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Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules...
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Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze Out New Ones

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotics Use and Antimicrobial Stewardship".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 72967

Special Issue Editor

Dr. Stefano Di Bella

E-Mail Website
Guest Editor
Clinical Department of Medical, Surgical and Health Sciences, Trieste University, Trieste, Italy
Interests: antibiotics; synergism; pharmacokinetic; Clostridioides difficile; antimicrobial stewardship
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Knowing how to manage old and new antibiotics makes the difference in the clinical course of severe infections. In this Special Issue, we present papers that can provide insights to optimize old and new antimicrobial use in particular situations. Manuscripts on unconventional antimicrobial strategies to optimize outcomes are also warmly welcomed.

Dr. Stefano Di Bella
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • cytokine adsorbers
  • old antibiotics
  • off-label use of new antibiotics
  • phage therapy
  • VRE
  • aztreonam
  • antibiotic comparison

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Published Papers (8 papers)

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Editorial

Jump to: Research, Review

2 pages, 181 KiB  
Editorial
Editorial for the Special Issue: “Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze out New Ones”
by Stefano Di Bella
Antibiotics 2022, 11(5), 597; https://doi.org/10.3390/antibiotics11050597 - 29 Apr 2022
Viewed by 1531
Abstract
The optimization of a number of strategies is required to overcome the problem of antibiotic resistance [...] Full article
(This article belongs to the Special Issue Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze Out New Ones)

Research

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10 pages, 630 KiB  
Article
Determination of a Tentative Epidemiological Cut-Off Value (ECOFF) for Dalbavancin and Enterococcus faecium
by Robert E. Weber, Carola Fleige, Franziska Layer, Bernd Neumann, Michael Kresken and Guido Werner
Antibiotics 2021, 10(8), 915; https://doi.org/10.3390/antibiotics10080915 - 27 Jul 2021
Cited by 11 | Viewed by 2878
Abstract
Dalbavancin is a lipoglycopeptide antibiotic that shows potent activity against Gram-positive bacteria. It circumvents vanB-type glycopeptide resistance mechanisms; however, data on the in vitro activity of dalbavancin for Enterococcus faecium (E. faecium) are scarce, and thus, no breakpoints are provided. [...] Read more.
Dalbavancin is a lipoglycopeptide antibiotic that shows potent activity against Gram-positive bacteria. It circumvents vanB-type glycopeptide resistance mechanisms; however, data on the in vitro activity of dalbavancin for Enterococcus faecium (E. faecium) are scarce, and thus, no breakpoints are provided. In recent years, there has been a continuing shift from vanA-type to vanB-type vancomycin-resistance in enterococci in Central Europe. Therefore, we aimed to investigate the in vitro activity of dalbavancin against different van-genotypes, with particular focus on vanB-type E. faecium. Dalbavancin susceptibility was determined for 25 van-negative, 50 vanA-positive, and 101 vanB-positive clinical E. faecium isolates (typed by cgMLST). Epidemiological Cut-Off Values (ECOFFs) were determined using ECOFFinder. For vanB-type E. faecium isolates, dalbavancin MICs were similar to those of vancomycin-susceptible isolates reaching values no higher than 0.125 mg/L. ECOFFs for van-negative and vanB-positive isolates were 0.5 mg/l and 0.25 mg/L respectively. In contrast, E. faecium possessing vanA predominantly showed dalbavancin MICs >8 mg/L, therefore preventing the determination of an ECOFF. We demonstrated the potent in vitro activity of dalbavancin against vancomycin-susceptible and vanB-type E. faecium. On the basis of the observed wildtype distribution, a dalbavancin MIC of 0.25 mg/L can be suggested as a tentative ECOFF for E. faecium. Full article
(This article belongs to the Special Issue Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze Out New Ones)
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Review

