Antibiotics

13 pages, 3971 KiB

Open AccessCommunication

Comprehensive Analysis of Antiphage Defense Mechanisms: Serovar-Specific Patterns

by Pavlo Petakh, Valentyn Oksenych, Yevheniya Khovpey and Oleksandr Kamyshnyi

Antibiotics 2024, 13(6), 522; https://doi.org/10.3390/antibiotics13060522 (registering DOI) - 3 Jun 2024

Leptospirosis is a major zoonotic disease caused by pathogenic spirochetes in the genus Leptospira, affecting over a million people annually and causing approximately 60,000 deaths. Leptospira interrogans, a key causative agent, likely possesses defense systems against bacteriophages (leptophages), yet these systems are [...] Read more.

Leptospirosis is a major zoonotic disease caused by pathogenic spirochetes in the genus Leptospira, affecting over a million people annually and causing approximately 60,000 deaths. Leptospira interrogans, a key causative agent, likely possesses defense systems against bacteriophages (leptophages), yet these systems are not well understood. We analyzed 402 genomes of L. interrogans using the DefenseFinder tool to identify and characterize the antiphage defense systems. We detected 24 unique systems, with CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated proteins), PrrC, Borvo, and Restriction-Modification (R-M) being the most prevalent. Notably, Cas were identified in all strains, indicating their central role in phage defense. Furthermore, there were variations in the antiphage system distribution across different serovars, suggesting unique evolutionary adaptations. For instance, Retron was found exclusively in the Canicola serovar, while prokaryotic Argonaute proteins (pAgo) were only detected in the Grippotyphosa serovar. These findings significantly enhance our understanding of Leptospira’s antiphage defense mechanisms. They reveal the potential for the development of serovar-specific phage-based therapies and underscore the importance of further exploring these defense systems. Full article

(This article belongs to the Special Issue Antibiotics vs. Phage Therapy, 2nd Edition)

► Show Figures

Figure 1

17 pages, 5960 KiB

Open AccessArticle

Antifungal Activity, Synergism with Fluconazole or Amphotericin B and Potential Mechanism of Direct Current against Candida albicans Biofilms and Persisters

by Peihui Zou, Jia Liu, Peng Li and Qingxian Luan

Antibiotics 2024, 13(6), 521; https://doi.org/10.3390/antibiotics13060521 (registering DOI) - 3 Jun 2024

Abstract

Candida albicans, as a notorious fungal pathogen, is associated with high morbidity and mortality worldwide due to its ability to form biofilms and persisters that can withstand currently available antifungals. Direct current (DC) has demonstrated a promising antimicrobial effect and synergistic effect [...] Read more.

Candida albicans, as a notorious fungal pathogen, is associated with high morbidity and mortality worldwide due to its ability to form biofilms and persisters that can withstand currently available antifungals. Direct current (DC) has demonstrated a promising antimicrobial effect and synergistic effect with antimicrobials against various infections. Here, we first found DC exerted a killing effect on C. albicans planktonic and biofilm cells. Moreover, DC showed a synergistic effect with fluconazole (FLC) and amphotericin B (AMB). Notably, near-to-complete eradication of AMB-tolerant C. albicans biofilm persisters was achieved upon DC treatment. Next, the mechanism of action of DC was explored through mapping the genes and proteomic profiles of DC-treated C. albicans. The multi-omics analysis, quantitative real-time PCR and assay of reactive oxygen species (ROS) demonstrated DC exerted an antifungal effect on C. albicans by increasing cellular oxidative stress. As revealed by multiple analyses (e.g., protein assay based on absorbance at 280 nm and rhodamine 6G assay), DC was able to enhance membrane permeability, inhibit drug efflux and increase cellular FLC/AMB concentration of C. albicans, thereby mediating its synergism with the antifungals. Furthermore, DC inhibited superoxide dismutase 2 (SOD2) expression and manganese-containing SOD (Mn SOD) activity, leading to ROS production and enhanced killing of C. albicans biofilm persisters. The current findings demonstrate that the adjunctive use of DC in combination with antifungals is a promising strategy for effective control of C. albicans infections and management of antifungal resistance/tolerance in Candida biofilms. Full article

(This article belongs to the Special Issue Antibiofilm Activity against Multidrug-Resistant Pathogens)

► Show Figures

Graphical abstract

15 pages, 574 KiB

Open AccessReview

Antimicrobial Stewardship: A Correct Management to Reduce Sepsis in NICU Settings

by Veronica Notarbartolo, Bintu Ayla Badiane, Vincenzo Insinga and Mario Giuffrè

Antibiotics 2024, 13(6), 520; https://doi.org/10.3390/antibiotics13060520 (registering DOI) - 3 Jun 2024

Abstract

The discovery of antimicrobial drugs has led to a significant increase in survival from infections; however, they are very often prescribed and administered, even when their use is not necessary and appropriate. Newborns are particularly exposed to infections due to the poor effectiveness [...] Read more.

The discovery of antimicrobial drugs has led to a significant increase in survival from infections; however, they are very often prescribed and administered, even when their use is not necessary and appropriate. Newborns are particularly exposed to infections due to the poor effectiveness and the immaturity of their immune systems. For this reason, in Neonatal Intensive Care Units (NICUs), the use of antimicrobial drugs is often decisive and life-saving, and it must be started promptly to ensure its effectiveness in consideration of the possible rapid evolution of the infection towards sepsis. Nevertheless, the misuse of antibiotics in the neonatal period leads not only to an increase in the development and wide spreading of antimicrobial resistance (AMR) but it is also associated with various short-term (e.g., alterations of the microbiota) and long-term (e.g., increased risk of allergic disease and obesity) effects. It appears fundamental to use antibiotics only when strictly necessary; specific decision-making algorithms and electronic calculators can help limit the use of unnecessary antibiotic drugs. The aim of this narrative review is to summarize the right balance between the risks and benefits of antimicrobial therapy in NICUs; for this purpose, specific Antimicrobial Stewardship Programs (ASPs) in neonatal care and the creation of a specific antimicrobial stewardship team are requested. Full article

(This article belongs to the Special Issue Infections and Sepsis in the Intensive Care Unit)

► Show Figures

Figure 1

19 pages, 3434 KiB

Open AccessArticle

Emergence of Rarely Reported Extensively Drug-Resistant Salmonella Enterica Serovar Paratyphi B among Patients in East China

by Jiefu Peng, Jingchao Feng, Hong Ji, Xiaoxiao Kong, Jie Hong, Liguo Zhu and Huimin Qian

Antibiotics 2024, 13(6), 519; https://doi.org/10.3390/antibiotics13060519 (registering DOI) - 2 Jun 2024

Abstract

Background: In recent years, global concern over increasing multidrug resistance (MDR) among various Salmonella serotypes has grown significantly. However, reports on MDR Salmonella Paratyphi B remain scarce, let alone the extensively drug-resistant (XDR) strains. Methods: In this retrospective study, we investigated the isolates [...] Read more.

