Antibiotics

14 pages, 1828 KiB

Open AccessArticle

Prevalence and Antimicrobial Resistance Profile of Diarrheagenic Escherichia coli from Fomites in Rural Households in South Africa

by Phathutshedzo Rakhalaru, Lutendo Munzhedzi, Akebe Luther King Abia, Jean Pierre Kabue, Natasha Potgieter and Afsatou Ndama Traore

Antibiotics 2023, 12(8), 1345; https://doi.org/10.3390/antibiotics12081345 - 21 Aug 2023

Cited by 3 | Viewed by 2154

Abstract

Diarrheagenic Escherichia coli (DEC) pathotypes are the leading cause of mortality and morbidity in South Asia and sub-Saharan Africa. Daily interaction between people contributes to the spreading of Escherichia coli (E. coli), and fomites are a common source of community-acquired bacterial [...] Read more.

Diarrheagenic Escherichia coli (DEC) pathotypes are the leading cause of mortality and morbidity in South Asia and sub-Saharan Africa. Daily interaction between people contributes to the spreading of Escherichia coli (E. coli), and fomites are a common source of community-acquired bacterial infections. The spread of bacterial infectious diseases from inanimate objects to the surrounding environment and humans is a serious problem for public health, safety, and development. This study aimed to determine the prevalence and antibiotic resistance of diarrheagenic E. coli found in toilets and kitchen cloths in the Vhembe district, South Africa. One hundred and five samples were cultured to isolate E. coli: thirty-five samples were kitchen cloths and seventy-five samples were toilet swabs. Biochemical tests, API20E, and the VITEK^®-2 automated system were used to identify E. coli. Pathotypes of E. coli were characterised using Multiplex Polymerase Chain Reaction (mPCR). Nine amplified gene fragments were sequenced using partial sequencing. A total of eight antibiotics were used for the antibiotic susceptibility testing of E. coli isolates using the Kirby–Bauer disc diffusion method. Among the collected samples, 47% were positive for E. coli. DEC prevalence was high (81%), with ETEC (51%) harboring lt and st genes being the most dominant pathotype found on both kitchen cloths and toilet surfaces. Diarrheagenic E. coli pathotypes were more prevalent in the kitchen cloths (79.6%) compared with the toilet surfaces. Notably, hybrid pathotypes were detected in 44.2% of the isolates, showcasing the co-existence of multiple pathotypes within a single E. coli strain. The antibiotic resistance testing of E. coli isolates from kitchen cloths and toilets showed high resistance to ampicillin (100%) and amoxicillin (100%). Only E. coli isolates with hybrid pathotypes were found to be resistant to more than three antibiotics. This study emphasizes the significance of fomites as potential sources of bacterial contamination in rural settings. The results highlight the importance of implementing proactive measures to improve hygiene practices and antibiotic stewardship in these communities. These measures are essential for reducing the impact of DEC infections and antibiotic resistance, ultimately safeguarding public health. Full article

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

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20 pages, 2406 KiB

Open AccessArticle

Rationally Designed Pyrimidine Compounds: Promising Novel Antibiotics for the Treatment of Staphylococcus aureus-Associated Bovine Mastitis

by Guillaume Millette, Evelyne Lacasse, Renaud Binette, Véronique Belley, Louis-Philippe Chaumont, Céline Ster, Francis Beaudry, Kumaraswamy Boyapelly, Pierre-Luc Boudreault and François Malouin

Antibiotics 2023, 12(8), 1344; https://doi.org/10.3390/antibiotics12081344 - 21 Aug 2023

Cited by 2 | Viewed by 1600

Abstract

Staphylococcus aureus is one of the major pathogens causing bovine mastitis, and antibiotic treatment is most often inefficient due to its virulence and antibiotic-resistance attributes. The development of new antibiotics for veterinary use should account for the One Health concept, in which humans, [...] Read more.

Staphylococcus aureus is one of the major pathogens causing bovine mastitis, and antibiotic treatment is most often inefficient due to its virulence and antibiotic-resistance attributes. The development of new antibiotics for veterinary use should account for the One Health concept, in which humans, animals, and environmental wellbeing are all interconnected. S. aureus can infect cattle and humans alike and antibiotic resistance can impact both if the same classes of antibiotics are used. New effective antibiotic classes against S. aureus are thus needed in dairy farms. We previously described PC1 as a novel antibiotic, which binds the S. aureus guanine riboswitch and interrupts transcription of essential GMP synthesis genes. However, chemical instability of PC1 hindered its development, evaluation, and commercialization. Novel PC1 analogs with improved stability have now been rationally designed and synthesized, and their in vitro and in vivo activities have been evaluated. One of these novel compounds, PC206, remains stable in solution and demonstrates specific narrow-spectrum activity against S. aureus. It is active against biofilm-embedded S. aureus, its cytotoxicity profile is adequate, and in vivo tests in mice and cows show that it is effective and well tolerated. PC206 and structural analogs represent a promising new antibiotic class to treat S. aureus-induced bovine mastitis. Full article

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

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Graphical abstract

15 pages, 674 KiB

Open AccessArticle

Hospital Pharmacists’ Viewpoint on Quality Use of Antibiotics and Resistance: A Qualitative Exploration from a Tertiary Care Hospital of Quetta City, Pakistan

by Maryam Farooqui, Zaffar Iqbal, Abdul Sadiq, Abdul Raziq, Mohammed Salem Alshammari, Qaiser Iqbal, Sajjad Haider and Fahad Saleem

Antibiotics 2023, 12(8), 1343; https://doi.org/10.3390/antibiotics12081343 - 21 Aug 2023

Cited by 2 | Viewed by 1608

Abstract

Suboptimal antibiotics use and the development of antibiotic resistance is a universal calamity. The theoretical model of therapeutic efficacy correlates quality use of antibiotics with healthcare practitioners’ understanding of antibiotic use and resistance. Keeping this phenomenon in mind, we aimed to evaluate hospital [...] Read more.

Suboptimal antibiotics use and the development of antibiotic resistance is a universal calamity. The theoretical model of therapeutic efficacy correlates quality use of antibiotics with healthcare practitioners’ understanding of antibiotic use and resistance. Keeping this phenomenon in mind, we aimed to evaluate hospital pharmacists’ understanding of antibiotic use and resistance at a public healthcare institute in Quetta city, Pakistan. This was a qualitative study that employed a semi-structured interview guide for data extraction. The phenomenology-based approach commissioned in-depth, face-to-face interviews with hospital pharmacists stationed at the surgical unit of Sandeman Provincial Hospital, Quetta. The interviews were audio taped followed by transcribed verbatim and were then analyzed for thematic contents by the standard content analysis framework. Although the saturation was reached after the 10th interview, we conducted two additional interviews for definite validation. Content analysis revealed five major themes: (1) Defining antibiotics, quality use of antibiotics and resistance, (2) antibiotic use: awareness and concern, (3) antimicrobial resistance: awareness and concern, (4) responding to antibiotic use and resistance, and (5) barriers to quality use of antibiotics and prevention of antibiotic resistance. The knowledge of quality use of antibiotics and resistance was promising, and the respondents were eager to address the drastic situation. The respondents were aware of the critical situation and provided valuable insights that can offer valued input while promoting the quality use of antibiotics in a developing country. The current study managed to identify an adequate understanding of antibiotic use and resistance among hospital pharmacists. Additionally, prospective concerns and possible predictors of antibiotic resistance were also highlighted. The current findings must be disseminated to the policymakers and prescribers to take prompt restorative actions to address antibiotic use and the development of antibiotic resistance in a developing country like Pakistan. Full article

(This article belongs to the Special Issue Antimicrobial Prescribing, Population Use and Resistance, Impact in Global Health)

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13 pages, 749 KiB

Open AccessReview

Antimicrobial Stewardship Programs in Latin America and the Caribbean: A Story of Perseverance, Challenges, and Goals

by Natalia Restrepo-Arbeláez, Juan Carlos Garcia-Betancur, Christian Jose Pallares and María Virginia Villegas

Antibiotics 2023, 12(8), 1342; https://doi.org/10.3390/antibiotics12081342 - 21 Aug 2023

Cited by 6 | Viewed by 2124

Abstract

Antimicrobial resistance is one of the major global health threats. Antimicrobial stewardship (AMS) has been set as a priority within international action plans to combat this issue. The region of Latin America and the Caribbean are recognized for their high antimicrobial resistance rates; [...] Read more.

