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Pharmaceuticals
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Infectious Disease Epidemiology and Pharmaceutical Development
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Infectious Disease Epidemiology and Pharmaceutical Development

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 April 2025 | Viewed by 12964

Special Issue Editors

Prof. Dr. Victoria Birlutiu

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Guest Editor
Faculty of Medicine, Lucian Blaga University of Sibiu, Romania;County Clinical Emergency Hospital, Sibiu, Romania
Interests: COVID-19; sepsis; clostridioides difficile; respiratory tract infections; bacterial infections; viral infections; arboviral disease; hospital aquired infections; bone and joint infection; surgical site infections
Special Issues, Collections and Topics in MDPI journals
Dr. Simin Aysel Florescu

E-Mail Website
Guest Editor
1. Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
2. Clinic of Infectious and Tropical Diseases "Dr. Victor Babes", Bucharest, Romania
Interests: tropical/imported diseases; antibiotics; sepsis; hospital-acquired infections
Special Issues, Collections and Topics in MDPI journals
Dr. Oana Săndulescu

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Guest Editor
National Institute for Infectious Diseases “Prof. Dr. Matei Balș”, No. 1 Dr. Calistrat Grozovici Street, 021105 Bucharest, Romania
Interests: infectious diseases; HIV; viral hepatitis; biofilm; influenza; vaccine-preventable diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As we are all aware, the past few years have presented us with a number of new challenges related to the emergence and re-emergence of viral, bacterial or parasitic infections. These infectious diseases are responsible for difficult-to-control pandemics or epidemics, and conflicts at the global level have also led to, or may lead to, the reemergence of conditions that were considered eradicated in recent decades. This has increased vigilance in the medical field and has made it imperative that we invest in intensive epidemiological surveillance, clinical and etiological diagnosis, and effective pharmaceutical research. This will ultimately lead to effective etiological and pathogenetic therapy, as well as prevention through vaccination.

The dynamic of infectious diseases is a challenge for everyone!

To combat these challenges, we need to work together and pool our knowledge and expertise. With this in mind, we would like to invite you to contribute to this Special Issue of Pharmaceuticals. We are looking for impactful manuscripts in the areas of epidemiology and pharmaceutical development related to infectious diseases. We want to hear about your personal and institutional efforts in recent years, as well as your knowledge and expertise in the field.

We welcome both reviews and original articles in the field of epidemiology of infectious diseases and pharmaceutical development. The topics we are interested include but are not limited to viral infections, re-emerging bacterial infections, healthcare-associated infections, tropical diseases, antibiotic resistance, and new therapeutic methods. By sharing our knowledge and experience, we can work towards better understanding and management of these diseases.

We look forward to receiving your submissions.

Prof. Dr. Victoria Bîrluţiu
Dr. Simin Aysel Florescu
Dr. Oana Săndulescu
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. Pharmaceuticals 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

  • viral infections
  • bacterial infections
  • healthcare-associated infections
  • tropical diseases
  • epidemiology of infectious diseases
  • antibiotic resistance
  • vaccination
  • epidemiology of bone and joint infections

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Published Papers (8 papers)