Background: In recent years, global concern over increasing multidrug resistance (MDR) among various Salmonella serotypes has grown significantly. However, reports on MDR Salmonella Paratyphi B remain scarce, let alone the extensively drug-resistant (XDR) strains. Methods: In this retrospective study, we investigated the isolates of Salmonella Paratyphi B in Jiangsu Province over the past decade and carried out antimicrobial susceptibility tests, then the strains were sequenced and bioinformatics analyses were performed. Results: 27 Salmonella Paratyphi B strains were identified, of which the predominant STs were ST42 (11), ST86 (10), and ST2814 (5). Among these strains, we uncovered four concerning XDR Salmonella Paratyphi B ST2814 strains (4/5) which were previously unreported. These alarmingly resistant isolates showed resistance to all three major antibiotic classes for Salmonella treatment and even the last resort treatment tigecycline. Bioinformatics analysis revealed high similarity between the plasmids harbored by these XDR strains and diverse Salmonella serotypes and Escherichia coli from China and neighboring regions. Notably, these four plasmids carried the ramAp gene responsible for multiple antibiotic resistance by regulating the AcrAB-TolC pump, predominantly originating from China. Additionally, a distinct MDR ST42(1/11) strain with an ICE on chromosome was also identified. Furthermore, phylogenetic analysis of global ST42/ST2814 isolates highlighted the regional specificity of these strains, with Jiangsu isolates clustering together with domestic isolates and XDR ST2814 forming a distinct branch, suggesting adaptation to local antibiotic pressures. Conclusions: This research underscores the pressing need for closely monitoring the MDR/XDR Salmonella Paratyphi B, particularly the emerging ST2814 strains in Jiangsu Province, to effectively curb its spread and protect public health. Moreover, surveillance should be strengthened across different ecological niches and genera to track resistance genes and horizontal gene transfer elements under the concept of “ONE HEALTH”. Full article

(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)

16 pages, 1939 KiB

Open AccessArticle

Exploring the Impact of Antibiotics on Fever Recovery Time and Hospital Stays in Children with Viral Infections: Insights from Advanced Data Analysis

by Mohammed Al Qahtani, Saleh Fahad AlFulayyih, Sarah Saleh Al Baridi, Sara Amer Alomar, Ahmed Nawfal Alshammari, Reem Jassim Albuaijan and Mohammed Shahab Uddin

Antibiotics 2024, 13(6), 518; https://doi.org/10.3390/antibiotics13060518 (registering DOI) - 1 Jun 2024

Abstract

Background: Antibiotic overuse in pediatric patients with upper respiratory tract infections (UR-TIs) raises concerns about antimicrobial resistance. This study examines the impact of antibiotics on hospital stay duration and fever resolution in pediatric patients diagnosed with viral infections via a multiplex polymerase chain [...] Read more.

Background: Antibiotic overuse in pediatric patients with upper respiratory tract infections (UR-TIs) raises concerns about antimicrobial resistance. This study examines the impact of antibiotics on hospital stay duration and fever resolution in pediatric patients diagnosed with viral infections via a multiplex polymerase chain reaction (PCR) respiratory panel. Methods: In the pediatric ward of Imam Abdulrahman Bin Faisal Hospital, a retrospective cohort analysis was conducted on pediatric patients with viral infections confirmed by nasopharyngeal aspirates from October 2016 to December 2021. Cohorts receiving antibiotics versus those not receiving them were balanced using the gradient boosting machine (GBM) technique for propensity score matching. Results: Among 238 patients, human rhinovirus/enterovirus (HRV/EV) was most common (44.5%), followed by respiratory syncytial virus (RSV) (18.1%). Co-infections occurred in 8.4% of cases. Antibiotic administration increased hospital length of stay (LOS) by an average of 2.19 days (p-value: 0.00). Diarrhea reduced LOS by 2.26 days, and higher albumin levels reduced LOS by 0.40 days. Fever and CRP levels had no significant effect on LOS. Time to recovery from fever showed no significant difference between antibiotic-free (Abx0) and antibiotic-received (Abx1) groups (p-value: 0.391), with a hazard ratio of 0.84 (CI: 0.57–1.2). Conclusions: Antibiotics did not expedite recovery but were associated with longer hospital stays in pediatric patients with acute viral respiratory infections. Clinicians should exercise caution in prescribing antibiotics to pediatric patients with confirmed viral infections, especially when non-critical. Full article

(This article belongs to the Special Issue Antibiotic Use in Outpatients and Hospitals)

► Show Figures

Figure 1

12 pages, 640 KiB

Open AccessArticle

The Molecular Mouse System: A New Useful Tool for Guiding Antimicrobial Therapy in Critically Ill Septic Patients

by Carola Mauri, Alessandra Consonni, Elena Briozzo, Chiara Giubbi, Elisa Meroni, Silvia Tonolo and Francesco Luzzaro

Antibiotics 2024, 13(6), 517; https://doi.org/10.3390/antibiotics13060517 (registering DOI) - 1 Jun 2024

Abstract

Bloodstream infections (BSI) caused by multidrug-resistant (MDR) bacteria, pose a major threat for patients, especially for those who are immunosuppressed. Rapid pathogen detection and characterization from positive blood cultures are crucial in the management of patients with BSI to enable an adequate and [...] Read more.

Bloodstream infections (BSI) caused by multidrug-resistant (MDR) bacteria, pose a major threat for patients, especially for those who are immunosuppressed. Rapid pathogen detection and characterization from positive blood cultures are crucial in the management of patients with BSI to enable an adequate and timely antimicrobial therapy. This study aimed to investigate the potential role of the Molecular Mouse system, a new CE IVD molecular test designed to rapidly detect the causative agents of bacteremia and their resistance determinants, in the management of the therapy in critically ill patients. Agreement between the results of the Molecular Mouse and the conventional routine method was also considered. Overall, 100 positive blood cultures were collected from septic critically ill patients from May 2023 to January 2024 and analyzed with Molecular Mouse and routine protocols. The new instrument consistently agreed with the routine protocols in the case of monomicrobial blood cultures, while some discrepancies were obtained in the polymicrobial samples. Antimicrobial resistance genes were detected in 35 samples, with vanA and CTX-M-1/9 groups being the most frequently detected targets. Therapy was adjusted in 42 critically ill patients confirming the importance of new rapid molecular tests in the management of positive blood cultures, to adjust empirical therapy and use new antibiotics accurately. Full article

(This article belongs to the Special Issue The Epidemiology of Antimicrobial Resistance in Bloodstream Infections: Focus on Activity of New Antibiotics)

► Show Figures

Figure 1

14 pages, 2313 KiB

Open AccessArticle

The Clinical Characteristics and Antimicrobial Resistance of Staphylococcus aureus Isolated from Patients with Staphylococcal Scalded Skin Syndrome (SSSS) in Southwestern China

by Yidan Wu, Hengfeng Wu, Man Wu, Wanchen Wei, Yuying Wei, Tiantian Li, Cunwei Cao and Zhijian Yao

Antibiotics 2024, 13(6), 516; https://doi.org/10.3390/antibiotics13060516 - 31 May 2024

Abstract

Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This study aimed to investigate the clinical characteristics of SSSS patients in our hospital, the relative proportion of methicillin-resistant Staphylococcus aureus (MRSA) [...] Read more.

Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This study aimed to investigate the clinical characteristics of SSSS patients in our hospital, the relative proportion of methicillin-resistant Staphylococcus aureus (MRSA) in skin and soft tissue secretions, and the drug sensitivity of S. aureus to better assist dermatologists in the diagnosis and treatment of SSSS. We reviewed the demographic characteristics, clinical manifestations, treatment regimens, therapeutic efficacy, laboratory test results, drug sensitivity, and outcome data of 79 SSSS patients from January 2012 to December 2021. Statistical analysis was performed using t tests and chi-square tests. Among the 79 SSSS patients, MRSA was detected in 35 (44.3%) isolates: 34 community-acquired (CA)-MRSA (97.1%) and 1 hospital-acquired (HA)-MRSA. The SSSS incidence increased annually from 2012 to 2014 and then decreased gradually after peaking in 2015. All the isolates were sensitive to vancomycin, tigecycline, linezolid, moxifloxacin, levofloxacin, and ciprofloxacin; were completely resistant to penicillin; and had low sensitivity to clindamycin and erythromycin. Interestingly, the sensitivity of MRSA to tetracycline increased annually after 2015. The resistance rates to common drugs previously used to treat SSSS increased. These findings may accelerate diagnosis and improve empirical antibiotic use, suggesting that clinicians should prescribe drugs according to antimicrobial susceptibility. Full article

