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Antibiotics
Volume 13
Issue 5
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Antibiotics, Volume 13, Issue 5 (May 2024) – 92 articles

Cover Story (view full-size image): Our study evaluated the effectiveness of the empirical use of anti-pseudomonal antibiotics among patients with empyema. Leveraging a Japanese large-scale database, we included 855 patients diagnosed with empyema who underwent thoracostomy and received intravenous antibiotics on admission. We used propensity score weighting to cope with clinically relevant confounders. The Cox proportional hazard models revealed that, compared to empirical non-anti-pseudomonal antibiotics, empirical anti-pseudomonal antibiotics were associated with higher hazard ratios for both thoracic surgery and death within 90 days. The directions of the associations were the same among patients with a risk for multidrug-resistant organisms. The sensitivity analysis for an unmeasured confounder also did not show any benefit of anti-pseudomonal antibiotics. View this paper
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11 pages, 285 KiB  
Article
Alcohol-Based Chlorhexidine and Potassium Sorbate Rub Strengthens the Effectiveness of Traditional Hand Scrubbing and Improves Long-Lasting Effectiveness—Evaluation of Hand Preparation Protocols According to EN 12791
by Elena Herráiz Soria, Luis Alou, Carlos Martin-Villa, Ricardo Becerro-de-Bengoa-Vallejo, Marta Losa-Iglesias and David Sevillano
Antibiotics 2024, 13(5), 470; https://doi.org/10.3390/antibiotics13050470 - 20 May 2024
Cited by 1 | Viewed by 1442
Abstract
Despite the advantages of surgical handrub in terms of the ease of application and effectiveness, chlorhexidine (CHG)-based hand scrubbing remains the preferred method for surgical hand preparation. However, it does not systematically meet the non-inferiority requirement of the European norm (EN) 12791 with [...] Read more.
Despite the advantages of surgical handrub in terms of the ease of application and effectiveness, chlorhexidine (CHG)-based hand scrubbing remains the preferred method for surgical hand preparation. However, it does not systematically meet the non-inferiority requirement of the European norm (EN) 12791 with respect to n-propanol (the reference product) and does not provide the sustained efficacy expected for these long-lasting agents. Commercially available alcohol-based products have also failed to demonstrate sustained efficacy according to EN 12791. Multi-step protocols enhance the efficacy of hand scrubbing, yet their extended disinfection duration might diminish their allure for healthcare professionals. In this study, we show that hand scrubbing with CHG 4% followed by a 1 min rubbing with the novel formulation of ethanol (Et) 70%/CHG 3% plus 0.3% potassium sorbate food additive (PS) meets the non-inferiority requirement and demonstrates sustained efficacy when tested according to EN 12791. The immediate and 3 h effect of this protocol was significantly higher than that of n-propanol and the homologous disinfection protocol without PS (CHG 4% hand scrub plus Et 70%/CHG 3% rub), demonstrating that the inclusion of PS confers a notable residual effect. We speculate that this non-volatile ingredient acts synergistically with CHG. This promising combination represents an alternative method for the development of new disinfection strategies. Full article
14 pages, 1338 KiB  
Article
Enhanced Efficacy of Ciprofloxacin and Tobramycin against Staphylococcus aureus When Combined with Corydalis Tuber and Berberine through Efflux Pump Inhibition
by Yena Seo, Minjun Kim and Tae-Jong Kim
Antibiotics 2024, 13(5), 469; https://doi.org/10.3390/antibiotics13050469 - 20 May 2024
Viewed by 1776
Abstract
One way that bacteria develop antibiotic resistance is by reducing intracellular antibiotic concentrations through efflux pumps. Therefore, enhancing the efficacy of antibiotics using efflux pump inhibitors provides a way to overcome this type of resistance. Notably, an increasing number of pathogenic Staphylococcus aureus [...] Read more.
One way that bacteria develop antibiotic resistance is by reducing intracellular antibiotic concentrations through efflux pumps. Therefore, enhancing the efficacy of antibiotics using efflux pump inhibitors provides a way to overcome this type of resistance. Notably, an increasing number of pathogenic Staphylococcus aureus strains have efflux pump genes. In this study, the extract from Corydalis ternata Nakai tuber (Corydalis Tuber) at 512 mg/L was demonstrated to have an antibiotic synergistic effect with ciprofloxacin at 2 mg/L and tobramycin at 1024 mg/L against methicillin-resistant S. aureus (MRSA). Berberine, an isoquinoline alkaloid identified in Corydalis Tuber, was identified as contributing to this effect. Ethidium bromide efflux pump activity assays showed that Corydalis Tuber extract and berberine inhibited efflux, suggesting that they are efflux pump inhibitors. Molecular docking simulations suggested that berberine binds to S. aureus efflux pump proteins MepA, NorA, NorB, and SdrM. Additionally, berberine and Corydalis Tuber extract inhibit biofilm formation, which can confer antibiotic resistance. This study’s findings suggest that Corydalis Tuber, a traditional herbal medicine, and berberine, a medicinal supplement, act as S. aureus efflux pump inhibitors, synergistically increasing the efficacy of ciprofloxacin and tobramycin and showing promise as a treatment for antibiotic-resistant S. aureus infections, including MRSA. Full article
(This article belongs to the Special Issue Advance in Natural Products: Potential Antimicrobial Targets)
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11 pages, 2530 KiB  
Article
Emergence of Neisseria gonorrhoeae Clone with Reduced Susceptibility to Sitafloxacin in China: An In Vitro and Genomic Study
by Meiping Ye, Linxin Yao, Xinying Lu, Fangyuan Ding, Danyang Zou, Tingli Tian, Yi Lin, Zhen Ning, Jianping Jiang and Pingyu Zhou
Antibiotics 2024, 13(5), 468; https://doi.org/10.3390/antibiotics13050468 - 20 May 2024
Viewed by 1419
Abstract
Drug-resistant Neisseria gonorrhoeae poses an urgent threat to public health. Recently, sitafloxacin, a new-generation fluoroquinolone, has shown high in vitro activity against drug-resistant N. gonorrhoeae. However, data on its effectiveness in clinical isolates remains limited. In this study, we collected 507 N. [...] Read more.
Drug-resistant Neisseria gonorrhoeae poses an urgent threat to public health. Recently, sitafloxacin, a new-generation fluoroquinolone, has shown high in vitro activity against drug-resistant N. gonorrhoeae. However, data on its effectiveness in clinical isolates remains limited. In this study, we collected 507 N. gonorrhoeae isolates from 21 hospitals in Shanghai, China, during 2020 and 2021. Antimicrobial susceptibility testing revealed that sitafloxacin minimum inhibitory concentrations (MICs) exhibited a bimodal distribution, ranging from <0.004 to 2 mg/L. The MIC50 and MIC90 for sitafloxacin were 0.125 mg/L and 0.5 mg/L, respectively, which are 32 and 16 times lower than those for ciprofloxacin (4 mg/L and 8 mg/L, respectively). Sitafloxacin demonstrated high in vitro activity against isolates resistant to either ceftriaxone, azithromycin, or both. Notably, among the isolates with reduced sitafloxacin susceptibility (MIC ≥ MIC90), 83.7% (36/43) were identified as sequence type (ST) 8123. Further phylogenetic analysis showed that ST8123 has evolved into two subclades, designated as subclade-I and subclade-II. A majority of the isolates (80%, 36/45) within subclade-I exhibited reduced susceptibility to sitafloxacin. In contrast, all isolates from subclade-II were found to be susceptible to sitafloxacin. Subsequent genomic investigations revealed that the GyrA-S91F, D95Y, and ParC-S87N mutations, which were exclusively found in ST8123 subclade-I, might be linked to reduced sitafloxacin susceptibility. Our study reveals that sitafloxacin is a promising antibiotic for combating drug-resistant N. gonorrhoeae. However, caution is advised in the clinical application of sitafloxacin for treating N. gonorrhoeae infections due to the emergence of a clone exhibiting reduced susceptibility. Full article
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13 pages, 1758 KiB  
Article
Antimicrobial Use Survey and Detection of ESBL-Escherichia coli in Commercial and Medium-/Small-Scale Poultry Farms in Selected Districts of Zambia
by Taona Sinyawa, Misheck Shawa, Geoffrey M. Muuka, Fusya Goma, Paul Fandamu, Joseph Yamweka Chizimu, Cynthia Sipho Khumalo, Malala Mulavu, Masuzyo Ngoma, Herman Moses Chambaro, Harvey Kakoma Kamboyi, Masahiro Kajihara, Hirofumi Sawa, Yasuhiko Suzuki, Hideaki Higashi, Geoffrey Mainda, Musso Munyeme, John Bwalya Muma, Christian Owusu Nyantakyi, Beverly Egyir and Bernard Mudenda Hang’ombeadd Show full author list remove Hide full author list
Antibiotics 2024, 13(5), 467; https://doi.org/10.3390/antibiotics13050467 - 20 May 2024
Viewed by 1897
Abstract
Antimicrobial resistance (AMR) among Escherichia coli from food animals is a rising problem, and heavy antimicrobial use in poultry is a contributing factor. In Zambia, studies linking poultry-associated AMR and antibiotic use (AMU) are rare. This study aimed to investigate commercial and medium-/small-scale [...] Read more.
