Antibiotics

8 pages, 514 KiB

Open AccessBrief Report

Early and Late Onset Neonatal Sepsis: Epidemiology and Effectiveness of Empirical Antibacterial Therapy in a III Level Neonatal Intensive Care Unit

by Marcello Mariani, Alessandro Parodi, Diego Minghetti, Luca A. Ramenghi, Candida Palmero, Elisabetta Ugolotti, Chiara Medici, Carolina Saffioti and Elio Castagnola

Antibiotics 2022, 11(2), 284; https://doi.org/10.3390/antibiotics11020284 - 21 Feb 2022

Cited by 8 | Viewed by 2784

Abstract

Bloodstream infections play an important role in neonatal morbidity and mortality. In this study, we retrospectively analyzed etiology and antibiotic resistance profiles of bacteria isolated from blood or Cerebro Spinal Fluid (CSF) cultures to evaluate the appropriateness of initial empirical therapy of neonatal [...] Read more.

Bloodstream infections play an important role in neonatal morbidity and mortality. In this study, we retrospectively analyzed etiology and antibiotic resistance profiles of bacteria isolated from blood or Cerebro Spinal Fluid (CSF) cultures to evaluate the appropriateness of initial empirical therapy of neonatal sepsis. Methods: microbiological data from patients admitted to Neonatal Intensive Care Unit (NICU), from January 2005 to October 2018, were anonymously extracted from the Laboratory of Microbiology database. According to the neonatal sepsis definition for patients admitted to NICU, positive cultures obtained within the first 72 h of life were labeled as Early Onset Sepsis (EOS); and Late Onset Sepsis (LOS) for those obtained later. Results: 859 bacterial strains, 846 from blood and 13 from CSF, were detected in 611 neonates. In EOS, 75 blood cultures were found: 61 yielded Gram-positives and 14 Gram-negatives. Coagulase Negative Staphylococci (CoNS) represented the majority (52% n = 39). Streptococcus agalactiae and Escherichia coli were both isolated in 8% (n = 6) of cases. 784 strains were isolated in LOS: 686 (87%) Gram-positives and 98 (13%) Gram-negatives. CoNS represented most pathogens (n = 560, 71.4%) followed by Staphylococcus aureus (n = 57, 7.3%) and Enterococcus faecalis (n = 33, 4.2%). Ampicillin/gentamicin therapy resulted effective in 15/20 (75%) of EOS isolates. Internal protocol for LOS initial empirical therapy, calling for piperacillin/tazobactam and vancomycin resulted effective in 98.5% (734/745) of LOS strains. Conclusions: knowledge of local epidemiology of resistant pathogens, both in EOS and LOS, is fundamental to set up an effective empirical therapy in NICU. Aminoglycosides were fundamental in EOS. On the other side, LOS empirical therapy with vancomycin is sustained by the observation of 38% of methicillin resistance among S. aureus and about 95% in CoNS. Full article

(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)

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13 pages, 1283 KiB

Open AccessArticle

PK-PD Modeling and Optimal Dosing Regimen of Acetylkitasamycin against Streptococcus suis in Piglets

by Anxiong Huang, Feng Mao, Lingli Huang, Shuyu Xie, Yuanhu Pan, Wei Qu, Guyue Cheng, Zhenli Liu, Zonghui Yuan, Dapeng Peng and Haihong Hao

Antibiotics 2022, 11(2), 283; https://doi.org/10.3390/antibiotics11020283 - 21 Feb 2022

Viewed by 1944

Abstract

Streptococcus suis (S. suis) causes severe respiratory diseases in pigs and is also an important pathogen causing hidden dangers to public health and safety. Acetylkitasamycin is a new macrolide agent that has shown good activity to Gram-positive cocci such as Streptococcus. [...] Read more.

Streptococcus suis (S. suis) causes severe respiratory diseases in pigs and is also an important pathogen causing hidden dangers to public health and safety. Acetylkitasamycin is a new macrolide agent that has shown good activity to Gram-positive cocci such as Streptococcus. The purpose of this study was to perform pharmacokinetic–pharmacodynamic (PK-PD) modeling to formulate a dosing regimen of acetylkitasamycin for treatment of S. suis and to decrease the emergence of acetylkitasamycin-resistant S. suis. The minimal inhibitory concentration (MIC) of 110 S. suis isolates was determined by broth micro dilution method. The MIC₅₀ of the 55 sensitive S. suis isolates was 1.21 μg/mL. The strain HB1607 with MIC close to MIC₅₀ and high pathogenicity was used for the PK-PD experiments. The MIC and MBC of HB1607 in both MH broth and pulmonary epithelial lining fluid (PELF) was 1 and 2 μg/mL, respectively. The liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was used to determine the concentration change of acetylkitasamycin in piglet plasma and PELF after intragastric administration of a single dose of 50 mg/kg b.w. acetylkitasamycin. The PK parameters were calculated by WinNolin software. The PK data showed that the maximum concentration (C_max), peak time (T_max), and area under the concentration–time curve (AUC) were 9.84 ± 0.39 μg/mL, 4.27 ± 0.19 h and 248.58 ± 21.17 h·μg/mL, respectively. Integration of the in vivo PK data and ex vivo PD data, an inhibition sigmoid E_max equation was established. The dosing regimen of acetylkitasamycin for the treatment S. suis infection established as 33.12 mg/kg b.w. every 12 h for 3 days. This study provided a reasonable dosing regimen for a new drug used in clinical treatment, which can effectively be used to treat S. suis infection and slow down the generation of drug resistance. Full article

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

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13 pages, 3853 KiB

Open AccessArticle

A Double Payload Complex between Hypericin and All-trans Retinoic Acid in the β-Lactoglobulin Protein

by Beatriz Rodríguez-Amigo, Cormac Hally, Núria Roig-Yanovsky, Pietro Delcanale, Stefania Abbruzzetti, Montserrat Agut, Cristiano Viappiani and Santi Nonell

Antibiotics 2022, 11(2), 282; https://doi.org/10.3390/antibiotics11020282 - 21 Feb 2022

Cited by 4 | Viewed by 1638

Abstract

Combined therapies are usually used to treat acne vulgaris since this approach can tackle various foci simultaneously. Using a combination of spectroscopic, computational, and microbiological techniques and methods, herein we report on the use of β-lactoglobulin as a double payload carrier of hypericin [...] Read more.

Combined therapies are usually used to treat acne vulgaris since this approach can tackle various foci simultaneously. Using a combination of spectroscopic, computational, and microbiological techniques and methods, herein we report on the use of β-lactoglobulin as a double payload carrier of hypericin (an antimicrobial photodynamic agent) and all-trans retinoic acid (an anti-inflammatory drug) for S. aureus in vitro photodynamic inactivation. The addition of all-trans retinoic acid to hypericin-β-lactoglobulin complex renders a photochemically safe vehicle due to the photophysical quenching of hypericin, which recovers its photodynamic activity when in contact with bacteria. The ability of hypericin to photoinactivate S. aureus was not affected by retinoic acid. β-Lactoglobulin is a novel biocompatible and photochemically safe nanovehicle with strong potential for the treatment of acne. Full article

(This article belongs to the Special Issue New and Innovative Applications of Antimicrobial Photodynamic Therapy, 2nd Edition)

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Graphical abstract

29 pages, 2839 KiB

Open AccessArticle

Quantitative Risk Assessment for the Introduction of Carbapenem-Resistant Enterobacteriaceae (CPE) into Dutch Livestock Farms

by Natcha Dankittipong, Egil A. J. Fischer, Manon Swanenburg, Jaap A. Wagenaar, Arjan J. Stegeman and Clazien J. de Vos

Antibiotics 2022, 11(2), 281; https://doi.org/10.3390/antibiotics11020281 - 21 Feb 2022

Cited by 8 | Viewed by 2784

Abstract

Early detection of emerging carbapenem-resistant Enterobacteriaceae (CPE) in food-producing animals is essential to control the spread of CPE. We assessed the risk of CPE introduction from imported livestock, livestock feed, companion animals, hospital patients, and returning travelers into livestock farms in The Netherlands, [...] Read more.

