Pub Date : 2024-09-02DOI: 10.3390/antibiotics13090832
Zahit Taş, Gökhan Metan, Gülçin Telli Dizman, Eren Yavuz, Ömer Dizdar, Yahya Büyükaşık, Ömrüm Uzun, Murat Akova
We investigated the influence of a local guideline on the quality of febrile neutropenia (FN) management and the applicability of a computerized decision support system (CDSS) using real-life data. The study included 227 FN patients between April 2016 and January 2019. The primary outcome measure was the achievement of a 20% increase in the rate of appropriate empirical treatment of FN in bacteremic patients. The compatibility of the CDSS (the development of which was completed in November 2021) with local protocols was tested using standard patient scenarios and empirical antibiotic recommendations for bacteremic FN patients. In total, 91 patients were evaluated before (P1: between April 2016 and May 2017) and 136 after (P2: between May 2017 and January 2019) the guideline’s release (May 2017). The demographic characteristics were similar. Appropriate empirical antibacterial treatment was achieved in 58.3% of P1 and 88.1% of P2 patients (p = 0.006). The need for escalation of antibacterial treatment was significantly lower in P2 (49.5% vs. 35.3%; p = 0.03). In P2, the performance of the CDSS and consulting physicians was similar (CDSS 88.8% vs. physician 88.83%; p = 1) regarding appropriate empirical antibacterial treatment. The introduction of the local guideline improved the appropriateness of initial empirical treatment and reduced escalation rates in FN patients. The high rate of compliance of the CDSS with the local guideline-based decisions in P2 highlights the usefulness of the CDSS for these patients.
{"title":"An Institutional Febrile Neutropenia Protocol Improved the Antibacterial Treatment and Encouraged the Development of a Computerized Clinical Decision Support System","authors":"Zahit Taş, Gökhan Metan, Gülçin Telli Dizman, Eren Yavuz, Ömer Dizdar, Yahya Büyükaşık, Ömrüm Uzun, Murat Akova","doi":"10.3390/antibiotics13090832","DOIUrl":"https://doi.org/10.3390/antibiotics13090832","url":null,"abstract":"We investigated the influence of a local guideline on the quality of febrile neutropenia (FN) management and the applicability of a computerized decision support system (CDSS) using real-life data. The study included 227 FN patients between April 2016 and January 2019. The primary outcome measure was the achievement of a 20% increase in the rate of appropriate empirical treatment of FN in bacteremic patients. The compatibility of the CDSS (the development of which was completed in November 2021) with local protocols was tested using standard patient scenarios and empirical antibiotic recommendations for bacteremic FN patients. In total, 91 patients were evaluated before (P1: between April 2016 and May 2017) and 136 after (P2: between May 2017 and January 2019) the guideline’s release (May 2017). The demographic characteristics were similar. Appropriate empirical antibacterial treatment was achieved in 58.3% of P1 and 88.1% of P2 patients (p = 0.006). The need for escalation of antibacterial treatment was significantly lower in P2 (49.5% vs. 35.3%; p = 0.03). In P2, the performance of the CDSS and consulting physicians was similar (CDSS 88.8% vs. physician 88.83%; p = 1) regarding appropriate empirical antibacterial treatment. The introduction of the local guideline improved the appropriateness of initial empirical treatment and reduced escalation rates in FN patients. The high rate of compliance of the CDSS with the local guideline-based decisions in P2 highlights the usefulness of the CDSS for these patients.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"181 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.3390/antibiotics13090830
Huyen Thanh Thi Le, Trang Thu Hoang, Ngoc Anh Thi Nguyen, Sang Ngoc Nguyen, Ung Dinh Nguyen, Cuong Xuan Hoang, Nam S. Vo, Duc Quang Le, Son Hoang Nguyen, Minh Duc Cao, Tho Huu Ho
