Antibiotics

14 pages, 3609 KiB

Open AccessArticle

Potent Anti-Inflammatory Effects of a Helix-to-Helix Peptide against Pseudomonas aeruginosa Endotoxin-Mediated Sepsis

by Hyosuk Son, Seong-Cheol Park, Young-Min Kim, Jong-Kook Lee, Soyoung Park, Taeuk Guk, A-Mi Yoon, Hye Song Lim, Mi-Kyeong Jang and Jung Ro Lee

Antibiotics 2022, 11(11), 1675; https://doi.org/10.3390/antibiotics11111675 - 21 Nov 2022

Cited by 4 | Viewed by 1618

Abstract

Although considerable scientific research data is available for sepsis and cytokine storm syndrome, there is a need to develop new treatments or drugs for sepsis management. Antimicrobial peptides (AMPs) possess anti-bacterial and anti-inflammatory activity, neutralizing toxins such as lipopolysaccharides (LPS, endotoxin). Most AMPs [...] Read more.

Although considerable scientific research data is available for sepsis and cytokine storm syndrome, there is a need to develop new treatments or drugs for sepsis management. Antimicrobial peptides (AMPs) possess anti-bacterial and anti-inflammatory activity, neutralizing toxins such as lipopolysaccharides (LPS, endotoxin). Most AMPs have been designed as a substitute for conventional antibiotics, which kill drug-resistant pathogens. The present study aimed to determine the anti-inflammatory potential of 10 designed XIW (X: lysine, arginine, or glutamic acid) α-helical peptides in macrophages and a mouse model in the presence of LPS. Among them, WIKE-14, a peptide with a helix-to-helix structure, having the 12th amino acid substituted with glutamic acid, suppressed pro-inflammatory cytokines in RAW 264.7 macrophages. This reaction was mediated by the inhibition of the binding between LPS and macrophages. In addition, the WIKE-14 peptide exhibited a potent anti-inflammatory activity in mice ears and lungs inflamed using LPS. Thus, our results may provide useful insights for the development of anti-sepsis agents via the sequence and structure information of the WIKE-14 peptide. Full article

(This article belongs to the Special Issue Action Mechanism of Peptide Variants with Antimicrobial, Anti-biofilm, or Anti-inflammatory Effects)

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11 pages, 650 KiB

Open AccessReview

Deep Learning and Antibiotic Resistance

by Stefan Lucian Popa, Cristina Pop, Miruna Oana Dita, Vlad Dumitru Brata, Roxana Bolchis, Zoltan Czako, Mohamed Mehdi Saadani, Abdulrahman Ismaiel, Dinu Iuliu Dumitrascu, Simona Grad, Liliana David, Gabriel Cismaru and Alexandru Marius Padureanu

Antibiotics 2022, 11(11), 1674; https://doi.org/10.3390/antibiotics11111674 - 21 Nov 2022

Cited by 8 | Viewed by 4291

Abstract

Antibiotic resistance (AR) is a naturally occurring phenomenon with the capacity to render useless all known antibiotics in the fight against bacterial infections. Although bacterial resistance appeared before any human life form, this process has accelerated in the past years. Important causes of [...] Read more.

Antibiotic resistance (AR) is a naturally occurring phenomenon with the capacity to render useless all known antibiotics in the fight against bacterial infections. Although bacterial resistance appeared before any human life form, this process has accelerated in the past years. Important causes of AR in modern times could be the over-prescription of antibiotics, the presence of faulty infection-prevention strategies, pollution in overcrowded areas, or the use of antibiotics in agriculture and farming, together with a decreased interest from the pharmaceutical industry in researching and testing new antibiotics. The last cause is primarily due to the high costs of developing antibiotics. The aim of the present review is to highlight the techniques that are being developed for the identification of new antibiotics to assist this lengthy process, using artificial intelligence (AI). AI can shorten the preclinical phase by rapidly generating many substances based on algorithms created by machine learning (ML) through techniques such as neural networks (NN) or deep learning (DL). Recently, a text mining system that incorporates DL algorithms was used to help and speed up the data curation process. Moreover, new and old methods are being used to identify new antibiotics, such as the combination of quantitative structure-activity relationship (QSAR) methods with ML or Raman spectroscopy and MALDI-TOF MS combined with NN, offering faster and easier interpretation of results. Thus, AI techniques are important additional tools for researchers and clinicians in the race for new methods of overcoming bacterial resistance. Full article

(This article belongs to the Special Issue Antibiotic Resistance: Opportunities and Challenges)

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26 pages, 3748 KiB

Open AccessReview

Potential of Aromatic Plant-Derived Essential Oils for the Control of Foodborne Bacteria and Antibiotic Resistance in Animal Production: A Review

by Lianhua Zhang, Fei Gao, Junwei Ge, Hui Li, Fei Xia, Hongtong Bai, Xiangshu Piao and Lei Shi

Antibiotics 2022, 11(11), 1673; https://doi.org/10.3390/antibiotics11111673 - 21 Nov 2022

Cited by 10 | Viewed by 2566

Abstract

Antibiotic resistance has become a severe public threat to human health worldwide. Supplementing antibiotic growth promoters (AGPs) at subtherapeutic levels has been a commonly applied method to improve the production performance of livestock and poultry, but the misuse of antibiotics in animal production [...] Read more.

Antibiotic resistance has become a severe public threat to human health worldwide. Supplementing antibiotic growth promoters (AGPs) at subtherapeutic levels has been a commonly applied method to improve the production performance of livestock and poultry, but the misuse of antibiotics in animal production plays a major role in the antibiotic resistance crisis and foodborne disease outbreaks. The addition of AGPs to improve production performance in livestock and poultry has been prohibited in some countries, including Europe, the United States and China. Moreover, cross-resistance could result in the development of multidrug resistant bacteria and limit therapeutic options for human and animal health. Therefore, finding alternatives to antibiotics to maintain the efficiency of livestock production and reduce the risk of foodborne disease outbreaks is beneficial to human health and the sustainable development of animal husbandry. Essential oils (EOs) and their individual compounds derived from aromatic plants are becoming increasingly popular as potential antibiotic alternatives for animal production based on their antibacterial properties. This paper reviews recent studies in the application of EOs in animal production for the control of foodborne pathogens, summarizes their molecular modes of action to increase the susceptibility of antibiotic-resistant bacteria, and provides a promising role for the application of nanoencapsulated EOs in animal production to control bacteria and overcome antibiotic resistance. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Animal and Zoonotic Pathogens)

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12 pages, 1091 KiB

Open AccessArticle

Colistin Resistance Mechanisms in Human and Veterinary Klebsiella pneumoniae Isolates

by Manuela Tietgen, Lisa Sedlaczek, Paul G. Higgins, Heike Kaspar, Christa Ewers and Stephan Göttig

Antibiotics 2022, 11(11), 1672; https://doi.org/10.3390/antibiotics11111672 - 21 Nov 2022

Cited by 3 | Viewed by 1745

Abstract

Colistin (polymyxin E) is increasingly used as a last-resort antibiotic for the treatment of severe infections with multidrug-resistant Gram-negative bacteria. In contrast to human medicine, colistin is also used in veterinary medicine for metaphylaxis. Our objective was to decipher common colistin resistance mechanisms [...] Read more.

Colistin (polymyxin E) is increasingly used as a last-resort antibiotic for the treatment of severe infections with multidrug-resistant Gram-negative bacteria. In contrast to human medicine, colistin is also used in veterinary medicine for metaphylaxis. Our objective was to decipher common colistin resistance mechanisms in Klebsiella pneumoniae isolates from animals. In total, 276 veterinary K. pneumoniae isolates, derived from companion animals or livestock, and 12 isolates from human patients were included for comparison. Six out of 276 veterinary isolates were colistin resistant (2.2%). Human isolates belonging to high-risk clonal lineages (e.g., ST15, ST101, ST258), displayed multidrug-resistant phenotypes and harboured many resistance genes compared to the veterinary isolates. However, the common colistin resistance mechanism in both human and animal K. pneumoniae isolates were diverse alterations of MgrB, a critical regulator of lipid A modification. Additionally, deleterious variations of lipopolysaccharide (LPS)-associated proteins (e.g., PmrB P95L, PmrE P89L, LpxB A152T) were identified. Phylogenetic analysis and mutation patterns in genes encoding LPS-associated proteins indicated that colistin resistance mechanisms developed independently in human and animal isolates. Since only very few antibiotics remain to treat infections with MDR bacteria, it is important to further analyse resistance mechanisms and the dissemination within different isolates and sources. Full article