Early detection of emerging carbapenem-resistant Enterobacteriaceae (CPE) in food-producing animals is essential to control the spread of CPE. We assessed the risk of CPE introduction from imported livestock, livestock feed, companion animals, hospital patients, and returning travelers into livestock farms in The Netherlands, including (1) broiler, (2) broiler breeder, (3) fattening pig, (4) breeding pig, (5) farrow-to-finish pig, and (6) veal calf farms. The expected annual number of introductions was calculated from the number of farms exposed to each CPE source and the probability that at least one animal in an exposed farm is colonized. The total number of farms with CPE colonization was estimated to be the highest for fattening pig farms, whereas the probability of introduction for an individual farm was the highest for broiler farms. Livestock feed and imported livestock are the most likely sources of CPE introduction into Dutch livestock farms. Sensitivity analysis indicated that the number of fattening pig farms determined the number of high introductions in fattening pigs from feed, and that uncertainty on CPE prevalence impacted the absolute risk estimate for all farm types. The results of this study can be used to inform risk-based surveillance for CPE in livestock farms. Full article

(This article belongs to the Special Issue Monitoring and Surveillance of Veterinary Antimicrobial Use and Antibiotic Resistance in Animals)

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12 pages, 3126 KiB

Open AccessArticle

Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process in Acanthamoeba spp.

by Rubén L. Rodríguez-Expósito, Ines Sifaoui, María Reyes-Batlle, Sutherland K. Maciver, José E. Piñero and Jacob Lorenzo-Morales

Antibiotics 2022, 11(2), 280; https://doi.org/10.3390/antibiotics11020280 - 21 Feb 2022

Cited by 7 | Viewed by 2062

Abstract

Acanthamoeba is a ubiquitous opportunistic protozoan pathogen that is known to cause blinding keratitis and rare, but usually fatal, granulomatous encephalitis. The difficulty in treating infections and the toxicity issues of the current treatments emphasize the need to use alternative agents with amoebicidal [...] Read more.

Acanthamoeba is a ubiquitous opportunistic protozoan pathogen that is known to cause blinding keratitis and rare, but usually fatal, granulomatous encephalitis. The difficulty in treating infections and the toxicity issues of the current treatments emphasize the need to use alternative agents with amoebicidal activity. The aim of this study was to evaluate the in vitro antiamoebic activity of three third-generation statins—cerivastatin, pitavastatin and rosuvastatin—against both cysts and trophozoites of the following four strains of Acanthamoeba: A. castellanii Neff, A. polyphaga, A. griffini and A. quina. Furthermore, programmed cell death (PCD) induction traits were evaluated by measuring chromatin condensation, damages at the mitochondrial level, production of reactive oxygen species (ROS) and the distribution of actin cytoskeleton fibers. Acanthamoeba castellanii Neff was the strain most sensitive to all the statins, where cerivastatin showed the lowest amoebicidal activity for both trophozoite and cyst forms (0.114 ± 0.050 and 0.704 ± 0.129 µM, respectively). All the statins were able to cause DNA condensation, collapse in the mitochondrial membrane potential and a reduction in ATP level production, and disorganization of the total actin fibers in the cytoskeleton of all the evaluated Acanthamoeba strains. Our results showed that the tested statins were able to induce PCD compatible events in the treated amoebae, including chromatin condensation, collapse in the mitochondrial potential and ATP levels, cytoskeleton disassembly and ROS generation. Full article

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

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23 pages, 402 KiB

Open AccessArticle

Surgical Antimicrobial Prophylaxis in Abdominal Surgery for Neonates and Paediatrics: A RAND/UCLA Appropriateness Method Consensus Study

by Sonia Bianchini, Erika Rigotti, Sara Monaco, Laura Nicoletti, Cinzia Auriti, Elio Castagnola, Giorgio Conti, Luisa Galli, Mario Giuffrè, Stefania La Grutta, Laura Lancella, Andrea Lo Vecchio, Giuseppe Maglietta, Nicola Petrosillo, Carlo Pietrasanta, Nicola Principi, Simonetta Tesoro, Elisabetta Venturini, Giorgio Piacentini, Mario Lima, Annamaria Staiano, Susanna Esposito and the Peri-Operative Prophylaxis in Neonatal and Paediatric Age (POP-NeoPed) Study Group Show full author list Hide full author list

Antibiotics 2022, 11(2), 279; https://doi.org/10.3390/antibiotics11020279 - 21 Feb 2022

Cited by 4 | Viewed by 3467

Abstract

Surgical site infections (SSIs), i.e., surgery-related infections that occur within 30 days after surgery without an implant and within one year if an implant is placed, complicate surgical procedures in up to 10% of cases, but an underestimation of the data is possible [...] Read more.

Surgical site infections (SSIs), i.e., surgery-related infections that occur within 30 days after surgery without an implant and within one year if an implant is placed, complicate surgical procedures in up to 10% of cases, but an underestimation of the data is possible since about 50% of SSIs occur after the hospital discharge. Gastrointestinal surgical procedures are among the surgical procedures with the highest risk of SSIs, especially when colon surgery is considered. Data that were collected from children seem to indicate that the risk of SSIs can be higher than in adults. This consensus document describes the use of preoperative antibiotic prophylaxis in neonates and children that are undergoing abdominal surgery and has the purpose of providing guidance to healthcare professionals who take care of children to avoid unnecessary and dangerous use of antibiotics in these patients. The following surgical procedures were analyzed: (1) gastrointestinal endoscopy; (2) abdominal surgery with a laparoscopic or laparotomy approach; (3) small bowel surgery; (4) appendectomy; (5) abdominal wall defect correction interventions; (6) ileo-colic perforation; (7) colorectal procedures; (8) biliary tract procedures; and (9) surgery on the liver or pancreas. Thanks to the multidisciplinary contribution of experts belonging to the most important Italian scientific societies that take care of neonates and children, this document presents an invaluable reference tool for perioperative antibiotic prophylaxis in the paediatric and neonatal populations. Full article

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

18 pages, 1946 KiB

Open AccessReview

Perspective, Opportunities and Challenges in Using Fennel (Foeniculum vulgare) in Poultry Health and Production as an Eco-Friendly Alternative to Antibiotics: A Review

by Rifat Ullah Khan, Adia Fatima, Shabana Naz, Marco Ragni, Simona Tarricone and Vincenzo Tufarelli

Antibiotics 2022, 11(2), 278; https://doi.org/10.3390/antibiotics11020278 - 20 Feb 2022

Cited by 29 | Viewed by 5488

Abstract

Following the European Union’s restriction on antibiotic growth promoters, research on enhancing gut health has been accelerated. As the poultry industry is facing issues that were previously managed by antimicrobial growth promoters, the hunt for the best remedies continues to find suitable alternatives. [...] Read more.

Following the European Union’s restriction on antibiotic growth promoters, research on enhancing gut health has been accelerated. As the poultry industry is facing issues that were previously managed by antimicrobial growth promoters, the hunt for the best remedies continues to find suitable alternatives. Simultaneously, social pressure is mounting to reduce the usage of antibiotics and replace them with other feed additives. Consumers believe a number of accessible options to be safe, with phytogenics playing a crucial role. This review describes how the use of fennel seeds could be beneficial for poultry. An overview of the broad chemical diversity of fennel is presented together with their physicochemical and biological properties. According to investigations, fennel seeds have a variety of biological effects in birds, including improved performance, higher immune cell proliferation, reduced oxidative stress, and boosted antibody titers against infectious diseases. The efficacy of poultry outcomes is determined by the stage and age of the plants, the extraction process, the geographical location, the chicken species, management techniques, and the concentrations administered. The present review focuses on the effects of fennel seeds as a feed additive on poultry growth, carcass quality, blood biochemistry, antioxidant activity, immunity, and microbiological aspects. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Treatment in Companion, Food and Exotic Animals)

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33 pages, 571 KiB

Open AccessReview

The Role of Colistin in the Era of New β-Lactam/β-Lactamase Inhibitor Combinations

by Abdullah Tarık Aslan and Murat Akova

Antibiotics 2022, 11(2), 277; https://doi.org/10.3390/antibiotics11020277 - 20 Feb 2022

Cited by 18 | Viewed by 5000

Abstract

With the current crisis related to the emergence of carbapenem-resistant Gram-negative bacteria (CR-GNB), classical treatment approaches with so-called “old-fashion antibiotics” are generally unsatisfactory. Newly approved β-lactam/β-lactamase inhibitors (BLBLIs) should be considered as the first-line treatment options for carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas [...] Read more.