Antimicrobial resistance is one of the major global health threats. Antimicrobial stewardship (AMS) has been set as a priority within international action plans to combat this issue. The region of Latin America and the Caribbean are recognized for their high antimicrobial resistance rates; nevertheless, a low number of studies describing implemented interventions for this topic have been published. This review aims to provide an overview of the status of AMS in our region, focusing on the main progress achieved and describing the different published efforts made by countries towards the implementation of antimicrobial stewardship programs (ASP). Common areas of intervention included were (a) education approaches, (b) antimicrobial guideline implementation and monitoring, (c) diagnostic stewardship, (d) technological tools: electronic clinical decision support systems in AMS, (e) pharmacy-driven protocols and collaborative practice agreements, and (f) economic impact. The search demonstrated the varied interventions implemented in diverse healthcare settings; the results accentuate their influence on antimicrobial consumption, antimicrobial resistance, clinical outcomes, and direct economic impact. The integration of multiple strategies within each hospital was highlighted as an essential key to ASP success. Even though the literature found demonstrated clear progress, there is still a special need for strengthening leadership from the top down, defining goals based on needs, and gaining support through policy and financing in LAC. Full article

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

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17 pages, 3978 KiB

Open AccessArticle

Molecular Cloning, Expression Analyses, and Physiological Roles of Cathelicidins in the Bursa of Fabricius of the Japanese Quail, Coturnix japonica

by Takumi Ikeda, Hirotada Kondo, Daiki Nunomura, Genki Sato, Machi Ito, Nanako Yamanaka, Shawichi Iwamuro, Itaru Hasunuma, Sakae Kikuyama and Tetsuya Kobayashi

Antibiotics 2023, 12(8), 1341; https://doi.org/10.3390/antibiotics12081341 - 19 Aug 2023

Viewed by 1282

Abstract

Antimicrobial peptides (AMPs) act directly on pathogens and maintain the anti-inflammatory effects and activation of immunocompetent cells. Therefore, the activation of the immune system in poultry via the elevation of endogenous AMPs has been attempted. In this study, we focused on the host [...] Read more.

Antimicrobial peptides (AMPs) act directly on pathogens and maintain the anti-inflammatory effects and activation of immunocompetent cells. Therefore, the activation of the immune system in poultry via the elevation of endogenous AMPs has been attempted. In this study, we focused on the host defense mechanisms in the bursa of Fabricius (BF) of Japanese quail, cloned the cDNA of cathelicidin (CATH)-1 to -3, and analyzed their expression sites. In situ hybridization experiments revealed the mRNA expression of the CATHs in the interfollicular epithelium surrounding the lumen of the quail BF, which suggests that each CATH may exert its antimicrobial action directly in the BF. The intravenous injection of bacterial lipoteichoic acid and lipopolysaccharide endotoxins into the quail promoted the mRNA expression of CATH-1 and CATH-3 in the BF. The addition of CATH-1 or CATH-2 at the time of the antigen injection into mice resulted in antiserum with high antibody titers. Ad libitum administration of butyrate, a short-chain fatty acid, in the drinking water induced an increase in CATH-2 mRNA expression in the BF under certain conditions. These results may improve the defense mechanisms of quail by stimulating CATH expression in the BF through their diet. Full article

(This article belongs to the Special Issue Alternatives to Antibiotics: Bacteriocins and Antimicrobial Peptides, 2nd Edition)

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27 pages, 6835 KiB

Open AccessReview

Sensing of Antibiotic–Bacteria Interactions

by Anna A. Baranova, Anton P. Tyurin, Vladimir A. Korshun and Vera A. Alferova

Antibiotics 2023, 12(8), 1340; https://doi.org/10.3390/antibiotics12081340 - 19 Aug 2023

Cited by 3 | Viewed by 2646

Abstract

Sensing of antibiotic–bacteria interactions is an important area of research that has gained significant attention in recent years. Antibiotic resistance is a major public health concern, and it is essential to develop new strategies for detecting and monitoring bacterial responses to antibiotics in [...] Read more.

Sensing of antibiotic–bacteria interactions is an important area of research that has gained significant attention in recent years. Antibiotic resistance is a major public health concern, and it is essential to develop new strategies for detecting and monitoring bacterial responses to antibiotics in order to maintain effective antibiotic development and antibacterial treatment. This review summarizes recent advances in sensing strategies for antibiotic–bacteria interactions, which are divided into two main parts: studies on the mechanism of action for sensitive bacteria and interrogation of the defense mechanisms for resistant ones. In conclusion, this review provides an overview of the present research landscape concerning antibiotic–bacteria interactions, emphasizing the potential for method adaptation and the integration of machine learning techniques in data analysis, which could potentially lead to a transformative impact on mechanistic studies within the field. Full article

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9 pages, 242 KiB

Open AccessArticle

Antimicrobial Resistance of Erysipelothrix rhusiopathiae Strains Isolated from Geese to Antimicrobials Widely Used in Veterinary Medicine

by Kamila Bobrek and Andrzej Gaweł

Antibiotics 2023, 12(8), 1339; https://doi.org/10.3390/antibiotics12081339 - 19 Aug 2023

Cited by 2 | Viewed by 1687

Abstract

The aim of this study was to determine the antibiotic resistance of E. rhusiopathiae when isolated from clinical outbreaks of erysipelas in geese to antimicrobials commonly used in poultry production. All isolates were susceptible to amoxicillin alone or with clavulanic acid, with MIC [...] Read more.

The aim of this study was to determine the antibiotic resistance of E. rhusiopathiae when isolated from clinical outbreaks of erysipelas in geese to antimicrobials commonly used in poultry production. All isolates were susceptible to amoxicillin alone or with clavulanic acid, with MIC values ranging from 0.016 to 0.125 μg/mL. Ninety-six percent of isolates were fully sensitive to penicillin G (MIC 0.125–0.5 μg/mL). All isolates were fully or moderately sensitive to erythromycin (MIC 0.125–0.5 μg/mL). Most E. rhusiopathiae isolates proved resistant to fluoroquinolones (76.6% of isolates were resistant to enrofloxacin, with MIC values ranging from 0.064 to 32 μg/mL, and 68% were resistant to norfloxacin, with MIC values ranging from 0.094 to 96 μg/mL), and tetracyclines (61.7% of isolates were resistant to doxycycline, with MIC values ranging from 0.25 to 64 μg/mL, and 63.8% were resistant to tetracycline, with MIC values ranging from 0.38 to 256 μg/mL). Point mutations in the gyrA gene (responsible for fluoroquinolone resistance) and the presence of the tetM gene (responsible for tetracycline resistance) were noted in most of the resistant isolates. Multidrug resistance, defined as resistance to at least one substance in three or more antimicrobial classes, was not observed. Full article

23 pages, 951 KiB

Open AccessSystematic Review

Physicochemical Characteristics of Antimicrobials and Practical Recommendations for Intravenous Administration: A Systematic Review

by Fabio Borgonovo, Massimiliano Quici, Antonio Gidaro, Davide Giustivi, Dario Cattaneo, Cristina Gervasoni, Maria Calloni, Elena Martini, Leyla La Cava, Spinello Antinori, Chiara Cogliati, Andrea Gori and Antonella Foschi

Antibiotics 2023, 12(8), 1338; https://doi.org/10.3390/antibiotics12081338 - 19 Aug 2023

Cited by 6 | Viewed by 3283

Abstract

Most antimicrobial drugs need an intravenous (IV) administration to achieve maximum efficacy against target pathogens. IV administration is related to complications, such as tissue infiltration and thrombo-phlebitis. This systematic review aims to provide practical recommendations about diluent, pH, osmolarity, dosage, infusion rate, vesicant [...] Read more.