(1) Background: Pediatric urinary tract infections (UTIs) pose significant challenges due to drug-resistant Escherichia coli (E. coli) strains. This study utilizes whole-genome sequencing to analyze temporal trends in antibiotic resistance genes (ARGs) in clinical E. coli isolates from pediatric UTI cases in central Vietnam. (2) Methods: We conducted whole-genome sequencing on 71 E. coli isolates collected from pediatric UTI patients between 2018 and 2020. ARGs were identified, and their prevalence over time was analyzed. Statistical tests were used to correlate ARG presence with antibiotic resistance. (3) Results: Of the 47 E. coli isolates with complete data, 40 distinct ARGs were identified, with a median of 10 resistance genes per isolate. A significant increase in the total number of ARGs per isolate was observed over time, from an average of 8.88 before June 2019 to 11.63 after. Notably, the prevalence of the aadA2 gene (aminoglycoside resistance) rose from 0% to 26.7%, and that of the blaNDM-5 gene (beta-lactam and carbapenem resistance) increased from 0% to 23.3%. Key correlations include blaEC with cephalosporin resistance, blaNDM-5 with carbapenem resistance, and sul2 with sulfamethoxazole/trimethoprim resistance. (4) Conclusions: Whole-genome sequencing reveals complex and evolving antibiotic resistance patterns in pediatric E. coli UTIs in central Vietnam, with a marked increase in ARG prevalence over time. Continuous surveillance and targeted treatments are essential to address these trends. Understanding genetic foundations is crucial for effective intervention strategies.
{"title":"Whole-Genome Sequencing Reveals Temporal Trends in Antibiotic Resistance Genes in Escherichia coli Causing Pediatric Urinary Tract Infections in Central Vietnam","authors":"Huyen Thanh Thi Le, Trang Thu Hoang, Ngoc Anh Thi Nguyen, Sang Ngoc Nguyen, Ung Dinh Nguyen, Cuong Xuan Hoang, Nam S. Vo, Duc Quang Le, Son Hoang Nguyen, Minh Duc Cao, Tho Huu Ho","doi":"10.3390/antibiotics13090830","DOIUrl":"https://doi.org/10.3390/antibiotics13090830","url":null,"abstract":"(1) Background: Pediatric urinary tract infections (UTIs) pose significant challenges due to drug-resistant Escherichia coli (E. coli) strains. This study utilizes whole-genome sequencing to analyze temporal trends in antibiotic resistance genes (ARGs) in clinical E. coli isolates from pediatric UTI cases in central Vietnam. (2) Methods: We conducted whole-genome sequencing on 71 E. coli isolates collected from pediatric UTI patients between 2018 and 2020. ARGs were identified, and their prevalence over time was analyzed. Statistical tests were used to correlate ARG presence with antibiotic resistance. (3) Results: Of the 47 E. coli isolates with complete data, 40 distinct ARGs were identified, with a median of 10 resistance genes per isolate. A significant increase in the total number of ARGs per isolate was observed over time, from an average of 8.88 before June 2019 to 11.63 after. Notably, the prevalence of the aadA2 gene (aminoglycoside resistance) rose from 0% to 26.7%, and that of the blaNDM-5 gene (beta-lactam and carbapenem resistance) increased from 0% to 23.3%. Key correlations include blaEC with cephalosporin resistance, blaNDM-5 with carbapenem resistance, and sul2 with sulfamethoxazole/trimethoprim resistance. (4) Conclusions: Whole-genome sequencing reveals complex and evolving antibiotic resistance patterns in pediatric E. coli UTIs in central Vietnam, with a marked increase in ARG prevalence over time. Continuous surveillance and targeted treatments are essential to address these trends. Understanding genetic foundations is crucial for effective intervention strategies.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.3390/antibiotics13090834
Blanca Lorente-Torres, Jesús Llano-Verdeja, Pablo Castañera, Helena Á. Ferrero, Sergio Fernández-Martínez, Farzaneh Javadimarand, Luis M. Mateos, Michal Letek, Álvaro Mourenza
Intracellular bacterial pathogens pose significant public health challenges due to their ability to evade immune defenses and conventional antibiotics. Drug repurposing has recently been explored as a strategy to discover new therapeutic uses for established drugs to combat these infections. Utilizing high-throughput screening, bioinformatics, and systems biology, several existing drugs have been identified with potential efficacy against intracellular bacteria. For instance, neuroleptic agents like thioridazine and antipsychotic drugs such as chlorpromazine have shown effectiveness against Staphylococcus aureus and Listeria monocytogenes. Furthermore, anticancer drugs including tamoxifen and imatinib have been repurposed to induce autophagy and inhibit bacterial growth within host cells. Statins and anti-inflammatory drugs have also demonstrated the ability to enhance host immune responses against Mycobacterium tuberculosis. The review highlights the complex mechanisms these pathogens use to resist conventional treatments, showcases successful examples of drug repurposing, and discusses the methodologies used to identify and validate these drugs. Overall, drug repurposing offers a promising approach for developing new treatments for bacterial infections, addressing the urgent need for effective antimicrobial therapies.