With the current crisis related to the emergence of carbapenem-resistant Gram-negative bacteria (CR-GNB), classical treatment approaches with so-called “old-fashion antibiotics” are generally unsatisfactory. Newly approved β-lactam/β-lactamase inhibitors (BLBLIs) should be considered as the first-line treatment options for carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections. However, colistin can be prescribed for uncomplicated lower urinary tract infections caused by CR-GNB by relying on its pharmacokinetic and pharmacodynamic properties. Similarly, colistin can still be regarded as an alternative therapy for infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) until new and effective agents are approved. Using colistin in combination regimens (i.e., including at least two in vitro active agents) can be considered in CRAB infections, and CRE infections with high risk of mortality. In conclusion, new BLBLIs have largely replaced colistin for the treatment of CR-GNB infections. Nevertheless, colistin may be needed for the treatment of CRAB infections and in the setting where the new BLBLIs are currently unavailable. In addition, with the advent of rapid diagnostic methods and novel antimicrobials, the application of personalized medicine has gained significant importance in the treatment of CRE infections. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Rello—Outstanding Contributions in the Fields of Management of Severe Infections and Sepsis)

12 pages, 960 KiB

Open AccessArticle

Evaluation of Bi-Lateral Co-Infections and Antibiotic Resistance Rates among COVID-19 Patients

by Naveed Ahmed, Madiha Khan, Waqas Saleem, Mohmed Isaqali Karobari, Roshan Noor Mohamed, Artak Heboyan, Ali A. Rabaan, Abbas Al Mutair, Saad Alhumaid, Salman A. Alsadiq, Ahmed S. Bueid, Eman Y. Santali and Jeehan H. Alestad

Antibiotics 2022, 11(2), 276; https://doi.org/10.3390/antibiotics11020276 - 19 Feb 2022

Cited by 24 | Viewed by 5451

Abstract

In addition to the pathogenesis of SARS-CoV-2, bacterial co-infection plays an essential role in the incidence and progression of SARS-CoV-2 infections by increasing the severity of infection, as well as increasing disease symptoms, death rate and antimicrobial resistance (AMR). The current study was [...] Read more.

In addition to the pathogenesis of SARS-CoV-2, bacterial co-infection plays an essential role in the incidence and progression of SARS-CoV-2 infections by increasing the severity of infection, as well as increasing disease symptoms, death rate and antimicrobial resistance (AMR). The current study was conducted in a tertiary-care hospital in Lahore, Pakistan, among hospitalized COVID-19 patients to see the prevalence of bacterial co-infections and the AMR rates among different isolated bacteria. Clinical samples for the laboratory diagnosis were collected from 1165 hospitalized COVID-19 patients, of which 423 were found to be positive for various bacterial infections. Most of the isolated bacteria were Gram-negative rods (n = 366), followed by Gram-positive cocci (n = 57). A significant association (p < 0.05) was noted between the hospitalized COVID-19 patients and bacterial co-infections. Staphylococcus aureus (S. aureus) showed high resistance against tetracycline (61.7%), Streptococcus pyogenes against penicillin (100%), E. coli against Amp-clavulanic acid (88.72%), Klebsiella pneumoniae against ampicillin (100%), and Pseudomonas aeruginosa against ciprofloxacin (75.40%). Acinetobacter baumannii was 100% resistant to the majority of tested antibiotics. The prevalence of methicillin-resistant S. aureus (MRSA) was 14.7%. The topmost symptoms of >50% of COVID-19 patients were fever, fatigue, dyspnea and chest pain with a significant association (p < 0.05) in bacterial co-infected patients. The current study results showed a comparatively high prevalence of AMR, which may become a severe health-related issue in the future. Therefore, strict compliance of antibiotic usage and employment of antibiotic stewardship programs at every public or private institutional level are recommended. Full article

(This article belongs to the Special Issue Antimicrobial Use and Stewardship during the COVID-19 Era)

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14 pages, 2021 KiB

Open AccessEditor’s ChoiceSystematic Review

Safety and Efficacy of Devices Delivering Inhaled Antibiotics among Adults with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and a Network Meta-Analysis

by Sofia Tejada, Sergio Ramírez-Estrada, Carlos G. Forero, Miguel Gallego, Joan B. Soriano, Pablo A. Cardinal-Fernández, Stephan Ehrmann and Jordi Rello

Antibiotics 2022, 11(2), 275; https://doi.org/10.3390/antibiotics11020275 - 19 Feb 2022

Cited by 4 | Viewed by 3049

Abstract

It remains unknown whether the type of aerosol generating device is affecting efficacy and safety among non-cystic fibrosis bronchiectasis (NCFB) adults. The proposal of this network meta-analysis (NMA) is to evaluate effectiveness and safety of inhaled antibiotics administered via dry powder inhaler (DPI) [...] Read more.

It remains unknown whether the type of aerosol generating device is affecting efficacy and safety among non-cystic fibrosis bronchiectasis (NCFB) adults. The proposal of this network meta-analysis (NMA) is to evaluate effectiveness and safety of inhaled antibiotics administered via dry powder inhaler (DPI) and via nebulizers (SVN) among adult patients with NCFB. Inclusion criteria were randomized-controlled trials, adults (≥18 years) with NCFB, and inhaled antibiotics administered via DPI as intervention. Search strategy was performed in PubMed, Web of Science, and Cochrane Library from 2000 to 2019. Sixteen trials (2870 patients) were included. Three trials (all ciprofloxacin) used DPIs and thirteen used SVN (three ciprofloxacin). Both DPI and SVN devices achieved similar safety outcomes (adverse events, antibiotic discontinuation, severe adverse events, and bronchospasm). Administration of ciprofloxacin via DPI significantly improved time to first exacerbation (87 days, 95% CI 34.3–139.7) and quality of life (MD −7.52; 95% CI −13.06 to −1.98) when compared with via SVN. No other significant differences were documented in clinical efficacy (at least one exacerbation, FEV₁% predicted) and microbiologic response (bacterial eradication, emergence of new potential pathogens, and emergence of antimicrobial resistance) when comparing devices. Our NMA documented that time to first exacerbation and quality of life, were more favorable for DPIs. Decisions on the choice of devices should incorporate these findings plus other criteria, such as simplicity, costs or maintenance requirements. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Rello—Outstanding Contributions in the Fields of Management of Severe Infections and Sepsis)

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14 pages, 7992 KiB

Open AccessReview

Recent Advance in Small Molecules Targeting RhlR of Pseudomonas aeruginosa

by Taehyeong Lim, So-Young Ham, SangJin Nam, Myoungsun Kim, Ki Yong Lee, Hee-Deung Park and Youngjoo Byun

Antibiotics 2022, 11(2), 274; https://doi.org/10.3390/antibiotics11020274 - 19 Feb 2022

Cited by 8 | Viewed by 2786

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic gram-negative pathogen that can cause various infections, particularly in patients with compromised host defenses. P. aeruginosa forms biofilms and produces virulence factors through quorum sensing (QS) network, resulting in resistance to [...] Read more.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic gram-negative pathogen that can cause various infections, particularly in patients with compromised host defenses. P. aeruginosa forms biofilms and produces virulence factors through quorum sensing (QS) network, resulting in resistance to antibiotics. RhlI/RhlR, one of key QS systems in P. aeruginosa, is considered an attractive target for inhibiting biofilm formation and attenuating virulence factors. Several recent studies examined small molecules targeting the RhlI/RhlR system and their in vitro and in vivo biological activities. In this review, RhlR-targeted modulators, including agonists and antagonists, are discussed with particular focus on structure-activity relationship studies and outlook for next-generation anti-biofilm agents. Full article

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16 pages, 1579 KiB

Open AccessEditor’s ChoiceArticle

Stapling of Peptides Potentiates the Antibiotic Treatment of Acinetobacter baumannii In Vivo

by Gina K. Schouten, Felix M. Paulussen, Oscar P. Kuipers, Wilbert Bitter, Tom N. Grossmann and Peter van Ulsen

Antibiotics 2022, 11(2), 273; https://doi.org/10.3390/antibiotics11020273 - 19 Feb 2022

Cited by 6 | Viewed by 3752

Abstract

The rising incidence of multidrug resistance in Gram-negative bacteria underlines the urgency for novel treatment options. One promising new approach is the synergistic combination of antibiotics with antimicrobial peptides. However, the use of such peptides is not straightforward; they are often sensitive to [...] Read more.

