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

Deadline for manuscript submissions: 28 February 2026 | Viewed by 12692

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Special Issue Editor

Dr. Darko Modun

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Guest Editor

Department of Pharmacy, University of Split School of Medicine, Split, Croatia
Interests: adverse drug reaction; drug-drug interaction; patient adherence; antimicrobial resistance; clinical guidelines
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Special Issue Information

Dear Colleagues,

Clinical guidelines for antimicrobial pharmacotherapy are crucial tools that are based on extensive research, expert consensus, and clinical trials for optimising the treatment of infections. They outline the best practices for selecting effective drugs, appropriate dosing, and treatment duration in order to standardise treatment, minimise antimicrobial resistance, and optimise drug efficacy and safety. However, the gap between these guidelines and real-world practice can be significant.

In clinical settings, variability in patient populations, comorbidities, and unique clinical scenarios necessitate deviations from standardised protocols. Clinicians may also face limitations such as drug availability, patient allergies, the pressure to prescribe quickly to address patient concerns, or limited access to diagnostic testing. Additionally, the dynamic nature of microbial resistance patterns requires the continuous adaptation of prescribed therapies, which is sometimes beyond the scope of existing guidelines.

Therefore, while clinical guidelines are a critical foundation for antimicrobial therapy, real-world practice demands a flexible, individualised approach. Clinicians must balance adherence to guidelines with the nuanced needs of their patients, thereby ensuring effective treatment and mitigating the development of resistance.

Indeed, tailoring guidelines to consider regional factors and implementing antimicrobial stewardship programs that promote responsible prescribing can optimise antibiotic use in real-world settings.

Accordingly, I invite you to contribute to this Special Issue of Antibiotics, titled “Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy”.

Dr. Darko Modun
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

adverse drug reaction
patient adherence
antimicrobial resistance
clinical guidelines
clinical settings
regional factors
pharmacotherapy

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Published Papers (7 papers)

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Research

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16 pages, 3955 KB

Open AccessArticle

Postβ-Lactamase-Inhibiting Effect of Sulbactam in Combination with Ceftriaxone on Extended-Spectrum-β-Lactamase-Producing Escherichia coli

by Ru Wang, Kun Mi, Aihua Lu, Chengyang Zhang, Lei Sun, Yuxiang Chen, Yuanhu Pan, Yanfei Tao and Lingli Huang

Antibiotics 2025, 14(9), 915; https://doi.org/10.3390/antibiotics14090915 - 11 Sep 2025

Viewed by 219

Abstract

Background/Objectives: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli poses a significant global health challenge, as it leads to antimicrobial treatment failure and is associated with elevated mortality rates. The use of β-lactam/β-lactamase inhibitor combinations offers an alternative approach for combating ESBL-producing bacteria. Ceftriaxone (CRO) and sulbactam have been coadministered in the clinical settings; however, discrepancies in their pharmacokinetics raise concerns regarding the rationality of this combination. Methods: This study was designed to investigate the postβ-lactamase inhibitor effect (PLIE) under both static and dynamic conditions, with the aim of supporting the clinical application of this combination. Results: The minimum inhibitory concentration (MIC) of CRO/SBT (2:1 ratio) against E. coli NCTC 13353 was determined to be 32/16 μg/mL. The PLIEs were determined to be −1.26, −0.57, and 0.37 h at CRO/SBT concentrations ranging from 1/2 MIC to 2 MIC, respectively. The results of CRO concentration, β-lactamase activity, bla_CTX-M-15 expression, and cell morphology collectively support that SBT exerts PLIEs and protects against the antibacterial activity of CRO. In the dynamic hollow-fiber infection model, CRO monotherapy showed no inhibitory effect on E. coli, whereas CRO/SBT combination therapy rapidly eliminated SBT, achieved comparable bactericidal effects, prolonged CRO exposure, and maintained low β-lactamase activity levels. Conclusions: In conclusion, CRO/SBT exerts an inhibitory effect on enzyme-producing strains by being able to produce PLIE to maintain the inhibition of β-lactamase. Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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20 pages, 2009 KB

Open AccessArticle

Optimizing the Routine Use of Clinical Guidelines by Addition of Supplements (Probiotics and/or Bismuth) to Helicobacter pylori Eradication Protocols in a Clarithromycin Resistant and Tetracycline/Bismuth Naive Area: A Real-World Data Retrospective Analysis of 402 Cases (2016–24) in a Single Gastroenterology Unit

by András Gelley, Noémi Kéri, Péter Birinyi, Kinga Komka, Vajk Hardy, László Döngölő, Dóra Szeli and Ibolya Czegle

