 2023. Full article

(This article belongs to the Special Issue Design and Synthesis of Antimicrobial Compounds)

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9 pages, 787 KiB

Open AccessArticle

Do or Don’t: Results of a Multinational Survey on Antibiotic Prophylaxis in Urodynamics

by Fabian P. Stangl, Laila Schneidewind, Florian M. Wagenlehner, Daniela Schultz-Lampel, Kaven Baeßler, Gert Naumann, Sandra Schönburg, Petra Anheuser, Susanne Winkelhog-Gran, Matthias Saar, Tanja Hüsch and Jennifer Kranz

Antibiotics 2023, 12(7), 1219; https://doi.org/10.3390/antibiotics12071219 - 22 Jul 2023

Viewed by 865

Abstract

Antibiotic prophylaxis contributes substantially to the increase in antibiotic resistance rates worldwide. This investigation aims to assess the current standard of practice in using antibiotic prophylaxis for urodynamics (UDS) and identify barriers to guideline adherence. An online survey using a 22-item questionnaire designed [...] Read more.

Antibiotic prophylaxis contributes substantially to the increase in antibiotic resistance rates worldwide. This investigation aims to assess the current standard of practice in using antibiotic prophylaxis for urodynamics (UDS) and identify barriers to guideline adherence. An online survey using a 22-item questionnaire designed according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) was circulated among urologists and gynecologists in Austria, Germany, and Switzerland between September 2021 and March 2022. A total of 105 questionnaires were eligible for analysis. Out of 105 completed surveys, most responders (n = 99, 94%) regularly perform dipstick urine analysis prior to urodynamics, but do not perform a urine culture (n = 68, 65%). Ninety-eight (93%) participants refrain from using antibiotic prophylaxis, and sixty-eight (65%) use prophylaxis if complicating factors exist. If asymptomatic bacteriuria is present, approximately 54 (52%) participants omit UDS and reschedule the procedure until antimicrobial susceptibility testing is available. Seventy-eight (78%) participants do not have a standard procedure for antibiotic prophylaxis in their department. Part of the strategy against the development of bacterial resistance is the optimized use of antibiotics, including antibiotic prophylaxis in urodynamics. Establishing a standard procedure is necessary and purposeful to harmonize both aspects in the field of urological diagnostics. Full article

(This article belongs to the Special Issue Diagnosis, Management and Antibiotic Therapy of Urinary Tract Infections)

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16 pages, 703 KiB

Open AccessArticle

Cefto Real-Life Study: Real-World Data on the Use of Ceftobiprole in a Multicenter Spanish Cohort

by Carmen Hidalgo-Tenorio, Inés Pitto-Robles, Daniel Arnés García, F. Javier Membrillo de Novales, Laura Morata, Raul Mendez, Olga Bravo de Pablo, Vicente Abril López de Medrano, Miguel Salavert Lleti, Pilar Vizcarra, Jaime Lora-Tamayo, Ana Arnáiz García, Leonor Moreno Núñez, Mar Masiá, Maria Pilar Ruiz Seco and Svetlana Sadyrbaeva-Dolgova

Antibiotics 2023, 12(7), 1218; https://doi.org/10.3390/antibiotics12071218 - 21 Jul 2023

Cited by 2 | Viewed by 1169

Abstract

Background: Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infections in hospital or [...] Read more.

Background: Ceftobiprole is a fifth-generation cephalosporin that has been approved in Europe solely for the treatment of community-acquired and nosocomial pneumonia. The objective was to analyze the use of ceftobiprole medocaril (Cefto-M) in Spanish clinical practice in patients with infections in hospital or outpatient parenteral antimicrobial therapy (OPAT). Methods: This retrospective, observational, multicenter study included patients treated from 1 September 2021 to 31 December 2022. Results: A total of 249 individuals were enrolled, aged 66.6 ± 15.4 years, of whom 59.4% were male with a Charlson index of four (IQR 2–6), 13.7% had COVID-19, and 4.8% were in an intensive care unit (ICU). The most frequent type of infection was respiratory (55.8%), followed by skin and soft tissue infection (21.7%). Cefto-M was administered to 67.9% of the patients as an empirical treatment, in which was administered as monotherapy for 7 days (5–10) in 53.8% of cases. The infection-related mortality was 11.2%. The highest mortality rates were identified for ventilator-associated pneumonia (40%) and infections due to methicillin-resistant Staphylococus aureus (20.8%) and Pseudomonas aeruginosa (16.1%). The mortality-related factors were age (OR: 1.1, 95%CI (1.04–1.16)), ICU admission (OR: 42.02, 95%CI (4.49–393.4)), and sepsis/septic shock (OR: 2.94, 95%CI (1.01–8.54)). Conclusions: In real life, Cefto-M is a safe antibiotic, comprising only half of prescriptions for respiratory infections, that is mainly administered as rescue therapy in pluripathological patients with severe infectious diseases. Full article

(This article belongs to the Special Issue Antimicrobial Use across Different Healthcare Settings, Countries and Specific Populations)

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15 pages, 5722 KiB

Open AccessArticle

Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes

by Maria Dehli Vigeland, Siri Tennebø Flåm, Magnus Dehli Vigeland, Ansgar Espeland, Manuela Zucknick, Monica Wigemyr, Lars Christian Haugli Bråten, Elisabeth Gjefsen, John-Anker Zwart, Kjersti Storheim, Linda Margareth Pedersen, Kaja Selmer, Benedicte Alexandra Lie, Kristina Gervin and The AIM Study Group

Antibiotics 2023, 12(7), 1217; https://doi.org/10.3390/antibiotics12071217 - 21 Jul 2023

Viewed by 2794

Abstract

Long-term antibiotics are prescribed for a variety of medical conditions, recently including low back pain with Modic changes. The molecular impact of such treatment is unknown. We conducted longitudinal transcriptome and epigenome analyses in patients (n = 100) receiving amoxicillin treatment or [...] Read more.

