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Antibiotics
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Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic
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Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 20654

Special Issue Editors

Prof. Dr. Carmelo A. Juárez-Castelló

E-Mail Website1 Website2 Website3
Guest Editor
Economy and Business, Universidad de La Rioja, Logrono, Spain
Interests: health economics; health technologies; economic analysis models in health policies and services
Prof. Dr. Marino J. González

E-Mail Website
Guest Editor
1. Departamento de Ciencias Económicas y Administrativas, Simon Bolivar University, Caracas, Venezuela
2. Health Economics Research Group, University of La Rioja, La Rioja, Spain
Interests: public policy analysis; analysis of health conditions through household surveys; health policy in Latin American countries; health economics

Special Issue Information

Dear Colleagues,

Antimicrobial resistance (AMR) is a major public health problem. It causes a great loss of life worldwide and even threatens to reverse some important medical advances of the last century, as the World Health Organization (WHO) has recognized by declaring it one of the top ten Public Health threats facing humanity.

The inappropriate and excessive use of antimicrobials in medicine and veterinary care is the main factor that determines the appearance of drug-resistant pathogens. The most dramatic consequences of the dissemination of resistance to antibiotics are observed in the medical environment, although the problem has its origin not only in it but also in the environment, in agriculture and livestock environments, which raises the convenience to assume the “One Health” approach advocated by WHO. Thus, plans and programs to improve the prescription and use of antibiotics are necessary.

In recent years, more and more high-quality, effective and adequate diagnostic tests have been developed to guide the appropriate use of antibiotics, which are becoming more available in any setting. These techniques and equipment not only contribute to the improvement of patients' health but, in the long term, can contribute to containing the problem of AMR.

This Special Issue hopes to receive manuscripts that promote a better understanding of the value that the improvement of the diagnoses of infections, in any type and scope of care, can bring to improve the precision and personalization of prescriptions and the impact of this improvement on the containment of antimicrobial resistance. In particular, studies that expand the information available on the comparative efficiency of diagnostic procedures susceptible to alternative use are desirable.

Prof. Dr. Carmelo A. Juárez-Castelló
Prof. Dr. Marino J. González
Guest Editors

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

  • Antibiotic prescription and use
  • Antimicrobial resistance (AMR)
  • Diagnostic methods and technologies
  • Precision medicine
  • Stratified medicine
  • Personalized medicine
  • One Health

Published Papers (7 papers)

