Antibiotics

12 pages, 1632 KiB

Open AccessEditor’s ChoiceArticle

Impact of COVID-19 on Antimicrobial Consumption and Spread of Multidrug-Resistance in Bacterial Infections

by Kibum Jeon, Seri Jeong, Nuri Lee, Min-Jeong Park, Wonkeun Song, Han-Sung Kim, Hyun Soo Kim and Jae-Seok Kim

Antibiotics 2022, 11(4), 535; https://doi.org/10.3390/antibiotics11040535 - 18 Apr 2022

Cited by 51 | Viewed by 5100

Abstract

The spread of COVID-19 pandemic may have affected antibiotic consumption patterns and the prevalence of colonized or infected by multidrug-resistant (MDR) bacteria. We investigated the differences in the consumption of antibiotics easily prone to resistance and the prevalence of MDR bacteria during the [...] Read more.

The spread of COVID-19 pandemic may have affected antibiotic consumption patterns and the prevalence of colonized or infected by multidrug-resistant (MDR) bacteria. We investigated the differences in the consumption of antibiotics easily prone to resistance and the prevalence of MDR bacteria during the COVID-19 pandemic (March 2020 to September 2021) compared to in the pre-pandemic period (March 2018 to September 2019). Data on usage of antibiotics and infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA) were obtained from hospitalized patients in four university hospitals. The consumption of penicillin with β-lactamase inhibitors (3.4% in ward, 5.8% in intensive care unit (ICU)), and carbapenems (25.9% in ward, 12.1% in ICU) increased during the pandemic period. The prevalence of MRSA (4.7%), VRE (49.0%), CRE (22.4%), and CRPA (20.1%) isolated in clinical samples from the ward and VRE (26.7%) and CRE (36.4%) isolated in clinical samples from the ICU were significantly increased, respectively. Meanwhile, only the prevalence of CRE (38.7%) isolated in surveillance samples from the ward increased. The COVID-19 pandemic is associated with increased consumption of antibiotics and has influenced the prevalence of infections caused by MDR isolates. Full article

(This article belongs to the Special Issue Social Dimensions of Antibiotic Resistance in Asia - a One Health Perspective)

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15 pages, 1634 KiB

Open AccessArticle

Fecal Shedding of Multidrug Resistant Escherichia coli Isolates in Dogs Fed with Raw Meat-Based Diets in Brazil

by Carolina Pantuzza Ramos, Carolina Yumi Iceri Kamei, Flávia Mello Viegas, Jonata de Melo Barbieri, João Luís Reis Cunha, Yaovi Mahuton Gildas Hounmanou, Fernanda Morcatti Coura, Jordana Almeida Santana, Francisco Carlos Faria Lobato, Anders Miki Bojesen and Rodrigo Otávio Silveira Silva

Antibiotics 2022, 11(4), 534; https://doi.org/10.3390/antibiotics11040534 - 17 Apr 2022

Cited by 10 | Viewed by 4483

Abstract

The practice of feeding dogs raw meat-based diets (RMBDs) is growing in several countries, and the risks associated with the ingestion of pathogenic and antimicrobial-resistant Escherichia coli in dogs fed these diets are largely unknown. We characterized E. coli strains isolated from dogs [...] Read more.

The practice of feeding dogs raw meat-based diets (RMBDs) is growing in several countries, and the risks associated with the ingestion of pathogenic and antimicrobial-resistant Escherichia coli in dogs fed these diets are largely unknown. We characterized E. coli strains isolated from dogs fed either an RMBD or a conventional dry feed, according to the phylogroup, virulence genes, and antimicrobial susceptibility profiles of the bacteria. Two hundred and sixteen E. coli strains were isolated. Dogs fed RMBDs shed E. coli strains from the phylogroup E more frequently and were positive for the E. coli heat-stable enterotoxin 1-encoding gene. Isolates from RMBD-fed dogs were also frequently positive for multidrug-resistant E. coli isolates including extended-spectrum beta-lactamase (ESBL) producers. Whole-genome sequencing of seven ESBL-producing E. coli strains revealed that they predominantly harbored blaCTX-M-55, and two strains were also positive for the colistin-resistant gene mcr-1. These results suggest that feeding an RMBD can affect the dog’s microbiota, change the frequency of certain phylogroups, and increase the shedding of diarrheagenic E. coli. Also, feeding an RMBD seemed to be linked with the fecal shedding of multidrug-resistant E. coli, including the spread of strains harboring mobilizable colistin resistance and ESBL genes. This finding is of concern for both animal and human health. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Antimicrobial Use in Companion Animals)

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18 pages, 1224 KiB

Open AccessEditor’s ChoiceReview

Companion Animals—An Overlooked and Misdiagnosed Reservoir of Carbapenem Resistance

by Joana Moreira da Silva, Juliana Menezes, Cátia Marques and Constança Ferreira Pomba

Antibiotics 2022, 11(4), 533; https://doi.org/10.3390/antibiotics11040533 - 17 Apr 2022

Cited by 25 | Viewed by 5115

Abstract

The dissemination of antimicrobial-resistance is a major global threat affecting both human and animal health. Carbapenems are human use β-lactams of last resort; thus. the dissemination of carbapenemase-producing (CP) bacteria creates severe limitations for the treatment of multidrug-resistant bacteria in hospitalized patients. Even [...] Read more.

The dissemination of antimicrobial-resistance is a major global threat affecting both human and animal health. Carbapenems are human use β-lactams of last resort; thus. the dissemination of carbapenemase-producing (CP) bacteria creates severe limitations for the treatment of multidrug-resistant bacteria in hospitalized patients. Even though carbapenems are not routinely used in veterinary medicine, reports of infection or colonization by carbapenemase-producing Enterobacterales in companion animals are being reported. NDM-5 and OXA-48-like carbapenemases are among the most frequently reported in companion animals. Like in humans, Escherichia coli and Klebsiella pneumoniae are the most represented CP Enterobacterales found in companion animals, alongside with Acinetobacter baumannii. Considering that the detection of carbapenemase-producing Enterobacterales presents several difficulties, misdiagnosis of CP bacteria in companion animals may lead to important animal and public-health consequences. It is of the upmost importance to ensure an adequate monitoring and detection of CP bacteria in veterinary microbiology in order to safeguard animal health and minimise its dissemination to humans and the environment. This review encompasses an overview of the carbapenemase detection methods currently available, aiming to guide veterinary microbiologists on the best practices to improve its detection for clinical or research purposes. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Antimicrobial Use in Companion Animals)

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14 pages, 1800 KiB

Open AccessReview

Antibiotic Resistance of Salmonella Typhimurium Monophasic Variant 1,4,[5],12:i:-in China: A Systematic Review and Meta-Analysis

by Xiaojie Qin, Mingzhe Yang, Hua Cai, Yangtai Liu, Leon Gorris, Muhammad Zohaib Aslam, Kai Jia, Tianmei Sun, Xiang Wang and Qingli Dong

Antibiotics 2022, 11(4), 532; https://doi.org/10.3390/antibiotics11040532 - 16 Apr 2022

Cited by 30 | Viewed by 6153

Abstract

Antibiotic resistance in Salmonella is a global public health problem. Salmonella enterica serovar 1,4,[5],12:i:- (S. 1,4,[5],12:i:-), a monophasic variant of Salmonella Typhmurium, is one of the leading Salmonella serovars in several countries. This study aimed to assess the prevalence of antibiotic [...] Read more.