Antimicrobial resistance (AMR) among Escherichia coli from food animals is a rising problem, and heavy antimicrobial use in poultry is a contributing factor. In Zambia, studies linking poultry-associated AMR and antibiotic use (AMU) are rare. This study aimed to investigate commercial and medium-/small-scale poultry farmers’ usage of antimicrobials based on a questionnaire survey in ten districts of Zambia. In addition, the study characterized extended-spectrum β-lactamase (ESBL)-producing E. coli isolates obtained from poultry in the same districts. Data regarding knowledge and usage of antimicrobials were collected from commercial and medium-/small-scale poultry farmers using a pre-tested structured questionnaire. At the same time, cloacal samples were collected and analyzed. One hundred and fifty E. coli isolates were tested for antimicrobial susceptibility using eight antibiotic classes. The isolates were further screened for ESBL production by streaking them on cefotaxime (CTX)-supplemented MacConkey agar, then subjecting them to sequencing on a NextSeq. The questionnaire survey showed that more medium-/small-scale than commercial poultry farmers used antimicrobials (OR = 7.70, 95% CI = 2.88–20.61) but less prescriptions (OR = 0.02, 95% CI = 0.00–0.08). Susceptibility testing revealed that resistance was highest to ampicillin (128/148, 86.5%) and tetracycline (101/136, 74.3%) and that the prevalence of multidrug resistance (MDR) (28/30, 93.3%) was high. Whole-genome sequencing (WGS) of eight (8/30, 26.7%) isolates with CTX Minimum Inhibitory Concentration (MIC) ≥ 4 µg/mL revealed the presence of ESBL-encoding genes blaCTX-M-14, blaCTX-M-55, and blaTEM. WGS also detected other AMR genes for quinolones, aminoglycosides, phenicols, tetracycline, macrolides, and folate-pathway antagonists. Altogether, the questionnaire survey results showed a higher proportion of AMU and lower prescription usage among medium-/small-scale farmers. In addition, our results emphasize the circulation of ESBL-producing E. coli strains with associated MDR. It is critical to educate farmers about AMR risks and to encourage responsible usage of antimicrobials. Furthermore, there is a need to strengthen regulations limiting access to antimicrobials. Finally, there is a need to establish a one health system to guide public health response. Full article
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8 pages, 230 KiB  
Review
Efficacy of Expired Antibiotics: A Real Debate in the Context of Repeated Drug Shortages
by Benjamin Davido, Hugues Michelon, Christel Mamona, Pierre de Truchis, Karim Jaffal and Azzam Saleh-Mghir
Antibiotics 2024, 13(5), 466; https://doi.org/10.3390/antibiotics13050466 - 19 May 2024
Cited by 2 | Viewed by 3102
Abstract
This narrative review aims to discuss the main interest in and cautions associated with the use of expired antibiotics in the context of repeated shortages, notably in Europe. Articles concerning the topic of expiry dates related to antibiotic use were reviewed using keywords [...] Read more.
This narrative review aims to discuss the main interest in and cautions associated with the use of expired antibiotics in the context of repeated shortages, notably in Europe. Articles concerning the topic of expiry dates related to antibiotic use were reviewed using keywords in the PubMed®/MEDLINE and Google Scholar databases to identify the most extensive evidence-based documentation. The present review evaluates the potential interest and efficacy of using expired drugs and their possible related adverse events. Overall, in the context of drug shortages, expiry dates could be safely extended for at least one year for most solid antibiotics (tablets or powder) used in daily clinical practice, as long as they are stored under the right conditions, in accordance with the summary of product characteristics. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
12 pages, 1069 KiB  
Article
Comparing the Prognostic Impacts of Delayed Administration of Appropriate Antimicrobials in Older Patients with Afebrile and Febrile Community-Onset Bacteremia
by Shu-Chun Hsueh, Po-Lin Chen, Ching-Yu Ho, Ming-Yuan Hong, Ching-Chi Lee and Wen-Chien Ko
Antibiotics 2024, 13(5), 465; https://doi.org/10.3390/antibiotics13050465 - 19 May 2024
Viewed by 986
Abstract
Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression [...] Read more.
Although prompt administration of an appropriate antimicrobial therapy (AAT) is crucial for reducing mortality in the general population with community-onset bacteremia, the prognostic effects of delayed AAT in older individuals with febrile and afebrile bacteremia remain unclear. A stepwise and backward logistic regression analysis was used to identify independent predictors of 30-day mortality. In a 7-year multicenter cohort study involving 3424 older patients (≥65 years) with community-onset bacteremia, febrile bacteremia accounted for 27.1% (912 patients). A crucial association of afebrile bacteremia and 30-day mortality (adjusted hazard ratio [AHR], 1.69; p < 0.001) was revealed using Cox regression and Kaplan–Meier curves after adjusting for the independent predictors of mortality. Moreover, each hour of delayed AAT was associated with an average increase of 0.3% (adjusted odds ratio [AOR], 1.003; p < 0.001) and 0.2% (AOR, 1.002; p < 0.001) in the 30-day crude mortality rates among patients with afebrile and febrile bacteremia, respectively, after adjusting for the independent predictors of mortality. Similarly, further analysis based on Cox regression and Kaplan–Meier curves revealed that inappropriate empirical therapy (i.e., delayed AAT administration > 24 h) had a significant prognostic impact, with AHRs of 1.83 (p < 0.001) and 1.76 (p < 0.001) in afebrile and febrile patients, respectively, after adjusting for the independent predictors of mortality. In conclusion, among older individuals with community-onset bacteremia, the dissimilarity of the prognostic impacts of delayed AAT between afebrile and febrile presentation was evident. Full article
(This article belongs to the Special Issue Successful Antimicrobial Stewardship Approaches to Address Nosocomial Infections)
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8 pages, 595 KiB  
Article
Whooping Cough Cases Increase in Central Italy after COVID-19 Pandemic
by Giulia Linardos, Luana Coltella, Stefania Ranno, Velia Chiara Di Maio, Luna Colagrossi, Elisabetta Pandolfi, Maria Beatrice Chiarini Testa, Leonardo Genuini, Francesca Stoppa, Matteo Di Nardo, Annalisa Grandin, Renato Cutrera, Corrado Cecchetti, Alberto Villani, Massimiliano Raponi, Paola Bernaschi, Cristina Russo, Carlo Federico Perno and Rossana Scutari
Antibiotics 2024, 13(5), 464; https://doi.org/10.3390/antibiotics13050464 - 19 May 2024
Cited by 2 | Viewed by 2094
Abstract
Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B. [...] Read more.
Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B. pertussis prevalence in pediatric patients admitted to the Reference Italian Pediatric Hospital, located in Rome, from January 2015 to July 2023. A total of 5464 tests for B. pertussis were performed during the study period, and 6.9% were positive. At the time of the COVID-19 pandemic, there was a sharp decrease in the presence of B. pertussis, which reappeared only in August 2023, recording five new cases. All five children presented with paroxysmal cough 5 to 10 days before admission. Four patients had other mild respiratory symptoms and moderate B. pertussis DNA levels (Ct mean: 26). Only one child, with very high B. pertussis DNA levels (Ct: 9), presented with severe respiratory failure. The patients with mild/moderate infection achieved clinical recovery while the patient with the severe manifestation died of cardiac arrest. These observations highlight the reemergence of pertussis even in vaccinated countries and its association with morbidity and mortality especially in young children. This emphasizes the importance of rapid diagnosis to immediately implement appropriate treatment and monitoring of immune status. Full article
(This article belongs to the Special Issue Epidemiology, Clinical Microbiology and Antimicrobial Therapy: A Shared Effort against Infectious Diseases)
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13 pages, 276 KiB  
Article
Risk Factors for Therapeutic Failure and One-Year Mortality in Patients with Intramedullary Nail-Associated Infection after Trochanteric and Subtrochanteric Hip Fracture Repair
by Bernadette Pfang, Marco A. Villegas García, Antonio Blanco García, Álvaro Auñón Rubio, Jaime Esteban and Joaquín García Cañete
Antibiotics 2024, 13(5), 463; https://doi.org/10.3390/antibiotics13050463 - 18 May 2024
Cited by 1 | Viewed by 1194
Abstract
Despite the implications of trochanteric and subtrochanteric intramedullary (IM) nail infection for patients with hip fracture, little is known about risk factors for therapeutic failure and mortality in this population. We performed a retrospective observational analysis including patients diagnosed with trochanteric and subtrochanteric [...] Read more.
Despite the implications of trochanteric and subtrochanteric intramedullary (IM) nail infection for patients with hip fracture, little is known about risk factors for therapeutic failure and mortality in this population. We performed a retrospective observational analysis including patients diagnosed with trochanteric and subtrochanteric IM nail infection at a Spanish academic hospital during a 10-year period, with a minimum follow-up of 22 months. Of 4044 trochanteric and subtrochanteric IM nail implants, we identified 35 cases of infection during the study period (0.87%), 17 of which were chronic infections. Patients with therapeutic failure (n = 10) presented a higher average Charlson Comorbidity Index (CCI) (5.40 vs. 4.21, p 0.015, CI 0.26–2.13) and higher rates of polymicrobial (OR 5.70, p 0.033, CI 1.14–28.33) and multidrug-resistant (OR 7.00, p 0.027, CI 1.24–39.57) infections. Upon multivariate analysis, polymicrobial infection and the presence of multidrug-resistant pathogens were identified as independent risk factors for therapeutic failure. Implant retention was associated with an increased risk of failure in chronic infection and was found to be an independent risk factor for overall one-year mortality in the multivariate analysis. Our study highlights the importance of broad-spectrum empirical antibiotics as initial treatment of trochanteric and subtrochanteric IM nail-associated infection while awaiting microbiological results. It also provides initial evidence for the importance of implant removal in chronic IM-nail infection. Full article
(This article belongs to the Special Issue Antibiotic Therapy in Implant Related Orthopedic Infections)
17 pages, 5646 KiB  
Article
The Impact of Urinary Catheterization on the Antibiotic Susceptibility of ESBL-Producing Enterobacterales: A Challenging Duo
by Ionela-Larisa Miftode, Andrei Vâță, Radu-Ștefan Miftode, Tudorița Parângă, Mihaela Cătălina Luca, Carmen Manciuc, Amalia Stefana Țimpău, Viorel Radu, Manuel Florin Roșu, Lidia Oana Stămăteanu, Daniela Leca, Dana Teodora Anton-Păduraru and Egidia Gabriela Miftode
Antibiotics 2024, 13(5), 462; https://doi.org/10.3390/antibiotics13050462 - 17 May 2024
Viewed by 1648
Abstract
Introduction: Antimicrobial resistance (AMR) is currently a growing concern among healthcare providers, underscoring the importance of describing the regional susceptibility profile for common microorganisms that are associated with urinary tract infections (UTIs). This knowledge serves as the foundation for proper empirical therapeutic recommendations [...] Read more.
Introduction: Antimicrobial resistance (AMR) is currently a growing concern among healthcare providers, underscoring the importance of describing the regional susceptibility profile for common microorganisms that are associated with urinary tract infections (UTIs). This knowledge serves as the foundation for proper empirical therapeutic recommendations tailored to local susceptibility patterns. Results: We found a high prevalence of ESBL-producing strains (36.9%), with Escherichia coli and Klebsiella spp. being the most prevalent isolated bacteria. Among the catheterized patients, Klebsiella spp. emerged as the primary etiology, with a significant correlation between catheterization and Proteus spp. (p = 0.02) and Providencia stuartii (p < 0.0001). We observed significant correlations between urinary catheterization and older age (68.9 ± 13.7 years vs. 64.2 ± 18.1 years in non-catheterized patients, p = 0.026) and with the presence of an isolate with extensive drug resistance (p < 0.0001) or even pandrug resistance (p < 0.0001). Susceptibility rates significantly decreased for almost all the tested antibiotics during the study period. Notably, susceptibility was markedly lower among catheterized patients, with the most pronounced differences observed for carbapenems (59.6% versus 83.4%, p < 0.0001) and aminoglycosides (37.1% versus 46.9%, p = 0.0001). Materials and Methods: We conducted a retrospective study analyzing the susceptibility profiles of 724 extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales isolated from urine cultures. Our focus was on highlighting susceptibility profiles among isolates associated with urinary catheterization and assessing the shifts in the susceptibility rates over time. Conclusions: The constant rise in AMR rates among Enterobacterales presents significant challenges in treating severe infections, particularly among urinary catheterized patients. This trend leaves clinicians with limited or no effective treatment options. Consequently, the development and implementation of personalized treatment protocols are imperative to ensure efficient empirical therapies. Full article
(This article belongs to the Special Issue From Detection to Treatment: Navigating Urinary Tract Infections with Antibiotics)
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18 pages, 751 KiB  
Article
“Primum, non nocere”: The Epidemiology of Toxigenic Clostridioides difficile Strains in the Antibiotic Era—Insights from a Prospective Study at a Regional Infectious Diseases Hospital in Eastern Europe
by Lidia Oana Stămăteanu, Claudia Elena Pleşca, Ionela Larisa Miftode, Aida Corina Bădescu, Doina Carmen Manciuc, Mihnea Eudoxiu Hurmuzache, Manuel Florin Roșu, Radu Ștefan Miftode, Maria Obreja and Egidia Gabriela Miftode
Antibiotics 2024, 13(5), 461; https://doi.org/10.3390/antibiotics13050461 - 17 May 2024
Viewed by 1331
Abstract
Clostridioides difficile infection (CDI), though identified nearly five decades ago, still remains a major challenge, being associated with significant mortality rates. The strains classified as hypervirulent, notably 027/NAP1/BI, have garnered substantial attention from researchers and clinicians due to their direct correlation with the [...] Read more.
Clostridioides difficile infection (CDI), though identified nearly five decades ago, still remains a major challenge, being associated with significant mortality rates. The strains classified as hypervirulent, notably 027/NAP1/BI, have garnered substantial attention from researchers and clinicians due to their direct correlation with the severity of the disease. Our study aims to elucidate the significance of toxigenic Clostridioides difficile (CD) strains in the clinical and therapeutic aspects of managing patients diagnosed with CDI. We conducted a single-center prospective study, including patients with CDI from north-eastern Romania. We subsequently conducted molecular biology testing to ascertain the prevalence of the presumptive 027/NAP1/BI strain within aforementioned geographic region. The patients were systematically compared and assessed both clinically and biologically, employing standardized and comparative methodologies. The study enrolled fifty patients with CDI admitted between January 2020 and June 2020. Among the investigated patients, 43 (86%) exhibited infection with toxigenic CD strains positive for toxin B genes (tcdB), binary toxin genes (cdtA and cdtB), and deletion 117 in regulatory genes (tcdC), while the remaining 7 (14%) tested negative for binary toxin genes (cdtA and cdtB) and deletion 117 in tcdC. The presence of the presumptive 027/NAP1/BI strains was linked to a higher recurrence rate (35.56%, p = 0.025), cardiovascular comorbidities (65.1% vs. 14.2%, p = 0.016), and vancomycin treatment (55.8% vs. 14.3%, p = 0.049). The findings of our investigation revealed an elevated incidence of colitis attributed to presumptive 027/NAP1/BI. Despite the prevalence of the presumptive 027 strain and its associated heightened inflammation among the patients studied, no significant differences were observed regarding the clinical course or mortality outcomes. Full article
(This article belongs to the Special Issue Bacterial-Associated Infections: Epidemiology, Antimicrobial Resistance and Its Impact on Health)
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9 pages, 1277 KiB  
Brief Report
Rational Antibiotic Prescribing Is Underpinned by Dental Ethics Principles: Survey on Postgraduate and Undergraduate Dental Students’ Perceptions
by Jelena Roganović and Milena Barać
Antibiotics 2024, 13(5), 460; https://doi.org/10.3390/antibiotics13050460 - 17 May 2024
Cited by 3 | Viewed by 1283
Abstract
Background: Dentists bear the burden of responsibility for antimicrobial resistance since antibiotics are the drugs most prescribed by dentists. Often, “inappropriate” antibiotic use is considered as a “gray area” by dentists mainly due to ethical challenges associated with the clinical judgement depending on [...] Read more.
