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Do DT, Yang MR, Vo TNS, Le NQK, Wu YW. Unitig-centered pan-genome machine learning approach for predicting antibiotic resistance and discovering novel resistance genes in bacterial strains. Comput Struct Biotechnol J 2024; 23:1864-1876. [PMID: 38707536 PMCID: PMC11067008 DOI: 10.1016/j.csbj.2024.04.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 04/13/2024] [Accepted: 04/13/2024] [Indexed: 05/07/2024] Open
Abstract
In current genomic research, the widely used methods for predicting antimicrobial resistance (AMR) often rely on prior knowledge of known AMR genes or reference genomes. However, these methods have limitations, potentially resulting in imprecise predictions owing to incomplete coverage of AMR mechanisms and genetic variations. To overcome these limitations, we propose a pan-genome-based machine learning approach to advance our understanding of AMR gene repertoires and uncover possible feature sets for precise AMR classification. By building compacted de Brujin graphs (cDBGs) from thousands of genomes and collecting the presence/absence patterns of unique sequences (unitigs) for Pseudomonas aeruginosa, we determined that using machine learning models on unitig-centered pan-genomes showed significant promise for accurately predicting the antibiotic resistance or susceptibility of microbial strains. Applying a feature-selection-based machine learning algorithm led to satisfactory predictive performance for the training dataset (with an area under the receiver operating characteristic curve (AUC) of > 0.929) and an independent validation dataset (AUC, approximately 0.77). Furthermore, the selected unitigs revealed previously unidentified resistance genes, allowing for the expansion of the resistance gene repertoire to those that have not previously been described in the literature on antibiotic resistance. These results demonstrate that our proposed unitig-based pan-genome feature set was effective in constructing machine learning predictors that could accurately identify AMR pathogens. Gene sets extracted using this approach may offer valuable insights into expanding known AMR genes and forming new hypotheses to uncover the underlying mechanisms of bacterial AMR.
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Affiliation(s)
- Duyen Thi Do
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
| | - Ming-Ren Yang
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- Department of Electrical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan
| | - Tran Nam Son Vo
- Department of Business Administration, College of Management, Lunghwa University of Science and Technology, Taoyuan City, Taiwan
| | - Nguyen Quoc Khanh Le
- Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yu-Wei Wu
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
- Clinical Big Data Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
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Tripathi A, Park J, Pho T, Champion JA. Dual Antibacterial Properties of Copper-Coated Nanotextured Stainless Steel. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2311546. [PMID: 38766975 DOI: 10.1002/smll.202311546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 05/07/2024] [Indexed: 05/22/2024]
Abstract
Bacterial adhesion to stainless steel, an alloy commonly used in shared settings, numerous medical devices, and food and beverage sectors, can give rise to serious infections, ultimately leading to morbidity, mortality, and significant healthcare expenses. In this study, Cu-coated nanotextured stainless steel (nSS) fabrication have been demonstrated using electrochemical technique and its potential as an antibiotic-free biocidal surface against Gram-positive and negative bacteria. As nanotexture and Cu combine for dual methods of killing, this material should not contribute to drug-resistant bacteria as antibiotic use does. This approach involves applying a Cu coating on nanotextured stainless steel, resulting in an antibacterial activity within 30 min. Comprehensive characterization of the surface revealing that the Cu coating consists of metallic Cu and oxidized states (Cu2+ and Cu+), has been performed by this study. Cu-coated nSS induces a remarkable reduction of 97% in Gram-negative Escherichia coli and 99% Gram-positive Staphylococcus epidermidis bacteria. This material has potential to be used to create effective, scalable, and sustainable solutions to prevent bacterial infections caused by surface contamination without contributing to antibiotic resistance.
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Affiliation(s)
- Anuja Tripathi
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, Georgia, 30332, USA
| | - Jaeyoung Park
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, Georgia, 30332, USA
| | - Thomas Pho
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, Georgia, 30332, USA
| | - Julie A Champion
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, Georgia, 30332, USA
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Garousi M, MonazamiTabar S, Mirazi H, Farrokhi Z, Khaledi A, Shakerimoghaddam A. Epidemiology of Pseudomonas aeruginosa in diabetic foot infections: a global systematic review and meta-analysis. Germs 2023; 13:362-372. [PMID: 38361543 PMCID: PMC10866166 DOI: 10.18683/germs.2023.1406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 11/09/2023] [Accepted: 12/18/2023] [Indexed: 02/17/2024]
Abstract
Pseudomonas aeruginosa is one of the most common causes of diabetic foot infection globally. This study aimed to determine the global distribution of P. aeruginosa isolated from diabetic foot ulcer infection. PRISMA procedure was used to perform the current systematic review and meta-analysis. The Web of Science, MEDLINE/PubMed, Scopus, and other databases were searched for studies published in English from 2000 to 2022. Data was analyzed using the Comprehensive Meta-Analysis software (CMA). Keywords and MESH phrases included Pseudomonas aeruginosa, diabetic foot ulcer, P. aeruginosa, and diabetic foot infection. As a result of this review, 16.6% of diabetic foot wound infections were caused by P. aeruginosa. About 37.9% of strains were multidrug resistant (MDR). P. aeruginosa infection rates in diabetic foot ulcers ranged from 0.5 to 100% globally. In total, the prevalence rates of P. aeruginosa in diabetic foot ulcer infection from Asia, Africa, and Western countries were reported at 18.5%, 16.3%, and 11.1%, respectively. Data have shown that the prevalence of P. aeruginosa, particularly MDR strains, isolated from diabetic foot ulcer infection was relatively high; inherent resistance to antibiotics is also high; the wound either does not heal or if it does, it will be delayed. Therefore, timely treatment is essential.
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Affiliation(s)
- Mitra Garousi
- MD, Department of Internal Medicine, Faculty of Medical Sciences, Hamedan University of Medical Sciences, Shaheed Fahmideh Ave, postal code: 6517838636, Hamedan, Iran
| | - Sina MonazamiTabar
- MD, Department of Internal Medicine, Faculty of Medical Sciences, Hamedan University of Medical Sciences, Shaheed Fahmideh Ave, postal code: 6517838636, Hamedan, Iran
| | - Hosein Mirazi
- PhD, Department of Biomedical Engineering, Faculty of New Sciences and Technology, University of Tehran, 16 Azar St., Enghelab Sq, postal address: 1417466191, Tehran, Iran
| | - Zahra Farrokhi
- MD, Medical School, Shahid Beheshti University of Medical Sciences, P.O. Box 4739-19395, 7 Floor, Bldg. No.2, SBUMS Sh. Arabi Ave, Tehran, Iran
| | - Azad Khaledi
- PhD, Infectious Diseases Research Center, Kashan University of Medical Sciences, 5 of Qotb –e Ravandi Blvd. P.O. Box: 87155-111, Postal code: 87154, Kashan, Iran
| | - Ali Shakerimoghaddam
- PhD, Medical Biotechnology Research Center, AJA University of Medical Sciences, Etemad Zadeh street, Fatemi-Gharbi Street. P.O. Box: 1411718541, Tehran, Iran
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Abo-zeid Y, Amer A, Bakkar MR, El-Houssieny B, Sakran W. Antimicrobial Activity of Azithromycin Encapsulated into PLGA NPs: A Potential Strategy to Overcome Efflux Resistance. Antibiotics (Basel) 2022; 11:1623. [PMID: 36421266 PMCID: PMC9686761 DOI: 10.3390/antibiotics11111623] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
Antimicrobial resistance represents a public health problem with a major negative impact on health and socioeconomic development, and is one of the biggest threats in the modern era. This requires the discovery of new approaches to control microbial infections. Nanomedicine could be one of the promising strategies to improve the treatment of microbial infections. Polymer nanoparticles (PNPs) were reported to overcome the efflux-resistant mechanism toward chemotherapeutic agents. However, to the best of our knowledge, no studies were performed to explore their ability to overcome the efflux-resistant mechanism in bacteria. In the current study, azithromycin (AZI), a macrolide antibiotic, was encapsulated into a biocompatible polymer, poly (lactic-co-glycolic acid) (PLGA) using the nano-precipitation method. The effect of the drug to polymer ratio, surfactant, and pH of the aqueous medium on particle size and drug loading percentage (DL%) were investigated in order to maximize the DL% and control the size of NPs to be around 100 nm. The antibacterial activity of AZI-PLGA NPs was investigated against AZI-resistant bacteria; Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis (E. faecalis), where the efflux mechanism was demonstrated to be one of the resistant mechanisms. AZI-PLGA NPs were safer than free AZI, as revealed from the cytotoxicity test, and were able to overcome the efflux-resistant mechanism, as revealed by decreasing the MIC of AZI-PLGA NPs by four times than free AZI. The MIC value reduced from 256 to 64 µg/mL and from >1000 to 256 µg/mL for MRSA and E. faecalis, respectively. Therefore, encapsulation of AZI into PNPs was shown to be a promising strategy to overcome the efflux-resistant mechanism towards AZI and improve its antibacterial effect. However, future investigations are necessary to explore the effect (if any) of particle size, surface charge, and material composition of PNPs on antibacterial activity. Moreover, it is essential to ascertain the safety profiles of these PNPs, the possibility of their large-scale manufacture, and if this concept could be extended to other antibiotics.
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Affiliation(s)
- Yasmin Abo-zeid
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt
- Helwan Nanotechnology Center, Helwan University, Cairo 11792, Egypt
| | - Amr Amer
- National Organization for Drug Control and Research (NODCAR), Giza 12511, Egypt
| | - Marwa Reda Bakkar
- Botany and Microbiology Department, Faculty of Science, Helwan University, Cairo 11795, Egypt
| | | | - Wedad Sakran
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt
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Ali A, Imran M, Sial S, Khan A. Effective antibiotic dosing in the presence of resistant strains. PLoS One 2022; 17:e0275762. [PMID: 36215219 PMCID: PMC9551627 DOI: 10.1371/journal.pone.0275762] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 09/22/2022] [Indexed: 11/25/2022] Open
Abstract
Mathematical models can be very useful in determining efficient and successful antibiotic dosing regimens. In this study, we consider the problem of determining optimal antibiotic dosing when bacteria resistant to antibiotics are present in addition to susceptible bacteria. We consider two different models of resistance acquisition, both involve the horizontal transfer (HGT) of resistant genes from a resistant to a susceptible strain. Modeling studies on HGT and study of optimal antibiotic dosing protocols in the literature, have been mostly focused on transfer of resistant genes via conjugation, with few studies on HGT via transformation. We propose a deterministic ODE based model of resistance acquisition via transformation, followed by a model that takes into account resistance acquisition through conjugation. Using a numerical optimization algorithm to determine the 'best' antibiotic dosing strategy. To illustrate our optimization method, we first consider optimal dosing when all the bacteria are susceptible to the antibiotic. We then consider the case where resistant strains are present. We note that constant periodic dosing may not always succeed in eradicating the bacteria while an optimal dosing protocol is successful. We determine the optimal dosing strategy in two different scenarios: one where the total bacterial population is to be minimized, and the next where we want to minimize the bacterial population at the end of the dosing period. We observe that the optimal strategy in the first case involves high initial dosing with dose tapering as time goes on, while in the second case, the optimal dosing strategy is to increase the dosing at the beginning of the dose cycles followed by a possible dose tapering. As a follow up study we intend to look at models where 'persistent' bacteria may be present in additional to resistant and susceptible strain and determine the optimal dosing protocols in this case.
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Affiliation(s)
- Asgher Ali
- Department of Mathematics, Lahore University of Management Sciences, Lahore, Pakistan
- * E-mail:
| | - Mudassar Imran
- Department of Mathematics and Sciences, Ajman University, Ajman, UAE
| | - Sultan Sial
- Department of Mathematics, Lahore University of Management Sciences, Lahore, Pakistan
| | - Adnan Khan
- Department of Mathematics, Lahore University of Management Sciences, Lahore, Pakistan
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Mohamed HMA, Alnasser SM, Abd-Elhafeez HH, Alotaibi M, Batiha GES, Younis W. Detection of β-Lactamase Resistance and Biofilm Genes in Pseudomonas Species Isolated from Chickens. Microorganisms 2022; 10:microorganisms10101975. [PMID: 36296251 PMCID: PMC9611058 DOI: 10.3390/microorganisms10101975] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/26/2022] [Accepted: 09/30/2022] [Indexed: 11/16/2022] Open
Abstract
Bacteria of the genus Pseudomonas are pathogens in both humans and animals. The most prevalent nosocomial pathogen is P. aeruginosa, particularly strains with elevated antibiotic resistance. In this study, a total of eighteen previously identified Pseudomonas species strains, were isolated from chicken. These strains were screened for biofilm formation and antibiotic resistance. In addition, we evaluated clove oil’s effectiveness against Pseudomonas isolates as an antibiofilm agent. The results showed that Pseudomonas species isolates were resistant to most antibiotics tested, particularly those from the β-lactamase family. A significant correlation (p < 0.05) between the development of multidrug-resistant isolates and biofilms is too informal. After amplifying the AmpC-plasmid-mediated genes (blaCMY, blaMIR, DHA, and FOX) and biofilm-related genes (psld, rhlA, and pelA) in most of our isolates, PCR confirmed this relationship. Clove oil has a potent antibiofilm effect against Pseudomonas isolates, and may provide a treatment for bacteria that form biofilms and are resistant to antimicrobials.