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17 pages, 1280 KiB  
Review
Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic
by Tommaso Lupia, Ilaria De Benedetto, Giacomo Stroffolini, Stefano Di Bella, Simone Mornese Pinna, Verena Zerbato, Barbara Rizzello, Roberta Bosio, Nour Shbaklo, Silvia Corcione and Francesco Giuseppe De Rosa
Antibiotics 2022, 11(4), 493; https://doi.org/10.3390/antibiotics11040493 - 7 Apr 2022
Cited by 11 | Viewed by 4664
Abstract
Temocillin is an old antibiotic, but given its particular characteristics, it may be a suitable alternative to carbapenems for treating infections due to ESBL-producing Enterobacterales and uncomplicated UTI due to KPC-producers. In this narrative review, the main research question was to summarize current [...] Read more.
Temocillin is an old antibiotic, but given its particular characteristics, it may be a suitable alternative to carbapenems for treating infections due to ESBL-producing Enterobacterales and uncomplicated UTI due to KPC-producers. In this narrative review, the main research question was to summarize current evidence on temocillin and its uses in infectious diseases. A search was run on PubMed using the terms (‘Temocillin’ [Mesh]) AND (‘Infection’ [Mesh]). Current knowledge regarding temocillin in urinary tract infection, blood-stream infections, pneumonia, intra-abdominal infections, central nervous system infections, skin and soft tissues infections, surgical sites infections and osteoarticular Infections were summarized. Temocillin retain a favourable profile on microbiota and risk of Clostridioides difficile infections and could be an option for treating outpatients. Temocillin may be a valuable tool to treat susceptible pathogens and for which a carbapenem could be spared. Other advantages in temocillin use are that it is well-tolerated; it is associated with a low rate of C. difficile infections; it is active against ESBL, AmpC, and KPC-producing Enterobacterales; and it can be used in the OPAT clinical setting. Full article
(This article belongs to the Special Issue Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze Out New Ones)
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6 pages, 219 KiB  
Review
The Effects of Hemoadsorption on the Kinetics of Antibacterial and Antifungal Agents
by Giorgio Berlot, Stefano Di Bella, Ariella Tomasini and Erik Roman-Pognuz
Antibiotics 2022, 11(2), 180; https://doi.org/10.3390/antibiotics11020180 - 29 Jan 2022
Cited by 6 | Viewed by 3004
Abstract
The extracorporeal elimination of a pathogen or damage-associated molecular pattern via blood purification techniques is increasingly being used in patients with septic shock and other clinical conditions characterized by a life-threatening inflammatory response. The removal of these substances can be accomoplished by means [...] Read more.
The extracorporeal elimination of a pathogen or damage-associated molecular pattern via blood purification techniques is increasingly being used in patients with septic shock and other clinical conditions characterized by a life-threatening inflammatory response. The removal of these substances can be accomoplished by means of ultrafiltration or hemoadsorption. Independently from the blood putification technique used, they could also affect the clearance of antibacterial and antifungal agents with a potentially significant clinical impact. In our review, we describe the basic principles of ultrafiltration and hemoadsorption, the available devices for this latter and the existing experimental and clinical studies; the final paragraph is dedicated to practical considerations that can help clinicians to consider the clearance of antibiotics and antifungals attributable to these techniques to minimize the risk of a iatrogenic underdosage. Full article
(This article belongs to the Special Issue Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze Out New Ones)
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19 pages, 732 KiB  
Review
Antibiotics and Liver Cirrhosis: What the Physicians Need to Know
by Caterina Zoratti, Rita Moretti, Lisa Rebuzzi, Irma Valeria Albergati, Antonietta Di Somma, Giuliana Decorti, Stefano Di Bella, Lory Saveria Crocè and Mauro Giuffrè
Antibiotics 2022, 11(1), 31; https://doi.org/10.3390/antibiotics11010031 - 28 Dec 2021
Cited by 19 | Viewed by 23856
Abstract
The liver is the primary site of drug metabolism, which can be altered by a variety of diseases affecting the liver parenchyma, especially in patients with liver cirrhosis. The use of antibiotics in patients with cirrhosis is usually a matter of concern for [...] Read more.
The liver is the primary site of drug metabolism, which can be altered by a variety of diseases affecting the liver parenchyma, especially in patients with liver cirrhosis. The use of antibiotics in patients with cirrhosis is usually a matter of concern for physicians, given the lack of practical knowledge for drug choice and eventual dose adjustments in several clinical scenarios. The aim of the current narrative review is to report, as broadly as possible, basic, and practical knowledge that any physician should have when approaching a patient with liver cirrhosis and an ongoing infection to efficiently choose the best antibiotic therapy. Full article
(This article belongs to the Special Issue Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze Out New Ones)