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Research

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11 pages, 1110 KiB  
Communication
Formulation and Stability of a 1% Clarithromycin-Based Topical Skin Cream: A New Option to Treat Buruli Ulcers?
by Maria Sebti, Arnaud Schweitzer-Chaput, Salvatore Cisternino, Mélanie Hinterlang, Dimitri Ancedy, Sandrine Lam, Sylvain Auvity, Camille Cotteret, Olivier Lortholary and Joël Schlatter
Pharmaceuticals 2024, 17(6), 691; https://doi.org/10.3390/ph17060691 - 27 May 2024
Viewed by 1258
Abstract
There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli ulcers, a neglected tropical disease endemic in more than 33 countries and caused by Mycobacterium ulcerans [...] Read more.
There are more than 170 known species of non-tuberculous mycobacteria, and some are responsible for serious diseases in people infected with them. One of these is Buruli ulcers, a neglected tropical disease endemic in more than 33 countries and caused by Mycobacterium ulcerans, which infects skin tissue. Treatment consists of a long-term regimen combining the use of oral rifampin with another anti-tuberculosis drug (e.g., clarithromycin). Patients in these countries face difficulties in accessing and adhering to this therapy. This study investigates the feasibility of formulating stable, optimized clarithromycin as a topical cutaneous cream. The cream was formulated, and its stability was evaluated under different storage temperature conditions and using a stability indicator method. The results showed that the clarithromycin cream was stable for at least 60 days, even at extreme temperatures (40 °C). In conclusion, the data presented here demonstrate the stability of a new form of topical cutaneous clarithromycin, which may offer a new approach to the treatment of Buruli ulcers and clarithromycin-sensitive infections. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology and Pharmaceutical Development)
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12 pages, 1757 KiB  
Article
Evaluation of Serial Procalcitonin Levels for the Optimization of Antibiotic Use in Non-Critically Ill COVID-19 Patients
by Abdulaziz S. Almulhim, Mohammed A. Alabdulwahed, Fatimah F. Aldoughan, Ali M. Aldayyen, Faisal Alghamdi, Rawan Alabdulqader, Norah Alnaim, Dimah Alghannam, Yasmin Aljamaan, Saleh Almutairi, Feras T. Al Mogbel, Ahmad Alamer and Haytham A. Wali
Pharmaceuticals 2024, 17(5), 624; https://doi.org/10.3390/ph17050624 - 12 May 2024
Cited by 1 | Viewed by 1449
Abstract
Background: Procalcitonin (PCT) has been used as a biomarker to guide antibiotic therapy in various patient populations. However, its role in optimizing antibiotic use in COVID-19 patients has not been well studied to date. Thus, we aimed to evaluate the use of serial [...] Read more.
Background: Procalcitonin (PCT) has been used as a biomarker to guide antibiotic therapy in various patient populations. However, its role in optimizing antibiotic use in COVID-19 patients has not been well studied to date. Thus, we aimed to evaluate the use of serial PCT monitoring as an antimicrobial stewardship tool for COVID-19 patients. Methods: This retrospective study included 240 COVID-19 patients who were admitted to a tertiary medical institution in Saudi Arabia between January 2020 and February 2022. Patients who received empiric antibiotic therapy for community-acquired pneumonia (CAP) and had serial procalcitonin levels were included. The patients were divided into two groups: the normal procalcitonin arm (PCT level < 0.5 ng/mL) and the elevated PCT arm (PCT level > 0.5 ng/mL). The primary and secondary outcomes were the effect of PCT monitoring on the duration of antibiotic exposure and the length of hospital stay, respectively. To measure the accuracy of PCT, the receiver-operating characteristic area under the curve (ROC-AUC) was determined. Results: Among the included patients, 142 were in the normal procalcitonin arm (median PCT, 0.12 ng/mL), and 78 were in the elevated PCT arm (median PCT, 4.04 ng/mL). The baseline characteristics were similar between the two arms, except for the higher prevalence of kidney disease in the elevated PCT arm. There was no statistically significant difference in the duration of antibiotic exposure between the normal and elevated PCT arms (median duration: 7 days in both arms). However, the length of hospital stay was significantly shorter in the normal PCT arm (median stay, 9 days) than in the elevated PCT arm (median stay, 13 days; p = 0.028). The ROC-AUC value was 0.54 (95% CI: 0.503–0.595). Conclusions: Serial PCT monitoring did not lead to a reduction in the duration of antibiotic exposure in COVID-19 patients. However, it was associated with a shorter hospital stay. These findings suggest that PCT monitoring may be useful for optimizing antibiotic use and improving outcomes in COVID-19 patients. While PCT-guided algorithms have the potential to enable antibiotic stewardship, their role in the context of COVID-19 treatment requires further investigation. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology and Pharmaceutical Development)
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36 pages, 1179 KiB  
Article
Identification of Factors Associated with Mortality in the Elderly Population with SARS-CoV-2 Infection: Results from a Longitudinal Observational Study from Romania
by Victoria Birlutiu, Bogdan Neamtu and Rares-Mircea Birlutiu
Pharmaceuticals 2024, 17(2), 202; https://doi.org/10.3390/ph17020202 - 3 Feb 2024
Cited by 2 | Viewed by 1761
Abstract
The progression of SARS-CoV-2 infection has been linked to a hospitalization rate of 20%. The susceptibility of SARS-CoV-2 infection increases with age, resulting in severe and atypical clinical forms of the disease. The severity of SARS-CoV-2 infection in the elderly population can be [...] Read more.
The progression of SARS-CoV-2 infection has been linked to a hospitalization rate of 20%. The susceptibility of SARS-CoV-2 infection increases with age, resulting in severe and atypical clinical forms of the disease. The severity of SARS-CoV-2 infection in the elderly population can be attributed to several factors, including the overexpression of angiotensin-converting enzyme 2 (ACE2) receptors, immunosenescence, and alterations in the intestinal microbiota that facilitate the cytokine storm. In light of these observations, we conducted a retrospective analysis based on prospectively collected data between 23 December 2021 and 30 April 2022 (the fourth wave of SARS-CoV-2 infection). We analyzed patients aged over 60 years who were hospitalized in a county hospital in Romania. The primary objective of our study was to assess the risk factors for an unfavorable outcome, while the secondary objective was to assess the clinical and baseline characteristics of the enrolled patients. We included 287 cases with a complete electronic medical record from this available cohort of patients. We aimed to retrospectively evaluate a group of 127 patients that progressed, unfortunately, toward an unfavorable outcome versus 160 patients with a favorable outcome. We used the Combined Ordinal Scale of Severity that combines the WHO ordinal scale and the degrees of inflammation to assess the severity of the patients at the time of the initial assessment. The age group between 70 and 79 years had the highest percentage, accounting for 48.0%—61 patients, of the deceased patients. We noted statistically significant differences between groups related to other cardiovascular diseases, nutritional status, hematological diseases, other neurological/mental or digestive disorders, and other comorbidities. Regarding the nutritional status of the patients, there was a statistically significant unfavorable outcome for all the age groups and the patients with a BMI > 30 kg/m2, p = 0.004. The presence of these factors was associated with an unfavorable outcome. Our results indicate that with the presence of cough, there was a statistically significant favorable outcome in the age group over 80 years, p ≤ 0.049. In terms of the presence of dyspnea in all groups of patients, it was associated with an unfavorable outcome, p ≤ 0.001. In our study, we analyzed laboratory test results to assess the level of inflammation across various WHO categories, focusing on the outcome groups determined by the average values of specific biomarkers. Our findings show that, with the exception of IL-6, all other biomarkers tend to rise progressively with the severity of the disease. Moreover, these biomarkers are significantly higher in patients experiencing adverse outcomes. The differences among severity categories and the outcome group are highly significant (p-values < 0.001). CART algorithm revealed a specific cut-off point for the WHO ordinal scale of 4 to stand out as an important reference value for patients at a high risk of developing critical forms of COVID-19. The high death rate can be attributed to proinflammatory status, hormonal changes, nutritional and vitamin D deficiencies, comorbidities, and atypical clinical pictures. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology and Pharmaceutical Development)