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Affiliation(s)
- Hams M. A. Mohamed
- Department of Microbiology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt
- Correspondence: (H.M.A.M.); (S.M.A.); (H.H.A.-E.)
| | - Sulaiman Mohammed Alnasser
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Buraydah 52571, Saudi Arabia
- Correspondence: (H.M.A.M.); (S.M.A.); (H.H.A.-E.)
| | - Hanan H. Abd-Elhafeez
- Department of Cells and Tissues, Faculty of Veterinary Medicine, Assiut University, Assiut 71526, Egypt
- Correspondence: (H.M.A.M.); (S.M.A.); (H.H.A.-E.)
| | - Meshal Alotaibi
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Albatin, Hafr Albatin 39524, Saudi Arabia
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhur University, Damanhur 22511, Egypt
| | - Waleed Younis
- Department of Microbiology, Faculty of Veterinary Medicine, South Valley University, Qena 83523, Egypt
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Pfanzelt M, Maher TE, Absmeier RM, Schwarz M, Sieber SA. Tailored Pyridoxal Probes Unravel Novel Cofactor-Dependent Targets and Antibiotic Hits in Critical Bacterial Pathogens. Angew Chem Int Ed Engl 2022; 61:e202117724. [PMID: 35199904 PMCID: PMC9321722 DOI: 10.1002/anie.202117724] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Indexed: 01/21/2023]
Abstract
Unprecedented bacterial targets are urgently needed to overcome the resistance crisis. Herein we systematically mine pyridoxal phosphate‐dependent enzymes (PLP‐DEs) in bacteria to focus on a target class which is involved in crucial metabolic processes. For this, we tailored eight pyridoxal (PL) probes bearing modifications at various positions. Overall, the probes exceeded the performance of a previous generation and provided a detailed map of PLP‐DEs in clinically relevant pathogens including challenging Gram‐negative strains. Putative PLP‐DEs with unknown function were exemplarily characterized via in‐depth enzymatic assays. Finally, we screened a panel of PLP binders for antibiotic activity and unravelled the targets of hit molecules. Here, an uncharacterized enzyme, essential for bacterial growth, was assigned as PLP‐dependent cysteine desulfurase and confirmed to be inhibited by the marketed drug phenelzine. Our approach provides a basis for deciphering novel PLP‐DEs as essential antibiotic targets along with corresponding ways to decipher small molecule inhibitors.
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Affiliation(s)
- Martin Pfanzelt
- Center for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany
| | - Thomas E Maher
- Center for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany.,Department of Chemistry, Molecular Sciences Research Hub, White City Campus and Institute of Chemical Biology, Molecular Sciences Research Hub, White City Campus, Imperial College London, 82 Wood Lane, London, W12 0BZ, UK
| | - Ramona M Absmeier
- Center for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany
| | - Markus Schwarz
- Center for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany
| | - Stephan A Sieber
- Center for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Str. 8, 85748, Garching, Germany
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8
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Mutuku C, Melegh S, Kovacs K, Urban P, Virág E, Heninger R, Herczeg R, Sonnevend Á, Gyenesei A, Fekete C, Gazdag Z. Characterization of β-Lactamases and Multidrug Resistance Mechanisms in Enterobacterales from Hospital Effluents and Wastewater Treatment Plant. Antibiotics (Basel) 2022; 11:antibiotics11060776. [PMID: 35740182 PMCID: PMC9219941 DOI: 10.3390/antibiotics11060776] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 06/02/2022] [Accepted: 06/04/2022] [Indexed: 01/11/2023] Open
Abstract
Antimicrobials in wastewater promote the emergence of antibiotic resistance, facilitated by selective pressure and transfer of resistant genes. Enteric bacteria belonging to Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Citrobacter species (n = 126) from hospital effluents and proximate wastewater treatment plant were assayed for susceptibility to four antimicrobial classes. The β-lactamase encoding genes harbored in plasmids were genotyped and the plasmids were sequenced. A multidrug resistance phenotype was found in 72% (n = 58) of E. coli isolates, 70% (n = 43) of Klebsiella species isolates, and 40% (n = 25) of Enterobacter and Citrobacter species. Moreover, 86% (n = 50) of E. coli, 77% (n = 33) of Klebsiella species, and 25% (n = 4) of Citrobacter species isolates phenotypically expressed extended spectrum β-lactamase. Regarding ESBL genes, blaCTX-M-27 and blaTEM-1 were found in E. coli, while Klebsiella species harbored blaCTX-M-15, blaCTX-M-30, or blaSHV-12. Genes coding for aminoglycoside modifying enzymes, adenylyltransferases (aadA1, aadA5), phosphotransferases (aph(6)-1d, aph(3″)-Ib), acetyltransferases (aac(3)-IIa), (aac(6)-Ib), sulfonamide/trimethoprim resistant dihydropteroate synthase (sul), dihydrofolate reductase (dfrA), and quinolone resistance protein (qnrB1) were also identified. Monitoring wastewater from human sources for acquired resistance in clinically important bacteria may provide a cheaper alternative in regions facing challenges that limit clinical surveillance.
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Affiliation(s)
- Christopher Mutuku
- Department of General and Environmental Microbiology, Faculty of Sciences, University of Pécs, 7622 Pécs, Hungary; (R.H.); (C.F.)
- Correspondence: (C.M.); (Z.G.)
| | - Szilvia Melegh
- Department of Medical Microbiology and Immunology, Medical School, University of Pécs, 7622 Pécs, Hungary; (S.M.); (K.K.); (Á.S.)
| | - Krisztina Kovacs
- Department of Medical Microbiology and Immunology, Medical School, University of Pécs, 7622 Pécs, Hungary; (S.M.); (K.K.); (Á.S.)
| | - Peter Urban
- Bioinformatics Research Group, Szentágothai Research Centre, 7624 Pécs, Hungary; (P.U.); (R.H.); (A.G.)
| | - Eszter Virág
- Educomat Ltd., Iskola utca 12/A, 8360 Keszthely, Hungary;
- Department of Molecular Biotechnology and Microbiology, Institute of Biotechnology, Faculty of Science and Technology, University of Debrecen, Egyetem Square 1, 4032 Debrecen, Hungary
| | - Reka Heninger
- Department of General and Environmental Microbiology, Faculty of Sciences, University of Pécs, 7622 Pécs, Hungary; (R.H.); (C.F.)
| | - Robert Herczeg
- Bioinformatics Research Group, Szentágothai Research Centre, 7624 Pécs, Hungary; (P.U.); (R.H.); (A.G.)
| | - Ágnes Sonnevend
- Department of Medical Microbiology and Immunology, Medical School, University of Pécs, 7622 Pécs, Hungary; (S.M.); (K.K.); (Á.S.)
| | - Attila Gyenesei
- Bioinformatics Research Group, Szentágothai Research Centre, 7624 Pécs, Hungary; (P.U.); (R.H.); (A.G.)
| | - Csaba Fekete
- Department of General and Environmental Microbiology, Faculty of Sciences, University of Pécs, 7622 Pécs, Hungary; (R.H.); (C.F.)
| | - Zoltan Gazdag
- Department of General and Environmental Microbiology, Faculty of Sciences, University of Pécs, 7622 Pécs, Hungary; (R.H.); (C.F.)
- Correspondence: (C.M.); (Z.G.)
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Abdul Razak S, Bauman JM, Marsh TL, Scribner KT. Changes in Lake Sturgeon Gut Microbiomes Relative to Founding Origin and in Response to Chemotherapeutant Treatments. Microorganisms 2022; 10:microorganisms10051005. [PMID: 35630448 PMCID: PMC9144364 DOI: 10.3390/microorganisms10051005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 04/19/2022] [Accepted: 04/19/2022] [Indexed: 12/15/2022] Open
Abstract
Antibiotics, drugs, and chemicals (collectively referred to as chemotherapeutants) are widely embraced in fish aquaculture as important tools to control or prevent disease outbreaks. Potential negative effects include changes in microbial community composition and diversity during early life stages, which can reverse the beneficial roles of gut microbiota for the maintenance of host physiological processes and homeostatic regulation. We characterized the gut microbial community composition and diversity of an ecologically and economically important fish species, the lake sturgeon (Acipenser fulvescens), during the early larval period in response to weekly treatments using chemotherapeutants commonly used in aquaculture (chloramine-T, hydrogen peroxide, and NaCl2 followed by hydrogen peroxide) relative to untreated controls. The effects of founding microbial community origin (wild stream vs. hatchery water) were also evaluated. Gut communities were quantified using massively parallel next generation sequencing based on the V4 region of the 16S rRNA gene. Members of the phylum Firmicutes (principally unclassified Clostridiales and Clostridium_sensu_stricto) and Proteobacteria were the dominant taxa in all gut samples regardless of treatment. The egg incubation environment (origin) and its interaction with chemotherapeutant treatment were significantly associated with indices of microbial taxonomic diversity. We observed large variation in the beta diversity of lake sturgeon gut microbiota between larvae from eggs incubated in hatchery and wild (stream) origins based on nonmetric dimensional scaling (NMDS). Permutational ANOVA indicated the effects of chemotherapeutic treatments on gut microbial community composition were dependent on the initial source of the founding microbial community. Influences of microbiota colonization during early ontogenetic stages and the resilience of gut microbiota to topical chemotherapeutic treatments are discussed.
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Affiliation(s)
- Shairah Abdul Razak
- Department of Fisheries & Wildlife, Michigan State University, East Lansing, MI 48824, USA;
- Department of Applied Physics, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Malaysia
| | - John M. Bauman
- Michigan Department of Natural Resources Fisheries Division, Escanaba Customer Service Center, Gladstone, MI 49837, USA;
| | - Terence L. Marsh
- Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA;
| | - Kim T. Scribner
- Department of Fisheries & Wildlife, Michigan State University, East Lansing, MI 48824, USA;
- Department of Integrative Biology, Michigan State University, East Lansing, MI 48824, USA
- Correspondence:
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10
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Tailored Pyridoxal Probes Unravel Novel Cofactor‐Dependent Targets and Antibiotic Hits in Critical Bacterial Pathogens. Angew Chem Int Ed Engl 2022. [DOI: 10.1002/ange.202117724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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11
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Enhancement of photodynamic bactericidal activity of curcumin against Pseudomonas Aeruginosa using polymyxin B. Photodiagnosis Photodyn Ther 2021; 37:102677. [PMID: 34890782 DOI: 10.1016/j.pdpdt.2021.102677] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 11/23/2021] [Accepted: 12/06/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND Pseudomonas aeruginosa (P. aeruginosa) is an emerging opportunistic pathogen, which can cause bacterial skin diseases such as green nail syndrome, interdigital infections and folliculitis. Curcumin-mediated antimicrobial photodynamic therapy (aPDT) has been demonstrated as a promising therapeutic option for the treatment of skin infection though its inactivation of gram-negative bacteria such as P. aeruginosa. MATERIALS AND METHODS In the present study, we examined the adjuvant effect of polymyxin B on the antibacterial activity of curcumin-mediated aPDT against P. aeruginosa. P. aeruginosa was treated with curcumin in the presence of 0.1-0.5 mg/L polymyxin B and irradiated by blue LED light (10 J/cm2). Bacterial cultures treated with curcumin alone served as controls. Colony forming units (CFU) were counted and the viability of P. aeruginosa was calculated after aPDT treatment. The possible underlying mechanisms for the enhanced killing effects were also explored. RESULTS The killing effects of curcumin-mediated aPDT against P. aeruginosa was significantly enhanced by polymyxin B (over 2-log reductions). Moreover, it was also observed that addition of polymyxin B in the curcumin-mediated aPDT led to the apparent bacterial membrane damage with increased leakage of cytoplasmic contents and extensive DNA and protein degradation. DISCUSSION The photodynamic action of curcumin against P. aeruginosa could be significantly enhanced by the FDA-approved drug polymyxin B. Our results highlight the potential of introducing polymyxin B to enhance the effects of aPDT treatment against gram-negative skin infections, in particular, P. aeruginosa.