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16 pages, 1484 KiB  
Review
Daptomycin versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infection with or without Endocarditis: A Systematic Review and Meta-Analysis
by Alberto Enrico Maraolo, Agnese Giaccone, Ivan Gentile, Annalisa Saracino and Davide Fiore Bavaro
Antibiotics 2021, 10(8), 1014; https://doi.org/10.3390/antibiotics10081014 - 21 Aug 2021
Cited by 32 | Viewed by 6460
Abstract
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of invasive infections, mainly bloodstream infections (BSI) with or without endocarditis. The purpose of this meta-analysis was to compare vancomycin, the mainstay treatment, with daptomycin as therapeutic options in this context. Materials: PubMed, Embase [...] Read more.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of invasive infections, mainly bloodstream infections (BSI) with or without endocarditis. The purpose of this meta-analysis was to compare vancomycin, the mainstay treatment, with daptomycin as therapeutic options in this context. Materials: PubMed, Embase and the Cochrane Database were searched from their inception to 15 February 2020. The primary outcome was all-cause mortality. Secondary outcomes included clinical failure, infection recurrence, persistence of infection, length-of-stay, antibiotic discontinuation due to adverse events (AEs) and 30-day re-admission. This study was registered with PROSPERO, CRD42020169413. Results: Eight studies (1226 patients, 554 vs. 672 in daptomycin vs. vancomycin, respectively) were included. No significant difference in terms of overall mortality was observed [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.40–1.33, I2 = 67%]. Daptomycin was associated with a significantly reduced risk of clinical failure (OR 0.58, 95% CI 0.38–0.89, I2 = 60%), as confirmed by pooling adjusted effect sizes (adjusted OR against the use of vancomycin 1.94, 95%CI 1.33–1.82, I2 = 41%), and was linked with fewer treatment-limiting AEs (OR 0.15, 95%CI 0.06–0.36, I2 = 19%). No difference emerged between the two treatments as secondary outcomes. Results were not robust to unmeasured confounding (E-value lower than 95% CI 1.00 for all-cause mortality). Conclusions: Against MRSA BSI, with or without endocarditis, daptomycin seems to be associated with a lower risk of clinical failure and treatment-limiting AEs compared with vancomycin. Further studies are needed to better characterize the differences between the two drugs. Full article
(This article belongs to the Special Issue Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze Out New Ones)
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32 pages, 1196 KiB  
Review
The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases
by Carola Mauri, Alberto Enrico Maraolo, Stefano Di Bella, Francesco Luzzaro and Luigi Principe
Antibiotics 2021, 10(8), 1012; https://doi.org/10.3390/antibiotics10081012 - 20 Aug 2021
Cited by 99 | Viewed by 17054
Abstract
Infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales and Pseudomonas are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. [...] Read more.
Infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales and Pseudomonas are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing Enterobacterales, 85% of Stenotrophomonas and 6% of MBL-producing Pseudomonas. Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially Enterobacterales, much less for Pseudomonas) while waiting for new antimicrobials. Full article
(This article belongs to the Special Issue Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze Out New Ones)
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14 pages, 996 KiB  
Review
Old and New Beta-Lactamase Inhibitors: Molecular Structure, Mechanism of Action, and Clinical Use
by Davide Carcione, Claudia Siracusa, Adela Sulejmani, Valerio Leoni and Jari Intra
Antibiotics 2021, 10(8), 995; https://doi.org/10.3390/antibiotics10080995 - 17 Aug 2021
Cited by 54 | Viewed by 11911
Abstract
The β-lactams have a central place in the antibacterial armamentarium, but the increasing resistance to these drugs, especially among Gram-negative bacteria, is becoming one of the major threats to public health worldwide. Treatment options are limited, and only a small number of novel [...] Read more.
The β-lactams have a central place in the antibacterial armamentarium, but the increasing resistance to these drugs, especially among Gram-negative bacteria, is becoming one of the major threats to public health worldwide. Treatment options are limited, and only a small number of novel antibiotics are in development. However, one of the responses to this threat is the combination of β-lactam antibiotics with β-lactamase inhibitors, which are successfully used in the clinic for overcoming resistance by inhibiting β-lactamases. The existing inhibitors inactivate most of class A and C serine β-lactamases, but several of class D and B (metallo-β-lactamase) are resistant. The present review provides the status and knowledge concerning current β-lactamase inhibitors and an update on research efforts to identify and develop new and more efficient β-lactamase inhibitors. Full article
(This article belongs to the Special Issue Antibiotic Use in Clinical Infection: How to Reinvent Old Molecules and How to Squeeze Out New Ones)
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