{"title":"Innovative Strategies in Drug Repurposing to Tackle Intracellular Bacterial Pathogens","authors":"Blanca Lorente-Torres, Jesús Llano-Verdeja, Pablo Castañera, Helena Á. Ferrero, Sergio Fernández-Martínez, Farzaneh Javadimarand, Luis M. Mateos, Michal Letek, Álvaro Mourenza","doi":"10.3390/antibiotics13090834","DOIUrl":"https://doi.org/10.3390/antibiotics13090834","url":null,"abstract":"Intracellular bacterial pathogens pose significant public health challenges due to their ability to evade immune defenses and conventional antibiotics. Drug repurposing has recently been explored as a strategy to discover new therapeutic uses for established drugs to combat these infections. Utilizing high-throughput screening, bioinformatics, and systems biology, several existing drugs have been identified with potential efficacy against intracellular bacteria. For instance, neuroleptic agents like thioridazine and antipsychotic drugs such as chlorpromazine have shown effectiveness against Staphylococcus aureus and Listeria monocytogenes. Furthermore, anticancer drugs including tamoxifen and imatinib have been repurposed to induce autophagy and inhibit bacterial growth within host cells. Statins and anti-inflammatory drugs have also demonstrated the ability to enhance host immune responses against Mycobacterium tuberculosis. The review highlights the complex mechanisms these pathogens use to resist conventional treatments, showcases successful examples of drug repurposing, and discusses the methodologies used to identify and validate these drugs. Overall, drug repurposing offers a promising approach for developing new treatments for bacterial infections, addressing the urgent need for effective antimicrobial therapies.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"169 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.3390/antibiotics13090836
Wesam Abd El-Fattah, Mohammad Y. Alfaifi, Jafar Alkabli, Heba A. Ramadan, Ali A. Shati, Serag Eldin I. Elbehairi, Reda F. M. Elshaarawy, Islam Kamal, Moustafa M. Saleh
In the original publication [...]
在最初的出版物中 [...]
{"title":"Correction: Abd El-Fattah et al. Immobilization of ZnO-TiO2 Nanocomposite into Polyimidazolium Amphiphilic Chitosan Film, Targeting Improving Its Antimicrobial and Antibiofilm Applications. Antibiotics 2023, 12, 1110","authors":"Wesam Abd El-Fattah, Mohammad Y. Alfaifi, Jafar Alkabli, Heba A. Ramadan, Ali A. Shati, Serag Eldin I. Elbehairi, Reda F. M. Elshaarawy, Islam Kamal, Moustafa M. Saleh","doi":"10.3390/antibiotics13090836","DOIUrl":"https://doi.org/10.3390/antibiotics13090836","url":null,"abstract":"In the original publication [...]","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.3390/antibiotics13090835
Emory G. Johnson, Kayla Maki Ortiz, David T. Adams, Satwinder Kaur, Andrew C. Faust, Hui Yang, Carlos A. Alvarez, Ronald G. Hall
Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem’s activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study’s primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP.