Antibiotic resistance in Salmonella is a global public health problem. Salmonella enterica serovar 1,4,[5],12:i:- (S. 1,4,[5],12:i:-), a monophasic variant of Salmonella Typhmurium, is one of the leading Salmonella serovars in several countries. This study aimed to assess the prevalence of antibiotic resistance to this serovar in China through a systematic review and meta-analysis. Nineteen eligible studies during 2011–2021 were included. A total of 4514 isolates from humans, animals, foods, and the environment were reported, which mainly concerned isolates found in Guangdong, Guangxi, Jiangsu, and Shanghai. A random-effects model was used to estimate the pooled resistance rate of S. 1,4,[5],12:i:-. Rates were found to be very high (values ≥ 75%) for tetracycline, ampicillin, sulfisoxazole, and streptomycin; high (50–75%) for nalidixic acid, amoxicillin–clavulanic acid, and chloramphenicol; and moderate (25–50%) for trimethoprim–sulfamethoxazole, kanamycin, trimethoprim, and gentamicin. The rates of resistance to ciprofloxacin, cefotaxime, ceftriaxone, cefepime, ceftazidime, and colistin were low (values ≤ 25%), but of great concern in terms of their current clinical importance. Furthermore, a high multidrug resistance rate (86%, 95% CI: 78–92%) was present in S. 1,4,[5],12:i:-, with the ASSuT pattern largely dominating. Subgroup analysis results showed that the high heterogeneity of resistance rates was not entirely dependent on isolated sources. Taken together, the severity of antibiotic resistance in S. 1,4,[5],12:i:- urgently requires the rational use of antibiotics in future infection control and antibiotic stewardship programs. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Food-borne Pathogens)

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17 pages, 1901 KiB

Open AccessArticle

Effect of Danofloxacin Treatment on the Development of Fluoroquinolone Resistance in Campylobacter jejuni in Calves

by Debora Brito Goulart, Ashenafi Feyisa Beyi, Zuowei Wu, Mehmet Cemal Adiguzel, Anastasia Schroeder, Kritika Singh, Changyun Xu, Melda Meral Ocal, Renee Dewell, Grant A. Dewell, Paul J. Plummer, Qijing Zhang and Orhan Sahin

Antibiotics 2022, 11(4), 531; https://doi.org/10.3390/antibiotics11040531 - 15 Apr 2022

Cited by 5 | Viewed by 2641

Abstract

Campylobacter is a leading cause of foodborne gastroenteritis. Recent studies have indicated a rise in fluoroquinolone-resistant (FQ-R) Campylobacter in cattle, where FQ is used to control bovine respiratory disease (BRD). To assess the effect of danofloxacin treatment on the development of FQ-resistance in [...] Read more.

Campylobacter is a leading cause of foodborne gastroenteritis. Recent studies have indicated a rise in fluoroquinolone-resistant (FQ-R) Campylobacter in cattle, where FQ is used to control bovine respiratory disease (BRD). To assess the effect of danofloxacin treatment on the development of FQ-resistance in C. jejuni, 30 commercial calves were divided into Group 1, Group 2, and Group 3 (n = 10), and were all inoculated orally with FQ-susceptible (FQ-S) C. jejuni; seven days later, Group 3 was challenged with transtracheal Mannheimia haemolytica, and one week later, Group 2 and Group 3 were injected subcutaneously with danofloxacin. Rectal feces were collected to determine relative percentages of FQ-R Campylobacter via culture. Before oral inoculation with C. jejuni, 87% of calves were naturally colonized by FQ-R C. jejuni. Two days after the inoculation, FQ-R C. jejuni decreased substantially in the majority of calves. Within 24 h of danofloxacin injection, almost all C. jejuni populations shifted to an FQ-R phenotype in both FQ-treated groups, which was only transitory, as FQ-S strains became predominant during later periods. Genotyping indicated that the spike seen in FQ-R C. jejuni populations following the injection was due mainly to enrichment of preexisting FQ-R C. jejuni, rather than development of de novo FQ resistance in susceptible strains. These results provide important insights into the dynamic changes of FQ-resistant Campylobacter in cattle in response to FQ treatment. Full article

(This article belongs to the Special Issue Epidemiology, Impact and Mitigation of Antimicrobial Resistance in Veterinary Medicine)

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10 pages, 468 KiB

Open AccessCommunication

Wild Duck (Anas platyrhynchos) as a Source of Antibiotic-Resistant Salmonella enterica subsp. diarizonae O58—The First Report in Poland

by Joanna Pławińska-Czarnak, Karolina Wódz, Lidia Piechowicz, Ewa Tokarska-Pietrzak, Zbigniew Bełkot, Janusz Bogdan, Jan Wiśniewski, Piotr Kwieciński, Adam Kwieciński and Krzysztof Anusz

Antibiotics 2022, 11(4), 530; https://doi.org/10.3390/antibiotics11040530 - 15 Apr 2022

Cited by 9 | Viewed by 2979

Abstract

The “One Health” approach increasingly demonstrates the global spread of pathogenic microorganisms and their antimicrobial resistance in the environment, both in animals and humans. Salmonella enterica subsp. diarizonae is nowadays very often isolated from cold-blooded reptiles to a lesser extent from sheep, but [...] Read more.

The “One Health” approach increasingly demonstrates the global spread of pathogenic microorganisms and their antimicrobial resistance in the environment, both in animals and humans. Salmonella enterica subsp. diarizonae is nowadays very often isolated from cold-blooded reptiles to a lesser extent from sheep, but unfortunately more and more often from humans. However, there are a few studies describing the isolation of Salmonella enterica subsp. diarizonae from migratory wild birds. The mallard duck (Anas platyrhynchos), a wild animal that traverses the continent of Eurasia, can be an excellent indicator of the spread of intestinal microbes as well as their resistance to antibiotics. This is the first report of the Salmonella enterica subsp. diarizonae detection in Poland in a migrating mallard duck. This research presented the identification difficulties associated with the isolation of Salmonella enterica subsp. diarizonae using three different biochemical tests and advanced serology tests. At the same time, we detected very high antimicrobial resistance in the isolated strain. By using the minimum inhibitory concentration (MIC) method, it was found that the isolated strain of S. enterica subsp. diarizonae has high antibiotic resistance against 14 of the 33 tested antimicrobials agents. The resistance genes that have been identified in S. enterica subsp. diarizonae include aadA, strA/strB, and bla_TEM. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Zoonoses)

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24 pages, 1190 KiB

Open AccessReview

Current Knowledge on Biomaterials for Orthopedic Applications Modified to Reduce Bacterial Adhesive Ability

by Valeria Allizond, Sara Comini, Anna Maria Cuffini and Giuliana Banche

Antibiotics 2022, 11(4), 529; https://doi.org/10.3390/antibiotics11040529 - 15 Apr 2022

Cited by 28 | Viewed by 4462

Abstract

A significant challenge in orthopedics is the design of biomaterial devices that are able to perform biological functions by substituting or repairing various tissues and controlling bone repair when required. This review presents an overview of the current state of our recent research [...] Read more.

A significant challenge in orthopedics is the design of biomaterial devices that are able to perform biological functions by substituting or repairing various tissues and controlling bone repair when required. This review presents an overview of the current state of our recent research into biomaterial modifications to reduce bacterial adhesive ability, compared with previous reviews and excellent research papers, but it is not intended to be exhaustive. In particular, we investigated biomaterials for replacement, such as metallic materials (titanium and titanium alloys) and polymers (ultra-high-molecular-weight polyethylene), and biomaterials for regeneration, such as poly(ε-caprolactone) and calcium phosphates as composites. Biomaterials have been designed, developed, and characterized to define surface/bulk features; they have also been subjected to bacterial adhesion assays to verify their potential capability to counteract infections. The addition of metal ions (e.g., silver), natural antimicrobial compounds (e.g., essential oils), or antioxidant agents (e.g., vitamin E) to different biomaterials conferred strong antibacterial properties and anti-adhesive features, improving their capability to counteract prosthetic joint infections and biofilm formation, which are important issues in orthopedic surgery. The complexity of biological materials is still far from being reached by materials science through the development of sophisticated biomaterials. However, close interdisciplinary work by materials scientists, engineers, microbiologists, chemists, physicists, and orthopedic surgeons is indeed necessary to modify the structures of biomaterials in order to achieve implant integration and tissue regeneration while avoiding microbial contamination. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Medical Materials)

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14 pages, 5309 KiB

Open AccessArticle

Discovery of MurA Inhibitors as Novel Antimicrobials through an Integrated Computational and Experimental Approach

by Fangyuan Zhang, Joshua Graham, Tianhua Zhai, Yanhong Liu and Zuyi Huang

Antibiotics 2022, 11(4), 528; https://doi.org/10.3390/antibiotics11040528 - 14 Apr 2022

Cited by 10 | Viewed by 2979

Abstract

The bacterial cell wall is essential for protecting bacteria from the surrounding environment and maintaining the integrity of bacteria cells. The MurA enzyme, which is an essential enzyme involved in bacterial cell wall synthesis, could be a good drug target for antibiotics. Although [...] Read more.

