Antibiotics

31 pages, 405 KiB

Open AccessReview

Rapid Molecular Diagnostics of Pneumonia Caused by Gram-Negative Bacteria: A Clinician’s Review

by Ionela-Anca Pintea-Simon, Ligia Bancu, Anca Delia Mare, Cristina Nicoleta Ciurea, Felicia Toma and Adrian Man

Antibiotics 2024, 13(9), 805; https://doi.org/10.3390/antibiotics13090805 (registering DOI) - 25 Aug 2024

Abstract

With approximately half a billion events per year, lower respiratory tract infections (LRTIs) represent a major challenge for the global public health. Among LRTI cases, those caused by Gram-negative bacteria (GNB) are associated with a poorer prognostic. Standard-of-care etiologic diagnostics is lengthy and [...] Read more.

With approximately half a billion events per year, lower respiratory tract infections (LRTIs) represent a major challenge for the global public health. Among LRTI cases, those caused by Gram-negative bacteria (GNB) are associated with a poorer prognostic. Standard-of-care etiologic diagnostics is lengthy and difficult to establish, with more than half of cases remaining microbiologically undocumented. Recently, syndromic molecular diagnostic panels became available, enabling simultaneous detection of tens of pathogen-related and antimicrobial-resistance genetic markers within a few hours. In this narrative review, we summarize the available data on the performance of molecular diagnostics in GNB pneumonia, highlighting the main strengths and limitations of these assays, as well as the main factors influencing their clinical utility. We searched MEDLINE and Web of Science databases for relevant English-language articles. Molecular assays have higher analytical sensitivity than cultural methods, and show good agreement with standard-of-care diagnostics regarding detection of respiratory pathogens, including GNB, and identification of frequent patterns of resistance to antibiotics. Clinical trials reported encouraging results on the usefulness of molecular assays in antibiotic stewardship. By providing early information on the presence of pathogens and their probable resistance phenotypes, these assays assist in the choice of targeted therapy, in shortening the time from sample collection to appropriate antimicrobial treatment, and in reducing unnecessary antibiotic use. Full article

(This article belongs to the Special Issue Diagnosis, Drug Resistance Mechanism and Molecular Epidemiology of Clinical Pathogens)

11 pages, 847 KiB

Open AccessArticle

Days of Antibiotic Spectrum Coverage (DASC) as a Metric for Evaluating the Impact of Prospective Audit and Feedback (PAF) against Long-Term Broad-Spectrum Antibiotic Use

by Yuichi Shibata, Jun Hirai, Nobuaki Mori, Nobuhiro Asai, Mao Hagihara and Hiroshige Mikamo

Antibiotics 2024, 13(9), 804; https://doi.org/10.3390/antibiotics13090804 (registering DOI) - 25 Aug 2024

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Abstract

The present study aimed to evaluate the impact of prospective audit and feedback (PAF) on the use of inpatient broad-spectrum antibiotics for more than 10 days using days of therapy (DOT) and a novel metric called days of antibiotic spectrum coverage (DASC) to [...] Read more.

The present study aimed to evaluate the impact of prospective audit and feedback (PAF) on the use of inpatient broad-spectrum antibiotics for more than 10 days using days of therapy (DOT) and a novel metric called days of antibiotic spectrum coverage (DASC) to assess whether the antimicrobial spectrum was narrowed. Conducted at Aichi Medical University Hospital in Japan, the study compared a six-month baseline period (April to September 2022) with a six-month intervention period (April to September 2023). The primary outcome measures were changes in DOT/patient and DASC/patient for broad-spectrum antibiotics. Propensity score matching was performed between two periods and a total of 172 patients were included in the study (pre-intervention, n = 86; intervention, n = 86). The DASC/patient of broad-spectrum antibiotics was statistically decreased in the intervention period compared to that in the baseline period (153.3 vs. 122.7, p < 0.05). Additionally, our PAF intervention led to a switch to narrow-spectrum antimicrobial therapy without increasing all-cause 30-day mortality (5.8% vs. 5.8%, p = 1.0). However, the DOT/patient, DASC/patient, and DASC/DOT of all antimicrobials were not significantly changed. Our study concluded that we should reconsider the timing of PAF intervention by evaluating the effort of PAF by using DOT and DASC. Full article