Long-term antibiotics are prescribed for a variety of medical conditions, recently including low back pain with Modic changes. The molecular impact of such treatment is unknown. We conducted longitudinal transcriptome and epigenome analyses in patients (n = 100) receiving amoxicillin treatment or placebo for 100 days in the Antibiotics in Modic Changes (AIM) study. Gene expression and DNA methylation were investigated at a genome-wide level at screening, after 100 days of treatment, and at one-year follow-up. We identified intra-individual longitudinal changes in gene expression and DNA methylation in patients receiving amoxicillin, while few changes were observed in patients receiving placebo. After 100 days of amoxicillin treatment, 28 genes were significantly differentially expressed, including the downregulation of 19 immunoglobulin genes. At one-year follow-up, the expression levels were still not completely restored. The significant changes in DNA methylation (n = 4548 CpGs) were mainly increased methylation levels between 100 days and one-year follow-up. Hence, the effects on gene expression occurred predominantly during treatment, while the effects on DNA methylation occurred after treatment. In conclusion, unrecognized side effects of long-term amoxicillin treatment were revealed, as alterations were observed in both gene expression and DNA methylation that lasted long after the end of treatment. Full article

(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics of Antibacterial and Antivirulence Drugs)

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17 pages, 2669 KiB

Open AccessArticle

Adsorption/Desorption of Cationic-Hydrophobic Peptides on Zwitterionic Lipid Bilayer Is Associated with the Possibility of Proton Transfer

by Lea Pašalić, Andreja Jakas, Barbara Pem and Danijela Bakarić

Antibiotics 2023, 12(7), 1216; https://doi.org/10.3390/antibiotics12071216 - 21 Jul 2023

Cited by 1 | Viewed by 1156

Abstract

Cell-penetrating peptides (CPPs) are short peptides built up from dominantly cationic and hydrophobic amino acid residues with a distinguished ability to pass through the cell membrane. Due to the possibility of linking and delivering the appropriate cargo at the desired location, CPPs are [...] Read more.

Cell-penetrating peptides (CPPs) are short peptides built up from dominantly cationic and hydrophobic amino acid residues with a distinguished ability to pass through the cell membrane. Due to the possibility of linking and delivering the appropriate cargo at the desired location, CPPs are considered an economic and less invasive alternative to antibiotics. Besides knowing that their membrane passage mechanism is a complex function of CPP chemical composition, the ionic strength of the solution, and the membrane composition, all other details on how they penetrate cell membranes are rather vague. The aim of this study is to elucidate the ad(de)sorption of arginine-/lysine- and phenylalanine-rich peptides on a lipid membrane composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipids. DSC and temperature-dependent UV-Vis measurements confirmed the impact of the adsorbed peptides on thermotropic properties of DPPC, but in an inconclusive way. On the other hand, FTIR spectra acquired at 30 °C and 50 °C (when DPPC lipids are found in the gel and fluid phase, respectively) unambiguously confirmed the proton transfer between particular titratable functional groups of R5F2/K5F2 that highly depend on their immediate surroundings (DPPC or a phosphate buffer). Molecular dynamic simulations showed that both peptides may adsorb onto the bilayer, but K5F2 desorbs more easily and favors the solvent, while R5F2 remains attached. The results obtained in this work highlight the importance of proton transfer in the design of CPPs with their desired cargo, as its charge and composition dictates the possibility of entering the cell. Full article

(This article belongs to the Special Issue Membranes to Fight Drug-Resistant Microbes)

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10 pages, 447 KiB

Open AccessArticle

Evaluation of the BD Phoenix CPO Detect Panel for Detection and Classification of Carbapenemase Producing Enterobacterales

by Harshad Lade, Seri Jeong, Kibum Jeon, Han-Sung Kim, Hyun Soo Kim, Wonkeun Song and Jae-Seok Kim

Antibiotics 2023, 12(7), 1215; https://doi.org/10.3390/antibiotics12071215 - 21 Jul 2023

Viewed by 1121

Abstract

Carbapenem-resistant Enterobacterales (CRE) pose a serious public health threat due to their resistance to most antibiotics. Rapid and correct detection of carbapenemase producing organisms (CPOs) can help inform clinician decision making on antibiotic therapy. The BD Phoenix™ CPO detect panel, as part of [...] Read more.

Carbapenem-resistant Enterobacterales (CRE) pose a serious public health threat due to their resistance to most antibiotics. Rapid and correct detection of carbapenemase producing organisms (CPOs) can help inform clinician decision making on antibiotic therapy. The BD Phoenix™ CPO detect panel, as part of antimicrobial susceptibility testing (AST), detects carbapenemase activity (P/N) and categorizes CPOs according to Ambler classes. We evaluated a CPO detect panel against 109 carbapenemase producing Enterobacterales (CPE) clinical isolates from Korea. The panel correctly detected carbapenemases production in 98.2% (n = 107/109) isolates and identified 78.8% (n = 26/33) class A, 65.9% (n = 29/44) class B, and 56.3% (n = 18/32) class D carbapenemase producers as harboring their corresponding Ambler classes. Specifically, the panel correctly classified 81.3% (n = 13/16) of K. pneumoniae KPC isolates to class A. However, the panel failed to classify 40.0% (n = 4/10) IMP and 63.6% (n = 7/11) VIM isolates to class B. Despite 27.5% (n = 30/109) CPE not being assigned Ambler classes, all of them tested carbapenemase positive. Our results demonstrate that the CPO detect panel is a sensitive test for detecting CPE and classifying KPC as class A, helping with antibiotics selection, but one-third of CPE remained unclassified for Ambler classes. Full article

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11 pages, 1292 KiB

Open AccessArticle

Real-Life Experience of Continuously Infused Ceftolozane/Tazobactam in Patients with Bronchiectasis and Multidrug-Resistant Pseudomonas aeruginosa Infection in the Outpatient Setting

by Francesco Venuti, Alberto Gaviraghi, Amedeo De Nicolò, Giacomo Stroffolini, Bianca Maria Longo, Alessia Di Vincenzo, Fabio Antonino Ranzani, Matilde Quaranta, Francesca Romano, Eleonora Catellani, Carlotta Marchiaro, Giacoma Cinnirella, Antonio D’Avolio, Stefano Bonora and Andrea Calcagno

Antibiotics 2023, 12(7), 1214; https://doi.org/10.3390/antibiotics12071214 - 21 Jul 2023

Viewed by 1336

Abstract

(1) Background: Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor with excellent activity against the multidrug-resistant (MDR) P. aeruginosa. Continuous infusion (CI) dosing allows the optimization of pharmacokinetic and pharmacodynamic (PK/PD) properties of β-lactam antibiotics and may support patients’ treatment as outpatients. (2) [...] Read more.