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Research

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14 pages, 2383 KiB  
Article
Blood Culture Headspace Gas Analysis Enables Early Detection of Escherichia coli Bacteremia in an Animal Model of Sepsis
by Maximilian Euler, Thorsten Perl, Isabell Eickel, Anna Dudakova, Esther Maguilla Rosado, Carolin Drees, Wolfgang Vautz, Johannes Wieditz, Konrad Meissner and Nils Kunze-Szikszay
Antibiotics 2022, 11(8), 992; https://doi.org/10.3390/antibiotics11080992 - 23 Jul 2022
Cited by 3 | Viewed by 1615
Abstract
(1) Background: Automated blood culture headspace analysis for the detection of volatile organic compounds of microbial origin (mVOC) could be a non-invasive method for bedside rapid pathogen identification. We investigated whether analyzing the gaseous headspace of blood culture (BC) bottles through gas chromatography-ion [...] Read more.
(1) Background: Automated blood culture headspace analysis for the detection of volatile organic compounds of microbial origin (mVOC) could be a non-invasive method for bedside rapid pathogen identification. We investigated whether analyzing the gaseous headspace of blood culture (BC) bottles through gas chromatography-ion mobility spectrometry (GC-IMS) enables differentiation of infected and non-infected; (2) Methods: BC were gained out of a rabbit model, with sepsis induced by intravenous administration of E. coli (EC group; n = 6) and control group (n = 6) receiving sterile LB medium intravenously. After 10 h, a pair of blood cultures was obtained and incubated for 36 h. The headspace from aerobic and anaerobic BC was sampled every two hours using an autosampler and analyzed using a GC-IMS device. MALDI-TOF MS was performed to confirm or exclude microbial growth in BCs; (3) Results: Signal intensities (SI) of 113 mVOC peak regions were statistically analyzed. In 24 regions, the SI trends differed between the groups and were considered to be useful for differentiation. The principal component analysis showed differentiation between EC and control group after 6 h, with 62.2% of the data variance described by the principal components 1 and 2. Single peak regions, for example peak region P_15, show significant SI differences after 6 h in the anaerobic environment (p < 0.001) and after 8 h in the aerobic environment (p < 0.001); (4) Conclusions: The results are promising and warrant further evaluation in studies with an extended microbial panel and indications concerning its transferability to human samples. Full article
(This article belongs to the Special Issue Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic)
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13 pages, 1930 KiB  
Article
Assessing, Pricing and Funding Point-of-Care Diagnostic Tests for Community-Acquired Acute Respiratory Tract Infections–Overview of Policies Applied in 17 European Countries
by Sabine Vogler and Friederike Windisch
Antibiotics 2022, 11(8), 987; https://doi.org/10.3390/antibiotics11080987 - 22 Jul 2022
Cited by 1 | Viewed by 1996
Abstract
Point-of-care diagnostic tests for community-acquired acute respiratory tract infections (CA-ARTI) can support doctors by improving antibiotic prescribing. However, little is known about health technology assessment (HTA), pricing and funding policies for CA-ARTI diagnostics. Thus, this study investigated these policies for this group of [...] Read more.
Point-of-care diagnostic tests for community-acquired acute respiratory tract infections (CA-ARTI) can support doctors by improving antibiotic prescribing. However, little is known about health technology assessment (HTA), pricing and funding policies for CA-ARTI diagnostics. Thus, this study investigated these policies for this group of devices applied in the outpatient setting in Europe. Experts from competent authority responded to a questionnaire in Q4/2020. Information is available for 17 countries. Studied countries do not base their pricing and funding decision for CA-ARTI diagnostics on an HTA. While a few countries impose price regulation for some publicly funded medical devices, the prices of CA-ARTI diagnostics are not directly regulated in any of the surveyed countries. Indirect price regulation through public procurement is applied in some countries. Reimbursement lists of medical devices eligible for public funding exist in several European countries, and in some countries these lists include CA-ARTI diagnostics. In a few countries, the public payer funds the health professional for performing the service of conducting the test. Given low levels of regulation and few incentives, the study findings suggest room for strengthening pricing and funding policies of CA-ARTI diagnostics to contribute to increased acceptance and use of these point-of-care tests. Full article
(This article belongs to the Special Issue Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic)
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14 pages, 924 KiB  
Article
Antibacterial and Antifungal Management in Relation to the Clinical Characteristics of Elderly Patients with Infective Endocarditis: A Retrospective Analysis
by Camelia Melania Budea, Marius Pricop, Felix Bratosin, Iulia Bogdan, Miriam Saenger, Ovidiu Ciorica, Laurentiu Braescu, Eugenia Maria Domuta, Mirela Loredana Grigoras, Cosmin Citu, Mircea Mihai Diaconu and Iosif Marincu
Antibiotics 2022, 11(7), 956; https://doi.org/10.3390/antibiotics11070956 - 15 Jul 2022
Cited by 6 | Viewed by 2389
Abstract
Infective endocarditis (IE) is increasingly prevalent in the elderly, particularly due to the rising frequency of invasive procedures and intracardiac devices placed on these individuals. Several investigations have highlighted the unique clinical and echocardiographic characteristics, the microorganisms implicated, and the prognosis of IE [...] Read more.
Infective endocarditis (IE) is increasingly prevalent in the elderly, particularly due to the rising frequency of invasive procedures and intracardiac devices placed on these individuals. Several investigations have highlighted the unique clinical and echocardiographic characteristics, the microorganisms implicated, and the prognosis of IE in the elderly. In addition, the old population seems to be fairly diverse, ranging from healthy individuals with no medical history to patients with many ailments and those who are immobile. Furthermore, the therapy of IE in this group has not been well investigated, and worldwide recommendations do not propose tailoring the treatment approach to the patient’s functional state and comorbid conditions. A multicenter research study was designed as a retrospective study of hospitalized patients with infective endocarditis, aiming to examine the characteristics of elderly patients over 65 years old with infective endocarditis in relation to the antibiotic and antifungal treatments administered, as well as to quantify the incidence of treatment resistance, adverse effects, and mortality in comparison to patients younger than 65. Based on a convenience sampling method, we included in the analysis a total of 78 patients younger than 65 and 131 patients older than 65 years. A total of 140 patients had endocarditis on native valves and 69 patients had endocarditis on prosthetic valves. A significantly higher proportion of elderly patients had signs of heart failure on admission, and the mortality rate was significantly higher in the elderly population. A majority of infections had a vascular cause, followed by dental, maxillo-facial, and ENT interventions. The most common complications of IE were systemic sepsis (48.1% of patients older than 65 years vs. 30.8% in the younger group). The most frequent bacterium involved was Staphylococcus aureus, followed by Streptococcus spp. in a total of more than 50% of all patients. The most commonly used antibiotics were cephalosporins in 33.5% of cases, followed by penicillin in 31.2% and glycopeptides in 28.7%, while Fluconazole was the initial option of treatment for fungal endocarditis in 24.9% of cases. Heart failure at admission (OR = 4.07), the development of septic shock (OR = 6.19), treatment nephrotoxicity (OR = 3.14), severe treatment complications (OR = 4.65), and antibiotic resistance (OR = 3.24) were significant independent risk factors for mortality in the elderly patients. Even though therapeutic management was initiated sooner in the older patients, the associated complications and mortality rate remained significantly greater than those in the patients under 65 years old. Full article
(This article belongs to the Special Issue Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic)
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10 pages, 1167 KiB  
Article
Susceptibility Testing by Volatile Organic Compound Detection Direct from Positive Blood Cultures: A Proof-of-Principle Laboratory Study
by Sacha Daniëlle Kuil, Soemeja Hidad, Caroline Schneeberger, Pragya Singh, Paul Rhodes, Menno Douwe de Jong and Caroline Elisabeth Visser
Antibiotics 2022, 11(6), 705; https://doi.org/10.3390/antibiotics11060705 - 24 May 2022
Cited by 5 | Viewed by 2135
Abstract
Background: Bacteria produce volatile organic compounds (VOCs) during growth, which can be detected by colorimetric sensor arrays (CSAs). The SpecifAST® system (Specific Diagnostics) employs this technique to enable antibiotic susceptibility testing (AST) directly from blood cultures without prior subculture of isolates. The [...] Read more.
Background: Bacteria produce volatile organic compounds (VOCs) during growth, which can be detected by colorimetric sensor arrays (CSAs). The SpecifAST® system (Specific Diagnostics) employs this technique to enable antibiotic susceptibility testing (AST) directly from blood cultures without prior subculture of isolates. The aim of this study was to compare the SpecifAST® AST results and analysis time to the VITEK®2 (bioMérieux) system. Methods: In a 12-month single site prospective study, remnants of clinical positive monomicrobial blood cultures were combined with a series of antibiotic concentrations. Volatile emission was monitored at 37 °C via CSAs. Minimal Inhibitory Concentrations (MICs) of seven antimicrobial agents for Enterobacterales, Staphylococcus, and Enterococcus spp. were compared to VITEK®2 AST results. MICs were interpreted according to EUCAST clinical breakpoints. Performance was assessed by calculating agreement and discrepancy rates. Results: In total, 96 positive blood cultures containing Enterobacterales, Staphylococcus, and Enterococcus spp. were tested (269 bug–drug combinations). The categorical agreement of the SpecifAST® system compared to the VITEK®2 system was 100% and 91% for Gram-negatives and Gram-positives, respectively. Errors among Gram-positives were from coagulase-negative staphylococci. Overall results were available in 3.1 h (±0.9 h) after growth detection without the need for subculture steps. Conclusion: The AST results based on VOC detection are promising and warrant further evaluation in studies with a larger sample of bacterial species and antimicrobials. Full article
(This article belongs to the Special Issue Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic)
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Review