Antibiotics 2025, 14(9), 870; https://doi.org/10.3390/antibiotics14090870 - 29 Aug 2025

Viewed by 549

Abstract

Background: The official current guideline for Helicobacter pylori (H. pylori) eradication is to use tetracycline–bismuth-based protocols as first line treatment due to the increasing incidence of clarithromycin resistance in the last decade. The unavailability of tetracycline and bismuth-containing medicines, however, is an issue in many countries, limiting the routine use of these protocols. The value of using additional probiotics in eradication protocols is also unclear. Direct comparison data on the effect of available bismuth compounds and different probiotic strains on eradication outcome are limited. Goal: The aim of our investigation was to find optimal eradication protocols, supplementations and treatment duration for routine clinical use in our gastroenterology unit, located in a highly clarithromycin-resistant and tetracycline–bismuth-naïve area. Materials and Methods: We conducted a retrospective real-world data analysis of 402 H. pylori positive patients between 2016 and 2024. H. pylori infection was diagnosed using histological examination of gastroscopy samples obtained from the gastric antrum. For the evaluation of treatment success or failure, ¹⁴C breath tests and stool H. pylori antigen tests were performed. Data on patient characteristics and treatment protocols were collected from our electronic patient record system, and treatment success was compared between the different treatment regimes. Results: Despite the regional clarithromycin resistance, supplementing clarithromycin-based regimens with bismuth and probiotic during the 14-day treatment duration showed a high and comparable cure rate when compared to tetracycline-based regimens, which are the current first-line therapies. When tetracycline-based combination is available, it is recommended to use it with an additional probiotic to achieve the best possible outcome. Comparison of the effect of available bismuth preparations on treatment success showed no significant difference. Generally, probiotic-containing protocols are more successful, compared to those treatments without this supplement. There was no statistical difference in the cure rates amongst the four probiotic strains used, where sample size allowed statistical analysis. Furthermore, supplementation with probiotics Lactobacillus reuteri ATCC PTA 6475 or Lactobacillus reuteri Protectis^® DSM 17938 showed promising high treatment success rates (85.2% and 100.0%, respectively) in our study. Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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17 pages, 675 KB

Open AccessArticle

Caught Between Stewardship and Resistance: How to Treat Acute Complicated Diverticulitis in Areas of Low Antimicrobial Susceptibility?

by Octavian Enciu, Elena-Adelina Toma, Adrian Miron, Gabriela Loredana Popa, Andrei-Alexandru Muntean, Andrei Ludovic Porosnicu and Mircea Ioan Popa

Antibiotics 2024, 13(12), 1150; https://doi.org/10.3390/antibiotics13121150 - 1 Dec 2024

Viewed by 1418

Abstract

Antimicrobial resistance is one of the main threats to public health, with multidrug-resistant (MDR) pathogens on the rise across continents. Although treatment guidelines generally recommend antimicrobial therapy for acute complicated diverticulitis, they do not specify treatment pathways according to local or national resistance profiles. There is sparse data regarding specific pathogens involved in Hinchey II–IV patients who undergo surgery. This study seeks to address these issues and determine how often and what types of MDR bacteria occur in patients undergoing emergency surgery. We prospectively enrolled patients admitted between 2020–2023 and who underwent emergency surgery for complicated acute diverticulitis. We analysed the inflammatory response parameters at admission, the type of surgery employed for source control, identified pathogens in the peritoneal samples, their antimicrobial susceptibility, the efficacy of antimicrobial empiric therapy, and mortality. Gram-negative bacteria were identified most often, with Escherichia coli being mostly MDR (43.9%) or extended-spectrum beta-lactamase producing (ESBL +ve) (24.4%), while most strains of Klebsiella pneumoniae were extended-spectrum beta-lactamase positive (ESBL +ve) (80%) and MDR (80%). Of the Enterococcus spp., 57.14% were vancomycin-resistant (VRE) strains. Patients with Hinchey III/IV were significantly more associated with MDR. Patients with multiple pathogens were significantly associated with ESBL+/VRE strains. Age, leucocytosis, and procalcitonin levels at admission were good indicators for mortality prediction, which occurred in four cases. In an age when antibiotic stewardship is advisable especially in emergency settings, the treatment should be tailored according to local profiles of MDR to ensure adequate outcomes for patients. Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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9 pages, 869 KB