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Mohamed Z, Shin JH, Ghosh S, Sharma AK, Pinnock F, Bint E Naser Farnush S, Dörr T, Daniel S. Clinically Relevant Bacterial Outer Membrane Models for Antibiotic Screening Applications. ACS Infect Dis 2021; 7:2707-2722. [PMID: 34227387 DOI: 10.1021/acsinfecdis.1c00217] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Antibiotic resistance is a growing global health concern that has been increasing in prevalence over the past few decades. In Gram-negative bacteria, the outer membrane is an additional barrier through which antibiotics must traverse to kill the bacterium. In addition, outer membrane features and properties, like membrane surface charge, lipopolysaccharide (LPS) length, and membrane porins, can be altered in response to antibiotics and therefore, further mediate resistance. Model membranes have been used to mimic bacterial membranes to study antibiotic-induced membrane changes but often lack the compositional complexity of the actual outer membrane. Here, we developed a surface-supported membrane platform using outer membrane vesicles (OMVs) from clinically relevant Gram-negative bacteria and use it to characterize membrane biophysical properties and investigate its interaction with antibacterial compounds. We demonstrate that this platform maintains critical features of outer membranes, like fluidity, while retaining complex membrane components, like OMPs and LPS, which are central to membrane-mediated antibiotic resistance. This platform offers a non-pathogenic, cell-free surface to study such phenomena that is compatible with advanced microscopy and surface characterization tools like quartz crystal microbalance. We confirm these OMV bilayers recapitulate membrane interactions (or lack thereof) with the antibiotic compounds polymyxin B, bacitracin, and vancomycin, validating their use as representative models for the bacterial surface. By forming OMV bilayers from different strains, we envision that this platform could be used to investigate underlying biophysical differences in outer membranes leading to resistance, to screen and identify membrane-active antibiotics, or for the development of phage technologies targeting a particular membrane surface component.
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Affiliation(s)
- Zeinab Mohamed
- Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York United States
| | - Jung-Ho Shin
- Weill Institute for Cell and Molecular Biology and Department of Microbiology, Cornell University, Ithaca, New York United States
| | - Surajit Ghosh
- Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York United States
| | - Abhishek K Sharma
- Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York United States
| | - Ferra Pinnock
- Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York United States
| | - Samavi Bint E Naser Farnush
- Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York United States
| | - Tobias Dörr
- Weill Institute for Cell and Molecular Biology and Department of Microbiology, Cornell University, Ithaca, New York United States
| | - Susan Daniel
- Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York United States
- Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York United States
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13
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Langendonk RF, Neill DR, Fothergill JL. The Building Blocks of Antimicrobial Resistance in Pseudomonas aeruginosa: Implications for Current Resistance-Breaking Therapies. Front Cell Infect Microbiol 2021; 11:665759. [PMID: 33937104 PMCID: PMC8085337 DOI: 10.3389/fcimb.2021.665759] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/29/2021] [Indexed: 12/12/2022] Open
Abstract
P. aeruginosa is classified as a priority one pathogen by the World Health Organisation, and new drugs are urgently needed, due to the emergence of multidrug-resistant (MDR) strains. Antimicrobial-resistant nosocomial pathogens such as P. aeruginosa pose unwavering and increasing threats. Antimicrobial stewardship has been a challenge during the COVID-19 pandemic, with a majority of those hospitalized with SARS-CoV2 infection given antibiotics as a safeguard against secondary bacterial infection. This increased usage, along with increased handling of sanitizers and disinfectants globally, may further accelerate the development and spread of cross-resistance to antibiotics. In addition, P. aeruginosa is the primary causative agent of morbidity and mortality in people with the life-shortening genetic disease cystic fibrosis (CF). Prolonged periods of selective pressure, associated with extended antibiotic treatment and the actions of host immune effectors, results in widespread adaptive and acquired resistance in P. aeruginosa found colonizing the lungs of people with CF. This review discusses the arsenal of resistance mechanisms utilized by P. aeruginosa, how these operate under high-stress environments such as the CF lung and how their interconnectedness can result in resistance to multiple antibiotic classes. Intrinsic, adaptive and acquired resistance mechanisms will be described, with a focus on how each layer of resistance can serve as a building block, contributing to multi-tiered resistance to antimicrobial activity. Recent progress in the development of anti-resistance adjuvant therapies, targeting one or more of these building blocks, should lead to novel strategies for combatting multidrug resistant P. aeruginosa. Anti-resistance adjuvant therapy holds great promise, not least because resistance against such therapeutics is predicted to be rare. The non-bactericidal nature of anti-resistance adjuvants reduce the selective pressures that drive resistance. Anti-resistance adjuvant therapy may also be advantageous in facilitating efficacious use of traditional antimicrobials, through enhanced penetration of the antibiotic into the bacterial cell. Promising anti-resistance adjuvant therapeutics and targets will be described, and key remaining challenges highlighted. As antimicrobial stewardship becomes more challenging in an era of emerging and re-emerging infectious diseases and global conflict, innovation in antibiotic adjuvant therapy can play an important role in extending the shelf-life of our existing antimicrobial therapeutic agents.
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Affiliation(s)
- R. Frèdi Langendonk
- Institute of Infection, Veterinary and Ecological Science, University of Liverpool, Liverpool, United Kingdom
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Makhlynets OV, Caputo GA. Characteristics and therapeutic applications of antimicrobial peptides. BIOPHYSICS REVIEWS 2021; 2:011301. [PMID: 38505398 PMCID: PMC10903410 DOI: 10.1063/5.0035731] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 12/31/2020] [Indexed: 12/20/2022]
Abstract
The demand for novel antimicrobial compounds is rapidly growing due to the phenomenon of antibiotic resistance in bacteria. In response, numerous alternative approaches are being taken including use of polymers, metals, combinatorial approaches, and antimicrobial peptides (AMPs). AMPs are a naturally occurring part of the immune system of all higher organisms and display remarkable broad-spectrum activity and high selectivity for bacterial cells over host cells. However, despite good activity and safety profiles, AMPs have struggled to find success in the clinic. In this review, we outline the fundamental properties of AMPs that make them effective antimicrobials and extend this into three main approaches being used to help AMPs become viable clinical options. These three approaches are the incorporation of non-natural amino acids into the AMP sequence to impart better pharmacological properties, the incorporation of AMPs in hydrogels, and the chemical modification of surfaces with AMPs for device applications. These approaches are being developed to enhance the biocompatibility, stability, and/or bioavailability of AMPs as clinical options.
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Affiliation(s)
- Olga V. Makhlynets
- Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, USA
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15
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Soleymanzadeh Moghadam S, Mohammad N, Ghooshchian M, FathiZadeh S, Khodaii Z, Faramarzi M, Fagheei Aghmiyuni Z, Roudbari M, Pazouki A, Mousavi Shabestari T. Comparison of the effects of Lactobacillus plantarum versus imipenem on infected burn wound healing. Med J Islam Repub Iran 2020; 34:94. [PMID: 33315993 PMCID: PMC7722975 DOI: 10.34171/mjiri.34.94] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Indexed: 12/13/2022] Open
Abstract
Background: Infection of burn wounds is one of the most important problems in the world. Lactobacillus plantarum is known for burn wound healing because of the immunomodulatory and anti-microbial roles. This study was performed to compare the effects of L. plantarum and imipenem - alone and in combination - on infected burn wound healing. Methods: Burn wounds were experimentally induced on 50 rats in three test groups (germ and supernatant of L. plantarum ) and two control groups (n=10 each) and were inoculated with Pseudomonas aeruginosa. During a 14-day period, wounds in all groups were daily treated topically. The data were analyzed using one-way analysis of variance followed by Tukey-Kramer and LSD. A p-value of < 0.05 was considered as statistically significant. Results: The mean size of the wound on day 14 after the treatment in the probiotic group was significantly lower than the control and the supernatant treated groups (p<0.05). The percentage of wound healing was significantly higher in the probiotic pellet treated group compared to the imipenem and the supernatant groups (by Anova test: 69.58%, p=0.022). The mean leukocyte count in the probiotic pellet group (12110) and supernatant group (13650) was significantly higher than the imipenem group (7670) (p=0.002 and 0.001, respectively). Wound cultures revealed that the percentage of cases where the pathogens had no growth was significantly different among the comparison groups. In all three test groups, P. aeruginosa was completely eliminated in comparison to the positive control group (p<0.05). Conclusion: The results of our study showed that L. plantarum and its by-products promote wound healing and can be used as an alternative to antibiotics to treat ulcer infections caused by resistant bacteria.
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Affiliation(s)
- Somayeh Soleymanzadeh Moghadam
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Nazanin Mohammad
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Ghooshchian
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Sara FathiZadeh
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Zohreh Khodaii
- Dietary Supplements and Probiotic Research Center, Alborz University of Medical Science, Karaj, Iran
| | - Mahmood Faramarzi
- Research Center of Pediatric Infectious Diseases, Institute of immunology and infectious diseases, Iran University of medical sciences, Tehran, Iran
| | - Zeinab Fagheei Aghmiyuni
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Masoud Roudbari
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
- Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Abdolreza Pazouki
- Division of Minimally Invasive Surgery Fellowship Program, Rasoul Akram Hospital, Iran University of Medical Science, Tehran, Iran
| | - Tahereh Mousavi Shabestari
- Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
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16
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Salih M, Omolo CA, Devnarain N, Elrashedy AA, Mocktar C, Soliman MES, Govender T. Supramolecular self-assembled drug delivery system (SADDs) of vancomycin and tocopherol succinate as an antibacterial agent: in vitro, in silico and in vivo evaluations. Pharm Dev Technol 2020; 25:1090-1108. [PMID: 32684052 DOI: 10.1080/10837450.2020.1797786] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
In this study self-assembled drug delivery system (SADDs) composed of a hydrophobic d-α-tocopherol succinate (TS) and a hydrophilic vancomycin (VCM) were formulated, and its potential for enhancing the antibacterial activity of VCM against Staphylococcus aureus (SA) and Methicillin-resistant Staphylococcus aureus (MRSA) were explored. The SADDs were synthesized via supramolecular complexation, then characterized for in silico, in vitro and in vivo studies. In silico studies confirmed the self-assembly of VCM/TS into NPs. The size, surface charge and drug loading of the SADDs was ˂100 nm, -27 mV and 68%, respectively. The SADDs were non-hemolytic and biosafe. A sustained release of VCM from SADDs was noted, with 52.2% release after 48 hr. The in vitro antibacterial test showed a twofold decrease in Minimum inhibitory concentration (MIC) against SA and MRSA, and a significantly higher reduction in MRSA biofilms compared to bare VCM. Further, in silico studies confirmed strong and stable binding of TS to MRSA efflux pumps. The in vivo study using mice skin infection models showed a 9.5-fold reduction in bacterial load after treatment with SADDs, in comparison with bare VCM. These findings affirmed that VCM/TS NPs as a promising novel nano-delivery for treating bacterial infections.
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Affiliation(s)
- Mohammed Salih
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Calvin A Omolo
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.,School of Pharmacy and Health Sciences, United States International University, Nairobi, Kenya
| | - Nikita Devnarain
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Ahmed A Elrashedy
- Molecular Bio-computation and Drug Design Lab, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Chunderika Mocktar
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Mahmoud E S Soliman
- Molecular Bio-computation and Drug Design Lab, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Thirumala Govender
- Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa
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17
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Strategies for improving antimicrobial properties of stainless steel. MATERIALS 2020; 13:ma13132944. [PMID: 32630130 PMCID: PMC7372344 DOI: 10.3390/ma13132944] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/27/2020] [Accepted: 06/28/2020] [Indexed: 12/27/2022]
Abstract
In this review, strategies for improving the antimicrobial properties of stainless steel (SS) are presented. The main focus given is to present current strategies for surface modification of SS, which alter surface characteristics in terms of surface chemistry, topography and wettability/surface charge, without influencing the bulk attributes of the material. As SS exhibits excellent mechanical properties and satisfactory biocompatibility, it is one of the most frequently used materials in medical applications. It is widely used as a material for fabricating orthopedic prosthesis, cardiovascular stents/valves and recently also for three dimensional (3D) printing of custom made implants. Despite its good mechanical properties, SS lacks desired biofunctionality, which makes it prone to bacterial adhesion and biofilm formation. Due to increased resistance of bacteria to antibiotics, it is imperative to achieve antibacterial properties of implants. Thus, many different approaches were proposed and are discussed herein. Emphasis is given on novel approaches based on treatment with highly reactive plasma, which may alter SS topography, chemistry and wettability under appropriate treatment conditions. This review aims to present and critically discuss different approaches and propose novel possibilities for surface modification of SS by using highly reactive gaseous plasma in order to obtain a desired biological response.