Background: Dentists bear the burden of responsibility for antimicrobial resistance since antibiotics are the drugs most prescribed by dentists. Often, “inappropriate” antibiotic use is considered as a “gray area” by dentists mainly due to ethical challenges associated with the clinical judgement depending on patients and/or prescribers. Aim: The study aimed to assess whether and in what way dental ethical principles underpin rational antibiotic use by investigating perceptions of postgraduate and undergraduate dental students without formal knowledge of dental ethics. Method: A cross-sectional anonymous survey comprised nine close-ended questions and was conducted among dental students (n = 125). The investigated practice of appropriate antibiotic prescribing in the survey relied on the respect of three basic principles of ethics: autonomy, non-maleficence, and beneficence. Results: Results show that dental students exhibit a lack of dental ethics knowledge that results in an inappropriate antibiotic-prescribing practice: prescribing an antibiotic when it is not necessary, without examination, or for indications that are not within the competence of the dentist. Multivariate regression analysis revealed that there was a significant difference between under- and postgraduates. Conclusions: Within the pharmacology course, a review of the clinical scenarios which cover both ethical and clinical complexities regarding the appropriate use of antibiotics should be introduced as an educational approach. Full article
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19 pages, 4786 KiB  
Article
Genomic Analysis of Kitasatospora setae to Explore Its Biosynthetic Potential Regarding Secondary Metabolites
by Yutong Xue, Zhiyan Zhou, Fangjian Feng, Hang Zhao, Shuangling Tan, Jinling Li, Sitong Wu, Zhiran Ju, Shan He and Lijian Ding
Antibiotics 2024, 13(5), 459; https://doi.org/10.3390/antibiotics13050459 - 16 May 2024
Viewed by 1440
Abstract
Actinomycetes have long been recognized as important sources of clinical antibiotics. However, the exploration of rare actinomycetes, despite their potential for producing bioactive molecules, has remained relatively limited compared to the extensively studied Streptomyces genus. The extensive investigation of Streptomyces species and their [...] Read more.
Actinomycetes have long been recognized as important sources of clinical antibiotics. However, the exploration of rare actinomycetes, despite their potential for producing bioactive molecules, has remained relatively limited compared to the extensively studied Streptomyces genus. The extensive investigation of Streptomyces species and their natural products has led to a diminished probability of discovering novel bioactive compounds from this group. Consequently, our research focus has shifted towards less explored actinomycetes, beyond Streptomyces, with particular emphasis on Kitasatospora setae (K. setae). The genome of K. setae was annotated and analyzed through whole-genome sequencing using multiple bio-informatics tools, revealing an 8.6 Mbp genome with a 74.42% G + C content. AntiSMASH analysis identified 40 putative biosynthetic gene clusters (BGCs), approximately half of which were recessive and unknown. Additionally, metabolomic mining utilizing mass spectrometry demonstrated the potential for this rare actinomycete to generate numerous bioactive compounds such as glycosides and macrolides, with bafilomycin being the major compound produced. Collectively, genomics- and metabolomics-based techniques confirmed K. setae’s potential as a bioactive secondary metabolite producer that is worthy of further exploration. Full article
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14 pages, 2136 KiB  
Article
Detection of Salmonella Pathogenicity Islands and Antimicrobial-Resistant Genes in Salmonella enterica Serovars Enteritidis and Typhimurium Isolated from Broiler Chickens
by Tsepo Ramatla, Ntelekwane G. Khasapane, Lungile N. Mlangeni, Prudent Mokgokong, Taole Ramaili, Rendani Ndou, Jane S. Nkhebenyane, Kgaugelo Lekota and Oriel Thekisoe
Antibiotics 2024, 13(5), 458; https://doi.org/10.3390/antibiotics13050458 - 16 May 2024
Viewed by 1940
Abstract
Rapid growth in commercial poultry production is one of the major sources of Salmonella infections that leads to human salmonellosis. The two main Salmonella enterica serovars associated with human salmonellosis are enteritidis and typhimurium. The aim of this study was to determine the [...] Read more.
Rapid growth in commercial poultry production is one of the major sources of Salmonella infections that leads to human salmonellosis. The two main Salmonella enterica serovars associated with human salmonellosis are enteritidis and typhimurium. The aim of this study was to determine the prevalence of S. enterica serovars Enteritidis and S. Typhimurium as well as their Salmonella pathogenicity islands (SPI) and antibiotic resistance profiles in broiler chicken feces from slaughterhouses. A total of 480 fecal samples from broiler chickens that were grouped into 96 pooled samples were identified to have Salmonella spp. using the invA gene, whilst the Spy and sdfI genes were used to screen for the presence of S. Enteritidis and S. Typhimurium serovars, respectively, by polymerase chain reaction (PCR) assays. The isolates were also screened for the presence of Salmonella pathogenicity islands (SPIs) using PCR. The disc diffusion assay was performed to determine the antibiotic resistance profiles of the isolates. A total of 36 isolates were confirmed as Salmonella spp. through amplification of the invA gene. Out of 36 confirmed Salmonella spp. a total of 22 isolates were classified as S. Enteritidis (n = 8) and were S. Typhimurium (n = 14) serovars. All (n = 22) S. Enteritidis and S. Typhimurium isolates possessed the hilA (SPI-1), ssrB (SPI-2) and pagC (SPI-11) pathogenicity islands genes. Amongst these serovars, 50% of the isolates (n = 11/22) were resistant to tetracycline and nalidixic acid. Only 22% of the isolates, S. Typhimurium (13.6%) and S. Enteritidis (9.1%) demonstrated resistance against three or more antibiotic classes. The most detected antibiotic resistance genes were tet(K), mcr-1, sulI and strA with 13 (59.1%), 9 (40.9%), 9 (40.9%) and 7 (31.8%), respectively. The findings of this study revealed that S. Typhimurium is the most prevalent serotype detected in chicken feces. To reduce the risk to human health posed by salmonellosis, a stringent public health and food safety policy is required. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Infections in Veterinary Settings)
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18 pages, 1560 KiB  
Review
Pharmacovigilance Strategies to Address Resistance to Antibiotics and Inappropriate Use—A Narrative Review
by Valcieny Sandes, Albert Figueras and Elisangela Costa Lima
Antibiotics 2024, 13(5), 457; https://doi.org/10.3390/antibiotics13050457 - 16 May 2024
Viewed by 2590
Abstract
The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and [...] Read more.
The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and monitoring the ineffectiveness, resistance, and inappropriate use of antibiotics (ABs). The terms “drug ineffective”, “therapeutic failure”, “drug resistance”, “pathogen resistance”, and “multidrug resistance” were found in PV databases and dictionaries, denoting ineffectiveness. These terms cover a range of problems that should be better investigated because they are useful in warning about possible causes of AMR. “Medication errors”, especially those related to dose and indication, and “Off-label use” are highlighted in the literature, suggesting inappropriate use of ABs. Hence, the included studies show that the terms of interest related to AMR and use are not only present but frequent in PV surveillance programs. This review illustrates the feasibility of using PV as a complementary tool for antimicrobial stewardship activities, especially in scenarios where other resources are scarce. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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14 pages, 3597 KiB  
Article
Dissemination of Ceftriaxone-Resistant Salmonella Enteritidis Harboring Plasmids Encoding blaCTX-M-55 or blaCTX-M-14 Gene in China
by Siyuan Yang, Jianzhong Fan, Lifei Yu, Jintao He, Linghong Zhang, Yunsong Yu and Xiaoting Hua
Antibiotics 2024, 13(5), 456; https://doi.org/10.3390/antibiotics13050456 - 16 May 2024
Viewed by 1285
Abstract
Salmonella Enteritidis was the primary foodborne pathogen responsible for acute gastroenteritis. The growing ceftriaxone resistance poses a significant threat to public health. Infection with S. Enteritidis has emerged as a major public health concern, particularly in developing countries. However, research on ceftriaxone-resistant S. [...] Read more.