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

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21 pages, 11964 KiB

Open AccessArticle

Novel Antimicrobial Agents Based on Zinc-Doped Hydroxyapatite Loaded with Tetracycline

by Simona Liliana Iconaru, Daniela Predoi, Carmen Steluta Ciobanu, Catalin Constantin Negrila, Roxana Trusca, Steinar Raaen, Krzysztof Rokosz, Liliana Ghegoiu, Monica Luminita Badea and Carmen Cimpeanu

Antibiotics 2024, 13(9), 803; https://doi.org/10.3390/antibiotics13090803 (registering DOI) - 25 Aug 2024

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Abstract

In this paper, we present for the first time the development of zinc-doped hydroxyapatite enriched with tetracycline (ZnHApTe) powders and provide a comprehensive evaluation of their physico-chemical and biological properties. Various techniques such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron [...] Read more.

In this paper, we present for the first time the development of zinc-doped hydroxyapatite enriched with tetracycline (ZnHApTe) powders and provide a comprehensive evaluation of their physico-chemical and biological properties. Various techniques such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were used for the sample’s complex evaluation. Moreover, the biocompatibility of zinc-doped hydroxyapatite (ZnHAp) and ZnHApTe nanoparticles was evaluated with the aid of human fetal osteoblastic cells (hFOB 1.19 cell line). The results of the biological assays suggested that these nanoparticles hold great promise as potential candidates for the future development of novel biocompatible and antimicrobial agents for biomedical applications. The antimicrobial properties of the ZnHAp and ZnHApTe nanoparticles were assessed using the standard reference microbial strains Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Candida albicans ATCC 10231. The results of the in vitro antimicrobial assay demonstrated that both tested materials exhibited good antimicrobial activity. Additionally, these data also indicated that the antimicrobial effects of the ZnHAp nanoparticles were intensified by the presence of tetracycline (Te). Furthermore, the results also suggested that the antimicrobial activity of the samples increased with the incubation time. Full article

(This article belongs to the Special Issue Nanomaterials as Antimicrobial Agents for Biomedical Applications)

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13 pages, 232 KiB

Open AccessArticle

Antibiotic Susceptibility of Aerobic and Facultative Anaerobic Gram-Negative Rods in Hong Kong and Implications on Usefulness of Ceftazidime-Avibactam and Ceftolozane-Tazobactam

by Jade L. L. Teng, Elaine Chan, Tsz Tuen Li, Tsz Ying Kwan, Ka Fai Chan, Wing Ho Li, Viki W. K. Tang, Man Lung Yeung, Susanna K. P. Lau and Patrick C. Y. Woo

Antibiotics 2024, 13(9), 802; https://doi.org/10.3390/antibiotics13090802 (registering DOI) - 24 Aug 2024

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Abstract

Due to the increasing resistance of aerobic and facultative anaerobic Gram-negative rods, ceftazidime-avibactam and ceftolozane-tazobactam have been launched in the market in the last few years. In this study, we analyzed the susceptibility pattern of the major aerobic and facultative anaerobic Gram-negative rods [...] Read more.

Due to the increasing resistance of aerobic and facultative anaerobic Gram-negative rods, ceftazidime-avibactam and ceftolozane-tazobactam have been launched in the market in the last few years. In this study, we analyzed the susceptibility pattern of the major aerobic and facultative anaerobic Gram-negative rods in Hong Kong for ceftazidime-avibactam, ceftolozane-tazobactam, four other broad-spectrum antibiotics commonly used in Hong Kong and colistin. For 300 isolates collected from January to December 2021, non-ESBL-producing Enterobacterales, ESBL-producing Enterobacterales and Pseudomonas aeruginosa were highly susceptible to ceftazidime-avibactam (all 100%) and ceftolozane-tazobactam (98.7%, 99.7% and 94.3%). For 32 archived ESBL-producing Klebsiella pneumoniae isolates collected between January 2014 and March 2023, all were susceptible to ceftazidime-avibactam and ceftolozane-tazobactam. For 101 archived carbapenemase-producing Enterobacterales, their susceptibilities to ceftazidime-avibactam and ceftolozane-tazobactam varied depending on the type of carbapenemase produced. Both had high activities against OXA-producing strains (97.1% and 76.5%, respectively) but were 100% resistant for NDM-producing and NDM+OXA-producing strains. All KPC-producing strains were susceptible to ceftazidime-avibactam but resistant to ceftolozane-tazobactam. Ceftazidime-avibactam and ceftolozane-tazobactam are good alternatives for the management of infections caused by ESBL-producing Enterobacterales and selective strains of carbapenemase-producing Enterobacterales in Hong Kong. Full article