(This article belongs to the Special Issue The Genetic Differences among Colistin-Resistant Enterobacterales, Acinetobacter spp. and Pseudomonas aeruginosa)

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2 pages, 1078 KiB

Open AccessCorrection

Correction: Wang et al. Diverse Metabolites and Pharmacological Effects from the Basidiomycetes Inonotus hispidus. Antibiotics 2022, 11, 1097

by Zhen-xin Wang, Xi-long Feng, Chengwei Liu, Jin-ming Gao and Jianzhao Qi

Antibiotics 2022, 11(11), 1671; https://doi.org/10.3390/antibiotics11111671 - 21 Nov 2022

Cited by 3 | Viewed by 767

Abstract

In the original publication, there were publisher errors in the names of authors Zhen-xin Wang, Xi-long Feng and Jin-ming Gao and affiliation (1) of the first, second, fourth and fifth authors (name of the Key Laboratory and city) [...] Full article

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20 pages, 2487 KiB

Open AccessArticle

Characterisation of Non-Carbapenemase-Producing Carbapenem-Resistant Klebsiella pneumoniae Based on Their Clinical and Molecular Profile in Malaysia

by Yee Qing Lee, Sasheela Sri La Sri Ponnampalavanar, Chun Wie Chong, Rina Karunakaran, Kumutha Malar Vellasamy, Kartini Abdul Jabar, Zhi Xian Kong, Min Yi Lau and Cindy Shuan Ju Teh

Antibiotics 2022, 11(11), 1670; https://doi.org/10.3390/antibiotics11111670 - 21 Nov 2022

Cited by 4 | Viewed by 1768

Abstract

Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia [...] Read more.

Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia from January 2013 to October 2019. During the study period, 54 NC-CRKP-infected/colonised patients’ isolates were obtained. Clinical parameters were assessed in 52 patients. The all-cause in-hospital mortality rate among NC-CRKP patients was 46.2% (24/52). Twenty-three (44.2%) patients were infected, while others were colonised. Based on the Charlson Comorbidity Index (CCI) score, 92.3% (48/52) of the infected/colonised patients had a score of ≥ 1. Resistance genes found among the 54 NC-CRKP isolates were bla_TEM, bla_SHV, bla_CTX-M, bla_OXA, and bla_DHA. Porin loss was detected in 25/54 (46.3%) strains. None of the isolated strains conferred carbapenem resistance through the efflux pumps system. In conclusion, only 25/54 (46.3%) NC-CRKP conferred carbapenem resistance through a combination of porin loss and the acquisition of non-carbapenemase resistance mechanisms. The carbapenem resistance mechanisms for the remaining strains (53.7%) should be further investigated as rapid identification and distinction of the NC-CRKP mechanisms enable optimal treatment and infection control efforts. Full article

(This article belongs to the Special Issue Antibiotics Resistance in Gram-Negative Bacteria)

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11 pages, 1145 KiB

Open AccessArticle

International Survey of Practice for Prophylactic Systemic Antibiotic Therapy in Hip and Knee Arthroplasty

by Thomas Parsons, Jonathan French, Takeshi Oshima, Francisco Figueroa, Thomas Neri, Antonio Klasan and Sven Putnis

Antibiotics 2022, 11(11), 1669; https://doi.org/10.3390/antibiotics11111669 - 21 Nov 2022

Cited by 3 | Viewed by 1357

Abstract

(1) Background: Prophylactic systemic antibiotics are acknowledged to be an important part of mitigating prosthetic joint infections. Controversy persists regarding optimal antibiotic regimes. We sought to evaluate current international antibiotics guidelines for total joint arthroplasty (TJA) of the hip and knee. (2) Methods: [...] Read more.

(1) Background: Prophylactic systemic antibiotics are acknowledged to be an important part of mitigating prosthetic joint infections. Controversy persists regarding optimal antibiotic regimes. We sought to evaluate current international antibiotics guidelines for total joint arthroplasty (TJA) of the hip and knee. (2) Methods: 42 arthroplasty societies across 6 continents were contacted and their published literature reviewed. (3) Results: 17 societies had guidelines; of which 11 recommended an antibiotic agent or antibiotic class (10—cephalosporin; 1—cloxacillin); 15 recommended antibiotic infusion within an hour of incision and 10 advised for post-operative doses (8—up to 24 h; 1—up to 36 h; 1—up to 48 h). (4) Conclusions: Prophylactic antibiotic guidelines for TJA are often absent or heterogenous in their advice. Full article

(This article belongs to the Special Issue Antibiotics Prophylaxis for Knee Arthroplasty: Benefits and Problems)

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12 pages, 1421 KiB

Open AccessArticle

Genome-Wide Analysis of Innate Susceptibility Mechanisms of Escherichia coli to Colistin

by Muhammad Yasir, A. Keith Turner, Sarah Bastkowski, Martin Lott, Emma R. Holden, Andrea Telatin, Andrew J. Page, Mark A. Webber and Ian G. Charles

Antibiotics 2022, 11(11), 1668; https://doi.org/10.3390/antibiotics11111668 - 21 Nov 2022

Viewed by 1571

Abstract

Colistin is an antibiotic that has seen increasing clinical use for the treatment of human infections caused by Gram-negative pathogens, particularly due to the emergence of multidrug-resistant pathogens. Colistin resistance is also a growing problem and typically results from alterations to lipopolysaccharides mediated [...] Read more.

Colistin is an antibiotic that has seen increasing clinical use for the treatment of human infections caused by Gram-negative pathogens, particularly due to the emergence of multidrug-resistant pathogens. Colistin resistance is also a growing problem and typically results from alterations to lipopolysaccharides mediated by phosphoethanolamine (pETn) transferase enzymes which can be encoded on the chromosome, or plasmids. In this study, we used ‘TraDIS-Xpress’ (Transposon Directed Insertion site Sequencing with expression), where a high-density transposon mutant library including outward facing promoters in Escherichia coli BW25113 identified genes involved in colistin susceptibility. We examined the genome-wide response of E. coli following exposure to a range of concentrations of colistin. Our TraDIS-Xpress screen confirmed the importance of overexpression of the two-component system basSR (which regulates pETn transferases) but also identified a wider range of genes important for survival in the presence of colistin, including genes encoding membrane associated proteins, DNA repair machinery, various transporters, RNA helicases, general stress response genes, fimbriae and phosphonate metabolism. Validation experiments supported a role in colistin susceptibility for novel candidate genes tested. TraDIS-Xpress is a powerful tool that expands our understanding of the wider landscape of genes involved in response to colistin susceptibility mechanisms. Full article

(This article belongs to the Special Issue Mechanisms of Bacterial Antibiotic Resistance and Interventions to Prevent Their Spread)

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11 pages, 15063 KiB

Open AccessArticle

Colonization with Carbapenem-Resistant Enterobacteriaceae Contributes to Unfavorable Outcomes in End-Stage Liver Disease Patients

by Guofen Zeng, Yihua Pang, Jiaxin Zheng, Chuyue Zhuo, Yingyi Guo, Jiayin Liang, Xiaojie Li, Ziying Lei, Jianyun Zhu, Lejia Xu, Zhiliang Gao, Chao Zhuo and Jing Liu

Antibiotics 2022, 11(11), 1667; https://doi.org/10.3390/antibiotics11111667 - 20 Nov 2022

Cited by 1 | Viewed by 1264

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) are the highest priority pathogens of the World Health Organization, and their prevalence in end-stage liver disease (ESLD) patients is increasing. CRE colonization is an independent risk factor for CRE infections. We aimed to assess risk factors and explore the [...] Read more.