(1) Background: Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor with excellent activity against the multidrug-resistant (MDR) P. aeruginosa. Continuous infusion (CI) dosing allows the optimization of pharmacokinetic and pharmacodynamic (PK/PD) properties of β-lactam antibiotics and may support patients’ treatment as outpatients. (2) Methods: Adult patients receiving their entire course of C/T as a CI in the outpatient setting were retrospectively included in the study. The primary outcome evaluated was clinical resolution. The secondary outcomes evaluated were PK/PD target attainment (ƒT > 4 × MIC) and microbiologic clearance at the end of treatment. Therapeutic drug monitoring to assess C/T concentration was performed. (3) Results: Three patients were enrolled in the study and received 9 g of C/T in CI every 24 h. One patient received an additional course of antimicrobial therapy due to disease exacerbation six months after initial treatment, accounting for four evaluated treatments. The primary outcome was achieved in 3/4 treatments and the secondary outcome was achieved in 4/4 and 3/3, respectively. In all patients, free ceftolozane concentrations were >10 times higher than the EUCAST breakpoint (4 mg/L). (4) Conclusions: Elastomeric infusion of C/T delivered in CI can be an effective and convenient way to treat acute diseases caused by MDR-P. aeruginosa, avoid hospital admission, and contribute to infection control strategies. Despite the small number of enrolled patients, clinical and microbiological results support this strategy. Full article

(This article belongs to the Special Issue Current Trends, Recent Advances and Applications of Outpatient Parenteral Antimicrobial Therapy (OPAT))

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15 pages, 9462 KiB

Open AccessArticle

Discovery of Bactericidal Proteins from Staphylococcus Phage Stab21 Using a High-Throughput Screening Method

by Ellisiv Nyhamar, Paige Webber, Olivia Liong, Özgenur Yilmaz, Maria Pajunen, Mikael Skurnik and Xing Wan

Antibiotics 2023, 12(7), 1213; https://doi.org/10.3390/antibiotics12071213 - 21 Jul 2023

Viewed by 1115

Abstract

In the escalating battle against antimicrobial resistance, there is an urgent need to discover and investigate new antibiotic strategies. Bacteriophages are untapped reservoirs of such potential antimicrobials. This study focused on Hypothetical Proteins of Unknown Function (HPUFs) from a Staphylococcus phage Stab21. We [...] Read more.

In the escalating battle against antimicrobial resistance, there is an urgent need to discover and investigate new antibiotic strategies. Bacteriophages are untapped reservoirs of such potential antimicrobials. This study focused on Hypothetical Proteins of Unknown Function (HPUFs) from a Staphylococcus phage Stab21. We examined its HPUFs for bactericidal activity against E. coli using a Next Generation Sequencing (NGS)-based approach. Among the 96 HPUFs examined, 5 demonstrated cross-species toxicity towards E. coli, suggesting the presence of shared molecular targets between E. coli and S. aureus. One toxic antibacterial HPUF (toxHPUF) was found to share homology with a homing endonuclease. The implications of these findings are profound, particularly given the potential broad applicability of these bactericidal agents. This study confirms the efficacy of NGS in streamlining the screening process of toxHPUFs, contributes significantly to the ongoing exploration of phage biology, and offers promises in the search for potent antimicrobial agents. Full article

(This article belongs to the Special Issue Design and Synthesis of Novel Antibiotics)

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15 pages, 2597 KiB

Open AccessArticle

Comparison of Disk Diffusion, E-Test, and Broth Microdilution Methods for Testing In Vitro Activity of Cefiderocol in Acinetobacter baumannii

by Natalia Kolesnik-Goldmann, Helena M. B. Seth-Smith, Klara Haldimann, Frank Imkamp, Tim Roloff, Reinhard Zbinden, Sven N. Hobbie, Adrian Egli and Stefano Mancini

Antibiotics 2023, 12(7), 1212; https://doi.org/10.3390/antibiotics12071212 - 20 Jul 2023

Viewed by 2121

Abstract

The reference method for cefiderocol antimicrobial susceptibility testing is broth microdilution (BMD) with iron-depleted-Mueller-Hinton (ID-MH) medium, whereas breakpoints recommended for disk diffusion (DD) are based on MH-agar plates. We aimed to compare the performance of the commercial BMD tests ComASP (Liofilchem) and UMIC [...] Read more.

The reference method for cefiderocol antimicrobial susceptibility testing is broth microdilution (BMD) with iron-depleted-Mueller-Hinton (ID-MH) medium, whereas breakpoints recommended for disk diffusion (DD) are based on MH-agar plates. We aimed to compare the performance of the commercial BMD tests ComASP (Liofilchem) and UMIC (Bruker), and DD and E-test using MH- and ID-MH-agar plates with the reference BMD method using 100 carbapenem-resistant-A. baumannii isolates. Standard BMD was performed according to the EUCAST guidelines; DD and E-test were carried out using two commercial MH-agar plates (BioMérieux and Liofilchem) and an in-house ID-MH-agar plate, while ComASP and UMIC were performed according to the manufacturer’s guidelines. DD performed with the ID-MH-agar plates led to a higher categorical agreement (CA, 95.1%) with standard BMD and fewer categorization errors compared to the commercial MH-agar plates (CA BioMérieux 91.1%, Liofilchem 89.2%). E-test on ID-MH-agar plates exhibited a significantly higher essential agreement (EA, 75%) with standard BMD compared to the two MH-agar plates (EA BioMérieux 57%, Liofilchem 44%), and showed a higher performance in detecting high-level resistance than ComASP and UMIC (mean log2 difference with standard BMD for resistant isolates of 0.5, 2.83, and 2.08, respectively). In conclusion, DD and E-test on ID-MH-agar plates exhibit a higher diagnostic performance than on MH-agar plates and the commercial BMD methods. Therefore, we recommend using ID-MH-agar plates for cefiderocol susceptibility testing of A. baumannii. Full article

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20 pages, 4036 KiB

Open AccessArticle

Isolation, Characterization of Pyraclostrobin Derived from Soil Actinomycete Streptomyces sp. HSN-01 and Its Antimicrobial and Anticancer Activity

by Halaswamy Hire Math, Sreenivasa Nayaka, Muthuraj Rudrappa, Raju Suresh Kumar, Abdulrahman I. Almansour, Karthikeyan Perumal and Girish Babu Kantli

Antibiotics 2023, 12(7), 1211; https://doi.org/10.3390/antibiotics12071211 - 20 Jul 2023

Viewed by 1381

Abstract

The present study demonstrated the isolation, characterization, and antimicrobial and anticancer activity of active metabolite produced from mining-soil-derived actinomycetes. Among the 21 actinomycete isolates, the isolate HSN-01 exhibited significant antimicrobial activity in primary screening and was identified as Streptomyces sp. through 16S rRNA [...] Read more.