Salmonella Enteritidis was the primary foodborne pathogen responsible for acute gastroenteritis. The growing ceftriaxone resistance poses a significant threat to public health. Infection with S. Enteritidis has emerged as a major public health concern, particularly in developing countries. However, research on ceftriaxone-resistant S. Enteritidis (CRO-RSE) remains limited, particularly concerning its resistance mechanism, plasmid structure, and transmission characteristics. This study aims to address these gaps comprehensively. We collected 235 S. Enteritidis isolates from Hangzhou First People’s Hospital between 2010 and 2020. Among these, 8.51% (20/235) exhibited resistance to ceftriaxone. Whole-genome analysis revealed that 20 CRO-RSE isolates harbored blaCTX-M-55 or blaCTX-M-14 on the plasmid. Moreover, the dissemination of the blaCTX-M-type gene was associated with IS26 and ISEcp1. Plasmid fusion entailing the integration of the p1 plasmid with antibiotic resistance genes and the p2 (pSEV) virulence plasmid was observed in certain CRO-RSE. Additionally, the structural analysis of the plasmids unveiled two types carrying the blaCTX-M-type gene: type A with multiple replicons and type B with IncI1 (Alpha) replicon. Type B plasmids exhibited superior adaptability and stability compared to type A plasmids within Enterobacteriaceae. Interestingly, although the type B (S808-p1) plasmid displayed the potential to spread to Acinetobacter baumannii, it failed to maintain stability in this species. Full article
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13 pages, 1619 KiB  
Article
Genomic Characterization of Carbapenemase-Producing Enterobacter hormaechei, Serratia marcescens, Citrobacter freundii, Providencia stuartii, and Morganella morganii Clinical Isolates from Bulgaria
by Stefana Sabtcheva, Ivan Stoikov, Ivan N. Ivanov, Deyan Donchev, Magdalena Lesseva, Sylvia Georgieva, Deana Teneva, Elina Dobreva and Iva Christova
Antibiotics 2024, 13(5), 455; https://doi.org/10.3390/antibiotics13050455 - 16 May 2024
Cited by 3 | Viewed by 1443
Abstract
Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp., and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole-genome sequencing and conjugation [...] Read more.
Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp., and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole-genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36), and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii, and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 were observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates we observed highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening infection control measures. Full article
(This article belongs to the Special Issue The Evolution of Plasmid-Mediated Antimicrobial Resistance)
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14 pages, 2382 KiB  
Article
Rumi and Pasteurized Kareish Cheeses Are a Source of β-Lactam-Resistant Salmonella in the Nile Delta Region of Egypt: Insights into Their Incidence, AMR Pattern, Genotypic Determinants of Virulence and β-Lactam Resistance
by Fatma Elzhraa, Maha Al-Ashmawy, Mohammed El-Sherbini, Ahmed M. El-Sebaey, Csilla Mohácsi-Farkas, Gabriella Kiskó and Ágnes Belák
Antibiotics 2024, 13(5), 454; https://doi.org/10.3390/antibiotics13050454 - 16 May 2024
Cited by 1 | Viewed by 1268
Abstract
The spread of superbugs in dairy products can jeopardize global public health. To date, information on the incidence rates of virulent and β-lactams-resistant (BLR) Salmonella in cheeses from rural areas of Egypt has been lacking. Biochemical, serological, antibiotic susceptibility, and multiplex PCR (M-PCR) [...] Read more.
The spread of superbugs in dairy products can jeopardize global public health. To date, information on the incidence rates of virulent and β-lactams-resistant (BLR) Salmonella in cheeses from rural areas of Egypt has been lacking. Biochemical, serological, antibiotic susceptibility, and multiplex PCR (M-PCR) tests were performed to identify and characterize Salmonella isolates. In this study, 44 (15.71%) Salmonella isolates of eight different serotypes were recovered from 280 samples of Rumi and pasteurized Kariesh cheeses across the Nile Delta region of Egypt. The most predominant serotypes were S. Typhimurium, S. Enteritidis, and S. Infantis. The virulence genes (invA, stn, and hilA) were identified in all isolates. However, spvC was only detected in S. Typhimurium. The highest resistance was developed against Erythromycin and Clindamycin (90.91%), followed by Ceftazidime and Cephalothin (84.09%). Meropenem and colistin were the most effective antibiotics. A high proportion (79.55%) of multi-drug resistance (MDR) isolates carried narrow spectrum (NS), extended-spectrum (ES), and AmpC-BLR genes. The blaOXA-1, blaOXA-2, blaTEM-1, blaCTX-M, blaCMY-1, and blaCMY-2 BLR genes were positive in 37.04%, 29.63%, 25.93%, 14.81%, 37.04%, and 3.70% of isolates, respectively. In conclusion, a high prevalence of virulence and BLR genes harboring Salmonella strains in Egyptian cheeses is considered a great threat to public health. Full article
(This article belongs to the Special Issue Research of Antimicrobial Resistance in the Food Chain)
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9 pages, 1391 KiB  
Article
Role of Cefiderocol in Multidrug-Resistant Gram-Negative Central Nervous System Infections: Real Life Experience and State-of-the-Art
by Alessio Sollima, Francesco Rossini, Paola Lanza, Carlo Pallotto, Marianna Meschiari, Ivan Gentile, Roberto Stellini, Angelica Lenzi, Alice Mulé, Francesca Castagna, Silvia Lorenzotti, Silvia Amadasi, Evelyn Van Hauwermeiren, Barbara Saccani, Benedetta Fumarola, Liana Signorini, Francesco Castelli and Alberto Matteelli
Antibiotics 2024, 13(5), 453; https://doi.org/10.3390/antibiotics13050453 - 16 May 2024
Cited by 1 | Viewed by 1920
Abstract
Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is [...] Read more.
Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is no consensus on the dosing scheme of cefiderocol to penetrate the blood–brain barrier. We present a case series and a literature review of CNS infections caused by MDR pathogens that were treated with cefiderocol: some of these patients were treated with different dose schemes of cefiderocol and underwent therapeutic drug monitoring both on plasma and cerebrospinal fluid (CSF). The CSF penetration rates and the clinical outcomes were evaluated. Full article
(This article belongs to the Special Issue Antimicrobial Treatment and Management of Central Nervous System Infections)
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14 pages, 1614 KiB  
Article
Genetic Alternatives for Experimental Adaptation to Colistin in Three Pseudomonas aeruginosa Lineages
by Igor Chebotar, Tatiana Savinova, Julia Bocharova, Dmitriy Korostin, Peter Evseev and Nikolay Mayanskiy
Antibiotics 2024, 13(5), 452; https://doi.org/10.3390/antibiotics13050452 - 15 May 2024
Cited by 2 | Viewed by 1448
Abstract
Pseudomonas aeruginosa is characterized by a high adaptive potential, developing resistance in response to antimicrobial pressure. We employed a spatiotemporal evolution model to disclose the pathways of adaptation to colistin, a last-resort polymyxin antimicrobial, among three unrelated P. aeruginosa lineages. The P. aeruginosa [...] Read more.