► Show Figures

Figure 1

10 pages, 1314 KiB

Open AccessCorrection

Correction: Furugaito et al. Antimicrobial Susceptibility to 27 Drugs and the Molecular Mechanisms of Macrolide, Tetracycline, and Quinolone Resistance in Gemella sp. Antibiotics 2023, 12, 1538

by Michiko Furugaito, Yuko Arai, Yutaka Uzawa, Toshinori Kamisako, Kohei Ogura, Shigefumi Okamoto and Ken Kikuchi

Antibiotics 2024, 13(6), 515; https://doi.org/10.3390/antibiotics13060515 - 31 May 2024

Abstract

The authors wish to make the following corrections to this paper [...] Full article

► Show Figures

Figure 1

16 pages, 2956 KiB

Open AccessArticle

In Vitro Virucidal Activity of Different Essential Oils against Bovine Viral Diarrhea Virus Used as Surrogate of Human Hepatitis C Virus

by Gianvito Lanave, Francesco Pellegrini, Francesco Triggiano, Osvalda De Giglio, Maria Stella Lucente, Georgia Diakoudi, Cristiana Catella, Arturo Gentile, Roberta Tardugno, Giuseppe Fracchiolla, Vito Martella and Michele Camero

Antibiotics 2024, 13(6), 514; https://doi.org/10.3390/antibiotics13060514 - 31 May 2024

Abstract

The hepatitis C virus (HCV) is a major hepatotropic virus that affects humans with increased risk of developing hepatocellular carcinoma. The bovine viral diarrhea virus (BVDV) causes abortion, calf mortality and poor reproductive performance in cattle. Due the difficulties of in vitro cultivation [...] Read more.

The hepatitis C virus (HCV) is a major hepatotropic virus that affects humans with increased risk of developing hepatocellular carcinoma. The bovine viral diarrhea virus (BVDV) causes abortion, calf mortality and poor reproductive performance in cattle. Due the difficulties of in vitro cultivation for HCV, BVDV has been used as surrogate for in vitro assessment of the efficacy of antivirals. Essential oils (EOs) display antiviral and virucidal activity on several viral pathogens. In this study, the virucidal activity of five EOs, Salvia officinalis L. EO (SEO), Melissa officinalis L. EO (MEO), Citrus lemon EO (LEO), Rosmarinus officinalis L. EO (REO) and Thymus vulgaris L. EO (TEO) against BVDV was evaluated in vitro at different concentrations for several time contacts. MEO and LEO were able to considerably inactivate BVDV with a time- and dose-dependent fashion. MEO and LEO at the highest concentrations decreased viral titer by 2.00 and 2.25 log₁₀ TCID₅₀/50 μL at 8 h contact time, respectively. SEO, REO and TEO displayed mild virucidal activity at the highest concentrations for 8 h contact times. In this study, the virucidal efficacies of MEO and LEO against BVDV were observed regardless of compound concentration and contact time. Further studies are needed to confirm the potential use of MEO and LEO as surface disinfectants. Full article

(This article belongs to the Special Issue Natural Products and Bio-Nanomaterials: Novel Strategies to Overcome Antibiotic Resistance)

► Show Figures

Figure 1

30 pages, 2194 KiB

Open AccessReview

Multidisciplinary Perspectives of Challenges in Infective Endocarditis Complicated by Septic Embolic-Induced Acute Myocardial Infarction

by Elena Stamate, Oana Roxana Ciobotaru, Manuela Arbune, Alin Ionut Piraianu, Oana Monica Duca, Ana Fulga, Iuliu Fulga, Alexia Anastasia Stefania Balta, Adrian George Dumitrascu and Octavian Catalin Ciobotaru

Antibiotics 2024, 13(6), 513; https://doi.org/10.3390/antibiotics13060513 - 31 May 2024

Abstract

Background: Infective endocarditis (IE) management is challenging, usually requiring multidisciplinary collaboration from cardiologists, infectious disease specialists, interventional cardiologists, and cardiovascular surgeons, as more than half of the cases will require surgical procedures. Therefore, it is essential for all healthcare providers involved in managing [...] Read more.

Background: Infective endocarditis (IE) management is challenging, usually requiring multidisciplinary collaboration from cardiologists, infectious disease specialists, interventional cardiologists, and cardiovascular surgeons, as more than half of the cases will require surgical procedures. Therefore, it is essential for all healthcare providers involved in managing IE to understand the disease’s characteristics, potential complications, and treatment options. While systemic embolization is one of the most frequent complications of IE, the coronary localization of emboli causing acute myocardial infarction (AMI) is less common, with an incidence ranging from 1% to 10% of cases, but it has a much higher rate of morbidity and mortality. There are no guidelines for this type of AMI management in IE. Methods: This narrative review summarizes the current knowledge regarding septic coronary embolization in patients with IE. Additionally, this paper highlights the diagnosis and management challenges in such cases, particularly due to the lack of protocols or consensus in the field. Results: Data extracted from case reports indicate that septic coronary embolization often occurs within the first two weeks of the disease. The aortic valve is most commonly involved with vegetation, and the occluded vessel is frequently the left anterior descending artery. Broad-spectrum antibiotic therapy followed by targeted antibiotic therapy for infection control is essential, and surgical treatment offers promising results through surgical embolectomy, concomitant with valve replacement or aspiration thrombectomy, with or without subsequent stent insertion. Thrombolytics are to be avoided due to the increased risk of bleeding. Conclusions: All these aspects should constitute future lines of research, allowing the integration of all current knowledge from multidisciplinary team studies on larger patient cohorts and, subsequently, creating a consensus for assessing the risk and guiding the management of this potentially fatal complication. Full article

(This article belongs to the Special Issue Sepsis Management and Antibiotic Therapy)

► Show Figures

Figure 1

11 pages, 1347 KiB

Open AccessArticle

Antibiotic Resistance Trends in Uropathogens during the COVID-19 Pandemic in Western Romania: A Cross-Sectional Study

by Elena Hogea, Alexandra Cristina Muntean, Felix Bratosin, Iulia Georgiana Bogdan, Oana Plavitu, Adelina Fratutu, Cristian Oancea, Mihai Calin Bica, Delia Muntean, Ingrid Hrubaru, Zoran Laurentiu Popa and Adrian Cosmin Ilie

Antibiotics 2024, 13(6), 512; https://doi.org/10.3390/antibiotics13060512 - 30 May 2024

Abstract

The emergence and spread of antimicrobial resistance have been significant global health challenges, exacerbated by the COVID-19 pandemic. As healthcare systems faced unprecedented pressures, the management of non-COVID conditions, including urinary tract infections (UTIs), also encountered obstacles due to changes in microbial flora [...] Read more.