美罗培南是一种广谱抗生素，用于治疗多重耐药感染。由于其药代动力学特征，美罗培南的活性可通过延长输注（EI）、连续输注或间歇输注等给药策略，在特定时间内使血清浓度保持在最低抑菌浓度（MIC）以上。关于这些给药策略的优劣，现有文献说法不一。本研究的主要目的是确定静脉推注（IVP）和 EI 给药在临床稳定时间上的差异。我们对 100 名重症患者进行了回顾性试点队列研究，这些患者在入住重症监护病房（ICU）期间通过静脉推注（50 人）或电子输入（50 人）接受了美罗培南治疗。IVP和EI在总体临床稳定率上没有明显的统计学差异（48%对44%，P = 0.17）。不过，EI 组临床稳定的中位时间更短（20.4 小时对 66.2 小时，p = 0.01）。使用 EI 可缩短住院时间（13 天 vs. 17 天；p = 0.05）和重症监护室住院时间（6 天 vs. 9 天；p = 0.02）。虽然我们在临床稳定的总体时间上没有发现显著的统计学差异，但这项试点研究的结果表明，与静脉输液相比，使用 EI 可以更快地解决临床问题。
{"title":"A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients","authors":"Emory G. Johnson, Kayla Maki Ortiz, David T. Adams, Satwinder Kaur, Andrew C. Faust, Hui Yang, Carlos A. Alvarez, Ronald G. Hall","doi":"10.3390/antibiotics13090835","DOIUrl":"https://doi.org/10.3390/antibiotics13090835","url":null,"abstract":"Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem’s activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study’s primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.3390/antibiotics13090831
Ramona Wissmann, Dolf Kümmerlen, Thomas Echtermann
(1) Background: The aim of this retrospective observational study was to observe the trends in antimicrobial usage (AMU) from 2018 to 2021 in Swiss pigs based on an electronic treatment journal used nationwide by farmers. Thus, for the first time, standardized, longitudinal comparisons of AMU between the years could be analyzed, as well as the influence of targeted interventions, on farms with higher consumption. (2) Methods: The data was evaluated by different indicators, such as the amount of active ingredient in kilograms, treatment days per farm (ATI) and treatment incidence (TI) based either on animal-defined daily doses (TIADD) or used daily doses (TIUDD). Calculations were performed across the following five age categories: suckling piglets, weaners, fattening pigs, and gestating and lactating sows, and the proportions of antimicrobial classes were evaluated for each age category. (3) Results: The highest amount of the active ingredient was administered to the group of fattening pigs, while the suckling piglets received the lowest amount of the active ingredient. In 2021, there was a significant decrease in active ingredient consumption per pig, but a significant increase in ATI, TIADD and TIUDD compared to 2018. The largest proportion of AMU was attributed to penicillins each year, followed by sulfonamides and tetracyclines. The “Highest Priority Critically Important Antimicrobials” represented a proportion of overall usage, declining from 5.2% in 2018 to 3.1% in 2021, while polypeptides were the most used class of critical antimicrobials. Interventions on high-usage farms showed that some farms decreased their AMU in the following year while others did not. (4) Conclusions: This study reveals a decrease in the overall usage measured in kilograms per pig of antimicrobials in Swiss pigs between 2019 and 2021 through the monitoring of AMU, but, at the same time, there was an increase in treatment days or incidence per farm. Critical antimicrobials can be reduced regardless of the indicator. The significance and quality of interventions should be investigated in future studies.
