Antibiotics

15 pages, 3278 KiB

Open AccessArticle

The pH-Insensitive Antimicrobial and Antibiofilm Activities of the Frog Skin Derived Peptide Esc(1-21): Promising Features for Novel Anti-Infective Drugs

by Maria Rosa Loffredo, Floriana Cappiello, Giacomo Cappella, Elisabetta Capuozzo, Luisa Torrini, Fabiana Diaco, Yuanpu Peter Di, Maria Luisa Mangoni and Bruno Casciaro

Antibiotics 2024, 13(8), 701; https://doi.org/10.3390/antibiotics13080701 - 26 Jul 2024

Abstract

The number of antibiotic-resistant microbial infections is dramatically increasing, while the discovery of new antibiotics is significantly declining. Furthermore, the activity of antibiotics is negatively influenced by the ability of bacteria to form sessile communities, called biofilms, and by the microenvironment of the [...] Read more.

The number of antibiotic-resistant microbial infections is dramatically increasing, while the discovery of new antibiotics is significantly declining. Furthermore, the activity of antibiotics is negatively influenced by the ability of bacteria to form sessile communities, called biofilms, and by the microenvironment of the infection, characterized by an acidic pH, especially in the lungs of patients suffering from cystic fibrosis (CF). Antimicrobial peptides represent interesting alternatives to conventional antibiotics, and with expanding properties. Here, we explored the effects of an acidic pH on the antimicrobial and antibiofilm activities of the AMP Esc(1-21) and we found that it slightly lost activity (from 2- to 4-fold) against the planktonic form of a panel of Gram-negative bacteria, with respect to a ≥ 32-fold of traditional antibiotics. Furthermore, it retained its activity against the sessile form of these bacteria grown in media with a neutral pH, and showed similar or higher effectiveness against the biofilm form of bacteria grown in acidic media, simulating a CF-like acidic microenvironment, compared to physiological conditions. Full article

(This article belongs to the Special Issue Antimicrobial Peptides (AMPs): Structure, Target, Spatiotemporal Relationship, and Druggability)

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17 pages, 1177 KiB

Open AccessArticle

Bacterial and Genetic Features of Raw Retail Pork Meat: Integrative Analysis of Antibiotic Susceptibility, Whole-Genome Sequencing, and Metagenomics

by Michelle Lowe, Wilhelmina Strasheim, Wai Yin Chan and Olga Perovic

Antibiotics 2024, 13(8), 700; https://doi.org/10.3390/antibiotics13080700 - 26 Jul 2024

Abstract

The global antibiotic resistance crisis, driven by overuse and misuse of antibiotics, is multifaceted. This study aimed to assess the microbiological and genetic characteristics of raw retail pork meat through various methods, including the isolation, antibiotic susceptibility testing (AST), whole-genome sequencing (WGS) of [...] Read more.

The global antibiotic resistance crisis, driven by overuse and misuse of antibiotics, is multifaceted. This study aimed to assess the microbiological and genetic characteristics of raw retail pork meat through various methods, including the isolation, antibiotic susceptibility testing (AST), whole-genome sequencing (WGS) of selected indicator bacteria, antibiotic residue testing, and metagenomic sequencing. Samples were purchased from 10 pre-selected retail stores in Gauteng, South Africa. The samples were aseptically separated, with portions sent to an external laboratory for isolating indicator bacteria and testing for antibiotic residues. Identification of the isolated bacteria was reconfirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). AST was performed using the Microscan Walkaway system (Beckman Coulter, Brea, CA, USA). WGS and metagenomic sequencing were performed using the Illumina NextSeq 550 instrument (San Diego, CA, USA). The isolated E. coli and E. faecalis exhibited minimal phenotypic resistance, with WGS revealing the presence of tetracycline resistance genes. Both the isolated bacteria and meat samples harboured tetracycline resistance genes and the antibiotic residue concentrations were within acceptable limits for human consumption. In the metagenomic context, most identified bacteria were of food/meat spoilage and environmental origin. The resistome analysis primarily indicated beta-lactam, tetracycline and multidrug resistance genes. Further research is needed to understand the broader implications of these findings on environmental health and antibiotic resistance. Full article

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9 pages, 231 KiB

Open AccessArticle

Clinical Outcomes of Ceftazidime–Avibactam versus Ceftolozane–Tazobactam in Managing Pseudomonal Infections in Patients Undergoing Renal Replacement Therapy

by Wasim S. El Nekidy, Mooza Al Ali, Emna Abidi, Rania El Lababidi, Diaa Alrahmany, Islam M. Ghazi, Mohamad Mooty, Fadi Hijazi, Muriel Ghosn and Jihad Mallat

Antibiotics 2024, 13(8), 699; https://doi.org/10.3390/antibiotics13080699 - 26 Jul 2024

Abstract

The optimal doses of ceftazidime–avibactam (CZA) and ceftolozane–tazobactam (C/T) for treating multidrug-resistant (MDR) Pseudomonas aeruginosa (PSA) in patients utilizing renal replacement therapy (RRT) are not well established. Hence, the objective of this study is to evaluate the clinical outcomes associated with the suggested [...] Read more.