Carbapenem-resistant Enterobacteriaceae (CRE) are the highest priority pathogens of the World Health Organization, and their prevalence in end-stage liver disease (ESLD) patients is increasing. CRE colonization is an independent risk factor for CRE infections. We aimed to assess risk factors and explore the relationship between CRE colonization, infection, and prognosis in patients with ESLD. A total of 311 patients with ESLD were screened for CRE colonization by fecal swabs from October 2020 to January 2022. Antimicrobial susceptibility was tested using the broth microdilution method. Carbapenem resistance genes, multilocus sequence type, and capsular serotype were analyzed by polymerase chain reaction (PCR). Seventeen CRE strains were detected, among which the most common was Klebsiella pneumoniae. The CRE colonization rate was 5.5%. Artificial liver support was an independent risk factor for CRE colonization. Compared to the non-CRE colonization group, the colonization group had a higher incidence of CRE infection and a worse prognosis. Furthermore, these strains were not closely related, and all were sensitive to polymyxin and tigecycline. There was a high colonization rate in ESLD patients, and colonization strains were highly diverse. CRE colonization deserves attention in these patients, especially when treated with artificial liver support. Full article

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13 pages, 1134 KiB

Open AccessArticle

Virulence Determinants and Methicillin Resistance in Biofilm-Forming Staphylococcus aureus from Various Food Sources in Bangladesh

by Fatimah Muhammad Ballah, Md. Saiful Islam, Md. Liton Rana, Md. Ashek Ullah, Farhana Binte Ferdous, Fahim Haque Neloy, Samina Ievy, Md. Abdus Sobur, AMM Taufiquer Rahman, Mst. Minara Khatun, Marzia Rahman and Md. Tanvir Rahman

Antibiotics 2022, 11(11), 1666; https://doi.org/10.3390/antibiotics11111666 - 20 Nov 2022

Cited by 8 | Viewed by 2791

Abstract

The eradication of staphylococcal infections has become more difficult due to the development of antibiotic resistance and virulence in biofilm-forming Staphylococcus aureus. The presence of the life-threatening zoonotic pathogen, methicillin-resistant S. aureus (MRSA), in foods indicates a public health issue. This study, [...] Read more.

The eradication of staphylococcal infections has become more difficult due to the development of antibiotic resistance and virulence in biofilm-forming Staphylococcus aureus. The presence of the life-threatening zoonotic pathogen, methicillin-resistant S. aureus (MRSA), in foods indicates a public health issue. This study, therefore, aimed to determine virulence factors and methicillin resistance in biofilm-forming S. aureus isolates from different foods and food handlers. A total of 100 PCR-positive S. aureus isolates (97 biofilm formers and three non-biofilm formers) were screened using the disk diffusion method and PCR assay. By PCR, genes encoding virulence factors, e.g., enterotoxin (sea, 30%, 95% CI: 21.90–39.59%), toxic shock syndrome toxin (tst, 20%, 95% CI: 13.34–28.88%), and Panton–Valentine leukocidin toxin (PVL, 15%, 95% CI: 9.31–23.28%), were detected in the S. aureus isolates. By the disk diffusion method, 100% (95% CI: 96.30–100.00%) of S. aureus isolates were phenotypically MRSA in nature, showing 100% resistance to oxacillin and cefoxitin. Moreover, the methicillin-resistant gene mecA was found in 61 (61%, 95% CI: 51.20–69.98%) MRSA isolates. Furthermore, all the S. aureus isolates were phenotypically resistant to ampicillin and penicillin, 30% to erythromycin, and 11% to gentamycin. Among them, 51% (95% CI: 41.35–60.58%) of S. aureus isolates were phenotypically multidrug-resistant in nature, and the multiple antibiotic resistance index varied from 0.33 to 0.55. Genes encoding resistance to beta-lactams (blaZ, 100%, 95% CI: 96.30–100.00%) and tetracyclines (tetA and tetC, 3%, 95% CI: 0.82–8.45%) were found positive in the S. aureus isolates. Genes encoding virulence determinants and MRSA were significantly (p < 0.05) higher in strong biofilm-forming S. aureus than in moderate and non-biofilm-forming isolates. To our knowledge, this is the first study in Bangladesh to incorporate preliminary data on the occurrence of virulence determinants and methicillin resistance, including resistance to clinically important antibiotics, in biofilm-forming S. aureus isolates from different foods and food handlers in Bangladesh, emphasizing a potential threat to human health. Full article

(This article belongs to the Special Issue Staphylococci Antimicrobial Tolerance, Persistent Infection and Antimicrobial Strategies)

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14 pages, 1377 KiB

Open AccessArticle

Octenidine’s Efficacy: A Matter of Interpretation or the Influence of Experimental Setups?

by Djenana Vejzovic, Azra Iftic, Ayse Ön, Enrico F. Semeraro and Nermina Malanovic

Antibiotics 2022, 11(11), 1665; https://doi.org/10.3390/antibiotics11111665 - 19 Nov 2022

Cited by 1 | Viewed by 1670

Abstract

With its broad antimicrobial spectrum and non-specific mode of action via membrane disruption, any resistance to octenidine (OCT) seems unlikely and has not been observed in clinical settings so far. In this study, we aimed to investigate the efficacy of OCT against Escherichia [...] Read more.

With its broad antimicrobial spectrum and non-specific mode of action via membrane disruption, any resistance to octenidine (OCT) seems unlikely and has not been observed in clinical settings so far. In this study, we aimed to investigate the efficacy of OCT against Escherichia coli and mutants lacking specific lipid head groups which, due to altered membrane properties, might be the root cause for resistance development of membrane-active compounds. Furthermore, we aimed to test its efficacy under different experimental conditions including different solvents for OCT, bacterial concentration and methods for analysis. Our primary goal was to estimate how many OCT molecules are needed to kill one bacterium. We performed susceptibility assays by observing bacterial growth behavior, using a Bioscreen in an analogous manner for every condition. The growth curves were recorded for 20 h at 420–580 nm in presence of different OCT concentrations and were used to assess the inhibitory concentrations (IC_100%) for OCT. Bacterial concentrations given in cell numbers were determined, followed by Bioscreen measurement by manual colony counting on agar plates and QUANTOM^TM cell staining. This indicated a significant variance between both methods, which influenced IC_100% of OCT, especially when used at low doses. The binding capacity of OCT to E. coli was investigated by measuring UV-absorbance of OCT exposed to bacteria and a common thermodynamic framework based on Bioscreen measurements. Results showed that OCT’s antimicrobial activity in E. coli is not affected by changes at the membrane level but strongly dependent on experimental settings in respect to solvents and applied bacterial counts. More OCT was required when the active was dissolved in phosphate or Hepes buffers instead of water and when higher bacterial concentration was used. Furthermore, binding studies revealed that 10⁷–10⁸ OCT molecules bind to bacteria, which is necessary for the saturation of the bacterial surface to initiate the killing cascade. Our results clearly demonstrate that in vitro data, depending on the applied materials and the methods for determination of IC_100%, can easily be misinterpreted as reduced bacterial susceptibility towards OCT. Full article

(This article belongs to the Special Issue Multidrug Resistance as Trigger for the Development of Novel Antimicrobials)

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15 pages, 821 KiB

Open AccessArticle

Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment

by Olivier Pajot, Karim Lakhal, Jérome Lambert, Antoine Gros, Cédric Bruel, Thierry Boulain, Denis Garot, Vincent Das, Jean François Timsit, Charles Cerf, Bertrand Souweine, Cendrine Chaffaut, Hervé Mentec, Jean Ralph Zahar, Jean Paul Mira and Vincent Jullien

Antibiotics 2022, 11(11), 1664; https://doi.org/10.3390/antibiotics11111664 - 19 Nov 2022

Viewed by 2375

Abstract

Background: Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target [...] Read more.

Background: Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target attainment considering both antibiotics serum concentrations and measured MICs in these patients. Method: A multicentric prospective open-label trial conducted in 11 French ICUs involved patients with Gram-negative bacilli (GNB) ventilator-associated pneumonia (VAP) confirmed by quantitative cultures. Results: We included 117 patients. Causative GNBs were P. aeruginosa (40%), Enterobacter spp. (23%), E. coli (20%), and Klebsiella spp. (16%). Hence, 117 (100%) patients received β-lactams, 65 (58%) aminoglycosides, and two (1.5%) fluoroquinolones. For β-lactams, 83% of the patients achieved a C_min/MIC > 1 and 70% had a C_min/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m²), 70.4% of the patients achieved a C_min/MIC ratio > 1 versus 91% otherwise (p = 0.041), and 52% achieved a C_min/MIC ratio > 4 versus 81% (p = 0.018). For aminoglycosides, 94% of the patients had a C_max/MIC ratio > 8. Neither β-lactams nor aminoglycosides PK/PD parameters were associated clinical outcomes, but our data suggest a correlation between β-lactams C_min/MIC and microbiological success. Conclusion: In our ICU patients treated for GNB VAP, using recommended antibiotic dosage led in most cases to PK/PD targets attainment for aminoglycosides and β-lactams. High creatinine clearance should encourage clinicians to focus on PK/PD issues. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jean-Francois Timsit—Outstanding Contributions in the Fields of Hospital-Acquired Infections and Optimization of Anti-infective Treatments)

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13 pages, 2930 KiB

Open AccessArticle

Investigating the Role of Antibiotics on Induction, Inhibition and Eradication of Biofilms of Poultry Associated Escherichia coli Isolated from Retail Chicken Meat

by Aisha Noreen, Hamid Masood, Jaweria Zaib, Zara Rafaque, Areeta Fatima, Hira Shabbir, Javaria Alam, Aisha Habib, Saba Noor, Kinza Dil and Javid Iqbal Dasti

Antibiotics 2022, 11(11), 1663; https://doi.org/10.3390/antibiotics11111663 - 19 Nov 2022

Cited by 1 | Viewed by 2056

Abstract

Background: Widespread use of antibiotics as growth promoters and prophylactic agents has dramatic consequences for the development of antibiotic resistance. In this study, we investigated effects of selected antibiotics on bacterial biofilms and performed extensive antibiotic and VF profiling of poultry-meat associated E. [...] Read more.