The rising incidence of multidrug resistance in Gram-negative bacteria underlines the urgency for novel treatment options. One promising new approach is the synergistic combination of antibiotics with antimicrobial peptides. However, the use of such peptides is not straightforward; they are often sensitive to proteolytic degradation, which greatly limits their clinical potential. One approach to increase stability is to apply a hydrocarbon staple to the antimicrobial peptide, thereby fixing them in an α-helical conformation, which renders them less exposed to proteolytic activity. In this work we applied several different hydrocarbon staples to two previously described peptides shown to act on the outer membrane, L6 and L8, and tested their activity in a zebrafish embryo infection model using a clinical isolate of Acinetobacter baumannii as a pathogen. We show that the introduction of such a hydrocarbon staple to the peptide L8 improves its in vivo potentiating activity on antibiotic treatment, without increasing its in vivo antimicrobial activity, toxicity or hemolytic activity. Full article

(This article belongs to the Topic Novel Antimicrobial Agents: Discovery, Design and New Therapeutic Strategies)

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9 pages, 271 KiB

Open AccessArticle

Low Level of Colistin Resistance and mcr Genes Presence in Salmonella spp.: Evaluation of Isolates Collected between 2000 and 2020 from Animals and Environment

by Fabrizio Bertelloni, Giulia Cagnoli, Barbara Turchi and Valentina Virginia Ebani

Antibiotics 2022, 11(2), 272; https://doi.org/10.3390/antibiotics11020272 - 19 Feb 2022

Cited by 7 | Viewed by 2235

Abstract

Salmonellosis is one of the most important zoonoses in Europe and the world. Human infection may evolve in severe clinical diseases, with the need for hospitalization and antimicrobial treatment. Colistin is now considered an important antimicrobial to treat infections from multidrug- resistant Gram-negative [...] Read more.

Salmonellosis is one of the most important zoonoses in Europe and the world. Human infection may evolve in severe clinical diseases, with the need for hospitalization and antimicrobial treatment. Colistin is now considered an important antimicrobial to treat infections from multidrug- resistant Gram-negative bacteria, but the spreading of mobile colistin-resistance (mcr) genes has limited this option. We aimed to evaluate colistin minimum inhibitory concentration and the presence of mcr (mcr-1 to mcr-9) genes in 236 Salmonella isolates previously collected from different animals and the environment between 2000 and 2020. Overall, 17.79% of isolates were resistant to colistin; no differences were observed in relation to years of isolation (2000–2005, 2009–2014, and 2015–2020), Salmonella enterica subspecies (enterica, salamae, diarizonae, and houtenae), origin of samples (domestic animals, wildlife, and environment), or animal category (birds, mammals, and reptiles); only recently isolated strains from houseflies showed the most resistance. Few isolates (5.93%) scored positive for mcr genes, in particular for mcr-1, mcr-2, mcr-4, mcr-6, and mcr-8; furthermore, only 2.54% of isolates were mcr-positive and colistin-resistant. Detected resistance to colistin was equally distributed among all examined Salmonella isolates and not always related to the presence of mcr genes. Full article

(This article belongs to the Special Issue Colistin Resistance: The Need for a One Health Approach)

10 pages, 243 KiB

Open AccessArticle

Microbiological Diagnoses on Clinical Mastitis—Comparison between Diagnoses Made in Veterinary Clinics versus in Laboratory Applying MALDI-TOF MS

by Lærke Boye Astrup, Karl Pedersen and Michael Farre

Antibiotics 2022, 11(2), 271; https://doi.org/10.3390/antibiotics11020271 - 19 Feb 2022

Cited by 12 | Viewed by 1664

Abstract

The present study compares the diagnoses on clinical bovine mastitis made in veterinary clinics using conventional diagnostic methods with diagnoses on the same samples made by a veterinary reference laboratory using MALDI-TOF MS as diagnostics. The study enables targeted and evidence-based consulting on [...] Read more.

The present study compares the diagnoses on clinical bovine mastitis made in veterinary clinics using conventional diagnostic methods with diagnoses on the same samples made by a veterinary reference laboratory using MALDI-TOF MS as diagnostics. The study enables targeted and evidence-based consulting on prudent mastitis diagnostics and related antibiotic usage. In total, 492 samples from clinical mastitis were included. When applying MALDI-TOF MS as gold standard, only 90 out of 492 diagnoses made in veterinary clinics, equal to 18%, were correct. Four main findings were important: (1) the veterinary clinics overlooked contamination in mastitis samples; (2) the veterinary clinics only assigned 2 fully correct diagnoses out of 119 samples with mixed growth cultures; (3) the veterinary clinics made close to half of their diagnoses on pure culture erroneously; (4) the veterinary clinics applied a limited number of the relevant pathogen identifications on pure culture samples. Altogether, the present study shows that a large part of Danish clinical mastitis cases are misdiagnosed. Lack of correct diagnoses and diagnostic quality control may lead to the choice of wrong treatment and thus hamper prudent use of antibiotics. Hence, the present study warns a risk of overuse of antibiotics in Denmark. Consequently, the present study calls for training of veterinary clinics in diagnostics of mastitis pathogens and national guidelines on quality assurance of mastitis diagnostics. Full article

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

20 pages, 1698 KiB

Open AccessArticle

Effect of Farm Management Practices on Morbidity and Antibiotic Usage on Calf Rearing Farms

by Atte Sandelin, Outi Hälli, Heidi Härtel, Tuomas Herva, Liisa Kaartinen, Erja Tuunainen, Helena Rautala, Timo Soveri and Heli Simojoki

Antibiotics 2022, 11(2), 270; https://doi.org/10.3390/antibiotics11020270 - 18 Feb 2022

Cited by 3 | Viewed by 2094

Abstract

Antimicrobial resistance has been recognized as one of the top health threats to human society. Abundant use of antibiotics in both humans and animals has led to ever-increasing antibiotic resistance in bacteria. In food production, decreasing morbidity in beef herds would be an [...] Read more.

Antimicrobial resistance has been recognized as one of the top health threats to human society. Abundant use of antibiotics in both humans and animals has led to ever-increasing antibiotic resistance in bacteria. In food production, decreasing morbidity in beef herds would be an effective way to reduce the use of antibiotics. The objective of this retrospective observational study was to determine overall morbidity on calf rearing farms and to identify associated risk factors. Data were collected by questionnaire, meat companies’ databases and the national cattle register for 28,228 calves transported to 87 calf rearing farms. All medications given to these calves were retrospectively followed for 180 days from calf arrival to the farm. In total, 34,532 parenteral antibiotic medications were administered to the 28,228 study calves (122.3%), and 17,180 calves (60.9%) were medicated with antibiotics at least once during the follow-up. Higher numbers of calves transported to the same farm and larger age variation in calves in the same arrival batch were both associated with increased morbidity. In contrast, higher arrival age of individual calves was associated with decreased morbidity. Our study identifies several factors to consider in decreasing morbidity and antibiotic usage on calf rearing farms. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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12 pages, 1481 KiB

Open AccessArticle

Recurring Cystitis: How Can We Do Our Best to Help Patients Help Themselves?

by Sarah Ben Hadj Messaoud, Elisa Demonchy and Véronique Mondain

Antibiotics 2022, 11(2), 269; https://doi.org/10.3390/antibiotics11020269 - 18 Feb 2022

Cited by 4 | Viewed by 2021

Abstract

Recurrent cystitis (RC) has rarely been studied; its management varies and research on a holistic approach of these patients is scarce. We attempted to characterize patients suffering from RC and investigated their current care pathways, aiming to offer customized and autonomous management. In [...] Read more.