The optimal doses of ceftazidime–avibactam (CZA) and ceftolozane–tazobactam (C/T) for treating multidrug-resistant (MDR) Pseudomonas aeruginosa (PSA) in patients utilizing renal replacement therapy (RRT) are not well established. Hence, the objective of this study is to evaluate the clinical outcomes associated with the suggested doses of CZA and C/T in patients with PSA infection utilizing RRT. Methods: This is a retrospective study conducted at our hospital between September 2018 and March 2022. Clinical cure was the primary endpoint, while microbiologic cure, 30-day recurrence, and 30-day mortality were the secondary endpoints. Results: In total, 45 subjects met the inclusion criteria, with 25 receiving CZA and 20 receiving C/T. The median age was 69 (52–81) and 69 (61.5–83) years, respectively, while the median weight was 70 (55.5–81.5) and 66 (57–79) kg, respectively. Clinical cure was achieved in 12 (48%) subjects in the CZA group and 12 (60%) in the C/T group (p = 0.432). Of the 36 subjects who had repeated cultures, a microbiologic cure was achieved in 14/23 (60%) subjects and 10/13 (76.9%) subjects (p = 0.273). Thirty-day recurrence was reported in 3 (12%) cases in the CZA group and 6 (30%) in the C/T group (p = 0.082). The 30-day mortality was 13 (52%) subjects in the CZA group and 10 (50%) in the C/T group (p = 0.894). The median maintenance dose of CZA was 1.88 (0.94–3.75) g and 2.25 (1.5–2.25) g for C/T. Multivariate logistic regression analysis indicated that both drugs did not differ significantly in clinical cure. Bloodstream infection (BSI) (OR = 25, 95% CI: 1.63–411.7, p = 0.021) was the only independent factor associated with clinical cure in this population. Conclusions: Our findings indicated that C/T and CZA did not significantly differ in achieving clinical cure in patients with MDR PSA infections undergoing RRT. Larger clinical trials are needed to confirm our findings. Full article

(This article belongs to the Special Issue Novelties in Antibiotic Therapy, Microbial Resistance and Best Stewardship Practices)

13 pages, 2685 KiB

Open AccessArticle

The Roles of a Multidrug-Resistant Klebsiella pneumoniae High-Risk Clone and Its Resistance Plasmids on the Gastrointestinal Colonization and Host-Defense Effectors in the Gut

by Balazs Stercz, Judit Domokos, Zsuzsanna A. Dunai, Nora Makra, Janos Juhasz, Eszter Ostorhazi, Bela Kocsis and Dora Szabo

Antibiotics 2024, 13(8), 698; https://doi.org/10.3390/antibiotics13080698 - 26 Jul 2024

Abstract

The asymptomatic gastrointestinal colonization of multidrug-resistant (MDR) bacteria can lead to difficult-to-treat infections. We investigated the role of host factors influencing colonization in an orogastrical murine infection model using a CTX-M-15- and OXA-162-producing Klebsiella pneumoniae ST15 (MDR-KP) strain, as well as Escherichia coli [...] Read more.

The asymptomatic gastrointestinal colonization of multidrug-resistant (MDR) bacteria can lead to difficult-to-treat infections. We investigated the role of host factors influencing colonization in an orogastrical murine infection model using a CTX-M-15- and OXA-162-producing Klebsiella pneumoniae ST15 (MDR-KP) strain, as well as Escherichia coli J53 (EC) and E. coli transconjugants with an IncFII(K) plasmid carrying CTX-M-15 (EC-CTXM), and with an IncL plasmid carrying OXA-162 (EC-OXA) genes. The fecal bacterial count in colony-forming unit/gram stool (CFU/g) was determined by cultivation, IgA and defensin levels by ELISA, and gut microbiota by 16S rRNA analysis. The CFU was the lowest in EC, followed by EC-OXA and EC-CTXM, and the highest in the MDR-KP group. The IgA level in feces increased in MDR-KP, EC-CTXM, and EC-OXA, and did not change in EC. The beta-defensin 3 level markedly increased in all groups, with the highest values in MDR-KP and EC-CTXM. Alpha-defensin-5 increased in all groups especially in EC. In microbiota, the Bacteroidota phylum was dominant in MDR-KP, EC-CTXM, and EC-OXA, whereas Proteobacteria was dominant in EC. The Muribaculaceae family was significantly more common in the MDR-KP and EC-OXA groups, while the Lachnospiraceae family was dominant in the EC group. While fecal IgA levels positively correlated with colonizing bacterial CFU, the alpha-defensin 5 levels inversely correlated with CFUs and IgA levels. The presence of the IncFII(K) plasmid induced beta-defensin 3 production. The amounts of the Muribaculaceae family members exhibited a correlation with the IncL plasmid. The detected amounts of the Lachnospiraceae family indicated the protective role against the high-risk clone and the resistance plasmids’ dissemination. Our results suggest that not only the MDR-KP clone itself but also the resistance plasmids play a primary role in the colonization rate in the gastrointestinal tract. Both the MDR-KP clone as well as the IncFII(K) and IncL resistance plasmids provide survival and colonization benefits in the gut. Full article

(This article belongs to the Special Issue Colonization and Infection of Multi-Drug Resistant Organisms)

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25 pages, 2344 KiB

Open AccessReview

Vitis vinifera L. Leaf Extract, a Microbiota Green Ally against Infectious and Inflammatory Skin and Scalp Diseases: An In-Depth Update

by Marta Armari, Elisa Zavattaro, Cesar Francisco Trejo, Alice Galeazzi, Alessia Grossetti, Federica Veronese, Paola Savoia and Barbara Azzimonti

Antibiotics 2024, 13(8), 697; https://doi.org/10.3390/antibiotics13080697 - 26 Jul 2024

Abstract

The skin microbiota, with its millions of bacteria, fungi, and viruses, plays a key role in balancing the health of the skin and scalp. Its continuous exposure to potentially harmful stressors can lead to abnormalities such as local dysbiosis, altered barrier function, pathobiont [...] Read more.