{"title":"Trends in Antimicrobial Usage on Swiss Pig Farms from 2018 to 2021: Based on an Electronic Treatment Journal","authors":"Ramona Wissmann, Dolf Kümmerlen, Thomas Echtermann","doi":"10.3390/antibiotics13090831","DOIUrl":"https://doi.org/10.3390/antibiotics13090831","url":null,"abstract":"(1) Background: The aim of this retrospective observational study was to observe the trends in antimicrobial usage (AMU) from 2018 to 2021 in Swiss pigs based on an electronic treatment journal used nationwide by farmers. Thus, for the first time, standardized, longitudinal comparisons of AMU between the years could be analyzed, as well as the influence of targeted interventions, on farms with higher consumption. (2) Methods: The data was evaluated by different indicators, such as the amount of active ingredient in kilograms, treatment days per farm (ATI) and treatment incidence (TI) based either on animal-defined daily doses (TIADD) or used daily doses (TIUDD). Calculations were performed across the following five age categories: suckling piglets, weaners, fattening pigs, and gestating and lactating sows, and the proportions of antimicrobial classes were evaluated for each age category. (3) Results: The highest amount of the active ingredient was administered to the group of fattening pigs, while the suckling piglets received the lowest amount of the active ingredient. In 2021, there was a significant decrease in active ingredient consumption per pig, but a significant increase in ATI, TIADD and TIUDD compared to 2018. The largest proportion of AMU was attributed to penicillins each year, followed by sulfonamides and tetracyclines. The “Highest Priority Critically Important Antimicrobials” represented a proportion of overall usage, declining from 5.2% in 2018 to 3.1% in 2021, while polypeptides were the most used class of critical antimicrobials. Interventions on high-usage farms showed that some farms decreased their AMU in the following year while others did not. (4) Conclusions: This study reveals a decrease in the overall usage measured in kilograms per pig of antimicrobials in Swiss pigs between 2019 and 2021 through the monitoring of AMU, but, at the same time, there was an increase in treatment days or incidence per farm. Critical antimicrobials can be reduced regardless of the indicator. The significance and quality of interventions should be investigated in future studies.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.3390/antibiotics13090827
Soraya Herrera-Espejo, Marta Carretero-Ledesma, Manuel Anselmo Bahamonde-García, Elisa Cordero, Jerónimo Pachón, María Eugenia Pachón-Ibáñez
In vitro studies have suggested that acidic pH may reduce and increase the efficacy of ciprofloxacin and fosfomycin, respectively, when used to treat Escherichia coli and Klebsiella pneumoniae infections. We assessed the effects of acidic, neutral, and alkaline urine pH on the efficacy of optimized ciprofloxacin and fosfomycin dosages in UTI murine model of E. coli and K. pneumoniae. Immunocompetent and immunocompromised mice with adjusted urine pH were inoculated with E. coli and K. pneumoniae strains, and the efficacy was assessed based on the bacterial concentrations in tissues and fluids at 72 h, with respect to untreated controls. At acidic urine pH, both antimicrobials were effective, achieving similar reductions in E. coli concentrations in the kidneys in immunocompetent and immunocompromised mice and in K. pneumoniae in immunocompetent mice. At a neutral urine pH, both therapies reduced the presence of E. coli in the kidneys of immunocompetent mice. However, in immunocompromised mice, antimicrobials were ineffective at treating E. coli infection in the kidneys at a neutral urine pH and showed reduced efficacy against K. pneumoniae at both acidic and neutral urine pH. The results showed no correlation between urine pH and antimicrobial efficacy, suggesting that the reduced effectiveness is associated with the animals’ immunocompetence status.