Recurrent cystitis (RC) has rarely been studied; its management varies and research on a holistic approach of these patients is scarce. We attempted to characterize patients suffering from RC and investigated their current care pathways, aiming to offer customized and autonomous management. In this paper, we present a descriptive, single-center, cross-sectional study of women presenting with RC at an infectious disease (ID) clinic. A questionnaire was developed and was completed by ID physicians during patient visits. From October 2016 to January 2019, 202 women were included (mean age 59 years). Sexual intercourse, stress and diarrhoea/digestive symptoms were reported as trigger factors by 35%, 34% and 19% of patients, respectively. A majority (54%) were at risk for complications and were those more exposed to inappropriate antibiotic prescriptions. In total, 56% of women suffered from more than 10 episodes/year and 48% suffered from relapses, mainly due to E. coli. Genitourinary syndrome of menopause (GSM) was a frequent complaint (74.5% of women). Fluoroquinolones and 3rd generation cephalosporins were prescribed in 38% and 30% of women, respectively. Most women wished for non-antimicrobial approaches and autonomy. Patients require comprehensive, tailored care in order to benefit from a broader range of treatment options in compliance with recommendations. Full article

(This article belongs to the Special Issue Uropathogens - Antibiotic Resistance and Alternative Therapies)

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9 pages, 5574 KiB

Open AccessArticle

Screening of Anorectal and Oropharyngeal Samples Fails to Detect Bacteriophages Infecting Neisseria gonorrhoeae

by Jolein Gyonne Elise Laumen, Saïd Abdellati, Sheeba Santhini Manoharan-Basil, Christophe Van Dijck, Dorien Van den Bossche, Irith De Baetselier, Tessa de Block, Surbhi Malhotra-Kumar, Patrick Soentjes, Jean-Paul Pirnay, Chris Kenyon and Maia Merabishvili

Antibiotics 2022, 11(2), 268; https://doi.org/10.3390/antibiotics11020268 - 18 Feb 2022

Cited by 1 | Viewed by 1879

Abstract

There are real concerns that Neisseria gonorrhoeae may become untreatable in the near future due to the rapid emergence of antimicrobial resistance. Alternative therapies are thus urgently required. Bacteriophages active against N. gonorrhoeae could play an important role as an antibiotic-sparing therapy. To [...] Read more.

There are real concerns that Neisseria gonorrhoeae may become untreatable in the near future due to the rapid emergence of antimicrobial resistance. Alternative therapies are thus urgently required. Bacteriophages active against N. gonorrhoeae could play an important role as an antibiotic-sparing therapy. To the best of our knowledge, no bacteriophages active against N. gonorrhoeae have ever been found. The aim of this study was to screen for bacteriophages able to lyse N. gonorrhoeae in oropharyngeal and anorectal swabs of 74 men who have sex with men attending a sexual health clinic in Antwerp, Belgium. We screened 210 swabs but were unable to identify an anti-gonococcal bacteriophage. This is the first report of a pilot screening that systematically searched for anti-gonococcal phages directly from clinical swabs. Further studies may consider screening for phages at other anatomical sites (e.g., stool samples, urine) or in environmental settings (e.g., toilet sewage water of sex clubs or sexually transmitted infection clinics) where N. gonorrhoeae can be found. Full article

(This article belongs to the Special Issue Frontiers in Phage Therapy)

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16 pages, 2409 KiB

Open AccessArticle

Altered Gut Structure and Anti-Bacterial Defense in Adult Mice Treated with Antibiotics during Early Life

by Tnia Martins Garcia, Manon van Roest, Jacqueline L. M. Vermeulen, Sander Meisner, Jan Koster, Manon E. Wildenberg, Ruurd M. van Elburg, Vanesa Muncan and Ingrid B. Renes

Antibiotics 2022, 11(2), 267; https://doi.org/10.3390/antibiotics11020267 - 18 Feb 2022

Cited by 2 | Viewed by 1949

Abstract

The association between prolonged antibiotic (AB) use in neonates and increased incidence of later life diseases is not yet fully understood. AB treatment in early life alters intestinal epithelial cell composition, functioning, and maturation, which could be the basis for later life health [...] Read more.

The association between prolonged antibiotic (AB) use in neonates and increased incidence of later life diseases is not yet fully understood. AB treatment in early life alters intestinal epithelial cell composition, functioning, and maturation, which could be the basis for later life health effects. Here, we investigated whether AB-induced changes in the neonatal gut persisted up to adulthood and whether early life AB had additional long-term consequences for gut functioning. Mice received AB orally from postnatal day 10 to 20. Intestinal morphology, permeability, and gene and protein expression at 8 weeks were analyzed. Our data showed that the majority of the early life AB-induced gut effects did not persist into adulthood, yet early life AB did impact later life gut functioning. Specifically, the proximal small intestine (SI) of adult mice treated with AB in early life was characterized by hyperproliferative crypts, increased number of Paneth cells, and alterations in enteroendocrine cell-specific gene expression profiles. The distal SI of adult mice displayed a reduced expression of antibacterial defense markers. Together, our results suggest that early life AB leads to structural and physiological changes in the adult gut, which may contribute to disease development when homeostatic conditions are under challenge. Full article

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7 pages, 1052 KiB

Open AccessBrief Report

Potentiation of β-Lactams against Methicillin-Resistant Staphylococcus aureus (MRSA) Using Octyl Gallate, a Food-Grade Antioxidant

by Migma Dorji Tamang, Junghee Bae, Myungseo Park and Byeonghwa Jeon

Antibiotics 2022, 11(2), 266; https://doi.org/10.3390/antibiotics11020266 - 18 Feb 2022

Cited by 6 | Viewed by 2053

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to a number of antibiotics of clinical importance and is a serious threat to public health. Since bacteria rapidly develop resistance even to newly discovered antibiotics, this study aimed to develop drug potentiators to enhance the antibacterial [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to a number of antibiotics of clinical importance and is a serious threat to public health. Since bacteria rapidly develop resistance even to newly discovered antibiotics, this study aimed to develop drug potentiators to enhance the antibacterial activity of existing antibiotics for the control of MRSA. Based on our previous studies, screening of antimicrobial synergy was conducted with gallic acid and its derivatives using checkerboard assays. Antimicrobial synergy was confirmed with MRSA isolates from clinical cases. Combinations of penicillin, ampicillin, and cephalothin with octyl gallate (OG), an antioxidant approved by the US Food and Drug Administration (FDA), consistently exhibited synergistic bacteriostatic and bactericidal activities against MRSA, rendering MRSA sensitive to β-lactams. The fractional inhibitory concentration (FIC) and fractional bactericidal concentration (FBC) indices exhibited that the antimicrobial effects of OG were synergistic. The results of a permeability assay showed that OG significantly increased the permeability of the bacterial cell wall. Despite the intrinsic resistance of MRSA to β-lactams, the findings in this study demonstrated that OG enhanced the activity of β-lactams in MRSA and sensitized MRSA to β-lactams, suggesting that OG can be used as a drug potentiator to control MRSA using existing antibiotics. Full article

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17 pages, 2780 KiB

Open AccessArticle

Ethyl Acetate Fraction of Punica granatum and Its Galloyl-HHDP-Glucose Compound, Alone or in Combination with Fluconazole, Have Antifungal and Antivirulence Properties against Candida spp.

by Aline Michelle Silva Mendonça, Cristina de Andrade Monteiro, Roberval Nascimento Moraes-Neto, Andrea Souza Monteiro, Renata Mondego-Oliveira, Camila Evangelista Carnib Nascimento, Luís Cláudio Nascimento da Silva, Lidio Gonçalves Lima-Neto, Rafael Cardoso Carvalho and Eduardo Martins de Sousa

Antibiotics 2022, 11(2), 265; https://doi.org/10.3390/antibiotics11020265 - 18 Feb 2022

Cited by 6 | Viewed by 2281

Abstract

Candidiasis is the most common fungal infection among immunocompromised patients. Its treatment includes the use of antifungals, which poses limitations such as toxicity and fungal resistance. Plant-derived extracts, such as Punica granatum, have been reported to have antimicrobial activity, but their antifungal [...] Read more.

