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Antibiotics
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The Emergence of Drug-Resistant Staphylococcus aureus Infection and Recent Advances...
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The Emergence of Drug-Resistant Staphylococcus aureus Infection and Recent Advances in Treatment Options

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (30 November 2024) | Viewed by 13968

Special Issue Editor

Dr. Rajan P. Adhikari

E-Mail Website
Guest Editor
Integrated Biotherapeutics, Inc., Rockville, MD, USA
Interests: bacterial toxins; host-pathogen interactions; bacterial pathogens; Staphylococcus aureus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Staphylococcus aureus is a facultative pathogen that can cause a wide range of diseases, from mild infections of the skin and soft tissues to life-threatening conditions such as pneumonia, septicemia, and endocarditis. In addition, it is highly successful in acquiring drug resistance. Penicillin was the first antibiotic discovered and was widely used until 80% of S. aureus acquired penicillin resistance. The first semisynthetic penicillinase-resistant penicillin, called 'methicillin', was introduced in 1959 to address this problem. However, within two years, in 1961, methicillin-resistant S. aureus (MRSA) was reported. Soon, Penicillin-resistant S. aureus was replaced by hospital-acquired MRSA strains. Some clones of MRSA led to an MRSA epidemic that rapidly spread throughout Europe. Along with the introduction of new antibiotics, new waves of MRSA strains appeared. In early 2000, a new version of the MRSA strain, known as community MRSA (CMRSA), emerged.  Vancomycin was introduced as a last-resort drug to cope with these new MRSA waves. However, vancomycin-intermediate-resistant (VISA) and vancomycin-resistant S. aureus (VRSA) emerged soon. This bug has successfully overcome every new antibiotic introduced so far. Moreover, all vaccines and therapeutic efforts against this bug have failed clinical trials. Hopefully, the continuous efforts using novel approaches will result in more effective classes of anti-MRSA drugs. This Special issue aims to track the emergence and mechanism of new antibiotic resistance in S. aureus along with the recent advancements and progress in drug development.

Dr. Rajan P. Adhikari
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • S. aureus
  • Methicillin Resistant S. aureus (MRSA)
  • Vancomycin Resistant S. aureus (VRSA)
  • antimicrobial resistance (AMR)
  • multiple drug resistance (MDR)
  • skin and soft tissue infection
  • antibiotics
  • anti-Staphylococcal vaccine, and therapy

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Published Papers (5 papers)