The bacterial cell wall is essential for protecting bacteria from the surrounding environment and maintaining the integrity of bacteria cells. The MurA enzyme, which is an essential enzyme involved in bacterial cell wall synthesis, could be a good drug target for antibiotics. Although fosfomycin is used clinically as a MurA inhibitor, resistance to this antibiotic is a concern. Here we used molecular docking-based virtual screening approaches to identify potential MurA inhibitors from 1.412 million compounds from three databases. Thirty-three top compounds from virtual screening were experimentally tested in Listeria innocua (Gram-positive bacterium) and Escherichia coli (Gram-negative bacterium). Compound 2-Amino-5-bromobenzimidazole (S17) showed growth inhibition effect in both L. innocua and E. coli, with the same Minimum Inhibitory Concentration (MIC) value of 0.5 mg/mL. Compound 2-[4-(dimethylamino)benzylidene]-n-nitrohydrazinecarboximidamide (C1) had growth inhibition effect only in L. innocua, with a MIC value of 0.5 mg/mL. Two FDA-approved drugs, albendazole (S4) and diflunisal (S8), had a growth inhibition effect only in E. coli, with a MIC value of 0.0625 mg/mL. The identified MurA inhibitors could be potential novel antibiotics. Furthermore, they could be potential fosfomycin substitutes for the fosfomycin-resistant strains. Full article

(This article belongs to the Special Issue Optimization and Improvement of Veterinary Antimicrobial Treatment to Reduce Antimicrobial Resistance)

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11 pages, 476 KiB

Open AccessArticle

Expression of Staphylococcal Virulence Genes In Situ in Human Skin and Soft Tissue Infections

by Michael S. Pulia, Jennifer Anderson, Zhan Ye, Noha S. Elsayed, Thao Le, Jacob Patitucci, Krishna Ganta, Matthew Hall, Vineet K. Singh and Sanjay K. Shukla

Antibiotics 2022, 11(4), 527; https://doi.org/10.3390/antibiotics11040527 - 14 Apr 2022

Cited by 4 | Viewed by 2451

Abstract

Background: Staphylococcus aureus, the most common pathogen in skin and soft tissue infections (SSTI), harbors many well-characterized virulence genes. However, the expression of many of them in SSTIs is unknown. In this study, S. aureus virulence genes expressed in SSTI were investigated. [...] Read more.

Background: Staphylococcus aureus, the most common pathogen in skin and soft tissue infections (SSTI), harbors many well-characterized virulence genes. However, the expression of many of them in SSTIs is unknown. In this study, S. aureus virulence genes expressed in SSTI were investigated. Methods: Fifty-three subjects presenting to the outpatient’s care and emergency departments with a purulent SSTI at two medical centers in Wisconsin, USA, were enrolled in the study. Total mRNA was extracted from the purulent or swab materials, made into cDNA and sequenced on MiSeq platform. The relative cDNA counts to gmk and identifications of the transcripts were carried out with respect to USA300 reference genome and using SAMTOOLS v.1.3 and BWA, respectively. Result: A significantly higher cDNA count was observed for many of the virulence and regulatory gene transcripts in the pus samples compared to the swab samples relative to the cDNA counts for gmk, a housekeeping gene. They were for lukS-PV (18.6 vs. 14.2), isaA (13.4 vs. 8.5), ssaA (4.8 vs. 3.1), hlgC (1.4 vs. 1.33), atl (17.7 vs. 8.33), clfA (3.9 vs. 0.83), eno (6.04 vs. 3.16), fnbA (5.93 vs. 0.33), saeS (6.3 vs. 1.33), saeR (5.4 vs. 3.33) and agrC (5.6 vs. 1.5). Conclusions: A relative increase in the transcripts of several toxins, adhesion and regulatory genes with respect to a gmk in purulent materials suggests their role in situ during SSTIs, perhaps in an orchestrated manner. Full article

(This article belongs to the Special Issue Molecular Evolution and Pathogenicity of Methicillin-Resistant Staphylococcus aureus)

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10 pages, 2478 KiB

Open AccessArticle

Comparative Risk of Acute Kidney Injury Following Concurrent Administration of Vancomycin with Piperacillin/Tazobactam or Meropenem: A Systematic Review and Meta-Analysis of Observational Studies

by Abdulmajeed M. Alshehri, Mohammed Y. Alzahrani, Mohammed A. Abujamal, Mariam H. Abdalla, Shuroug A. Alowais, Osamah M. Alfayez, Majed S. Alyami, Abdulaali R. Almutairi and Omar A. Almohammed

Antibiotics 2022, 11(4), 526; https://doi.org/10.3390/antibiotics11040526 - 14 Apr 2022

Cited by 9 | Viewed by 4414

Abstract

The study aims to comparatively assess the nephrotoxicity of vancomycin when combined with piperacillin-tazobactam (V + PT) or meropenem (V + M) in adult patients hospitalized in general wards or intensive care units. We searched MEDLINE, Google Scholar, and Web of Science for [...] Read more.

The study aims to comparatively assess the nephrotoxicity of vancomycin when combined with piperacillin-tazobactam (V + PT) or meropenem (V + M) in adult patients hospitalized in general wards or intensive care units. We searched MEDLINE, Google Scholar, and Web of Science for observational studies evaluating incidences of AKI in adult patients receiving V + PT or V + M for at least 48 h in general wards or intensive care units. The primary outcome was AKI events, while the secondary outcomes were hospital length of stay, need for renal replacement therapy (RRT), and mortality events. The odds ratio (OR), or mean difference for the hospital length of stay, with a corresponding 95% confidence interval (CI) from the inverse variance weighting random-effects model were estimated for the risk of AKI, RRT, and mortality. Of the 112 studies identified, twelve observational studies were included in this meta-analysis with a total of 14,511 patients. The odds of having AKI were significantly higher in patients receiving V + PT compared with V + M (OR = 2.31; 95%CI 1.69–3.15). There were no differences between V + PT and V + M in the hospital length of stay, RRT, or mortality outcomes. Thus, clinicians should be vigilant while using V + PT, especially in patients who are at high risk of AKI. Full article

(This article belongs to the Special Issue Antibiotic Therapy Optimization in Special Populations)

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14 pages, 648 KiB

Open AccessReview

Plasmid-Mediated Transfer of Antibiotic Resistance Genes in Soil

by Miaoling Meng, Yaying Li and Huaiying Yao

Antibiotics 2022, 11(4), 525; https://doi.org/10.3390/antibiotics11040525 - 14 Apr 2022

Cited by 44 | Viewed by 8370

Abstract

Due to selective pressure from the widespread use of antibiotics, antibiotic resistance genes (ARGs) are found in human hosts, plants, and animals and virtually all natural environments. Their migration and transmission in different environmental media are often more harmful than antibiotics themselves. ARGs [...] Read more.

Due to selective pressure from the widespread use of antibiotics, antibiotic resistance genes (ARGs) are found in human hosts, plants, and animals and virtually all natural environments. Their migration and transmission in different environmental media are often more harmful than antibiotics themselves. ARGs mainly move between different microorganisms through a variety of mobile genetic elements (MGEs), such as plasmids and phages. The soil environment is regarded as the most microbially active biosphere on the Earth’s surface and is closely related to human activities. With the increase in human activity, soils are becoming increasingly contaminated with antibiotics and ARGs. Soil plasmids play an important role in this process. This paper reviews the current scenario of plasmid-mediated migration and transmission of ARGs in natural environments and under different antibiotic selection pressures, summarizes the current methods of plasmid extraction and analysis, and briefly introduces the mechanism of plasmid splice transfer using the F factor as an example. However, as the global spread of drug-resistant bacteria has increased and the knowledge of MGEs improves, the contribution of soil plasmids to resistance gene transmission needs to be further investigated. The prevalence of multidrug-resistant bacteria has also made the effective prevention of the transmission of resistance genes through the plasmid-bacteria pathway a major research priority. Full article

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16 pages, 312 KiB

Open AccessReview

Efficacy of Combination Therapies for the Treatment of Multi-Drug Resistant Gram-Negative Bacterial Infections Based on Meta-Analyses

by Takumi Umemura, Hideo Kato, Mao Hagihara, Jun Hirai, Yuka Yamagishi and Hiroshige Mikamo

Antibiotics 2022, 11(4), 524; https://doi.org/10.3390/antibiotics11040524 - 14 Apr 2022

Cited by 13 | Viewed by 5255

Abstract

There is increasing evidence regarding the optimal therapeutic strategies for multidrug-resistant (MDR) bacteria that cause common infections and are resistant to existing antibiotics. Combination therapies, such as β-lactam combined with β-lactamase inhibitors or combination antibiotics, is a therapeutic strategy to overcome MDR bacteria. [...] Read more.