The emergence and spread of antimicrobial resistance have been significant global health challenges, exacerbated by the COVID-19 pandemic. As healthcare systems faced unprecedented pressures, the management of non-COVID conditions, including urinary tract infections (UTIs), also encountered obstacles due to changes in microbial flora and antibiotic usage patterns. This cross-sectional study aimed to characterize the antimicrobial resistance trends among bacterial uropathogens isolated from patients in the Western region of Romania, between January 2020 and December 2022. The objectives were to map the resistance patterns and observe the pandemic’s influence on antimicrobial resistance, particularly among enterobacterial Gram-negative species, to guide treatment and infection control strategies. From a total of 2472 urine samples collected during the study period, 378 positive samples were analyzed. This study found that Escherichia coli was the most commonly isolated uropathogen, making up 46.3% of the cases (n = 175), with Klebsiella pneumoniae at 20.6% (n = 78). There was a high resistance of Klebsiella pneumoniae to several antibiotics, while carbapenemase production increased to 52.5% and extended-spectrum beta-lactamase (ESBL) present in 24.3% of the strains. Escherichia coli showed high resistance rates to amoxicillin–clavulanic acid (from 45.4% in 2020 to 53.8% in 2022) and trimethoprim/sulfamethoxazole (from 27.5% in 2020 to 47.2% in 2022). The increasing trend of antimicrobial resistance noted during the pandemic, especially in Gram-negative enterobacterial species, highlights the urgent need for robust infection control measures and rational antibiotic use. This study underscores the critical importance of continuous surveillance to adapt antibiotic therapies effectively and prevent the further spread of resistance, thereby ensuring effective management of UTIs in the evolving healthcare landscape influenced by the pandemic. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Epidemiological Study of Clinically Relevant Pathogens)

► Show Figures

Figure 1

17 pages, 1297 KiB

Open AccessArticle

Five-Year Evaluation of the PROA-NEN Pediatric Antimicrobial Stewardship Program in a Spanish Tertiary Hospital

by Aurora Fernández-Polo, Susana Melendo-Perez, Nieves Larrosa Escartin, Natalia Mendoza-Palomar, Marie Antoinette Frick, Pere Soler-Palacin and on behalf of the PROA-NEN Working Group

Antibiotics 2024, 13(6), 511; https://doi.org/10.3390/antibiotics13060511 - 30 May 2024

Abstract

Abstract: Introduction: Actions to reduce and optimize antimicrobial use are crucial in the management of infectious diseases to counteract the emergence of short- and long-term resistance. This is particularly important for pediatric patients due to the increasing incidence of serious infections caused [...] Read more.

Abstract: Introduction: Actions to reduce and optimize antimicrobial use are crucial in the management of infectious diseases to counteract the emergence of short- and long-term resistance. This is particularly important for pediatric patients due to the increasing incidence of serious infections caused by resistant bacteria in this population. The aim of this study was to evaluate the impact of a pediatric antimicrobial stewardship program (PROA-NEN) implemented in a Spanish tertiary hospital by assessing the use of systemic antimicrobials, clinical indicators, antimicrobial resistance, and costs. Methods: In this quasi-experimental, single-center study, we included pediatric patients (0–18 years) admitted to specialized pediatric medical and surgical units, as well as pediatric and neonatal intensive care units, from January 2015 to December 2019. The impact of the PROA-NEN program was assessed using process (consumption trends and prescription quality) and outcome indicators (clinical and microbiological). Antibiotic prescription quality was determined using quarterly point prevalence cross-sectional analyses. Results: Total antimicrobial consumption decreased during the initial three years of the PROA-NEN program, followed by a slight rebound in 2019. This decrease was particularly evident in intensive care and surgical units. Antibiotic use, according to the WHO Access, Watch and Reserve (AWaRe) classification, remained stable during the study period. The overall rate of appropriate prescription was 83.2%, with a significant increase over the study period. Clinical indicators did not substantially change over the study period. Direct antimicrobial expenses decreased by 27.3% from 2015 to 2019. Conclusions: The PROA-NEN program was associated with reduced antimicrobial consumption, improved appropriate use, and decreased costs without compromising clinical and/or microbiological outcomes in patients. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

11 pages, 4973 KiB

Open AccessArticle

Mouldable Collagen–Tricalciumphosphate Is a Safe Carrier for Local Antibiotics—Short-Term Results in Revision Hip Arthroplasty

by Yannik Hanusrichter, Carsten Gebert, Sven Frieler, Burkhard Moellenbeck, Marcel Dudda, Martin Wessling and Christoph Theil

Antibiotics 2024, 13(6), 510; https://doi.org/10.3390/antibiotics13060510 - 30 May 2024

Viewed by 80

Abstract

Background: Improving local antibiotic delivery is a promising approach to improve infection control and potentially shorten systemic treatment in periprosthetic joint infection (PJI). This study investigates the use of an antibiotic-loaded, mouldable collagen–tricalciumphosphate composite in treatment of hip PJI. Methods: 124 application cases [...] Read more.

Background: Improving local antibiotic delivery is a promising approach to improve infection control and potentially shorten systemic treatment in periprosthetic joint infection (PJI). This study investigates the use of an antibiotic-loaded, mouldable collagen–tricalciumphosphate composite in treatment of hip PJI. Methods: 124 application cases in 79 patients were included from a referral centre; systemic adverse infects, local complications, and infection control were analysed. Results: In most cases, either vancomycin or meropenem were used. Pathogens were previously known in 82 (66%) cases with polymicrobial infection in 20 (25%) patients. There were no cases of hypercalcaemia. Acute kidney injure was present in 14 (11%) cases. Chronic kidney failure persisted in two cases. During a mean follow-up of 12 (SD 9.3; range 3–35) months, implant survival was achieved in 73 (92%) patients; revision due to PJI was performed in 19 cases. Conclusion: Mouldable collagen–tricalciumphosphate composite bone substitute as a local antibiotic carrier in revision hip arthroplasty appears to be a valid option for local antibiotic delivery without systemic complications. Implant survival of 92% supports the hypothesis that local antibiotic therapy is an important component in the treatment of PJI. Full article

(This article belongs to the Special Issue Antibiotics in Orthopedic Infections, 2nd Volume)

► Show Figures

Figure 1

13 pages, 639 KiB

Open AccessReview

Antibiofilm Strategies in Neonatal and Pediatric Infections

by Chrysoula Kosmeri, Vasileios Giapros, Anastasios Serbis, Foteini Balomenou and Maria Baltogianni

Antibiotics 2024, 13(6), 509; https://doi.org/10.3390/antibiotics13060509 - 30 May 2024

Viewed by 133

Abstract

Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial communities, comprising bacteria and fungi, exhibit resilience against antibiotics and host immune responses. Bacterial species such as Enterococcus faecalis, Pseudomonas aeruginosa, [...] Read more.

Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial communities, comprising bacteria and fungi, exhibit resilience against antibiotics and host immune responses. Bacterial species such as Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis commonly form biofilms on medical devices, exacerbating infection risks. Neonates and children, particularly those in intensive care units, are highly susceptible to biofilm-associated infections due to the prolonged use of invasive devices, such as central lines and endotracheal tubes. Enteral feeding tubes, crucial for neonatal nutritional support, also serve as potential sites for biofilm formation, contributing to recurrent microbial contamination. Moreover, Candida species, including Candida pelliculosa, present emerging challenges in neonatal care, with multi-drug resistant strains posing treatment complexities. Current antimicrobial therapies, while important in managing infections, often fall short in eradicating biofilms, necessitating alternative strategies. The aim of this review is to summarize current knowledge regarding antibiofilm strategies in neonates and in children. Novel approaches focusing on biofilm inhibition and dispersal show promise, including surface modifications, matrix-degrading enzymes, and quorum-sensing inhibitors. Prudent use of medical devices and exploration of innovative antibiofilm therapies are imperative in mitigating neonatal and pediatric biofilm infections. Full article

(This article belongs to the Section Antibiofilm Strategies)

► Show Figures

Figure 1

11 pages, 3242 KiB

Open AccessArticle

Efficacy of Short Novel Antimicrobial Peptides in a Mouse Model of Staphylococcus pseudintermedius Skin Infection

by Mingyu Ouyang, Fangrong Wu and Changmin Hu

Antibiotics 2024, 13(6), 508; https://doi.org/10.3390/antibiotics13060508 - 30 May 2024

Viewed by 117

Abstract

As the clinical application of antibiotics for bacterial skin infections in companion animals becomes increasingly prevalent, the issue of bacterial resistance has become more pronounced. Antimicrobial peptides, as a novel alternative to traditional antibiotics, have garnered widespread attention. In our study, synthetic peptides [...] Read more.