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Research

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12 pages, 923 KiB  
Article
Target Attainment and Population Pharmacokinetics of Cefazolin in Patients with Invasive Staphylococcus aureus Infections: A Prospective Cohort Study
by Severin Bausch, Sarah Dräger, Panteleimon Charitos-Fragkakis, Adrian Egli, Stephan Moser, Vladimira Hinic, Richard Kuehl, Stefano Bassetti, Martin Siegemund, Katharina M. Rentsch, Laura Hermann, Verena Schöning, Felix Hammann, Parham Sendi and Michael Osthoff
Antibiotics 2024, 13(10), 928; https://doi.org/10.3390/antibiotics13100928 - 29 Sep 2024
Viewed by 1236
Abstract
This study aimed to determine cefazolin target attainment in patients with invasive Staphylococcus aureus (S. aureus) infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive S. aureus infections treated with cefazolin bolus infusions were included. Unbound and [...] Read more.
This study aimed to determine cefazolin target attainment in patients with invasive Staphylococcus aureus (S. aureus) infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive S. aureus infections treated with cefazolin bolus infusions were included. Unbound and total trough and mid-dose cefazolin concentrations were measured, and strain-specific MICs were determined. The primary outcome was the proportion of patients attaining 100% fT>MIC at all time points evaluated. A population PK model was developed, using non-linear mixed-effects modelling. Overall, 51 patients were included, with a total of 226 unbound and total cefazolin concentrations measured (mean: 4.4 per patient). The median daily dosage in patients with an estimated glomerular filtration rate of >60 mL/min/m2 was 8 g. The median age was 74 years (interquartile range (IQR) 57–82) and 26% were female. A history of chronic kidney disease and acute kidney injury were present in 10/51 (19.6%) and 6/51 (11.7%), respectively. Achievement of 100% fT>MIC occurred in 86% of the patients and decreased to 45% when a target of 100% fT>4xMIC was evaluated. The mean unbound cefazolin fraction was 27.0% (standard deviation (SD) 13.4). Measured and estimated mean cefazolin trough concentrations differed significantly [13.1 mg/L (SD 23.5) vs. 7.4 mg/L (SD 7.9), p < 0.001]. In the population PK model, elevated estimated creatinine clearance and bolus instead of continuous application were covariates for target non-attainment. In conclusion, cefazolin target achievement was high, and the measurement of the unbound cefazolin concentration may be favored. The Monte Carlo simulations indicated that target attainment was significantly improved with continuous infusion. Full article
(This article belongs to the Special Issue The Emergence of Drug-Resistant Staphylococcus aureus Infection and Recent Advances in Treatment Options)
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28 pages, 20130 KiB  
Article
A Novel Bacitracin-like Peptide from Mangrove-Isolated Bacillus paralicheniformis NNS4-3 against MRSA and Its Genomic Insights
by Namfa Sermkaew, Apichart Atipairin, Thamonwan Wanganuttara, Sucheewin Krobthong, Chanat Aonbangkhen, Yodying Yingchutrakul, Jumpei Uchiyama and Nuttapon Songnaka
Antibiotics 2024, 13(8), 716; https://doi.org/10.3390/antibiotics13080716 - 30 Jul 2024
Cited by 2 | Viewed by 1644
Abstract
The global rise of antimicrobial resistance (AMR) presents a critical challenge necessitating the discovery of novel antimicrobial agents. Mangrove microbes are valuable sources of new antimicrobial compounds. This study reports the discovery of a potent antimicrobial peptide (AMP) from Bacillus paralicheniformis NNS4-3, isolated [...] Read more.
The global rise of antimicrobial resistance (AMR) presents a critical challenge necessitating the discovery of novel antimicrobial agents. Mangrove microbes are valuable sources of new antimicrobial compounds. This study reports the discovery of a potent antimicrobial peptide (AMP) from Bacillus paralicheniformis NNS4-3, isolated from mangrove sediment, exhibiting significant activity against methicillin-resistant Staphylococcus aureus (MRSA). The AMP demonstrated a minimum inhibitory concentration ranging from 1 to 16 µg/mL in the tested bacteria and exhibited bactericidal effects at higher concentrations. Structural analysis revealed a bacitracin-like configuration and the peptide acted by disrupting bacterial membranes in a time- and concentration-dependent manner. The AMP maintained stability under heat, proteolytic enzymes, surfactants, and varying pH treatments. The ten biosynthetic gene clusters (BGCs) of secondary metabolites were found in the genome. Detailed sequence comparison of the predicted bacitracin BGC indicated distinct DNA sequences compared to previously reported strains. Although the antibiotic resistance genes were found, this strain was susceptible to antibiotics. Our findings demonstrated the potential of Bacillus paralicheniformis NNS4-3 and its AMP as a promising agent in combating AMR. The genetic information could be pivotal for future applications in the healthcare industry, emphasizing the need for continued exploration of marine microbial diversity in drug discovery. Full article
(This article belongs to the Special Issue The Emergence of Drug-Resistant Staphylococcus aureus Infection and Recent Advances in Treatment Options)
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17 pages, 6090 KiB  
Article
Using Targeted Nano-Antibiotics to Improve Antibiotic Efficacy against Staphylococcus aureus Infections
by Hung Le, Emmanuelle Dé, Didier Le Cerf and Carole Karakasyan
Antibiotics 2023, 12(6), 1066; https://doi.org/10.3390/antibiotics12061066 - 16 Jun 2023
Cited by 2 | Viewed by 2971
Abstract
The poor bioavailability of antibiotics at infection sites is one of the leading causes of treatment failure and increased bacterial resistance. Therefore, developing novel, non-conventional antibiotic delivery strategies to deal with bacterial pathogens is essential. Here, we investigated the encapsulation of two fluoroquinolones, [...] Read more.
The poor bioavailability of antibiotics at infection sites is one of the leading causes of treatment failure and increased bacterial resistance. Therefore, developing novel, non-conventional antibiotic delivery strategies to deal with bacterial pathogens is essential. Here, we investigated the encapsulation of two fluoroquinolones, ciprofloxacin and levofloxacin, into polymer-based nano-carriers (nano-antibiotics), with the goal of increasing their local bioavailability at bacterial infection sites. The formulations were optimized to achieve maximal drug loading. The surfaces of nano-antibiotics were modified with anti-staphylococcal antibodies as ligand molecules to target S. aureus pathogens. The interaction of nano-antibiotics with the bacterial cells was investigated via fluorescent confocal microscopy. Conventional tests (MIC and MBC) were used to examine the antibacterial properties of nano-antibiotic formulations. Simultaneously, a bioluminescence assay model was employed, revealing the rapid and efficient assessment of the antibacterial potency of colloidal systems. In comparison to the free-form antibiotic, the targeted nano-antibiotic exhibited enhanced antimicrobial activity against both the planktonic and biofilm forms of S. aureus. Furthermore, our data suggested that the efficacy of a targeted nano-antibiotic treatment can be influenced by its antibiotic release profile. Full article
(This article belongs to the Special Issue The Emergence of Drug-Resistant Staphylococcus aureus Infection and Recent Advances in Treatment Options)
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Review