There is increasing evidence regarding the optimal therapeutic strategies for multidrug-resistant (MDR) bacteria that cause common infections and are resistant to existing antibiotics. Combination therapies, such as β-lactam combined with β-lactamase inhibitors or combination antibiotics, is a therapeutic strategy to overcome MDR bacteria. In recent years, the therapeutic options have expanded as certain combination drugs have been approved in more countries. However, only a handful of guidelines support these options, and the recommendations are based on low-quality evidence. This review describes the significance and efficacy of combination therapy as a therapeutic strategy against Gram-negative MDR pathogens based on previously reported meta-analyses. Full article

(This article belongs to the Special Issue Clinical Pharmacology and Pharmacy of Antimicrobial Agents)

19 pages, 2410 KiB

Open AccessArticle

Availability, Prices and Affordability of Antibiotics Stocked by Informal Providers in Rural India: A Cross-Sectional Survey

by Meenakshi Gautham, Rosalind Miller, Sonia Rego and Catherine Goodman

Antibiotics 2022, 11(4), 523; https://doi.org/10.3390/antibiotics11040523 - 14 Apr 2022

Cited by 8 | Viewed by 5302

Abstract

Providers without formal training deliver healthcare and antibiotics across rural India, but little is known about the antibiotics that they stock. We conducted a cross-sectional survey of such informal providers (IPs) in two districts of West Bengal, and assessed the availability of the [...] Read more.

Providers without formal training deliver healthcare and antibiotics across rural India, but little is known about the antibiotics that they stock. We conducted a cross-sectional survey of such informal providers (IPs) in two districts of West Bengal, and assessed the availability of the antibiotics, as well as their sales volumes, retail prices, percentage markups for IPs and affordability. Of the 196 IPs that stocked antibiotics, 85% stocked tablets, 74% stocked syrups/suspensions/drops and 18% stocked injections. Across all the IPs, 42 antibiotic active ingredients were stocked, which comprised 278 branded generics from 74 manufacturers. The top five active ingredients that were stocked were amoxicillin potassium clavulanate (52% of the IPs), cefixime (39%), amoxicillin (33%), azithromycin (25%) and ciprofloxacin (21%). By the WHO’s AWaRe classification, 71% of the IPs stocked an ACCESS antibiotic and 84% stocked a WATCH antibiotic. The median prices were in line with the government ceiling prices, but with substantial variation between the lowest and highest priced brands. The most affordable among the top five tablets were ciprofloxacin, azithromycin, cefixime and amoxicillin (US$ 0.8, 0.9, 1.9 and 1.9 per course), and the most affordable among the syrups/suspensions/drops were azithromycin and ofloxacin (US$ 1.7 and 4.5 per course, respectively), which are mostly WATCH antibiotics. IPs are a key source of healthcare and antibiotics in rural communities; practical interventions that target IPs need to balance restricting WATCH antibiotics and expanding the basket of affordable ACCESS antibiotics. Full article

(This article belongs to the Special Issue Access, Consumption and Use of Antimicrobials)

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7 pages, 2018 KiB

Open AccessCase Report

Granulomatous Cheilitis or Tuberculid?

by Georgi Tomov, Parvan Voynov and Svitlana Bachurska

Antibiotics 2022, 11(4), 522; https://doi.org/10.3390/antibiotics11040522 - 14 Apr 2022

Cited by 2 | Viewed by 7034

Abstract

The granulomatous cheilitis (GC) presents a heterogeneous group of disorders characterised by a granulomatous inflammation/reaction of the lips to various stimuli. Numerous etiologies have been proposed, including genetic, immunologic, allergic and infectious. Among the secondary causes of GC, an infection by Mycobacterium tuberculosis [...] Read more.

The granulomatous cheilitis (GC) presents a heterogeneous group of disorders characterised by a granulomatous inflammation/reaction of the lips to various stimuli. Numerous etiologies have been proposed, including genetic, immunologic, allergic and infectious. Among the secondary causes of GC, an infection by Mycobacterium tuberculosis (MBT) should be considered. In such cases, the GC could be the clinical presentation of a tuberculid resulting from a hypersensitivity reaction to an underlying focus of active (ATBI) or latent tuberculosis infection (LTBI). This communication describes an immunocompetent patient diagnosed with GC resulting from tuberculid, who responded well to Isoniazid monotherapy. Full article

(This article belongs to the Special Issue Tuberculosis and Non-tuberculous Mycobacterial Infections: Control, Diagnosis and Antimicrobial Therapies)

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14 pages, 4172 KiB

Open AccessArticle

Effects of Curcumin and Tetracycline Gel on Experimental Induced Periodontitis as an Anti-Inflammatory, Osteogenesis Promoter and Enhanced Bone Density through Altered Iron Levels: Histopathological Study

by Chenar Anwar Mohammad, Khadeeja Mohammed Ali, Rafal AbdulRazaq Al-Rawi and Sarhang Sarwat Gul

Antibiotics 2022, 11(4), 521; https://doi.org/10.3390/antibiotics11040521 - 13 Apr 2022

Cited by 8 | Viewed by 2663

Abstract

Adjunctive use of antimicrobials with scaling and root planing (SRP) is necessary to better eradicate dental biofilm. Tetracycline (T) is the most commonly used antimicrobial; however, it has limitations. This study evaluates the effect of curcumin (CU) as adjunct to SRP on inflammatory [...] Read more.

Adjunctive use of antimicrobials with scaling and root planing (SRP) is necessary to better eradicate dental biofilm. Tetracycline (T) is the most commonly used antimicrobial; however, it has limitations. This study evaluates the effect of curcumin (CU) as adjunct to SRP on inflammatory markers, collagen fiber deposition, and altered iron level. A total of 32 Wistar rats were divided into five groups: no experimental periodontitis (healthy control), experimental periodontitis (EPD), EPD treated with SRP alone (SRP), EPD treated with SRP+T (SRP+T), and EPD treated with SRP+CU (SRP+CU). After 2 and 4 weeks of treatment, tissue samples were assessed by hematoxylin and eosin, and special stains (Perls’ stain and Masson’s Trichrome) for counting of inflammatory cells, angiogenesis, collagen fibers, and iron deposition. Significant reductions in inflammatory cells infiltration and alveolar bone resorption with angiogenesis and collagen fibers deposition were detected after 2 and 4 weeks in both SRP+T and SRP+CU groups. SRP+CU resulted in a significant reduction in osteoclast numbers (week 2) and iron deposition (week 4) in bone trabeculae as compared to SRP and SRP+T groups. The adjunctive use of CU showed comparable results to T in the reduction in inflammation and bone resorption. Furthermore, CU has potential osteogenesis and healing effects. Full article

(This article belongs to the Special Issue Recent Advances in Antimicrobial Drug Discovery)

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18 pages, 381 KiB

Open AccessReview

Bacterial Multidrug Efflux Pumps at the Frontline of Antimicrobial Resistance: An Overview

by Lulu Huang, Cuirong Wu, Haijiao Gao, Chao Xu, Menghong Dai, Lingli Huang, Haihong Hao, Xu Wang and Guyue Cheng

Antibiotics 2022, 11(4), 520; https://doi.org/10.3390/antibiotics11040520 - 13 Apr 2022

Cited by 71 | Viewed by 10288

Abstract

Multidrug efflux pumps function at the frontline to protect bacteria against antimicrobials by decreasing the intracellular concentration of drugs. This protective barrier consists of a series of transporter proteins, which are located in the bacterial cell membrane and periplasm and remove diverse extraneous [...] Read more.