The present study demonstrated the isolation, characterization, and antimicrobial and anticancer activity of active metabolite produced from mining-soil-derived actinomycetes. Among the 21 actinomycete isolates, the isolate HSN-01 exhibited significant antimicrobial activity in primary screening and was identified as Streptomyces sp. through 16S rRNA gene sequencing. The active metabolite was separated, purified, and confirmed through UV–Vis spectroscopy, FTIR, HR-ESI-MS, and NMR analysis and identified as pyraclostrobin. Further, the active metabolite pyraclostrobin was tested for antimicrobial and anticancer activity against the hepatocellular carcinoma (HepG2) cell line. The metabolite exhibited maximum antimicrobial potential with 17.0, 13.33, 17.66, 15.66, 14.66, and 14.0 mm of inhibition against B. cereus, S. aureus, E. coli, P. aeruginosa, S. flexneri, and C. glabrata. The active metabolite exhibited dose-dependent anticancer potential against the hepatocellular carcinoma (HepG2) cell line with the IC₅₀ 56.76 µg/mL. This study suggests that Streptomyces sp. HSN-01 is an excellent source of active secondary metabolites with various biological activities. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Secondary Metabolites Produced in Nature)

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15 pages, 2135 KiB

Open AccessArticle

Effect of Escin Alone or in Combination with Antifungal Agents on Resistant Candida glabrata Biofilms: Mechanisms of Action

by Angela Maione, Marianna Imparato, Marilena Galdiero, Elisabetta de Alteriis, Antonia Feola, Emilia Galdiero and Marco Guida

Antibiotics 2023, 12(7), 1210; https://doi.org/10.3390/antibiotics12071210 - 20 Jul 2023

Cited by 1 | Viewed by 998

Abstract

Nowadays, the increase in antimicrobial-resistant fungi (AMR) is certainly a major health concern, and the development of alternative therapeutic strategies has become crucial. Natural products have been used to treat various infections, and their chemical properties contribute to the performance of their biological [...] Read more.

Nowadays, the increase in antimicrobial-resistant fungi (AMR) is certainly a major health concern, and the development of alternative therapeutic strategies has become crucial. Natural products have been used to treat various infections, and their chemical properties contribute to the performance of their biological activities, such as antifungal action. The various virulence factors and mechanisms of resistance to antifungals contribute to making Candida glabrata one of the most frequent agents of candidiasis. Here we investigate the in vitro and in vivo activity of β-escin against Candida glabrata. The β-escin MICs were determined for a reference strain and two clinical isolates of C. glabrata. Furthermore, growth kinetics assays and biofilm inhibition/eradication assays (crystal violet) were performed. The differences in the expression of some anti-biofilm-associated genes were analyzed during biofilm inhibition treatment so that reactive oxygen species could be detected. The efficacy of β-escin was evaluated in combination with fluconazole, ketoconazole, and itraconazole. In addition, a Galleria mellonella infection model was used for in vivo treatment assays. Results have shown that β-escin had no toxicity in vitro or in vivo and was able to inhibit or destroy biofilm formation by downregulating some important genes, inducing ROS activity and affecting the membrane integrity of C. glabrata cells. Furthermore, our study suggests that the combination with azoles can have synergistic effects against C. glabrata biofilm. In summary, the discovery of new antifungal drugs against these resistant fungi is crucial and could potentially lead to the development of future treatment strategies. Full article

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14 pages, 664 KiB

Open AccessArticle

High Emergence of Multidrug-Resistant Sequence Type 131 Subclade C2 among Extended-Spectrum β-Lactamase (ESBL)-Producing Escherichia coli Isolated from the University Hospital Bratislava, Slovakia

by Ján Koreň, Michal Andrezál, Elham Ozaee, Hana Drahovská, Martin Wawruch, Adriána Liptáková and Tibor Maliar

Antibiotics 2023, 12(7), 1209; https://doi.org/10.3390/antibiotics12071209 - 20 Jul 2023

Viewed by 1031

Abstract

The expansion of sequence type 131 (ST131) extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) represents major worldwide challenges. E. coli strains originating from healthcare facilities (labeled No. 1 and No. 2) of the University Hospital Bratislava (UHB) were analyzed for ST131 [...] Read more.

The expansion of sequence type 131 (ST131) extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) represents major worldwide challenges. E. coli strains originating from healthcare facilities (labeled No. 1 and No. 2) of the University Hospital Bratislava (UHB) were analyzed for ST131 emergence, including its (sub)lineages and clonal relatedness. Antimicrobial resistance was determined in most strains. Of a total of 354 E. coli strains, 263 (74.3%) belonged to ST131; of these, 177 (67.3%) were from No. 1. Generally, among 260 ST131 E. coli, clades A/B were confirmed in 20 (7.7%), while clade C was noted in 240 (92.3%) strains; within them, subclades were detected as follows: C0 (17; 7.1%), C1 (3; 1.2%), and C2 (220; 91.7%). Among fifteen randomly selected E. coli strains that were investigated for ST and clonal relatedness, seven STs were identified: eight (53.3%) ST131, two (13.3%) ST73, and one each (6.7%) of ST10, ST12, ST14, ST1193, and ST1196. From No. 1, two ST131 in the first internal clinic and one ST131 from No. 2 in the aftercare department were highly clonally related, suggesting possible epidemiological association. Antimicrobial resistance was as follows: ciprofloxacin 93.8%, ceftazidime 78.4%, meropenem 0%, fosfomycin 2.9% and nitrofurantoin 1.4%. Prevention of ESBL-producing E. coli dissemination, especially for ST131 clade C2, is inevitably necessary for reducing drug resistance and decreasing healthcare-associated infections. Full article