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23 pages, 4140 KiB  
Review
The Opportunistic Pathogen Staphylococcus warneri: Virulence and Antibiotic Resistance, Clinical Features, Association with Orthopedic Implants and Other Medical Devices, and a Glance at Industrial Applications
by Stefano Ravaioli, Andrea De Donno, Giulia Bottau, Davide Campoccia, Alessandra Maso, Paolo Dolzani, Paulraj Balaji, Francesco Pegreffi, Maria Daglia and Carla Renata Arciola
Antibiotics 2024, 13(10), 972; https://doi.org/10.3390/antibiotics13100972 - 15 Oct 2024
Cited by 1 | Viewed by 3583
Abstract
In recent decades, the risk of developing opportunistic infections has increased in parallel with the ever-increasing number of people suffering from chronic immunosuppressive diseases or undergoing prosthetic surgery. Staphylococcus warneri is a Gram-positive and coagulase-negative bacterium. Usually found as a component of the [...] Read more.
In recent decades, the risk of developing opportunistic infections has increased in parallel with the ever-increasing number of people suffering from chronic immunosuppressive diseases or undergoing prosthetic surgery. Staphylococcus warneri is a Gram-positive and coagulase-negative bacterium. Usually found as a component of the healthy human and animal microbiota of the skin and mucosae, it can take on the role of an opportunistic pathogen capable of causing a variety of infections, ranging from mild to life-threatening, not only in immunocompromised patients but even, although rarely, in healthy people. Here, in addition to a concise discussion of the identification and distinguishing features of S. warneri compared to other staphylococcal species, a systematic overview of the findings from case reports and clinical studies is provided. The paper highlights the virulence and antibiotic resistance profiles of S. warneri, the different clinical contexts in which it has proven to be a serious pathogen, emphasizing its ability to colonize artificial prosthetic materials and its tropism for musculoskeletal and cardiovascular tissues. Some original data on orthopedic implant infections by S. warneri complement the discussion. Finally, from a different perspective, the paper addresses the possibilities of industrial exploitation of this bacterium. Full article
(This article belongs to the Special Issue The Emergence of Drug-Resistant Staphylococcus aureus Infection and Recent Advances in Treatment Options)
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17 pages, 703 KiB  
Review
The Epidemiology of Animal-Associated Methicillin-Resistant Staphylococcus aureus
by Martyna Kasela, Mateusz Ossowski, Ewelina Dzikoń, Katarzyna Ignatiuk, Łukasz Wlazło and Anna Malm
Antibiotics 2023, 12(6), 1079; https://doi.org/10.3390/antibiotics12061079 - 20 Jun 2023
Cited by 8 | Viewed by 3234
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) remains an important etiological factor of human and animal infectious diseases, causing significant economic losses not only in human healthcare but also in the large-scale farming sector. The constantly changing epidemiology of MRSA observed globally affects animal welfare and [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) remains an important etiological factor of human and animal infectious diseases, causing significant economic losses not only in human healthcare but also in the large-scale farming sector. The constantly changing epidemiology of MRSA observed globally affects animal welfare and raises concerns for public health. High MRSA colonization rates in livestock raise questions about the meaning of reservoirs and possible transmission pathways, while the prevalence of MRSA colonization and infection rates among companion animals vary and might affect human health in multiple ways. We present the main findings concerning the circulation of animal-associated MRSA (AA-MRSA) in the environment and factors influencing the direction, mechanisms, and routes of its transmission. Studies have shown it that S. aureus is a multi-host bacterial pathogen; however, its adaptation mechanisms enabling it to colonize and infect both animal and human hosts are still rarely discussed. Finally, we elaborate on the most successful strategies and programs applied limiting the circulation of AA-MRSA among animals and humans. Although MRSA strains colonizing animals rarely infect humans, they undergo host-adaptive evolution enabling them to spread and persist in human populations. Full article
(This article belongs to the Special Issue The Emergence of Drug-Resistant Staphylococcus aureus Infection and Recent Advances in Treatment Options)
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