Most antimicrobial drugs need an intravenous (IV) administration to achieve maximum efficacy against target pathogens. IV administration is related to complications, such as tissue infiltration and thrombo-phlebitis. This systematic review aims to provide practical recommendations about diluent, pH, osmolarity, dosage, infusion rate, vesicant properties, and phlebitis rate of the most commonly used antimicrobial drugs evaluated in randomized controlled studies (RCT) till 31 March 2023. The authors searched for available IV antimicrobial drugs in RCT in PUBMED EMBASE^®, EBSCO^® CINAHL^®, and the Cochrane Controlled Clinical trials. Drugs’ chemical features were searched online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, osmolarity >600 mOsm/L, high incidence of phlebitis reported in the literature, and vesicant drugs need the adoption of utmost caution during administration. We evaluated 931 papers; 232 studies were included. A total of 82 antimicrobials were identified. Regarding antibiotics, 37 reach the “caution” criterion, as well as seven antivirals, 10 antifungals, and three antiprotozoals. In this subgroup of antimicrobials, the correct vascular access device (VAD) selection is essential to avoid complications due to the administration through a peripheral vein. Knowing the physicochemical characteristics of antimicrobials is crucial to improve the patient’s safety significantly, thus avoiding administration errors and local side effects. Full article

(This article belongs to the Collection Antimicrobial Prescribing and Antimicrobial Use in Healthcare Settings)

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17 pages, 1636 KiB

Open AccessArticle

Ceftobiprole Medocaril Is an Effective Post-Exposure Treatment in the Fischer 344 Rat Model of Pneumonic Tularemia

by Mark M. Hahn, Cheryl A. Triplett, Michael S. Anderson, Jennifer I. Smart, Karine Litherland, Stephen Keech, Franziska von Siebenthal, Mark Jones, Andrew J. Phipps and Lisa N. Henning

Antibiotics 2023, 12(8), 1337; https://doi.org/10.3390/antibiotics12081337 - 19 Aug 2023

Cited by 1 | Viewed by 1525

Abstract

Francisella tularensis subspecies tularensis is a category-A biothreat agent that can cause lethal tularemia. Ceftobiprole medocaril is being explored as a medical countermeasure for the treatment of pneumonic tularemia. The efficacy of ceftobiprole medocaril against inhalational tularemia was evaluated in the Fischer 344 [...] Read more.

Francisella tularensis subspecies tularensis is a category-A biothreat agent that can cause lethal tularemia. Ceftobiprole medocaril is being explored as a medical countermeasure for the treatment of pneumonic tularemia. The efficacy of ceftobiprole medocaril against inhalational tularemia was evaluated in the Fischer 344 rat model of infection. The dose was expected to be effective against F. tularensis isolates with ceftobiprole minimum inhibitory concentrations ≤0.5 µg/mL. Animals treated with ceftobiprole medocaril exhibited a 92% survival rate 31 days post-challenge, identical to the survival of levofloxacin-treated rats. By comparison, rats receiving placebo experienced 100% mortality. Terminally collected blood, liver, lung, and spleen samples confirmed disseminated F. tularensis infections in most animals that died prior to completing treatments (placebo animals and a rat treated with ceftobiprole medocaril), although levels of bacteria detected in the placebo samples were significantly elevated compared to the ceftobiprole-medocaril-treated group geometric mean. Furthermore, no evidence of infection was detected in any rat that completed ceftobiprole medocaril or levofloxacin treatment and survived to the end of the post-treatment observation period. Overall, survival rates, body weights, and bacterial burdens consistently demonstrated that treatment with ceftobiprole medocaril is efficacious against otherwise fatal cases of pneumonic tularemia in the rat model. Full article

(This article belongs to the Special Issue Animal Models of Biodefence Pathogens: Exploring Treatment)

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15 pages, 1873 KiB

Open AccessArticle

A Study on the Epidemiological-Molecular Role of Staphylococcus aureus Strains in the Development of Ventilator-Associated Pneumonia in a Tertiary Hospital in Brazil

by Mariana Fávero Bonesso, Carlos Magno Castelo Branco Fortaleza, Ricardo de Souza Cavalcante, Moises Teixeira Sobrinho, Carlos Fernando Ronchi, Lígia Maria Abraão, Hwang-Soo Joo, Michael Otto and Maria de Lourdes Ribeiro de Souza da Cunha

Antibiotics 2023, 12(8), 1336; https://doi.org/10.3390/antibiotics12081336 - 18 Aug 2023

Viewed by 1511

Abstract

This study aimed to explore the molecular epidemiology of Staphylococcus aureus isolated from patients on mechanical ventilation and the participation of virulence factors in the development of ventilator-associated pneumonia (VAP). A prospective cohort study was conducted on patients under mechanical ventilation, with periodic [...] Read more.

This study aimed to explore the molecular epidemiology of Staphylococcus aureus isolated from patients on mechanical ventilation and the participation of virulence factors in the development of ventilator-associated pneumonia (VAP). A prospective cohort study was conducted on patients under mechanical ventilation, with periodic visits for the collection of tracheal aspirates and clinical data. The S. aureus isolates were analyzed regarding resistance profile, virulence, expression of protein A and alpha-toxin using Western blot, clonal profile using PFGE, sequence type using MLST, and characterization and quantification of phenol-soluble modulins. Among the 270 patients in the study, 51 S. aureus strains were isolated from 47 patients. The incidence density of S. aureus and MRSA VAP was 2.35/1000 and 1.96/1000 ventilator days, respectively; of these, 45% (n = 5) were resistant to oxacillin, with 100% (n = 5) harboring SCCmec types II and IV. The most frequent among the tested virulence factors were icaA, hla, and hld. The clonal profile showed a predominance of sequence types originating from the community. Risk factors for VAP were the presence of solid tumors and the sea gene. In conclusion, patient-related risk factors, together with microbiological factors, are involved in the development of S. aureus VAP, which is caused by the patient’s own strains. Full article

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11 pages, 2454 KiB

Open AccessArticle

Ciprofloxacin and Tetracycline Resistance Cause Collateral Sensitivity to Aminoglycosides in Salmonella Typhimurium

by Mahadi Hasan, Jun Wang and Juhee Ahn

Antibiotics 2023, 12(8), 1335; https://doi.org/10.3390/antibiotics12081335 - 18 Aug 2023

Cited by 6 | Viewed by 2265

Abstract

The objective of this study was to evaluate collateral sensitivity and cross-resistance of antibiotic-induced resistant Salmonella Typhimurium to various antibiotics. S. Typhimurium ATCC 19585 (ST^WT) was exposed to ciprofloxacin, gentamicin, kanamycin, and tetracycline to induce antibiotic resistance, respectively, assigned as [...] Read more.

The objective of this study was to evaluate collateral sensitivity and cross-resistance of antibiotic-induced resistant Salmonella Typhimurium to various antibiotics. S. Typhimurium ATCC 19585 (ST^WT) was exposed to ciprofloxacin, gentamicin, kanamycin, and tetracycline to induce antibiotic resistance, respectively, assigned as ST^CIP, ST^GEN, ST^KAN, and ST^TET. The susceptibilities of the antibiotic-induced resistant mutants to cefotaxime, chloramphenicol, ciprofloxacin, gentamicin, kanamycin, polymyxin B, streptomycin, tetracycline, and tobramycin were determined in the absence and presence of CCCP and PAβN. ST^CIP showed the cross-resistance to tetracycline and collateral sensitivity to gentamicin (1/2 fold) and kanamycin (1/4 fold). ST^TET was also cross-resistant to ciprofloxacin (128-fold) and collateral sensitive to gentamicin (1/4-fold) and kanamycin (1/8-fold). The cross-resistance and collateral sensitivity of ST^CIP and ST^TET were associated with the AcrAB-TolC efflux pump and outer membrane porin proteins (OmpC). This study provides new insight into the collateral sensitivity phenomenon, which can be used for designing effective antibiotic treatment regimens to control antibiotic-resistant bacteria. Full article

(This article belongs to the Section Mechanisms and Structural Biology of Antibiotic Action)

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17 pages, 1188 KiB

Open AccessReview

Managing Corneal Infections: Out with the old, in with the new?

by Sanjay Marasini, Jennifer P. Craig, Simon J. Dean and Leon G. Leanse

Antibiotics 2023, 12(8), 1334; https://doi.org/10.3390/antibiotics12081334 - 18 Aug 2023

Cited by 4 | Viewed by 2443

Abstract

There have been multiple reports of eye infections caused by antibiotic-resistant bacteria, with increasing evidence of ineffective treatment outcomes from existing therapies. With respect to corneal infections, the most commonly used antibiotics (fluoroquinolones, aminoglycosides, and cephalosporines) are demonstrating reduced efficacy against bacterial keratitis [...] Read more.

There have been multiple reports of eye infections caused by antibiotic-resistant bacteria, with increasing evidence of ineffective treatment outcomes from existing therapies. With respect to corneal infections, the most commonly used antibiotics (fluoroquinolones, aminoglycosides, and cephalosporines) are demonstrating reduced efficacy against bacterial keratitis isolates. While traditional methods are losing efficacy, several novel technologies are under investigation, including light-based anti-infective technology with or without chemical substrates, phage therapy, and probiotics. Many of these methods show non-selective antimicrobial activity with potential development as broad-spectrum antimicrobial agents. Multiple preclinical studies and a limited number of clinical case studies have confirmed the efficacy of some of these novel methods. However, given the rapid evolution of corneal infections, their treatment requires rapid institution to limit the impact on vision and prevent complications such as scarring and corneal perforation. Given their rapid effects on microbial viability, light-based technologies seem particularly promising in this regard. Full article

(This article belongs to the Collection Antibiotics in Ophthalmology Practice)

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14 pages, 2382 KiB

Open AccessFeature PaperArticle

Antimicrobial Effect of Low-Fluoride Toothpastes Containing Polyphosphate and Polyols: An In Vitro Assessment of Inhibition Zones

by Igor Zen, Alberto Carlos Botazzo Delbem, Thayse Yumi Hosida, Caio Sampaio, Leonardo Antônio de Morais, Tamires Passadori Martins, Douglas Roberto Monteiro and Juliano Pelim Pessan

Antibiotics 2023, 12(8), 1333; https://doi.org/10.3390/antibiotics12081333 - 18 Aug 2023

Cited by 4 | Viewed by 1736

Abstract

This study evaluated the antimicrobial effect of toothpastes containing 200 ppm fluoride (200F), xylitol (X, 16%), erythritol (E, 4%), and sodium trimetaphosphate (TMP, 0.25%), alone or in different associations, against Streptococcus mutans (SM), Lactobacillus casei (LC), Actinomyces israelii (AI), and Candida albicans (CA). [...] Read more.

This study evaluated the antimicrobial effect of toothpastes containing 200 ppm fluoride (200F), xylitol (X, 16%), erythritol (E, 4%), and sodium trimetaphosphate (TMP, 0.25%), alone or in different associations, against Streptococcus mutans (SM), Lactobacillus casei (LC), Actinomyces israelii (AI), and Candida albicans (CA). Suspensions of the micro-organisms were added to a BHI Agar medium. Five wells were made on each plate to receive toothpaste suspensions at different dilutions. Toothpastes containing no actives (placebo) or 1100 ppm F (1100F) were used as negative and positive controls. Two-way ANOVA and Tukey’s HDS test were used (p < 0.05). For SM, the largest halo was for 200F+TMP at all dilutions, followed by the 200F+X+E toothpaste (p < 0.001). For LC, the overall trend showed that the polyols effectively inhibited microbial growth, and the association with the other compounds enhanced such effects (p < 0.001). For AI, a less-defined trend was observed. For CA, the experimental toothpaste (200F+X+E+TMP) was consistently more effective than the other treatments, followed by 200F+X+E (p < 0.001). The association of polyols and TMP in a low-fluoride toothpaste effectively reduced the growth of cariogenic micro-organisms (SM, CA, and LC), suggesting that this formulation could be an interesting alternative for children due to its low fluoride content. Full article

(This article belongs to the Special Issue Synthesis and Biological Activity of Antimicrobial Agents, 2nd Volume)

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17 pages, 1639 KiB

Open AccessArticle

Exploring the Multifaceted Potential of a Peptide Fraction Derived from Saccharomyces cerevisiae Metabolism: Antimicrobial, Antioxidant, Antidiabetic, and Anti-Inflammatory Properties

by Patrícia Branco, Elisabete Muchagato Maurício, Ana Costa, Diogo Ventura, Catarina Roma-Rodrigues, Maria Paula Duarte, Alexandra R. Fernandes and Catarina Prista

Antibiotics 2023, 12(8), 1332; https://doi.org/10.3390/antibiotics12081332 - 18 Aug 2023

Cited by 9 | Viewed by 2169

Abstract

The rising demand for minimally processed, natural, and healthier food products has led to the search for alternative and multifunctional bioactive food components. Therefore, the present study focuses on the functional proprieties of a peptide fraction derived from Saccharomyces cerevisiae metabolism. The antimicrobial [...] Read more.

The rising demand for minimally processed, natural, and healthier food products has led to the search for alternative and multifunctional bioactive food components. Therefore, the present study focuses on the functional proprieties of a peptide fraction derived from Saccharomyces cerevisiae metabolism. The antimicrobial activity of the peptide fraction is evaluated against various foodborne pathogens, including Candida albicans, Candida krusei, Escherichia coli, Listeria monocytogenes, and Salmonella sp. The peptide fraction antioxidant properties are assessed using FRAP and DPPH scavenging capacity assays. Furthermore, the peptide fraction’s cytotoxicity is evaluated in colorectal carcinoma and normal colon epithelial cells while its potential as an antidiabetic agent is investigated through α-amylase and α-glucosidase inhibitory assays. The results demonstrate that the 2–10 kDa peptide fraction exhibits antimicrobial effects against all tested microorganisms, except C. krusei. The minimal inhibitory concentration for E. coli, L. monocytogenes, and Salmonella sp. remains consistently low, at 0.25 mg/mL, while C. albicans requires a higher concentration of 1.0 mg/mL. Furthermore, the peptide fraction displays antioxidant activity, as evidenced by DPPH radical scavenging activity of 81.03%, and FRAP values of 1042.50 ± 32.5 µM TE/mL at 1.0 mg/mL. The peptide fraction exhibits no cytotoxicity in both tumor and non-tumoral human cells at a concentration up to 0.3 mg/mL. Moreover, the peptide fraction presents anti-inflammatory activity, significantly reducing the expression of the TNFα gene by more than 29.7% in non-stimulated colon cells and by 50% in lipopolysaccharide-stimulated colon cells. It also inhibits the activity of the carbohydrate digestive enzymes α-amylase (IC₅₀ of 199.3 ± 0.9 µg/mL) and α-glucosidase (IC₂₀ of 270.6 ± 6.0 µg/mL). Overall, the findings showed that the peptide fraction exhibits antibacterial, antioxidant, anti-inflammatory, and antidiabetic activity. This study represents a step forward in the evaluation of the functional biological properties of S. cerevisiae bioactive peptides. Full article

(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)

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16 pages, 2605 KiB

Open AccessArticle

Antimicrobial Activity and Molecular Docking Studies of the Biotransformation of Diterpene Acanthoic Acid Using the Fungus Xylaria sp.

by Andrey Moacir do Rosario Marinho, Claudia Maria S. C. de Oliveira, João Victor Silva-Silva, Samara C. Anchieta de Jesus, José Edson S. Siqueira, Luana C. de Oliveira, Jéssica Fernandes Auzier, Liviane N. Soares, Maria Lúcia Belém Pinheiro, Sebastião C. Silva, Lívia S. Medeiros, Emmanoel V. Costa and Patrícia S. Barbosa Marinho

Antibiotics 2023, 12(8), 1331; https://doi.org/10.3390/antibiotics12081331 - 18 Aug 2023

Cited by 4 | Viewed by 1966

Abstract

Biotransformations are reactions mediated by microorganisms, such as fungi. These bioreactions have high chemo- and stereoselectivity on organic substrates and can be applied in the search for new bioactive compounds. In this study, acanthoic acid (AA) was biotransformed using the fungus Xylaria sp., [...] Read more.

Biotransformations are reactions mediated by microorganisms, such as fungi. These bioreactions have high chemo- and stereoselectivity on organic substrates and can be applied in the search for new bioactive compounds. In this study, acanthoic acid (AA) was biotransformed using the fungus Xylaria sp., giving the novel compound 3β,7β-dihydroxyacanthoic acid (S1). Both the AA and the product S1 were tested against Gram-positive and Gram-negative bacteria. To identify and validate possible biological targets as enzymes or proteins involved in the activity observed in vitro, we used the molecular docking method. Hydroxylation at the C-3 and C-7 positions of the biotransformation product enhanced its activity against Escherichia coli as well as its binding affinity and interactions with superoxide dismutase 1 (SOD1; PDB ID 4A7G). Based on our results, the SOD1 enzyme was suggested to be a possible target for the antioxidant activity of product S1. Full article

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

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18 pages, 1331 KiB

Open AccessFeature PaperArticle

Multidrug-Resistant Salmonella Species and Their Mobile Genetic Elements from Poultry Farm Environments in Malaysia

by Syahidiah Syed Abu Thahir, Sakshaleni Rajendiran, Rafiza Shaharudin and Yuvaneswary Veloo

Antibiotics 2023, 12(8), 1330; https://doi.org/10.3390/antibiotics12081330 - 18 Aug 2023

Cited by 3 | Viewed by 3455

Abstract

The prevalence and persistent outbreaks of multidrug-resistant (MDR) Salmonella in low-income countries have received growing attention among the public and scientific community. Notably, the excessive use of antibiotics in chicken feed for the purpose of treatment or as prophylaxis in the poultry industry [...] Read more.

The prevalence and persistent outbreaks of multidrug-resistant (MDR) Salmonella in low-income countries have received growing attention among the public and scientific community. Notably, the excessive use of antibiotics in chicken feed for the purpose of treatment or as prophylaxis in the poultry industry have led to a rising rate of antimicrobial resistance. Therefore, this study aimed to determine the presence of antimicrobial-resistant Salmonella species and its mobile genetic elements from soil and effluent samples of 33 randomly selected poultry farms in Selangor, Malaysia. Salmonella species were isolated on selective media (CHROMagar™ Salmonella). VITEK^® 2 system was used to identify the isolates and their antimicrobial susceptibility. Subsequently, eight isolates were subjected to the whole genome sequencing (WGS). Based on the results, Salmonella spp. was detected in 38.1% (24/63) of samples, with the highest resistance to ampicillin (62.5%), followed by ampicillin/sulbactam (50.0%) and ciprofloxacin (45.8%). Meanwhile, the identified serovars were Salmonella enterica subspecies enterica serovar Weltevreden (S. Weltevreden), S. Jedburgh, and S. Brancaster. The most prevalent resistance genes detected include qnrS1, bla_TEM-176, dfrA14, and tet(A). The IncX1 plasmid, with encoded resistance genes, was also detected in four isolates. Furthermore, mutations in the quinolone resistant-determining regions (QRDR) were discovered, specifically in the gyrA, gyrB, and parC genes. In short, surveillance such as continuous monitoring of antimicrobial resistance and emerging trends in resistance patterns through farm environmental samples could provide information to formulate public health interventions for effective infection prevention and disease control. Full article

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

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17 pages, 359 KiB

Open AccessReview

The Potential of Bacteriophage-Antibiotic Combination Therapy in Treating Infections with Multidrug-Resistant Bacteria

by Abdul-Halim Osman, Fleischer C. N. Kotey, Alex Odoom, Samuel Darkwah, Raphael K. Yeboah, Nicholas T. K. D. Dayie and Eric S. Donkor

Antibiotics 2023, 12(8), 1329; https://doi.org/10.3390/antibiotics12081329 - 17 Aug 2023

Cited by 19 | Viewed by 6253

Abstract

The growing threat of antibiotic resistance is a significant global health challenge that has intensified in recent years. The burden of antibiotic resistance on public health is augmented due to its multifaceted nature, as well as the slow-paced and limited development of new [...] Read more.

The growing threat of antibiotic resistance is a significant global health challenge that has intensified in recent years. The burden of antibiotic resistance on public health is augmented due to its multifaceted nature, as well as the slow-paced and limited development of new antibiotics. The threat posed by resistance is now existential in phage therapy, which had long been touted as a promising replacement for antibiotics. Consequently, it is imperative to explore the potential of combination therapies involving antibiotics and phages as a feasible alternative for treating infections with multidrug-resistant bacteria. Although either bacteriophage or antibiotics can potentially treat bacterial infections, they are each fraught with resistance. Combination therapies, however, yielded positive outcomes in most cases; nonetheless, a few combinations did not show any benefit. Combination therapies comprising the synergistic activity of phages and antibiotics and combinations of phages with other treatments such as probiotics hold promise in the treatment of drug-resistant bacterial infections. Full article

(This article belongs to the Special Issue Antibiotics vs. Phage Therapy, 2nd Edition)

9 pages, 2247 KiB

Open AccessCase Report

Ceftazidime-Avibactam as Osteomyelitis Therapy: A Miniseries and Review of the Literature

by Alessandro Mancuso, Luca Pipitò, Raffaella Rubino, Salvatore Antonino Distefano, Donatella Mangione and Antonio Cascio

Antibiotics 2023, 12(8), 1328; https://doi.org/10.3390/antibiotics12081328 - 17 Aug 2023

Cited by 1 | Viewed by 3035

Abstract

Bone and joint infections (BJIs) caused by multidrug-resistant gram-negative bacteria are becoming a concern due to limited therapeutic options. Although not approved for these indications, an ever-growing amount of evidence supports the efficacy and safety of ceftazidime–avibactam as a therapy for osteomyelitis and [...] Read more.

Bone and joint infections (BJIs) caused by multidrug-resistant gram-negative bacteria are becoming a concern due to limited therapeutic options. Although not approved for these indications, an ever-growing amount of evidence supports the efficacy and safety of ceftazidime–avibactam as a therapy for osteomyelitis and prosthetic joint infections. Here, we present three cases of difficult-to-treat resistant Pseudomonas aeruginosa osteomyelitis that were successfully treated with ceftazidime–avibactam alone or in combination therapy with fosfomycin and amikacin. Ceftazidime–avibactam was prescribed at a daily dose of 2.5 g every 8 h for 42 days in all cases. One potential drug-related adverse effect was observed, i.e., Clostridioides difficile infection, which occurred after fourteen days of treatment with ceftazidime–avibactam. Full article

(This article belongs to the Special Issue Antimicrobial Therapeutics for Bone and Periprosthetic Joint Infection)

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16 pages, 325 KiB

Open AccessReview

Evaluation of Enterococcal Probiotic Usage and Review of Potential Health Benefits, Safety, and Risk of Antibiotic-Resistant Strain Emergence

by Eric Jeeho Im, Harry Hyun-Yup Lee, Minzae Kim and Myo-Kyoung Kim

Antibiotics 2023, 12(8), 1327; https://doi.org/10.3390/antibiotics12081327 - 17 Aug 2023

Cited by 14 | Viewed by 2407

Abstract

Enterococci are often used in probiotics but can also cause nosocomial infections. As such, enterococcal consumption may have beneficial health effects, but a thorough evaluation of virulence absence and risk of antibiotic resistance spread is needed at the strain level. This article reviewed [...] Read more.

Enterococci are often used in probiotics but can also cause nosocomial infections. As such, enterococcal consumption may have beneficial health effects, but a thorough evaluation of virulence absence and risk of antibiotic resistance spread is needed at the strain level. This article reviewed ten online health product shopping websites in the US. On these websites, 23 probiotic products using enterococci were found across 12 companies. In addition, this article reviewed studies that demonstrated the probiotic potential of enterococcal consumption (e.g., gastrointestinal and respiratory disease, hyperlipidemia alleviation, as well as infection prevention). To investigate the safety aspects of enterococci, the present work examined studies evaluating virulence factors and antibiotic resistance. Furthermore, this article assessed research that explored these virulent factors, specifically in probiotics containing enterococci, as well as the potential transfer mechanism of their antibiotic resistance. Based on reviewed data, enterococcal probiotic consumption has been proven beneficial for conditions or symptoms of multiple diseases without any apparent adverse effects. However, due to the plasmid- or transposon-mediated gene transfer ability of enterococci, surveillance monitoring and further studies regarding enterococcal consumption are warranted. Future studies that identify enterococcal strains safe to use in probiotics without virulence factors and antibiotic resistance are imperative for evidence-based decisions by health organizations and government agencies. Full article

(This article belongs to the Special Issue Antibiotic Treatment and Antibiotic Resistance of Enterococcus Infections)

12 pages, 2995 KiB

Open AccessArticle

Enhancing Chemical Stability through Structural Modification of Antimicrobial Peptides with Non-Proteinogenic Amino Acids

by Takahito Ito, Natsumi Matsunaga, Megumi Kurashima, Yosuke Demizu and Takashi Misawa

Antibiotics 2023, 12(8), 1326; https://doi.org/10.3390/antibiotics12081326 - 17 Aug 2023

Cited by 4 | Viewed by 1898

Abstract

Multidrug-resistant bacteria (MDRB) remain a significant threat to humanity, resulting in over 1.2 million deaths per year. To combat this problem effectively, the development of therapeutic agents with diverse mechanisms of action is crucial. Antimicrobial peptides (AMPs) have emerged as promising next-generation therapeutics [...] Read more.

Multidrug-resistant bacteria (MDRB) remain a significant threat to humanity, resulting in over 1.2 million deaths per year. To combat this problem effectively, the development of therapeutic agents with diverse mechanisms of action is crucial. Antimicrobial peptides (AMPs) have emerged as promising next-generation therapeutics to combat infectious diseases, particularly MDRB. By targeting microbial membranes and inducing lysis, AMPs can effectively inhibit microbial growth, making them less susceptible to the development of resistance. Numerous structural advancements have been made to optimize the efficacy of AMPs. Previously, we developed 17KKV-Aib, a derivative of the Magainin 2 (Mag2) peptide, by incorporating a,a-disubstituted amino acids (dAAs) to modulate its secondary structure. 17KKV-Aib demonstrated potent antimicrobial activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant Pseudomonas aeruginosa (MDRP), with minimal hemolytic activity against human red blood cells. However, 17KKV-Aib faces challenges regarding its susceptibility to digestive enzymes, hindering its potential as an antimicrobial agent. In this study, we designed and synthesized derivatives of 17KKV-Aib, replacing Lys residues with 4-aminopiperidine-4-carboxylic acid (Api), which is a cyclized dAA residue possessing cationic properties on its side chain. We investigated the impact of Api substitution on the secondary structure, antimicrobial activity, hemolytic activity, and resistance to digestive enzymes. Our findings revealed that introducing Api residues preserved the helical structure and antimicrobial activity and enhanced resistance to digestive enzymes, with a slight increase in hemolytic activity. Full article

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9 pages, 617 KiB

Open AccessArticle

Surveillance of Antimicrobial Prescriptions in Community Pharmacies Located in Tokyo, Japan

by Kosuke Hasegawa, Tomoko Mori, Toshio Asakura, Yuriko Matsumura and Hidemasa Nakaminami

Antibiotics 2023, 12(8), 1325; https://doi.org/10.3390/antibiotics12081325 - 17 Aug 2023

Cited by 1 | Viewed by 1997

Abstract

An antimicrobial resistance (AMR) Action Plan was launched in 2016 to prevent the spread of antimicrobial-resistant bacteria in Japan. Additional support for the appropriate use of pediatric antimicrobial agents was initiated in 2018 to promote the appropriate use of antimicrobial agents in the [...] Read more.

An antimicrobial resistance (AMR) Action Plan was launched in 2016 to prevent the spread of antimicrobial-resistant bacteria in Japan. Additional support for the appropriate use of pediatric antimicrobial agents was initiated in 2018 to promote the appropriate use of antimicrobial agents in the community. To evaluate the effectiveness of the AMR Action Plan in the community, we investigated antimicrobial prescriptions in community pharmacies. Data on prescriptions for antimicrobial agents dispensed in 42 community pharmacies located in the Tama district, Tokyo, Japan, were collected between April 2013 and December 2019. In this study, we employed the DPY, which was calculated as defined daily doses (DDDs)/1000 prescriptions/year. The DPY is the number of antimicrobial agents used (potency) per 1000 antimicrobial prescriptions dispensed in pharmacies per year. The number of prescriptions for third-generation cephalosporins, fluoroquinolones, and macrolides decreased after the initiation of the AMR Action Plan; the DPYs of these antimicrobial agents decreased significantly by 31.4%, increased by 15.8%, and decreased by 23.6%, respectively (p < 0.05). The number of antimicrobial prescriptions for pediatric patients has been decreasing since 2018. Declines in the DPYs of third-generation cephalosporins, fluoroquinolones, and macrolides were higher in pediatric pharmacies than in other pharmacies. Our data suggest that the AMR Action Plan and additional support for the appropriate use of antimicrobial agents in children influenced the number of antimicrobial prescriptions in community pharmacies in Japan. Full article

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

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15 pages, 580 KiB

Open AccessFeature PaperArticle

Molecular Analysis of Anti-Tuberculosis Drug Resistance of Mycobacterium tuberculosis Isolated in the Republic of Korea

by Se-Mi Jeon, Sanghee Park, Na-Ra Lim, Noori Lee, Jihee Jung, Nackmoon Sung and Seonghan Kim

Antibiotics 2023, 12(8), 1324; https://doi.org/10.3390/antibiotics12081324 - 17 Aug 2023

Cited by 2 | Viewed by 1499

Abstract

Rapid and accurate detection of tuberculosis (TB) drug resistance is critical for the successful treatment and control of TB. Here, we investigated resistance to anti-TB drugs and genetic variations in 215 drug-resistant Mycobacterium tuberculosis isolates in Korea. Genetic variations were observed in rpoB [...] Read more.

Rapid and accurate detection of tuberculosis (TB) drug resistance is critical for the successful treatment and control of TB. Here, we investigated resistance to anti-TB drugs and genetic variations in 215 drug-resistant Mycobacterium tuberculosis isolates in Korea. Genetic variations were observed in rpoB Ser531Leu, katG Ser315Thr, and gyrA Asp94Gly; however, the minimum inhibitory concentrations varied, which can be attributed to other resistance mechanisms. Examination of genetic relatedness among drug-resistant isolates revealed that the cluster size of resistant bacteria was less than six strains, suggesting no evidence of a large-scale epidemic caused by a specific strain. However, rpoC mutants of the rifampicin-resistant isolates were composed of five types of clusters, suggesting that these compensatory mutations advance propagation. In the present study, more than 90% of the resistance mechanisms to major anti-TB drugs were identified, and the effect of each mutation on drug resistance was estimated. With the clinical application of recent next-generation sequencing-based susceptibility testing, the present study is expected to improve the clinical utilization of genotype-based drug susceptibility testing for the diagnosis and treatment of patients with drug-resistant TB. Full article

(This article belongs to the Special Issue Multidrug-Resistant Mycobacterium tuberculosis)

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9 pages, 434 KiB

Open AccessArticle

Clinical Efficacy of Fidaxomicin and Oral Metronidazole for Treating Clostridioides difficile Infection and the Associated Recurrence Rate: A Retrospective Cohort Study

by Nobuaki Mori, Jun Hirai, Wataru Ohashi, Nobuhiro Asai, Yuichi Shibata and Hiroshige Mikamo

Antibiotics 2023, 12(8), 1323; https://doi.org/10.3390/antibiotics12081323 - 16 Aug 2023

Viewed by 1722

Abstract

Clostridioides difficile infection (CDI) has significant implications for healthcare economics. Although clinical trials have compared fidaxomicin (FDX) and vancomycin, comparisons of FDX and oral metronidazole (MNZ) are limited. Therefore, we compared the therapeutic effects of FDX and oral MNZ. Patients diagnosed with CDI [...] Read more.

Clostridioides difficile infection (CDI) has significant implications for healthcare economics. Although clinical trials have compared fidaxomicin (FDX) and vancomycin, comparisons of FDX and oral metronidazole (MNZ) are limited. Therefore, we compared the therapeutic effects of FDX and oral MNZ. Patients diagnosed with CDI between January 2015 and March 2023 were enrolled. Those treated with oral MNZ or FDX were selected and retrospectively analyzed. The primary outcome was the global cure rate. Secondary outcomes included factors contributing to the CDI global cure rate; the rate of medication change owing to initial treatment failure; and incidence rates of clinical cure, recurrence, and all-cause mortality within 30 days. Of the 264 enrolled patients, 75 and 30 received initial oral MNZ and FDX treatments, respectively. The corresponding CDI global cure rates were 53.3% and 70% (p = 0.12). In multivariate analysis, FDX was not associated with the global cure rate. In the MNZ group, 18.7% of the patients had to change medications owing to initial treatment failure. The FDX group had a higher clinical cure rate and lower recurrence rate than the MNZ group, although not significant. However, caution is necessary owing to necessary treatment changes due to MNZ failure. Full article

(This article belongs to the Special Issue Clostridioides difficile Infection, 2nd Edition)

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18 pages, 1003 KiB

Open AccessArticle

A Qualitative Study on the Policy Process and Development of the National Action Plan on Antimicrobial Resistance in Singapore

by Alvin Qijia Chua, Monica Verma, Karen Azupardo, Maria Margarita Lota, Li Yang Hsu and Helena Legido-Quigley

Antibiotics 2023, 12(8), 1322; https://doi.org/10.3390/antibiotics12081322 - 16 Aug 2023

Viewed by 1558

Abstract

The global public health threat of antimicrobial resistance (AMR) has been accelerated by many interrelated factors spanning across One Health—human health, animal health, and the environment. Singapore launched its own National Strategic Action Plan (NSAP) on AMR in November 2017 with the aim [...] Read more.

The global public health threat of antimicrobial resistance (AMR) has been accelerated by many interrelated factors spanning across One Health—human health, animal health, and the environment. Singapore launched its own National Strategic Action Plan (NSAP) on AMR in November 2017 with the aim of tackling the growing threat of AMR in Singapore through coordinated approaches. However, little is known about the policy process and development of the NSAP in Singapore. In this study, we analysed these aspects using an AMR governance framework. In-depth interviews were conducted with 20 participants across the One Health spectrum. The interviews were transcribed verbatim and analysed thematically. Areas that were well executed included (1) good coordination across various agencies, (2) a dedicated office to coordinate the work on the NSAP, and (3) a high level of governmental support. Areas that were lacking included (1) a lack of participation from certain sectors, (2) insufficient awareness around the AMR issue, (3) constraints in information sharing, and (4) a lack of ideal indicators to track the progress in addressing AMR. Improvements in these areas will provide a more holistic One Health engagement in support of the effective planning and implementation of the NSAP. Full article

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14 pages, 304 KiB

Open AccessArticle

The Antimicrobial Resistance (AMR) Rates of Enterobacterales in a Rural Hospital from the Eastern Region, Ghana: A Retrospective Study, 2022

by Laura Seijas-Pereda, Carlos Rescalvo-Casas, Marcos Hernando-Gozalo, Vida Angmorkie-Eshun, Eunice Agyei, Vivian Adu-Gyamfi, Isaac Sarsah, Maite Alfonso-Romero, Juan Cuadros-González, Juan Soliveri-de Carranza and Ramón Pérez-Tanoira

Antibiotics 2023, 12(8), 1321; https://doi.org/10.3390/antibiotics12081321 - 16 Aug 2023

Cited by 1 | Viewed by 1534

Abstract

Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance and often lack adequate surveillance due to a paucity of microbiological studies. In this 2022 study, our goal was to contribute to a more precise antimicrobial treatment by understanding the prevalence of [...] Read more.

Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance and often lack adequate surveillance due to a paucity of microbiological studies. In this 2022 study, our goal was to contribute to a more precise antimicrobial treatment by understanding the prevalence of resistance in a rural environment, promoting antibiotic stewardship, and raising awareness about antimicrobial resistance. We assessed the prevalence of Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) Enterobacterales in clinical samples from 2905 patients being treated at Saint Dominic’s Hospital, Akwatia, in the countryside of the Eastern Region, Ghana, in the year 2022. To this purpose, the samples were cultured on agar plates prepared in the laboratory using purified Oxoid™ Thermo Scientific™ agar (Thermo Fisher Scientific; Waltham, MA, USA). Cystine Lactose Electrolyte-Deficient (CLED) agar was used for urine samples, while blood agar, chocolate agar, and MacConkey agar were used for the rest of the specimens tested (HVS, blood, BFA, sputum). Antimicrobial susceptibility was determined on site using the disc diffusion method (Kirby-Bauer test). MDR bacteria accounted for more than half (53.7%) of all microorganisms tested for three or more antibiotics and 37.3% of these were XDR. Multivariate regression analysis was performed to identify risk factors associated with acquiring MDR/XDR bacteria. The results showed an increased likelihood of MDR acquisition linked to being male (OR 2.39, p < 0.001 for MDR and OR 1.95, p = 0.027 for XDR), higher age (OR 1.01, p = 0.049 for MDR), non-sputum samples (OR 0.32, p = 0.009 for MDR), and urine samples (OR 7.46, p < 0.001 for XDR). These findings emphasize the urgency for surveillance and control of antimicrobial resistance; to this end, making accurate diagnostics, studying the microorganism in question, and conducting susceptibility testing is of the utmost importance. Full article

(This article belongs to the Special Issue Gram-Negative Multidrug Resistant Pathogen and Its Treatment)

21 pages, 2897 KiB

Open AccessEditor’s ChoiceArticle

Size-Controlled Ammonium-Based Homopolymers as Broad-Spectrum Antibacterials

by Meltem Haktaniyan, Richa Sharma and Mark Bradley

Antibiotics 2023, 12(8), 1320; https://doi.org/10.3390/antibiotics12081320 - 16 Aug 2023

Viewed by 1779

Abstract

Ammonium group containing polymers possess inherent antimicrobial properties, effectively eliminating or preventing infections caused by harmful microorganisms. Here, homopolymers based on monomers containing ammonium groups were synthesized via Reversible Addition Fragmentation Chain Transfer Polymerization (RAFT) and evaluated as potential antibacterial agents. The antimicrobial [...] Read more.

Ammonium group containing polymers possess inherent antimicrobial properties, effectively eliminating or preventing infections caused by harmful microorganisms. Here, homopolymers based on monomers containing ammonium groups were synthesized via Reversible Addition Fragmentation Chain Transfer Polymerization (RAFT) and evaluated as potential antibacterial agents. The antimicrobial activity was evaluated against Gram-positive (M. luteus and B. subtilis) and Gram-negative bacteria (E. coli and S. typhimurium). Three polymers, poly(diallyl dimethyl ammonium chloride), poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride), and poly(vinyl benzyl trimethylammonium chloride), were examined to explore the effect of molecular weight (10 kDa, 20 kDa, and 40 kDa) on their antimicrobial activity and toxicity to mammalian cells. The mechanisms of action of the polymers were investigated with dye-based assays, while Scanning Electron Microscopy (SEM) showed collapsed and fused bacterial morphologies due to the interactions between the polymers and components of the bacterial cell envelope, with some polymers proving to be bactericidal and others bacteriostatic, while being non-hemolytic. Among all the homopolymers, the most active, non-Gram-specific polymer was poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride), with a molecular weight of 40 kDa, with minimum inhibitory concentrations between 16 and 64 µg/mL, showing a bactericidal mode of action mediated by disruption of the cytoplasmic membrane. This homopolymer could be useful in biomedical applications such as surface dressings and in areas such as eye infections. Full article

(This article belongs to the Special Issue Molecular Methods in Antibiotics Discovery)

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19 pages, 6195 KiB

Open AccessArticle

In Vitro Evaluation of Antiviral Activities of Funicone-like Compounds Vermistatin and Penisimplicissin against Canine Coronavirus Infection

by Claudia Cerracchio, Maria Michela Salvatore, Luca Del Sorbo, Francesco Serra, Maria Grazia Amoroso, Marina DellaGreca, Rosario Nicoletti, Anna Andolfi and Filomena Fiorito

Antibiotics 2023, 12(8), 1319; https://doi.org/10.3390/antibiotics12081319 - 15 Aug 2023

Cited by 2 | Viewed by 1492

Abstract

Recent studies have demonstrated that 3-O-methylfunicone (OMF), a fungal secondary metabolite from Talaromyces pinophilus belonging to the class of funicone-like compounds, has antiviral activity against canine coronaviruses (CCoV), which causes enteritis in dogs. Herein, we selected two additional funicone-like compounds named [...] Read more.

Recent studies have demonstrated that 3-O-methylfunicone (OMF), a fungal secondary metabolite from Talaromyces pinophilus belonging to the class of funicone-like compounds, has antiviral activity against canine coronaviruses (CCoV), which causes enteritis in dogs. Herein, we selected two additional funicone-like compounds named vermistatin (VER) and penisimplicissin (PS) and investigated their inhibitory activity towards CCoV infection. Thus, both compounds have been tested for their cytotoxicity and for antiviral activity against CCoV in A72 cells, a fibrosarcoma cell line suitable for investigating CCoV. Our findings showed an increase in cell viability, with an improvement of morphological features in CCoV-infected cells at the non-toxic doses of 1 μM for VER and 0.5 μM for PS. In addition, we observed that these compounds caused a strong inhibition in the expression of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor which is activated during CCoV infection. Our results also showed the alkalinization of lysosomes in the presence of VER or PS, which may be involved in the observed antiviral activities. Full article

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18 pages, 3528 KiB

Open AccessArticle

Gatifloxacin Loaded Nano Lipid Carriers for the Management of Bacterial Conjunctivitis

by Poorva H. Joshi, Ahmed Adel Ali Youssef, Mihir Ghonge, Corinne Varner, Siddharth Tripathi, Narendar Dudhipala and Soumyajit Majumdar

Antibiotics 2023, 12(8), 1318; https://doi.org/10.3390/antibiotics12081318 - 15 Aug 2023

Cited by 4 | Viewed by 2115

Abstract

Bacterial conjunctivitis (BC) entails inflammation of the ocular mucous membrane. Early effective treatment of BC can prevent the spread of the infection to the intraocular tissues, which could lead to bacterial endophthalmitis or serious visual disability. In 2003, gatifloxacin (GTX) eyedrops were introduced [...] Read more.

Bacterial conjunctivitis (BC) entails inflammation of the ocular mucous membrane. Early effective treatment of BC can prevent the spread of the infection to the intraocular tissues, which could lead to bacterial endophthalmitis or serious visual disability. In 2003, gatifloxacin (GTX) eyedrops were introduced as a new broad-spectrum fluoroquinolone to treat BC. Subsequently, GTX use was extended to other ocular bacterial infections. However, due to precorneal loss and poor ocular bioavailability, frequent administration of the commercial eyedrops is necessary, leading to poor patient compliance. Thus, the goal of the current investigation was to formulate GTX in a lipid-based drug delivery system to overcome the challenges with the existing marketed eyedrops and, thus, improve the management of bacterial conjunctivitis. GTX-NLCs and SLNs were formulated with a hot homogenization–probe sonication method. The lead GTX-NLC formulation was characterized and assessed for in vitro drug release, antimicrobial efficacy (against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa), and ex vivo permeation. The lead formulation exhibited desired physicochemical characteristics, an extended release of GTX over a 12 h period, and was stable over three months at the three storage conditions (refrigerated, room temperature, and accelerated). The transcorneal flux and permeability of GTX from the GTX-NLC formulation were 5.5- and 6.0-fold higher in comparison to the commercial eyedrops and exhibited a similar in vitro antibacterial activity. Therefore, GTX-NLCs could serve as an alternative drug delivery platform to improve treatment outcomes in BC. Full article

(This article belongs to the Special Issue Antimicrobial Nanoformulations against Bacterial Infections)

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12 pages, 827 KiB

Open AccessFeature PaperArticle

Comparison between Colistin and Polymyxin B in the Treatment of Bloodstream Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii-calcoaceticus Complex

by Rebeca Carvalho Lacerda Garcia, Rodrigo Douglas Rodrigues, Ester Carvalho Lacerda Garcia and Maria Helena Rigatto

Antibiotics 2023, 12(8), 1317; https://doi.org/10.3390/antibiotics12081317 - 15 Aug 2023

Cited by 5 | Viewed by 3411

Abstract

Polymyxins are still widely used for the treatment of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa bloodstream infections (BSIs). This study seeks to evaluate the impact of polymyxin B versus colistin on mortality and nephrotoxicity in BSI caused by these bacteria. We conducted a [...] Read more.

Polymyxins are still widely used for the treatment of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa bloodstream infections (BSIs). This study seeks to evaluate the impact of polymyxin B versus colistin on mortality and nephrotoxicity in BSI caused by these bacteria. We conducted a retrospective cohort study from 2014 to 2021 in Porto Alegre, Brazil. We included patients aged ≥18 years and excluded patients with polymicrobial infection or treatment for ≤48 h. The 30-day mortality was the primary outcome evaluated through Cox regression. We included 259 patients with BSI episodes: 78.8% caused by A. baumannii and 21.2% caused by P. aeruginosa. Polymyxin B did not impact mortality compared to colistin (adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI), 0.52–1.30; p = 0.40 (when adjusted for COVID-19 comorbidity, p = 0.05), Pitt bacteremia score, p < 0.01; Charlson comorbidity index, p < 0.001; time to start active antimicrobial therapy, p = 0.02). Results were maintained in the subgroups of BSI caused by A. baumannii (aHR, 0.92; 95% CI, 0.55–1.54; p = 0.74), P. aeruginosa (aHR, 0.47; 95% CI, 0.17–1.32; p = 0.15) and critical care patients (aHR, 0.77; 95% CI, 0.47–1.26; p = 0.30). Treatment with polymyxin B or colistin did not impact 30-day mortality in patients with carbapenem-resistant A. baumannii or P. aeruginosa BSI. Full article

(This article belongs to the Special Issue Antibiotics Use and Therapy in Gram-Negative Bacterial Infection)

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13 pages, 881 KiB

Open AccessReview

Early Intra-Abdominal Bacterial Infections after Orthotopic Liver Transplantation: A Narrative Review for Clinicians

by Riccardo Taddei, Niccolò Riccardi, Giusy Tiseo, Valentina Galfo and Giandomenico Biancofiore

Antibiotics 2023, 12(8), 1316; https://doi.org/10.3390/antibiotics12081316 - 15 Aug 2023

Cited by 5 | Viewed by 1720

Abstract

Despite recent advances in the transplant field, infectious complications after orthotopic liver transplantation (OLT) are major causes of morbidity and mortality. Bacterial intra-abdominal infections (IAIs) are predominant during the first month post-transplantation and affect patient and graft survival. Recently, the emergence of multidrug [...] Read more.

Despite recent advances in the transplant field, infectious complications after orthotopic liver transplantation (OLT) are major causes of morbidity and mortality. Bacterial intra-abdominal infections (IAIs) are predominant during the first month post-transplantation and affect patient and graft survival. Recently, the emergence of multidrug resistant bacteria has generated great concern in OLT patients. We performed this narrative review of the literature in order to propose a “ready-to-use” flowchart for reasoned empirical antibiotic therapy in the case of suspected post-OLT IAIs. The review was ultimately organized into four sections: “Epidemiology and predisposing factors for IAI”; “Surgical-site infections and perioperative prophylaxis”; “MDRO colonization and infections”; and “Reasoned-empirical antibiotic therapy in early intra-abdominal infections post OLT and source control”. Multidisciplinary teamwork is warranted to individualize strategies for the prevention and treatment of IAIs in OLT recipients, taking into account each patient’s risk factors, the surgical characteristics, and the local bacterial epidemiology. Full article

(This article belongs to the Special Issue Intra-abdominal Infections: From Diagnosis to Source Control)

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Antibiotics, Volume 12, Issue 8 (August 2023) – 118 articles

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