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18
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D'Souza A, Yoon JH, Beaman H, Gosavi P, Lengyel-Zhand Z, Sternisha A, Centola G, Marshall LR, Wehrman MD, Schultz KM, Monroe MB, Makhlynets OV. Nine-Residue Peptide Self-Assembles in the Presence of Silver to Produce a Self-Healing, Cytocompatible, Antimicrobial Hydrogel. ACS APPLIED MATERIALS & INTERFACES 2020; 12:17091-17099. [PMID: 32154701 DOI: 10.1021/acsami.0c01154] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Silver compounds have been used extensively for wound healing because of their antimicrobial properties, but high concentrations of silver are toxic to mammalian cells. We designed a peptide that binds silver and releases only small amounts of this ion over time, therefore overcoming the problem of silver toxicity. Silver binding was achieved through incorporation of an unnatural amino acid, 3'-pyridyl alanine (3'-PyA), into the peptide sequence. Upon the addition of silver ions, the peptide adopts a beta-sheet secondary structure and self-assembles into a strong hydrogel as characterized by rheology, circular dichroism, and transmission electron microscopy. We show that the resulting hydrogel kills Escherichia coli and Staphylococcus aureus but is not toxic to fibroblasts and could be used for wound healing. The amount of Ag(I) released by hydrogels into the solution is less than 4% and this low amount of Ag(I) does not change in the pH range 6-8. These studies provide an initial indication for use of the designed hydrogel as injectable, antimicrobial wound dressing.
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Affiliation(s)
- Areetha D'Souza
- Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, United States
| | - Jennifer H Yoon
- Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, United States
| | - Henry Beaman
- Biomedical & Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, New York 13244, United States
| | - Pallavi Gosavi
- Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, United States
| | - Zsofia Lengyel-Zhand
- Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, United States
| | - Alex Sternisha
- Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, United States
| | - Garrick Centola
- Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, United States
| | - Liam R Marshall
- Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, United States
| | - Matthew D Wehrman
- Chemical and Biomolecular Engineering, Lehigh University, Iacocca Hall, 111 Research Drive, Bethlehem, Pennsylvania 18015, United States
| | - Kelly M Schultz
- Chemical and Biomolecular Engineering, Lehigh University, Iacocca Hall, 111 Research Drive, Bethlehem, Pennsylvania 18015, United States
| | - Mary Beth Monroe
- Biomedical & Chemical Engineering, Syracuse University, 318 Bowne Hall, Syracuse, New York 13244, United States
| | - Olga V Makhlynets
- Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, United States
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19
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A novel method to determine antibiotic sensitivity in Bdellovibrio bacteriovorus reveals a DHFR-dependent natural trimethoprim resistance. Sci Rep 2020; 10:5315. [PMID: 32210253 PMCID: PMC7093396 DOI: 10.1038/s41598-020-62014-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 03/04/2020] [Indexed: 11/13/2022] Open
Abstract
Bdellovibrio bacteriovorus is a small Gram-negative bacterium and an obligate predator of other Gram-negative bacteria. Prey resistance to B. bacteriovorus attack is rare and transient. This consideration together with its safety and low immunogenicity makes B. bacteriovorus a valid alternative to antibiotics, especially in the treatment of multidrug resistant pathogens. In this study we developed a novel technique to estimate B. bacteriovorus sensitivity against antibiotics in order to make feasible the development and testing of co-therapies with antibiotics that would increase its antimicrobial efficacy and at the same time reduce the development of drug resistance. Results from tests performed with this technique show that among all tested antibiotics, trimethoprim has the lowest antimicrobial effect on B. bacteriovorus. Additional experiments revealed that the mechanism of trimethoprim resistance in B. bacteriovorus depends on the low affinity of this compound for the B. bacteriovorus dihydrofolate reductase (Bd DHFR).
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20
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Garza-González E, Franco-Cendejas R, Morfín-Otero R, Echaniz-Aviles G, Rojas-Larios F, Bocanegra-Ibarias P, Flores-Treviño S, Ponce-de-León A, Rodríguez-Noriega E, Alavez-Ramírez N, Mena-Ramirez JP, Rincón-Zuno J, Fong-Camargo MG, Morales-De-la-Peña CT, Huerta-Baltazar CR, López-Jacome LE, Carnalla-Barajas MN, Soto-Noguerón A, Sanchez-Francia D, Moncada-Barrón D, Ortíz-Brizuela E, García-Mendoza L, Newton-Sánchez OA, Choy-Chang EV, Aviles-Benitez LK, Martínez-Miranda R, Feliciano-Guzmán JM, Peña-Lopez CD, Couoh-May CA, López-Gutiérrez E, Gil-Veloz M, Armenta-Rodríguez LC, Manriquez-Reyes M, Gutierrez-Brito M, López-Ovilla I, Adame-Álvarez C, Barajas-Magallón JM, Aguirre-Burciaga E, Coronado-Ramírez AM, Rosales-García AA, Sida-Rodríguez S, Urbina-Rodríguez RE, López-Moreno LI, Juárez-Velázquez GE, Martínez-Villarreal RT, Canizales-Oviedo JL, Cetina-Umaña CM, Perez-Juárez MM, González-Moreno A, Romero-Romero D, Bello-Pazos FD, Aguilar-Orozco G, Barlandas-Rendón NRE, Maldonado-Anicacio JY, Valadez-Quiroz A, Camacho-Ortiz A. The Evolution of Antimicrobial Resistance in Mexico During the Last Decade: Results from the INVIFAR Group. Microb Drug Resist 2020; 26:1372-1382. [PMID: 32027229 DOI: 10.1089/mdr.2019.0354] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Background: Surveillance of antimicrobial resistance (AMR) requires an international approach with national and local strategies. Our aim was to summarize a retrospective 10-year report of antibiotic resistance of gram-positive and gram-negative bacteria in Mexico. Methods: A total of 46 centers from 22 states of Mexico participated. Databases of AMR from January 2009 to December 2018 were included for most species. The 10-year period was divided into five 2-year periods. Results: For Staphylococcus aureus, a decrease in resistance in all specimens was observed for erythromycin and oxacillin (p < 0.0001 for each). For Enterobacter spp., resistance to meropenem increased for urine specimens (p = 0.0042). For Klebsiella spp., increased drug resistance in specimens collected from blood was observed for trimethoprim/sulfamethoxazole, gentamicin, tobramycin (p < 0.0001 for each), meropenem (p = 0.0014), and aztreonam (p = 0.0030). For Acinetobacter baumannii complex, high drug resistance was detected for almost all antibiotics, including carbapenems, except for tobramycin, which showed decreased resistance for urine, respiratory, and blood isolates (p < 0.0001 for each), and for amikacin, which showed a decrease in resistance in urine specimens (p = 0.0002). An increase in resistance to cefepime was found for urine, respiratory, and blood specimens (p < 0.0001 for each). For Pseudomonas aeruginosa, aztreonam resistance increased for isolates recovered from blood (p = 0.0001). Conclusion: This laboratory-based surveillance of antibiotic resistance shows that resistance is increasing for some antibiotics in different bacterial species in Mexico and highlights the need for continuous monitoring of antibiotic resistance.
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Affiliation(s)
- Elvira Garza-González
- Hospital Universitario Dr. José E. González, Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Rafael Franco-Cendejas
- Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, Mexico
| | - Rayo Morfín-Otero
- Hospital Civil de Guadalajara e Instituto de Patología Infecciosa, Universidad de Guadalajara, Guadalajara, Mexico
| | | | | | - Paola Bocanegra-Ibarias
- Hospital Universitario Dr. José E. González, Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Samantha Flores-Treviño
- Hospital Universitario Dr. José E. González, Universidad Autónoma de Nuevo León, Monterrey, Mexico
| | - Alfredo Ponce-de-León
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Eduardo Rodríguez-Noriega
- Hospital Civil de Guadalajara e Instituto de Patología Infecciosa, Universidad de Guadalajara, Guadalajara, Mexico
| | - Norma Alavez-Ramírez
- Hospital Regional Tipo B, de Alta Especialidad Bicentenario de La Independencia, Tultitlán de Mariano Escobedo, Mexico
| | - Juan Pablo Mena-Ramirez
- Hospital General de Zona No. 21 IMSS, Centro Universitario de los Altos (CUALTOS), Universidad de Guadalajara, Tepatitlán de Morelos, Mexico
| | - Joaquín Rincón-Zuno
- Hospital Para el Niño de Toluca, Instituto Materno Infantil del Estado De México, Toluca, Mexico
| | | | | | | | - Luis Esau López-Jacome
- Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, Mexico
| | | | | | | | | | - Edgar Ortíz-Brizuela
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Jorge Luis Canizales-Oviedo
- Centro Universitario De Salud, Universidad Autónoma de Nuevo León, Laboratorio Pueblo Nuevo, Monterrey, Mexico
| | | | | | | | | | | | | | | | | | | | - Adrián Camacho-Ortiz
- Hospital Universitario Dr. José E. González, Universidad Autónoma de Nuevo León, Monterrey, Mexico
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Supramolecular amphiphiles of Beta-cyclodextrin and Oleylamine for enhancement of vancomycin delivery. Int J Pharm 2020; 574:118881. [DOI: 10.1016/j.ijpharm.2019.118881] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2019] [Revised: 11/12/2019] [Accepted: 11/13/2019] [Indexed: 12/12/2022]
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22
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Lakes JE, Richards CI, Flythe MD. Inhibition of Bacteroidetes and Firmicutes by select phytochemicals. Anaerobe 2019; 61:102145. [PMID: 31918362 DOI: 10.1016/j.anaerobe.2019.102145] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 12/11/2019] [Accepted: 12/23/2019] [Indexed: 01/26/2023]
Abstract
Current research indicates that changes in gut microbiota can impact the host, but it is not always clear how dietary and environmental factors alter gut microbiota. One potential factor is antimicrobial activity of compounds ingested by the host. The goal of this study was to determine the antimicrobial activity of common plant secondary metabolites against pure cultures of paired, structurally and phylogenetically distinct gastrointestinal bacteria of human or bovine origin: Prevotella bryantii B14, Bacteroides fragilis 25285, Acetoanaerobium (Clostridium) sticklandii SR and Clostridioides difficile 9689. When growth media were amended with individual phytochemicals (the alkaloids: berberine, capsaicin, nicotine, piperine and quinine and the phenolic: curcumin), growth of each species was inhibited to varying degrees at the three greatest concentrations tested (0.10-10.00 mg mL-1). The viable cell numbers of all the cultures were reduced, ≥4-logs, by berberine at concentrations ≥1.00 mg mL-1. Quinine performed similarly to berberine for B14, 25285, and SR at the same concentrations. The other phytochemicals were inhibitory, but not as much as quinine or berberine. Nicotine had activity against all four species (≥2-log reduction in viable cell number at 10.00 mg mL-1), but had stronger activity against the Gram-positive bacteria, SR and 9689, (≥4-log reductions at 10.00 mg mL-1). In conclusion, the phytochemicals had varying spectra of antimicrobial activity. These results are consistent with the hypothesis that ingested phytochemicals have the ability to differentially impact gut microbiota through antimicrobial activity.
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Affiliation(s)
- Jourdan E Lakes
- Department of Chemistry, College of Arts & Sciences, University of Kentucky, Lexington, KY, USA
| | - Christopher I Richards
- Department of Chemistry, College of Arts & Sciences, University of Kentucky, Lexington, KY, USA
| | - Michael D Flythe
- USDA Agricultural Research Service Forage-Animal Production Research Unit, Lexington, KY, USA; Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, USA.