As the clinical application of antibiotics for bacterial skin infections in companion animals becomes increasingly prevalent, the issue of bacterial resistance has become more pronounced. Antimicrobial peptides, as a novel alternative to traditional antibiotics, have garnered widespread attention. In our study, synthetic peptides ADD-A and CBD3-ABU were tested against Staphylococcus pseudintermedius skin infections in KM mice. ADD-A was applied topically and through intraperitoneal injection, compared with control groups and treatments including CBD3-ABU, ampicillin sodium, and saline. Wound contraction, bacterial counts and histology were assessed on days 3 and 11 post-infection. ADD-A and ampicillin treatments significantly outperformed saline in wound healing (p < 0.0001 and p < 0.001, respectively). ADD-A also showed a markedly lower bacterial count than ampicillin (p < 0.0001). Histologically, ADD-A-applied wounds had better epidermal continuity and a thicker epidermis than normal, with restored follicles and sebaceous glands. ADD-A’s effectiveness suggests it as a potential alternative to antibiotics for treating skin infections in animals. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Bioactive Peptides and Their Derivatives)

► Show Figures

Figure 1

9 pages, 489 KiB

Open AccessArticle

Detection of KPC-216, a Novel KPC-3 Variant, in a Clinical Isolate of Klebsiella pneumoniae ST101 Co-Resistant to Ceftazidime-Avibactam and Cefiderocol

by Maria Giufrè, Giulia Errico, Maria Del Grosso, Michela Pagnotta, Bernardetta Palazzotti, Milva Ballardini, Annalisa Pantosti, Marcello Meledandri and Monica Monaco

Antibiotics 2024, 13(6), 507; https://doi.org/10.3390/antibiotics13060507 - 29 May 2024

Viewed by 198

Abstract

Background: Carbapenemase-producing Klebsiella pneumoniae (CP-KP) represents a global threat to public health, with limited antimicrobial therapeutic options. In this study, we analyzed a ceftazidime/avibactam (CAZ-AVI)-resistant K. pneumoniae isolate obtained from a patient previously exposed to CAZ-AVI expressing a novel K. pneumoniae carbapenemase (KPC)-3 [...] Read more.

Background: Carbapenemase-producing Klebsiella pneumoniae (CP-KP) represents a global threat to public health, with limited antimicrobial therapeutic options. In this study, we analyzed a ceftazidime/avibactam (CAZ-AVI)-resistant K. pneumoniae isolate obtained from a patient previously exposed to CAZ-AVI expressing a novel K. pneumoniae carbapenemase (KPC)-3 variant. Methods: Antimicrobial susceptibility testing was performed using reference broth microdilution. Whole-genome sequencing (WGS) was performed using Illumina and Nanopore Technologies. Short- and long-reads were combined with Unicycler. Assemblies were investigated for multilocus sequence typing (MLST), antimicrobial resistance genes, porins, and plasmids. Results: The K. pneumoniae isolate (KP_RM_1) was resistant to CAZ-AVI, expanded-spectrum cephalosporins, amikacin, ertapenem, and cefiderocol (FDC) but was susceptible to tigecycline, colistin, trimethoprim/sulfamethoxazole, meropenem–vaborbactam, and imipenem–relebactam. WGS revealed that the KP_RM_1 genome is composed of a single chromosome of 5 Mbp and five circular plasmids. Further analysis showed the presence of novel bla_KPC-216 located on a 72 kb plasmid. KPC-216 differs from KPC-3 by a Lysin (K) insertion at position 168 (+K168). Conclusions: We report the identification of a new KPC-3 variant associated with CAZ-AVI resistance. The KPC variants associated with CAZ-AVI resistance should be determined to promptly inform clinicians and start the appropriate antimicrobial therapy. Full article

(This article belongs to the Special Issue Editorial Board Members' Collection Series: Antibiotic Resistance Mechanisms and Molecular Epidemiology of ESKAPEE)

► Show Figures

Figure 1

16 pages, 463 KiB

Open AccessReview

Antibiotic Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections in View of the Newly Developed β-Lactams: A Narrative Review of the Existing Evidence

by Francesca Serapide, Maurizio Guastalegname, Sara Palma Gullì, Rosaria Lionello, Andrea Bruni, Eugenio Garofalo, Federico Longhini, Enrico Maria Trecarichi and Alessandro Russo

Antibiotics 2024, 13(6), 506; https://doi.org/10.3390/antibiotics13060506 - 29 May 2024

Viewed by 136

Abstract

It is estimated that antimicrobial resistance (AMR) is responsible for nearly 5 million human deaths worldwide each year and will reach 10 million by 2050. Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a [...] Read more.

It is estimated that antimicrobial resistance (AMR) is responsible for nearly 5 million human deaths worldwide each year and will reach 10 million by 2050. Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. Among the antibiotics under consideration, Sulbactam/durlobactam seems to be the best candidate to replace current back-bone agents. Cefiderocol could play a pivotal role within combination therapy regimens. Due to toxicity and the pharmacokinetics/pharmacodynamics (PK/PD) limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the efficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with improved lung activity, as well as on the iv rifabutin formulation. In this narrative review, we focused the antibiotic treatment of CRAB infections in view of newly developed β-lactam agents (NBLs). Full article

(This article belongs to the Special Issue Antibiotic Resistance in Acinetobacter and Associated Treatment Strategies)

13 pages, 236 KiB

Open AccessReview

Evaluation of Surveillance Strategies of Antimicrobial Consumption in Animals

by Carly Ching, Muhammad H. Zaman and Veronika J. Wirtz

Antibiotics 2024, 13(6), 505; https://doi.org/10.3390/antibiotics13060505 - 29 May 2024

Viewed by 158

Abstract

The aim of this paper is to explore and assess various strategies for monitoring antimicrobial consumption (AMC) in animals, within the context of the One Health approach. Recent studies have shed light on the limited surveillance and data collection for AMC in animals. [...] Read more.

The aim of this paper is to explore and assess various strategies for monitoring antimicrobial consumption (AMC) in animals, within the context of the One Health approach. Recent studies have shed light on the limited surveillance and data collection for AMC in animals. Using the United States Center for Disease Control and Prevention Policy Analytical Framework, we assess global, national, and farm-level surveillance strategies on public health impact and feasibility using evidence from primary, secondary, and grey literature. From this, we identify key policy mechanisms that support the adoption of surveillance while providing specific recommendations. We find that a global strategy, though valuable for benchmarking and policy guidance, faces participation and data visibility challenges. National-level surveillance offers direct inputs into national action plans but struggles with data uniformity and comparability. Farm-level surveillance, while resource-intensive, provides the most granular data for informing specific interventions. We advocate for a multi-faceted approach to AMC surveillance, emphasizing that legal mandates and financial incentives are crucial for encouraging surveillance participation, along with international cooperation for enhancing participation and data quality. Drawing parallels with public reporting challenges in other sectors can provide valuable lessons on how to address data collection, analysis, and reporting barriers. Full article

(This article belongs to the Special Issue Antibiotics Use in Farms, 2nd Volume)

11 pages, 687 KiB

Open AccessArticle

One Health Landscape of Antimicrobial Resistance in Bacteria Isolated from Virginia between 2007–2021

by Jimin Kim and Eunice Ndegwa

Antibiotics 2024, 13(6), 504; https://doi.org/10.3390/antibiotics13060504 - 29 May 2024

Viewed by 143

Abstract

The emergence of antimicrobial-resistant (AMR) bacteria has become a critical global One Health issue, mainly attributed to the extensive use of antimicrobial agents in human and agricultural settings. Regional and local AMR surveillance data is essential for implementing awareness and mitigation strategies. This [...] Read more.