27 pages, 2606 KiB

Open AccessSystematic Review

Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review

by Laura Gras-Martín, Adrián Plaza-Diaz, Borja Zarate-Tamames, Paula Vera-Artazcoz, Olga H. Torres, Carla Bastida, Dolors Soy and Jesús Ruiz-Ramos

Antibiotics 2024, 13(9), 801; https://doi.org/10.3390/antibiotics13090801 (registering DOI) - 24 Aug 2024

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Abstract

(1) Background: Knowledge about the behavior of antibiotics in critically ill patients has been increasing in recent years. Some studies have concluded that a high percentage may be outside the therapeutic range. The most likely cause of this is the pharmacokinetic variability of [...] Read more.

(1) Background: Knowledge about the behavior of antibiotics in critically ill patients has been increasing in recent years. Some studies have concluded that a high percentage may be outside the therapeutic range. The most likely cause of this is the pharmacokinetic variability of critically ill patients, but it is not clear which factors have the greatest impact. The aim of this systematic review is to identify risk factors among critically ill patients that may exhibit significant pharmacokinetic alterations, compromising treatment efficacy and safety. (2) Methods: The search included the PubMed, Web of Science, and Embase databases. (3) Results: We identified 246 observational studies and ten clinical trials. The most studied risk factors in the literature were renal function, weight, age, sex, and renal replacement therapy. Risk factors with the greatest impact included renal function, weight, renal replacement therapy, age, protein or albumin levels, and APACHE or SAPS scores. (4) Conclusions: The review allows us to identify which critically ill patients are at a higher risk of not reaching therapeutic targets and helps us to recognize the extensive number of risk factors that have been studied, guiding their inclusion in future studies. It is essential to continue researching, especially in real clinical practice and with clinical outcomes. Full article

(This article belongs to the Special Issue Featured Reviews in Pharmacokinetics and Pharmacodynamics of Antibiotics)

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23 pages, 4568 KiB

Open AccessArticle

Bacteriophage Therapy on an In Vitro Wound Model and Synergistic Effects in Combination with Beta-Lactam Antibiotics

by Guillermo Santamaría-Corral, John Jairo Aguilera-Correa, Jaime Esteban and Meritxell García-Quintanilla

Antibiotics 2024, 13(9), 800; https://doi.org/10.3390/antibiotics13090800 (registering DOI) - 24 Aug 2024

Viewed by 269

Abstract

One of the primary opportunistic pathogens that can cause a wide range of diseases is Pseudomonas aeruginosa. This microorganism can become resistant to practically every antibacterial currently in use, including beta-lactam antibiotics. Its ability to proliferate as biofilm has been linked to, [...] Read more.

One of the primary opportunistic pathogens that can cause a wide range of diseases is Pseudomonas aeruginosa. This microorganism can become resistant to practically every antibacterial currently in use, including beta-lactam antibiotics. Its ability to proliferate as biofilm has been linked to, among other things, the failure of antimicrobial therapies. Due to a variety of virulence factors and host immune system modifications, P. aeruginosa is one of the most significant and common bacteria that colonize wounds and burns. A novel therapeutic option for treating these multidrug-resistant (MDR) bacterial infections is the combination of antibiotics and bacteriophages. This approach has been linked to improved biofilm penetration, a decreased selection of antibiotic and bacteriophage resistance, and an enhanced antibacterial impact. Combining the F1Pa bacteriophage and beta-lactam antibiotics reduced the viability of the mature biofilm of MDR P. aeruginosa strains and suppressed bacterial growth in vitro. F1Pa critically reduced the amount of biofilm that MDR P. aeruginosa clinical strains formed in the in vitro wound model. These findings highlight the bacteriophage F1Pa’s therapeutic potential as a prophylactic topical treatment against MDR pseudomonal infections in wounds and burns. Full article