The skin microbiota, with its millions of bacteria, fungi, and viruses, plays a key role in balancing the health of the skin and scalp. Its continuous exposure to potentially harmful stressors can lead to abnormalities such as local dysbiosis, altered barrier function, pathobiont overabundance, and infections often sustained by multidrug-resistant bacteria. These factors contribute to skin impairment, deregulation of immune response, and chronic inflammation, with local and systemic consequences. In this scenario, according to the needs of the bio-circular-green economy model, novel harmless strategies, both for regulating the diverse epidermal infectious and inflammatory processes and for preserving or restoring the host skin eubiosis and barrier selectivity, are requested. Vitis vinifera L. leaves and their derived extracts are rich in plant secondary metabolites, such as polyphenols, with antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties that can be further exploited through microbe-driven fermentation processes. On this premise, this literature review aims to provide an informative summary of the most updated evidence on their interactions with skin commensals and pathogens and on their ability to manage inflammatory conditions and restore microbial biodiversity. The emerging research showcases the potential novel beneficial ingredients for addressing various skincare concerns and advancing the cosmeceutics field as well. Full article

(This article belongs to the Special Issue Synthetic and Natural Products-Based Antimicrobial and Antiparasitic Agents)

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10 pages, 502 KiB

Open AccessArticle

Adverse Events Comparison of Double Beta-Lactam Combinations for Bloodstream Infections: Ampicillin plus Ceftriaxone and Ampicillin/Cloxacillin

by Kazuhiro Ishikawa, Daiki Kobayashi and Nobuyoshi Mori

Antibiotics 2024, 13(8), 696; https://doi.org/10.3390/antibiotics13080696 - 25 Jul 2024

Abstract

In Japan, only ampicillin/cloxacillin (ABPC/MCIPC) is available as an anti-staphylococcal penicillin-based treatment for Staphylococcus aureus bacteremia. However, the incidence of adverse events associated with double beta-lactam administration remains unknown. Therefore, we investigated the adverse events of double beta-lactam administration in patients with bacteremia. [...] Read more.

In Japan, only ampicillin/cloxacillin (ABPC/MCIPC) is available as an anti-staphylococcal penicillin-based treatment for Staphylococcus aureus bacteremia. However, the incidence of adverse events associated with double beta-lactam administration remains unknown. Therefore, we investigated the adverse events of double beta-lactam administration in patients with bacteremia. Adult patients (≥18 years) with bacteremia treated with ABPC, ABPC + ceftriaxone (CTRX), or ABPC/MCIPC were retrospectively analyzed. The primary outcome of this study was the incidence of adverse events such as acute kidney injury, liver dysfunction, and myelosuppression. Chi-square tests and t-tests were used for bivariate analysis. Propensity score (PS) matching was conducted to adjust for confounding factors. We included 277 ABPC-, 57 ABPC + CTRX-, and 43 ABPC/MCIPC-treated patients. Significant differences were noted in age, number of male patients, proportion of patients with qSOFA score ≥2, incidence of chronic kidney disease, treatment duration, mechanical ventilation use, vasopressor use, and proportion of patients with acute kidney injury (AKI) KDIGO grade ≥2. Further, a significant difference was observed between ABPC and ABPC/MCIPC, with a hazard ratio of 1.83 in AKI. In the PS-matched cohort, AKI incidence associated with ABPC/MCIPC was significantly higher than that associated with ABPC. ABPC + CTRX may be safe, whereas ABPC/MCIPC presents a higher risk of AKI and may not be suitable. Full article

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9 pages, 562 KiB

Open AccessArticle

Prescribing Antibiotics for Children with Acute Conditions in Public Primary Care Clinics in Singapore: A Retrospective Cohort Database Study

by Vivien Min Er Lee, Si Hui Low, Sky Wei Chee Koh, Anna Szuecs, Victor Weng Keong Loh, Meena Sundram, José M. Valderas and Li Yang Hsu

Antibiotics 2024, 13(8), 695; https://doi.org/10.3390/antibiotics13080695 - 25 Jul 2024

Abstract

Data on primary care antibiotic prescription practices for children in Singapore, which are essential for health care policy, are lacking. We aimed to address this gap and to benchmark prescription practices against international standards. A retrospective cohort database study on antibiotic prescriptions for [...] Read more.

Data on primary care antibiotic prescription practices for children in Singapore, which are essential for health care policy, are lacking. We aimed to address this gap and to benchmark prescription practices against international standards. A retrospective cohort database study on antibiotic prescriptions for children (aged < 18 years) who visited six public primary care clinics in Singapore between 2018 and 2021 was conducted. Data were categorised according to the World Health Organization’s Access, Watch, Reserve (WHO AWaRe) classification. Quality indicators from the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) and the National Institute for Health and Care Excellence (NICE) guidelines were used as a measure of appropriateness of antibiotic prescribing at the individual and overall patient level. In 831,669 polyclinic visits by children between 2018 and 2021, there was a significant reduction in mean antibiotics prescribed per month during pandemic years (2020–2021) compared to pre-pandemic (2018–2019) (MD 458.3, 95% CI 365.9–550.7). Most prescriptions (95.8%) for acute conditions fell within the WHO AWaRe “Access” group. Antibiotic prescription significantly exceeded (55.2%) the relevant quality indicator for otitis media (0–20%). The proportion of children receiving appropriate antibiotics for acute respiratory infections (n = 4506, 51.3%) and otitis media (n = 174, 49.4%) was low compared to the quality indicator (80–100%). There is a need to develop local evidence-based primary care antibiotic guidelines, as well as to support the development of stewardship programmes. Full article