Candidiasis is the most common fungal infection among immunocompromised patients. Its treatment includes the use of antifungals, which poses limitations such as toxicity and fungal resistance. Plant-derived extracts, such as Punica granatum, have been reported to have antimicrobial activity, but their antifungal effects are still unknown. We aimed to evaluate the antifungal and antiviral potential of the ethyl acetate fraction of P. granatum (PgEA) and its isolated compound galloyl-hexahydroxydiphenoyl-glucose (G-HHDP-G) against Candida spp. In silico analyses predicted the biological activity of G-HHDP-G. The minimum inhibitory concentrations (MIC) of PgEA and G-HHDP-G, and their effects on biofilm formation, preformed biofilms, and phospholipase production were determined. In silico analysis showed that G-HHDP-G has antifungal and hepatoprotective effects. An in vitro assay confirmed the antifungal effects of PgEA and G-HHDP-G, with MIC in the ranges of 31.25–250 μg/mL and 31.25 ≥ 500 μg/mL, respectively. G-HHDP-G and PgEA synergistically worked with fluconazole against planktonic cells. The substances showed antibiofilm action, alone or in combination with fluconazole, and interfered with phospholipase production. The antifungal and antibiofilm actions of PgEA and G-HHDP-G, alone or in combination with fluconazole, in addition to their effects on reducing Candida phospholipase production, identify them as promising candidates for therapeutics. Full article

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

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17 pages, 1511 KiB

Open AccessArticle

Interrupted Time Series Analysis of Pediatric Infectious Diseases and the Consumption of Antibiotics in an Atlantic European Region during the SARS-CoV-2 Pandemic

by Ana Clavería, María Victoria Delgado-Martín, Ana Goicoechea-Castaño, José Manuel Iglesias-Moreno, Clara García-Cendón, María Victoria Martín-Miguel, Rita Villarino-Moure, Carolina Barreiro-Arceiz, Isabel Rey-Gómez-Serranillos and Javier Roca

Antibiotics 2022, 11(2), 264; https://doi.org/10.3390/antibiotics11020264 - 18 Feb 2022

Cited by 2 | Viewed by 2541

Abstract

The increasing concern about bacterial resistance has made the rational prescription of antibiotics even more urgent. The non-pharmacological measures established to reduce the impact of the SARS-CoV-2 pandemic have modified the epidemiology of pediatric infections and, consequently, the use of antibiotics. Interrupted time [...] Read more.

The increasing concern about bacterial resistance has made the rational prescription of antibiotics even more urgent. The non-pharmacological measures established to reduce the impact of the SARS-CoV-2 pandemic have modified the epidemiology of pediatric infections and, consequently, the use of antibiotics. Interrupted time series (ITS) analyses are quasi-experimental studies that allow for the estimation of causal effects with observational data in “natural experiments”, such as changes in health policies or pandemics. The effect of the SARS-CoV-2 pandemic on the incidence of infectious diseases and the use of antibiotics between 2018 and 2020 in the Health Area of Vigo (Galicia, Spain) was quantified and analyzed. This paper outlines a real-world data study with administrative records from primary care services provided for the pediatric population. The records were related to episodes classified as infectious by the International Classification of Primary Care (ICPC-2) and oral medication in the therapeutic subgroup J01, corresponding to antibiotics for systemic use, according to the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification system. The records were classified according to incident episodes, age, dose per inhabitant, and year. Segmented regression models were applied using an algorithm that automatically identifies the number and position of the change points. During the SARS-CoV-2 pandemic, the number of infectious diseases being transmitted between individuals, through the air and through the fecal–oral route, significantly decreased, and a slight decrease in infections transmitted via other mechanisms (urinary tract infections) was also found. In parallel, during the months of the pandemic, there has been a marked and significant reduction in antibacterial agent utilization, mainly of penicillins, cephalosporins, and macrolides. Full article

(This article belongs to the Special Issue Impact of Pandemic of COVID-19 on Antibiotic Prescription/Sales and on Antibiotic Resistances)

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7 pages, 213 KiB

Open AccessArticle

Enteral Vancomycin to Eliminate MRSA Carriership of the Digestive Tract in Critically Ill Patients

by Sophie H. Buitinck, Matty Koopmans, Rogier M. Determann, Rogier R. Jansen and Peter H. J. van der Voort

Antibiotics 2022, 11(2), 263; https://doi.org/10.3390/antibiotics11020263 - 17 Feb 2022

Viewed by 1415

Abstract

Background: Carriership with methicillin resistant Staphylococcus aureus (MRSA) is a risk for the development of secondary infections in critically ill patients. Previous studies suggest that enteral vancomycin is able to eliminate enteral carriership with MRSA. Data on individual effects of this treatment are [...] Read more.

Background: Carriership with methicillin resistant Staphylococcus aureus (MRSA) is a risk for the development of secondary infections in critically ill patients. Previous studies suggest that enteral vancomycin is able to eliminate enteral carriership with MRSA. Data on individual effects of this treatment are lacking. Methods: Retrospective analysis of a database containing 15 year data of consecutive patients from a mixed medical-(cardio)surgical 18 bedded intensive care unit was conducted. All consecutive critically ill patients with enteral MRSA carriership detected in throat and/or rectal samples were collected. We analyzed those with follow-up cultures to determine the success rate of enteral vancomycin. Topical application of 2% vancomycin in a sticky oral paste was performed combined with a vancomycin solution of 500 mg four times daily in the nasogastric tube. This treatment was added to a regimen of selective digestive tract decontamination (SDD) to prevent ICU acquired infection. Results: Thirteen patients were included. The mean age was 65 years and the median APACHE II score was 21. MRSA was present in the throat in 8 patients and in both throat and rectum in 5 patients. In all patients MRSA was successfully eliminated from both throat and rectum, which took 2–11 days with a median duration until decontamination of 4 days. Secondary infections with MRSA did not occur. Conclusions: Topical treatment with vancomycin in a 2% sticky oral paste four times daily in the nasogastric tube was effective in all patients in the elimination of MRSA and prevented secondary MRSA infections. Full article

18 pages, 3512 KiB

Open AccessArticle

Transcriptome Analysis of the Response of Mature Helicobacter pylori Biofilm to Different Doses of Lactobacillus salivarius LN12 with Amoxicillin and Clarithromycin

by Fang Jin and Hong Yang

Antibiotics 2022, 11(2), 262; https://doi.org/10.3390/antibiotics11020262 - 17 Feb 2022

Cited by 5 | Viewed by 2111

Abstract

Helicobacter pylori is a gastrointestinal pathogen with a high infection rate. Probiotics are clinically used as an adjuvant to improve the cure rate and reduce the side effects of antibiotic treatment for H. pylori. This study is the first to explore the [...] Read more.