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Antimicrobial Resistance Prediction for Gram-Negative Bacteria via Game Theory-Based Feature Evaluation. Sci Rep 2019; 9:14487. [PMID: 31597945 PMCID: PMC6785542 DOI: 10.1038/s41598-019-50686-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 09/13/2019] [Indexed: 12/16/2022] Open
Abstract
The increasing prevalence of antimicrobial-resistant bacteria drives the need for advanced methods to identify antimicrobial-resistance (AMR) genes in bacterial pathogens. With the availability of whole genome sequences, best-hit methods can be used to identify AMR genes by differentiating unknown sequences with known AMR sequences in existing online repositories. Nevertheless, these methods may not perform well when identifying resistance genes with sequences having low sequence identity with known sequences. We present a machine learning approach that uses protein sequences, with sequence identity ranging between 10% and 90%, as an alternative to conventional DNA sequence alignment-based approaches to identify putative AMR genes in Gram-negative bacteria. By using game theory to choose which protein characteristics to use in our machine learning model, we can predict AMR protein sequences for Gram-negative bacteria with an accuracy ranging from 93% to 99%. In order to obtain similar classification results, identity thresholds as low as 53% were required when using BLASTp.
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Pourakbari B, Movahedi Z, Mahmoudi S, Sabouni F, Ashtiani MTH, Sadeghi RH, Mamishi S. Genotypic characteristics of Pseudomonas aeruginosa strains circulating in the tertiary referral Children's Medical Hospital in Tehran, Iran. Br J Biomed Sci 2019. [DOI: 10.1080/09674845.2012.12069147] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Affiliation(s)
- B. Pourakbari
- Pediatrics Infectious Diseases Research Center, Tehran University of Medical Sciences
| | - Z. Movahedi
- Department of Infectious Disease, School of Medicine, Qom University of Medical Sciences
| | - S. Mahmoudi
- Pediatrics Infectious Diseases Research Center, Tehran University of Medical Sciences
| | - F. Sabouni
- Department of Pediatric Infectious Disease, School of Medicine Tehran University of Medical Sciences
| | - M. T. H. Ashtiani
- Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Iran
| | - R. H. Sadeghi
- Pediatrics Infectious Diseases Research Center, Tehran University of Medical Sciences
| | - S. Mamishi
- Pediatrics Infectious Diseases Research Center, Tehran University of Medical Sciences
- Department of Pediatric Infectious Disease, School of Medicine Tehran University of Medical Sciences
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Abodakpi H, Wanger A, Tam VH. What the Clinical Microbiologist Should Know About Pharmacokinetics/Pharmacodynamics in the Era of Emerging Multidrug Resistance: Focusing on β-Lactam/β-Lactamase Inhibitor Combinations. Clin Lab Med 2019; 39:473-485. [PMID: 31383269 DOI: 10.1016/j.cll.2019.05.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
As a class, β-lactamase inhibitors have proved successful in extending the clinical utility of β-lactam antibiotics by circumventing β-lactamase-mediated resistance. However, the rapid evolution of these β-lactamases calls for a critical reevaluation of the relationships between susceptibility, drug exposures, and bacterial response. The existing paradigm for in vitro susceptibility testing and development of β-lactam/β-lactamase inhibitor combinations may not optimally facilitate clinical use. Thus, alternative approaches for pairing these combinations and evaluating in vitro susceptibility are needed to provide better guidance to clinicians.
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Affiliation(s)
- Henrietta Abodakpi
- Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA
| | - Audrey Wanger
- Department of Pathology and Laboratory Medicine, McGovern Medical School, 6431 Fannin, Houston, Texas 77030, USA
| | - Vincent H Tam
- Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA; Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, 4849 Calhoun Road, Houston, TX 77204, USA.
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Kaarme J, Riedel H, Schaal W, Yin H, Nevéus T, Melhus Å. Rapid Increase in Carriage Rates of Enterobacteriaceae Producing Extended-Spectrum β-Lactamases in Healthy Preschool Children, Sweden. Emerg Infect Dis 2019; 24:1874-1881. [PMID: 30226162 PMCID: PMC6154144 DOI: 10.3201/eid2410.171842] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
By collecting and analyzing diapers, we identified a >6-fold increase in carriage of extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae for healthy preschool children in Sweden (p<0.0001). For 6 of the 50 participating preschools, the carriage rate was >40%. We analyzed samples from 334 children and found 56 containing >1 ESBL producer. The prevalence in the study population increased from 2.6% in 2010 to 16.8% in 2016 (p<0.0001), and for 6 of the 50 participating preschools, the carriage rate was >40%. Furthermore, 58% of the ESBL producers were multidrug resistant, and transmission of ESBL-producing and non–ESBL-producing strains was observed at several of the preschools. Toddlers appear to be major carriers of ESBL producers in Sweden.
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Prevalence and Antibiotic Susceptibility among Gram Negative Bacteria Isolated from Intensive Care Units at a Tertiary Care Hospital in Riyadh, Saudi Arabia. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2019. [DOI: 10.22207/jpam.13.1.21] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Garza-González E, Morfín-Otero R, Mendoza-Olazarán S, Bocanegra-Ibarias P, Flores-Treviño S, Rodríguez-Noriega E, Ponce-de-León A, Sanchez-Francia D, Franco-Cendejas R, Arroyo-Escalante S, Velázquez-Acosta C, Rojas-Larios F, Quintanilla LJ, Maldonado-Anicacio JY, Martínez-Miranda R, Ostos-Cantú HL, Gomez-Choel A, Jaime-Sanchez JL, Avilés-Benítez LK, Feliciano-Guzmán JM, Peña-López CD, Couoh-May CA, Molina-Jaimes A, Vázquez -Narvaez EG, Rincón-Zuno J, Rivera-Garay R, Galindo-Espinoza A, Martínez-Ramirez A, Mora JP, Corte- Rojas RE, López-Ovilla I, Monroy-Colin VA, Barajas-Magallón JM, Morales-De-la-Peña CT, Aguirre-Burciaga E, Coronado-Ramírez M, Rosales-García AA, Ayala-Tarín MDJ, Sida-Rodríguez S, Pérez-Vega BA, Navarro-Rodríguez A, Juárez-Velázquez GE, Cetina-Umaña CM, Mena-Ramírez JP, Canizales-Oviedo J, Moreno-Méndez MI, Romero-Romero D, Arévalo-Mejía A, Cobos-Canul DI, Aguilar-Orozco G, Silva-Sánchez J, Camacho-Ortiz A. A snapshot of antimicrobial resistance in Mexico. Results from 47 centers from 20 states during a six-month period. PLoS One 2019; 14:e0209865. [PMID: 30913243 PMCID: PMC6435111 DOI: 10.1371/journal.pone.0209865] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 12/12/2018] [Indexed: 01/22/2023] Open
Abstract
Aim We aimed to assess the resistance rates of antimicrobial-resistant, in bacterial pathogens of epidemiological importance in 47 Mexican centers. Material and methods In this retrospective study, we included a stratified sample of 47 centers, covering 20 Mexican states. Selected isolates considered as potential causatives of disease collected over a 6-month period were included. Laboratories employed their usual methods to perform microbiological studies. The results were deposited into a database and analyzed with the WHONET 5.6 software. Results In this 6-month study, a total of 22,943 strains were included. Regarding Gram-negatives, carbapenem resistance was detected in ≤ 3% in Escherichia coli, 12.5% in Klebsiella sp. and Enterobacter sp., and up to 40% in Pseudomonas aeruginosa; in the latter, the resistance rate for piperacillin-tazobactam (TZP) was as high as 19.1%. In Acinetobacter sp., resistance rates for cefepime, ciprofloxacin, meropenem, and TZP were higher than 50%. Regarding Gram-positives, methicillin resistance in Staphylococcus aureus (MRSA) was as high as 21.4%, and vancomycin (VAN) resistance reached up to 21% in Enterococcus faecium. Acinetobacter sp. presented the highest multidrug resistance (53%) followed by Klebsiella sp. (22.6%) and E. coli (19.4%). Conclusion The multidrug resistance of Acinetobacter sp., Klebsiella sp. and E. coli and the carbapenem resistance in specific groups of enterobacteria deserve special attention in Mexico. Vancomycin-resistant enterococci (VRE) and MRSA are common in our hospitals. Our results present valuable information for the implementation of measures to control drug resistance.
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Affiliation(s)
- Elvira Garza-González
- Hospital Universitario Dr. José Eleuterio González, Monterrey, Nuevo León, Mexico
- * E-mail:
| | - Rayo Morfín-Otero
- Hospital Civil de Guadalajara e Instituto de Patología Infecciosa, Guadalajara, Jalisco, Mexico
| | | | | | | | | | - Alfredo Ponce-de-León
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | | | - Rafael Franco-Cendejas
- Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, Mexico
| | | | | | - Fabián Rojas-Larios
- Hospital Regional Universitario de los Servicios de Salud del Estado de Colima y Facultad de Medicina, Universidad de Colima, Colima, Colima, Mexico
| | | | | | - Rafael Martínez-Miranda
- Hospital General de Mexicali/Facultad de Medicina Mexicali UABC, Mexicali, Baja California, Mexico
| | | | | | | | | | | | | | - Carlos A. Couoh-May
- Hospital General de Mérida Yucatán “Dr. Agustín O ‘Horan”, Mérida, Yucatán, Mexico
| | - Aaron Molina-Jaimes
- Hospital Regional de Alta Especialidad Bicentenario de la Independencia, Tultitlán de Mariano Escobedo, Estado de México, Mexico
| | | | | | - Raúl Rivera-Garay
- Hospital Regional de Alta Especialidad del Bajío, León, Guanajuato, Mexico
| | | | | | - Javier P. Mora
- Hospital de Alta Especialidad de Veracruz, Veracruz, Veracruz, Mexico
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Juan P. Mena-Ramírez
- Hospital General de zona 21 Tepatitlán de Morelos, Tepatitlán de Morelos, Jalisco, Mexico
| | - Jorge Canizales-Oviedo
- Centro Universitario de Salud, UANL Pueblo Nuevo, Monterrey, Nuevo León, Mexico
- Centro Universitario de Salud, UANL Vicente Guerrero, Monterrey, Nuevo León, Mexico
| | | | - Daniel Romero-Romero
- Laboratorio de Análisis Bioquímico Clínicos "Louis Pasteur", Toluca, Estado de México, Mexico
| | | | | | | | | | - Adrián Camacho-Ortiz
- Hospital Universitario Dr. José Eleuterio González, Monterrey, Nuevo León, Mexico
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Tiwari V. Post-translational modification of ESKAPE pathogens as a potential target in drug discovery. Drug Discov Today 2018; 24:814-822. [PMID: 30572117 DOI: 10.1016/j.drudis.2018.12.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 11/23/2018] [Accepted: 12/12/2018] [Indexed: 12/19/2022]
Abstract
ESKAPE pathogens are gaining clinical importance owing to their high pervasiveness and increasing resistance to various antimicrobials. These bacteria have several post-translational modifications (PTMs) that destabilize or divert host cell pathways. Prevalent PTMs of ESKAPE pathogens include addition of chemical groups (acetylation, phosphorylation, methylation and hydroxylation) or complex molecules (AMPylation, ADP-ribosylation, glycosylation and isoprenylation), covalently linked small proteins [ubiquitylation, ubiquitin-like proteins (UBL) conjugation and small ubiquitin-like modifier (SUMO)] or modification of amino acid side-chains (eliminylation and deamidation). Therefore, the understanding of different bacterial PTMs and host proteins manipulated by these PTMs provides better insight into host-pathogen interaction and will also help to develop new antibacterial agents against ESKAPE pathogens.
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Affiliation(s)
- Vishvanath Tiwari
- Department of Biochemistry, Central University of Rajasthan, Bandarsindri, Ajmer 305817, India.
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Zhao Y, Qi BW, Wang YQ, Liu D, Chen F, Huang Z, Pan ZY. Hardware removal or preservation? Decision making based on a newly developed rating scale. Injury 2018; 49:1999-2004. [PMID: 30193911 DOI: 10.1016/j.injury.2018.08.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 08/29/2018] [Indexed: 02/02/2023]
Abstract
Hardware exposure following open reduction and internal fixation (ORIF) surgery is a tricky problem. It is always hard for surgeons to decide whether to keep or remove the hardware. In this study, a rating scale and corresponding clinical path is developed based on former published paper as well as our own experience. New admitted patients are first evaluated and scored once they enter the department. Based on the score they get, patients are assigned to different therapeutic schedule, i.e. (1) hardware preservation with pedicel flap transplantation, (2) debridement for further reevaluation and (3) hardware removal with external fixation. Satisfying clinical outcome is achieved that is characterized with high osseous consolidation rate and low complication rate. The result showed that this newly developed rating scale and the related therapeutic schedule could be an available tool to help surgeons to make decisions in the treatment of hardware exposure.