(This article belongs to the Special Issue Strategies for Combatting Multidrug-Resistant and Extensively Drug-Resistant Bacteria: Current Challenges and Future Prospects)

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10 pages, 705 KiB

Open AccessArticle

Compliance with a Procalcitonin-Based Protocol in Patients with Ventilation-Associated Pneumonia: An Observational, Retrospective Study

by Matthieu Rossi, Louis Delamarre, Gary Duclos, Ines Lakbar, Emmanuelle Hammad, Charlotte Arbelot, Laurent Zieleskiewicz and Marc Leone

Antibiotics 2023, 12(7), 1208; https://doi.org/10.3390/antibiotics12071208 - 20 Jul 2023

Viewed by 909

Abstract

Background: Procalcitonin (PCT) protocols to guide antibiotic treatment for ventilator-associated pneumonia (VAP) in the intensive care unit aim at reducing antibiotic exposure. Our study goal was to measure compliance with a PCT protocol for VAP and to determine the associated variables. Methods: From [...] Read more.

Background: Procalcitonin (PCT) protocols to guide antibiotic treatment for ventilator-associated pneumonia (VAP) in the intensive care unit aim at reducing antibiotic exposure. Our study goal was to measure compliance with a PCT protocol for VAP and to determine the associated variables. Methods: From 2017 to 2021, we conducted a retrospective, monocentric study including patients treated for VAP. In our PCT protocol, PCT was measured at the initiation of antibiotic treatment and every 48 h until treatment completion; antibiotics were stopped if PCT decreased by more than 80% from its highest value or fell below 0.5 ng/mL. We assessed the compliance with the PCT protocol and compared the compliant and noncompliant groups. Results: Among the 177 included patients, compliance with the PCT protocol was assessed at 58%. Noncompliance was due to lack of PCT measurements in 76% of cases. Compliance was higher in the medical patients (p = 0.04) and in those admitted for SARS-CoV-2 (p = 0.02). Compliance regarding the interruption of antibiotic therapy based on PCT was lower on weekends and holidays (p = 0.01). Outcomes did not differ according to compliance. Conclusion: This study assessed real-life compliance with the PCT protocol to monitor antibiotic treatment for VAP. Improving the measurement of PCT at the bedside would increase the rate. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Critical Care)

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14 pages, 7278 KiB

Open AccessArticle

Development of a Polymicrobial Checkerboard Assay as a Tool for Determining Combinatorial Antibiotic Effectiveness in Polymicrobial Communities

by Caroline Black, Hafij Al Mahmud, Victoria Howle, Sabrina Wilson, Allie C. Smith and Catherine A. Wakeman

Antibiotics 2023, 12(7), 1207; https://doi.org/10.3390/antibiotics12071207 - 20 Jul 2023

Viewed by 3102

Abstract

The checkerboard assay is a well-established tool used to determine the antimicrobial effects of two compounds in combination. Usually, data collected from the checkerboard assay use visible turbidity and optical density as a readout. While helpful in traditional checkerboard assays, these measurements become [...] Read more.

The checkerboard assay is a well-established tool used to determine the antimicrobial effects of two compounds in combination. Usually, data collected from the checkerboard assay use visible turbidity and optical density as a readout. While helpful in traditional checkerboard assays, these measurements become less useful in a polymicrobial context as they do not enable assessment of the drug effects on the individual members of the community. The methodology described herein allows for the determination of cell viability through selective and differential plating of each individual species in a community while retaining much of the high-throughput nature of a turbidity-based analysis and requiring no specialized equipment. This methodology further improves turbidity-based measurements by providing a distinction between bacteriostatic versus bactericidal concentrations of antibiotics. Herein, we use this method to demonstrate that the clinically used antibiotic combination of ceftazidime and gentamicin works synergistically against Pseudomonas aeruginosa in monoculture but antagonistically in a polymicrobial culture also containing Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus faecalis, highlighting the fundamental importance of this methodology in improving clinical practices. We propose that this method could be implemented in clinical microbiology laboratories with minimal impact on the overall time for diagnosis. Full article

(This article belongs to the Special Issue Improving Antimicrobial Use in the Hospital: Challenges and Possible Solutions)

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12 pages, 2153 KiB

Open AccessArticle

Probable Three-Species In Vivo Transfer of bla_NDM-1 in a Single Patient in Greece: Occurrence of NDM-1-Producing Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii

by Georgios Meletis, Andigoni Malousi, Areti Tychala, Angeliki Kassomenaki, Nikoletta Vlachodimou, Paraskevi Mantzana, Simeon Metallidis, Lemonia Skoura and Efthymia Protonotariou

Antibiotics 2023, 12(7), 1206; https://doi.org/10.3390/antibiotics12071206 - 20 Jul 2023

Viewed by 1394

Abstract

NDM carbapenemase-encoding genes disseminate commonly among Enterobacterales through transferable plasmids carrying additional resistance determinants. Apart from the intra-species dissemination, the inter-species exchange of plasmids seems to play an additional important role in the spread of bla_NDM. We here present the genetics [...] Read more.

NDM carbapenemase-encoding genes disseminate commonly among Enterobacterales through transferable plasmids carrying additional resistance determinants. Apart from the intra-species dissemination, the inter-species exchange of plasmids seems to play an additional important role in the spread of bla_NDM. We here present the genetics related to the isolation of three species (Klebsiella pneumoniae, Proteus mirabilis, and Morganella morganii) harboring the bla_NDM-1 gene from a single patient in Greece. Bacterial identification and antimicrobial susceptibility testing were performed using the Vitek2. Whole genome sequencing and bioinformatic tools were used to identify resistance genes and plasmids. Bla_NDM-1 harboring plasmids were found in all three isolates. Moreover, the plasmid constructs of the respective incomplete or circular contigs showed that the bla_NDM-1 and its neighboring genes form a cluster that was found in all isolates. Our microbiological findings, together with the patient’s history, suggest the in vivo transfer of the bla_NDM-1-containing cluster through three different species in a single patient. Full article

(This article belongs to the Special Issue Molecular Characterization of Gram-Negative Bacteria: Antimicrobial Resistance, Virulence and Epidemiology)

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11 pages, 550 KiB

Open AccessFeature PaperArticle

Real-World Data Regarding Dalbavancin Use before and during the COVID-19 Pandemic—A Single-Center Retrospective Study

by Petros Ioannou, Nora Wolff, Anna Mathioudaki, Christos Spanias, Nikolaos Spernovasilis and Diamantis P. Kofteridis

Antibiotics 2023, 12(7), 1205; https://doi.org/10.3390/antibiotics12071205 - 19 Jul 2023

Cited by 2 | Viewed by 1646

Abstract

Dalbavancin is a semisynthetic lipoglycopeptide, which possesses great potential for bactericidal activity similar to antimicrobials with the same mechanism of action, such as vancomycin and teicoplanin. Due to its very prolonged half-life, it can be used in a single or two-dose regimen to [...] Read more.