Helicobacter pylori is a gastrointestinal pathogen with a high infection rate. Probiotics are clinically used as an adjuvant to improve the cure rate and reduce the side effects of antibiotic treatment for H. pylori. This study is the first to explore the effects of a cell-free supernatant of high- or low-dose Lactobacillus salivarius LN12 combined with amoxicillin (AMX) and clarithromycin (CLR) on H. pylori 3192 biofilms in terms of the biofilm biomass, survival rates, biofilm structure, and transcriptome. The results showed that the combination of the CFS of high-dose LN12 with AMX and CLR had stronger effects on the biofilm biomass, survival rate, and structure of H. pylori 3192 biofilms. H. pylori 3192 biofilms may increase the expression of NADH-related genes and downregulate flagellar assembly and quorum sensing-related receptor genes to deal with the stronger stress effects of high-dose LN12 with AMX and CLR. In conclusion, the biofilm biomass, survival rate, structure, and transcriptome results showed that the combination of LN12 CFS with AMX and CLR had dose effects. We recommend that compared with low doses, high doses of L. salivarus LN12 combined with AMX and CLR may be more effective for H. pylori biofilm than low doses. Full article

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

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14 pages, 578 KiB

Open AccessArticle

Antimicrobial Susceptibility, Virulence, and Genomic Features of a Hypervirulent Serotype K2, ST65 Klebsiella pneumoniae Causing Meningitis in Italy

by Aurora Piazza, Matteo Perini, Carola Mauri, Francesco Comandatore, Elisa Meroni, Francesco Luzzaro and Luigi Principe

Antibiotics 2022, 11(2), 261; https://doi.org/10.3390/antibiotics11020261 - 17 Feb 2022

Cited by 9 | Viewed by 2121

Abstract

The rise of a new hypervirulent variant of Klebsiella pneumoniae (hvKp) was recently reported, mainly linked to the ST23 lineage. The hvKp variants can cause severe infections, including hepatic abscesses, bacteremia, and meningitis, with a particularly disconcerting propensity to cause community-acquired, life-threatening infection [...] Read more.

The rise of a new hypervirulent variant of Klebsiella pneumoniae (hvKp) was recently reported, mainly linked to the ST23 lineage. The hvKp variants can cause severe infections, including hepatic abscesses, bacteremia, and meningitis, with a particularly disconcerting propensity to cause community-acquired, life-threatening infection among young and otherwise healthy individuals. The present study aimed to report the clinical characteristics of a hypermucoviscous K. pneumoniae strain isolated in Italy and sustaining recurrent meningitis in a patient of Peruvian origin. A further objective was to retrospectively investigate, by means of whole-genome sequencing (WGS) analysis, the genomic features of such an isolate. The hypermucoviscosity phenotype of the strain (sk205y205t) was determined using the string test. Genomic information was obtained by WGS (Illumina) and bioinformatic analysis. Strain sk205y205t was susceptible to most antibiotics, despite the presence of some resistance genes, including bla_SHV-11, bla_SHV-67, fosA, and acrR. The isolate belonged to ST65 and serotype K2, and exhibited several virulence factors related to the hvKp variant. Among these, were the siderophore genes entB, irp2, iroN, iroB, and iucA; the capsule-regulating genes rmpA and rmpA2; and the type 1 and 3 fimbriae fimH27 and mrkD, respectively. A further operon, encoding the genotoxin colibactin (clbA-Q), was also identified. The virulence plasmids pK2044, pRJA166b, and pNDM. MAR were also detected. Phylogenetic investigation showed that this Italian strain is highly similar to a Chinese isolate, suggesting a hidden circulation of this hvKp ST65 K2 lineage. Full article

(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)

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18 pages, 1605 KiB

Open AccessArticle

by Elizabeth Liedhegner, Brandon Bojar, Rachelle E. Beattie, Caitlin Cahak, Krassimira R. Hristova and Troy Skwor

Antibiotics 2022, 11(2), 260; https://doi.org/10.3390/antibiotics11020260 - 17 Feb 2022

Cited by 6 | Viewed by 3059

Abstract

The World Health Organization has identified antibiotic resistance as one of the largest threats to human health and food security. In this study, we compared antibiotic resistance patterns between ESBL-producing Escherichia coli from human clinical diseases and cefotaxime-resistant environmental strains, as well as [...] Read more.

The World Health Organization has identified antibiotic resistance as one of the largest threats to human health and food security. In this study, we compared antibiotic resistance patterns between ESBL-producing Escherichia coli from human clinical diseases and cefotaxime-resistant environmental strains, as well as their potential to be pathogenic. Antibiotic susceptibility was tested amongst clinical isolates (n = 11), hospital wastewater (n = 22), and urban wastewater (n = 36, both influent and treated effluents). Multi-drug resistance predominated (>70%) among hospitalwastewater and urban wastewater influent isolates. Interestingly, isolates from clinical and urban treated effluents showed similar multi-drug resistance rates (~50%). Most hospital wastewater isolates were Phylogroup A, while clinical isolates were predominately B2, with a more diverse phylogroup population in urban wastewater. ESBL characterization of cefotaxime-resistant populations identified bla_CTX-M-1 subgroup as the most common, whereby bla_KPC was more associated with ceftazidime and ertapenem resistance. Whole-genome sequencing of a carbapenemase-producing hospital wastewater E. coli strain revealed plasmid-mediated bla_KPC-2. Among cefotaxime-resistant populations, over 60% of clinical and 30% of treated effluent E. coli encoded three or more virulence genes exhibiting a pathogenic potential. Together, the similarity among treated effluent E. coli populations and clinical strains suggest effluents could serve as a reservoir for future multi-drug resistant E. coli clinical infections. Full article

(This article belongs to the Special Issue Antibiotic Resistance in Wastewater and Its Treatment)

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11 pages, 855 KiB

Open AccessArticle

Cell Differentiation of Bovine Milk Control Samples to Improve Prognosis of Mastitis Cure

by Anne Bunge, Sonja Dreyer, Jan-Hendrik Paduch, Doris Klocke, Stefanie Leimbach, Nicole Wente, Julia Nitz and Volker Krömker

Antibiotics 2022, 11(2), 259; https://doi.org/10.3390/antibiotics11020259 - 17 Feb 2022

Viewed by 1622

Abstract

To optimise udder health at the herd level, identifying incurable mastitis cases as well as providing an adequate therapy and culling strategy are necessary. Cows with clinical mastitis should be administered antibiotic medication if it is most likely to improve mammary cure. The [...] Read more.

To optimise udder health at the herd level, identifying incurable mastitis cases as well as providing an adequate therapy and culling strategy are necessary. Cows with clinical mastitis should be administered antibiotic medication if it is most likely to improve mammary cure. The somatic cell count (SCC) in milk of the monthly implemented Dairy Herd Improvement (DHI) test represents the most important tool to decide whether a cow has a promising mammary cure rate. Differential cell count (DCC) facilitates the specification of the immunological ability of defence, for example by characterising leukocyte subpopulations or cell viability. The aim of this study was to assess the DCC and cell viability in DHI milk samples regarding the cytological (CC) and bacteriological cure (BC) of the udder within a longitudinal study, thereby gaining a predictive evaluation of whether a clinical mastitis benefits from an antibiotic treatment or not. The cows enrolled in this study had an SCC above 200,000 cells/mL in the previous DHI test. Study 1 assessed the CC by reference to the SCC of two consecutive DHI tests and included 1010 milk samples: 28.4% of the mammary glands were classified as cytologically cured and 71.6% as uncured. The final mixed logistic regression model identified the total number of non-vital cells as a significant factor associated with CC. An increasing amount of non-vital cells was related to a lower individual ability for CC. Cows which were in the first or second lactation possessed a higher probability of CC than cows having a lactation number above two. If animals developed a clinical mastitis after flow cytometric investigation, the BC was examined in study 2 by analysing quarter foremilk samples microbiologically. Taking 48 milk samples, 81.3% of the mammary glands were classified as bacteriologically cured and 18.7% as uncured. The percentage of total non-vital cells tended to be lower for cows which were cured, but no significance could be observed. This study revealed that the investigation of the proportion of non-vital cells in DHI milk samples can enhance the prognosis of whether an antibiotic treatment of clinical mastitis might be promising or not. Prospectively, this tool may be integrated in the DHI tests to facilitate the decision between therapy or culling. Full article

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

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11 pages, 636 KiB

Open AccessReview

Genetic Mechanisms of Vancomycin Resistance in Clostridioides difficile: A Systematic Review

by Taryn A. Eubank, Anne J. Gonzales-Luna, Julian G. Hurdle and Kevin W. Garey

Antibiotics 2022, 11(2), 258; https://doi.org/10.3390/antibiotics11020258 - 16 Feb 2022

Cited by 17 | Viewed by 3392

Abstract

Antimicrobial resistance to treatments for Clostridioides difficile infection (CDI) poses a significant threat to global health. C. difficile is widely thought to be susceptible to oral vancomycin, which is increasingly the mainstay of CDI treatment. However, clinical labs do not conduct C. difficile [...] Read more.