Background: Widespread use of antibiotics as growth promoters and prophylactic agents has dramatic consequences for the development of antibiotic resistance. In this study, we investigated effects of selected antibiotics on bacterial biofilms and performed extensive antibiotic and VF profiling of poultry-meat associated E. coli strains. Methods: Antibiotic susceptibility was performed by a disc diffusion method, followed by molecular screening of resistance and virulence determinants. Further biofilm formation assays, MIC-p, MIC-b, MBIC and MBEC, were performed using standard tissue culture plate method. Results: In total, 83 (75%) samples were confirmed as E. coli from poultry sources, 26 different antibiotics were tested, and maximum numbers of the isolates were resistant to lincomycin (100%), while the least resistance was seen against cefotaxime (1%) and polymyxin B (1%). Overall, 48% of the isolates were ESBL producers and 40% showed carbapenemase activity; important virulence genes were detected in following percentages: fimH32 (39%), papC21 (25%), iutA34 (41%), kpsMT-II23 (28%), papEF9 (11%), papGII22 (27%) and fyuA13 (16%). Colistin showed remarkable anti-biofilm activity, while at sub-MIC levels, gentamicin, ceftriaxone and enrofloxin significantly (p < 0.01) inhibited the biofilms. A strong induction of bacterial biofilm, after exposure to sub-minimal levels of colistin clearly indicates risk of bacterial overgrowth in a farm environment, while use of colistin aggravates the risk of emergence of colistin resistant Enterobacteriaceae, a highly undesirable public health scenario. Full article

(This article belongs to the Special Issue Antibacterial Resistance and Novel Strategies to Eradicate Bacterial Biofilms, 2nd Volume)

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13 pages, 1268 KiB

Open AccessArticle

Targeting SAM-I Riboswitch Using Antisense Oligonucleotide Technology for Inhibiting the Growth of Staphylococcus aureus and Listeria monocytogenes

by Martina Traykovska and Robert Penchovsky

Antibiotics 2022, 11(11), 1662; https://doi.org/10.3390/antibiotics11111662 - 19 Nov 2022

Cited by 8 | Viewed by 1638

Abstract

With the discovery of antibiotics, a productive period of antibacterial drug innovation and application in healthcare systems and agriculture resulted in saving millions of lives. Unfortunately, the misusage of antibiotics led to the emergence of many resistant pathogenic strains. Some riboswitches have risen [...] Read more.

With the discovery of antibiotics, a productive period of antibacterial drug innovation and application in healthcare systems and agriculture resulted in saving millions of lives. Unfortunately, the misusage of antibiotics led to the emergence of many resistant pathogenic strains. Some riboswitches have risen as promising targets for developing antibacterial drugs. Here, we describe the design and applications of the chimeric antisense oligonucleotide (ASO) as a novel antibacterial agent. The pVEC-ASO-1 consists of a cell-penetrating oligopeptide known as pVEC attached to an oligonucleotide part with modifications of the first and the second generations. This combination of modifications enables specific mRNA degradation under multiple turnover conditions via RNase H. The pVEC-ASO targets the S-adenosyl methionine (SAM)-I riboswitch found in the genome of many Gram-positive bacteria. The SAM-I riboswitch controls not only the biosynthesis but also the transport of SAM. We have established an antibiotic dosage of 700 nM (4.5 µg/mL) of pVEC-ASO that inhibits 80% of the growth of Staphylococcus aureus and Listeria monocytogenes. The pVEC-ASO-1 does not show any toxicity in the human cell line at MIC80’s concentration. We have proven that the SAM-I riboswitch is a suitable target for antibacterial drug development based on ASO. The approach is rational and easily adapted to other bacterial RNA targets. Full article

(This article belongs to the Special Issue Finding Innovative Targets and Mechanisms While Discovering Novel Antimicrobial Agents)

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13 pages, 820 KiB

Open AccessArticle

Association of Physcion and Chitosan Can Efficiently Control Powdery Mildew in Rosa roxburghii

by Cheng Zhang, Jiaohong Li, Yue Su and Xiaomao Wu

Antibiotics 2022, 11(11), 1661; https://doi.org/10.3390/antibiotics11111661 - 19 Nov 2022

Cited by 9 | Viewed by 1317

Abstract

Powdery mildew is an extremely serious disease of all Rosa roxburghii production regions in China and frequently causes 30~40% of economic losses. Natural products are considered excellent alternatives to chemical fungicides. In this work, we investigated the efficacy of physcion used together with [...] Read more.

Powdery mildew is an extremely serious disease of all Rosa roxburghii production regions in China and frequently causes 30~40% of economic losses. Natural products are considered excellent alternatives to chemical fungicides. In this work, we investigated the efficacy of physcion used together with chitosan controls R. roxburghii powdery mildew and impacts its resistance, growth, yield, and quality. The results reveal that the foliar application of 12.5 mg L⁻¹ 0.5% physcion aqueous solutions (AS) + 250 mg L⁻¹ chitosan efficiently controlled powdery mildew with the efficacies of 92.65% and 90.68% after 7 d and 14 d, respectively, which conspicuously (p < 0.05) higher than 83.62% and 80.43% of 25 mg L⁻¹ 0.5% physcion AS, as well as 70.75% and 77.80% of 500 mg L⁻¹ chitosan. Meanwhile, this association prominently ameliorated the resistant and photosynthetic capabilities of R. roxburghii. Simultaneously, this association was more efficient than physcion or chitosan alone for ameliorating the yield and quality of R. roxburghii. This work emphasizes that the association of physcion and chitosan can be nominated as a natural, efficient and environmental-friendly alternative ingredient in controlling R. roxburghii powdery mildew and ameliorating its resistant, photosynthesis, yield, and quality. Full article

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11 pages, 994 KiB

Open AccessArticle

Defining Exposure Predictors of Meropenem That Are Associated with Improved Survival for Severe Bacterial Infection: A Preclinical PK/PD Study in Sepsis Rat Model

by Yan Wang, Lanyu Liu, Qiping Wu, Qiufen Yin and Feifan Xie

Antibiotics 2022, 11(11), 1660; https://doi.org/10.3390/antibiotics11111660 - 19 Nov 2022

Cited by 2 | Viewed by 1453

Abstract

Background: The pharmacokinetic/pharmacodynamic (PK/PD) index of carbapenems that best correlates with in vivo antimicrobial activity is percent time of dosing interval in which free drug concentration remains above MIC (%fT > MIC), while the magnitudes of the PK/PD index of [...] Read more.

Background: The pharmacokinetic/pharmacodynamic (PK/PD) index of carbapenems that best correlates with in vivo antimicrobial activity is percent time of dosing interval in which free drug concentration remains above MIC (%fT > MIC), while the magnitudes of the PK/PD index of carbapenems remains undefined in critically ill sepsis patients. Methods: A sepsis rat model was first developed by comparing the survival outcomes after intraperitoneal injection of different inoculum size (1–10 × 10⁷ CFU) of Pseudomonas aeruginosa ATCC9027 (MIC = 0.125 mg/L) in neutropenic rats. The PK characteristics of the model drug meropenem in the developed sepsis rat model was then evaluated, and PK modeling and simulation was applied to design meropenem dosing regimens attaining various PD targets (40%fT > MIC, 100%fT > MIC, and 100%fT > 4 × MIC). The microbiological response and survival outcomes for different meropenem treatment regimens were investigated in the rat sepsis model (n = 12 for each group). Results: The optimal inoculum for the rat sepsis model was 1 × 10⁷ CFU of Pseudomonas aeruginosa ATCC9027. A one-compartment model with first-order absorption best described the PK of meropenem in sepsis rats. Pronounced survival prolongation and lower hazard risk were observed in the treatment groups of 50 or 75 mg/kg/q2.4h (100%fT > MIC) and 75 mg/kg/q2h (100%fT > 4 × MIC) compared to the 75 mg/kg/q6h (40%fT > MIC) group, while meropenem groups with PD targets of 100%fT > MIC and 100%fT > 4 × MIC showed comparable survival curves. Microbiological response for different PD targets is inconclusive due to irregular bacterial counts in blood samples. Conclusions: The PD target of 40%fT > MIC is suboptimal for sepsis rats, and the aggressive 100%fT > 4 × MIC target does not provide a survival benefit against the target of 100%fT > MIC. Full article