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14 pages, 1129 KiB  
Review
Antibiotic Allergy De-Labeling: A Pathway against Antibiotic Resistance
by Inmaculada Doña, Marina Labella, Gádor Bogas, Rocío Sáenz de Santa María, María Salas, Adriana Ariza and María José Torres
Antibiotics 2022, 11(8), 1055; https://doi.org/10.3390/antibiotics11081055 - 03 Aug 2022
Cited by 5 | Viewed by 4155
Abstract
Antibiotics are one of the most frequently prescribed drugs. Unfortunately, they also are the most common cause for self-reported drug allergy, limiting the use of effective therapies. However, evidence shows that more than 90% of patients labeled as allergic to antibiotics are not [...] Read more.
Antibiotics are one of the most frequently prescribed drugs. Unfortunately, they also are the most common cause for self-reported drug allergy, limiting the use of effective therapies. However, evidence shows that more than 90% of patients labeled as allergic to antibiotics are not allergic. Importantly, the label of antibiotic allergy, whether real or not, constitutes a major public health problem as it directly impacts antimicrobial stewardship: it has been associated with broad-spectrum antibiotic use, often resulting in the emergence of bacterial resistance. Therefore, an accurate diagnosis is crucial for de-labeling patients who claim to be allergic but are not really allergic. This review presents allergy methods for achieving successful antibiotic allergy de-labeling. Patient clinical history is often inaccurately reported, thus not being able to de-label most patients. In vitro testing offers a complementary approach but it shows limitations. Immunoassay for quantifying specific IgE is the most used one, although it gives low sensitivity and is limited to few betalactams. Basophil activation test is not validated and not available in all centers. Therefore, true de-labeling still relies on in vivo tests including drug provocation and/or skin tests, which are not risk-exempt and require specialized healthcare professionals for results interpretation and patient management. Moreover, differences on the pattern of antibiotic consumption cause differences in the diagnostic approach among different countries. A multidisciplinary approach is recommended to reduce the risks associated with the reported penicillin allergy label. Full article
(This article belongs to the Special Issue Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic)
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15 pages, 481 KiB  
Review
Diagnostic Testing for Sepsis: A Systematic Review of Economic Evaluations
by Paula Rojas-Garcia, Simon van der Pol, Antoinette D. I. van Asselt, Maarten J. Postma, Roberto Rodríguez-Ibeas, Carmelo A. Juárez-Castelló, Marino González and Fernando Antoñanzas
Antibiotics 2022, 11(1), 27; https://doi.org/10.3390/antibiotics11010027 - 27 Dec 2021
Cited by 1 | Viewed by 3181
Abstract
Introduction: Sepsis is a serious and expensive healthcare problem, when caused by a multidrug-resistant (MDR) bacteria mortality and costs increase. A reduction in the time until the start of treatment improves clinical results. The objective is to perform a systematic review of economic [...] Read more.
Introduction: Sepsis is a serious and expensive healthcare problem, when caused by a multidrug-resistant (MDR) bacteria mortality and costs increase. A reduction in the time until the start of treatment improves clinical results. The objective is to perform a systematic review of economic evaluations to analyze the cost-effectiveness of diagnostic methods in sepsis and to draw lessons on the methods used to incorporate antimicrobial resistance (AMR) in these studies. Material and Methods: the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the Consolidated Health Economic Evaluation Reporting standards (CHEERS) checklist was used to extract the information from the texts. Results: A total of 16 articles were found. A decision model was performed in 14. We found two ways to handle resistance while modelling: the test could identify infections caused by a resistant pathogen or resistance-related inputs, or outcomes were included (the incidence of AMR in sepsis patients, antibiotic use, and infection caused by resistant bacterial pathogens). Conclusion: Using a diagnostic technique to detect sepsis early on is more cost-effective than standard care. Setting a direct relationship between the implementation of a testing strategy and the reduction of AMR cases, we made several assumptions about the efficacy of antibiotics and the length-of-stay of patients. Full article
(This article belongs to the Special Issue Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic)
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Other