Open AccessArticle

Improving Turnaround Times for Routine Antimicrobial Sensitivity Testing Following European Committee on Antimicrobial Susceptibility Testing Methodology in Patients with Bacteraemia

by Raewyn Edmondson, Kordo Saeed, Steve Green and Matthew O’Dwyer

Antibiotics 2024, 13(11), 1094; https://doi.org/10.3390/antibiotics13111094 - 17 Nov 2024

Cited by 1 | Viewed by 1594

Abstract

Background/Objectives: Bacteraemia can be fatal without antibiotic intervention. Antibiotic Susceptibility Testing (AST) provides the necessary information for targeted antibiotic therapy; however, the traditional method using disc diffusion can take over two days from a positive blood culture. Inappropriate empiric therapy is associated with increased mortality and increased antibiotic resistance, highlighting the need for more rapid turnaround times for AST. By making changes to an established method, turnaround times can be reduced. Methods: Eighty-two patient positive blood culture samples were collected from January to April 2022, representing the range of common bacteria causing sepsis. This followed the normal methodology in the laboratory of inoculating agar from positive blood cultures in preparation for European Committee on Antimicrobial Susceptibility Testing (EUCAST) disc diffusion AST method. EUCAST methodology outlines that disc diffusion should be performed on isolates from an overnight culture of 16–24 h. This study looked at comparing disc diffusion results from cultures with 6 h of incubation to those with incubation times of 24 h, after organism identification by MALDI-ToF. Results from 6-h and 24-h cultures were compared by disc zone sizes and by interpreted susceptibility reading following EUCAST guidelines of sensitive, resistant, susceptible with increased exposure, or an area of technical uncertainty. Results: A total of 99.65% interpreted susceptibility readings matched across all organisms to all relevant antibiotics, with an average zone size difference of 1.08 mm between results from 6 h versus 24 h cultures. Conclusions: This method offers a non-automated way of using the traditional disc diffusion method, reducing turnaround times while still producing reliable and accurate results. This would mean validated ASTs can be set up in the same day as a blood culture flags positive rather than waiting for a longer culture. As this method is widely used within the laboratory already, it would mean that additional training is not required, as the process is the same, and only incubation time varies. This would positively impact patient outlook due to the shorter use of empiric therapy, and benefit antimicrobial stewardship (AMS). Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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10 pages, 572 KB

Open AccessArticle

Epidemiology and Impact of Anti-Pneumococcal Vaccination and COVID-19 on Resistance of Streptococcus pneumoniae Causing Invasive Disease in Piedmont, Italy

by Alessandro Bondi, Emanuele Koumantakis, Antonio Curtoni, Anna Maria Barbui, Marco Peradotto, Daniela Lombardi, Roberto Casale, Silvia Alizzi, Elisa Zanotto, Lorena Charrier, Rossana Cavallo and Cristina Costa

Antibiotics 2024, 13(8), 740; https://doi.org/10.3390/antibiotics13080740 - 6 Aug 2024

Cited by 3 | Viewed by 1646

Abstract

Background: The international surveillance of antimicrobial resistance (AMR) reports S. pneumoniae as one of leading causes of death associated with AMR. Against invasive disease, several vaccinations are available and a reduction in AMR in S. pneumoniae has been observed. Here, we evaluated the impact of anti-pneumococcal vaccination policy and the SARS-CoV2 outbreak on AMR in S. pneumoniae causing invasive disease. Methods: We collected all strains of S. pneumoniae causing invasive disease from 2008 in the Piedmont region (Italy). Each strain was typed in order to identify the serogroup and data about AMR were collected. The population under surveillance was classified as infants, children, adults, and the old population. Results: We collected n = 2076 S. pneumoniae strains, with 21.9% and 40.3% being resistant to penicillin G and erythromycin, respectively. We reported an increased risk of infection with penicillin-resistant S. pneumoniae among all populations and evaluated whether the infection was caused by a serotype included in the vaccine formulation. A similar increase was observed after the SARS-CoV2 outbreak. Conclusions: In the Piedmont region, subsequently to the introduction of anti-pneumococcal vaccination, a significant increase in the risk of penicillin G-resistant invasive pneumococcal disease among infants and old population was reported. No significant impact was found for the SARS-CoV2 outbreak. Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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Review