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17 pages, 1584 KiB

Open AccessArticle

Randomized, Double-Blind, Placebo-Controlled Study of Anti-Mycobacterial Therapy (RHB-104) in Active Crohn’s Disease

by David Y. Graham, Saleh A. Naser, Thomas Borody, Zbigniew Hebzda, Harry Sarles, Scott Levenson, Robert Hardi, Tomasz Arłukowicz, Petar Svorcan, Reza Fathi, Aida Bibliowicz, Patricia Anderson, Patrick McLean, Clara Fehrmann, M. Scott Harris, Shuhong Zhao and Ira N. Kalfus

Antibiotics 2024, 13(8), 694; https://doi.org/10.3390/antibiotics13080694 - 25 Jul 2024

Abstract

This study, conducted between 4 October 2013, and 30 November 2018, tested the hypothesis that triple antimicrobial therapy, targeting Mycobacterium avium subspecies paratuberculosis (MAP), long considered a putative cause, would favorably affect Crohn’s disease. A double-blind multicenter study of adults with active Crohn’s [...] Read more.

This study, conducted between 4 October 2013, and 30 November 2018, tested the hypothesis that triple antimicrobial therapy, targeting Mycobacterium avium subspecies paratuberculosis (MAP), long considered a putative cause, would favorably affect Crohn’s disease. A double-blind multicenter study of adults with active Crohn’s disease, (i.e., Crohn’s Disease Activity Index [CDAI] 220–450 plus C-reactive protein ≥ 1.0 mg/dL, fecal calprotectin (FCP) >162.9 µg/g stool, or recent endoscopic or radiographic confirmation of active disease) receiving concomitant standard-of-care Crohn’s disease treatment (Clinicaltrials.gov: NCT01951326) were stratified by anti-tumor necrosis factor use and randomized (1:1) to anti-MAP RHB-104 (clarithromycin 95 mg, rifabutin 45 mg, and clofazimine 10 mg per capsule) (n = 166), resulting in clarithromycin 950 mg/day, rifabutin 450 mg/day, and clofazimine 100 mg/day, or placebo (n = 165) for up to 52 weeks. A greater proportion of RHB-104 versus placebo-treated patients met the primary endpoint—remission (i.e., CDAI < 150)—at week 26 (36.7% [61/166] vs. 22.4% [37/165], respectively; 95% CI for difference: 4.6, 24.0, p = 0.0048; chi-square test). Clinical response (reduction of CDAI by ≥100 points from baseline) at week 26 (first secondary endpoint) was also higher among the patients treated with RHB-104 (73/166 [44.0%]) compared with placebo (50/165 [30.3%]; 95% CI for difference: 3.4, 24.0, p = 0.0116), and it remained higher at week 52 among the patients treated with RHB-104 (59/166 [35.5%] vs. (35/165 [21.2%] for placebo; 95% CI for difference: 4.7, 23.9, p = 0.0042). A statistically significantly greater decline in FCP (another prospective efficacy endpoint) was also observed in RHB-104-treated patients, compared with placebo, at weeks 12, 26, and 52. The rates of serious adverse events were similar between groups (RHB-104: 18.7%; placebo: 18.8%). No patient died during the study. Antimicrobial therapy directed against MAP resulted in significantly greater improvement in clinical and laboratory (FCP) measures of active Crohn’s disease. Full article

(This article belongs to the Special Issue Gastroenterology: The Pathogenic Potential of Mycobacterium paratuberculosis and Emerging Treatment Targets to Address Increasing Resistance)

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18 pages, 1600 KiB

Open AccessArticle

Biomarker-Based Analysis of Pain in Patients with Tick-Borne Infections before and after Antibiotic Treatment

by Kunal Garg, Abbie Thoma, Gordana Avramovic, Leona Gilbert, Marc Shawky, Minha Rajput Ray and John Shearer Lambert

Antibiotics 2024, 13(8), 693; https://doi.org/10.3390/antibiotics13080693 - 25 Jul 2024

Abstract

Tick-borne illnesses (TBIs), especially those caused by Borrelia, are increasingly prevalent worldwide. These diseases progress through stages of initial localization, early spread, and late dissemination. The final stage often leads to post-treatment Lyme disease syndrome (PTLDS) or chronic Lyme disease (CLD), characterized by [...] Read more.

Tick-borne illnesses (TBIs), especially those caused by Borrelia, are increasingly prevalent worldwide. These diseases progress through stages of initial localization, early spread, and late dissemination. The final stage often leads to post-treatment Lyme disease syndrome (PTLDS) or chronic Lyme disease (CLD), characterized by persistent and non-specific multisystem symptoms affecting multiple systems, lasting over six months after antibiotic therapy. PTLDS significantly reduces functional ability, with 82–96% of patients experiencing pain, including arthritis, arthralgia, and myalgia. Inflammatory markers like CRP and TNF-alpha indicate ongoing inflammation, but the link between chronic pain and other biomarkers is underexplored. This study examined the relationship between pain and biomarkers in TBI patients from an Irish hospital and their response to antibiotic treatment. Pain ratings significantly decreased after antibiotic treatment, with median pain scores dropping from 7 to 5 (U = 27215.50, p < 0.001). This suggests a persistent infection responsive to antibiotics. Age and gender did not influence pain ratings before and after treatment. The study found correlations between pain ratings and biomarkers such as transferrin, CD4%, platelets, and neutrophils. However, variations in these biomarkers did not significantly predict pain changes when considering biomarkers outside the study. These findings imply that included biomarkers do not directly predict pain changes, possibly indicating allostatic load in symptom variability among long-term TBI patients. The study emphasizes the need for appropriate antibiotic treatment for TBIs, highlighting human rights issues related to withholding pain relief. Full article

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14 pages, 3106 KiB

Open AccessArticle

Development of a Galleria mellonella Infection Model to Evaluate the Efficacy of Antibiotic-Loaded Polymethyl Methacrylate (PMMA) Bone Cement

by You Zhao, Gopala Krishna Mannala, Raphaëlle Youf, Markus Rupp, Volker Alt and Martijn Riool

Antibiotics 2024, 13(8), 692; https://doi.org/10.3390/antibiotics13080692 - 25 Jul 2024

Abstract

Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and [...] Read more.

Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and antimicrobial efficacy of antimicrobial coatings and compounds. Here, we aim to utilize Galleria mellonella implant infection models to assess the antimicrobial activity of antibiotic-loaded bone cement (ALBC) implants. Therefore, we used commercially available bone cement loaded with either gentamicin alone (PALACOS R+G) or with a combination of gentamicin and vancomycin (COPAL G+V), compared to bone cement without antibiotics (PALACOS R). Firstly, the in vitro antimicrobial activity of ALBC was determined against Staphylococcus aureus. Next, the efficacy of ALBC implants was analyzed in both the G. mellonella hematogenous and early-stage biofilm implant infection model, by monitoring the survival of larvae over time. After 24 h, the number of bacteria on the implant surface and in the tissue was determined. Larvae receiving dual-loaded COPAL G+V implants showed higher survival rates compared to implants loaded with only gentamicin (PALACOS R+G) and the control implants without antibiotics (PALACOS R). In conclusion, G. mellonella larvae infection models with antibiotic-loaded bone cements are an excellent option to study (novel) antimicrobial approaches. Full article

(This article belongs to the Special Issue Local Antibiotics: Antibiotic Loaded Bone Cement and Drug Containing Medical Devices in Orthopaedic Surgery)

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3 pages, 163 KiB

Open AccessEditorial

Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria

by Georgios Meletis, Lemonia Skoura and Efthymia Protonotariou

Antibiotics 2024, 13(8), 691; https://doi.org/10.3390/antibiotics13080691 - 25 Jul 2024

Abstract

Antimicrobial resistance is a major public health problem, and the World Health Organization (WHO) has warned that the current antibiotic armamentarium is not sufficient to face future challenges [...] Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

17 pages, 1955 KiB

Open AccessArticle

Peri-Implant Microbial Signature Shifts in Titanium, Zirconia and Ceria-Stabilized Zirconia Reinforced with Alumina Sites Subjected to Experimental Peri-Implantitis: A Preclinical Study in Dogs

by Roberto López-Píriz, David Sevillano, Manuel Fernández Domínguez, Luis Alou, Natalia González, Lidia Goyos-Ball, Belén Cabal, José Serafín Moya, María Luisa Gómez-Lus and Ramón Torrecillas

Antibiotics 2024, 13(8), 690; https://doi.org/10.3390/antibiotics13080690 - 24 Jul 2024

Abstract

This study evaluates the dynamic shift in the microbiota at the peri-implant site of titanium (Ti) and zirconia (Zr) implants subjected to experimental peri-implantitis (PI) and, for the first time, of implants made of ceria-stabilized alumina-reinforced zirconia (Ce-TZP/Al), a revolutionary zirconia that is [...] Read more.

This study evaluates the dynamic shift in the microbiota at the peri-implant site of titanium (Ti) and zirconia (Zr) implants subjected to experimental peri-implantitis (PI) and, for the first time, of implants made of ceria-stabilized alumina-reinforced zirconia (Ce-TZP/Al), a revolutionary zirconia that is set to play a key role in modern implant dentistry. One- and two-piece (TP) implants, including Ce-TZP/AL TP/G3 glass, were placed bilaterally (six implants/side) in five beagle dogs to mimic a natural vs. ligature-induced PI following a split-mouth design. The experiment spanned 30 weeks from tooth extraction. Both PI models promoted plaque deposition at peri-implant sites. Comparatively, the PI induced by ligatures favored the deposition of anaerobes (p = 0.047 vs. natural). Regardless of the model, the plaque deposition pattern was entirely dependent on the implanted material. Ligated Ti and Zr implant sites accumulated up to 2.14 log CFU/mL unit anaerobic load (p ≤ 0.033 vs. non-ligated implant sites), predominantly comprising obligate anaerobes. Naturally occurring PI induced the deposition of co-occurring networks of obligate anaerobes and less oxygen-dependent bacteria. PI induction favored the enrichment of Ti and Zr sites with bacterial taxa belonging to the orange and red complexes (up to 28% increase naturally and up to 71% in the ligated hemiarch). Anaerobic deposition was significantly lower in ligated Ce-TZP/Al implant sites (p ≤ 0.014 vs. TI and Zr) and independent of the induction model (0.63–1 log units of increase). Facultative bacteria prevailed at Ce-TZP/AL sites. The abundance was lower in the Ce-TZP/AL TP implant. Unlike Ti and Zr sites, taxa from the orange and red complexes were negligible. Biofilms configured at the Ti and Zr sites after ligation-induced PI resemble those found in severe IP. We hypothesize that, although surface properties (surface energy and surface roughness) and physicochemical properties of the substrate play an important role in bacterial adhesion and subsequent plaque formation, Ce-TZP/Al modulates several biological activities that preserve the integrity of the gingival seal by limiting PI progression. In conclusion, biofilm progression differs in peri-implant sites according to the specific properties of the material. Ce-TZP/A, unlike titanium or zirconia, prevents dysbiosis in sites subjected to experimental PI and preserves the microbial signature of emergent obligate anaerobes related to PI development. Full article