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

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18 pages, 2312 KiB

Open AccessArticle

Design of a Bacteriophage Cocktail Active against Shigella Species and Testing of Its Therapeutic Potential in Galleria mellonella

by Andrey A. Filippov, Wanwen Su, Kirill V. Sergueev, Richard T. Kevorkian, Erik C. Snesrud, Apichai Srijan, Yunxiu He, Derrick E. Fouts, Woradee Lurchachaiwong, Patrick T. McGann, Damon W. Ellison, Brett E. Swierczewski and Mikeljon P. Nikolich

Antibiotics 2022, 11(11), 1659; https://doi.org/10.3390/antibiotics11111659 - 19 Nov 2022

Cited by 1 | Viewed by 1955

Abstract

Shigellosis is a leading global cause of diarrheal disease and travelers’ diarrhea now being complicated by the dissemination of antibiotic resistance, necessitating the development of alternative antibacterials such as therapeutic bacteriophages (phages). Phages with lytic activity against Shigella strains were isolated from sewage. [...] Read more.

Shigellosis is a leading global cause of diarrheal disease and travelers’ diarrhea now being complicated by the dissemination of antibiotic resistance, necessitating the development of alternative antibacterials such as therapeutic bacteriophages (phages). Phages with lytic activity against Shigella strains were isolated from sewage. The genomes of 32 phages were sequenced, and based on genomic comparisons belong to seven taxonomic genera: Teetrevirus, Teseptimavirus, Kayfunavirus, Tequatrovirus, Mooglevirus, Mosigvirus and Hanrivervirus. Phage host ranges were determined with a diverse panel of 95 clinical isolates of Shigella from Southeast Asia and other geographic regions, representing different species and serotypes. Three-phage mixtures were designed, with one possessing lytic activity against 89% of the strain panel. This cocktail exhibited lytic activity against 100% of S. sonnei isolates, 97.2% of S. flexneri (multiple serotypes) and 100% of S. dysenteriae serotypes 1 and 2. Another 3-phage cocktail composed of two myophages and one podophage showed both a broad host range and the ability to completely sterilize liquid culture of a model virulent strain S. flexneri 2457T. In a Galleria mellonella model of lethal infection with S. flexneri 2457T, this 3-phage cocktail provided a significant increase in survival. Full article

(This article belongs to the Special Issue Bacteriophages and Other Alternative Antimicrobials to Combat Multidrug Resistance)

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19 pages, 2986 KiB

Open AccessReview

Bioactive Peptides against Human Apicomplexan Parasites

by Norma Rivera-Fernández, Jhony Anacleto-Santos, Brenda Casarrubias-Tabarez, Teresa de Jesús López-Pérez, Marcela Rojas-Lemus, Nelly López-Valdez and Teresa I. Fortoul

Antibiotics 2022, 11(11), 1658; https://doi.org/10.3390/antibiotics11111658 - 19 Nov 2022

Cited by 1 | Viewed by 2279

Abstract

Apicomplexan parasites are the causal agents of different medically important diseases, such as toxoplasmosis, cryptosporidiosis, and malaria. Toxoplasmosis is considered a neglected parasitosis, even though it can cause severe cerebral complications and death in immunocompromised patients, including children and pregnant women. Drugs against [...] Read more.

Apicomplexan parasites are the causal agents of different medically important diseases, such as toxoplasmosis, cryptosporidiosis, and malaria. Toxoplasmosis is considered a neglected parasitosis, even though it can cause severe cerebral complications and death in immunocompromised patients, including children and pregnant women. Drugs against Toxoplasma gondii, the etiological agent of toxoplasmosis, are highly toxic and lack efficacy in eradicating tissue cysts, promoting the establishment of latent infection and acute relapsing disease. Cryptosporidiosis has been recognized as the most frequent waterborne parasitosis in US outbreaks; anti-cryptosporidium drug discovery still faces a major obstacle: drugs that can act on the epicellular parasite. Severe malaria is most commonly caused by the progression of infection with Plasmodium falciparum. In recent years, great progress has been made in the field of antimalarial drugs and vaccines, although the resistance of P. falciparum to artemisinin has recently gained a foothold in Africa. As seen, the search for new drugs against these parasites remains a challenge. Peptide-based drugs seem to be attractive alternative therapeutic agents recently recognized by the pharmaceutical industry, as they can kill different infectious agents and modulate the immune response. A review of the experimental effects of bioactive peptides on these parasites follows, along with comments. In addition, some biological and metabolomic generalities of the parasites are reviewed to elucidate peptide mechanisms of action on Apicomplexan targets. Full article

(This article belongs to the Special Issue Computational Approaches in Discovery & Design of Antimicrobial Peptides)

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12 pages, 2707 KiB

Open AccessArticle

Comparison of Fitness Cost, Stability, and Conjugation Frequencies of tet(X4)-Positive Plasmids in Chicken and Pig Escherichia coli

by Ziyi Liu, Huiru Zhang, Xia Xiao, Yuan Liu, Ruichao Li and Zhiqiang Wang

Antibiotics 2022, 11(11), 1657; https://doi.org/10.3390/antibiotics11111657 - 19 Nov 2022

Cited by 3 | Viewed by 1286

Abstract

The large-scale epidemic of the tet(X4) gene in the livestock and poultry industry is threatening public health; however, there is still a lack of comparative studies on tet(X4)-bearing plasmids in chicken and pig Escherichia coli. To evaluate the prevalence trend [...] Read more.

The large-scale epidemic of the tet(X4) gene in the livestock and poultry industry is threatening public health; however, there is still a lack of comparative studies on tet(X4)-bearing plasmids in chicken and pig Escherichia coli. To evaluate the prevalence trend of tet(X4)-bearing plasmids and the factors influencing their persistence in the livestock and poultry industry, we examined the fitness cost, stability under tetracyclines pressure, and conjugation frequencies at various temperatures of six tet(X4)-bearing plasmids in four representative pig E. coli isolates and chicken E. coli isolates. Compared with pig E. coli, the plasmid in chicken E. coli showed lower fitness cost, and stronger ability to promote bacterial biofilm formation and motility. Meanwhile, the presence of tetracycline may favor the stability of tet(X4)-bearing plasmids, which was more common in chicken E. coli. Furthermore, the optimal temperature for IncX1 tet(X4)-bearing plasmid conjugation was 42 °C, and its conjugation frequency in chicken E. coli was higher than that in pig E. coli, whereas the optimal temperature for IncFII tet(X4)-bearing plasmid conjugation was 37 °C and it performed better in pig E. coli, suggesting the predominant plasmid types circulating in chicken E. coli and pig E. coli may be distinct. Collectively, although tet(X4) currently appears to be more prevalent in pig E. coli, this is probably independent of the fitness cost caused by tet(X4)-plasmids. To curb the future spread of the tet(X4) gene, reduced tetracyclines usage and tailored interventions should be applied in different breeding industries. Full article

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

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9 pages, 478 KiB

Open AccessArticle

Limited Therapeutic Options in Mexico for the Treatment of Urinary Tract Infections

by Guadalupe Miranda-Novales, Karen Flores-Moreno, Yolanda López-Vidal, Samuel Ponce de León-Rosales and PUCRA Network Members

Antibiotics 2022, 11(11), 1656; https://doi.org/10.3390/antibiotics11111656 - 18 Nov 2022

Cited by 2 | Viewed by 3701

Abstract

The rise in antimicrobial resistance (AMR) has complicated the management of urinary tract infections (UTIs). The objective of this study was to evaluate the antimicrobial susceptibility patterns of Escherichia coli and Klebsiella pneumoniae. Design: prospective observational study. Bacteria were classified as susceptible or [...] Read more.