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10 pages, 463 KB

Open AccessReview

Tetracyclines in Rheumatoid Arthritis: Dual Anti-Inflammatory and Immunomodulatory Roles, Effectiveness, and Safety Insights

by Mislav Radić, Andrej Belančić, Hana Đogaš, Marijana Vučković, Andrea Gelemanović, Andrea Faour, Ivan Vlak and Josipa Radić

Antibiotics 2025, 14(1), 65; https://doi.org/10.3390/antibiotics14010065 - 10 Jan 2025

Cited by 1 | Viewed by 2959

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint pain, and progressive cartilage and bone erosion. Despite advancements in RA management with disease-modifying antirheumatic drugs (DMARDs) and biologics, some patients remain refractory to conventional treatments. Tetracyclines, such as minocycline and doxycycline, exhibit anti-inflammatory and immunomodulatory properties, making them potential supplementary treatments. This narrative review explores their effectiveness, mechanisms of action, safety profiles, and current challenges in RA care. Tetracyclines have demonstrated significant immunomodulatory effects, including the inhibition of pro-inflammatory cytokines and matrix metalloproteinases (MMPs), which are critical in RA pathology. Clinical trials, including double-blind, placebo-controlled studies, have shown efficacy in reducing RA symptoms, particularly in early and refractory cases. However, their use remains limited by inconsistent evidence, small sample sizes, and concerns about antimicrobial resistance. Current guidelines for RA management do not explicitly recommend tetracyclines due to these limitations, although off-label use may be considered in specific cases. The use of tetracycline for RA is restricted by drug interactions causing bacterial resistance alongside unpredictable patient responses, hence the necessity for prudence in its prescription within a clinical setting. To overcome these limitations, the development of safer compounds, in-depth in silico analyses, and integration with personalized medicine approaches are needed. Overall, tetracyclines show promise as adjunct therapies in RA management due to their dual anti-inflammatory and immunomodulatory actions. This review highlights the need for further research to address gaps in evidence, including the development of modified tetracyclines with reduced antimicrobial effects and improved safety profiles, as well as the integration of personalized medicine approaches to optimize patient outcomes. Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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22 pages, 1059 KB

Open AccessReview

Infective Endocarditis by Biofilm-Producing Methicillin-Resistant Staphylococcus aureus—Pathogenesis, Diagnosis, and Management

by Ashlesha Kaushik, Helen Kest, Mangla Sood, Corey Thieman, Bryan W. Steussy, Michael Padomek and Sandeep Gupta

Antibiotics 2024, 13(12), 1132; https://doi.org/10.3390/antibiotics13121132 - 25 Nov 2024

Cited by 3 | Viewed by 3589

Abstract

Infective endocarditis (IE) is a life-threatening condition with increasing global incidence, primarily caused by Staphylococcus aureus, especially methicillin-resistant strains (MRSA). Biofilm formation by S. aureus is a critical factor in pathogenesis, contributing to antimicrobial resistance and complicating the treatment of infections involving prosthetic valves and cardiovascular devices. Biofilms provide a protective matrix for MRSA, shielding it from antibiotics and host immune defenses, leading to persistent infections and increased complications, particularly in cases involving prosthetic materials. Clinical manifestations range from acute to chronic presentations, with complications such as heart failure, embolic events, and neurological deficits. Diagnosis relies on the Modified Duke Criteria, which have been updated to incorporate modern cardiovascular interventions and advanced imaging techniques, such as PET/CT (positron emission tomography, computed tomography), to improve the detection of biofilm-associated infections. Management of MRSA-associated IE requires prolonged antimicrobial therapy, often with vancomycin or daptomycin, needing a combination of antimicrobials in the setting of prosthetic materials and frequently necessitates surgical intervention to remove infected prosthetic material or repair damaged heart valves. Anticoagulation remains controversial, with novel therapies like dabigatran showing potential benefits in reducing thrombus formation. Despite progress in treatment, biofilm-associated resistance poses ongoing challenges. Emerging therapeutic strategies, including combination antimicrobial regimens, bacteriophage therapy, antimicrobial peptides (AMPs), quorum sensing inhibitors (QSIs), hyperbaric oxygen therapy, and nanoparticle-based drug delivery systems, offer promising approaches to overcoming biofilm-related resistance and improving patient outcomes. This review provides an overview of the pathogenesis, current management guidelines, and future directions for treating biofilm-related MRSA IE. Full article

(This article belongs to the Special Issue Clinical Guidelines and Real Practice of Antimicrobial Pharmacotherapy)

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