(This article belongs to the Section Antimicrobial Materials and Surfaces)

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15 pages, 3630 KiB

Open AccessArticle

Anti-Biofilm Action of Cineole and Hypericum perforatum to Combat Pneumonia-Causing Drug-Resistant P. aeruginosa

by Sourav Chakraborty, Piyush Baindara, Pralay Sharma, Austin Jose T, Kumaravel V, Raja Manoharan and Santi M. Mandal

Antibiotics 2024, 13(8), 689; https://doi.org/10.3390/antibiotics13080689 - 24 Jul 2024

Abstract

Hospital-acquired antibiotic-resistant pneumonia is one of the major causes of mortality around the world that pose a catastrophic threat. Pseudomonas aeruginosa is one of the most significant opportunistic pathogens responsible for hospital-acquired pneumonia and gained resistance to the majority of conventional antibiotics. There [...] Read more.

Hospital-acquired antibiotic-resistant pneumonia is one of the major causes of mortality around the world that pose a catastrophic threat. Pseudomonas aeruginosa is one of the most significant opportunistic pathogens responsible for hospital-acquired pneumonia and gained resistance to the majority of conventional antibiotics. There is an urgent need for antibiotic alternatives to control drug-resistant pneumonia and other related respiratory infections. In the present study, we explored the antibacterial potential of cineole in combination with homeopathic medicines against biofilm-forming drug-resistant P. aeruginosa. Out of 26 selected and screened homeopathic medicines, Hypericum Perforatum (HyPer) was found to eradicate biofilm-forming drug-resistant P. aeruginosa most effectively when used in combination with cineole. Interestingly, the synergistic action of HyPer and cineole was also found to be similarly effective against planktonic cells of P. aeruginosa. Further, the potential synergistic killing mechanisms of cineole and HyPer were determined by analyzing zeta membrane potential, outer membrane permeability, and DNA release from P. aeruginosa cells upon treatment with cineole and HyPer. Additionally, molecular docking analysis revealed strong binding affinities of hypericin (an active ingredient of HyPer) with the PqsA (a quorum sensing protein) of P. aeruginosa. Overall, our findings revealed the potential synergistic action of cineole and HyPer against biofilm-forming drug-resistant P. aeruginosa. Cineole and HyPer could be used in combination with other bronchodilators as inhalers to control the biofilm-forming drug-resistant P. aeruginosa. Full article

(This article belongs to the Special Issue Antimicrobial and Anti-infective Activity of Natural Products, 2nd Edition)

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24 pages, 2844 KiB

Open AccessReview

Pseudomonas aeruginosa Biofilm Lifecycle: Involvement of Mechanical Constraints and Timeline of Matrix Production

by Audrey David, Ali Tahrioui, Anne-Sophie Tareau, Adrien Forge, Mathieu Gonzalez, Emeline Bouffartigues, Olivier Lesouhaitier and Sylvie Chevalier

Antibiotics 2024, 13(8), 688; https://doi.org/10.3390/antibiotics13080688 - 24 Jul 2024

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic infections, especially in immunocompromised patients. Its remarkable adaptability and resistance to various antimicrobial treatments make it difficult to eradicate. Its persistence is enabled by its ability to form a biofilm. Biofilm is a [...] Read more.

Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic infections, especially in immunocompromised patients. Its remarkable adaptability and resistance to various antimicrobial treatments make it difficult to eradicate. Its persistence is enabled by its ability to form a biofilm. Biofilm is a community of sessile micro-organisms in a self-produced extracellular matrix, which forms a scaffold facilitating cohesion, cell attachment, and micro- and macro-colony formation. This lifestyle provides protection against environmental stresses, the immune system, and antimicrobial treatments, and confers the capacity for colonization and long-term persistence, often characterizing chronic infections. In this review, we retrace the events of the life cycle of P. aeruginosa biofilm, from surface perception/contact to cell spreading. We focus on the importance of extracellular appendages, mechanical constraints, and the kinetics of matrix component production in each step of the biofilm life cycle. Full article

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16 pages, 2663 KiB

Open AccessArticle

Biofilm Formation and Antibiotic Resistance Profiles in Carbapenemase-Producing Gram-Negative Rods—A Comparative Analysis between Screening and Pathological Isolates

by Camelia Vintilă, Răzvan Lucian Coșeriu, Anca Delia Mare, Cristina Nicoleta Ciurea, Radu Ovidiu Togănel, Anastasia Simion, Anca Cighir and Adrian Man

Antibiotics 2024, 13(8), 687; https://doi.org/10.3390/antibiotics13080687 - 24 Jul 2024

Abstract

(1) Background: Carbapenem-resistant (CR) bacteria pose a significant global public health challenge due to their ability to evade treatment with beta-lactam antibiotics, including carbapenems. This study investigates the biofilm-forming capabilities of CR clinical bacterial isolates and examines the impact of serum on biofilm [...] Read more.