The emergence of antimicrobial-resistant (AMR) bacteria has become a critical global One Health issue, mainly attributed to the extensive use of antimicrobial agents in human and agricultural settings. Regional and local AMR surveillance data is essential for implementing awareness and mitigation strategies. This article assesses AMR frequency in 1604 bacterial isolates consisting of Escherichia coli (E. coli) and Salmonella spp. isolated from diverse sources in Virginia, including farm animals, wildlife, environment, and food samples from 2007 to 2021. The results are based on the Kirby–Bauer disc diffusion assessment method of susceptibility to select antimicrobial agents, spanning nine distinct categories approved by the US Food and Drug Administration for clinical use. Streptomycin (STR) and tetracycline (TCY) exhibited the highest frequency of resistance in E. coli (39.1%) and Salmonella (25.2%), respectively. Multidrug resistance (MDR) was evident in 6.6% of E. coli and 10.9% of Salmonella isolates. Notably, 51% of E. coli and 36% of Salmonella isolates demonstrated resistance to more than one antimicrobial. None of the tested antimicrobials guaranteed effectiveness against the bacteria isolated from the surveyed sources and regions. The study found heightened MDR and distinct AMR patterns in bacteria isolated from food products compared to other sampled sources. These findings are vital for comprehending the current AMR landscape, prompting the development of strategies to mitigate the emergence of AMR bacteria, and advocating prudent antimicrobial use from a One Health perspective. Full article

(This article belongs to the Special Issue A One Health Approach to Antimicrobial Resistance)

► Show Figures

Figure 1

15 pages, 290 KiB

Open AccessReview

Antibiotic–Drug Interactions in the Intensive Care Unit: A Literature Review

by Paweł Radkowski, Maria Derkaczew, Michał Mazuchowski, Annas Moussa, Katarzyna Podhorodecka, Justyna Dawidowska-Fidrych, Małgorzata Braczkowska-Skibińska, Daria Synia, Karol Śliwa, Marta Wiszpolska and Marta Majewska

Antibiotics 2024, 13(6), 503; https://doi.org/10.3390/antibiotics13060503 - 29 May 2024

Viewed by 177

Abstract

Interactions between drugs are a common problem in Intensive Care Unit patients, as they mainly have a critical condition that often demands the administration of multiple drugs simultaneously. Antibiotics are among the most frequently used medications, as infectious diseases are often observed in [...] Read more.

Interactions between drugs are a common problem in Intensive Care Unit patients, as they mainly have a critical condition that often demands the administration of multiple drugs simultaneously. Antibiotics are among the most frequently used medications, as infectious diseases are often observed in ICU patients. In this review, the most important antibiotic–drug interactions, based on the pharmacokinetic and pharmacodynamic mechanisms, were gathered together and described. In particular, some of the most important interactions with main groups of antibacterial drugs were observed in patients simultaneously prescribed oral anticoagulants, NSAIDs, loop diuretics, and valproic acid. As a result, the activity of drugs can be increased or decreased, as dosage modification might be necessary. It should be noted that these crucial interactions can help predict and avoid negative consequences, leading to better patient recovery. Moreover, since there are other factors, such as fluid therapy or albumins, which may also modify the effectiveness of antibacterial therapy, it is important for anaesthesiologists to be aware of them. Full article

15 pages, 3711 KiB

Open AccessPerspective

Implications of Artificial Intelligence in Addressing Antimicrobial Resistance: Innovations, Global Challenges, and Healthcare’s Future

by Francesco Branda and Fabio Scarpa

Antibiotics 2024, 13(6), 502; https://doi.org/10.3390/antibiotics13060502 - 29 May 2024

Viewed by 296

Abstract

Antibiotic resistance poses a significant threat to global public health due to complex interactions between bacterial genetic factors and external influences such as antibiotic misuse. Artificial intelligence (AI) offers innovative strategies to address this crisis. For example, AI can analyze genomic data to [...] Read more.

Antibiotic resistance poses a significant threat to global public health due to complex interactions between bacterial genetic factors and external influences such as antibiotic misuse. Artificial intelligence (AI) offers innovative strategies to address this crisis. For example, AI can analyze genomic data to detect resistance markers early on, enabling early interventions. In addition, AI-powered decision support systems can optimize antibiotic use by recommending the most effective treatments based on patient data and local resistance patterns. AI can accelerate drug discovery by predicting the efficacy of new compounds and identifying potential antibacterial agents. Although progress has been made, challenges persist, including data quality, model interpretability, and real-world implementation. A multidisciplinary approach that integrates AI with other emerging technologies, such as synthetic biology and nanomedicine, could pave the way for effective prevention and mitigation of antimicrobial resistance, preserving the efficacy of antibiotics for future generations. Full article

(This article belongs to the Special Issue Artificial Intelligence and Antimicrobial Resistance: Innovation, Global Challenges and the Future of Healthcare)

► Show Figures

Figure 1

22 pages, 1017 KiB

Open AccessReview

RND Efflux Pump Induction: A Crucial Network Unveiling Adaptive Antibiotic Resistance Mechanisms of Gram-Negative Bacteria

by Marine Novelli and Jean-Michel Bolla

Antibiotics 2024, 13(6), 501; https://doi.org/10.3390/antibiotics13060501 - 28 May 2024

Viewed by 216

Abstract

The rise of multi-drug-resistant (MDR) pathogenic bacteria presents a grave challenge to global public health, with antimicrobial resistance ranking as the third leading cause of mortality worldwide. Understanding the mechanisms underlying antibiotic resistance is crucial for developing effective treatments. Efflux pumps, particularly those [...] Read more.

The rise of multi-drug-resistant (MDR) pathogenic bacteria presents a grave challenge to global public health, with antimicrobial resistance ranking as the third leading cause of mortality worldwide. Understanding the mechanisms underlying antibiotic resistance is crucial for developing effective treatments. Efflux pumps, particularly those of the resistance-nodulation-cell division (RND) superfamily, play a significant role in expelling molecules from bacterial cells, contributing to the emergence of multi-drug resistance. These are transmembrane transporters naturally produced by Gram-negative bacteria. This review provides comprehensive insights into the modulation of RND efflux pump expression in bacterial pathogens by numerous and common molecules (bile, biocides, pharmaceuticals, additives, plant extracts, etc.). The interplay between these molecules and efflux pump regulators underscores the complexity of antibiotic resistance mechanisms. The clinical implications of efflux pump induction by non-antibiotic compounds highlight the challenges posed to public health and the urgent need for further investigation. By addressing antibiotic resistance from multiple angles, we can mitigate its impact and preserve the efficacy of antimicrobial therapies. Full article

(This article belongs to the Special Issue Rise of Antibiotic Resistance: Mechanisms Involved and Solutions to Tackle It)

27 pages, 4236 KiB

Open AccessArticle

Antimicrobial Susceptibility of Canine and Feline Urinary Tract Infection Pathogens Isolated from Animals with Clinical Signs in European Veterinary Practices during the Period 2013–2018

by Robin Temmerman, Helena Berlamont, Farid El Garch, Markus Rose, Shabbir Simjee, Sylvie Meschi and Anno de Jong

Antibiotics 2024, 13(6), 500; https://doi.org/10.3390/antibiotics13060500 - 28 May 2024

Viewed by 237

Abstract

Bacterial urinary tract infections (UTIs) occur frequently in companion animals and are often treated with antibiotics. However, antimicrobial resistance can severely hamper treatment success. Therefore, antimicrobial susceptibility monitoring is key. UTI isolates were obtained from dogs and cats in two collection periods (ComPath [...] Read more.