The rise in antimicrobial resistance (AMR) has complicated the management of urinary tract infections (UTIs). The objective of this study was to evaluate the antimicrobial susceptibility patterns of Escherichia coli and Klebsiella pneumoniae. Design: prospective observational study. Bacteria were classified as susceptible or resistant to ampicillin-sulbactam, amikacin, gentamicin, ciprofloxacin, norfloxacin, nitrofurantoin, trimethoprim-sulfamethoxazole (TMP/SMZ), ertapenem, meropenem, and fosfomycin. The sensitivity to fosfomycin and chloramphenicol was evaluated by the disk diffusion method. Statistical analysis: the chi-square test and Fisher’s exact test were used to compare differences between categories. A p value < 0.05 was considered statistically significant. Isolates were collected from January 2019 to November 2020 from 21 hospitals and laboratories. A total of 238 isolates were received: a total of 156 E. coli isolates and 82 K. pneumoniae isolates. The majority were community-acquired infections (64.1%). Resistance was >20% for beta-lactams, aminoglycosides, fluoroquinolones, and TMP/SMZ. For E. coli isolates, resistance was <20% for amikacin, fosfomycin, and nitrofurantoin; for K. pneumoniae, amikacin, fosfomycin, chloramphenicol, and norfloxacin. All were susceptible to carbapenems. K. pneumoniae isolates registered a higher proportion of extensively drug-resistant bacteria in comparison with E. coli (p = 0.0004). In total, multidrug-resistant bacteria represented 61% of all isolates. Isolates demonstrated high resistance to beta-lactams, fluoro-quinolones, and TMP/SMZ. Full article

(This article belongs to the Special Issue Resistant Bacteria: Molecular Studies and Antimicrobial Resistance)

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14 pages, 3265 KiB

Open AccessArticle

Antibacterial and Anti-Biofilm Activity of Pyrones from a Pseudomonas mosselii Strain

by Xueling Liu, Yali Wang, Diana A. Zaleta-Pinet, Robert P. Borris and Benjamin R. Clark

Antibiotics 2022, 11(11), 1655; https://doi.org/10.3390/antibiotics11111655 - 18 Nov 2022

Cited by 1 | Viewed by 1587

Abstract

The emergence of drug resistant microbes over recent decades represents one of the greatest threats to human health; the resilience of many of these organisms can be attributed to their ability to produce biofilms. Natural products have played a crucial role in drug [...] Read more.

The emergence of drug resistant microbes over recent decades represents one of the greatest threats to human health; the resilience of many of these organisms can be attributed to their ability to produce biofilms. Natural products have played a crucial role in drug discovery, with microbial natural products in particular proving a rich and diverse source of antimicrobial agents. During antimicrobial activity screening, the strain Pseudomonas mosselii P33 was found to inhibit the growth of multiple pathogens. Following chemical investigation of this strain, pseudopyronines A-C were isolated as the main active principles, with all three pseudopyronines showing outstanding activity against Staphylococcus aureus. The analogue pseudopyronine C, which has not been well-characterized previously, displayed sub-micromolar activity against S. aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. Moreover, the inhibitory abilities of the pseudopyronines against the biofilms of S. aureus were further studied. The results indicated all three pseudopyronines could directly reduce the growth of biofilm in both adhesion stage and maturation stage, displaying significant activity at micromolar concentrations. Full article

(This article belongs to the Special Issue Antimicrobial Agents that Interfere with Bacterial and Fungal Biofilms)

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21 pages, 3546 KiB

Open AccessArticle

Experimental and In Silico Evaluation of New Heteroaryl Benzothiazole Derivatives as Antimicrobial Agents

by Alexander Zubenko, Victor Kartsev, Anthi Petrou, Athina Geronikaki, Marija Ivanov, Jasmina Glamočlija, Marina Soković, Lyudmila Divaeva, Anatolii Morkovnik and Alexander Klimenko

Antibiotics 2022, 11(11), 1654; https://doi.org/10.3390/antibiotics11111654 - 18 Nov 2022

Cited by 2 | Viewed by 1538

Abstract

In this manuscript, we describe the design, preparation, and studies of antimicrobial activity of a series of novel heteroarylated benzothiazoles. A molecular hybridization approach was used for the designing compounds. The in vitro evaluation exposed that these compounds showed moderate antibacterial activity. Compound [...] Read more.

In this manuscript, we describe the design, preparation, and studies of antimicrobial activity of a series of novel heteroarylated benzothiazoles. A molecular hybridization approach was used for the designing compounds. The in vitro evaluation exposed that these compounds showed moderate antibacterial activity. Compound 2j was found to be the most potent (MIC/MBC at 0.23–0.94 mg/mL and 0.47–1.88 mg/mL) On the other hand, compounds showed good antifungal activity (MIC/MFC at 0.06–0.47 and 0.11–0.94 mg/mL respectively) with 2d being the most active one. The docking studies revealed that inhibition of E. coli MurB and 14-lanosterol demethylase probably represent the mechanism of antibacterial and antifungal activities. Full article

(This article belongs to the Special Issue New Insights into Antimicrobial Discovery)

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28 pages, 3806 KiB

Open AccessSystematic Review

Prevalence of Multidrug-Resistant and Extended-Spectrum Beta-Lactamase-Producing Shigella Species in Asia: A Systematic Review and Meta-Analysis

by Mohd Zulkifli Salleh, Nik Mohd Noor Nik Zuraina, Khalid Hajissa, Mohamad Ikram Ilias, Kirnpal Kaur Banga Singh and Zakuan Zainy Deris

Antibiotics 2022, 11(11), 1653; https://doi.org/10.3390/antibiotics11111653 - 18 Nov 2022

Cited by 9 | Viewed by 2912

Abstract

Shigellosis remains one of the leading causes of morbidity and mortality worldwide and is the second leading cause of diarrheal mortality among all age groups. However, the global emergence of antimicrobial-resistant Shigella strains, limiting the choice of effective drugs for shigellosis, has become [...] Read more.

Shigellosis remains one of the leading causes of morbidity and mortality worldwide and is the second leading cause of diarrheal mortality among all age groups. However, the global emergence of antimicrobial-resistant Shigella strains, limiting the choice of effective drugs for shigellosis, has become the major challenge in the treatment of Shigella infections. The aim of this systematic review and meta-analysis was to provide an updated picture of the prevalence of antimicrobial-resistant Shigella species in Asia. A comprehensive and systematic search was performed on three electronic databases (PubMed, ScienceDirect and Scopus), in which 63 eligible studies published between 2010 and 2022 were identified. From our meta-analysis of proportions using a random-effects model, the overall prevalence of Shigella spp. in Asian patients was estimated to be 8.0% (95% CI: 5.5–10.5). The pooled prevalence rates of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing Shigella strains were 68.7% (95% CI: 59.9–77.5) and 23.9% (95% CI: 12.9–34.8), respectively. Concerning recommended antimicrobial drugs for Shigella, the prevalence of resistance was highest for ciprofloxacin (29.8%) and azithromycin (29.2%), followed by ceftriaxone (23.8%), in spite of their importance as first- and second-line treatments for shigellosis. In contrast, resistance to carbapenems, such as ertapenem (0.0%), imipenem (0.1%) and meropenem (0.0%), was almost non-existent among the 49 tested antibiotics. The significantly high prevalence estimation suggests that the multidrug-resistant Shigella is a pressing threat to public health worthy of careful and justified interventions. Effective antibiotic treatment strategies, which may lead to better outcomes for the control and treatment of shigellosis in Asia, are essential. Full article

(This article belongs to the Special Issue Multi-Drug Resistant Gram-Negative Infections: Molecular Epidemiology, Microbiological Diagnosis and Antimicrobial Treatment)

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21 pages, 6465 KiB

Open AccessArticle

Phytochemical Profile of the Ethanol Extract of Malvaviscus arboreus Red Flower and Investigation of the Antioxidant, Antimicrobial, and Cytotoxic Activities

by Hanaa S. S. Gazwi, Nagwa A. Shoeib, Magda E. Mahmoud, Osama I. A. Soltan, Moaz M. Hamed and Amany E. Ragab

Antibiotics 2022, 11(11), 1652; https://doi.org/10.3390/antibiotics11111652 - 18 Nov 2022

Cited by 11 | Viewed by 2135

Abstract

Flowers are rich sources of bioactive antimicrobial, antioxidant, and anticancer components. This study aimed to determine the constituents of the ethanol extract of Malvaviscus arboreus red flower (ERF) by GC-MS analysis and HPLC identification of phenolic compounds and flavonoids, in addition to the ¹ [...] Read more.