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12 pages, 1911 KiB  
Systematic Review
Assessment of the Impact of a Meningitis/Encephalitis Panel on Hospital Length of Stay: A Systematic Review and Meta-Analysis
by Kyle D. Hueth, Philippe Thompson-Leduc, Todor I. Totev, Katherine Milbers, Tristan T. Timbrook, Noam Kirson and Rodrigo Hasbun
Antibiotics 2022, 11(8), 1028; https://doi.org/10.3390/antibiotics11081028 - 30 Jul 2022
Cited by 7 | Viewed by 3240
Abstract
Meningitis and encephalitis are central nervous system infections with considerable morbidity and mortality. The BioFire® FilmArray® Meningitis/Encephalitis Panel (multiplex ME panel) can identify pathogens rapidly potentially aiding in targeted therapy and curtail antimicrobial exposure. This systematic review and meta-analysis synthesized the [...] Read more.
Meningitis and encephalitis are central nervous system infections with considerable morbidity and mortality. The BioFire® FilmArray® Meningitis/Encephalitis Panel (multiplex ME panel) can identify pathogens rapidly potentially aiding in targeted therapy and curtail antimicrobial exposure. This systematic review and meta-analysis synthesized the literature on the association between the multiplex ME panel and length of hospital stay (LOS), length of acyclovir therapy, and days with antibiotics. MEDLINE and EMBASE were searched. Only studies presenting novel data were retained. Random-effects meta-analyses were performed to assess the impact of the multiplex ME panel on outcomes. Of 169 retrieved publications, 13 met the criteria for inclusion. Patients tested with the multiplex ME panel had a reduction in the average LOS (mean difference [MD] [95% CI]: −1.20 days [−1.96, −0.44], n = 11 studies). Use of the multiplex ME panel was also associated with a reduction in the length of acyclovir therapy (MD [95% CI]: −1.14 days [−1.78, −0.50], n = 7 studies) and a nonsignificant reduction in the average number of days with antibiotics (MD [95% CI]: −1.01 days [−2.39, 0.37], n = 6 studies). The rapidity of pathogen identification contributes to an overall reduced LOS, reductions in the duration of empiric antiviral utilization, and a nonsignificant reduction in antibiotic therapy. Full article
(This article belongs to the Special Issue Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic)
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