(1) Background: Carbapenem-resistant (CR) bacteria pose a significant global public health challenge due to their ability to evade treatment with beta-lactam antibiotics, including carbapenems. This study investigates the biofilm-forming capabilities of CR clinical bacterial isolates and examines the impact of serum on biofilm formation. Additionally, the study evaluates the resistance profiles and genetic markers for carbapenemase production. (2) Methods: Bacterial isolates were collected from the microbiology laboratory of Mures County Clinical Hospital between October 2022 and September 2023. Pharyngeal and rectal swabs were screened for carbapenem-resistant bacteria using selective media. Lower respiratory tract samples were also analyzed for CR Gram-negative bacteria. The isolates were tested for their ability to form biofilms in the presence and absence of fetal bovine serum at 24 and 48 h. Carbapenemase production was detected phenotypically and confirmed via PCR for relevant genes. (3) Results: Out of 846 screened samples, 4.25% from pharyngeal swabs and 6.38% from rectal swabs tested positive for CR bacteria. Acinetobacter baumannii and Klebsiella pneumoniae were the most common species isolated. Biofilm formation varied significantly between clinical isolates and standard strains, with clinical isolates generally showing higher biofilm production. The presence of serum had no significant effect on biofilm formation in Klebsiella spp., but stimulated biofilm formation for Acinetobacter spp. Carbapenemase genes bla_KPC, bla_OXA-48-like, and bla_NDM were detected in various isolates, predominantly in Klebsiella spp., but were not the main determinants of carbapenem resistance, at least in screening isolates. (4) Conclusions: This study highlights the variability in biofilm formation among CR clinical isolates and underscores the differences between the bacteria found as carriage versus infection. Both bacterial species and environmental factors variably influence biofilm formation. These insights are crucial for the development of effective treatment and infection control strategies in clinical settings. Full article

(This article belongs to the Special Issue Mechanisms of Biofilm Development and Antibiofilm Therapeutics Strategies)

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14 pages, 2315 KiB

Open AccessArticle

Green Synthesis of Silver Nanoparticle Using Black Mulberry and Characterization, Phytochemical, and Bioactivity

by Yoo-Na Jeon, Su-Ji Ryu, Ha-Yeon Lee, Jang-Oh Kim and Jong-Suep Baek

Antibiotics 2024, 13(8), 686; https://doi.org/10.3390/antibiotics13080686 - 24 Jul 2024

Abstract

Synthesis of silver nanoparticles (AgNPs) using plant extracts has been proposed as a more advantageous and environmentally friendly alternative compared to existing physical/chemical methods. In this study, AgNPs were synthesized from silver nitrate using black mulberry (BM) extract. The biosynthesized AgNPs were characterized [...] Read more.

Synthesis of silver nanoparticles (AgNPs) using plant extracts has been proposed as a more advantageous and environmentally friendly alternative compared to existing physical/chemical methods. In this study, AgNPs were synthesized from silver nitrate using black mulberry (BM) extract. The biosynthesized AgNPs were characterized through an UV-visible spectrometer, X-ray diffraction, and transmission electron microscopy. Additionally, BM-AgNPs were subjected to antioxidant, antibacterial, anti-inflammatory, and anticancer activities. AgNPs biosynthesized from BM extract were dark brown in color and showed a strong peak at 437 nm, confirming that AgNPs were successfully synthesized. The size of AgNPs was 170.17 ± 12.65 nm, the polydispersity index was 0.281 ± 0.07, and the zeta potential value was −56.6 ± 0.56 mV, indicating that the particles were stable. The higher total phenol, flavonoid, and anthocyanin content of BM-AgNPs compared to BM extract indicates that the particles contain multiple active substances due to the formation of AgNPs. The DPPH and ABTS assays showed decreased IC₅₀ values compared to BM extract, demonstrating improved antioxidant activity. AgNPs inhibited the growth of S. aureus and E. coli at 600 μg/mL, with minimum bactericidal concentrations determined to be 1000 and 1200 μg/mL, respectively. The anti-inflammatory activity was 64.28% at a BM-AgNPs concentration of 250 μg/mL. As the concentration increased, the difference from the standard decreased, indicating the inhibitory effect of AgNPs on bovine serum albumin denaturation. The viability of MCF-7 cells treated with BM-AgNPs was found to be significantly lower than that of cells treated with BM extract. The IC₅₀ value of BM-AgNPs was determined to be 96.9 μg/mL. This study showed that BM-AgNPs have the potential to be used in the pharmaceutical industry as antioxidant, antibacterial, anti-inflammatory, and anticancer agents. Full article

(This article belongs to the Special Issue Plants, Lichens, Fungi, and Algae Extracts and Derivatives with Antimicrobial Properties for Nutrition and Health)

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Graphical abstract

11 pages, 413 KiB

Open AccessArticle

Long-Term Outcomes of Multidrug-Resistant Pseudomonas aeruginosa Bacteriuria: A Retrospective Cohort Study

by Chisook Moon, Jin Suk Kang, Seok Jun Mun, Si-Ho Kim and Yu Mi Wi

Antibiotics 2024, 13(8), 685; https://doi.org/10.3390/antibiotics13080685 - 24 Jul 2024

Abstract

The relationship between bacteriuria and subsequent symptomatic infections, particularly bacteraemia, has been a subject of ongoing research. We aim to investigate the clinical characteristics, long-term outcomes, and factors associated with subsequent symptomatic infection following an initial multidrug-resistant P. aeruginosa (MDRP) bacteriuria episode. A [...] Read more.