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Affiliation(s)
- Yong Zhao
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Bai-Wen Qi
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Yao-Qing Wang
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Di Liu
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Fan Chen
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Zhen Huang
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430072, China
| | - Zhen-Yu Pan
- Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430072, China.
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In Vitro Activity of LYS228, a Novel Monobactam Antibiotic, against Multidrug-Resistant Enterobacteriaceae. Antimicrob Agents Chemother 2018; 62:AAC.00552-18. [PMID: 30038040 DOI: 10.1128/aac.00552-18] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 07/14/2018] [Indexed: 12/30/2022] Open
Abstract
LYS228 is a novel monobactam with potent activity against Enterobacteriaceae LYS228 is stable to metallo-β-lactamases (MBLs) and serine carbapenemases, including Klebsiella pneumoniae carbapenemases (KPCs), resulting in potency against the majority of extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae strains tested. Overall, LYS228 demonstrated potent activity against 271 Enterobacteriaceae strains, including multidrug-resistant isolates. Based on MIC90 values, LYS228 (MIC90, 1 μg/ml) was ≥32-fold more active against those strains than were aztreonam, ceftazidime, ceftazidime-avibactam, cefepime, and meropenem. The tigecycline MIC90 was 4 μg/ml against the strains tested. Against Enterobacteriaceae isolates expressing ESBLs (n = 37) or displaying carbapenem resistance (n = 77), LYS228 had MIC90 values of 1 and 4 μg/ml, respectively. LYS228 exhibited potent bactericidal activity, as indicated by low minimal bactericidal concentration (MBC) to MIC ratios (MBC/MIC ratios of ≤4) against 97.4% of the Enterobacteriaceae strains tested (264/271 strains). In time-kill studies, LYS228 consistently achieved reductions in CFU per milliliter of 3 log10 units (≥99.9% killing) at concentrations ≥4× MIC for Escherichia coli and K. pneumoniae reference strains, as well as isolates encoding TEM-1, SHV-1, CTX-M-14, CTX-M-15, KPC-2, KPC-3, and NDM-1 β-lactamases.
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Djordjevic ZM, Folic MM, Jankovic SM. Correlation between cefepime utilisation and Pseudomonas aeruginosa resistance rates to β-lactams and carbapenems in patients with healthcare-associated infections. J Glob Antimicrob Resist 2018; 13:60-64. [DOI: 10.1016/j.jgar.2017.11.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 10/28/2017] [Accepted: 11/08/2017] [Indexed: 12/19/2022] Open
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Gautam V, Sharma M, Singhal L, Kumar S, Kaur P, Tiwari R, Ray P. MALDI-TOF mass spectrometry: An emerging tool for unequivocal identification of non-fermenting Gram-negative bacilli. Indian J Med Res 2018; 145:665-672. [PMID: 28948958 PMCID: PMC5644302 DOI: 10.4103/ijmr.ijmr_1105_15] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND & OBJECTIVES Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) has been instrumental in revolutionizing microbiological identification, especially in high-throughput laboratories. It has enabled the identification of organisms like non-fermenting Gram-negative bacilli (NFGNB), which has been a challenging task using conventional methods alone. In this study an attempt was made to validate MALDI-TOF MS for the identification of clinical isolates of each of the three most common NFGNB, other than Pseudomonas spp., taking molecular methods as the gold standard. METHODS One hundred and fifty clinical isolates of NFGNB, confirmed by molecular methods such as Acinetobacter baumannii[oxa-51 polymerase chain reaction (PCR)], Burkholderia cepacia complex (expanded multilocus sequence typing) and Stenotrophomonas maltophilia (species-specific PCR), were taken. Isolated colonies from fresh cultures of all 150 isolates were smeared onto ground steel plate, with and without formic acid extraction step. The identification was carried out using MALDI-TOF MS Biotyper database. RESULTS A concordance of 100 and 73.33 per cent was found between the molecular techniques and MALDI-TOF MS system in the identification of these isolates up to genus and species levels, respectively. Using a cut-off of 1.9 for reliable identification, rate of species identification rose to 82.66 per cent. Principal component analysis dendrogram and cluster analysis further increased discrimination of isolates. INTERPRETATION & CONCLUSIONS Our findings showed MALDI-TOF MS-based identification of NFGNB as a good, robust method for high-throughput laboratories.
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Affiliation(s)
- Vikas Gautam
- Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Megha Sharma
- Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Lipika Singhal
- Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Sunil Kumar
- Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Parvinder Kaur
- Department of Biotechnology, Panjab University, Chandigarh, India
| | - Rupinder Tiwari
- Department of Biotechnology, Panjab University, Chandigarh, India
| | - Pallab Ray
- Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
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KHAN ADNAN, IMRAN MUDASSAR. OPTIMAL DOSING STRATEGIES AGAINST SUSCEPTIBLE AND RESISTANT BACTERIA. J BIOL SYST 2018. [DOI: 10.1142/s0218339018500031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Mathematical models can be very useful in determining efficient and successful antibiotic dosing techniques against bacterial infections. There are several challenging issues involved, the presence of drug resistant bacteria being one. Recent rise in antibiotic resistant strains of bacteria is a grave public health hazard, hence there is a need to develop dosing protocols taking into account the presence of these resistant strains. In this study, we consider a model for antibiotic treatment of a bacterial infection where the bacteria are divided into two sub-populations: susceptible and resistant. The mechanism of acquisition of resistance by the susceptible bacteria considered is via the process of conjugation. We find the steady-state solutions under an antibiotic protocol of discrete periodic doses and analyze their stability. We also prove an extension of a result that pertains to the persistence of bacteria. In addition, we perform the bifurcation analysis under this dosing protocol and show that bi-stability exists for the bacterial population. Furthermore, efficient treatment strategies are devised that ensure bacterial elimination while minimizing the quantity of antibiotic used. Such treatments are necessary to decrease the chances of further development of resistance in bacteria and to minimize the overall treatment cost. We consider the cases of varying antibiotic costs, different initial bacterial densities and bacterial attachment to solid surfaces, and obtain the optimal strategies for all the cases. The results show that the optimal treatments ensure disinfection for a wide range of scenarios.
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Affiliation(s)
- ADNAN KHAN
- Mathematics Department, Lahore University of Management Sciences, Opposite Sector U, D.H.A. Lahore, Pakistan
| | - MUDASSAR IMRAN
- Gulf University of Science and Technology, Masjid Al Aqsa Street, Mubarak Al Abdullah, Kuwait
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Bokaeian M, Shahraki Zahedani S, Delarampoor A, Atashgah M, Dahmarde B, Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Department of Microbiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran, Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Department of Microbiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran, Department of Microbiology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran, Department of Microbiology, Faculty of Medicine, Zahedan University of Medical Science, Zahedan, Iran, Department of Microbiology, Faculty of Medicine, Zahedan University of Medical Science, Zahedan, Iran. Evaluation of Antibiotic Resistance Patterns of Clinical Klebsiella pneumoniae Isolates from Educational Hospitals in Zahedan, Iran. MEDICAL LABORATORY JOURNAL 2018. [DOI: 10.29252/mlj.12.3.41] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
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Mohapatra DP, Singh SK, Sahoo M, Patole S, Mishra M, Debata NK, Mohapatra H. Retrospective study on clonal relationship of multidrug-resistant Klebsiella spp. indicates closed circulation and initiation of clonal divergence. J Med Microbiol 2018. [PMID: 29521617 DOI: 10.1099/jmm.0.000715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
PURPOSE Antibiotic resistance patterns often exhibit geographical variations. Periodic analyses of resistance spectra and phylogenetic trends are important guides for facilitating judicious use of therapeutic interventions. The present study retrospectively analysed the infection trends, resistance patterns, and clonal relationships between isolates of Klebsiella spp. from a tertiary care hospital. METHODOLOGY Bacterial isolates were collected from January 2013 to June 2014 and their resistance profiles were identified using an automated bacterial identification system. A phylogenetic tree was constructed using housekeeping genes with Molecular Evolutionary Genetic Analysis software. The dN/dS ratio was determined by the Synonymous Non-synonymous Analysis Program while polymorphic sites, and the difference per site was calculated using DNA Sequence Polymorphism software. Statistical Package for Social Science software was used to perform all statistical analyses. KEY FINDINGS The results of this study indicated the prevalence of community-acquired urinary tract and lower respiratory tract infections caused by Klebsiella spp. among geriatric patients. The occurrence of new allelic profiles, a low dN/dS ratio and the lack of strong evolutionary descent between isolates indicated that mutations play a major role in the evolution of the organism. CONCLUSION The findings of this study highlight the consequences of antimicrobial agents exerting a silent and strong selective force on the evolution of Klebsiella spp. The expansion of such analyses is of great importance for addressing rapidly emerging antibiotic-resistant opportunistic pathogens.
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Affiliation(s)
- Debi Prasad Mohapatra
- Department of Microbiology, Institute of Medical Sciences, Kalinga Nagar, Bhubaneswar, Odisha, India
| | - Santosh Kumar Singh
- School of Biological Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar, Jatni, Odisha, India
| | - Minu Sahoo
- School of Biological Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar, Jatni, Odisha, India
| | - Shashank Patole
- School of Biological Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar, Jatni, Odisha, India
| | - Mitali Mishra
- School of Biological Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar, Jatni, Odisha, India
| | - Nagen Kumar Debata
- Department of Microbiology, Institute of Medical Sciences, Kalinga Nagar, Bhubaneswar, Odisha, India
| | - Harapriya Mohapatra
- School of Biological Sciences, National Institute of Science Education and Research, HBNI, Bhubaneswar, Jatni, Odisha, India
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Abrar S, Hussain S, Khan RA, Ul Ain N, Haider H, Riaz S. Prevalence of extended-spectrum-β-lactamase-producing Enterobacteriaceae: first systematic meta-analysis report from Pakistan. Antimicrob Resist Infect Control 2018; 7:26. [PMID: 29484173 PMCID: PMC5819302 DOI: 10.1186/s13756-018-0309-1] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2017] [Accepted: 01/26/2018] [Indexed: 12/18/2022] Open
Abstract
Background South-Asia is known as a hub for multidrug-resistant (MDR) bacteria. Unfortunately, proper surveillance and documentation of MDR pathogens is lacking in Pakistan. The alarming increase in the prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is a serious problem. From this perspective, we analysed published data regarding ESBL-producing Enterobacteriaceae in different regions of Pakistan. Methods A meta-analysis was performed to determine the prevalence of ESBL-producing Enterobacteriaceae in Pakistan. A Web-based search was conducted in electronic databases, including PubMed, Scopus and PakMedi Net (for non-indexed Pakistani journals). Articles published (in either indexed or non-indexed journals) between January 2002 and July 2016 were included in the study. Relevant data were extracted, and statistical analysis was performed using the Metaprop command of STATA version 14.1. Results A total of 68 studies were identified from the electronic data base search, and 55 of these studies met our inclusion criteria. Pakistan’s overall pooled proportion of ESBL-producers was 0.40 (95% CI: 0.34–0.47). The overall heterogeneity was significant (I2 = 99.75%, p < 0.001), and significant ES = 0 (Z = 18.41, p < 0.001) was found. OXA, SHV, TEM and CTX-M were the most commonly found gene variants for ESBLs in these studies. Conclusion The prevalence of ESBL-producing Enterobacteriaceae is high in Pakistan. Little is known about the annual frequency of ESBLs and their prevalence in different provinces of Pakistan. No data are available regarding ESBL frequency in Baluchistan. This underscores an urgent demand for regular surveillance to address this antimicrobial resistance problem. Surveillance to better understand the annual ESBL burden is crucial to improve national and regional guidelines.