Bacterial urinary tract infections (UTIs) occur frequently in companion animals and are often treated with antibiotics. However, antimicrobial resistance can severely hamper treatment success. Therefore, antimicrobial susceptibility monitoring is key. UTI isolates were obtained from dogs and cats in two collection periods (ComPath II: 2013–2014 and ComPath III: 2017–2018) as part of CEESA’s ComPath programme. Susceptibility testing of the UTI isolates (2021 in total) was carried out at one central laboratory using agar and broth dilution methodology as recommended by the Clinical and Laboratory Standards Institute. Escherichia coli was the most frequently isolated bacterium in UTI in both dogs (46.9%, 43.1%) and cats (61.2%, 48.3%) across ComPath II and ComPath III, respectively. The percentage of resistance in E. coli was low (<10%) across both programmes in both dogs and cats except for trimethoprim-sulfamethoxazole (dogs ComPath III: 12.9%; cats ComPath II: 13.0%) and enrofloxacin (10.5%), marbofloxacin (11.4%), and doxycycline (98.8%) for dogs in ComPath III. Three (7.5%) of the 40 isolated S. aureus bacteria in total were MRSA and harboured mecA. The level of multidrug resistance (MDR) was generally low and ranged from 0.0% for feline coagulase-negative Staphylococcus spp. to 11.7% for canine Proteus spp., except for a peak of MDR observed in canine Klebsiella isolates from ComPath II (36.7%). Overall, antimicrobial resistance for most canine and feline UTI pathogens isolated during the ComPath II and ComPath III programmes was low (1–10%) to moderate (10–20%). Full article

(This article belongs to the Special Issue Epidemiology, Impact and Mitigation of Antimicrobial Resistance in Veterinary Medicine, 2nd Volume)

► Show Figures

Figure 1

19 pages, 2936 KiB

Open AccessArticle

Combination of Chromatographic Analysis and Chemometric Methods with Bioactivity Evaluation of the Antibacterial Properties of Helichrysum italicum Essential Oil

by Tijana Zeremski, Olja Šovljanski, Vladimir Vukić, Biljana Lončar, Milica Rat, Nataša Perković Vukčević, Milica Aćimović and Lato Pezo

Antibiotics 2024, 13(6), 499; https://doi.org/10.3390/antibiotics13060499 - 28 May 2024

Viewed by 229

Abstract

Helichrysum italicum (immortelle) essential oil is one of the most popular essential oils worldwide and it has many beneficial properties, including antimicrobial. However, in this plant, the chemical diversity of the essential oil is very pronounced. The aim of this work was to [...] Read more.

Helichrysum italicum (immortelle) essential oil is one of the most popular essential oils worldwide and it has many beneficial properties, including antimicrobial. However, in this plant, the chemical diversity of the essential oil is very pronounced. The aim of this work was to process the GC-MS results of four samples of H. italicum essential oil of Serbian origin by chemometric tools, and evaluate the antimicrobial activity in vitro and in silico. Overall, 47 compounds were identified, the most abundant were γ-curcumene, α-pinene, and ar-curcumene, followed by α-ylangene, neryl acetate, trans-caryophyllene, italicene, α-selinene, limonene, and italidiones. Although the four samples of H. italicum essential oil used in this study were obtained from different producers in Serbia, they belong to the type of essential oil rich in sesquiterpenes (γ-curcumene and ar-curcumene chemotype). In vitro antimicrobial potential showed that five were sensitive among ten strains of tested microorganisms: Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Saccharomyces cerevisiae, and Candida albicans. Therefore, these microorganism models were used further for in silico molecular docking through the mechanism of ATP-ase inhibitory activity. Results showed that among all compounds from H. italicum essential oil, neryl acetate has the highest predicted binding energy. Artificial neural network modeling (ANN) showed that two major compounds γ-curcumene and α-pinene, as well as minor compounds such as trans-β-ocimene, terpinolene, terpinene-4-ol, isoitalicene, italicene, cis-α-bergamotene, trans-α-bergamotene, italidiones, trans-β-farnesene, γ-selinene, β-selinene, α-selinene, and guaiol are responsible for the antimicrobial activity of H. italicum essential oil. The results of this study indicate that H. italicum essential oil samples rich in γ-curcumene, α-pinene, and ar-curcumene cultivated in Serbia (Balkan) have antimicrobial potential both in vitro and in silico. In addition, according to ANN modeling, the proportion of neryl acetate and other compounds detected in these samples has the potential to exhibit antimicrobial activity. Full article

(This article belongs to the Special Issue Exploring Antimicrobial Properties and Bioactive Compounds of Edible and Medicinal Plants)

10 pages, 1976 KiB

Open AccessArticle

The Impact of National Activities on Antibiotic Consumption in Hospitals and Different Departments over a 14-Year Period

by Milan Čižman, Tamara Kastrin, Bojana Beović, Aleksander Mahnič, Tom Bajec and Slovenian Surveillance Antibiotic Consumption Group

Antibiotics 2024, 13(6), 498; https://doi.org/10.3390/antibiotics13060498 - 28 May 2024

Viewed by 182

Abstract

The aim of this study was to assess the use of antibiotics in hospitals and different departments over 14 years (2006–2019) and the impact of various national activities related to this, including national audits of the use of antibiotics for systemic use. The [...] Read more.

The aim of this study was to assess the use of antibiotics in hospitals and different departments over 14 years (2006–2019) and the impact of various national activities related to this, including national audits of the use of antibiotics for systemic use. The consumption of antibiotics for systemic use (J01) from all Slovenian hospitals (n = 29) and five departments (internal medicine, surgery, ICU (medicine, surgery), paediatrics and gynaecology/obstetrics) was collected. Total hospital consumption was expressed as the number of defined daily doses (DDDs) per 1000 inhabitants per day (DID), the number of DDDs/100 bed days and the number of DDDs/100 admissions. Over 14 years, J01 hospital consumption increased by 13.8%, expressed in DDDs/100 bed days (p = 0.002). In 2019, compared to 2006, the consumption of J01, expressed in DDD/100 bed days, increased from 19.9% to 33.1% in all departments, except intensive care units. J01 consumption expressed in DDD/100 admissions increased by 7.0% to 39.4% in all but paediatric wards (where it decreased by 12.7%). In all years, we observed large variations in the consumption of antibiotics in departments of the same type. The effectiveness of audit interventions aimed at optimizing antibiotic consumption exhibited notable variation across hospitals, with specialized facilities generally demonstrating superior outcomes compared to general hospitals. Full article

(This article belongs to the Special Issue Irrational Antibiotic Use in Primary Care)

► Show Figures

Figure 1

20 pages, 2608 KiB

Open AccessArticle

Is It Still Beneficial to Monitor the Trough Concentration of Vancomycin? A Quantitative Meta-Analysis of Nephrotoxicity and Efficacy

by Wanqiu Yang, Kaiting Zhang, Yuancheng Chen, Yaxin Fan and Jing Zhang

Antibiotics 2024, 13(6), 497; https://doi.org/10.3390/antibiotics13060497 - 28 May 2024

Viewed by 197

Abstract

This study conducted a quantitative meta-analysis to investigate the association of vancomycin indicators, particularly area under the curve over 24 h (AUC₂₄) and trough concentrations (C_trough), and their relationship with both nephrotoxicity and efficacy. Literature research was performed in [...] Read more.