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14 pages, 286 KiB  
Article
Changes in Epidemiology and Antibiotic Prescription of Influenza: Before and after the Emergence of COVID-19
by Mihai Aronel Rus, Bogdan Ghițoaica, Andrei Lucian Lazăr, Maria Ancuța Man, Violeta Tincuța Briciu, Monica Iuliana Muntean, Daniel Corneliu Leucuța and Mihaela Sorina Lupșe
Pharmaceuticals 2024, 17(2), 181; https://doi.org/10.3390/ph17020181 - 30 Jan 2024
Cited by 1 | Viewed by 1301
Abstract
Background: The appearance of COVID-19 had a major impact on healthcare and the epidemiology of other diseases. Following the cessation of non-pharmacologic interventions destined to limit the spread of COVID-19, influenza reemerged. The aim of this study was to compare the pre-pandemic influenza [...] Read more.
Background: The appearance of COVID-19 had a major impact on healthcare and the epidemiology of other diseases. Following the cessation of non-pharmacologic interventions destined to limit the spread of COVID-19, influenza reemerged. The aim of this study was to compare the pre-pandemic influenza seasons with the influenza seasons after the emergence of the COVID-19 pandemic, and to identify differences in terms of clinical characteristics, risk factors, complications, outcomes, and antiviral and antibiotic treatments. Methods: We conducted a retrospective cohort study from the Teaching Hospital of Infectious Diseases database in Cluj-Napoca, Romania. We analyzed four pre-pandemic seasons and the seasons after the onset of COVID-19. We included adult patients hospitalized with confirmed influenza between October 2016 and August 2023. Variables such as age, sex, duration of hospitalization, severity, clinical manifestations, comorbidities, and Charlson comorbidity index were assessed. Results: A total of 941 patients were included in the analysis. The percentage of severe influenza was similar in both groups, but mortality from influenza was significantly lower after 2022. Virtually all patients were prescribed antivirals; antibiotic prescriptions decreased in the post-COVID-19 influenza seasons. Conclusion: The present study suggests that influenza seasons after 2022 had lower mortality and attenuated clinical presentation. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology and Pharmaceutical Development)
19 pages, 1225 KiB  
Article
Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre
by Monica Muntean, Violeta Briciu, Mihaela Lupse, Doina Colcear, Raul Vlad Macicasan, Agnes Csiszer, Alexandra Manole and Amanda Radulescu
Pharmaceuticals 2024, 17(1), 3; https://doi.org/10.3390/ph17010003 - 19 Dec 2023
Cited by 2 | Viewed by 1421
Abstract
The aim of this study was to ascertain patient characteristics, outcomes, and liver injuries in patients infected with different SARS-CoV-2 variants. Data from consecutive adult patients with severe/critical COVID-19 admitted to our hospital during the peak month of the Delta wave were compared [...] Read more.
The aim of this study was to ascertain patient characteristics, outcomes, and liver injuries in patients infected with different SARS-CoV-2 variants. Data from consecutive adult patients with severe/critical COVID-19 admitted to our hospital during the peak month of the Delta wave were compared to the ancestral, Alpha, and Omicron waves. The dataset of 551 hospitalized patients was similar in the Delta/non-Delta waves. At admission and discharge, the median aminotransferase levels were normal or slightly increased. During the Delta wave (172 vs. 379 non-Delta patients), more patients died (OR 1.69, 95%CI 1.09–2.56) or had liver injury at discharge (alanine aminotransferase, ALT ≥ 2 ULN) (OR 1.97, 95%CI 1.08–3.54). In-hospital mortality was associated with age, lung injury, intensive care unit admission, number of and cardiovascular comorbidities, diabetes, chronic kidney disease, and all inflammatory biomarkers. Serious liver injury at admission (ALT ≥ 5 × ULN) was significantly associated with in-hospital mortality (OR = 7.9, 95%CI 2–28.9). At discharge, drug-induced liver injury (DILI) was found in patients treated with remdesivir, ALT ≥ 2 ULN (OR = 2.62, 95%CI 1.22–5.75). Treatment with dexamethasone, remdesivir, and immunomodulators showed improved survival, OR = 0.50 (95%CI 0.33–0.77). Regardless of the variant and treatment options, less than 2% of patients displayed serious liver injury, which was not found to be a death predictor in multivariable analysis. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology and Pharmaceutical Development)
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16 pages, 1882 KiB  
Article
A Pharmacovigilance Study Regarding the Risk of Antibiotic-Associated Clostridioides difficile Infection Based on Reports from the EudraVigilance Database: Analysis of Some of the Most Used Antibiotics in Intensive Care Units
by Bogdan Ioan Vintila, Anca Maria Arseniu, Claudiu Morgovan, Anca Butuca, Mihai Sava, Victoria Bîrluțiu, Luca Liviu Rus, Steliana Ghibu, Alina Simona Bereanu, Ioana Roxana Codru and Felicia Gabriela Gligor
Pharmaceuticals 2023, 16(11), 1585; https://doi.org/10.3390/ph16111585 - 9 Nov 2023
Cited by 8 | Viewed by 1916
Abstract
The Gram-positive anaerobic bacterium Clostridioides difficile (CD) can produce intense exotoxins, contributing to nosocomial infections, and it is the most common cause of health-care-associated infectious diarrhea. Based on spontaneous Individual Case Safety Reports from EudraVigilance (EV), we conducted a descriptive analysis of Clostridioides [...] Read more.
The Gram-positive anaerobic bacterium Clostridioides difficile (CD) can produce intense exotoxins, contributing to nosocomial infections, and it is the most common cause of health-care-associated infectious diarrhea. Based on spontaneous Individual Case Safety Reports from EudraVigilance (EV), we conducted a descriptive analysis of Clostridioides difficile infection (CDI) cases that reported a spontaneous adverse reaction related to using ceftriaxone, colistimethate, ciprofloxacin, gentamicin, linezolid, meropenem, and piperacillin/tazobactam. Most ADR reports registered in EV that were related to CDI were associated with ceftriaxone (33%), ciprofloxacin (28%), and piperacillin/tazobactam (21%). Additionally, the disproportionality analysis performed showed that all studied antibiotics had a lower reporting probability when compared to clindamycin. A causal relationship between a drug and the occurrence of an adverse reaction cannot be established from EV data alone because the phenomena of underreporting, overreporting, and reporting bias may affect the results. Based on the analysis of the collected data, this study underlines the importance of surveillance and monitoring programs for the consumption of antibiotics. Furthermore, it is essential to use standardized laboratory tests to define CDI’s nature accurately. To prevent this infection, specialists should collaborate and adhere strictly to antibiotic stewardship programs, hygiene practices, and isolation protocols. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology and Pharmaceutical Development)
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Review