{"title":"Assessing the Influence of Urine pH on the Efficacy of Ciprofloxacin and Fosfomycin in Immunocompetent and Immunocompromised Murine Models of Escherichia coli and Klebsiella pneumoniae Infection in the Lower Urinary Tract","authors":"Soraya Herrera-Espejo, Marta Carretero-Ledesma, Manuel Anselmo Bahamonde-García, Elisa Cordero, Jerónimo Pachón, María Eugenia Pachón-Ibáñez","doi":"10.3390/antibiotics13090827","DOIUrl":"https://doi.org/10.3390/antibiotics13090827","url":null,"abstract":"In vitro studies have suggested that acidic pH may reduce and increase the efficacy of ciprofloxacin and fosfomycin, respectively, when used to treat Escherichia coli and Klebsiella pneumoniae infections. We assessed the effects of acidic, neutral, and alkaline urine pH on the efficacy of optimized ciprofloxacin and fosfomycin dosages in UTI murine model of E. coli and K. pneumoniae. Immunocompetent and immunocompromised mice with adjusted urine pH were inoculated with E. coli and K. pneumoniae strains, and the efficacy was assessed based on the bacterial concentrations in tissues and fluids at 72 h, with respect to untreated controls. At acidic urine pH, both antimicrobials were effective, achieving similar reductions in E. coli concentrations in the kidneys in immunocompetent and immunocompromised mice and in K. pneumoniae in immunocompetent mice. At a neutral urine pH, both therapies reduced the presence of E. coli in the kidneys of immunocompetent mice. However, in immunocompromised mice, antimicrobials were ineffective at treating E. coli infection in the kidneys at a neutral urine pH and showed reduced efficacy against K. pneumoniae at both acidic and neutral urine pH. The results showed no correlation between urine pH and antimicrobial efficacy, suggesting that the reduced effectiveness is associated with the animals’ immunocompetence status.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.3390/antibiotics13090828
Ji-Hyun Nam, Jung Sik Yoo
Sodium hypochlorite (NaOCl) is widely used in public healthcare facilities; this exposure can result in the development of bacterial tolerance to disinfectants, which has known links to antibiotic cross-resistance. However, the mechanism through which cross-resistance to antibiotics and disinfectants develops remains ambiguous. Therefore, this study aimed to examine the phenotypic and transcriptomic changes caused by disinfectant exposure in Gram-negative bacteria and determine the cause of cross-resistance to antibiotics. The results demonstrated that the misuse of disinfectants plays an important role in the emergence of disinfectant resistance and in the increase in antibiotic resistance. Antibiotic resistance may occur from the exposure of Gram-negative bacteria to subminimal inhibitory concentrations (MICs) of NaOCl. Ten passages of Gram-negative bacteria in increasingly higher subMICs of the NaOCl disinfectant were sufficient to increase the MIC to >2500 µg/mL NaOCl, particularly in K. pneumoniae and P. aeruginosa. To determine the development of cross-resistance to antibiotics due to NaOCl exposure, the MICs for each antibiotic before and after the exposure of each strain to sublethal concentrations of NaOCl were compared. After overnight incubation with a sublethal concentration of NaOCl, a statistically significant increase in MIC was only observed for imipenem (p < 0.01). An investigation of the mechanism of cross-resistance by means of transcriptome analysis revealed that 1250 µg/mL of NaOCl-adapted K. pneumoniae and P. aeruginosa strains increased resistance to imipenem due to the increased expression of resistance-nodulation-cell division (RND) efflux pumps, such as AcrAB-TolC and MexAB/XY-OprM. Therefore, we suggest that exposure to NaOCl can influence the expression of RND efflux pump genes, contributing to imipenem cross-resistance.
{"title":"Sublethal Sodium Hypochlorite Exposure: Impact on Resistance-Nodulation-Cell Division Efflux Pump Overexpression and Cross-Resistance to Imipenem","authors":"Ji-Hyun Nam, Jung Sik Yoo","doi":"10.3390/antibiotics13090828","DOIUrl":"https://doi.org/10.3390/antibiotics13090828","url":null,"abstract":"Sodium hypochlorite (NaOCl) is widely used in public healthcare facilities; this exposure can result in the development of bacterial tolerance to disinfectants, which has known links to antibiotic cross-resistance. However, the mechanism through which cross-resistance to antibiotics and disinfectants develops remains ambiguous. Therefore, this study aimed to examine the phenotypic and transcriptomic changes caused by disinfectant exposure in Gram-negative bacteria and determine the cause of cross-resistance to antibiotics. The results demonstrated that the misuse of disinfectants plays an important role in the emergence of disinfectant resistance and in the increase in antibiotic resistance. Antibiotic resistance may occur from the exposure of Gram-negative bacteria to subminimal inhibitory concentrations (MICs) of NaOCl. Ten passages of Gram-negative bacteria in increasingly higher subMICs of the NaOCl disinfectant were sufficient to increase the MIC to >2500 µg/mL NaOCl, particularly in K. pneumoniae and P. aeruginosa. To determine the development of cross-resistance to antibiotics due to NaOCl exposure, the MICs for each antibiotic before and after the exposure of each strain to sublethal concentrations of NaOCl were compared. After overnight incubation with a sublethal concentration of NaOCl, a statistically significant increase in MIC was only observed for imipenem (p < 0.01). An investigation of the mechanism of cross-resistance by means of transcriptome analysis revealed that 1250 µg/mL of NaOCl-adapted K. pneumoniae and P. aeruginosa strains increased resistance to imipenem due to the increased expression of resistance-nodulation-cell division (RND) efflux pumps, such as AcrAB-TolC and MexAB/XY-OprM. Therefore, we suggest that exposure to NaOCl can influence the expression of RND efflux pump genes, contributing to imipenem cross-resistance.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.3390/antibiotics13090826