The relationship between bacteriuria and subsequent symptomatic infections, particularly bacteraemia, has been a subject of ongoing research. We aim to investigate the clinical characteristics, long-term outcomes, and factors associated with subsequent symptomatic infection following an initial multidrug-resistant P. aeruginosa (MDRP) bacteriuria episode. A retrospective cohort study was conducted among patients with MDRP bacteriuria who were hospitalized at a tertiary care hospital from 2009 to 2018, with a 12-month follow-up period for each patient. The primary endpoint was the incidence of subsequent symptomatic MDRP infections at any site, and the secondary endpoint was the overall mortality rate. A total of 260 patients with MDRP bacteriuria were included in the analysis, of whom 155 patients (59.6%) had asymptomatic bacteriuria. Subsequent symptomatic MDRP infections were documented in 79 patients (30.3%) within 12 months of the initial bacteriuria episode: UTI (n = 47, 18.1%), pneumonia (n = 21, 8.1%), bacteraemia (n = 9, 3.5%), soft tissue infection (n = 7, 2.7%), and bone and joint infection (n = 4, 1.5%). Intensive care unit (ICU) acquisition and recurrent bacteriuria were independent risk factors of subsequent symptomatic infections in patients with MDRP bacteriuria. The overall mortality rate was 16.9%, with 31.8% of deaths estimated to be associated with MDRP infection. Solid tumours, cardiovascular diseases, chronic liver disease, chronic lung disease, ICU acquisition, absence of pyuria, and concurrent MDRP bacteraemia were independent predictors of mortality. MDRP bacteriuria has the potential for progression to symptomatic infection and associated mortality. Targeted interventions and prevention strategies were crucial to reduce subsequent infections in patients with MDRP bacteriuria, especially in high-risk patients. Full article

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20 pages, 2328 KiB

Open AccessArticle

General Characteristics and Current State of Antibiotic Resistance in Pediatric Urinary Tract Infection—A Single Center Experience

by Raluca Isac, Gabriela Doros, Cristiana-Alexandra Stolojanu, Ruxandra Maria Steflea, Ramona Florina Stroescu, Ioana-Cristina Olariu, Andrada-Mara Micsescu-Olah and Mihai Gafencu

Antibiotics 2024, 13(8), 684; https://doi.org/10.3390/antibiotics13080684 - 24 Jul 2024

Abstract

Urinary tract infection (UTI) represents one of the most common bacterial infections in children, mainly caused by Gram-negative bacteria. Empirical antibiotic treatment is based on international and national guidelines for treating UTIs in children and is individualized with local antibiotic resistance patterns. The [...] Read more.

Urinary tract infection (UTI) represents one of the most common bacterial infections in children, mainly caused by Gram-negative bacteria. Empirical antibiotic treatment is based on international and national guidelines for treating UTIs in children and is individualized with local antibiotic resistance patterns. The aim of this study is to bring a clear view of present-day particularities of UTIs in children. Methods: We analyzed 210 positive urine cultures identified in 141 pediatric patients admitted to the hospital over a 6-month period. Results: The majority of patients were females (57%) with a median age of 5 years (IQR 12), while male patients revealed a median age of 2 (IQR 7). Most patients originated from urban areas (53%). Only 18 patients (12.76%) were identified with underlying Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). Escherichia Coli was the most frequent pathogen. Increased antibiotic resistance was found in commonly-used antibiotics Ampicillin and Trimethoprim/Sulfamethoxazole, and in the case of patients with CAKUT. Suitable antibiotics for treating a Gram-negative UTI are aminoglycosides, Meropenem, third-generation Cephalosporins, and Nitrofurantoin. Vancomycin upholds efficacy in treating a Gram-positive pediatric UTI. Conclusion: Periodical analysis needs to be performed in order to constantly update clinicians on uropathogenic antibiotic resistance and optimal empirical treatment options. Full article

(This article belongs to the Special Issue Uropathogens—Antibiotic Resistance and Alternative Therapies, 2nd Edition)

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16 pages, 4204 KiB

Open AccessArticle

Activity of Synthetic Peptide KP and Its Derivatives against Biofilm-Producing Escherichia coli Strains Resistant to Cephalosporins

by Lorenza Artesani, Tecla Ciociola, Alice Vismarra, Cristina Bacci, Stefania Conti and Laura Giovati

Antibiotics 2024, 13(8), 683; https://doi.org/10.3390/antibiotics13080683 - 24 Jul 2024

Abstract

Bacterial resistance to β-lactam antibiotics, particularly new generation cephalosporins, is a major public health concern. In Escherichia coli, resistance to these antibiotics is mainly mediated by extended-spectrum β-lactamases (ESBL), which complicates a range of health-threatening infections. These infections may also be biofilm-related, [...] Read more.

Bacterial resistance to β-lactam antibiotics, particularly new generation cephalosporins, is a major public health concern. In Escherichia coli, resistance to these antibiotics is mainly mediated by extended-spectrum β-lactamases (ESBL), which complicates a range of health-threatening infections. These infections may also be biofilm-related, making them more difficult to treat because of the higher tolerance to conventional antibiotics and the host immune response. In this study, we tested as potential new drug candidates against biofilm-forming ESBL-producing E. coli four antimicrobial peptides previously shown to have antifungal properties. The peptides proved to be active in vitro at micromolar concentrations against both sensitive and ESBL-producing E. coli strains, effectively killing planktonic cells and inhibiting biofilm formation. Quantitative fluorescence intensity analysis of three-dimensional reconstructed confocal laser scanning microscopy (CLSM) images of mature biofilm treated with the most active peptide showed significant eradication and a reduction in viable bacteria, while scanning electron microscopy (SEM) revealed gross morphological alterations in treated bacteria. The screening of the investigated peptides for antibacterial and antibiofilm activity led to the selection of a leading candidate to be further studied for developing new antimicrobial drugs as an alternative treatment against microbial infections, primarily associated with biofilms. Full article

(This article belongs to the Section Antibiofilm Strategies)

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