(This article belongs to the Special Issue Bacteriophage Therapy: Recent Developments and Applications of a Renaissance Weapon, 2nd Edition)

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11 pages, 2771 KiB

Open AccessArticle

Precision Phage Cocktail Targeting Surface Appendages for Biocontrol of Salmonella in Cold-Stored Foods

by Seongok Kim, Bokyung Son, Hyeryen Kim, Hakdong Shin and Sangryeol Ryu

Antibiotics 2024, 13(9), 799; https://doi.org/10.3390/antibiotics13090799 (registering DOI) - 24 Aug 2024

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Abstract

Salmonella enterica is a major food-borne pathogen causing food poisoning. The use of bacteriophages as alternative biocontrol agents has gained renewed interest due to the rising issue of antibiotic-resistant bacteria. We isolated and characterized three phages targeting Salmonella: SPN3US, SPN3UB, and SPN10H. [...] Read more.

Salmonella enterica is a major food-borne pathogen causing food poisoning. The use of bacteriophages as alternative biocontrol agents has gained renewed interest due to the rising issue of antibiotic-resistant bacteria. We isolated and characterized three phages targeting Salmonella: SPN3US, SPN3UB, and SPN10H. Morphological and genomic analyses revealed that they belong to the class Caudoviricetes. SPN3UB, SPN3US, and SPN10H specifically target bacterial surface molecules as receptors, including O-antigens of lipopolysaccharides, flagella, and BtuB, respectively. The phages exhibited a broad host range against Salmonella strains, highlighting their potential for use in a phage cocktail. Bacterial challenge assays demonstrated significant lytic activity of the phage cocktail consisting of the three phages against S. typhimurium UK1, effectively delaying the emergence of phage-resistant bacteria. The phage cocktail effectively reduced Salmonella contamination in foods, including milk and pork and chicken meats, during cold storage. These results indicate that a phage cocktail targeting different host receptors could serve as a promising antimicrobial strategy to control Salmonella. Full article

(This article belongs to the Special Issue Bacteriophage Therapy: Recent Developments and Applications of a Renaissance Weapon, 2nd Edition)

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9 pages, 394 KiB

Open AccessArticle

An Eco-Friendly Method to Synthesize Potent Antimicrobial Tricyclic Flavonoids

by Loredana-Elena Mantea, Cristina-Veronica Moldovan, Mihaela Savu, Laura Gabriela Sarbu, Marius Stefan and Mihail Lucian Birsa

Antibiotics 2024, 13(9), 798; https://doi.org/10.3390/antibiotics13090798 (registering DOI) - 24 Aug 2024

Viewed by 248

Abstract

The rapid emergence and spread of multidrug-resistant microorganisms is threatening our ability to treat common infections, with serious medical, social, and economic consequences. Despite substantial progress in the global fight against antibiotic resistance, the number of effective antibiotics is rapidly decreasing, underlying the [...] Read more.

The rapid emergence and spread of multidrug-resistant microorganisms is threatening our ability to treat common infections, with serious medical, social, and economic consequences. Despite substantial progress in the global fight against antibiotic resistance, the number of effective antibiotics is rapidly decreasing, underlying the urgent need to develop novel antimicrobials. In the present study, the green synthesis of novel iodine-substituted tricyclic flavonoids has been accomplished using an eco-friendly reagent, HPW-SiO₂, as a cyclization agent for the precursor 3-dithiocarmamic flavanones. In vitro antimicrobial activity of the new compounds was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentrations. All tested compounds displayed potent inhibitory activity against all tested microbial strains, with the lowest MIC values of 0.12 µg/mL and 0.48 µg/mL recorded for compound 5c against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. Higher MIC values (7.81 µg/mL) were registered for several flavonoids against Gram-negative bacteria Escherichia coli and Acinetobacter pittii. No inhibitory activity was evidenced against Pseudomonas aeruginosa strain. The highest antifungal activity was displayed by flavonoid 5d against Candida krusei (MIC = 3.9 µg/mL). The same compound also exhibited the most potent bactericidal and fungicidal activity against Bacillus subtilis (0.9 µg/mL) and Staphylococcus aureus (1.97 µg/mL), Candida albicans, and Candida krusei (7.81 µg/mL). Based on the reported results, we believe that the novel iodine-substituted tricyclic flavonoids have good potential to become new antimicrobial agents effective against bacterial and fungal strains, including WHO-priority pathogens. Full article