Juan Francisco Martín, Paloma Liras
The biosynthesis of antibiotics and other secondary metabolites (also named special metabolites) is regulated by multiple regulatory networks and cascades that act by binding transcriptional factors to the promoter regions of different biosynthetic gene clusters. The binding affinity of transcriptional factors is frequently modulated by their interaction with specific ligand molecules. In the last decades, it was found that the biosynthesis of penicillin is induced by two different molecules, 1,3-diaminopropane and spermidine, but not by putrescine (1,4-diaminobutane) or spermine. 1,3-diaminopropane and spermidine induce the expression of penicillin biosynthetic genes in Penicillium chrysogenum. Proteomic studies clearly identified two different proteins that respond to the addition to cultures of these inducers and are involved in β-alanine and pantothenic acid biosynthesis. These compounds are intermediates in the biosynthesis of phosphopantetheine that is required for the activation of non-ribosomal peptide synthetases, polyketide synthases, and fatty acid synthases. These large-size multidomain enzymes are inactive in the “apo” form and are activated by covalent addition of the phosphopantetheine prosthetic group by phosphopantetheinyl transferases. Both 1,3-diaminopropane and spermidine have a similar effect on the biosynthesis of cephalosporin by Acremonium chrysogenum and lovastatin by Aspergillus terreus, suggesting that this is a common regulatory mechanism in the biosynthesis of bioactive secondary metabolites/natural products.
{"title":"Diamine Fungal Inducers of Secondary Metabolism: 1,3-Diaminopropane and Spermidine Trigger Enzymes Involved in β-Alanine and Pantothenic Acid Biosynthesis, Precursors of Phosphopantetheine in the Activation of Multidomain Enzymes","authors":"Juan Francisco Martín, Paloma Liras","doi":"10.3390/antibiotics13090826","DOIUrl":"https://doi.org/10.3390/antibiotics13090826","url":null,"abstract":"The biosynthesis of antibiotics and other secondary metabolites (also named special metabolites) is regulated by multiple regulatory networks and cascades that act by binding transcriptional factors to the promoter regions of different biosynthetic gene clusters. The binding affinity of transcriptional factors is frequently modulated by their interaction with specific ligand molecules. In the last decades, it was found that the biosynthesis of penicillin is induced by two different molecules, 1,3-diaminopropane and spermidine, but not by putrescine (1,4-diaminobutane) or spermine. 1,3-diaminopropane and spermidine induce the expression of penicillin biosynthetic genes in Penicillium chrysogenum. Proteomic studies clearly identified two different proteins that respond to the addition to cultures of these inducers and are involved in β-alanine and pantothenic acid biosynthesis. These compounds are intermediates in the biosynthesis of phosphopantetheine that is required for the activation of non-ribosomal peptide synthetases, polyketide synthases, and fatty acid synthases. These large-size multidomain enzymes are inactive in the “apo” form and are activated by covalent addition of the phosphopantetheine prosthetic group by phosphopantetheinyl transferases. Both 1,3-diaminopropane and spermidine have a similar effect on the biosynthesis of cephalosporin by Acremonium chrysogenum and lovastatin by Aspergillus terreus, suggesting that this is a common regulatory mechanism in the biosynthesis of bioactive secondary metabolites/natural products.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01DOI: 10.3390/antibiotics13090829
Davorka Repac Antić, Bruno Kovač, Marko Kolenc, Irena Brčić Karačonji, Ivana Gobin, Mirna Petković Didović
Enterococcus faecalis, responsible for a majority of human and nosocomial enterococcal infections, is intrinsically resistant to aminoglycoside antibiotics (such as gentamicin, GEN), which must be used in a combined therapy to be effective. Nitroxoline (NTX) is an old antibiotic, underused for decades, but rediscovered now in an era of growing antibiotic resistance. In this in vitro study, the types of interactions between NTX and GEN on 29 E. faecalis strains were analyzed with an aim to find synergistic antimicrobial and antiadhesion combinations. Transmission electron microscopy (TEM) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to analyze changes in cell morphology and bacterial proteome after monotreatments and combined treatments. The results showed the synergistic effect for six combinations on eight strains, including the ATCC29212, and an additive effect for most strains. Combinations causing a complete inhibition of adhesion were established. Cell membrane integrity was affected by NTX, while combined NTX/GEN treatment caused dramatic changes in cell morphology. Upregulation of the expression of many proteins was established, with some emerging only after combined treatment. The results strongly imply that NTX has the potential for use in combined therapy with GEN against enterococci and it could further provide a substantial contribution to an ongoing fight against antimicrobial resistance and nosocomial infections.