Dalbavancin is a semisynthetic lipoglycopeptide, which possesses great potential for bactericidal activity similar to antimicrobials with the same mechanism of action, such as vancomycin and teicoplanin. Due to its very prolonged half-life, it can be used in a single or two-dose regimen to treat infections by Gram-positive microorganisms, even resistant ones, such as methicillin-resistant Staphylococcus aureus (MRSA). Currently, it is approved only for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). The aim of this study was to investigate the clinical and microbiological characteristics of patients to whom dalbavancin was administered at the University Hospital of Heraklion and evaluate its use in regard to the COVID-19 pandemic. In total, 146 patients were included in this retrospective cohort study evaluating the use of dalbavancin from the first time it was used in 2017 until the end of 2022. The median age was 68 years (range: 21–96 years), and 86 (59%) patients were male. The most common indications for dalbavancin use were osteoarticular infections in 43%, followed by ABSSSIs in 37%, and cardiovascular infections in 10%. Dalbavancin was used empirically in one out of three patients, most commonly with the indication of ABSSSIs, and most commonly in the post-COVID-19 era. The most frequently isolated pathogens were coagulase-negative staphylococci in 70%, S. aureus in 27%, Enterococcus spp. in 22%, and Streptococcus spp. in 8%, while one out of three infections were polymicrobial. In 12% of patients, the infection was not cured, but no patients died. For patients with ABSSSIs, endocarditis and vascular infections, and bacteremia, the cure rates were more than 90%, and in osteoarticular infections, the cure rate was 76%. Thus, dalbavancin has great potential for use in complicated and invasive infections that may require prolonged intravenous antimicrobial treatment. However, further studies are required to formally investigate its role in such infections. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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17 pages, 1811 KiB

Open AccessArticle

Incidence and Genomic Background of Antibiotic Resistance in Food-Borne and Clinical Isolates of Salmonella enterica Serovar Derby from Spain

by Xenia Vázquez, Raquel García-Fierro, Javier Fernández, Margarita Bances, Ana Herrero-Fresno, John E. Olsen, Rosaura Rodicio, Víctor Ladero, Vanesa García and M. Rosario Rodicio

Antibiotics 2023, 12(7), 1204; https://doi.org/10.3390/antibiotics12071204 - 19 Jul 2023

Cited by 1 | Viewed by 1259

Abstract

Salmonella enterica serovar Derby (S. Derby) ranks fifth among nontyphoidal Salmonella serovars causing human infections in the European Union. S. Derby isolates (36) collected between 2006 and 2018 in a Spanish region (Asturias) from human clinical samples (20) as well [...] Read more.

Salmonella enterica serovar Derby (S. Derby) ranks fifth among nontyphoidal Salmonella serovars causing human infections in the European Union. S. Derby isolates (36) collected between 2006 and 2018 in a Spanish region (Asturias) from human clinical samples (20) as well as from pig carcasses, pork- or pork and beef-derived products, or wild boar (16) were phenotypically characterized with regard to resistance, and 22 (12 derived from humans and 10 from food-related samples) were also subjected to whole genome sequence analysis. The sequenced isolates belonged to ST40, a common S. Derby sequence type, and were positive for SPI-23, a Salmonella pathogenicity island involved in adherence and invasion of the porcine jejune enterocytes. Isolates were either susceptible (30.6%), or resistant to one or more of the 19 antibiotics tested for (69.4%). Resistances to tetracycline [tet(A), tet(B) and tet(C)], streptomycin (aadA2), sulfonamides (sul1), nalidixic acid [gyrA (Asp87 to Asn)] and ampicillin (bla_TEM-1-like) were detected, with frequencies ranging from 8.3% to 66.7%, and were higher in clinical than in food-borne isolates. The fosA7.3 gene was present in all sequenced isolates. The most common phenotype was that conferred by the tet(A), aadA2 and sul1 genes, located within identical or closely related variants of Salmonella Genomic Island 1 (SGI1), where mercury resistance genes were also present. Diverse IncI1-I(α) plasmids belonging to distinct STs provided antibiotic [bla_TEM-1, tet(A) and/or tet(B)] and heavy metal resistance genes (copper and silver), while small pSC101-like plasmids carried tet(C). Regardless of their location, most resistance genes were associated with genetic elements involved in DNA mobility, including a class one integron, multiple insertion sequences and several intact or truncated transposons. By phylogenetic analysis, the isolates were distributed into two distinct clades, both including food-borne and clinical isolates. One of these clades included all SGI1-like positive isolates, which were found in both kinds of samples throughout the entire period of study. Although the frequency of S. Derby in Asturias was very low (0.5% and 3.1% of the total clinical and food isolates of S. enterica recovered along the period of study), it still represents a burden to human health linked to transmission across the food chain. The information generated in the present study can support further epidemiological surveillance aimed to control this zoonotic pathogen. Full article

(This article belongs to the Special Issue Foodborne Antimicrobial Resistance: A Cause for Concern)

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14 pages, 324 KiB

Open AccessArticle

Surveys on Pet-Reptile-Associated Multi-Drug-Resistant Salmonella spp. in the Timișoara Metropolitan Region—Western Romania

by János Dégi, Viorel Herman, Isidora Radulov, Florica Morariu, Tiana Florea and Kálmán Imre

Antibiotics 2023, 12(7), 1203; https://doi.org/10.3390/antibiotics12071203 - 19 Jul 2023

Cited by 4 | Viewed by 1137

Abstract

The number of reptiles owned as pets has risen worldwide. Additionally, urban expansion has resulted in more significant human encroachment and interactions with the habitats of captive reptiles. Between May and October 2022, 48 reptiles from pet shops and 69 from households were [...] Read more.