Multidrug efflux pumps function at the frontline to protect bacteria against antimicrobials by decreasing the intracellular concentration of drugs. This protective barrier consists of a series of transporter proteins, which are located in the bacterial cell membrane and periplasm and remove diverse extraneous substrates, including antimicrobials, organic solvents, toxic heavy metals, etc., from bacterial cells. This review systematically and comprehensively summarizes the functions of multiple efflux pumps families and discusses their potential applications. The biological functions of efflux pumps including their promotion of multidrug resistance, biofilm formation, quorum sensing, and survival and pathogenicity of bacteria are elucidated. The potential applications of efflux pump-related genes/proteins for the detection of antibiotic residues and antimicrobial resistance are also analyzed. Last but not least, efflux pump inhibitors, especially those of plant origin, are discussed. Full article

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

14 pages, 1747 KiB

Open AccessArticle

Effect of β-Glucan Supplementation on Growth Performance and Intestinal Epithelium Functions in Weaned Pigs Challenged by Enterotoxigenic Escherichia coli

by Yuankang Zhou, Yuheng Luo, Bing Yu, Ping Zheng, Jie Yu, Zhiqing Huang, Xiangbing Mao, Junqiu Luo, Hui Yan and Jun He

Antibiotics 2022, 11(4), 519; https://doi.org/10.3390/antibiotics11040519 - 13 Apr 2022

Cited by 14 | Viewed by 2650

Abstract

Background: To examine the effect of β-glucan (BGL) supplementation on growth performance and intestinal epithelium functions in weaned pigs upon Enterotoxigenic Escherichia coli (ETEC) challenge. Methods: Thirty-two weaned pigs (Duroc × Landrace × Yorkshire) were assigned into four groups. Pigs fed with a [...] Read more.

Background: To examine the effect of β-glucan (BGL) supplementation on growth performance and intestinal epithelium functions in weaned pigs upon Enterotoxigenic Escherichia coli (ETEC) challenge. Methods: Thirty-two weaned pigs (Duroc × Landrace × Yorkshire) were assigned into four groups. Pigs fed with a basal diet or basal diet containing 500 mg/kg BGL were orally infused with ETEC or culture medium. Results: Results showed BGL tended to increase the average daily gain (ADG) in ETEC-challenged pigs (0.05 < p < 0.1). Dietary BGL supplementation had no significant influence on nutrient digestibility (p > 0.05). However, BGL improved the serum concentrations of immunoglobulin (Ig) A and IgG, and was beneficial to relieve the increasement of the concentrations of inflammatory cytokines such as the TNF-α and IL-6 upon ETEC-challenge (p < 0.05). Interestingly, BGL significantly increased the duodenal, jejunal and ileal villus height, and increased the jejunal ratio of villus height to crypt depth (V/C) upon ETEC challenge (p < 0.05). BGL also increased the activities of mucosal, sucrase and maltase in the ETEC-challenged pigs (p < 0.05). Moreover, BGL elevated the abundance of Lactobacillus and the concentration of propanoic acid in colon in the ETEC-challenged pigs (p < 0.05). Importantly, BGL elevated the expression levels of zonula occludins-1 (ZO-1) and mucin-2 (MUC-2) in the small intestinal mucosa upon ETEC challenge (p < 0.05). BGL also upregulated the expressions of functional genes such as the claudin-1, cationic amino acid transporter-1 (CAT-1), LAT-1, L amino acid transporter-1 (LAT1), fatty acid transport proteins (FATP1), FATP4, and sodium/glucose cotransporter-1 (SGLT-1) in the duodenum, and the occludin-1 and CAT-1 in the jejunum upon ETEC challenge (p < 0.05). Conclusions: These results suggested that BGL can attenuate intestinal damage in weaned pigs upon ETEC challenge, which was connected with the suppressed secretion of inflammatory cytokines and enhanced serum immunoglobulins, as well as improved intestinal epithelium functions and microbiota. Full article

(This article belongs to the Special Issue Green Antimicrobials)

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14 pages, 2208 KiB

Open AccessArticle

Antimicrobial Activity of the Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate (EGCG) against Clinical Isolates of Multidrug-Resistant Vibrio cholerae

by Achiraya Siriphap, Anong Kiddee, Acharaporn Duangjai, Atchariya Yosboonruang, Grissana Pook-In, Surasak Saokaew, Orasa Sutheinkul and Anchalee Rawangkan

Antibiotics 2022, 11(4), 518; https://doi.org/10.3390/antibiotics11040518 - 13 Apr 2022

Cited by 17 | Viewed by 3842

Abstract

The spread of multidrug-resistant (MDR) Vibrio cholerae necessitates the development of novel prevention and treatment strategies. This study aims to evaluate the in vitro antibacterial activity of green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) against MDR V. cholerae. First, MIC and MBC values were [...] Read more.

The spread of multidrug-resistant (MDR) Vibrio cholerae necessitates the development of novel prevention and treatment strategies. This study aims to evaluate the in vitro antibacterial activity of green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) against MDR V. cholerae. First, MIC and MBC values were evaluated by broth microdilution techniques against 45 V. cholerae strains. The checkerboard assay was then used to determine the synergistic effect of EGCG and tetracycline. The pharmaceutical mode of action of EGCG was clarified by time-killing kinetics and membrane disruption assay. Our results revealed that all of the 45 clinical isolates were susceptible to EGCG, with MIC and MBC values in the range of 62.5–250 µg/mL and 125–500 µg/mL, respectively. Furthermore, the combination of EGCG and tetracycline was greater than either treatment alone, with a fractional inhibitory concentration index (FICI) of 0.009 and 0.018 in the O1 and O139 representative serotypes, respectively. Time-killing kinetics analysis suggested that EGCG had bactericidal activity for MDR V. cholerae after exposure to at least 62.5 µg/mL EGCG within 1 h. The mode of action of EGCG might be associated with membrane disrupting permeability, as confirmed by scanning electron microscopy. This is the first indication that EGCG is a viable anti-MDR V. cholerae treatment. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Natural Products and Plants)

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12 pages, 289 KiB

Open AccessArticle

Optimizing Doses of Ceftolozane/Tazobactam as Monotherapy or in Combination with Amikacin to Treat Carbapenem-Resistant Pseudomonas aeruginosa

by Worapong Nasomsong, Parnrada Nulsopapon, Dhitiwat Changpradub, Supanun Pungcharoenkijkul, Patomroek Hanyanunt, Tassanawan Chatreewattanakul and Wichai Santimaleeworagun

Antibiotics 2022, 11(4), 517; https://doi.org/10.3390/antibiotics11040517 - 13 Apr 2022

Cited by 2 | Viewed by 2773

Abstract

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a hospital-acquired pathogen with a high mortality rate and limited treatment options. We investigated the activity of ceftolozane/tazobactam (C/T) and its synergistic effects with amikacin to extend the range of optimal therapeutic choices with appropriate doses. The E-test [...] Read more.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a hospital-acquired pathogen with a high mortality rate and limited treatment options. We investigated the activity of ceftolozane/tazobactam (C/T) and its synergistic effects with amikacin to extend the range of optimal therapeutic choices with appropriate doses. The E-test method is used to determine in vitro activity. The optimal dosing regimens to achieve a probability of target attainment (PTA) and a cumulative fraction of response (CFR) of ≥90% were simulated using the Monte Carlo method. Of the 66 CRPA isolates, the rate of susceptibility to C/T was 86.36%, with an MIC₅₀ and an MIC₉₀ of 0.75 and 24 µg/mL, respectively. Synergistic and additive effects between C/T and amikacin were observed in 24 (40%) and 18 (30%) of 60 CRPA isolates, respectively. The extended infusion of C/T regimens achieved a ≥90% PTA of 75% and a 100% fT > MIC at C/T MICs of 4 and 2 µg/mL, respectively. Only the combination of either a short or prolonged C/T infusion with a loading dose of amikacin of 20–25 mg/kg, followed by 15–20 mg/kg/day amikacin dosage, achieved ≥90% CFR. The C/T infusion, combined with currently recommended amikacin dose regimens, should be considered to manage CRPA infections. Full article

(This article belongs to the Special Issue Clinical Pharmacology and Pharmacy of Antimicrobial Agents)

11 pages, 272 KiB

Open AccessArticle

The Molecular Characterization of Virulence Determinants and Antibiotic Resistance Patterns in Human Bacterial Uropathogens

by Naveed Ahmed, Hira Khalid, Mariam Mushtaq, Sakeenabi Basha, Ali A. Rabaan, Mohammed Garout, Muhammad A. Halwani, Abbas Al Mutair, Saad Alhumaid, Zainab Al Alawi and Chan Yean Yean

Antibiotics 2022, 11(4), 516; https://doi.org/10.3390/antibiotics11040516 - 13 Apr 2022

Cited by 20 | Viewed by 3327

Abstract

The high rates of bacterial infections affect the economy worldwide by contributing to the increase in morbidity and treatment costs. The present cross-sectional study was carried out to evaluate the prevalence of bacterial infection in urinary tract infection (UTI) patients and to evaluate [...] Read more.