(This article belongs to the Special Issue Green Antimicrobials in Biomedical Engineering: Recent Advances Proposal)

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14 pages, 981 KiB

Open AccessArticle

Increasing Fluroquinolone Susceptibility and Genetic Diversity of ESBL-Producing E. coli from the Lower Respiratory Tract during the COVID-19 Pandemic

by Katja Hrovat, Katja Seme and Jerneja Ambrožič Avguštin

Antibiotics 2024, 13(9), 797; https://doi.org/10.3390/antibiotics13090797 (registering DOI) - 23 Aug 2024

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Abstract

Lower respiratory tract infections (LRTIs) are the fourth leading cause of death worldwide, among which Escherichia coli (E. coli) pneumonia is considered a rare phenomenon. Treatment options for LRTIs have become limited, especially for extended-spectrum β-lactamase-producing E. coli (ESBL-EC), which are [...] Read more.

Lower respiratory tract infections (LRTIs) are the fourth leading cause of death worldwide, among which Escherichia coli (E. coli) pneumonia is considered a rare phenomenon. Treatment options for LRTIs have become limited, especially for extended-spectrum β-lactamase-producing E. coli (ESBL-EC), which are usually resistant to other groups of antimicrobials as well. The aim of our study was to compare the phenotypic resistance profiles and genotypes of ESBL-EC isolates associated with LRTIs before (pre-COVID-19) and during (COVID-19) the COVID-19 pandemic. All isolates were screened for antimicrobial resistance genes (ARGs) and virulence-associated genes (VAGs) and assigned to phylogenetic groups, sequence types and clonal groups by PCR. During the pandemic, a significantly lower proportion of ciprofloxacin-, levofloxacin- and trimethoprim-sulfamethoxazole-resistant ESBL-EC isolates was retrieved from lower respiratory tract (LRT) samples. PCR-based genotypization revealed greater clonal diversity and a significantly lower proportion of isolates with bla_TEM, aac(6′)-Ib-cr and qacEΔ1 genes. In addition, a higher proportion of isolates with the integrase gene int1 and virulence genes sat and tsh was confirmed. The lower prevalence of fluoroquinolone resistance and greater genetic diversity of ESBL-EC isolated during the COVID-19 period may have been due to the introduction of new bacterial strains into the hospital environment, along with changes in clinical establishment guidelines and practices. Full article

(This article belongs to the Special Issue Antibiotics Use in COVID-19 and Respiratory Tract Infections)

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20 pages, 1065 KiB

Open AccessArticle

Genomic Characterization of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Implicated in Bloodstream Infections, KwaZulu-Natal, South Africa: A Pilot Study

by Bakoena A. Hetsa, Jonathan Asante, Joshua Mbanga, Arshad Ismail, Akebe L. K. Abia, Daniel G. Amoako and Sabiha Y. Essack

Antibiotics 2024, 13(9), 796; https://doi.org/10.3390/antibiotics13090796 (registering DOI) - 23 Aug 2024

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Abstract

Staphylococcus aureus is an opportunistic pathogen and a leading cause of bloodstream infections, with its capacity to acquire antibiotic resistance genes posing significant treatment challenges. This pilot study characterizes the genomic profiles of S. aureus isolates from patients with bloodstream infections in KwaZulu-Natal, [...] Read more.