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28 pages, 723 KiB  
Review
Multidrug-Resistant Bacteria in Immunocompromised Patients
by Alexandru Duhaniuc, Diana Păduraru, Eduard-Vasile Nastase, Felicia Trofin, Luminița-Smaranda Iancu, Cristina-Mihaela Sima and Olivia-Simona Dorneanu
Pharmaceuticals 2024, 17(9), 1151; https://doi.org/10.3390/ph17091151 - 30 Aug 2024
Viewed by 956
Abstract
The increasing incidence of antibiotic resistance in bacteria is a major problem in terms of therapeutic options, especially in immunocompromised patients, such as patients from intensive care units (ICUs), HIV-positive patients, patients with malignancies or transplant patients. Commensal bacteria, especially anaerobes, serve to [...] Read more.
The increasing incidence of antibiotic resistance in bacteria is a major problem in terms of therapeutic options, especially in immunocompromised patients, such as patients from intensive care units (ICUs), HIV-positive patients, patients with malignancies or transplant patients. Commensal bacteria, especially anaerobes, serve to maintain microbial stability by preventing overpopulation with pathogenic bacteria. In immunocompromised patients, microbiota imbalance caused by antibiotic therapy and decreased host immunity favors intestinal overpopulation with pathogenic species, leading to increased bacterial translocation and susceptibility to systemic infections. Infections with multidrug-resistant (MDR) bacteria pose major challenges to the establishment of appropriate treatment and lead to increased mortality. Asymptomatic colonization with MDR bacteria usually precedes infection and tends to persist for long periods of time, and in immunocompromised patients, colonization with MDR bacteria is a risk factor for systemic infections. This review aims to assess the relation between colonization and infection with MDR bacteria in immunocompromised patients such as ICU patients, HIV-positive patients and cancer patients and to identify the prevalence and patterns of MDR bacterial colonization and infection in this category of patients. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology and Pharmaceutical Development)
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Other