The high rates of bacterial infections affect the economy worldwide by contributing to the increase in morbidity and treatment costs. The present cross-sectional study was carried out to evaluate the prevalence of bacterial infection in urinary tract infection (UTI) patients and to evaluate the antimicrobial resistance rate (AMR) in a Tertiary Care Hospital in Lahore, Pakistan. The study was conducted for the period of one year from January 2020 to December 2020. A total of 1899 different clinical samples were collected and examined for bacterial cultures using standard procedures. Samples were inoculated on different culture media to isolate bacterial isolates and for identification and susceptibility testing. A total of 1107/1899 clinical samples were positive for Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and other bacterial isolates. Methicillin-resistant S. aureus (MRSA) prevalence was 16.93% from these positive cases. MRSA strains were found to be highly resistant to amikacin, clindamycin, fusidic acid, gentamicin and tobramycin, while highest sensitivity was noted against vancomycin (100%) and linezolid (100%). MRSA and high rates of multidrug resistance (MDR) pose a serious therapeutic burden to critically ill patients. A systematic and concerted effort is essential to rapidly identify high-risk patients and to reduce the burden of AMR. Full article

(This article belongs to the Special Issue Antibiotic-Resistant Enterobacteriaceae)

6 pages, 231 KiB

Open AccessCase Report

Azithromycin: An Underappreciated Quinolone-Sparing Oral Treatment for Pseudomonas aeruginosa Infections

by Erlinda R. Ulloa and George Sakoulas

Antibiotics 2022, 11(4), 515; https://doi.org/10.3390/antibiotics11040515 - 13 Apr 2022

Cited by 6 | Viewed by 4247

Abstract

Outpatient treatment of Pseudomonas aeruginosa infections is challenged by increasing rates of resistance to fluoroquinolones, the only class of antibiotics which offers an established oral route of administration against this organism. Azithromycin does not demonstrate activity against P. aeruginosa when evaluated under standard [...] Read more.

Outpatient treatment of Pseudomonas aeruginosa infections is challenged by increasing rates of resistance to fluoroquinolones, the only class of antibiotics which offers an established oral route of administration against this organism. Azithromycin does not demonstrate activity against P. aeruginosa when evaluated under standard methods of susceptibility testing with bacteriologic media. However, growing evidence shows that azithromycin is very active against P. aeruginosa when using physiologic media that recapitulate the in vivo milieu and is supported by animal models of infection and various clinical settings, including cystic fibrosis. We present three cases of outpatient management of P. aeruginosa otolaryngological infections successfully treated with oral azithromycin, 500 mg daily ranging from 3–8 weeks, where use of fluoroquinolones was not possible due to either resistance or patient intolerance. We review the previous data supporting this clinical approach, in the hope that this will alert clinicians to this treatment option and to inspire a more thorough clinical trial evaluation of azithromycin in this environment of growing medical need. Full article

(This article belongs to the Special Issue Epidemiology, Prognosis and Antimicrobial Treatment of Extensively Antibiotic-Resistant Bacterial Infections)

8 pages, 696 KiB

Open AccessCommunication

Multicenter Study of Carbapenemase-Producing Enterobacterales in Havana, Cuba, 2016–2021

by Haiyang Yu, María Karla González Molina, Yenisel Carmona Cartaya, Marcia Hart Casares, Meiji Soe Aung, Nobumichi Kobayashi and Dianelys Quiñones Pérez

Antibiotics 2022, 11(4), 514; https://doi.org/10.3390/antibiotics11040514 - 12 Apr 2022

Cited by 5 | Viewed by 2314

Abstract

Surveillance of carbapenem resistance is particularly important for Enterobacterales, mainly in countries with limited healthcare resources. We conducted a cross-sectional study to detect carbapenem-resistant Enterobacterales at 10 sentinel hospitals in Havana, Cuba for a six year-period (2016–2021) by the National Reference Laboratory for [...] Read more.

Surveillance of carbapenem resistance is particularly important for Enterobacterales, mainly in countries with limited healthcare resources. We conducted a cross-sectional study to detect carbapenem-resistant Enterobacterales at 10 sentinel hospitals in Havana, Cuba for a six year-period (2016–2021) by the National Reference Laboratory for Health Care-Associated Infections in the Pedro Kourí Institute. A total of 152 isolates were collected with phenotypic production of metallo-β-lactamase. NDM-type carbapenemase was detected in all the 152 isolates, and KPC-type enzyme gene was simultaneously identified in four NDM-positive isolates. The most abundant carbapenemase-producing Enterobacterales (CPE) species was Klebsiella pneumoniae (69.7%), followed by Enterobacter cloacae complex (13.2%), and Escherichia coli (5.9%). Over the study period, among CPE, prevalence of K. pneumoniae was almost constant, while Enterobacter spp. showed slightly increasing tendency. The urinary tract (36.2%) was the most prevalent source of infection with CPE, followed by bloodstream (26.3%) and surgical wound (17.1%), being frequently derived from Intensive Care Units (35.5%) and urology wards (21.7%). This study revealed the present situation of CPE in hospitals in Havana, Cuba, showing the emergence and dissemination of Enterobacterales producing NDM-type carbapenemase, mainly K. pneumoniae. Full article

(This article belongs to the Special Issue Carbapenem-Resistant Enterobacterales)

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26 pages, 51969 KiB

Open AccessArticle

Secondary Metabolite Variation and Bioactivities of Two Marine Aspergillus Strains in Static Co-Culture Investigated by Molecular Network Analysis and Multiple Database Mining Based on LC-PDA-MS/MS

by Yuan Wang, Evgenia Glukhov, Yifan He, Yayue Liu, Longjian Zhou, Xiaoxiang Ma, Xueqiong Hu, Pengzhi Hong, William H. Gerwick and Yi Zhang

Antibiotics 2022, 11(4), 513; https://doi.org/10.3390/antibiotics11040513 - 12 Apr 2022

Cited by 29 | Viewed by 3566

Abstract

Co-culture is known as an efficient way to explore the metabolic potential of fungal strains for new antibiotics and other therapeutic agents that could counter emerging health issues. To study the effect of co-culture on the secondary metabolites and bioactivities of two marine [...] Read more.

Co-culture is known as an efficient way to explore the metabolic potential of fungal strains for new antibiotics and other therapeutic agents that could counter emerging health issues. To study the effect of co-culture on the secondary metabolites and bioactivities of two marine strains, Aspergillus terreus C23-3 and Aspergillus. unguis DLEP2008001, they were co-cultured in live or inactivated forms successively or simultaneously. The mycelial morphology and high-performance thin layer chromatography (HPTLC) including bioautography of the fermentation extracts were recorded. Furthermore, the agar cup-plate method was used to compare the antimicrobial activity of the extracts. Based on the above, liquid chromatography-photodiode array-tandem mass spectrometry (LC-PDA-MS/MS) together with Global Natural Products Social molecular networking (GNPS) and multiple natural products database mining were used to further analyze their secondary metabolite variations. The comprehensive results showed the following trends: (1) The strain first inoculated will strongly inhibit the growth and metabolism of the latter inoculated one; (2) Autoclaved A. unguis exerted a strong inducing effect on later inoculated A. terreus, while the autoclaved A. terreus showed high stability of its metabolites and still potently suppressed the growth and metabolism of A. unguis; (3) When the two strains are inoculated simultaneously, they both grow and produce metabolites; however, the A. terreus seemed to be more strongly induced by live A. unguis and this inducing effect surpassed that of the autoclaved A. unguis. Under some of the conditions, the extracts showed higher antimicrobial activity than the axenic cultures. Totally, A. unguis was negative in response but potent in stimulating its rival while A. terreus had the opposite effect. Fifteen MS detectable and/or UV active peaks showed different yields in co-cultures vs. the corresponding axenic culture. GNPS analysis assisted by multiple natural products databases mining (PubChem, Dictionary of Natural Products, NPASS, etc.) gave reasonable annotations for some of these peaks, including antimicrobial compounds such as unguisin A, lovastatin, and nidulin. However, some of the peaks were correlated with antagonistic properties and remain as possible novel compounds without mass or UV matching hits from any database. It is intriguing that the two strains both synthesize chemical ‘weapons’ for antagonism, and that these are upregulated when needed in competitive co-culture environment. At the same time, compounds not useful in this antagonistic setting are downregulated in their expression. Some of the natural products produced during antagonism are unknown chlorinated metabolites and deserve further study for their antimicrobial properties. In summary, this study disclosed the different responses of two Aspergillus strains in co-culture, revealed their metabolic variation, and displayed new opportunities for antibiotic discovery. Full article