Staphylococcus aureus is an opportunistic pathogen and a leading cause of bloodstream infections, with its capacity to acquire antibiotic resistance genes posing significant treatment challenges. This pilot study characterizes the genomic profiles of S. aureus isolates from patients with bloodstream infections in KwaZulu-Natal, South Africa, to gain insights into their resistance mechanisms, virulence factors, and clonal and phylogenetic relationships. Six multidrug-resistant (MDR) S. aureus isolates, comprising three methicillin-resistant S. aureus (MRSA) and three methicillin-susceptible S. aureus (MSSA), underwent whole genome sequencing and bioinformatics analysis. These isolates carried a range of resistance genes, including blaZ, aac(6′)-aph(2″), ant(9)-Ia, ant(6)-Ia, and fosB. The mecA gene, which confers methicillin resistance, was detected only in MRSA strains. The isolates exhibited six distinct spa types (t9475, t355, t045, t1265, t1257, and t7888) and varied in virulence gene profiles. Panton–Valentine leukocidin (Luk-PV) was found in one MSSA isolate. Two SCCmec types, IVd(2B) and I(1B), were identified, and the isolates were classified into four multilocus sequence types (MLSTs), with ST5 (n = 3) being the most common. These sequence types clustered into two clonal complexes, CC5 and CC8. Notably, two MRSA clones were identified: ST5-CC5-t045-SCCmec_I(1B) and the human-associated endemic clone ST612-CC8-t1257-SCCmec_IVd(2B). Phylogenomic analysis revealed clustering by MLST, indicating strong genetic relationships within clonal complexes. These findings highlight the value of genomic surveillance in guiding targeted interventions to reduce treatment failures and mortality. Full article

(This article belongs to the Special Issue Genomic Characterization of Antimicrobial Resistance and Evolution Mechanism of Bacteria)

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12 pages, 271 KiB

Open AccessReview

Harnessing Bacteriophages to Combat Antibiotic-Resistant Infections in Africa: A Comprehensive Review

by Kafayath Fabiyi, Kevin Sintondji, Jerrold Agbankpe, Phenix Assogba, Hornel Koudokpon, Boris Lègba, Elodie Gbotche, Lamine Baba-Moussa and Victorien Dougnon

Antibiotics 2024, 13(9), 795; https://doi.org/10.3390/antibiotics13090795 (registering DOI) - 23 Aug 2024

Viewed by 214

Abstract

The conventional treatment of bacterial infections with antibiotics is becoming increasingly ineffective due to the emergence of multidrug-resistant (MDR) pathogens. This literature review explores the potential of bacteriophages as an alternative or adjunctive therapy to antibiotics in combating MDR infections in Africa. This [...] Read more.

The conventional treatment of bacterial infections with antibiotics is becoming increasingly ineffective due to the emergence of multidrug-resistant (MDR) pathogens. This literature review explores the potential of bacteriophages as an alternative or adjunctive therapy to antibiotics in combating MDR infections in Africa. This analysis focuses on current research regarding the integration of phage therapy into African healthcare, highlighting its challenges and opportunities. This review begins with the AMR crisis and the need for new treatments, then covers the history, mechanisms, benefits, and limitations of phage therapy. Key African studies are summarized, identifying major obstacles such as regulatory issues, infrastructure, and research standardization. Research efforts in West Africa that have made notable progress in bacteriophage research are highlighted. This review concludes with recommendations for policymakers, researchers, and healthcare professionals to enhance the development and use of phage therapy in Africa, aiming to reduce antibiotic resistance and improve patient outcomes. By addressing the identified challenges and leveraging the unique advantages of phages, there is potential to significantly mitigate the impact of antibiotic resistance and improve patient outcomes in Africa. Full article

(This article belongs to the Section Bacteriophages)

23 pages, 2155 KiB

Open AccessReview

Antimicrobial Peptides and Their Biomedical Applications: A Review

by Ki Ha Min, Koung Hee Kim, Mi-Ran Ki and Seung Pil Pack

Antibiotics 2024, 13(9), 794; https://doi.org/10.3390/antibiotics13090794 (registering DOI) - 23 Aug 2024

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Abstract

The emergence of drug resistance genes and the detrimental health effects caused by the overuse of antibiotics are increasingly prominent problems. There is an urgent need for effective strategies to antibiotics or antimicrobial resistance in the fields of biomedicine and therapeutics. The pathogen-killing [...] Read more.