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Affiliation(s)
- Samyyia Abrar
- 1Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan
| | - Shahida Hussain
- 1Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan
| | - Rehan Ahmad Khan
- 3College of Statistical and Actuarial Sciences, University of the Punjab, Lahore, Pakistan
| | - Noor Ul Ain
- 1Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan
| | - Hayat Haider
- 1Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan
| | - Saba Riaz
- 1Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan.,Citilab and Research center, Lahore, Pakistan
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Risk factors for Pseudomonas aeruginosa infections in Asia-Pacific and consequences of inappropriate initial antimicrobial therapy: A systematic literature review and meta-analysis. J Glob Antimicrob Resist 2018; 14:33-44. [PMID: 29454906 DOI: 10.1016/j.jgar.2018.02.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 02/07/2018] [Accepted: 02/08/2018] [Indexed: 01/23/2023] Open
Abstract
OBJECTIVES Treating infections of Gram-negative pathogens, in particular Pseudomonas aeruginosa, is a challenge for clinicians in the Asia-Pacific region owing to inherent and acquired antimicrobial resistance. This systematic review and meta-analysis provides updated information on risk factors for P. aeruginosa infection in Asia-Pacific as well as the consequences (e.g. mortality, costs) of initial inappropriate antimicrobial therapy (IIAT). METHODS Embase and MEDLINE databases were searched for Asia-Pacific studies reporting the consequences of IIAT versus initial appropriate antimicrobial therapy (IAAT) in Gram-negative bacterial infections as well as risk factors for serious P. aeruginosa infection. A meta-analysis of unadjusted mortality was performed using a random-effects model. RESULTS A total of 22 studies reporting mortality and 13 reporting risk factors were identified. The meta-analysis demonstrated that mortality was significantly lower in patients receiving IAAT versus IIAT, with a 67% reduction observed for 28- or 30-day all-cause mortality (odds ratio=0.33, 95% confidence interval 0.20-0.55; P<0.001). Risk factors for serious P. aeruginosa infection include previous exposure to antimicrobials, mechanical ventilation and previous hospitalisation. CONCLUSION High rates of antimicrobial resistance in Asia-Pacific as well as the increased mortality associated with IIAT and the presence of risk factors for serious infection highlight the importance of access to newer and appropriate antimicrobials.
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Jang Y, Choi WT, Johnson CT, García AJ, Singh PM, Breedveld V, Hess DW, Champion JA. Inhibition of Bacterial Adhesion on Nanotextured Stainless Steel 316L by Electrochemical Etching. ACS Biomater Sci Eng 2018; 4:90-97. [PMID: 29333490 PMCID: PMC5761049 DOI: 10.1021/acsbiomaterials.7b00544] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 11/28/2017] [Indexed: 11/28/2022]
Abstract
Bacterial adhesion to stainless steel 316L (SS316L), which is an alloy typically used in many medical devices and food processing equipment, can cause serious infections along with substantial healthcare costs. This work demonstrates that nanotextured SS316L surfaces produced by electrochemical etching effectively inhibit bacterial adhesion of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, but exhibit cytocompatibility and no toxicity toward mammalian cells in vitro. Additionally, the electrochemical surface modification on SS316L results in formation of superior passive layer at the surface, improving corrosion resistance. The nanotextured SS316L offers significant potential for medical applications based on the surface structure-induced reduction of bacterial adhesion without use of antibiotic or chemical modifications while providing cytocompatibility and corrosion resistance in physiological conditions.
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Affiliation(s)
- Yeongseon Jang
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, Georgia 30332, United States
| | - Won Tae Choi
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, Georgia 30332, United States
- School of Material Science and Engineering, Georgia Institute of Technology, 500 10th Street, Northwest, Atlanta, Georgia 30332, United States
| | - Christopher T Johnson
- Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30332, United States
| | - Andrés J García
- Woodruff School of Mechanical Engineering, Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, Georgia 30332, United States
| | - Preet M Singh
- School of Material Science and Engineering, Georgia Institute of Technology, 500 10th Street, Northwest, Atlanta, Georgia 30332, United States
| | - Victor Breedveld
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, Georgia 30332, United States
| | - Dennis W Hess
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, Georgia 30332, United States
| | - Julie A Champion
- School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, Georgia 30332, United States
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Adjei CB, Govinden U, Moodley K, Essack SY. Molecular characterisation of multidrug-resistant Pseudomonas aeruginosa from a private hospital in Durban, South Africa. S Afr J Infect Dis 2017. [DOI: 10.1080/23120053.2017.1382090] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Affiliation(s)
- Cosmos B. Adjei
- Antimicrobial Research Unit, University of KwaZulu-Natal, Westville, Durban, South Africa
| | - Usha Govinden
- Antimicrobial Research Unit, University of KwaZulu-Natal, Westville, Durban, South Africa
| | | | - Sabiha Y. Essack
- Antimicrobial Research Unit, University of KwaZulu-Natal, Westville, Durban, South Africa
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In Vitro and In Vivo Efficacy of an LpxC Inhibitor, CHIR-090, Alone or Combined with Colistin against Pseudomonas aeruginosa Biofilm. Antimicrob Agents Chemother 2017; 61:AAC.02223-16. [PMID: 28461320 DOI: 10.1128/aac.02223-16] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Accepted: 04/18/2017] [Indexed: 11/20/2022] Open
Abstract
With the rapid spread of antimicrobial resistance in Gram-negative pathogens, biofilm-associated infections are increasingly harder to treat and combination therapy with colistin has become one of the most efficient therapeutic strategies. Our study aimed to evaluate the potential for the synergy of colistin combined with CHIR-090, a potent LpxC inhibitor, against in vitro and in vivoPseudomonas aeruginosa biofilms. Four P. aeruginosa isolates with various colistin susceptibilities were chosen for evaluation. The tested isolates of P. aeruginosa exhibited MIC values ranging from 1 to 64 and 0.0625 to 0.5 μg/ml for colistin and CHIR-090, respectively. Against 24-h static biofilms, minimum biofilm eradication concentration values ranged from 256 to 512 and 8 to >128 μg/ml for colistin and CHIR-090, respectively. Interestingly, subinhibitory concentrations of CHIR-090 contributed to the eradication of subpopulations of P. aeruginosa with the highest colistin MIC values. The combination of colistin and CHIR-090 at subinhibitory concentrations demonstrated synergistic activity both in vivo and in vitro and prevented the formation of colistin-tolerant subpopulations in in vitro biofilms. In summary, our study highlights the in vivo and in vitro synergistic activity of the colistin and CHIR-090 combination against both colistin-susceptible and -nonsusceptible P. aeruginosa biofilms. Further studies are warranted to investigate the clinical relevance of the combination of these two antimicrobials and outline the underlying mechanism for their synergistic action.
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Rangel M, Castro FFDS, Mota-Lima LD, Clissa PB, Martins DB, Cabrera MPDS, Mortari MR. Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction. PLoS One 2017; 12:e0178785. [PMID: 28570651 PMCID: PMC5453574 DOI: 10.1371/journal.pone.0178785] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 05/18/2017] [Indexed: 01/26/2023] Open
Abstract
The rapid spread of multi-drug resistant pathogens represents a serious threat to public health, considering factors such as high mortality rates, treatment restrictions and high prevalence of multi-drug resistant bacteria in the hospital environment. Antimicrobial peptides (AMPs) may exhibit powerful antimicrobial activity against different and diverse microorganisms, also presenting the advantage of absence or low toxicity towards animal cells. In this study, the evaluation of the antimicrobial activity against multi-drug resistant bacteria of a recently described AMP from wasp, Polydim-I, was performed. Polydim-I presented activity against standard strains (non-carriers of multi-resistant genes) that are susceptible to commercial antimicrobials, and also against multi-drug resistant strains at concentrations bellow 1μg/ml (0.41 μM). This is a rather low concentration among those reported for AMPs. At this concentration we found out that Polydim-I inhibits almost 100% of the tested pathogens growth, while with the ATCC strains the minimum inhibitory concentration (MIC100) is 400 times higher. Also, in relation to in vitro activity of conventional drugs against multi-drug resistant bacteria strains, Polydim-I is almost 10 times more efficient and with broader spectrum. Cationic AMPs are known as multi-target compounds and specially for targeting the phospholipid matrix of bacterial membranes. Exploring the interactions of Polydim-I with lipid bilayers, we have confirmed that this interaction is involved in the mechanism of action. Circular dichroism experiments showed that Polydim-I undergoes a conformational transition from random coil to a mostly helical conformation in the presence of membrane mimetic environments. Zeta potential measurements confirmed the binding and partial charge neutralization of anionic asolectin vesicles, and also suggested a possible aggregation of peptide molecules. FTIR experiments confirmed that some peptide aggregation occurs, which is minimized in the presence of strongly anionic micelles of sodium dodecyl sulfate. Also, Polydim-I induced channel-like structures formation to asolectin lipid bilayers, as demonstrated in the electrophysiology experiments. We suggest that cationic Polydim-I targets the membrane lipids due to electrostatic attraction, partially accumulates, neutralizing the opposite charges and induces pore formation. Similar mechanism of action has already been suggested for other peptides from wasp venoms, especially mastoparans.
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Affiliation(s)
- Marisa Rangel
- Immunopathology Laboratory, Butantan Institute, Sao Paulo-SP, Brazil
- Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília-DF, Brazil
- * E-mail:
| | - Fabíola Fernandes dos Santos Castro
- Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília-DF, Brazil
| | | | | | - Danubia Batista Martins
- Departamento de Física, Universidade Estadual Paulista, UNESP, São José do Rio Preto, SP, Brazil
| | - Marcia Perez dos Santos Cabrera
- Departamento de Física, Universidade Estadual Paulista, UNESP, São José do Rio Preto, SP, Brazil
- Departamento de Química e Ciências Ambientais, Universidade Estadual Paulista, UNESP, São José do Rio Preto, SP, Brazil
| | - Marcia Renata Mortari
- Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília-DF, Brazil
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Korth J, Kukalla J, Rath PM, Dolff S, Krull M, Guberina H, Bienholz A, Wilde B, Becker S, Ross B, Anastasiou OE, Kribben A, Witzke O. Increased resistance of gram-negative urinary pathogens after kidney transplantation. BMC Nephrol 2017; 18:164. [PMID: 28525997 PMCID: PMC5437586 DOI: 10.1186/s12882-017-0580-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Accepted: 05/11/2017] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Urinary tract infection is the most common complication after kidney transplantation. It can cause severe sepsis and transplant loss. Emergence of drug resistance among gram-negative urinary pathogens is the current challenge for urinary tract infection treatment after kidney transplantation. METHODS This study analyzes the antimicrobial susceptibility of gram-negative urinary pathogens after kidney transplantation from 2009 to 2012 at the Transplant Outpatient Clinic of the University Hospital Essen, Germany. Kidney transplant patients at the University Hospital Essen receive regular follow up examinations after transplantation. Midstream urines were examined for bacteriuria at each follow up visit. RESULTS From 2009 to 2012 15.741 urine samples were obtained from 859 patients. In 2985 (19%) samples bacterial growth was detected. The most frequently detected gram-negative bacteria were E.coli 1109 (37%), Klebsiella spp. 242 (8%) and Pseudomonas aeruginosa 136 (4.5%). Klebsiella spp. showed a significant increase of resistance to trimethoprim-sulfamethoxazole by 19% (p = 0.02), ciprofloxacin by 15% (p = 0.01) and ceftazidime by 17% (p = 0.004). E.coli and P. aeruginosa isolates presented no significant differences of antimicrobial susceptibility to the analyzed antibiotics. CONCLUSIONS Antimicrobial resistance of Klebsiella spp. increased significant to trimethoprim-sulfamethoxazole, ciprofloxacin and ceftazidime from 2009 to 2012.
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Affiliation(s)
- Johannes Korth
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.
| | - Julia Kukalla
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Peter-Michael Rath
- Institute for Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Sebastian Dolff
- Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Marco Krull
- Institute of Hygiene, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Hana Guberina
- Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Anja Bienholz
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Benjamin Wilde
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Stefan Becker
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Birgit Ross
- Institute of Hygiene, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Olympia Evdoxia Anastasiou
- Department of Gastroenterology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Andreas Kribben
- Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
| | - Oliver Witzke
- Department of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
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Carbapenem MICs in Escherichia coli and Klebsiella Species Producing Extended-Spectrum β-Lactamases in Critical Care Patients from 2001 to 2009. Antimicrob Agents Chemother 2017; 61:AAC.01718-16. [PMID: 28167543 DOI: 10.1128/aac.01718-16] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 01/10/2017] [Indexed: 12/21/2022] Open
Abstract
Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae strains are increasing in prevalence worldwide. Carbapenem antibiotics are used as a first line of therapy against ESBL-producing Enterobacteriaceae We examined a cohort of critical care patients for gastrointestinal colonization with carbapenem-resistant ESBL-producing strains (CR-ESBL strains). We cultured samples from this cohort of patients for ESBL-producing Klebsiella spp. and Escherichia coli and then tested the first isolate from each patient for susceptibility to imipenem, doripenem, meropenem, and ertapenem. Multilocus sequence typing was performed on isolates that produced an ESBL and that were carbapenem resistant. Among all patients admitted to an intensive care unit (ICU), 4% were positive for an ESBL-producing isolate and 0.64% were positive for a CR-ESBL strain on surveillance culture. Among the first ESBL-producing E. coli and Klebsiella isolates from the patients' surveillance cultures, 11.2% were carbapenem resistant. Sequence type 14 (ST14), ST15, ST42, and ST258 were the dominant sequence types detected in this cohort of patients, with ST15 and ST258 steadily increasing in prevalence from 2006 to 2009. Patients colonized by a CR-ESBL strain were significantly more likely to receive antipseudomonal and anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) therapy prior to ICU admission than patients colonized by carbapenem-susceptible ESBL-producing strains. They were also significantly more likely to have received a cephalosporin or a carbapenem antibiotic than patients colonized by carbapenem-susceptible ESBL-producing strains. In conclusion, in a cohort of patients residing in intensive care units within the United States, we found that 10% of the isolates were resistant to at least one carbapenem antibiotic. The continued emergence of carbapenem-resistant ESBL-producing strains is of significant concern, as infections due to these organisms are notoriously difficult to treat.