(This article belongs to the Special Issue Antimicrobial Natural Products)

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17 pages, 1250 KiB

Open AccessReview

The Bacterial Urban Resistome: Recent Advances

by Alberto Vassallo, Steve Kett, Diane Purchase and Massimiliano Marvasi

Antibiotics 2022, 11(4), 512; https://doi.org/10.3390/antibiotics11040512 - 12 Apr 2022

Cited by 8 | Viewed by 3837

Abstract

Cities that are densely populated are reservoirs of antibiotic resistant genes (ARGs). The overall presence of all resistance genes in a specific environment is defined as a resistome. Spatial proximity of surfaces and different hygienic conditions leads to the transfer of antibiotic resistant [...] Read more.

Cities that are densely populated are reservoirs of antibiotic resistant genes (ARGs). The overall presence of all resistance genes in a specific environment is defined as a resistome. Spatial proximity of surfaces and different hygienic conditions leads to the transfer of antibiotic resistant bacteria (ARB) within urban environments. Built environments, public transportation, green spaces, and citizens’ behaviors all support persistence and transfer of antimicrobial resistances (AMR). Various unique aspects of urban settings that promote spread and resilience of ARGs/ARB are discussed: (i) the role of hospitals and recreational parks as reservoirs; (ii) private and public transportation as carriers of ARGs/ARB; (iii) the role of built environments as a hub for horizontal gene transfer even though they support lower microbial biodiversity than outdoor environments; (iv) the need to employ ecological and evolutionary concepts, such as modeling the fate of a specific ARG/ARB, to gain enhanced health risk assessments. Our understanding and our ability to control the rise of AMR in an urban setting is linked to our knowledge of the network connecting urban reservoirs and the environment. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and the Environment: One Health Approach, 2nd Edition)

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25 pages, 3276 KiB

Open AccessEditor’s ChoiceReview

Diagnosis of Bloodstream Infections: An Evolution of Technologies towards Accurate and Rapid Identification and Antibiotic Susceptibility Testing

by Kristel C. Tjandra, Nikhil Ram-Mohan, Ryuichiro Abe, Marjan M. Hashemi, Jyong-Huei Lee, Siew Mei Chin, Manuel A. Roshardt, Joseph C. Liao, Pak Kin Wong and Samuel Yang

Antibiotics 2022, 11(4), 511; https://doi.org/10.3390/antibiotics11040511 - 12 Apr 2022

Cited by 26 | Viewed by 8048

Abstract

Bloodstream infections (BSI) are a leading cause of death worldwide. The lack of timely and reliable diagnostic practices is an ongoing issue for managing BSI. The current gold standard blood culture practice for pathogen identification and antibiotic susceptibility testing is time-consuming. Delayed diagnosis [...] Read more.

Bloodstream infections (BSI) are a leading cause of death worldwide. The lack of timely and reliable diagnostic practices is an ongoing issue for managing BSI. The current gold standard blood culture practice for pathogen identification and antibiotic susceptibility testing is time-consuming. Delayed diagnosis warrants the use of empirical antibiotics, which could lead to poor patient outcomes, and risks the development of antibiotic resistance. Hence, novel techniques that could offer accurate and timely diagnosis and susceptibility testing are urgently needed. This review focuses on BSI and highlights both the progress and shortcomings of its current diagnosis. We surveyed clinical workflows that employ recently approved technologies and showed that, while offering improved sensitivity and selectivity, these techniques are still unable to deliver a timely result. We then discuss a number of emerging technologies that have the potential to shorten the overall turnaround time of BSI diagnosis through direct testing from whole blood—while maintaining, if not improving—the current assay’s sensitivity and pathogen coverage. We concluded by providing our assessment of potential future directions for accelerating BSI pathogen identification and the antibiotic susceptibility test. While engineering solutions have enabled faster assay turnaround, further progress is still needed to supplant blood culture practice and guide appropriate antibiotic administration for BSI patients. Full article

(This article belongs to the Special Issue Rapid Diagnostics of the Antimicrobial Resistance)

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16 pages, 1513 KiB

Open AccessArticle

Synergistic Antibacterial and Anti-inflammatory Activities of Ocimum tenuiflorum Ethanolic Extract against Major Bacterial Mastitis Pathogens

by Janejira Srichok, Natthika Yingbun, Teerada Kowawisetsut, Sudsaijai Kornmatitsuk, Uthaiwan Suttisansanee, Piya Temviriyanukul and Boonrat Chantong

Antibiotics 2022, 11(4), 510; https://doi.org/10.3390/antibiotics11040510 - 12 Apr 2022

Cited by 13 | Viewed by 3780

Abstract

Mastitis is the most prevalent global illness affecting dairy cows. This bacterial infection damages and inflames the udder tissues. Several plant extracts have demonstrated synergistic antibacterial activities with standard drugs in mastitis treatment. Scant information exists on Ocimum tenuiflorum L. This study evaluated [...] Read more.

Mastitis is the most prevalent global illness affecting dairy cows. This bacterial infection damages and inflames the udder tissues. Several plant extracts have demonstrated synergistic antibacterial activities with standard drugs in mastitis treatment. Scant information exists on Ocimum tenuiflorum L. This study evaluated the antibacterial activity of O. tenuiflorum extract and its interaction with antibacterial drugs against common mastitis pathogens including Staphylococcus aureus, coagulase-negative Staphylococci (CNS), Streptococcus agalactiae, and Escherichia coli. Anti-inflammatory activities in LPS-stimulated RAW264.7 macrophage cells were also studied. The O. tenuiflorum extract exhibited antibacterial activities against S. aureus, CNS, and S. agalactiae with minimum inhibitory concentration (MIC) ranging from 3.9 to 31.2 µg/mL and minimum bactericidal concentration (MBC) ranging from 15.6 to 500 µg/mL. Combinations of O. tenuiflorum with penicillin or amoxicillin-clavulanic acid showed synergistic effects against all tested strains but an additive effect with cefazolin and gentamicin. Pretreatment of the extract significantly decreased the expression of inflammatory molecules (IL-6, TNF-α, IL-1β, iNOS, COX-2, and PGE2) generated by LPS in macrophages. Results suggested O. tenuiflorum effectiveness against various Gram-positive mastitis bacteria, with the potential to reduce antibacterial doses and combat inflammation. Full article

(This article belongs to the Special Issue Treatment of Mastitis in Dairy Cattle)

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12 pages, 1392 KiB

Open AccessArticle

Inactivation of a New Potassium Channel Increases Rifampicin Resistance and Induces Collateral Sensitivity to Hydrophilic Antibiotics in Mycobacterium smegmatis

by Thi Thuy Do, Jerónimo Rodríguez-Beltran, Esmeralda Cebrián-Sastre, Alexandro Rodríguez-Rojas, Alfredo Castañeda-García and Jesús Blázquez

Antibiotics 2022, 11(4), 509; https://doi.org/10.3390/antibiotics11040509 - 12 Apr 2022

Cited by 4 | Viewed by 2612

Abstract

Rifampicin is a critical first-line antibiotic for treating mycobacterial infections such as tuberculosis, one of the most serious infectious diseases worldwide. Rifampicin resistance in mycobacteria is mainly caused by mutations in the rpoB gene; however, some rifampicin-resistant strains showed no rpoB mutations. Therefore, [...] Read more.