Antimicrobial resistance to treatments for Clostridioides difficile infection (CDI) poses a significant threat to global health. C. difficile is widely thought to be susceptible to oral vancomycin, which is increasingly the mainstay of CDI treatment. However, clinical labs do not conduct C. difficile susceptibility testing, presenting a challenge to detecting the emergence and impact of resistance. In this systematic review, we describe gene determinants and associated clinical and laboratory mechanisms of vancomycin resistance in C. difficile, including drug-binding site alterations, efflux pumps, RNA polymerase mutations, and biofilm formation. Additional research is needed to further characterize these mechanisms and understand their clinical impact. Full article

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

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15 pages, 2285 KiB

Open AccessArticle

Influence of Glucose on Candida albicans and the Relevance of the Complement FH-Binding Molecule Hgt1 in a Murine Model of Candidiasis

by Verena Harpf, Samyr Kenno, Günter Rambach, Verena Fleischer, Nadia Parth, Christian X. Weichenberger, Peter Garred, Silke Huber, Cornelia Lass-Flörl, Cornelia Speth and Reinhard Würzner

Antibiotics 2022, 11(2), 257; https://doi.org/10.3390/antibiotics11020257 - 16 Feb 2022

Cited by 3 | Viewed by 2073

Abstract

Candidiasis is common in diabetic patients. Complement evasion is facilitated by binding complement factor H (FH). Since the expression of high-affinity glucose transporter 1 (Hgt1), a FH-binding molecule, is glucose-dependent, we aimed to study its relevance to the pathogenesis of Candida albicans. [...] Read more.

Candidiasis is common in diabetic patients. Complement evasion is facilitated by binding complement factor H (FH). Since the expression of high-affinity glucose transporter 1 (Hgt1), a FH-binding molecule, is glucose-dependent, we aimed to study its relevance to the pathogenesis of Candida albicans. Euglycemic and diabetic mice were intravenously challenged with either Candida albicans lacking Hgt1 (hgt1-/-) or its parental strain (SN152). Survival and clinical status were monitored over 14 days. In vitro, Candida albicans strains were grown at different glucose concentrations, opsonized with human serum, and checked for C3b/iC3b and FH deposition. Phagocytosis was studied by fluorescein isothiocyanate-labeled opsonized yeast cells incubated with granulocytes. The murine model demonstrated a significantly higher virulence of SN152 in diabetic mice and an overall increased lethality of mice challenged with hgt1-/-. In vitro lower phagocytosis and C3b/iC3b deposition and higher FH deposition were demonstrated for SN152 incubated at higher glucose concentrations, while there was no difference on hgt1-/- at physiological glucose concentrations. Despite C3b/iC3b and FH deposition being glucose-dependent, this effect has a minor influence on phagocytosis. The absence of Hgt1 is diminishing this dependency on complement deposition, but it cannot be attributed to being beneficial in a murine model. Full article

(This article belongs to the Special Issue Research on the Pathogenesis of Candida albicans and Other Candida Species)

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25 pages, 1515 KiB

Open AccessArticle

Assessing Knowledge, Beliefs, and Behaviors around Antibiotic Usage and Antibiotic Resistance among UK Veterinary Students: A Multi-Site, Cross-Sectional Survey

by Sarah E. Golding, Helen M. Higgins and Jane Ogden

Antibiotics 2022, 11(2), 256; https://doi.org/10.3390/antibiotics11020256 - 16 Feb 2022

Cited by 5 | Viewed by 2361

Abstract

Antimicrobial resistance (AMR) is a profound threat to human and animal health. Antimicrobial prescribing behaviours are influenced by psychological factors such as knowledge, beliefs, and emotions. As future antimicrobial prescribers, it is important to understand beliefs about AMR and stewardship among veterinary (vet) [...] Read more.

Antimicrobial resistance (AMR) is a profound threat to human and animal health. Antimicrobial prescribing behaviours are influenced by psychological factors such as knowledge, beliefs, and emotions. As future antimicrobial prescribers, it is important to understand beliefs about AMR and stewardship among veterinary (vet) students. This cross-sectional online survey assessed vet students’ self-reported behavior, knowledge, and beliefs in specific relation to antibiotic resistance (ABR) and antibiotic usage. Participants were early years (first- and second-year; n = 460) and later-years (third- and fourth-year; n = 113) undergraduate vet students from three UK universities. Self-reported antibiotic-related behaviors were responsible among most students. Knowledge about ABR and stewardship was moderate among early years students and good among later years students. Vet students typically believed that vets had less responsibility for both causing and preventing ABR than other groups (animal owners, human medics, and the public). This study offers evidence that vet students (along with other groups) tend to lay greater responsibility for ABR/AMR outside of their own profession, which may impact their future prescribing behaviors. It is vital that AMR and antimicrobial stewardship are embedded across veterinary curricula, and that the One Health nature of the challenge posed by AMR is emphasized to encourage shared responsibility across all stakeholder groups, thereby helping to reduce ‘other-blaming’ for AMR. Full article

(This article belongs to the Special Issue One Health: Opportunities and Challenges of Antibiotic Resistance and Stewardship)

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13 pages, 2820 KiB

Open AccessArticle

Impact of the Stringent Stress Response on the Expression of Methicillin Resistance in Staphylococcaceae Strains Carrying mecA, mecA1 and mecC

by Catarina Milheiriço, Alexander Tomasz and Hermínia de Lencastre

Antibiotics 2022, 11(2), 255; https://doi.org/10.3390/antibiotics11020255 - 16 Feb 2022

Cited by 4 | Viewed by 1741

Abstract

The acquisition of the resistance determinant mecA by Staphylococcus aureus is of major clinical importance, since it confers a resistant phenotype to virtually the entire large family of structurally diverse β-lactam antibiotics. While the common resistance determinant mecA is essential, the optimal expression [...] Read more.

The acquisition of the resistance determinant mecA by Staphylococcus aureus is of major clinical importance, since it confers a resistant phenotype to virtually the entire large family of structurally diverse β-lactam antibiotics. While the common resistance determinant mecA is essential, the optimal expression of the resistance phenotype also requires additional factors. Previous studies showed that the great majority of clinical isolates of methicillin-resistant S. aureus (MRSA) have a heterogeneous resistant phenotype, and we observed that strains carrying methicillin genetic determinants other than mecA also produce similar heterogeneous phenotypes. All these strains were able to express high and homogeneous levels of oxacillin resistance when sub-inhibitory concentrations of mupirocin, an effector of the stringent stress response, were added to growth media. Our studies show that the gene gmk, involved in guanine metabolism, was one of the first genes to exhibit mutations in homoresistant (H*R) derivatives obtained through serial passages (with increasing concentrations of oxacillin) of the prototype mecC-carrying MRSA strain LGA251. All these observations led us to propose that a common molecular mechanism for the establishment of high and homogeneous oxacillin resistance must be present among isolates carrying different methicillin resistance determinants. In this work, we tested this hypothesis using whole-genome sequencing (WGS) to compare isogenic populations differing only in their degrees of oxacillin resistance and carrying various methicillin genetic determinants Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)

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