The number of reptiles owned as pets has risen worldwide. Additionally, urban expansion has resulted in more significant human encroachment and interactions with the habitats of captive reptiles. Between May and October 2022, 48 reptiles from pet shops and 69 from households were sampled in the Timișoara metropolitan area (western Romania). Three different sample types were collected from each reptile: oral cavity, skin, and cloacal swabs. Salmonella identification was based on ISO 6579-1:2017 (Annex D), a molecular testing method (invA gene target), and strains were serotyped in accordance with the Kauffman–White–Le-Minor technique; the antibiotic susceptibility was assessed according to Decision 2013/652. This study showed that 43.28% of the pet reptiles examined from households and pet shops carried Salmonella spp. All of the strains isolated presented resistance to at least one antibiotic, and 79.32% (23/29) were multi-drug-resistant strains, with the most frequently observed resistances being to gentamicin, nitrofurantion, tobramycin, and trimethoprim–sulfamethoxazole. The findings of the study undertaken by our team reveal that reptile multi-drug-resistant Salmonella is present. Considering this aspect, the most effective way of preventing multi-drug-resistant Salmonella infections requires stringent hygiene control in reptile pet shops as well as ensuring proper animal handling once the animals leave the pet shop and are introduced into households. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Virulence in Veterinary Pathogens)

12 pages, 6743 KiB

Open AccessCommunication

Synthesis and Antibacterial Activity of Polyalthic Acid Analogs

by Marcela Nunes Argentin, Felipe de Paula Nogueira Cruz, Ariana Borges Souza, Elisa Marcela de Oliveira D’Aurea, Jairo Kenupp Bastos, Sérgio Ricardo Ambrósio, Rodrigo Cassio Sola Veneziani, Ilana Lopes Baratella Cunha Camargo and Cassia Suemi Mizuno

Antibiotics 2023, 12(7), 1202; https://doi.org/10.3390/antibiotics12071202 - 19 Jul 2023

Cited by 1 | Viewed by 3157

Abstract

Polyalthic acid (PA) is a diterpene found in copaiba oil. As a continuation of our work with PA, we synthesized PA analogs and investigated their antibacterial effects on preformed biofilms of Staphylococcus epidermidis and determined the minimal inhibitory concentration (MIC) of the best [...] Read more.

Polyalthic acid (PA) is a diterpene found in copaiba oil. As a continuation of our work with PA, we synthesized PA analogs and investigated their antibacterial effects on preformed biofilms of Staphylococcus epidermidis and determined the minimal inhibitory concentration (MIC) of the best analogs against planktonic bacterial cells. There was no difference in activity between the amides 2a and 2b and their corresponding amines 3a and 3b regarding their ability to eradicate biofilm. PA analogs 2a and 3a were able to significantly eradicate the preformed biofilm of S. epidermidis and were active against all the Gram-positive bacteria tested (Enterococcus faecalis, Enterococcus faecium, S. epidermidis, Staphylococcus aureus), with different MIC depending on the microorganism. Therefore, PA analogs 2a and 3a are of interest for further in vitro and in vivo testing to develop formulations for antibiotic drugs against Gram-positive bacteria. Full article

(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)

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15 pages, 1164 KiB

Open AccessArticle

Antimicrobial and Cytotoxic Activities of the Secondary Metabolites of Endophytic Fungi Isolated from the Medicinal Plant Hyssopus officinalis

by Farkhod Eshboev, Marina Karakozova, Jaloliddin Abdurakhmanov, Khayrulla Bobakulov, Khayotjon Dolimov, Akhror Abdurashidov, Asadali Baymirzaev, Artyom Makhnyov, Ekaterina Terenteva, Sobirdjan Sasmakov, Galina Piyakina, Dilfuza Egamberdieva, Pavel A. Nazarov and Shakhnoz Azimova

Antibiotics 2023, 12(7), 1201; https://doi.org/10.3390/antibiotics12071201 - 18 Jul 2023

Cited by 2 | Viewed by 2013

Abstract

According to the World Health Organization, it is estimated that by 2050, drug-resistant infections could cause up to 10 million deaths annually. Therefore, finding a new generation of antibiotics is crucial. Natural compounds from endophytic fungi are considered a potential source of new-generation [...] Read more.

According to the World Health Organization, it is estimated that by 2050, drug-resistant infections could cause up to 10 million deaths annually. Therefore, finding a new generation of antibiotics is crucial. Natural compounds from endophytic fungi are considered a potential source of new-generation antibiotics. The antimicrobial and cytotoxic effects of ethyl acetate extracts of nine endophytic fungal isolates obtained from Hyssopus officinalis were investigated for bioassay-guided isolation of the natural compounds. An extract of isolate VII showed the highest antimicrobial activities against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus (30.12 ± 0.20 mm and 35.21 ± 0.20 mm) and Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa (30.41 ± 0.23 mm and 25.12 ± 0.25 mm) among the tested extracts of isolates. Molecular identification of isolate VII confirmed it as Chaetomium elatum based on sequencing of its ITS genes, and it was discovered that this was the first time C. elatum had been isolated from H. officinalis. This isolate was cultured at a large scale for the isolation and identification of the active compound. Penicillic acid was isolated for the first time from C. elatum and its chemical structure was established by NMR spectroscopy. The penicillic acid showed strong antibacterial activities against Bacillus subtilis and Staphylococcus aureus with 20.68 mm and 25.51 mm inhibition zones, respectively. In addition, MIC and MBC values and antibiofilm activities of penicillic acid were determined. It was found that penicillic acid reduced the level of biofilms in proportion to antibacterial activity. Full article

(This article belongs to the Section Antibiofilm Strategies)

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14 pages, 2145 KiB

Open AccessEditor’s ChoiceArticle

Moving toward Extensively Drug-Resistant: Four-Year Antimicrobial Resistance Trends of Acinetobacter baumannii from the Largest Department of Internal Medicine in Slovakia

by Yashar Jalali, Adriána Liptáková, Monika Jalali and Juraj Payer

Antibiotics 2023, 12(7), 1200; https://doi.org/10.3390/antibiotics12071200 - 18 Jul 2023

Cited by 2 | Viewed by 1151

Abstract

A. baumannii imposes a great burden on medical systems worldwide. Surveillance of trends of antibiotic resistance provides a great deal of information needed for antimicrobial stewardship programmes nationwide. Clinical data from long-term, continuous surveillance on trends of antibiotic resistance of A. baumannii in [...] Read more.