Pseudomonas aeruginosa is characterized by a high adaptive potential, developing resistance in response to antimicrobial pressure. We employed a spatiotemporal evolution model to disclose the pathways of adaptation to colistin, a last-resort polymyxin antimicrobial, among three unrelated P. aeruginosa lineages. The P. aeruginosa ATCC-27833 reference strain (Pa_ATCC), an environmental P. aeruginosa isolate (Pa_Environment), and a clinical isolate with multiple drug resistance (Pa_MDR) were grown over an increasing 5-step colistin concentration gradient from 0 to 400 mg/L. Pa_Environment demonstrated the highest growth pace, achieving the 400 mg/L band in 15 days, whereas it took 37 and 60 days for Pa_MDR and Pa_ATCC, respectively. To identify the genome changes that occurred during adaptation to colistin, the isolates selected during the growth of the bacteria (n = 185) were subjected to whole genome sequencing. In total, 17 mutation variants in eight lipopolysaccharide-synthesis-associated genes were detected. phoQ and lpxL/PA0011 were affected in all three lineages, whereas changes in pmrB were found in Pa_Environment and Pa_MDR but not in Pa_ATCC. In addition, mutations were detected in 34 general metabolism genes, and each lineage developed mutations in a unique set of such genes. Thus, the three examined distinct P. aeruginosa strains demonstrated different capabilities and genetic pathways of colistin adaptation. Full article
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13 pages, 1511 KiB  
Article
Eminent Antimicrobial Peptide Resistance in Zymomonas mobilis: A Novel Advantage of Intrinsically Uncoupled Energetics
by Reinis Rutkis, Zane Lasa, Marta Rubina, Inese Strazdina and Uldis Kalnenieks
Antibiotics 2024, 13(5), 451; https://doi.org/10.3390/antibiotics13050451 - 15 May 2024
Viewed by 1162
Abstract
Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have elevated resistance to exogenous antimicrobial peptides (AMPs)— with regard to both peptide bulk concentration in the medium and the numbers of peptide molecules per cell. By monitoring the [...] Read more.
Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have elevated resistance to exogenous antimicrobial peptides (AMPs)— with regard to both peptide bulk concentration in the medium and the numbers of peptide molecules per cell. By monitoring the integration of AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to the disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings. Full article
(This article belongs to the Section Antimicrobial Peptides)
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22 pages, 7567 KiB  
Article
Potential Surviving Effect of Cleome droserifolia Extract against Systemic Staphylococcus aureus Infection: Investigation of the Chemical Content of the Plant
by Jawaher Alqahtani, Walaa A. Negm, Engy Elekhnawy, Ismail A. Hussein, Hassan Samy Hassan, Abdullah R. Alanzi, Ehssan Moglad, Rehab Ahmed, Sarah Ibrahim and Suzy A. El-Sherbeni
Antibiotics 2024, 13(5), 450; https://doi.org/10.3390/antibiotics13050450 - 15 May 2024
Viewed by 1883
Abstract
The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE [...] Read more.
The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3-O-alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on S. aureus isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished S. aureus cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (cna, fnbA, and icaA). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of S. aureus isolates. Regarding the in vivo model, CDE significantly decreased the S. aureus burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice’s survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies. Full article
(This article belongs to the Special Issue Antibacterial, Antibiofilm and Anti-virulence Activity Research of Both Natural and Synthetic Products, 2nd Edition)
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17 pages, 3276 KiB  
Article
The Tick Saliva Peptide HIDfsin2 TLR4-Dependently Inhibits the Tick-Borne Severe Fever with Thrombocytopenia Syndrome Virus in Mouse Macrophages
by Luyao Wang, Yishuo Liu, Rui Pang, Yiyuan Guo, Yingying Ren, Yingliang Wu and Zhijian Cao
Antibiotics 2024, 13(5), 449; https://doi.org/10.3390/antibiotics13050449 - 15 May 2024
Viewed by 1438
Abstract
Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The components of tick saliva can directly or indirectly trigger host biological responses in a manner that promotes [...] Read more.
Ticks transmit a variety of pathogens to their hosts by feeding on blood. The interactions and struggle between tick pathogens and hosts have evolved bilaterally. The components of tick saliva can directly or indirectly trigger host biological responses in a manner that promotes pathogen transmission; however, host cells continuously develop strategies to combat pathogen infection and transmission. Moreover, it is still unknown how host cells develop their defense strategies against tick-borne viruses during tick sucking. Here, we found that the tick saliva peptide HIDfsin2 enhanced the antiviral innate immunity of mouse macrophages by activating the Toll-like receptor 4 (TLR4) signaling pathway, thereby restricting tick-borne severe fever with thrombocytopenia syndrome virus (SFTSV) replication. HIDfsin2 was identified to interact with lipopolysaccharide (LPS), a ligand of TLR4, and then depolymerize LPS micelles into smaller particles, effectively enhancing the activation of the nuclear factor kappa-B (NF-κB) and type I interferon (IFN-I) signaling pathways, which are downstream of TLR4. Expectedly, TLR4 knockout completely eliminated the promotion effect of HIDfsin2 on NF-κB and type I interferon activation. Moreover, HIDfsin2 enhanced SFTSV replication in TLR4-knockout mouse macrophages, which is consistent with our recent report that HIDfsin2 hijacked p38 mitogen-activated protein kinase (MAPK) to promote the replication of tick-borne SFTSV in A549 and Huh7 cells (human cell lines) with low expression of TLR4. Together, these results provide new insights into the innate immune mechanism of host cells following tick bites. Our study also shows a rare molecular event relating to the mutual antagonism between tick-borne SFTSV and host cells mediated by the tick saliva peptide HIDfsin2 at the tick–host–virus interface. Full article
(This article belongs to the Special Issue Peptide Antibiotics from Microbes and Venomous Animals, 2nd Edition)
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11 pages, 1216 KiB  
Article
Colonization by Extended-Spectrum β-Lactamase-Producing Enterobacterales and Bacteremia in Hematopoietic Stem Cell Transplant Recipients
by Luiza Arcas Gonçalves, Beatriz Barbosa Anjos, Bruno Melo Tavares, Ana Paula Marchi, Marina Farrel Côrtes, Hermes Ryoiti Higashino, Bruna del Guerra de Carvalho Moraes, José Victor Bortolotto Bampi, Liliane Dantas Pinheiro, Fernanda de Souza Spadao, Vanderson Rocha, Thais Guimarães and Silvia Figueiredo Costa
Antibiotics 2024, 13(5), 448; https://doi.org/10.3390/antibiotics13050448 - 15 May 2024
Cited by 1 | Viewed by 1315
Abstract
Background: Assessing the risk of multidrug-resistant colonization and infections is pivotal for optimizing empirical therapy in hematopoietic stem cell transplants (HSCTs). Limited data exist on extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) colonization in this population. This study aimed to assess whether ESBL-E colonization constitutes a [...] Read more.
Background: Assessing the risk of multidrug-resistant colonization and infections is pivotal for optimizing empirical therapy in hematopoietic stem cell transplants (HSCTs). Limited data exist on extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) colonization in this population. This study aimed to assess whether ESBL-E colonization constitutes a risk factor for ESBL-E bloodstream infection (BSI) and to evaluate ESBL-E colonization in HSCT recipients. Methods: A retrospective analysis of ESBL-E colonization and BSI in HSCT patients was conducted from August 2019 to June 2022. Weekly swabs were collected and cultured on chromogenic selective media, with PCR identifying the β-lactamase genes. Pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) assessed the colonizing strains’ similarities. Results: Of 222 evaluated HSCT patients, 59.45% were colonized by ESBL-E, with 48.4% at admission. The predominant β-lactamase genes were blaTEM (52%) and blaSHV (20%). PFGE analysis did not reveal predominant clusters in 26 E. coli and 15 K. pneumoniae strains. WGS identified ST16 and ST11 as the predominant sequence types among K. pneumoniae. Thirty-three patients developed thirty-five Enterobacterales-BSIs, with nine being third-generation cephalosporin-resistant. No association was found between ESBL-E colonization and ESBL-BSI (p = 0.087). Conclusions: Although the patients presented a high colonization rate of ESBL-E upon admission, no association between colonization and infection were found. Thus, it seems that ESBL screening is not a useful strategy to assess risk factors and guide therapy for ESBL-BSI in HSCT-patients. Full article
(This article belongs to the Special Issue Colonization and Infection of Multi-Drug Resistant Organisms)
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16 pages, 876 KiB  
Article
Listeria monocytogenes from Food Products and Food Associated Environments: Antimicrobial Resistance, Genetic Clustering and Biofilm Insights
by Adriana Silva, Vanessa Silva, João Paulo Gomes, Anabela Coelho, Rita Batista, Cristina Saraiva, Alexandra Esteves, Ângela Martins, Diogo Contente, Lara Diaz-Formoso, Luis M. Cintas, Gilberto Igrejas, Vítor Borges and Patrícia Poeta
Antibiotics 2024, 13(5), 447; https://doi.org/10.3390/antibiotics13050447 - 14 May 2024
Cited by 4 | Viewed by 2631
Abstract
Listeria monocytogenes, a foodborne pathogen, exhibits high adaptability to adverse environmental conditions and is common in the food industry, especially in ready-to-eat foods. L. monocytogenes strains pose food safety challenges due to their ability to form biofilms, increased resistance to disinfectants, and [...] Read more.