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Sahu MK, Siddharth B, Choudhury A, Vishnubhatla S, Singh SP, Menon R, Kapoor PM, Talwar S, Choudhary S, Airan B. Incidence, microbiological profile of nosocomial infections, and their antibiotic resistance patterns in a high volume Cardiac Surgical Intensive Care Unit. Ann Card Anaesth 2017; 19:281-7. [PMID: 27052070 PMCID: PMC4900368 DOI: 10.4103/0971-9784.179625] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Background: Nosocomial infections (NIs) in the postoperative period not only increase morbidity and mortality, but also impose a significant economic burden on the health care infrastructure. This retrospective study was undertaken to (a) evaluate the incidence, characteristics, risk factors and outcomes of NIs and (b) identify common microorganisms responsible for infection and their antibiotic resistance profile in our Cardiac Surgical Intensive Care Unit (CSICU). Patients and Methods: After ethics committee approval, the CSICU records of all patients who underwent cardiovascular surgery between January 2013 and December 2014 were reviewed retrospectively. The incidence of NI, distribution of NI sites, types of microorganisms and their antibiotic resistance, length of CSICU stay, and patient-outcome were determined. Results: Three hundred and nineteen of 6864 patients (4.6%) developed NI after cardiac surgery. Lower respiratory tract infections (LRTIs) accounted for most of the infections (44.2%) followed by surgical-site infection (SSI, 11.6%), bloodstream infection (BSI, 7.5%), urinary tract infection (UTI, 6.9%) and infections from combined sources (29.8%). Acinetobacter, Klebsiella, Escherichia coli, and Staphylococcus were the most frequent pathogens isolated in patients with LRTI, BSI, UTI, and SSI, respectively. The Gram-negative bacteria isolated from different sources were found to be highly resistant to commonly used antibiotics. Conclusion: The incidence of NI and sepsis-related mortality, in our CSICU, was 4.6% and 1.9%, respectively. Lower respiratory tract was the most common site of infection and Gram-negative bacilli, the most common pathogens after cardiac surgery. Antibiotic resistance was maximum with Acinetobacter spp.
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Affiliation(s)
- Manoj Kumar Sahu
- Department of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences, New Delhi, India
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Júnior JGAS, Coutinho HDM, Boris TCC, Cristo JS, Pereira NLF, Figueiredo FG, Cunha FAB, Aquino PEA, Nascimento PAC, Mesquita FJC, Moreira PHF, Coutinho STB, Souza IT, Teixeira GC, Ferreira NMN, Farina EO, Torres CMG, Holanda VN, Pereira VS, Guedes MIF. Chemical Characterization and Cytoprotective Effect of the Hydroethanol Extract from Annona coriacea Mart. (Araticum). Pharmacognosy Res 2016; 8:253-257. [PMID: 27695264 PMCID: PMC5004515 DOI: 10.4103/0974-8490.188882] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
INTRODUCTION Annona coriacea Mart. (araticum) is a widely distributed tree in the cerrado. Its value is attributed principally to the consumption of its fruit which possesses a large nutritive potential. The objective was to identify the chemical profile and evaluate the antimicrobial and cytoprotective activity of the hydroethanol extract of A. coriacea Mart. (HEAC) leaves against the toxicity of mercury chloride. MATERIALS AND METHODS The characterization of components was carried out using high-performance liquid chromatography (HPLC). The minimum inhibitory concentration (MIC) was determined by microdilution method in broth with strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. For evaluation of the modulatory and cytoprotective activity of aminoglycoside antibiotics (gentamicin and amikacin) and mercury chloride (HgCl2), the substances were associated with the HEAC at subinhibitory concentrations (MIC/8). RESULTS AND DISCUSSION The HPLC analysis revealed the presence of flavonoids such as Luteolin (1.84%) and Quercetin (1.19%) in elevated concentrations. The HEAC presented an MIC ≥512 μg/mL and significant antagonistic action in aminoglycosides modulation, and it also showed cytoprotective activity to S. aureus (significance P < 0.0001) and E. coli (significance P < 0.05) bacteria against the mercury chloride heavy metal with significance, this action being attributed to the chelating properties of the flavonoids found in the chemical identification. CONCLUSIONS The results acquired in this study show that the HEAC presents cytoprotective activity over the tested strains in vitro and can also present antagonistic effect when associated with aminoglycosides, reinforcing the necessity of taking caution when combining natural and pharmaceutical products. SUMMARY The hydroalcoholic extract of A. coriacea Mart. presents in vitro cytoprotective activity against the toxic effect of Hg. Abbreviations Used: HPLC-DAD: High-performance liquid chromatography with a diode array detector; MIC: Minimum inhibitory concentration; DMSO: Dimethyl sulfoxide.
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Affiliation(s)
| | | | | | | | - Nara L. F. Pereira
- Department of Biotechnology, Ceará State University, Fortaleza (CE), Brazil
| | | | - Francisco A. B. Cunha
- Department of Biological Chemistry, Regional University of Cariri, Crato (CE), Brazil
| | - Pedro E. A. Aquino
- Department of Medical Microbiology, Federal University of Cearÿ, Fortaleza (CE), Brazil
| | | | | | | | | | - Ivon T. Souza
- Department of Biotechnology, Ceará State University, Fortaleza (CE), Brazil
| | - Gabriela C. Teixeira
- Department of Medicine, Medical School of Juazeiro do Norte - Estacio, Juazeiro do Norte (CE), Brazil
| | | | - Eleonora O. Farina
- Department of Biotechnology, Ceará State University, Fortaleza (CE), Brazil
| | - Cícero M. G. Torres
- Department of Health, University of Fortaleza – UNIFOR, Fortaleza (CE), Brazil
| | | | - Vandbergue S. Pereira
- Department of Medical Microbiology, Federal University of Cearÿ, Fortaleza (CE), Brazil
| | - Maria I. F. Guedes
- Department of Biotechnology, Ceará State University, Fortaleza (CE), Brazil
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Amin AN, Deruelle D. Healthcare-associated infections, infection control and the potential of new antibiotics in development in the USA. Future Microbiol 2016; 10:1049-62. [PMID: 26059625 DOI: 10.2217/fmb.15.33] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
ABSTRACT Healthcare-associated infections (HAIs) caused by drug-resistant Gram-negative pathogens are a significant burden on the US healthcare system. This problem has been further compounded by the recent decline in the development of new antibiotics targeting Gram-negative organisms. US healthcare agencies have been working to limit the occurrence of HAIs by several means, including surveillance systems, prevention practices, antimicrobial stewardship policies and financial incentives. Furthermore, efforts have been made to resume the development of antibiotics in the USA, with the US FDA and US government both implementing acts to boost the number of antibiotics in the clinical pipeline. This review discusses the policies instigated by the US government, including healthcare agencies and the FDA, and describes new antibiotics in development against HAIs.
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Affiliation(s)
- Alpesh N Amin
- Department of Medicine, University of California, Irvine, 101 The City Drive South, Orange, CA 92868, USA
| | - Dennis Deruelle
- IPC Healthcare, 4605 Lankershim Blvd, Ste 617, North Hollywood, CA 91602, USA
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Badura A, Pregartner G, Holzer JC, Feierl G, Grisold AJ. Susceptibility of Austrian Clinical Klebsiella and Enterobacter Isolates Linked to Patient-Related Data. Front Microbiol 2016; 7:34. [PMID: 26903953 PMCID: PMC4743402 DOI: 10.3389/fmicb.2016.00034] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Accepted: 01/11/2016] [Indexed: 11/13/2022] Open
Abstract
The aim of the study was to analyze the antimicrobial susceptibility of Austrian clinical Klebsiella sp. and Enterobacter sp. isolates linked to patient-related data over a time period from 1998 to 2014. The main findings of this study were (i) a marked difference of antibiotic susceptibility rates between different infection sites for both Klebsiella sp. and Enterobacter sp., (ii) significantly greater percentages of resistant isolates among both Klebsiella sp. and Enterobacter sp. in male patients compared to female patients and (iii) significantly greater percentages of resistant isolates among both Klebsiella sp. and Enterobacter sp. from hospital-derived samples compared to samples from the community. In conclusion, our statistical data analysis clearly indicated a strong association of patient-related data and Klebsiella sp. and Enterobacter sp. susceptibility profiles.
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Affiliation(s)
- Alexandra Badura
- Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz Graz, Austria
| | - Gudrun Pregartner
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz Graz, Austria
| | - Judith C Holzer
- Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz Graz, Austria
| | - Gebhard Feierl
- Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz Graz, Austria
| | - Andrea J Grisold
- Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz Graz, Austria
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Bioactivity of noble metal nanoparticles decorated with biopolymers and their application in drug delivery. Int J Pharm 2015; 496:159-72. [DOI: 10.1016/j.ijpharm.2015.10.059] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 10/10/2015] [Accepted: 10/25/2015] [Indexed: 12/19/2022]
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50
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Coya JM, Akinbi HT, Sáenz A, Yang L, Weaver TE, Casals C. Natural Anti-Infective Pulmonary Proteins: In Vivo Cooperative Action of Surfactant Protein SP-A and the Lung Antimicrobial Peptide SP-BN. THE JOURNAL OF IMMUNOLOGY 2015; 195:1628-36. [PMID: 26163587 DOI: 10.4049/jimmunol.1500778] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Accepted: 06/10/2015] [Indexed: 12/19/2022]
Abstract
The anionic antimicrobial peptide SP-B(N), derived from the N-terminal saposin-like domain of the surfactant protein (SP)-B proprotein, and SP-A are lung anti-infective proteins. SP-A-deficient mice are more susceptible than wild-type mice to lung infections, and bacterial killing is enhanced in transgenic mice overexpressing SP-B(N). Despite their potential anti-infective action, in vitro studies indicate that several microorganisms are resistant to SP-A and SP-B(N). In this study, we test the hypothesis that these proteins act synergistically or cooperatively to strengthen each other's microbicidal activity. The results indicate that the proteins acted synergistically in vitro against SP-A- and SP-B(N)-resistant capsulated Klebsiella pneumoniae (serotype K2) at neutral pH. SP-A and SP-B(N) were able to interact in solution (Kd = 0.4 μM), which enabled their binding to bacteria with which SP-A or SP-B(N) alone could not interact. In vivo, we found that treatment of K. pneumoniae-infected mice with SP-A and SP-B(N) conferred more protection against K. pneumoniae infection than each protein individually. SP-A/SP-B(N)-treated infected mice showed significant reduction of bacterial burden, enhanced neutrophil recruitment, and ameliorated lung histopathology with respect to untreated infected mice. In addition, the concentrations of inflammatory mediators in lung homogenates increased early in infection in contrast with the weak inflammatory response of untreated K. pneumoniae-infected mice. Finally, we found that therapeutic treatment with SP-A and SP-B(N) 6 or 24 h after bacterial challenge conferred significant protection against K. pneumoniae infection. These studies show novel anti-infective pathways that could drive development of new strategies against pulmonary infections.
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Affiliation(s)
- Juan Manuel Coya
- Department of Biochemistry and Molecular Biology I, Complutense University of Madrid, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain; and
| | - Henry T Akinbi
- Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229
| | - Alejandra Sáenz
- Department of Biochemistry and Molecular Biology I, Complutense University of Madrid, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain; and
| | - Li Yang
- Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229
| | - Timothy E Weaver
- Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229
| | - Cristina Casals
- Department of Biochemistry and Molecular Biology I, Complutense University of Madrid, 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, 28029 Madrid, Spain; and
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