粪肠球菌是大多数人类和病原性肠球菌感染的罪魁祸首，它对氨基糖苷类抗生素（如庆大霉素、GEN）具有固有的耐药性，必须使用联合疗法才能有效。硝唑啉（NTX）是一种古老的抗生素，数十年来一直未得到充分利用，但在抗生素耐药性不断增加的今天被重新发现。在这项体外研究中，我们分析了 NTX 和 GEN 对 29 株粪肠球菌的相互作用类型，目的是找到协同抗菌和抗粘附的组合。采用透射电子显微镜（TEM）和基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）分析了单一处理和联合处理后细胞形态和细菌蛋白质组的变化。结果表明，六种组合对包括 ATCC29212 在内的八种菌株具有协同效应，对大多数菌株具有相加效应。确定了可完全抑制粘附的组合。细胞膜完整性受到 NTX 的影响，而 NTX/GEN 联合处理会导致细胞形态发生巨大变化。许多蛋白质的表达都出现了上调，其中一些只有在联合处理后才会出现。这些结果有力地表明，NTX 具有与 GEN 联合治疗肠球菌的潜力，它还能为目前抗菌药耐药性和医院内感染的斗争做出重大贡献。
{"title":"Combinatory Effect of Nitroxoline and Gentamicin in the Control of Uropathogenic Enterococci Infections","authors":"Davorka Repac Antić, Bruno Kovač, Marko Kolenc, Irena Brčić Karačonji, Ivana Gobin, Mirna Petković Didović","doi":"10.3390/antibiotics13090829","DOIUrl":"https://doi.org/10.3390/antibiotics13090829","url":null,"abstract":"Enterococcus faecalis, responsible for a majority of human and nosocomial enterococcal infections, is intrinsically resistant to aminoglycoside antibiotics (such as gentamicin, GEN), which must be used in a combined therapy to be effective. Nitroxoline (NTX) is an old antibiotic, underused for decades, but rediscovered now in an era of growing antibiotic resistance. In this in vitro study, the types of interactions between NTX and GEN on 29 E. faecalis strains were analyzed with an aim to find synergistic antimicrobial and antiadhesion combinations. Transmission electron microscopy (TEM) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to analyze changes in cell morphology and bacterial proteome after monotreatments and combined treatments. The results showed the synergistic effect for six combinations on eight strains, including the ATCC29212, and an additive effect for most strains. Combinations causing a complete inhibition of adhesion were established. Cell membrane integrity was affected by NTX, while combined NTX/GEN treatment caused dramatic changes in cell morphology. Upregulation of the expression of many proteins was established, with some emerging only after combined treatment. The results strongly imply that NTX has the potential for use in combined therapy with GEN against enterococci and it could further provide a substantial contribution to an ongoing fight against antimicrobial resistance and nosocomial infections.","PeriodicalId":8151,"journal":{"name":"Antibiotics","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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