A. baumannii imposes a great burden on medical systems worldwide. Surveillance of trends of antibiotic resistance provides a great deal of information needed for antimicrobial stewardship programmes nationwide. Clinical data from long-term, continuous surveillance on trends of antibiotic resistance of A. baumannii in Slovakia is missing. One hundred and forty-nine samples of A. baumannii were isolated over a period of four years. A panel of 19 antibiotics from seven antibiotic categories were tested for the bacterium’s susceptibility. Resistance results were evaluated, and the significance of patterns was estimated using simple linear regression analysis. All isolates were more than 85% resistant to at least 13 out of the 19 tested antibiotics. A significant rise in resistance was recorded for aminoglycosides and imipenem from 2019 to 2022. Colistin and ampicillin-sulbactam have been the only antibiotics maintaining more than 80% efficacy on the bacterium to date. A significant rise in extensively drug-resistant (XDR) strains among carbapenem-resistant (CR) isolates has been recorded. Multidrug-resistance (MDR) among all A. baumannii isolates and XDR among CR strains of the bacterium have risen significantly in the last four years. Full article

(This article belongs to the Special Issue Strategies for Combatting Multidrug-Resistant and Extensively Drug-Resistant Bacteria: Current Challenges and Future Prospects)

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Open AccessArticle

Multi-Model Strategies for Prevention of Infection Caused by Certain Multi-Drug Resistant Organisms in A Rehabilitation Unit: A Semi-Experimental Study

by Shiyu Li, Ji Lin, Siyuan Tao, Linwen Guo, Wenzhi Huang, Jingwen Li, Chunping Du, Zhiting Wang, Liwen Liu, Yi Chen and Fu Qiao

Antibiotics 2023, 12(7), 1199; https://doi.org/10.3390/antibiotics12071199 - 18 Jul 2023

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Abstract

Objective: To assess the effectiveness of multi-model strategies on healthcare-associated infections (HAIs) caused by multi-drug resistant organisms (MDROs) in rehabilitation units. Methods: A semi-experimental study was conducted in a rehabilitation unit with 181 beds from January 2021 to December 2022 in a teaching [...] Read more.

Objective: To assess the effectiveness of multi-model strategies on healthcare-associated infections (HAIs) caused by multi-drug resistant organisms (MDROs) in rehabilitation units. Methods: A semi-experimental study was conducted in a rehabilitation unit with 181 beds from January 2021 to December 2022 in a teaching hospital with 4300 beds in China. In 2021, many basic prevention and control measures were conducted routinely. Based on the basic measures, strengthening multi-model strategies for the prevention and control of MDROs was pursued year-round since 1 January 2022. Results: A total of 6206 patients were enrolled during the study period. The incidence density of HAIs caused by MDROs decreased from 1.22 (95% CI, 0.96~1.54) cases/1000 patient-days in the pre-intervention period to 0.70 (95% CI, 0.50~0.95) cases/1000 patient-days (p = 0.004). Similarly, the incidence of HAIs in the intervention period was 50.85% lower than that in the pre-intervention period (2.02 (95% CI, 1.50~2.72) vs. 4.11 (95% CI, 3.45–4.85) cases/100 patients, p < 0.001). The rate of MDROs isolated from the environment decreased by 30.00%, although the difference was not statistically significant (p = 0.259). Conclusion: Multi-model strategies can reduce the incidence of HAIs and HAIs caused by certain MDROs in the rehabilitation unit. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Hospital- and Community-Associated Infections)

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10 pages, 2304 KiB

Open AccessArticle

Prevalence of Carbapenemases in Carbapenem-Resistant Acinetobacter baumannii Isolates from the Kingdom of Bahrain

by Nouf Al-Rashed, Khalid M. Bindayna, Mohammad Shahid, Nermin Kamal Saeed, Abdullah Darwish, Ronni Mol Joji and Ali Al-Mahmeed

Antibiotics 2023, 12(7), 1198; https://doi.org/10.3390/antibiotics12071198 - 17 Jul 2023

Cited by 2 | Viewed by 1518

Abstract

Background: Acinetobacter baumannii is regarded as a significant cause of death in hospitals. The WHO recently added carbapenem-resistant Acinetobacter baumannii (CRAB) to its global pathogen priority list. There is a dearth of information on CRAB from our region. Methods: Fifty CRAB isolates were [...] Read more.

Background: Acinetobacter baumannii is regarded as a significant cause of death in hospitals. The WHO recently added carbapenem-resistant Acinetobacter baumannii (CRAB) to its global pathogen priority list. There is a dearth of information on CRAB from our region. Methods: Fifty CRAB isolates were collected from four main hospitals in Bahrain for this study. Bacterial identification and antibiotic susceptibility tests were carried out using the BD Phoenix^TM and VITEK-2 compact, respectively. Using conventional PCR, these isolates were further screened for carbapenem resistance markers (bla_OXA-51, bla_OXA-23, blaO_XA-24, bla_OXA-40, bla_IMP, bla_NDM, bla_VIM, and bla_KPC). Results: All of the isolates were resistant to imipenem (100%), meropenem (98%), and cephalosporins (96–98%), followed by other commonly used antibiotics. All these isolates were least resistant to gentamicin (64%). The detection of resistance determinants showed that the majority harbored bla_OXA-51 (100%) and bla_IMP (94%), followed by bla_OXA-23 (82%), bla_OXA-24 (46%), bla_OXA-40 (14%), bla_NDM (6%), bla_VIM (2%), and bla_KPC (2%). Conclusion: The study isolates showed a high level of antibiotic resistance. Class D carbapenemases were more prevalent in our CRAB isolate collection. The resistance genes were found in various combinations. This study emphasizes the importance of strengthening surveillance and stringent infection control measures in clinical settings to prevent the emergence and further spread of such isolates. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

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Antibiotics, Volume 12, Issue 7 (July 2023) – 148 articles

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