Flowers are rich sources of bioactive antimicrobial, antioxidant, and anticancer components. This study aimed to determine the constituents of the ethanol extract of Malvaviscus arboreus red flower (ERF) by GC-MS analysis and HPLC identification of phenolic compounds and flavonoids, in addition to the ¹HNMR fingerprint. The antimicrobial, antioxidant, and cytotoxic activities of the ERF were investigated. The GC-MS analysis revealed twenty-one components, while HPLC analysis revealed the presence of phenolic and flavonoid compounds. The ERF showed antifungal and antibacterial activity. The highest antibacterial activity was found against Vibrio damsela where a time-kill assay revealed a decline in the amount of viable V. damsela. For fungi, the highest activity was observed against Aspergillus terreus. Using the SRB test on HepG2, the anti-proliferative efficacy of the ERF was evaluated. Cell cycle analysis was utilized to determine autophagic cell death. The ERF prevented the proliferation of the HepG2 cell line with an IC₅₀ of 67.182 µg/µL. The extract primarily promoted apoptosis in HepG2 cells by accumulating hypodiploid cells in the sub-G0/G1 phase, increased caspase 3/7 activity, and caused considerable autophagic cell death in apoptosis-deficient cells. Finally, the observed elevation of cancer cell death indicated that ERF had substantial anticancer potential against HepG2 cells. Full article

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

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12 pages, 710 KiB

Open AccessArticle

Ecological Distribution of Virulent Multidrug-Resistant Staphylococcus aureus in Livestock, Environment, and Dairy Products

by Basma Badawy, Mahmoud Elafify, Alshimaa M. M. Farag, Samar M. Moustafa, Mohamed Z. Sayed-Ahmed, Amira A. Moawad, Abdelazeem M. Algammal, Hazem Ramadan and Mahmoud Eltholth

Antibiotics 2022, 11(11), 1651; https://doi.org/10.3390/antibiotics11111651 - 18 Nov 2022

Cited by 4 | Viewed by 2145

Abstract

Staphylococcus aureus is one of the most common causes of mastitis, leading to severe economic losses in the dairy industry. It is also zoonotic, with potential risks to public health. This study aimed to detect the occurrence of S. aureus-resistant strains isolated [...] Read more.

Staphylococcus aureus is one of the most common causes of mastitis, leading to severe economic losses in the dairy industry. It is also zoonotic, with potential risks to public health. This study aimed to detect the occurrence of S. aureus-resistant strains isolated from cattle, buffalo, their environment, milk and dairy products; and to investigate the extent of animal, ecological, and food contamination by methicillin-resistant (MRSA) or enterotoxigenic S. aureus. Samples (n = 350) were collected from four animal (two cattle and two buffalo) farms, i.e., their environment. Thirty Karish cheese samples were collected from 10 markets in Mansoura, Egypt. S. aureus was detected in 17.9%, 17.6%, and 16.7% of samples collected from cattle, buffalo and Karish cheese, respectively. About 19% of isolated S. aureus strains carried the mecA gene. The distribution of the mecA gene was high in isolates from Karish cheese (60%), followed by samples collected from buffalo (16.2%) and cattle (16%). More than 34% of isolated S. aureus strains were enterotoxigenic, and the presence of enterotoxin genes was higher in isolates from Karish cheese (80%) than those from cattle (48%) and buffalo (18.9%). The most predominant enterotoxin gene among isolated S. aureus strains was the sea gene (26.9%), followed by sec (4.5%) and sed (3%) genes. Isolated strains were resistant to clindamycin (100%), kanamycin (97%), nalidixic acid (86.6%), cefotaxime (73.1%) sulphamethazole—trimethoprim (65.6%). Meanwhile, 95.5%, 94%, 86.6% and 77.7% of S. aureus strains were sensitive to ciprofloxacin, amikacin, imipenem and both cefoxitin and gentamycin, respectively. In conclusion, the presence of enterotoxigenic- and methicillin-resistant S. aureus strains in animals, their environment, and dairy products represents a public health concern, particularly in small-scale dairy farms in Egypt. To reduce the risk of infection of livestock and humans with resistant strains, strict regulations and guidelines for antimicrobial use in such a system are urgently required. Full article

(This article belongs to the Special Issue Mastitis: Causative Agents, Drug Resistance, and Treatment Approaches)

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14 pages, 1733 KiB

Open AccessArticle

Irrigation Ponds as Sources of Antimicrobial-Resistant Bacteria in Agricultural Areas with Intensive Use of Poultry Litter

by Eliene S. Lopes, Cláudio E. T. Parente, Renata C. Picão and Lucy Seldin

Antibiotics 2022, 11(11), 1650; https://doi.org/10.3390/antibiotics11111650 - 18 Nov 2022

Cited by 1 | Viewed by 1601

Abstract

Poultry litter is widely used worldwide as an organic fertilizer in agriculture. However, poultry litter may contain high concentrations of antibiotics and/or antimicrobial-resistant bacteria (ARB), which can be mobilized through soil erosion to water bodies, contributing to the spread of antimicrobial resistance genes [...] Read more.

Poultry litter is widely used worldwide as an organic fertilizer in agriculture. However, poultry litter may contain high concentrations of antibiotics and/or antimicrobial-resistant bacteria (ARB), which can be mobilized through soil erosion to water bodies, contributing to the spread of antimicrobial resistance genes (ARGs) in the environment. To better comprehend this kind of mobilization, the bacterial communities of four ponds used for irrigation in agricultural and poultry production areas were determined in two periods of the year: at the beginning (low volume of rainfall) and at the end of the rainy season (high volume of rainfall). 16S rRNA gene sequencing revealed not only significantly different bacterial community structures and compositions among the four ponds but also between the samplings. When the DNA obtained from the water samples was PCR amplified using primers for ARGs, those encoding integrases (intI1) and resistance to sulfonamides (sul1 and sul2) and β-lactams (bla_GES, bla_TEM and bla_SHV) were detected in three ponds. Moreover, bacterial strains were isolated from CHROMagar plates supplemented with sulfamethoxazole, ceftriaxone or ciprofloxacin and identified as belonging to clinically important Enterobacteriaceae. The results presented here indicate a potential risk of spreading ARB through water resources in agricultural areas with extensive fertilization with poultry litter. Full article

(This article belongs to the Special Issue Insights into Antibiotics in Human, Animal, and Agriculture: Resistance, Determinant, and Treatment)

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12 pages, 502 KiB

Open AccessArticle

Successful Control of an Outbreak by Phenotypically Identified Extended-Spectrum Beta-Lactamase–Producing Klebsiella pneumoniae in a Neonatal Intensive Care Unit

by Elena Priante, Chiara Minotti, Cristina Contessa, Margherita Boschetto, Paola Stano, Federico Dal Bello, Ettore De Canale, Elisabetta Lolli, Vincenzo Baldo, Eugenio Baraldi and Daniele Donà

Antibiotics 2022, 11(11), 1649; https://doi.org/10.3390/antibiotics11111649 - 18 Nov 2022

Cited by 2 | Viewed by 1848

Abstract

Background: Premature newborns represent a vulnerable population, at high risk of acquiring nosocomial infections during neonatal intensive care unit (NICU) admission. Multidrug-resistant organisms represent the greatest concern due to their intrinsic virulence and the limited therapeutic options. Resistant Enterobacterales are a growing threat [...] Read more.

Background: Premature newborns represent a vulnerable population, at high risk of acquiring nosocomial infections during neonatal intensive care unit (NICU) admission. Multidrug-resistant organisms represent the greatest concern due to their intrinsic virulence and the limited therapeutic options. Resistant Enterobacterales are a growing threat for critically ill neonates, with increasing numbers of NICU outbreaks caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales being described. This study reports the early detection and successful control of an outbreak caused by ESBL-producing Klebsiella pneumoniae (ESBL-KP) in an Italian NICU in February 2021. Results: A total of 13 newborns tested positive for ESBL-KP between 2–9 February 2021, of whom four (31%) had a bloodstream infection. Two were critically ill, extremely premature newborns who died because of multiple comorbidities, and two were cured after treatment with meropenem. All other patients survived and were either discharged home or moved to other hospitals/wards in good clinical condition. ESBL-KP ST45 was found in all isolates by multilocus sequence typing (MLST) analysis. An outbreak control plan was set, including surveillance cultures for all neonates, NICU environments, and medical devices, along with the extended use of contact precautions and cohorting. In addition, the infection control plan was carried out through reinforcement and enhancement measures to guarantee maximal compliance. The outbreak was successfully controlled in seven days, given that no further cases were identified after 9 February. The source of the ESBL-KP outbreak was not identified through environmental sampling. Conclusions: Thanks to multidisciplinary management, a threatening outbreak of ESBL-KP in a NICU was controlled in few days. The prompt recognition of the event onset and the adoption of infection control interventions helped contain the bacteria spread on the ward. Full article

(This article belongs to the Special Issue Tackling Antimicrobial Resistance in Neonatal Infections)

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16 pages, 3851 KiB

Open AccessArticle

Protective Effects of Glycyrrhiza Total Flavones on Liver Injury Induced by Streptococcus agalactiae in Tilapia (Oreochromis niloticus)

by Jinliang Du, Liping Cao, Jiancao Gao, Rui Jia, Haojun Zhu, Zhijuan Nie, Bingwen Xi, Guojun Yin, Yuzhong Ma and Gangchun Xu

Antibiotics 2022, 11(11), 1648; https://doi.org/10.3390/antibiotics11111648 - 18 Nov 2022

Cited by 1 | Viewed by 1577

Abstract

Clinical studies have confirmed that Glycyrrhiza total flavones (GTFs) have good anti-hepatic injury, but whether they have a good protective effect on anti-hepatic injury activity induced by Streptococcus agalactiae in tilapia (Oreochromis niloticus) is unknown. The aims of this study were [...] Read more.