The emergence of drug resistance genes and the detrimental health effects caused by the overuse of antibiotics are increasingly prominent problems. There is an urgent need for effective strategies to antibiotics or antimicrobial resistance in the fields of biomedicine and therapeutics. The pathogen-killing ability of antimicrobial peptides (AMPs) is linked to their structure and physicochemical properties, including their conformation, electrical charges, hydrophilicity, and hydrophobicity. AMPs are a form of innate immune protection found in all life forms. A key aspect of the application of AMPs involves their potential to combat emerging antibiotic resistance; certain AMPs are effective against resistant microbial strains and can be modified through peptide engineering. This review summarizes the various strategies used to tackle antibiotic resistance, with a particular focus on the role of AMPs as effective antibiotic agents that enhance the host’s immunological functions. Most of the recent studies on the properties and impregnation methods of AMPs, along with their biomedical applications, are discussed. This review provides researchers with insights into the latest advancements in AMP research, highlighting compelling evidence for the effectiveness of AMPs as antimicrobial agents. Full article

(This article belongs to the Special Issue The Role of Antimicrobial Peptides in Tackling Antimicrobial Resistance)

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21 pages, 8026 KiB

Open AccessArticle

Polygonum hydropiper Compound Extract Inhibits Clostridium perfringens-Induced Intestinal Inflammatory Response and Injury in Broiler Chickens by Modulating NLRP3 Inflammasome Signaling

by Jinwu Zhang, Chunzi Peng, Maojie Lv, Shisen Yang, Liji Xie, Jiaxun Feng, Yingyi Wei, Tingjun Hu, Jiakang He, Zhixun Xie and Meiling Yu

Antibiotics 2024, 13(9), 793; https://doi.org/10.3390/antibiotics13090793 (registering DOI) - 23 Aug 2024

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Abstract

Necrotic enteritis (NE) is a critical disease affecting broiler health, with Clostridium perfringens as its primary pathogen. Polygonum hydropiper compound extract (PHCE), formulated based on traditional Chinese veterinary principles, contains primarily flavonoids with antibacterial, anti-inflammatory, and antioxidant properties. However, PHCE’s efficacy [...] Read more.

Necrotic enteritis (NE) is a critical disease affecting broiler health, with Clostridium perfringens as its primary pathogen. Polygonum hydropiper compound extract (PHCE), formulated based on traditional Chinese veterinary principles, contains primarily flavonoids with antibacterial, anti-inflammatory, and antioxidant properties. However, PHCE’s efficacy against Clostridium perfringens-induced NE and its underlying mechanism remain unclear. This study employed network pharmacology and molecular docking to predict PHCE’s potential mechanisms in treating NE, followed by determining its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Clostridium perfringens (C. perf). Subsequently, the effects of various PHCE doses on intestinal damage, antioxidant capacity, and inflammatory factors in C. perf-infected broilers were assessed. Network pharmacology and molecular docking suggested that PHCE’s therapeutic mechanism for NE involves the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome signaling pathway, with flavonoids such as quercetin, kaempferol, and isorhamnetin as key active components. PHCE exhibited an MIC of 3.13 mg/mL and an MBC of 12.5 mg/mL against C. perf. High PHCE doses effectively reduced intestinal damage scores in both the jejunum and ileum, accompanied by attenuated intestinal pathological changes. Additionally, the high dose significantly increased superoxide dismutase (SOD) levels while decreasing malondialdehyde (MDA), hydrogen peroxide (H₂O₂), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in the jejunum and ileum (p < 0.01 or p < 0.05). PHCE also modulated the expression of caspase-1, IL-1β, gasdermin D (GSDMD), and NLRP3 mRNA, key components of the NLRP3 inflammasome signaling pathway, in both intestinal segments. These findings collectively indicate that PHCE protects against C. perf-induced oxidative stress and inflammatory damage in NE. By enhancing antioxidant capacity, PHCE likely reduces oxidative stress and inflammatory responses, subsequently modulating NLRP3 inflammasome signaling pathway key factor expression. Overall, this research provides valuable insights into the protective mechanism of the herbal compound PHCE and its potential benefits for avian health. Full article

(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents, 2nd Edition)

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12 pages, 1199 KiB

Open AccessArticle

Long-Term Clinical and Ecological Impact of an Antimicrobial Stewardship Program on the Incidence of Carbapenem-Resistant Klebsiella pneumoniae Infections in a High-Endemic Hospital

by Teresa López-Viñau, Montserrat Muñoz-Rosa, Lidia Mª Ruiz-Lara, Lucrecia García-Martínez, Isabel Machuca, Irene Gracia-Ahufinger, Rafael Ruiz Montero, Juan José Castón, Ángela Cano, Elisa Ruiz-Arabi, José Ramón del Prado, Inmaculada Salcedo, Luis Martínez-Martínez and Julián Torre-Cisneros

Antibiotics 2024, 13(9), 792; https://doi.org/10.3390/antibiotics13090792 (registering DOI) - 23 Aug 2024

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Abstract

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is currently a serious global concern. Antimicrobial stewardship programs (ASPs) are one of the key strategies to overcome this resistance. However, evidence about the long-term clinical and ecological impacts of ASPs is scarce. A multidisciplinary team conducted a multifaceted [...] Read more.

Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is currently a serious global concern. Antimicrobial stewardship programs (ASPs) are one of the key strategies to overcome this resistance. However, evidence about the long-term clinical and ecological impacts of ASPs is scarce. A multidisciplinary team conducted a multifaceted intervention in a CR-Kp endemic hospital over a 6-year period. We assessed the monthly long-term impacts of ASPs on carbapenem use, incidence density (ID), and crude death rates of hospital-acquired CR-Kp infections. Other variables potentially related to CR-Kp incidence and healthcare activity indicators were monitored. Carbapenem use showed a sustained reduction over the long term, with a difference of −66.19% (95% CI −87.03 to −45.34) between the expected pre-intervention trend consumption value and that obtained six years after starting the program. The ID of CR-Kp also decreased significantly and was maintained over the long term, with a relative reduction of −88.14% (95% CI; −100.4 to −75.85) at the end of the study period. The crude death rate of CR-Kp at 14 and 28 days decreased significantly after the intervention and remained steady after six years. Infection control indicator trends remained stable. This mixed ASP contributed to reducing the high incidence of infections and mortality rates of CR-Kp, achieving a sustained ecological and clinical effect. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship Program (ASP) in General Hospital: An Essential Practice)

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10 pages, 551 KiB

Open AccessArticle

Microbiological Profile of Instrumented Spinal Infections: 10-Year Study at a French Spine Center

by Sophie Reissier, Carine Couzigou, Romain Courseau, Elise Aubert, Alban Le Monnier, Eric Bonnet, Peter Upex, Pierre-Emmanuel Moreau, Guillaume Riouallon and Julie Lourtet-Hascoët

Antibiotics 2024, 13(9), 791; https://doi.org/10.3390/antibiotics13090791 (registering DOI) - 23 Aug 2024

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Abstract

Objective: The objective was to compare the microbiological characteristics and treatment of early and late surgical site infections (SSIs) in instrumented spinal surgery. Methods: Those patients admitted for SSIs in a single center between January 2010 and December 2022 were included. The subjects [...] Read more.

Objective: The objective was to compare the microbiological characteristics and treatment of early and late surgical site infections (SSIs) in instrumented spinal surgery. Methods: Those patients admitted for SSIs in a single center between January 2010 and December 2022 were included. The subjects were divided into early (eSSIs) and late (lSSIs) SSIs, and demographic, microbiological, treatment, and follow-up data were collected. Results: Instrumented spinal surgery was performed in 2136 patients. Ninety-six cases of infections were identified (prevalence = 4.5%), with 47.9% eSSIs and 52.1% lSSIs. In 58.7% of the cases, the eSSIs were monomicrobial: Staphylococcus aureus (37%) and Enterobacterales (33.3%) were the main bacteria involved. In 66% of the cases, the lSSIs, were monomicrobial: Cutibacterium acnes (30.3%) and staphylococci were predominant. Enterobacterales were isolated in more than 70% of the polymicrobial samples in both the eSSIs and lSSIs. The treatment of the eSSIs mostly consisted of lavage-debridement surgery associated with antibiotic treatment, while the treatment of the lSSIs combined hardware removal or replacement and long-duration antibiotic treatment. A negative outcome was observed in 17.1% of the eSSIs and 5.7% of the lSSIs. Enterobacterales were associated with negative outcomes of eSSIs. Conclusions: Enterobacterales were found in most of the polymicrobial infections regardless of the time of infection onset. Further large studies should be conducted to precisely determine the management and prevention regarding the increasing Gram-negative bacteria SSIs. Full article

(This article belongs to the Special Issue Orthopedic Infections: Epidemiology and Antimicrobial Treatment)

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Antibiotics, Volume 13, Issue 9 (September 2024) – 15 articles

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