Listeria monocytogenes, a foodborne pathogen, exhibits high adaptability to adverse environmental conditions and is common in the food industry, especially in ready-to-eat foods. L. monocytogenes strains pose food safety challenges due to their ability to form biofilms, increased resistance to disinfectants, and long-term persistence in the environment. The aim of this study was to evaluate the presence and genetic diversity of L. monocytogenes in food and related environmental products collected from 2014 to 2022 and assess antibiotic susceptibility and biofilm formation abilities. L. monocytogenes was identified in 13 out of the 227 (6%) of samples, 7 from food products (meat preparation, cheeses, and raw milk) and 6 from food-processing environments (slaughterhouse-floor and catering establishments). All isolates exhibited high biofilm-forming capacity and antibiotic susceptibility testing showed resistance to several classes of antibiotics, especially trimethoprim-sulfamethoxazole and erythromycin. Genotyping and core-genome clustering identified eight sequence types and a cluster of three very closely related ST3 isolates (all from food), suggesting a common contamination source. Whole-genome sequencing (WGS) analysis revealed resistance genes conferring resistance to fosfomycin (fosX), lincosamides (lin), fluoroquinolones (norB), and tetracycline (tetM). In addition, the qacJ gene was also detected, conferring resistance to disinfecting agents and antiseptics. Virulence gene profiling revealed the presence of 92 associated genes associated with pathogenicity, adherence, and persistence. These findings underscore the presence of L. monocytogenes strains in food products and food-associated environments, demonstrating a high virulence of these strains associated with resistance genes to antibiotics, but also to disinfectants and antiseptics. Moreover, they emphasize the need for continuous surveillance, effective risk assessment, and rigorous control measures to minimize the public health risks associated to severe infections, particularly listeriosis outbreaks. A better understanding of the complex dynamics of pathogens in food products and their associated environments can help improve overall food safety and develop more effective strategies to prevent severe health consequences and economic losses. Full article
(This article belongs to the Special Issue Rise of Antibiotic Resistance: Mechanisms Involved and Solutions to Tackle It)
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9 pages, 1459 KiB  
Brief Report
Characterization of Salmonella Phage P1-CTX and the Potential Mechanism Underlying the Acquisition of the blaCTX-M-27 Gene
by Qiu-Yun Zhao, Run-Mao Cai, Ping Cai, Lin Zhang, Hong-Xia Jiang and Zhen-Ling Zeng
Antibiotics 2024, 13(5), 446; https://doi.org/10.3390/antibiotics13050446 - 14 May 2024
Viewed by 1527
Abstract
The P1 phage has garnered attention as a carrier of antibiotic resistance genes (ARGs) in Enterobacteriaceae. However, the transferability of ARGs by P1-like phages carrying ARGs, in addition to the mechanism underlying ARG acquisition, remain largely unknown. In this study, we elucidated the [...] Read more.
The P1 phage has garnered attention as a carrier of antibiotic resistance genes (ARGs) in Enterobacteriaceae. However, the transferability of ARGs by P1-like phages carrying ARGs, in addition to the mechanism underlying ARG acquisition, remain largely unknown. In this study, we elucidated the biological characteristics, the induction and transmission abilities, and the acquisition mechanism of the blaCTX-M-27 gene in the P1 phage. The P1-CTX phage exhibited distinct lytic plaques and possessed a complete head and tail structure. Additionally, the P1-CTX phage was induced successfully under various conditions, including UV exposure, heat treatment at 42 °C, and subinhibitory concentrations (sub-MICs) of antibiotics. Moreover, the P1-CTX phage could mobilize the blaCTX-M-27 gene into three strains of Escherichia coli (E. coli) and the following seven different serotypes of Salmonella: Rissen, Derby, Kentucky, Typhimurium, Cerro, Senftenberg, and Muenster. The mechanism underlying ARG acquisition by the P1-CTX phage involved Tn1721 transposition-mediated movement of blaCTX-M-27 into the ref and mat genes within its genome. To our knowledge, this is the first report documenting the dynamic processes of ARG acquisition by a phage. Furthermore, this study enriches the research on the mechanism underlying the phage acquisition of drug resistance genes and provides a basis for determining the risk of drug resistance during phage transmission. Full article
(This article belongs to the Special Issue Antibiotic Residues, Antimicrobial Resistance and Intervention Strategies of Foodborne Pathogens, 2nd Edition)
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37 pages, 1964 KiB  
Review
Novel Siderophore Cephalosporin and Combinations of Cephalosporins with β-Lactamase Inhibitors as an Advancement in Treatment of Ventilator-Associated Pneumonia
by Szymon Viscardi, Ewa Topola, Jakub Sobieraj and Anna Duda-Madej
Antibiotics 2024, 13(5), 445; https://doi.org/10.3390/antibiotics13050445 - 14 May 2024
Viewed by 1612
Abstract
In an era of increasing antibiotic resistance among pathogens, the treatment options for infectious diseases are diminishing. One of the clinical groups especially vulnerable to this threat are patients who are hospitalized in intensive care units due to ventilator-associated pneumonia caused by multidrug-resistant/extensively [...] Read more.
In an era of increasing antibiotic resistance among pathogens, the treatment options for infectious diseases are diminishing. One of the clinical groups especially vulnerable to this threat are patients who are hospitalized in intensive care units due to ventilator-associated pneumonia caused by multidrug-resistant/extensively drug-resistant Gram-negative bacteria. In order to prevent the exhaustion of therapeutic options for this life-threatening condition, there is an urgent need for new pharmaceuticals. Novel β-lactam antibiotics, including combinations of cephalosporins with β-lactamase inhibitors, are proposed as a solution to this escalating problem. The unique mechanism of action, distinctive to this new group of siderophore cephalosporins, can overcome multidrug resistance, which is raising high expectations. In this review, we present the summarized results of clinical trials, in vitro studies, and case studies on the therapeutic efficacy of cefoperazone-sulbactam, ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol in the treatment of ventilator-associated pneumonia. We demonstrate that treatment strategies based on siderophore cephalosporins and combinations of β-lactams with β-lactamases inhibitors show comparable or higher clinical efficacy than those used with classic pharmaceuticals, like carbapenems, colistin, or tigecycline, and are often associated with a lower risk of adverse events. Full article
(This article belongs to the Special Issue Antimicrobial Activity of Different Plant Extracts, Plant-Derived Compounds and Synthetic Derivatives of Natural Compounds on Pathogenic Microorganisms, 2nd Edition)
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19 pages, 3991 KiB  
Article
Lippia graveolens Essential Oil to Enhance the Effect of Imipenem against Axenic and Co-Cultures of Pseudomonas aeruginosa and Acinetobacter baumannii
by Jorge O. Fimbres-García, Marcela Flores-Sauceda, Elsa Daniela Othón-Díaz, Alfonso García-Galaz, Melvin R. Tapia-Rodriguez, Brenda A. Silva-Espinoza, Andres Alvarez-Armenta and J. Fernando Ayala-Zavala
Antibiotics 2024, 13(5), 444; https://doi.org/10.3390/antibiotics13050444 - 14 May 2024
Viewed by 1222
Abstract
This research focuses on assessing the synergistic effects of Mexican oregano (Lippia graveolens) essential oil or carvacrol when combined with the antibiotic imipenem, aiming to reduce the pathogenic viability and virulence of Acinetobacter baumannii and Pseudomonas aeruginosa. The study highlighted the [...] Read more.