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14 pages, 1307 KiB  
Case Report
Uncommon Septic Arthritis of the Hip Joint in an Immunocompetent Adult Patient Due to Bacillus pumilus and Paenibacillus barengoltzii Managed with Long-Term Treatment with Linezolid: A Case Report and Short Literature Review
by Razvan Silviu Cismasiu, Rares-Mircea Birlutiu and Liliana Lucia Preoțescu
Pharmaceuticals 2023, 16(12), 1743; https://doi.org/10.3390/ph16121743 - 18 Dec 2023
Cited by 3 | Viewed by 1668
Abstract
The Bacillus and Paenibacillus genera are diverse soil-related bacterial pathogens. In this case report, we describe, to our knowledge, the first report of septic arthritis in a native hip joint in an immunocompetent adult patient caused by Bacillus pumilus and Paenibacillus barengoltzii. We describe [...] Read more.
The Bacillus and Paenibacillus genera are diverse soil-related bacterial pathogens. In this case report, we describe, to our knowledge, the first report of septic arthritis in a native hip joint in an immunocompetent adult patient caused by Bacillus pumilus and Paenibacillus barengoltzii. We describe the case of a 39-year-old Caucasian male patient who sought medical advice for chronic pain on the mobilization of the right hip, decreased range of motion, and physical asthenia. The patient underwent a surgical intervention (core decompression) for a right osteonecrosis of the femoral head, with a slightly favorable postoperative evolution after surgery for one month. Surgical treatment was planned on the basis of clinical and paraclinical investigations and the joint damage. The hip was explored using an anterior approach under spinal anesthesia and standard antibiotic prophylaxis. After resection of the femoral head, meticulous debridement of all inflammatory tissues was performed, and a preformed temporary spacer was inserted into the femoral canal. Bacteriological laboratory studies identified Bacillus pumilus and Paenibacillus barengoltzii via matrix-assisted laser desorption–ionization time-of-flight mass spectrometry analysis. The patient initially received nine days of empirical therapy with intravenous antibiotics (linezolid and meropenem). After the bacterial strains were identified, the patient received organism-specific antibiotic therapy with the same antibiotics and dose for eight days until discharge. After discharge, the patient was referred to another hospital, where he continued treatment with linezolid for seven weeks and, after that, four weeks of oral therapy with cotrimoxazole and rifampicin. During this period, no severe or potentially life-threatening adverse events were recorded during long-term treatment with linezolid or with the two oral antibiotics. In conclusion, our findings suggest that long-term treatment with linezolid may be a viable option for the management of bone and joint infections caused by Bacillus pumilus and Paenibacillus barengoltzii. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology and Pharmaceutical Development)
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