This study conducted a quantitative meta-analysis to investigate the association of vancomycin indicators, particularly area under the curve over 24 h (AUC₂₄) and trough concentrations (C_trough), and their relationship with both nephrotoxicity and efficacy. Literature research was performed in PubMed and Web of Science on vancomycin nephrotoxicity and efficacy in adult inpatients. Vancomycin C_trough, AUC₂₄, AUC₂₄/minimum inhibitory concentration (MIC), nephrotoxicity evaluation and treatment outcomes were extracted. Logistic regression and E_max models were conducted, stratified by evaluation criterion for nephrotoxicity and primary outcomes for efficacy. Among 100 publications on nephrotoxicity, 29 focused on AUC₂₄ and 97 on C_trough, while of 74 publications on efficacy, 27 reported AUC₂₄/MIC and 68 reported C_trough. The logistic regression analysis indicated a significant association between nephrotoxicity and vancomycin C_trough (odds ratio = 2.193; 95% CI 1.582–3.442, p < 0.001). The receiver operating characteristic curve had an area of 0.90, with a cut-off point of 14.55 mg/L. Additionally, 92.3% of the groups with a mean AUC₂₄ within 400–600 mg·h/L showed a mean C_trough of 10–20 mg/L. However, a subtle, non-statistically significant association was observed between the AUC₂₄ and nephrotoxicity, as well as between AUC₂₄/MIC and C_trough concerning treatment outcomes. Our findings suggest that monitoring vancomycin C_trough remains a beneficial and valuable approach to proactively identifying patients at risk of nephrotoxicity, particularly when C_trough exceeds 15 mg/L. C_trough can serve as a surrogate for AUC₂₄ to some extent. However, no definitive cut-off values were identified for AUC₂₄ concerning nephrotoxicity or for C_trough and AUC₂₄/MIC regarding efficacy. Full article

(This article belongs to the Section Pharmacokinetics and Pharmacodynamics of Drugs)

► Show Figures

Figure 1

22 pages, 2861 KiB

Open AccessArticle

Genetic Characterization and Population Structure of Drug-Resistant Mycobacterium tuberculosis Isolated from Brazilian Patients Using Whole-Genome Sequencing

by Leonardo Souza Esteves, Lia Lima Gomes, Daniela Brites, Fátima Cristina Onofre Fandinho, Marcela Bhering, Márcia Aparecida da Silva Pereira, Emilyn Costa Conceição, Richard Salvato, Bianca Porphirio da Costa, Reginalda Ferreira de Melo Medeiros, Paulo Cesar de Souza Caldas, Paulo Redner, Margareth Pretti Dalcolmo, Vegard Eldholm, Sebastien Gagneux, Maria Lucia Rossetti, Afrânio Lineu Kritski and Philip Noel Suffys

Antibiotics 2024, 13(6), 496; https://doi.org/10.3390/antibiotics13060496 - 28 May 2024

Viewed by 329

Abstract

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) [...] Read more.

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) or genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates. Full article

(This article belongs to the Special Issue Genomic Analysis of Antimicrobial Drug-Resistant Bacteria)

► Show Figures

Figure 1

9 pages, 442 KiB

Open AccessArticle

Accuracy of the Infectious Diseases Society of America and British Thoracic Society Criteria for Acute Pneumonia in Differentiating Chemical and Bacterial Complications of Aspiration in Comatose Ventilated Patients Following Drug Poisoning

by Quentin Delforge, Alexandre Gaudet, Pauline Boddaert, Frédéric Wallet, Benoit Voisin and Saad Nseir

Antibiotics 2024, 13(6), 495; https://doi.org/10.3390/antibiotics13060495 - 27 May 2024

Viewed by 248

Abstract

Drug poisoning frequently leads to admission to intensive care units, often resulting in aspiration, a potentially life-threatening condition if not properly managed. Aspiration can manifest as either bacterial aspiration pneumonia (BAP) or aspiration pneumonitis (AP), which are challenging to distinguish potentially leading to [...] Read more.

Drug poisoning frequently leads to admission to intensive care units, often resulting in aspiration, a potentially life-threatening condition if not properly managed. Aspiration can manifest as either bacterial aspiration pneumonia (BAP) or aspiration pneumonitis (AP), which are challenging to distinguish potentially leading to overprescription of antibiotics and the emergence of multidrug-resistant bacteria. This study aims to assess the accuracy of the Infectious Diseases Society of America (IDSA) and British Thoracic Society (BTS) criteria in differentiating BAP from AP in comatose ventilated patients following drug poisoning. This cross-sectional study included 95 patients admitted for drug poisoning at the Lille University Hospital intensive care department, between 2013 and 2017, requiring mechanical ventilation and receiving antibiotics for aspiration. Patients were categorized as having bacterial complications if tracheal sampling yielded positive culture results, and if they were otherwise considered to have chemical complications. The sensitivity, specificity, positive predictive value, and negative predictive value of IDSA and BTS criteria in identifying patients with bacterial complications were evaluated. Among the patients, 34 (36%) experienced BAP. The IDSA criteria demonstrated a sensitivity of 62% and specificity of 33%, while the BTS criteria showed a sensitivity of 50% and specificity of 38%. Both the IDSA and BTS criteria exhibited poor sensitivity and specificity in identifying microbiologically confirmed pneumonia in comatose ventilated patients following drug poisoning. Full article

4 pages, 154 KiB

Open AccessEditorial

Molecular Detection, Characterization, Antimicrobial Resistance and Genomic Epidemiology of Pathogenic Bacteria

by Andrey Shelenkov

Antibiotics 2024, 13(6), 494; https://doi.org/10.3390/antibiotics13060494 - 27 May 2024

Viewed by 369

Abstract

In recent decades, growing attention has been directed worldwide toward antimicrobial-resistant (AMR) bacterial pathogens causing infections in clinical, environmental, and food chain production settings [...] Full article

(This article belongs to the Special Issue Molecular Detection, Characterization, Antimicrobial Resistance and Genomic Epidemiology of Pathogenic Bacteria)

12 pages, 235 KiB

Open AccessArticle

Opinions of Medical Staff Regarding Antibiotic Resistance

by Aneta Krolak-Ulińska, Piotr Merks, Urszula Religioni, Beata Chełstowska, Agnieszka Drab, Krystian Wdowiak, Katarzyna Plagens-Rotman, Zbigniew Doniec and Anna Staniszewska

Antibiotics 2024, 13(6), 493; https://doi.org/10.3390/antibiotics13060493 - 27 May 2024

Viewed by 260

Abstract

Introduction: Antibiotic resistance poses a significant threat to public health, that can lead to reduced effectiveness of many therapies, increased morbidity, longer hospitalization times, increased deaths, and additional costs for health care systems. Unreasonable use of antibiotics may result from a lack of [...] Read more.

Introduction: Antibiotic resistance poses a significant threat to public health, that can lead to reduced effectiveness of many therapies, increased morbidity, longer hospitalization times, increased deaths, and additional costs for health care systems. Unreasonable use of antibiotics may result from a lack of adequate knowledge about antibiotic therapy and a lack of knowledge of the risks associated with antibiotic resistance, both among medical personnel and patients. Aim. The primary objective of the study was to verify the opinion of medical personnel on the risks associated with antibiotic resistance. Material and Methods: The study was conducted in 2023 among 605 Polish sanitary workers. An anonymous survey designed specifically for the purpose of the study was used. The survey was made available on the Internet through the Trade Unions of Pharmacy Workers and directly to hospitals with the support of local authorities. Results: The majority of respondents were women (77.36%). The largest group consisted of individuals over 40 years of age (55.04%). More than half of the respondents were nurses (56.20%), and every fourth of the respondents was a physician (23.64%). Most respondents consider antibiotic resistance to be a very serious (24.13%) or extremely serious (30.75%) problem. The problem of antibiotic resistance on a global scale was mentioned, especially in the opinions of physicians and nurses (p < 0.01), people working in the profession for over a year (p < 0.01), and people with a specialization or undergoing specialist training (p = 0.00). Similarly, these groups most often indicated that antibiotic resistance poses a problem in their workplace. The main problems of antibiotic resistance were the use of antibiotics in farm animals (36.69%), the pressure on patients to take antibiotics (38.84%), and the prophylactic use of antibiotics (43.15%). Conclusions: Medical personnel consider antibiotic resistance a somewhat serious problem, although not all agree in this regard. The risk of antibiotic resistance is much more seriously assessed by physicians and nurses, as well as by people with specializations or undergoing specialization training. Knowledge about antibiotic resistance should be further spread among all groups of medical personnel. Full article

Journal Menu

Journal Browser

Antibiotics, Volume 13, Issue 6 (June 2024) – 52 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI