Antibiotics

32 pages, 3536 KiB

Open AccessArticle

Antimicrobial Evaluation of Various Honey Types against Carbapenemase-Producing Gram-Negative Clinical Isolates

by Elisavet Stavropoulou, Chrysoula (Chrysa) Voidarou, Georgios Rozos, Natalia Vaou, Michael Bardanis, Theodoros Konstantinidis, Georgia Vrioni and Athanasios Tsakris

Antibiotics 2022, 11(3), 422; https://doi.org/10.3390/antibiotics11030422 - 21 Mar 2022

Cited by 13 | Viewed by 4169

Abstract

The development of antibiotic resistance is a major public health issue, as infections are increasingly unresponsive to antibiotics. Emerging antimicrobial resistance has raised researchers’ interest in the development of alternative strategies using natural compounds with antibacterial activity, like honey, which has emerged as [...] Read more.

The development of antibiotic resistance is a major public health issue, as infections are increasingly unresponsive to antibiotics. Emerging antimicrobial resistance has raised researchers’ interest in the development of alternative strategies using natural compounds with antibacterial activity, like honey, which has emerged as an agent to treat several infections and wound injuries. Nevertheless, the antibacterial effect of honey was mostly evaluated against Gram-positive bacteria. Hence, the objective of our study was to evaluate the antibacterial activity, as well as the physicochemical parameters, of genuine Greek honeys against multidrug-resistant Gram-negative pathogenic bacteria. In this vein, we aimed to study the in vitro antibacterial potential of rare Greek honeys against Verona integron-encoded metallo-β-lactamase (VIM)- or Klebsiella pneumoniae carbapenemase-producing multidrug-resistant Gram-negative pathogens. Physicochemical parameters such as pH, hydrogen peroxide, free acidity, lactonic acid, total phenols total flavonoids, free radical scavenging activities, tyrosinase enzyme inhibitory activity and kojic acid were examined. Moreover, the antimicrobial activity of 10 different honey types was evaluated in five consecutive dilutions (75%, 50%, 25%, 12.5% and 6.25%) against the clinical isolates by the well diffusion method, as well as by the determination of the minimum inhibition concentration after the addition of catalase and protease. Almost all the physicochemical parameters varied significantly among the different honeys. Fir and manuka honey showed the highest values in pH and H₂O₂, while the free acidity and lactonic acid levels were higher in chestnut honey. Total phenols, total flavonoids and free radical scavenging activities were found higher in cotton, arbutus and manuka honey, and finally, manuka and oregano honeys showed higher tyrosinase inhibition activity and kojic acid levels. The antimicrobial susceptibility depended on the type of honey, on its dilution, on the treatment methodology and on the microorganism. Arbutus honey was the most potent against VIM-producing Enterobacter cloacae subsp. dissolvens in 75% concentration, while fir honey was more lethal for the same microorganism in the 25% concentration. Many honeys outperformed manuka honey in their antibacterial potency. It is of interest that, for any given concentration in the well diffusion method and for any given type of honey, significant differences were not detected among the four multidrug-resistant pathogens, which explains that the damaging effect to the bacterial cells was the same regardless of the bacterial species or strain. Although the antimicrobial potency of different honey varieties dependents on their geographical origin and on their compositional differences, the exact underlying mechanism remains yet unclear. Full article

(This article belongs to the Special Issue Honey Bee Products as an Alternative or Complement to Classical Antibiotics – 2nd Edition)

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8 pages, 244 KiB

Open AccessReview

Mechanisms of Action of Carbapenem Resistance

by Caterina Aurilio, Pasquale Sansone, Manlio Barbarisi, Vincenzo Pota, Luca Gregorio Giaccari, Francesco Coppolino, Alfonso Barbarisi, Maria Beatrice Passavanti and Maria Caterina Pace

Antibiotics 2022, 11(3), 421; https://doi.org/10.3390/antibiotics11030421 - 21 Mar 2022

Cited by 99 | Viewed by 19454

Abstract

Carbapenem antibiotics are the most effective antimicrobials for the treatment of infections caused by the most resistant bacteria. They belong to the category of β-lactams that include the penicillins, cephalosporins, monobactams and carbapenems. This class of antimicrobials has a broader spectrum of activity [...] Read more.

Carbapenem antibiotics are the most effective antimicrobials for the treatment of infections caused by the most resistant bacteria. They belong to the category of β-lactams that include the penicillins, cephalosporins, monobactams and carbapenems. This class of antimicrobials has a broader spectrum of activity than most other beta-lactams antibiotics and are the most effective against Gram-positive and Gram-negative bacteria. All β-lactams antibiotics have a similar molecular structure: the carbapenems together with the β-lactams. This combination gives an extraordinary stability to the molecule against the enzymes inactivating the β-lactams. They are safe to use and therefore widespread use in many countries has given rise to carbapenem resistance which is a major global public health problem. The carbapenem resistance in some species is intrinsic and consists of the capacity to resist the action of antibiotics with several mechanisms: for the absence of a specific target, or an intrinsic difference in the composition of cytoplasmatic membrane or the inability to cross the outer membrane. In addition to intrinsic resistance, bacteria can develop resistance to antibiotics with several mechanisms that can be gathered in three main groups. The first group includes antibiotics with poor penetration into the outer membrane of bacterium or antibiotic efflux. The second includes bacteria that modify the target of the antibiotics through genetic mutations or post-translational modification of the target. The third includes bacteria that act with enzyme-catalyzed modification and this is due to the production of beta-lactamases, that are able to inactivate carbapenems and so called carbapenemases. In this review, we focus on the mode of action of carbapenem and the mechanisms of carbapenem resistance. Full article

(This article belongs to the Special Issue Severe Infections Due to Carbapenem-Resistant Pathogens)

20 pages, 21427 KiB

Open AccessArticle

Microbial Spectra and Clinical Outcomes from Endoscopically Drained Pancreatic Fluid Collections: A Descriptive Cohort Study

by Viktoria Hentschel, Benjamin Walter, Noemi Harder, Frank Arnold, Thomas Seufferlein, Martin Wagner, Martin Müller and Alexander Kleger

Antibiotics 2022, 11(3), 420; https://doi.org/10.3390/antibiotics11030420 - 21 Mar 2022

Cited by 3 | Viewed by 2518

Abstract

Pancreatic pseudocyst (PC) and walled-off necrosis (WON) are dreaded complications of acute pancreatitis. Standard therapy consists of endoscopic ultrasound-guided transmural placement of stents to expedite resolution through internal drainage of fluids or necrotic material. Either double pigtail plastic stents (DPPS) or lumen-apposing metal [...] Read more.

Pancreatic pseudocyst (PC) and walled-off necrosis (WON) are dreaded complications of acute pancreatitis. Standard therapy consists of endoscopic ultrasound-guided transmural placement of stents to expedite resolution through internal drainage of fluids or necrotic material. Either double pigtail plastic stents (DPPS) or lumen-apposing metal stents (LAMS), or a combination of both, are available for this purpose. The objective of this study was to examine the impact of different stent types on infection rates in addition to clinical outcome measures such as periprocedural adverse events. We conducted a retrospective study comprising 77 patients who had undergone endoscopic drainage for PC or WON in a pancreatitis tertiary referral center. Analysis revealed that both bacterial and fungal infections occurred more frequently in patients treated with LAMS with or without DPPS compared to DPPS only. The use of antibiotics and antimycotics followed the same pattern. Furthermore, a prolonged length of hospital stay and a higher likelihood of transfer to an intermediate care unit were observed in patients with LAMS with or without DPPS. These differences were eliminated if only WON patients were analyzed. Our data imply that the clinical course is primarily influenced by the complexity of the pancreatic fluid collection (PFC) itself rather than the stent type. Prospective large-scale cohort studies are mandatory to underpin these findings. Full article

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

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8 pages, 833 KiB

Open AccessEditor’s ChoiceOpinion

Persistent Bacterial Infections, Antibiotic Treatment Failure, and Microbial Adaptive Evolution

by Ruggero La Rosa, Helle Krogh Johansen and Søren Molin

Antibiotics 2022, 11(3), 419; https://doi.org/10.3390/antibiotics11030419 - 21 Mar 2022

Cited by 20 | Viewed by 5425

Abstract

Antibiotic resistance is expected by the WHO to be the biggest threat to human health before 2050. In this overview, we argue that this prediction may in fact be too optimistic because it is often overlooked that many bacterial infections frequently ‘go under [...] Read more.

Antibiotic resistance is expected by the WHO to be the biggest threat to human health before 2050. In this overview, we argue that this prediction may in fact be too optimistic because it is often overlooked that many bacterial infections frequently ‘go under the radar’ because they are difficult to diagnose and characterize. Due to our lifestyle, persistent infections caused by opportunistic bacteria—well-known or emerging—show increasing success of infecting patients with reduced defense capacity, and often antibiotics fail to be sufficiently effective, even if the bacteria are susceptible, leaving small bacterial populations unaffected by treatment in the patient. The mechanisms behind infection persistence are multiple, and therefore very difficult to diagnose in the laboratory and to treat. In contrast to antibiotic resistance associated with acute infections caused by traditional bacterial pathogens, genetic markers associated with many persistent infections are imprecise and mostly without diagnostic value. In the absence of effective eradication strategies, there is a significant risk that persistent infections may eventually become highly resistant to antibiotic treatment due to the accumulation of genomic mutations, which will transform colonization into persistence. Full article

(This article belongs to the Special Issue How Far Are We from Predicting the Evolution of Antibiotic Resistance?)

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13 pages, 2444 KiB

Open AccessArticle

IPA-3: An Inhibitor of Diadenylate Cyclase of Streptococcus suis with Potent Antimicrobial Activity

by Haotian Li, Tingting Li, Wenjin Zou, Minghui Ni, Qiao Hu, Xiuxiu Qiu, Zhiming Yao, Jingyan Fan, Lu Li, Qi Huang and Rui Zhou

Antibiotics 2022, 11(3), 418; https://doi.org/10.3390/antibiotics11030418 - 21 Mar 2022

Cited by 4 | Viewed by 3068

Abstract

Antimicrobial resistance (AMR) poses a huge threat to public health. The development of novel antibiotics is an effective strategy to tackle AMR. Cyclic diadenylate monophosphate (c-di-AMP) has recently been identified as an essential signal molecule for some important bacterial pathogens involved in various [...] Read more.

Antimicrobial resistance (AMR) poses a huge threat to public health. The development of novel antibiotics is an effective strategy to tackle AMR. Cyclic diadenylate monophosphate (c-di-AMP) has recently been identified as an essential signal molecule for some important bacterial pathogens involved in various bacterial physiological processes, leading to its synthase diadenylate cyclase becoming an attractive antimicrobial drug target. In this study, based on the enzymatic activity of diadenylate cyclase of Streptococcus suis (ssDacA), we established a high-throughput method of screening for ssDacA inhibitors. Primary screening with a compound library containing 1133 compounds identified IPA-3 (2,2′-dihydroxy-1,1′-dinapthyldisulfide) as an ssDacA inhibitor. High-performance liquid chromatography (HPLC) analysis further indicated that IPA-3 could inhibit the production of c-di-AMP by ssDacA in vitro in a dose-dependent manner. Notably, it was demonstrated that IPA-3 could significantly inhibit the growth of several Gram-positive bacteria which harbor an essential diadenylate cyclase but not E. coli, which is devoid of the enzyme, or Streptococcus mutans, in which the diadenylate cyclase is not essential. Additionally, the binding site in ssDacA for IPA-3 was predicted by molecular docking, and contains residues that are relatively conserved in diadenylate cyclase of Gram-positive bacteria. Collectively, our results illustrate the feasibility of ssDacA as an antimicrobial target and consider IPA-3 as a promising starting point for the development of a novel antibacterial. Full article

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6 pages, 381 KiB

Open AccessBrief Report

Concentrations of Ciprofloxacin in the World’s Rivers Are Associated with the Prevalence of Fluoroquinolone Resistance in Escherichia coli: A Global Ecological Analysis

by Chris Kenyon

Antibiotics 2022, 11(3), 417; https://doi.org/10.3390/antibiotics11030417 - 20 Mar 2022

Cited by 8 | Viewed by 2831

Abstract

Background: Extremely low concentrations of ciprofloxacin may select for antimicrobial resistance. A recent global survey found that ciprofloxacin concentrations exceeded safe levels at 64 sites. In this study, I assessed if national median ciprofloxacin concentrations in rivers were associated with fluoroquinolone resistance in [...] Read more.

Background: Extremely low concentrations of ciprofloxacin may select for antimicrobial resistance. A recent global survey found that ciprofloxacin concentrations exceeded safe levels at 64 sites. In this study, I assessed if national median ciprofloxacin concentrations in rivers were associated with fluoroquinolone resistance in Escherichia coli. Methods: Spearman’s regression was used to assess the country-level association between the national prevalence of fluoroquinolone resistance in E. coli and the median ciprofloxacin concentration in the country’s rivers. Results: The prevalence of fluoroquinolone resistance in E. coli was positively correlated with the concentration of ciprofloxacin in rivers (ρ = 0.36; p = 0.011; n = 48). Discussion: Steps to reducing the concentrations of fluoroquinolones in rivers may help prevent the emergence of resistance in E. coli and other bacterial species. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Infectious Diseases: A One Health Perspective)

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15 pages, 1706 KiB

Open AccessArticle

Combination of Amphiphilic Cyclic Peptide [R₄W₄] and Levofloxacin against Multidrug-Resistant Bacteria

by Muhammad Imran Sajid, Sandeep Lohan, Shun Kato and Rakesh Kumar Tiwari

Antibiotics 2022, 11(3), 416; https://doi.org/10.3390/antibiotics11030416 - 20 Mar 2022

Cited by 8 | Viewed by 3727

Abstract

Bacterial resistance is a growing global concern necessitating the discovery and development of antibiotics effective against the drug-resistant bacterial strain. Previously, we reported a cyclic antimicrobial peptide [R₄W₄] containing arginine (R) and tryptophan (W) with a MIC of 2.67 [...] Read more.

Bacterial resistance is a growing global concern necessitating the discovery and development of antibiotics effective against the drug-resistant bacterial strain. Previously, we reported a cyclic antimicrobial peptide [R₄W₄] containing arginine (R) and tryptophan (W) with a MIC of 2.67 µg/mL (1.95 µM) against methicillin-resistant Staphylococcus aureus (MRSA). Herein, we investigated the cyclic peptides [R₄W₄] or linear (R₄W₄) and their conjugates (covalent or noncovalent) with levofloxacin (Levo) with the intent to improve their potency to target drug-resistant bacteria. The physical mixture of the Levo with the cyclic [R₄W₄] proved to be significantly effective against all strains of bacteria used in the study as compared to covalent conjugation. Furthermore, the checkerboard assay revealed the significant synergistic effect of the peptides against all studied strains except for the wild type S. aureus, in which the partial synergy was observed. The hemolysis assay revealed less cytotoxicity of the physical mixture of the Levo with [R₄W₄] (22%) as compared to [R₄W₄] alone (80%). The linear peptide (R₄W₄) and the cyclic [R₄W₄] demonstrated ~90% and 85% cell viability at 300 µg/mL in the triple-negative breast cancer cells (MDA-MB-231) and the normal kidney cells (HEK-293), respectively. Similar trends were also observed in the cell viability of Levo-conjugates on these cell lines. Furthermore, the time-kill kinetic study of the combination of [R₄W₄] and Levo demonstrate rapid killing action at 4 h for MRSA (ATCC BAA-1556) and 12 h for E. coli (ATCC BAA-2452), P. aeruginosa (ATCC BAA-1744), and K. pneumoniae (ATCC BAA-1705). These results provide the effectiveness of a combination of Levo with cyclic [R₄W₄] peptide, which may provide an opportunity to solve the intriguing puzzle of treating bacterial resistance. Full article

(This article belongs to the Special Issue Combination Therapy against Multidrug-Resistant Pathogens)

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9 pages, 268 KiB

Open AccessArticle

Comparison of Fluoroquinolones and Other Antibiotic Prophylaxis Regimens for Preventing Complications in Patients Undergoing Transrectal Prostate Biopsy

by Gabriele Tulone, Sofia Giannone, Piero Mannone, Alessio Tognarelli, Tommaso Di Vico, Rosa Giaimo, Alessandro Zucchi, Marta Rossanese, Alberto Abrate, Nicola Pavan, Francesco Claps, Vincenzo Ficarra, Riccardo Bartoletti and Alchiede Simonato

Antibiotics 2022, 11(3), 415; https://doi.org/10.3390/antibiotics11030415 - 20 Mar 2022

Cited by 6 | Viewed by 3415

Abstract

Our study aimed to compare the incidence of infective complications after transrectal ultrasound-guided prostate biopsy (TRUSBx) when adopting different antimicrobial prophylaxis regimens. A multi-institutional cohort of 1150 patients who underwent TRUSBx was retrospectively analyzed. Procedures were performed between 2017 and 2019 (before and [...] Read more.

Our study aimed to compare the incidence of infective complications after transrectal ultrasound-guided prostate biopsy (TRUSBx) when adopting different antimicrobial prophylaxis regimens. A multi-institutional cohort of 1150 patients who underwent TRUSBx was retrospectively analyzed. Procedures were performed between 2017 and 2019 (before and after the EMA warning about the use of fluoroquinolones for the antibiotic prophylaxis of patient candidates to TRUSBx). The primary endpoint was the occurrence of infective complications, including sepsis and/or fever. The population was stratified according to the antibiotic prophylaxis adopted: fluoroquinolones (levofloxacin, ciprofloxacin, prulifloxacin), cephalosporins (cefixime, ceftriaxone) or trimethoprim/sulfamethoxazole. Univariable and multivariable binomial logistic regression models were used to assess the odds ratio (OR) with 95% confidence interval (CI) testing of the risk of infective complication after adjusting for each prebiopsy covariate. In total, 478 (41.6%) patients received fluoroquinolone-based prophylaxis. Among these, 443 (38.5%), 25 (2.2%) and 10 (0.9%) patients received levofloxacin prophylaxis, ciprofloxacin and prulifloxacin, respectively while 14.6% received cefixime, 20.7% received the comedication of ceftriaxone/fosfomycin and 23.1% received trimethoprim/sulfamethoxazole. The trimethoprim/sulfamethoxazole and fluoroquinolone regimens were significantly associated with a lower risk of infective complications (OR 0.15, 95% CI 0.03–0.48, p = 0.003 and OR 0.17, 95% CI 0.06–0.43, p < 0.001, respectively). The ceftriaxone/fosfomycin (OR 0.21, 95% CI 0.04–0.92, p = 0.04) and fluoroquinolone (OR 0.07, 95% CI 0.00–0.70, p = 0.048) prophylaxis were associated with a lower risk of infective sequelae. Fluoroquinolone-based prophylaxis was associated with a lower risk of infective complications after TRUSBx compared to other prophylaxis regimens although its clinical application was recently forbidden by European Medical Agency restrictions. Full article

(This article belongs to the Special Issue Difficult to Treat Infections in Urology)

14 pages, 3087 KiB

Open AccessArticle

The Effect of Toothpastes Containing Natural Extracts on Bacterial Species of a Microcosm Biofilm and on Enamel Caries Development

by Aline Silva Braga, Mohamed Mostafa Hefny Abdelbary, Rafaela Ricci Kim, Fernanda Pereira de Souza Rosa de Melo, Luiz Leonardo Saldanha, Anne Lígia Dokkedal, Georg Conrads, Marcella Esteves-Oliveira and Ana Carolina Magalhães

Antibiotics 2022, 11(3), 414; https://doi.org/10.3390/antibiotics11030414 - 19 Mar 2022

Cited by 10 | Viewed by 3852

Abstract

This study investigated the effects of herbal toothpaste on bacterial counts and enamel demineralization. Thirty-six bovine enamel samples were exposed to a microcosm biofilm using human saliva and McBain saliva (0.2% sucrose) for 5 days at 37 °C and first incubated anaerobically, then [...] Read more.

This study investigated the effects of herbal toothpaste on bacterial counts and enamel demineralization. Thirty-six bovine enamel samples were exposed to a microcosm biofilm using human saliva and McBain saliva (0.2% sucrose) for 5 days at 37 °C and first incubated anaerobically, then aerobically–capnophilically. The following experimental toothpaste slurries (2 × 2 min/day) were applied: (1) Vochysia tucanorum (10 mg/g); (2) Myrcia bella (5 mg/g); (3) Matricaria chamomilla (80 mg/g); (4) Myrrha and propolis toothpaste (commercial); (5) fluoride (F) and triclosan (1450 ppm F), 0.3% triclosan and sorbitol (Colgate^®, positive control); (6) placebo (negative control). The pH of the medium was measured, bacteria were analyzed using quantitative polymerase chain reaction, and enamel demineralization was quantified using transverse microradiography. The total bacterial count was reduced by toothpaste containing Myrcia bella, Matricaria chamomilla, fluoride, and triclosan (commercial) compared to the placebo. As far as assessable, Myrcia bella, Matricaria chamomilla, and Myrrha and propolis (commercial) inhibited the outgrowth of S. mutans, while Lactobacillus spp. were reduced/eliminated by all toothpastes except Vochysia tucanorum. Mineral loss and lesion depth were significantly reduced by all toothpastes (total: 1423.6 ± 115.2 vol% × μm; 57.3 ± 9.8 μm) compared to the placebo (2420.0 ± 626.0 vol% × μm; 108.9 ± 21.17 μm). Herbal toothpastes were able to reduce enamel demineralization. Full article

(This article belongs to the Special Issue Antimicrobial Strategies against Oral Pathogenic Bacteria and Biofilm)

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16 pages, 3187 KiB

Open AccessArticle

Antimicrobial Random Peptide Mixtures Eradicate Acinetobacter baumannii Biofilms and Inhibit Mouse Models of Infection

by Hannah E. Caraway, Jonathan Z. Lau, Bar Maron, Myung Whan Oh, Yael Belo, Aya Brill, Einav Malach, Nahed Ismail, Zvi Hayouka and Gee W. Lau

Antibiotics 2022, 11(3), 413; https://doi.org/10.3390/antibiotics11030413 - 19 Mar 2022

Cited by 11 | Viewed by 3650

Abstract

Antibiotic resistance is one of the greatest crises in human medicine. Increased incidents of antibiotic resistance are linked to clinical overuse and overreliance on antibiotics. Among the ESKAPE pathogens, Acinetobacter baumannii, especially carbapenem-resistant isolates, has emerged as a significant threat in the [...] Read more.

Antibiotic resistance is one of the greatest crises in human medicine. Increased incidents of antibiotic resistance are linked to clinical overuse and overreliance on antibiotics. Among the ESKAPE pathogens, Acinetobacter baumannii, especially carbapenem-resistant isolates, has emerged as a significant threat in the context of blood, urinary tract, lung, and wound infections. Therefore, new approaches that limit the emergence of antibiotic resistant A. baumannii are urgently needed. Recently, we have shown that random peptide mixtures (RPMs) are an attractive alternative class of drugs to antibiotics with strong safety and pharmacokinetic profiles. RPMs are antimicrobial peptide mixtures produced by incorporating two amino acids at each coupling step, rendering them extremely diverse but still defined in their overall composition, chain length, and stereochemistry. The extreme diversity of RPMs may prevent bacteria from evolving resistance rapidly. Here, we demonstrated that RPMs rapidly and efficiently kill different strains of A. baumannii, inhibit biofilm formation, and disrupt mature biofilms. Importantly, RPMs attenuated bacterial burden in mouse models of acute pneumonia and soft tissue infection and significantly reduced mouse mortality during sepsis. Collectively, our results demonstrate RPMs have the potential to be used as powerful therapeutics against antibiotic-resistant A. baumannii. Full article

(This article belongs to the Special Issue Peptide-Based Antibiotics: Challenges and Opportunities)

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28 pages, 3872 KiB

Open AccessReview

Antimicrobial Activity Enhancers: Towards Smart Delivery of Antimicrobial Agents

by Mariusz Skwarczynski, Sahra Bashiri, Ye Yuan, Zyta M. Ziora, Osama Nabil, Keita Masuda, Mattaka Khongkow, Natchanon Rimsueb, Horacio Cabral, Uracha Ruktanonchai, Mark A. T. Blaskovich and Istvan Toth

Antibiotics 2022, 11(3), 412; https://doi.org/10.3390/antibiotics11030412 - 18 Mar 2022

Cited by 35 | Viewed by 6723

Abstract

The development of effective treatments against infectious diseases is an extensive and ongoing process due to the rapid adaptation of bacteria to antibiotic-based therapies. However, appropriately designed activity enhancers, including antibiotic delivery systems, can increase the effectiveness of current antibiotics, overcoming antimicrobial resistance [...] Read more.

The development of effective treatments against infectious diseases is an extensive and ongoing process due to the rapid adaptation of bacteria to antibiotic-based therapies. However, appropriately designed activity enhancers, including antibiotic delivery systems, can increase the effectiveness of current antibiotics, overcoming antimicrobial resistance and decreasing the chance of contributing to further bacterial resistance. The activity/delivery enhancers improve drug absorption, allow targeted antibiotic delivery, improve their tissue and biofilm penetration and reduce side effects. This review provides insights into various antibiotic activity enhancers, including polymer, lipid, and silver-based systems, designed to reduce the adverse effects of antibiotics and improve formulation stability and efficacy against multidrug-resistant bacteria. Full article

(This article belongs to the Special Issue Antimicrobial Silver in Medicinal Applications)

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13 pages, 12614 KiB

Open AccessArticle

Novel Antimicrobial Peptides Designed Using a Recurrent Neural Network Reduce Mortality in Experimental Sepsis

by Albert Bolatchiev, Vladimir Baturin, Evgeny Shchetinin and Elizaveta Bolatchieva

Antibiotics 2022, 11(3), 411; https://doi.org/10.3390/antibiotics11030411 - 18 Mar 2022

Cited by 13 | Viewed by 3957

Abstract

The search and development of new antibiotics is relevant due to widespread antibiotic resistance. One of the promising strategies is the de novo design of novel antimicrobial peptides. The amino acid sequences of 198 novel peptides were obtained using a generative long short-term [...] Read more.

The search and development of new antibiotics is relevant due to widespread antibiotic resistance. One of the promising strategies is the de novo design of novel antimicrobial peptides. The amino acid sequences of 198 novel peptides were obtained using a generative long short-term memory recurrent neural network (LSTM RNN). To assess their antimicrobial effect, we synthesized five out of 198 generated peptides. The PEP-38 and PEP-137 peptides were active in vitro against carbapenem-resistant isolates of Klebsiella aerogenes and K. pneumoniae. PEP-137 was also active against Pseudomonas aeruginosa. The remaining three peptides (PEP-36, PEP-136 and PEP-174) showed no antibacterial effect. Then the effect of PEP-38 and PEP-137 (a single intraperitoneal administration of a 100 μg dose 30 min after infection) on animal survival in an experimental murine model of K. pneumoniae-induced sepsis was investigated. As a control, two groups of mice were used: one received sterile saline, and the other received inactive in vitro PEP-36 (a single 100 μg dose). The PEP-36 peptide was shown to provide the highest survival rate (66.7%). PEP-137 showed a survival rate of 50%. PEP-38 was found to be ineffective. The data obtained can be used to develop new antibacterial peptide drugs to combat antibiotic resistance. Full article

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

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15 pages, 1280 KiB

Open AccessArticle

Antimicrobial Susceptibility of Streptococcus suis Isolated from Diseased Pigs in Thailand, 2018–2020

by Kamonwan Lunha, Wiyada Chumpol, Sukuma Samngamnim, Surasak Jiemsup, Pornchalit Assavacheep and Suganya Yongkiettrakul

Antibiotics 2022, 11(3), 410; https://doi.org/10.3390/antibiotics11030410 - 18 Mar 2022

Cited by 19 | Viewed by 5207

Abstract

Streptococcus suis is a porcine and zoonotic pathogen that causes severe systemic infection in humans and pigs. The treatment of S. suis infection relies on antibiotics; however, antimicrobial resistance (AMR) is an urgent global problem, pushing research attention on the surveillance of antibiotic-resistant [...] Read more.

Streptococcus suis is a porcine and zoonotic pathogen that causes severe systemic infection in humans and pigs. The treatment of S. suis infection relies on antibiotics; however, antimicrobial resistance (AMR) is an urgent global problem, pushing research attention on the surveillance of antibiotic-resistant S. suis to the fore. This study investigated the antimicrobial susceptibility of 246 S. suis strains isolated from diseased pigs in Thailand from 2018–2020. The major sources of S. suis strains were lung and brain tissues. PCR-based serotyping demonstrated that the most abundant serotype was serotype 2 or ½, followed by serotypes 29, 8, 9, and 21. To the best of our knowledge, this is the first report describing the distribution of AMR S. suis serotype 29 in diseased pigs. The antimicrobial susceptibility test was performed to determine the minimum inhibitory concentrations of 35 antimicrobial agents. The results showed that important antimicrobial agents for human use, amoxicillin/clavulanic acid, daptomycin, ertapenem, meropenem, and vancomycin, were the most effective drugs. However, a slight decrease in the number of S. suis strains susceptible to amoxicillin/clavulanic acid and vancomycin raised awareness of the AMR problem in the future. The data indicated a tendency of reduced efficacy of available veterinary medicines, including ampicillin, cefepime, cefotaxime, ceftiofur, ceftriaxone, chloramphenicol, florfenicol, gentamicin, penicillin, and tiamulin, for the treatment of S. suis infection, thus emphasizing the importance of the prudent use of antibiotics. The widespread of multidrug-resistant S. suis strains was identified in all serotypes and from different time periods and different regions of the country, confirming the emergence of the AMR problem in the diseased pig-isolated S. suis population. Full article

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

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12 pages, 1141 KiB

Open AccessReview

A Systematic Review on Clinical Safety and Efficacy of Vancomycin Loading Dose in Critically Ill Patients

by Abdul Haseeb, Mayyasah Khalid Alqurashi, Areej Sultan Althaqafi, Jumana Majdi Alsharif, Hani Saleh Faidah, Mashael Bushyah, Amal F. Alotaibi, Mahmoud Essam Elrggal, Ahmad Jamal Mahrous, Safa S. Almarzoky Abuhussain, Najla A. Obaid, Manal Algethamy, Abdullmoin AlQarni, Asim A. Khogeer, Zikria Saleem, Muhammad Shahid Iqbal, Sami S. Ashgar and Aziz Sheikh

Antibiotics 2022, 11(3), 409; https://doi.org/10.3390/antibiotics11030409 - 18 Mar 2022

Cited by 7 | Viewed by 4144

Abstract

Background: The clinical significance of utilizing a vancomycin loading dose in critically ill patients remains unclear. Objective: The main aim of this systematic review is to evaluate the clinical safety and efficacy of the vancomycin loading dose in critically ill patients. Methods: We [...] Read more.

Background: The clinical significance of utilizing a vancomycin loading dose in critically ill patients remains unclear. Objective: The main aim of this systematic review is to evaluate the clinical safety and efficacy of the vancomycin loading dose in critically ill patients. Methods: We performed a systematic review using PRISMA guidelines. PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar, the Saudi Digital Library and other databases were searched. Studies that reported clinical outcomes among patients receiving the vancomycin LD were considered eligible. Data for this study were collected using PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar and the Saudi Digital Library using the following terms: “vancomycin”, “safety”, “efficacy” and “loading dose” combined with the Boolean operator “AND” or “OR”. Results: A total of 17 articles, including 2 RCTs, 11 retrospective cohorts and 4 other studies, met the inclusion/exclusion criteria out of a total 1189 studies. Patients had different clinical characteristics representing a heterogenous group, including patients in critical condition, with renal impairment, sepsis, MRSA infection and hospitalized patients for hemodialysis or in the emergency department. Conclusions: The study shows that the target therapeutic level is achieved more easily among patients receiving a weight-based LD as compared to patients received the usual dose without an increased risk of new-onset adverse drug reactions. Full article

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8 pages, 1045 KiB

Open AccessArticle

Incidence of Vancomycin-Resistant Staphylococcus aureus Strains among Patients with Urinary Tract Infections

by Samy Selim, Osama Ahmed Faried, Mohammed S. Almuhayawi, Fayez M. Saleh, Mohamed Sharaf, Nihal El Nahhas and Mona Warrad

Antibiotics 2022, 11(3), 408; https://doi.org/10.3390/antibiotics11030408 - 18 Mar 2022

Cited by 21 | Viewed by 4084

Abstract

There has been a substantial rise in the number of vancomycin-resistant Staphylococcus aureus (VRSA) strains during the last several years. The proportion of vancomycin-resistant strains among isolated S. aureus has risen steadily in recent years, with the first spike occurring in critical care [...] Read more.

There has been a substantial rise in the number of vancomycin-resistant Staphylococcus aureus (VRSA) strains during the last several years. The proportion of vancomycin-resistant strains among isolated S. aureus has risen steadily in recent years, with the first spike occurring in critical care units and thereafter in general hospital wards. S. aureus isolates from urinary tract infection patients were studied for their prevalence and antibiotic resistance. From 292 urine samples, 103 bacterial strains (35.3%) were identified as S. aureus. Various antibiotics were used to test the isolates’ antibacterial resistance profiles. Antibiotic resistance to erythromycin was found in most bacterial isolates, whereas tobramycin antibiotic sensitivity was found in most of them. Vancomycin resistance was found in 23 of all S. aureus isolates in this study. Analysis for β-lactamase found that 71% of S. aureus isolates were positive in all isolates. There was a single plasmid with a molecular weight of 39.306 Kbp in five selected VRSA isolates that was subjected to plasmid analysis. There was evidence of vancomycin resistance among the S. aureus isolates collected from UTI patients in this investigation. This vancomycin resistance pretenses a challenge in the treatment of S. aureus infections and the need to precisely recognize persons who require last-resort medication such as tobramycin. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of Professor Jordi Vila—Outstanding Contributions in the Fields of Antimicrobial Resistance)

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13 pages, 1288 KiB

Open AccessArticle

Estimates of Dietary Exposure to Antibiotics among a Community Population in East China

by Yingying Wang, Xinping Zhao, Jinxin Zang, Yurong Li, Xiaolian Dong, Feng Jiang, Na Wang, Lufang Jiang, Qingwu Jiang and Chaowei Fu

Antibiotics 2022, 11(3), 407; https://doi.org/10.3390/antibiotics11030407 - 17 Mar 2022

Cited by 10 | Viewed by 2735

Abstract

Background: Antibiotics are widely used in clinics, livestock farms and the aquaculture industry. A variety of antibiotics in foods and drinking water may lead to important and inadvertent dietary exposure However, the profile of dietary exposure to antibiotics in humans is not well-explored. [...] Read more.

Background: Antibiotics are widely used in clinics, livestock farms and the aquaculture industry. A variety of antibiotics in foods and drinking water may lead to important and inadvertent dietary exposure However, the profile of dietary exposure to antibiotics in humans is not well-explored. East China is an economically developed area with a high usage of antibiotics and a high rate of antibiotic resistance (ABR). This study aimed to evaluate the total intake level of antibiotics in humans via foods and drinking water based on a community population in East China. Methods: A total of 600 local residents from 194 households were recruited into this study in Deqing County of Zhejiang Province since June 2019. Each subject was asked to fill a food frequency questionnaire to report their daily consumption of foods and drinking water. Tap water samples were collected from ten households and twenty-one antibiotics of five categories were selected to detect in drinking water. Data of antibiotic residues in animal-derived foods were obtained from the notification of unqualified edible agricultural products after special supervision sampling inspection in Deqing County. The human dietary exposure to antibiotics was estimated by combining the data of antibiotic contamination in foods and drinking water, and the information of dietary consumption. Results: Of twenty-one antibiotics selected, subjects were exposed to a total of sixteen antibiotics, ranging from 15.12 to 1128 μg/day via two main dietary routes (animal-derived foods and drinking water). The overall dietary exposure level varied greatly in the antibiotics detected and their sources. Compared with other antibiotics, enrofloxacin made the most contributions in terms of dietary exposure, with a median exposure level of 120.19 μg/day (IQR: 8.39–698.78 μg/day), followed by sulfamethazine (median: 32.95 μg/day, IQR: 2.77–162.55 μg/day) and oxytetracycline (median: 28.50 μg/day, IQR: 2.22–146.58 μg/day). The estimated exposure level via drinking water (at the ng/day level, median: 26.74 ng/day, IQR: 16.05–37.44 ng/day) was significantly and substantially lower than those via animal-derived foods (at the μg/day level, median: 216.38 μg/day, IQR: 87.52–323.00 μg/day). The overall dietary exposure level also showed differences in sex and age. Males and youths were more likely to be exposed to antibiotics via dietary routes than others. Conclusions: The community population investigated in East China was extensively exposed to multiple antibiotics via dietary routes. Long-term exposure to low-dose antibiotics in animal-derived foods was the primary dietary exposure route, compared with drinking water. Enrofloxacin contributed to the major body burden of dietary exposure, based on the combination of consumption of aquatic products and considerable enrofloxacin residues in them. Although the human dietary exposure level to antibiotics via drinking water and animal-derived foods ranged from ng/day to μg/L, their chronic toxicity and the accumulation and spread of ABR may be potential hazards to humans. Therefore, long-term monitoring of antibiotic contaminations in foods and drinking water, and human dietary antibiotic exposure is warranted. Full article

(This article belongs to the Special Issue Recent Advances in Antibiotic and Antibiotic Resistance Research in Food)

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21 pages, 1082 KiB

Open AccessPerspective

Orthopaedic Implant-Associated Staphylococcal Infections: A Critical Reappraisal of Unmet Clinical Needs Associated with the Implementation of the Best Antibiotic Choice

by Milo Gatti, Simona Barnini, Fabio Guarracino, Eva Maria Parisio, Michele Spinicci, Bruno Viaggi, Sara D’Arienzo, Silvia Forni, Angelo Galano and Fabrizio Gemmi

Antibiotics 2022, 11(3), 406; https://doi.org/10.3390/antibiotics11030406 - 17 Mar 2022

Cited by 15 | Viewed by 4853

Abstract

Infections associated with orthopaedic implants represent a major health concern characterized by a remarkable incidence of morbidity and mortality. The wide variety of clinical scenarios encountered in the heterogeneous world of infections associated with orthopaedic implants makes the implementation of an optimal and [...] Read more.

Infections associated with orthopaedic implants represent a major health concern characterized by a remarkable incidence of morbidity and mortality. The wide variety of clinical scenarios encountered in the heterogeneous world of infections associated with orthopaedic implants makes the implementation of an optimal and standardized antimicrobial treatment challenging. Antibiotic bone penetration, anti-biofilm activity, long-term safety, and drug choice/dosage regimens favouring outpatient management (i.e., long-acting or oral agents) play a major role in regards to the chronic evolution of these infections. The aim of this multidisciplinary opinion article is to summarize evidence supporting the use of the different anti-staphylococcal agents in terms of microbiological and pharmacological optimization according to bone penetration, anti-biofilm activity, long-term safety, and feasibility for outpatient regimens, and to provide a useful guide for clinicians in the management of patients affected by staphylococcal infections associated with orthopaedic implants Novel long-acting lipoglycopeptides, and particularly dalbavancin, alone or in combination with rifampicin, could represent the best antibiotic choice according to real-world evidence and pharmacokinetic/pharmacodynamic properties. The implementation of a multidisciplinary taskforce and close cooperation between microbiologists and clinicians is crucial for providing the best care in this scenario. Full article

(This article belongs to the Special Issue Risk of Recurrence and Risk Reduction Strategies of Implant-Related Bone and Joint Infections)

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15 pages, 723 KiB

Open AccessArticle

ICU-Associated Gram-Negative Bloodstream Infection: Risk Factors Affecting the Outcome Following the Emergence of Colistin-Resistant Isolates in a Regional Greek Hospital

by Marios Karvouniaris, Garyphallia Poulakou, Konstantinos Tsiakos, Maria Chatzimichail, Panagiotis Papamichalis, Anna Katsiaflaka, Katerina Oikonomou, Antonios Katsioulis, Eleni Palli and Apostolos Komnos

Antibiotics 2022, 11(3), 405; https://doi.org/10.3390/antibiotics11030405 - 17 Mar 2022

Cited by 7 | Viewed by 3094

Abstract

Intensive care unit patients may present infections by difficult-to-treat-resistant Gram-negative microorganisms. Colistin resurfaced as a last resort antibiotic for the treatment of multi-drug-resistant Gram-negative bacteria. However, colistin might not improve survival, particularly after the emergence of colistin-resistant isolates. We aimed to (1) examine [...] Read more.

Intensive care unit patients may present infections by difficult-to-treat-resistant Gram-negative microorganisms. Colistin resurfaced as a last resort antibiotic for the treatment of multi-drug-resistant Gram-negative bacteria. However, colistin might not improve survival, particularly after the emergence of colistin-resistant isolates. We aimed to (1) examine the first Gram-negative-associated-bloodstream infection (GN-BSI) effect on 28-day mortality and (2) distinguish mortality risk factors. From 1 January 2018 to 31 December 2019, we retrospectively studied all adult patients admitted for more than 48 h in the critical care department of a regional Greek hospital, with prevalent difficult-to-treat Gram-negative pathogens. We examined the patient records for the first GN-BSI. The local laboratory used broth microdilution to evaluate bacterial susceptibility to colistin. Seventy-eight patients fulfilled the entry criteria: adult and first GN-BSI. They developed GN-BSI on day 10 (6–18), while the overall mortality was 26.9%. Thirty-two and 46 individuals comprised the respective colistin-resistant and colistin-sensitive groups. The admission Acute Physiology Assessment and Chronic Health Evaluation II score was associated with acquiring colistin-resistant GN-BSI in the multivariable logistic regression analysis (οdds ratio (CI), 1.11 (1.03–1.21)). Regarding mortality, the index day sequential organ failure assessment score was solely associated with the outcome (hazard-ratio (CI), 1.23 (1.03–1.48), Cox proportional hazard analysis). GN-BSI was often caused by colistin-resistant bacteria. Concerning our data, sepsis severity was the independent predictor of mortality regardless of the colistin-resistance phenotype or empirical colistin treatment. Full article

(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)

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8 pages, 404 KiB

Open AccessArticle

Pathogenic E. coli from Cattle as a Reservoir of Resistance Genes to Various Groups of Antibiotics

by Alexandra Tabaran, Virginie Soulageon, Flore Chirila, Oana Lucia Reget, Marian Mihaiu, Mihai Borzan and Sorin Daniel Dan

Antibiotics 2022, 11(3), 404; https://doi.org/10.3390/antibiotics11030404 - 17 Mar 2022

Cited by 9 | Viewed by 3116

Abstract

Antimicrobial resistance has become a worldwide concern in all public health domains and reducing the spread has become a global priority. Pathogenic E. coli is responsible for a number of illnesses in humans and outbreaks in the past have been correlated with the [...] Read more.

Antimicrobial resistance has become a worldwide concern in all public health domains and reducing the spread has become a global priority. Pathogenic E. coli is responsible for a number of illnesses in humans and outbreaks in the past have been correlated with the consumption of contaminated bovine products. This is why surveillance in all the steps of production is essential. This study focused on identifying the pathogenic strains of E. coli in two large bovine abattoirs from Romania and France, and on associating them with the antimicrobial resistance patterns. A total of 250 samples from intestinal content were aseptically collected during the evisceration step of the cattle slaughtering process, from which 242 E. coli strains were isolated. Seventeen percent of all samples tested positive to at least one E. coli isolate carrying eaeA, stx1 and stx2 genes. The most prevalent genetic profile found in the E. coli strains tested was Stx1-positive and Stx2/eaeA-negative. More than 68% of the pathogenic E. coli isolated in Romania showed multi-drug resistance (MDR) and in France, the percentage was significantly lower (38%). The MDR profiles showed a high gene diversity for antibiotic resistance, which represents a great risk for environmental spread and human health. Our results indicate that in Romania, bovines can represent a reservoir for MDR E. coli and, hence, a surveillance system for antimicrobials usage in farm animals is highly needed. Full article

(This article belongs to the Special Issue Food-Borne Pathogens and Antimicrobial Resistance)

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23 pages, 1706 KiB

Open AccessArticle

Rational Use of Danofloxacin for Treatment of Mycoplasma gallisepticum in Chickens Based on the Clinical Breakpoint and Lung Microbiota Shift

by Shuge Wang, Anxiong Huang, Yufeng Gu, Jun Li, Lingli Huang, Xu Wang, Yanfei Tao, Zhenli Liu, Congming Wu, Zonghui Yuan and Haihong Hao

Antibiotics 2022, 11(3), 403; https://doi.org/10.3390/antibiotics11030403 - 17 Mar 2022

Cited by 9 | Viewed by 3151

Abstract

The study was to explore the rational use of danofloxacin against Mycoplasma gallisepticum (MG) based on its clinical breakpoint (CBP) and the effect on lung microbiota. The CBP was established according to epidemiological cutoff value (ECV/CO_WT), pharmacokinetic–pharmacodynamic (PK–PD) cutoff [...] Read more.

The study was to explore the rational use of danofloxacin against Mycoplasma gallisepticum (MG) based on its clinical breakpoint (CBP) and the effect on lung microbiota. The CBP was established according to epidemiological cutoff value (ECV/CO_WT), pharmacokinetic–pharmacodynamic (PK–PD) cutoff value (CO_PD) and clinical cutoff value (CO_CL). The ECV was determined by the micro-broth dilution method and analyzed by ECOFFinder software. The CO_PD was determined according to PK–PD modeling of danofloxacin in infected lung tissue with Monte Carlo analysis. The CO_CL was performed based on the relationship between the minimum inhibitory concentration (MIC) and the possibility of cure (POC) from clinical trials. The CBP in infected lung tissue was 1 μg/mL according to CLSI M37-A3 decision tree. The 16S ribosomal RNA (rRNA) sequencing results showed that the lung microbiota, especially the phyla Firmicutes and Proteobacteria had changed significantly along with the process of cure regimen (the 24 h dosing interval of 16.60 mg/kg b.w for three consecutive days). Our study suggested that the rational use of danofloxacin for the treatment of MG infections should consider the MIC and effect of antibiotics on the respiratory microbiota. Full article

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

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11 pages, 13471 KiB

Open AccessArticle

Short and Concise Peer-to-Peer Teaching—Example of a Successful Antibiotic Stewardship Intervention to Increase Iv to Po Conversion

by Johannes Wild, Bettina Siegrist, Lukas Hobohm, Thomas Münzel, Thomas Schwanz and Ingo Sagoschen

Antibiotics 2022, 11(3), 402; https://doi.org/10.3390/antibiotics11030402 - 17 Mar 2022

Viewed by 2461

Abstract

Antibiotic stewardship (ABS) programs aim to combine effective treatment with minimized antibiotic-related harms. Common ABS interventions are simple and effective, but their implementation in daily practice is often difficult. The aim of our study was to investigate if a single, short, peer-to-peer teaching [...] Read more.

Antibiotic stewardship (ABS) programs aim to combine effective treatment with minimized antibiotic-related harms. Common ABS interventions are simple and effective, but their implementation in daily practice is often difficult. The aim of our study was to investigate if a single, short, peer-to-peer teaching intervention (junior doctor to junior doctor) during clinical routine can successfully improve antibiotic prescriptions. We performed a quasi-experimental before–after study on a regular care cardiology ward at a large academic medical center in Germany. We evaluated antibiotic use metrics retrospectively and calculated defined daily doses (DDD) with the anatomical therapeutic chemical/DDD classification system of the World Health Organization. We hypothesize that the over-representative use of intravenous administration is a potentially modifiable target, which can be proven by antibiotic use metrics analysis. After a single peer-to-peer teaching session with a focus on indications for iv to po conversion, the normalized percentage of intravenous compared to oral administration significantly decreased (from 86.5 ± 50.3% to 41.4 ± 70.3%). Moreover, after the intervention, antibiotics with high oral bioavailability were no longer administered intravenously at all during the following quarter. Our results indicate that even a single peer-to-peer training session is highly effective in improving the iv to po conversion rate in the short term. Full article

(This article belongs to the Special Issue The Optimization of Antimicrobial Prescribing and Stewardship)

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22 pages, 4027 KiB

Open AccessArticle

A Novel Network Science and Similarity-Searching-Based Approach for Discovering Potential Tumor-Homing Peptides from Antimicrobials

by Maylin Romero, Yovani Marrero-Ponce, Hortensia Rodríguez, Guillermin Agüero-Chapin, Agostinho Antunes, Longendri Aguilera-Mendoza and Felix Martinez-Rios

Antibiotics 2022, 11(3), 401; https://doi.org/10.3390/antibiotics11030401 - 17 Mar 2022

Cited by 12 | Viewed by 3542

Abstract

Peptide-based drugs are promising anticancer candidates due to their biocompatibility and low toxicity. In particular, tumor-homing peptides (THPs) have the ability to bind specifically to cancer cell receptors and tumor vasculature. Despite their potential to develop antitumor drugs, there are few available prediction [...] Read more.

Peptide-based drugs are promising anticancer candidates due to their biocompatibility and low toxicity. In particular, tumor-homing peptides (THPs) have the ability to bind specifically to cancer cell receptors and tumor vasculature. Despite their potential to develop antitumor drugs, there are few available prediction tools to assist the discovery of new THPs. Two webservers based on machine learning models are currently active, the TumorHPD and the THPep, and more recently the SCMTHP. Herein, a novel method based on network science and similarity searching implemented in the starPep toolbox is presented for THP discovery. The approach leverages from exploring the structural space of THPs with Chemical Space Networks (CSNs) and from applying centrality measures to identify the most relevant and non-redundant THP sequences within the CSN. Such THPs were considered as queries (Qs) for multi-query similarity searches that apply a group fusion (MAX-SIM rule) model. The resulting multi-query similarity searching models (SSMs) were validated with three benchmarking datasets of THPs/non-THPs. The predictions achieved accuracies that ranged from 92.64 to 99.18% and Matthews Correlation Coefficients between 0.894–0.98, outperforming state-of-the-art predictors. The best model was applied to repurpose AMPs from the starPep database as THPs, which were subsequently optimized for the TH activity. Finally, 54 promising THP leads were discovered, and their sequences were analyzed to encounter novel motifs. These results demonstrate the potential of CSNs and multi-query similarity searching for the rapid and accurate identification of THPs. Full article

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

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3 pages, 182 KiB

Open AccessEditorial

Antibiotics and Antimicrobials Resistance: Mechanisms and New Strategies to Fight Resistant Bacteria

by Cécile Muller

Antibiotics 2022, 11(3), 400; https://doi.org/10.3390/antibiotics11030400 - 17 Mar 2022

Cited by 7 | Viewed by 2690

Abstract

Antibiotics have revolutionized medicine over the past century and have helped to control most infectious bacterial diseases [...] Full article

(This article belongs to the Special Issue Antibiotics and Antimicrobials Resistance: Mechanisms and New Strategies to Fight Resistant Bacteria)

13 pages, 301 KiB

Open AccessArticle

Effective Clinical Pathway Improves Interprofessional Collaboration and Reduces Antibiotics Prophylaxis Use in Orthopedic Surgery in Hospitals in Indonesia

by Fauna Herawati, Adinda Dessi Irawati, Ella Viani, Nully Andaretha Sugianto, Nur Laili Rahmatin, Made Prita Artika, Sukmawati Eka Bima Sahputri, Setiasih, Kevin Kantono, Rika Yulia, Retnosari Andrajati and Diantha Soemantri

Antibiotics 2022, 11(3), 399; https://doi.org/10.3390/antibiotics11030399 - 16 Mar 2022

Cited by 3 | Viewed by 3181

Abstract

Clinical pathways can improve the quality of health services. The effectiveness and impact of implementing clinical pathways are controversial. The preparation of clinical pathways not only enacts therapeutic guidelines but requires mutual agreement in accordance with the roles, duties, and contributions of each [...] Read more.

Clinical pathways can improve the quality of health services. The effectiveness and impact of implementing clinical pathways are controversial. The preparation of clinical pathways not only enacts therapeutic guidelines but requires mutual agreement in accordance with the roles, duties, and contributions of each profession in the team. This study aimed to investigate the perception of interprofessional collaboration practices and the impact of clinical pathway implementation on collaborative and Defined Daily Dose (DDD) prophylactic antibiotics per 100 bed-days in orthopedic surgery. The Collaborative Practice Assessment Tool (CPAT) questionnaire was used as a tool to measure healthcare’ perceptions of collaborative practice. The clinical pathway (CP) in this study was adapted from existing CPs published by the Indonesian Orthopaedic Association (Perhimpunan Dokter Spesialis Orthopaedi dan Traumatologi Indonesia, PABOI) and was commended by local domestic surgeons and orthopedic bodies. We then compared post-implementation results with pre-implementation clinical pathway data using ANCOVA to explore our categorical data and its influence towards CPAT response. ANOVA was then employed for aggregated DDD per 100 bed-days to compare pre and post intervention. The results showed that the relationships among members were associated with the working length. Six to ten years of working had a significantly better relationship among members than those who have worked one to five years. Interestingly, pharmacists’ leadership score was significantly lower than other professions. The clinical pathway implementation reduced barriers in team collaboration, improved team coordination and organization, and reduced third-generation cephalosporin use for prophylaxis in surgery (pre: 59 DDD per 100 bed-days; post: 28 DDD per 100 bed-days). This shows that the clinical pathway could benefit antibiotic stewardship in improving antibiotic prescription, therefore reducing the incidence of resistant bacteria. Full article

(This article belongs to the Special Issue Antibiotics Use and Stewardship in Hospitals and Outpatients Care Facilities)

10 pages, 264 KiB

Open AccessArticle

Increased Association of Pulmonary Thromboembolism and Tuberculosis during COVID-19 Pandemic: Data from an Italian Infectious Disease Referral Hospital

by Virginia Di Bari, Gina Gualano, Maria Musso, Raffaella Libertone, Carla Nisii, Stefania Ianniello, Silvia Mosti, Annelisa Mastrobattista, Carlotta Cerva, Nazario Bevilacqua, Fabio Iacomi, Annalisa Mondi, Simone Topino, Delia Goletti, Enrico Girardi, Fabrizio Palmieri and on behalf of the TB-INMI Working Group

Antibiotics 2022, 11(3), 398; https://doi.org/10.3390/antibiotics11030398 - 16 Mar 2022

Cited by 3 | Viewed by 2745

Abstract

Pulmonary thromboembolism (PTE) has been associated with tuberculosis (TB), but the true incidence is unknown. The aim of our study was to retrospectively evaluate the PTE prevalence in TB patients hospitalized at the National Institute for Infectious Diseases L. Spallanzani during the January [...] Read more.

Pulmonary thromboembolism (PTE) has been associated with tuberculosis (TB), but the true incidence is unknown. The aim of our study was to retrospectively evaluate the PTE prevalence in TB patients hospitalized at the National Institute for Infectious Diseases L. Spallanzani during the January 2016–December 2021 period. Retrospective data collection and evaluation were conducted. Among 1801 TB patients, 29 (1.61%) exhibited PTE. Twenty (69%) had comorbidities; eleven (37.9%) had predisposing factors for PTE. Nineteen (65.5%) had extensive TB disease. The commonest respiratory symptoms were cough (37.9%), dyspnea (31%), chest pain (10.3%), and hemoptysis (6.9%). Twenty-five (86.2%) had elevated serum D-dimer levels. An increased prevalence of PTE from 0.6% in the pre-COVID-19 pandemic period to 4.6% in the pandemic period was found. Acute respiratory failure and extensive TB disease increased significantly in the pandemic period. The increase in PTE could be explained by the increased severity of TB in patients in the pandemic period and by increased clinical suspicion and, consequently, increased requests for D-dimer testing, including in patients with non-COVID-19 pneumonia. Patients with extensive pulmonary disease are at high risk of developing PTE. Clinicians should be aware of this potentially life-threatening complication of TB, and patients should receive a thromboembolism risk assessment. Full article

(This article belongs to the Special Issue Antibiotics and Infectious Respiratory Diseases)

15 pages, 1223 KiB

Open AccessArticle

Prevalence and Characteristics of Streptococcus agalactiae from Freshwater Fish and Pork in Hong Kong Wet Markets

by Dulmini Nanayakkara Sapugahawatte, Carmen Li, Priyanga Dharmaratne, Chendi Zhu, Yun Kit Yeoh, Jun Yang, Norman Wai Sing Lo, Kam Tak Wong and Margaret Ip

Antibiotics 2022, 11(3), 397; https://doi.org/10.3390/antibiotics11030397 - 16 Mar 2022

Cited by 14 | Viewed by 3518

Abstract

We report the antimicrobial resistance of 191 fish and 61 pork Group B Streptococcus (GBS) procured from Hong Kong wet markets. Two-hundred-and-fifty-two GBS strains were isolated from 992 freshwater fish and 361 pig offal during 2016–2019. The strains were isolated from homogenised samples [...] Read more.

We report the antimicrobial resistance of 191 fish and 61 pork Group B Streptococcus (GBS) procured from Hong Kong wet markets. Two-hundred-and-fifty-two GBS strains were isolated from 992 freshwater fish and 361 pig offal during 2016–2019. The strains were isolated from homogenised samples and plated on selective media, followed by identification through MALDI-TOF-MS. Molecular characterisation, an antibiotic susceptibility test, and biofilm formation were performed on the strains. The isolation rates of the fish GBS and pig GBS were 19.3% (191 strains from 992 freshwater fish) and 16.9% (61 strains from 361 pig organs), respectively. The fish GBS was predominantly serotype Ia, ST7, while pig GBS was serotype III, ST651 (45 strains). An antibiotic susceptibility test revealed that the fish GBS were mostly antibiotic-sensitive, while the pig GBS were multidrug-resistant. A biofilm formation experiment showed that over 71% of fish GBS and all pig GBS had moderate biofilm formation ability. In general, the prevalence rate of GBS in animals and the multidrug resistance phenotype presented in the strains raise concerns about its zoonotic potential and effects on public health. Full article

(This article belongs to the Special Issue Antibiotic Resistance and Infectious Diseases: A One Health Perspective)

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10 pages, 2321 KiB

Open AccessArticle

Studies on the Reactions of Biapenem with VIM Metallo β-Lactamases and the Serine β-Lactamase KPC-2

by Anka Lucic, Tika R. Malla, Karina Calvopiña, Catherine L. Tooke, Jürgen Brem, Michael A. McDonough, James Spencer and Christopher J. Schofield

Antibiotics 2022, 11(3), 396; https://doi.org/10.3390/antibiotics11030396 - 16 Mar 2022

Cited by 8 | Viewed by 2851

Abstract

Carbapenems are important antibacterials and are both substrates and inhibitors of some β-lactamases. We report studies on the reaction of the unusual carbapenem biapenem, with the subclass B1 metallo-β-lactamases VIM-1 and VIM-2 and the class A serine-β-lactamase KPC-2. X-ray diffraction studies with VIM-2 [...] Read more.

Carbapenems are important antibacterials and are both substrates and inhibitors of some β-lactamases. We report studies on the reaction of the unusual carbapenem biapenem, with the subclass B1 metallo-β-lactamases VIM-1 and VIM-2 and the class A serine-β-lactamase KPC-2. X-ray diffraction studies with VIM-2 crystals treated with biapenem reveal the opening of the β-lactam ring to form a mixture of the (2S)-imine and enamine complexed at the active site. NMR studies on the reactions of biapenem with VIM-1, VIM-2, and KPC-2 reveal the formation of hydrolysed enamine and (2R)- and (2S)-imine products. The combined results support the proposal that SBL/MBL-mediated carbapenem hydrolysis results in a mixture of tautomerizing enamine and (2R)- and (2S)-imine products, with the thermodynamically favoured (2S)-imine being the major observed species over a relatively long-time scale. The results suggest that prolonging the lifetimes of β-lactamase carbapenem complexes by optimising tautomerisation of the nascently formed enamine to the (2R)-imine and likely more stable (2S)-imine tautomer is of interest in developing improved carbapenems. Full article

(This article belongs to the Special Issue Targeting β-Lactamases to Fight Antimicrobial Resistance)

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11 pages, 1704 KiB

Open AccessArticle

The Effect of Tannin-Rich Witch Hazel on Growth of Probiotic Lactobacillus plantarum

by Reuven Rasooly, Alex C. Howard, Naomi Balaban, Bradley Hernlem and Emmanouil Apostolidis

Antibiotics 2022, 11(3), 395; https://doi.org/10.3390/antibiotics11030395 - 16 Mar 2022

Cited by 1 | Viewed by 3207

Abstract

Probiotic bacteria help maintain microbiome homeostasis and promote gut health. Maintaining the competitive advantage of the probiotics over pathogenic bacteria is a challenge, as they are part of the gut microbiome that is continuously exposed to digestive and nutritional changes and various stressors. [...] Read more.

Probiotic bacteria help maintain microbiome homeostasis and promote gut health. Maintaining the competitive advantage of the probiotics over pathogenic bacteria is a challenge, as they are part of the gut microbiome that is continuously exposed to digestive and nutritional changes and various stressors. Witch hazel that is rich in hamamelitannin (WH, whISOBAX^TM) is an inhibitor of growth and virulence of pathogenic bacteria. To test for its effect on probiotic bacteria, WH was tested on the growth and biofilm formation of a commercially available probiotic Lactobacillus plantarum PS128. As these bacteria are aerotolerant, the experiments were carried out aerobically and in nutritionally inadequate/poor (nutrient broth) or adequate/rich (MRS broth) conditions. Interestingly, despite its negative effect on the growth and biofilm formation of pathogenic bacteria such as Staphylococcus epidermidis, WH promotes the growth of the probiotic bacteria in a nutritionally inadequate environment while maintaining their growth under a nutritionally rich environment. In the absence of WH, no significant biofilm is formed on the surfaces tested (polystyrene and alginate), but in the presence of WH, biofilm formation was significantly enhanced. These results indicate that WH may thus be used to enhance the growth and survival of probiotics. Full article

(This article belongs to the Special Issue 10th Anniversary of Antibiotics - Recent Advances in Novel Antimicrobial Agents)

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12 pages, 1749 KiB

Open AccessArticle

Comparative Study on Synergistic Toxicity of Enrofloxacin Combined with Three Antibiotics on Proliferation of THLE-2 Cell

by Yehui Luan, Kexin Chen, Junjie Zhao and Linli Cheng

Antibiotics 2022, 11(3), 394; https://doi.org/10.3390/antibiotics11030394 - 16 Mar 2022

Cited by 9 | Viewed by 3150

Abstract

Little attention has been paid to the problem of the combined toxicity of accumulated antibiotics on humans from food and clinical treatments. Therefore, we used human hepatocytes to study the joint toxicity of four common antibiotics. The cytotoxicity of enrofloxacin (ENR), combined with [...] Read more.

Little attention has been paid to the problem of the combined toxicity of accumulated antibiotics on humans from food and clinical treatments. Therefore, we used human hepatocytes to study the joint toxicity of four common antibiotics. The cytotoxicity of enrofloxacin (ENR), combined with ciprofloxacin (CFX), florfenicol (FFC), or sulfadimidine (SMD) on THLE-2 cells was determined by CCK-8 assays; then their joint toxicity was evaluated using CalcuSyn 2.0. Dose–effect curves and median-effect plots established on large amounts of data and CI values were calculated to judge the nature of the combination’s interaction. ED50, ED75, and ED90 were predicted to elucidate the changing trend of the concentration on the toxicity of each drug pair. The ENR-CFX and ENR-FFC pairs exhibited synergistic toxicity only at special concentration rates, while ENR and SMD synergistically induced cytotoxicity at almost all the concentration rates studied. The mixed ratio was a significant factor for synergistic toxicity and should be evaluated in all combined effect studies. These results suggested that the combined toxicity of these four drugs should be taken into account in their risk assessment. Full article

(This article belongs to the Section Antibiotics in Animal Health)

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14 pages, 1731 KiB

Open AccessArticle

Ability of Essential Oil Vapours to Reduce Numbers of Culturable Aerosolised Coronavirus, Bacteria and Fungi

by Parthasarathi Kalaiselvan, Muhammad Yasir, Rajesh Kuppusamy, Mark Willcox and Ajay Kumar Vijay

Antibiotics 2022, 11(3), 393; https://doi.org/10.3390/antibiotics11030393 - 15 Mar 2022

Cited by 8 | Viewed by 4933

Abstract

Transmission of pathogens present in the indoor air can occur through aerosols. This study evaluated the efficacy of an evaporated mix of essential oils to reduce the numbers of culturable aerosolized coronavirus, bacterium and fungus. The essential oil-containing gel was allowed to vaporize [...] Read more.

Transmission of pathogens present in the indoor air can occur through aerosols. This study evaluated the efficacy of an evaporated mix of essential oils to reduce the numbers of culturable aerosolized coronavirus, bacterium and fungus. The essential oil-containing gel was allowed to vaporize inside a glass chamber for 10 or 20 min. Aerosols of a surrogate of SARS-CoV-2, murine hepatitis coronavirus MHV-1, Escherichia coli or Aspergillus flavus spores were produced using a collision nebuliser and passed through the essential oil vapours, then collected on a six-stage Andersen sampler. The six-stages of the impact sampler capture aerosols in sizes ranging from 7 to 0.65 µm. The number of culturable microbes present in the aerosols collected in the different stages were enumerated and compared to the number of culturable microbes in control microbial aerosols that were not exposed to the evaporated essential oils. After 10 and 20 min evaporation, the essential oils reduced the numbers of culturable aerosolized coronavirus by 48% (log₁₀ reduction = 0.3; p = 0.002 vs. control) and 53% (log₁₀ reduction = 0.3; p = 0.001 vs. control), respectively. The essential oils vaporised for 10 min, reduced the number of viable E. coli by 51% (log₁₀ reduction = 0.3; p = 0.032 vs. control). The Aspergillus flavus spores were mostly observed in the larger aerosols (7.00 µm to 2.10 µm) and the essential oils vaporised for 10 min reduced the number of viable spores by 72% (log₁₀ reduction = 0.6; p = 0.008 vs. control). The vapours produced by a gel containing naturally occurring essential oils were able to significantly reduce the viable numbers of aerosolized coronavirus, bacteria and fungal spores. The antimicrobial gel containing the essential oils may be able to reduce aerosol transmission of microbes when used in domestic and workplace settings. Full article

(This article belongs to the Special Issue Antimicrobial Activity of Essential Oils)

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Antibiotics, Volume 11, Issue 3 (March 2022) – 138 articles

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