Rifampicin is a critical first-line antibiotic for treating mycobacterial infections such as tuberculosis, one of the most serious infectious diseases worldwide. Rifampicin resistance in mycobacteria is mainly caused by mutations in the rpoB gene; however, some rifampicin-resistant strains showed no rpoB mutations. Therefore, alternative mechanisms must explain this resistance in mycobacteria. In this work, a library of 11,000 Mycobacterium smegmatis mc² 155 insertion mutants was explored to search and characterize new rifampicin-resistance determinants. A transposon insertion in the MSMEG_1945 gene modified the growth rate, pH homeostasis and membrane potential in M. smegmatis, producing rifampicin resistance and collateral susceptibility to other antitubercular drugs such as isoniazid, ethionamide and aminoglycosides. Our data suggest that the M. smegmatis MSMEG_1945 protein is an ion channel, dubbed MchK, essential for maintaining the cellular ionic balance and membrane potential, modulating susceptibility to antimycobacterial agents. The functions of this new gene point once again to potassium homeostasis impairment as a proxy to resistance to rifampicin. This study increases the known repertoire of mycobacterial ion channels involved in drug susceptibility/resistance to antimycobacterial drugs and suggests novel intervention opportunities, highlighting ion channels as druggable pathways. Full article

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

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13 pages, 4337 KiB

Open AccessArticle

High Carriage of Extended-Spectrum, Beta Lactamase-Producing, and Colistin-Resistant Enterobacteriaceae in Tibetan Outpatients with Diarrhea

by Zhe Li, Jiaqi Li, Jiaqi Liu, Yao Peng, Zhenpeng Li, Mengyu Wang, Ge Zhang, Geruo Qu, Jingyun Zhang, Xiuping Fu, Xia Chen, Ciren Dunzhu, Shan Lu, Xin Lu, Jialiang Xu and Biao Kan

Antibiotics 2022, 11(4), 508; https://doi.org/10.3390/antibiotics11040508 - 11 Apr 2022

Cited by 3 | Viewed by 2160

Abstract

Antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) have been detected in human-impacted habitats, especially in densely populated cities. The Qinghai–Tibet Plateau is located far from the heavily populated regions of China, and Tibetan residents have distinct dietary habits and gut microbes. Antibiotic-resistance monitoring [...] Read more.

Antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) have been detected in human-impacted habitats, especially in densely populated cities. The Qinghai–Tibet Plateau is located far from the heavily populated regions of China, and Tibetan residents have distinct dietary habits and gut microbes. Antibiotic-resistance monitoring in the Tibetan population is rare. Here, we collected stool samples from Tibetan outpatients with diarrhea. From 59 samples, 48 antibiotic-resistant Enterobacteriaceae isolates were obtained, including 19 extended-spectrum beta lactamase (ESBL)-producing isolates from 16 patients and 29 polymyxin-resistant isolates from 22 patients. Either ESBL or mcr genes were found in 17 Escherichia coli isolates, approximately 58.8% of which were multidrug-resistant, and ten incompatible plasmid types were found. The gene bla_CTX-M was a common genotype in the ESBL-producing E. coli isolates. Four E. coli isolates contained mcr-1. The same mcr-1-carrying plasmid was found in distinct E. coli isolates obtained from the same sample, thus confirming horizontal transmission of mcr-1 between bacteria. Genomic clustering of E. coli isolates obtained from Lhasa, with strains from other regions providing evidence of clone spreading. Our results reveal a strong presence of ARB and ARGs in Tibetan outpatients with diarrhea, implying that ARB and ARGs should be monitored in the Tibetan population. Full article

(This article belongs to the Special Issue Bacterial Drug Resistance and Transmission Mechanism)

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16 pages, 1426 KiB

Open AccessArticle

Association of Antibiotic Use during the First 6 Months of Life with Body Mass of Children

by Ji Hee Kwak, Seung Won Lee, Jung Eun Lee, Eun Kyo Ha, Hey-Sung Baek, Eun Lee, Ju Hee Kim and Man Yong Han

Antibiotics 2022, 11(4), 507; https://doi.org/10.3390/antibiotics11040507 - 11 Apr 2022

Cited by 7 | Viewed by 1989

Abstract

In this study, our objective was to assess the association of body mass in preschool children with the use of antibiotics within 6 months after birth. National administrative databases were used to examine all children born between 2008 and 2009 in Korea. Exposure [...] Read more.

In this study, our objective was to assess the association of body mass in preschool children with the use of antibiotics within 6 months after birth. National administrative databases were used to examine all children born between 2008 and 2009 in Korea. Exposure was defined as the use of systemic antibiotics during the first 6 months of age. The observed outcomes were stunting (height for age [HFA] z score < −2.0), short stature (HFA z score < −1.64), overweight (body mass index [BMI] for age z score ≥ 1.04), and obesity (BMI for age z score ≥ 1.64), and the children’s height and body weight were measured from three to six years of age. To balance characteristics between the antibiotic user and non-user groups, propensity score matching was performed. The outcomes were evaluated using a generalized estimation equation with the logit link function. Analysis of antibiotic use by children during the first 6 months of life indicated there were 203,073 users (54.9%) and 166,505 non-users (45.1%). After PS matching, there were 72,983 antibiotic users and 72,983 non-users. Antibiotic use was significantly associated with stunting (aOR = 1.198, 95% CI = 1.056 to 1.360) and short stature (aOR = 1.043, 95% CI = 1.004 to 1.083), and had significant negative association with HFA z score (weighted β = −0.023). The use of an antibiotic for 14 days or more had a marked association with stunting. Antibiotic use was also associated with overweight, obesity, and increased BMI for age z score. Antibiotic use during the first 6 months of life increased the risk of stunting, short stature, overweight, and obesity in preschool children. Full article

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17 pages, 688 KiB

Open AccessArticle

Surgical Antimicrobial Prophylaxis in Pediatric Patients Undergoing Plastic Surgery: A RAND/UCLA Appropriateness Method Consensus Study

by Susanna Esposito, Rossella Sgarzani, Sonia Bianchini, Sara Monaco, Laura Nicoletti, Erika Rigotti, Marilia Di Pietro, Roberta Opri, Caterina Caminiti, Matilde Ciccia, Giorgio Conti, Daniele Donà, Mario Giuffré, Stefania La Grutta, Laura Lancella, Mario Lima, Andrea Lo Vecchio, Gloria Pelizzo, Giorgio Piacentini, Carlo Pietrasanta, Matteo Puntoni, Alessandro Simonini, Elisabetta Venturini, Annamaria Staiano, Nicola Principi and on behalf of the Peri-Operative Prophylaxis in Neonatal and Paediatric Age (POP-NeoPed) Study Group Show full author list Hide full author list

Antibiotics 2022, 11(4), 506; https://doi.org/10.3390/antibiotics11040506 - 11 Apr 2022

Cited by 4 | Viewed by 3986

Abstract

For many years, it was clearly shown that surgical procedures might be associated with surgical site infection (SSI). Many scientific institutions prepared guidelines to use in surgery to reduce abuse and misuse of antibiotics. However, in the general guidelines for surgical antibiotic prophylaxis, [...] Read more.

For many years, it was clearly shown that surgical procedures might be associated with surgical site infection (SSI). Many scientific institutions prepared guidelines to use in surgery to reduce abuse and misuse of antibiotics. However, in the general guidelines for surgical antibiotic prophylaxis, plastic surgical procedures are not addressed or are only marginally discussed, and children were almost systematically excluded. The main aim of this Consensus document is to provide clinicians with recommendations on antimicrobial prophylaxis for pediatric patients undergoing plastic surgery. The following scenarios were considered: clean plastic surgery in elective procedures with an exclusive skin and subcutis involvement; clean-contaminated/contaminated plastic surgery in elective procedures with an exclusive skin and subcutis involvement; elective plastic surgery with use of local flaps; elective plastic surgery with the use of grafts; prolonged elective plastic surgery; acute burns; clean contused lacerated wounds without bone exposure; high-risk contused lacerated wounds or with bone exposure; contused lacerated wound involving the oral mucosa; plastic surgery following human bite; plastic surgery following animal bite; plastic surgery with tissue expander insertion. Our Consensus document shows that antimicrobial perioperative prophylaxis in pediatric patients undergoing plastic surgery is recommended in selected cases. While waiting the results of further pediatric studies, the application of uniform and shared protocols in these procedures will improve surgical practice, with a reduction in SSIs and consequent rationalization of resources and costs, as well as limiting the phenomenon of antimicrobial resistance. Full article

(This article belongs to the Special Issue Antimicrobial Use in Pediatrics)

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Antibiotics, Volume 11, Issue 4 (April 2022) – 113 articles

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