Clinical studies have confirmed that Glycyrrhiza total flavones (GTFs) have good anti-hepatic injury, but whether they have a good protective effect on anti-hepatic injury activity induced by Streptococcus agalactiae in tilapia (Oreochromis niloticus) is unknown. The aims of this study were to investigate the protective effects of Glycyrrhiza total flavones on liver injury induced by S. agalactiae (SA) and its underlying mechanism in fish. A total of 150 tilapia were randomly divided into five groups, each with three replicates containing 10 fish: normal control group, S. agalactiae infection group, and three Glycyrrhiza total flavone treatment groups (addition of 0.1, 0.5, or 1.0 g of GTF to 1 kg of feed). The normal control group was only fed with basic diet, after 60 d of feeding, and intraperitoneal injection of the same volume of normal saline (0.05 mL/10 g body weight); the S. agalactiae infection group was fed with basic diet, and the S. agalactiae solution was intraperitoneally injected after 60 d of feeding (0.05 mL/10 g body weight); the three GTF treatment groups were fed with a diet containing 0.1, 0.5, or 1.0 g/kg of GTF, and the S. agalactiae solution was intraperitoneally injected after 60 d of feeding (0.05 mL/10 g body weight). After 48 h injection, blood and liver tissues were collected to measure biochemical parameters and mRNA levels to evaluate the liver protection of GTFs. Compared with the control group, the serum levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (AKP) and glucose (GLU) in the streptococcal infection group increased significantly, while the levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) decreased significantly; observations of pathological sections showed obvious damage to the liver tissue structure in response to streptococcal infection. S. agalactiae can also cause fatty liver injury, affecting the function of fatty acid β-oxidation and biosynthesis in the liver of tilapia, and also causing damage to function of the immune system. The addition of GTFs to the diet could improve oxidative stress injury caused by S. agalactiae in tilapia liver tissue to different degrees, promote the β-oxidation of fatty acids in the liver, accelerate the lipid metabolism in the liver, and repair the damaged liver tissue. GTFs have a good protective effect on liver injury caused by streptococcus. Full article

(This article belongs to the Special Issue Antioxidant and Antibacterial Activity of Plant Extracts)

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9 pages, 5688 KiB

Open AccessArticle

Sterilization Procedures for Titanium Alloy Surfaces Leads to Higher Expression of Biofilm-Related Staphylococcus aureus Genes

by Christopher Spiegel, Michael Nogler and Débora C. Coraça-Huber

Antibiotics 2022, 11(11), 1647; https://doi.org/10.3390/antibiotics11111647 - 17 Nov 2022

Cited by 2 | Viewed by 1506

Abstract

Background: Around 1–2% of all implantation surgeries lead to implant-related infections, incurring costs of $40,000–$160,000 per total hip PJI. The 5-year mortality rate of prosthetic joint infections is up to 21%. To prevent infections during surgery, sterile surgery rooms and procedures have [...] Read more.

Background: Around 1–2% of all implantation surgeries lead to implant-related infections, incurring costs of $40,000–$160,000 per total hip PJI. The 5-year mortality rate of prosthetic joint infections is up to 21%. To prevent infections during surgery, sterile surgery rooms and procedures have been developed and certified standards have been established. To guarantee the sterility, implants can be acquired already sterile from manufacturers. Some titanium implants can be delivered unsterilized with a manual for sterilization procedure in compliance with ISO 17664. The aim of this study is to evaluate if the most used sterilization methods (steam sterilization in an autoclave and UV light sterilization) of titanium alloys, can influence the biofilm forming capacity of Staphylococcus aureus. In this study, we examined the influence of sterilization methods on the gene expression of biofilm-associated genes and regulators. Methods: We compared gene expression of icaADBC, SarA, SigB, and SodA on titanium CP4 and Ti6Al4V alloys sterilized by UV-light and pressurized saturated steam sterilization. We performed RT-qPCR after RNA extraction of Staphylococcus aureus ATCC 29213. In addition, bacterial cell growth on the sterilized titanium surfaces was examined by colony forming unit counting on agar plates after 24 h of incubation. Results: Colony forming units of S. aureus on titanium CP4 samples showed a higher tendency in colony counts when sterilized with UV light than with pressurized saturated steam (autoclaved). Similarly, colony forming unit counts on Ti6Al4V samples showed tendencies of higher numbers on UV light sterilized samples than on autoclaved samples. Gene expression of icaADBC, SarA and SodA between steamed samples and UV light sterilized samples showed no difference on titanium CP4 samples, whereas SigB showed higher gene expression on titanium CP4 samples when sterilized with UV light than in an autoclave. On autoclaved Ti6Al4V samples, all examined genes showed 4 to 9 times higher fold changes in gene expression than on UV light sterilized samples. Conclusions: This study indicates that steam sterilization of Ti6Al4V can increase biofilm formation of S. aureus on its surface. The significantly increased gene expression of biofilm responsible genes may indicate a modification of titanium surfaces on alloy components. This may promote biofilm formation that can lead to implant-infections in vivo. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Dental Biomaterials)

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20 pages, 3486 KiB

Open AccessArticle

Evaluation of In Vitro Activity of Double-Carbapenem Combinations against KPC-2-, OXA-48- and NDM-Producing Escherichia coli and Klebsiella pneumoniae

by Lisa Allander, Karin Vickberg, Pernilla Lagerbäck, Linus Sandegren and Thomas Tängdén

Antibiotics 2022, 11(11), 1646; https://doi.org/10.3390/antibiotics11111646 - 17 Nov 2022

Cited by 2 | Viewed by 1854

Abstract

Double-carbapenem combinations have shown synergistic potential against carbapenemase-producing Enterobacterales, but data remain inconclusive. This study evaluated the activity of double-carbapenem combinations against 51 clinical KPC-2-, OXA-48-, NDM-1, and NDM-5-producing Escherichia coli and Klebsiella pneumoniae and against constructed E. coli strains harboring genes encoding [...] Read more.

Double-carbapenem combinations have shown synergistic potential against carbapenemase-producing Enterobacterales, but data remain inconclusive. This study evaluated the activity of double-carbapenem combinations against 51 clinical KPC-2-, OXA-48-, NDM-1, and NDM-5-producing Escherichia coli and Klebsiella pneumoniae and against constructed E. coli strains harboring genes encoding KPC-2, OXA-48, or NDM-1 in an otherwise isogenic background. Two-drug combinations of ertapenem, meropenem, and doripenem were evaluated in 24 h time-lapse microscopy experiments with a subsequent spot assay and in static time-kill experiments. An enhanced effect in time-lapse microscopy experiments at 24 h and synergy in the spot assay was detected with one or more combinations against 4/14 KPC-2-, 17/17 OXA-48-, 2/17 NDM-, and 1/3 NDM-1+OXA-48-producing clinical isolates. Synergy rates were higher against meropenem- and doripenem-susceptible isolates and against OXA-48 producers. NDM production was associated with significantly lower synergy rates in E. coli. In time-kill experiments with constructed KPC-2-, OXA-48- and NDM-1-producing E. coli, 24 h synergy was not observed; however, synergy at earlier time points was found against the KPC-2- and OXA-48-producing constructs. Our findings indicate that the benefit of double-carbapenem combinations against carbapenemase-producing E. coli and K. pneumoniae is limited, especially against isolates that are resistant to the constituent antibiotics and produce NDM. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Hartmut Derendorf —Outstanding Contributions in the Fields of Quantitative Clinical Pharmacology)

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Antibiotics, Volume 11, Issue 11 (November 2022) – 223 articles

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