This research focuses on assessing the synergistic effects of Mexican oregano (Lippia graveolens) essential oil or carvacrol when combined with the antibiotic imipenem, aiming to reduce the pathogenic viability and virulence of Acinetobacter baumannii and Pseudomonas aeruginosa. The study highlighted the synergistic effect of combining L. graveolens essential oil or carvacrol with imipenem, significantly reducing the required doses for inhibiting bacterial growth. The combination treatments drastically lowered the necessary imipenem doses, highlighting a potent enhancement in efficacy against A. baumannii and P. aeruginosa. For example, the minimum inhibitory concentrations (MIC) for the essential oil/imipenem combinations were notably low, at 0.03/0.000023 mg/mL for A. baumannii and 0.0073/0.000023 mg/mL for P. aeruginosa. Similarly, the combinations significantly inhibited biofilm formation at lower concentrations than when the components were used individually, demonstrating the strategic advantage of this approach in combating antibiotic resistance. For OXA-51, imipenem showed a relatively stable interaction during 30 ns of dynamic simulation of their interaction, indicating changes (<2 nm) in ligand positioning during this period. Carvacrol exhibited similar fluctuations to imipenem, suggesting its potential inhibition efficacy, while thymol showed significant variability, particularly at >10 ns, suggesting potential instability. With IMP-1, imipenem also displayed very stable interactions during 38 ns and demonstrated notable movement and positioning changes within the active site, indicating a more dynamic interaction. In contrast, carvacrol and thymol maintained their position within the active site only ~20 and ~15 ns, respectively. These results highlight the effectiveness of combining L. graveolens essential oil and carvacrol with imipenem in tackling the difficult-to-treat pathogens A. baumannii and P. aeruginosa. Full article
(This article belongs to the Special Issue Essential Oil of the Plants: Chemical Composition, Antimicrobial Activity, and Biological Applications)
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14 pages, 2692 KiB  
Article
Prevalence and Antimicrobial Resistance Diversity of Salmonella Isolates in Jiaxing City, China
by Ping Li, Li Zhan, Henghui Wang, Yong Yan, Miaomiao Jia, Lei Gao, Yangming Sun, Guoying Zhu and Zhongwen Chen
Antibiotics 2024, 13(5), 443; https://doi.org/10.3390/antibiotics13050443 - 14 May 2024
Viewed by 1578
Abstract
Nontyphoidal Salmonella (NTS) is a cause of foodborne diarrheal diseases worldwide. Important emerging NTS serotypes that have spread as multidrug-resistant high-risk clones include S. Typhimurium monophasic variant and S. Kentucky. In this study, we isolated Salmonella in 5019 stool samples collected from patients [...] Read more.
Nontyphoidal Salmonella (NTS) is a cause of foodborne diarrheal diseases worldwide. Important emerging NTS serotypes that have spread as multidrug-resistant high-risk clones include S. Typhimurium monophasic variant and S. Kentucky. In this study, we isolated Salmonella in 5019 stool samples collected from patients with clinical diarrhea and 484 food samples. Antibiotic susceptibility testing and whole-genome sequencing were performed on positive strains. The detection rates of Salmonella among patients with diarrhea and food samples were 4.0% (200/5019) and 3.1% (15/484), respectively. These 215 Salmonella isolates comprised five main serotypes, namely S. Typhimurium monophasic variant, S. Typhimurium, S. London, S. Enteritidis, and S. Rissen, and were mainly resistant to ampicillin, tetracycline, chloramphenicol, and trimethoprim/sulfamethoxazole. The MDR rates of five major serotypes were 77.4%, 56.0%, 66.7%, 53.3%, and 80.0%, respectively. The most commonly acquired extended-spectrum β-lactamase-encoding genes were blaTEM−1B, blaOXA-10, and blaCTX-M-65. The S. Typhimurium monophasic variant strains from Jiaxing City belonged to a unique clone with broad antibiotic resistance. S. Kentucky isolates showed the highest drug resistance, and all were MDR strains. The discovery of high antibiotic resistance rates in this common foodborne pathogen is a growing concern; therefore, ongoing surveillance is crucial to effectively monitor this pathogen. Full article
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16 pages, 3926 KiB  
Systematic Review
Systematic Review and Meta-Analysis Provide no Guidance on Management of Asymptomatic Bacteriuria within the First Year after Kidney Transplantation
by José Medina-Polo, Eva Falkensammer, Béla Köves, Jennifer Kranz, Zafer Tandogdu, Ana María Tapia, Tommaso Cai, Florian M. E. Wagenlehner, Laila Schneidewind and Truls Erik Bjerklund Johansen
Antibiotics 2024, 13(5), 442; https://doi.org/10.3390/antibiotics13050442 - 14 May 2024
Viewed by 1623
Abstract
(1) Background: Urinary tract infections (UTIs) are among the most frequent complications in kidney transplant (KT) recipients. Asymptomatic bacteriuria (ASB) may be a risk factor for UTIs and graft rejection. We aimed to evaluate available evidence regarding the benefit of screening and treatment [...] Read more.
(1) Background: Urinary tract infections (UTIs) are among the most frequent complications in kidney transplant (KT) recipients. Asymptomatic bacteriuria (ASB) may be a risk factor for UTIs and graft rejection. We aimed to evaluate available evidence regarding the benefit of screening and treatment of ASB within the first year after KT. (2) Evidence acquisition: A systematic literature search was conducted in MEDLINE, the Cochrane Library CENTRAL and Embase. Inclusion criteria were manuscripts in English addressing the management of ASB after KT. The PICO questions concerned Patients (adults receiving a KT), Intervention (screening, diagnosis and treatment of ASB), Control (screening and no antibiotic treatment) and Outcome (UTIs, sepsis, kidney failure and death). (3) Evidence synthesis: The systematic review identified 151 studies, and 16 full-text articles were evaluated. Seven were excluded because they did not evaluate the effect of treatment of ASB. There was no evidence for a higher incidence of lower UTIs, acute pyelonephritis, graft loss, or mortality in patients not treated with antibiotics for ASB. Analysis of comparative non-randomized and observational studies did not provide supplementary evidence to guide clinical recommendations. We believe this lack of evidence is due to confounding risk factors that are not being considered in the stratification of study patients. Full article
(This article belongs to the Collection Antimicrobial Prescribing and Antimicrobial Use in Healthcare Settings)
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16 pages, 4037 KiB  
Article
Antimicrobial Properties of Newly Developed Silver-Enriched Red Onion–Polymer Composites
by Judita Puišo, Jonas Žvirgždas, Algimantas Paškevičius, Shirin Arslonova and Diana Adlienė
Antibiotics 2024, 13(5), 441; https://doi.org/10.3390/antibiotics13050441 - 14 May 2024
Cited by 1 | Viewed by 1591
Abstract
Simple low-cost, nontoxic, environmentally friendly plant-extract-based polymer films play an important role in their application in medicine, the food industry, and agriculture. The addition of silver nanoparticles to the composition of these films enhances their antimicrobial capabilities and makes them suitable for the [...] Read more.
Simple low-cost, nontoxic, environmentally friendly plant-extract-based polymer films play an important role in their application in medicine, the food industry, and agriculture. The addition of silver nanoparticles to the composition of these films enhances their antimicrobial capabilities and makes them suitable for the treatment and prevention of infections. In this study, polymer-based gels and films (AgRonPVA) containing silver nanoparticles (AgNPs) were produced at room temperature from fresh red onion peel extract (“Ron”), silver nitrate, and polyvinyl alcohol (PVA). Silver nanoparticles were synthesized directly in a polymer matrix, which was irradiated by UV light. The presence of nanoparticles was approved by analyzing characteristic local surface plasmon resonance peaks occurring in UV-Vis absorbance spectra of irradiated experimental samples. The proof of evidence was supported by the results of XRD and EDX measurements. The diffusion-based method was applied to investigate the antimicrobial activity of several types of microbes located in the environment of the produced samples. Bacteria Staphylococcus aureus ATCC 29213, Acinetobacter baumannii ATCC BAA 747, and Pseudomonas aeruginosa ATCC 15442; yeasts Candida parapsilosis CBS 8836 and Candida albicans ATCC 90028; and microscopic fungi assays Aspergillus flavus BTL G-33 and Aspergillus fumigatus BTL G-38 were used in this investigation. The greatest effect was observed on Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa bacteria, defining these films as potential candidates for antimicrobial applications. The antimicrobial features of the films were less effective against fungi and the weakest against yeasts. Full article
(This article belongs to the Special Issue Silver and Gold Compounds as Antibiotics)
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