Antibiotics

8 pages, 661 KiB

Open AccessArticle

Concentration-Dependent Activity of Pazufloxacin against Pseudomonas aeruginosa: An In Vivo Pharmacokinetic/Pharmacodynamic Study

by Yasuhiro Umezaki, Kazuaki Matsumoto, Kazuro Ikawa, Yuta Yokoyama, Yuki Enoki, Akari Shigemi, Erika Watanabe, Koyo Nakamura, Keiichiro Ueno, Hideyuki Terazono, Norifumi Morikawa and Yasuo Takeda

Antibiotics 2022, 11(7), 982; https://doi.org/10.3390/antibiotics11070982 - 21 Jul 2022

Viewed by 2086

Abstract

The bacterium Pseudomonas aeruginosa is known to be associated with nosocomial infections around the world. Pazufloxacin, a potent DNA gyrase inhibitor, is known to be an effective drug candidate. However, it has not been clarified whether the pharmacokinetic (PK)/pharmacodynamic (PD) of pazufloxacin was [...] Read more.

The bacterium Pseudomonas aeruginosa is known to be associated with nosocomial infections around the world. Pazufloxacin, a potent DNA gyrase inhibitor, is known to be an effective drug candidate. However, it has not been clarified whether the pharmacokinetic (PK)/pharmacodynamic (PD) of pazufloxacin was effective against P. aeruginosa. Herein, we demonstrated that the PK/PD index of pazufloxacin against P. aeruginosa infection is used to optimize the dosing regiments. We constructed an in vivo infection model by infecting P. aeruginosa into the thigh of a mouse to determine the PD, and we measured the serum concentration of pazufloxacin to construct the PK model using high-performance liquid chromatography. The therapeutic efficacy of pazufloxacin was correlated with the ratio of the area under the free concentration time curve at 24 h to the minimum inhibitory concentration (fAUC₂₄/MIC), and the maximum free concentration to the MIC (fC_max/MIC). Each contribution rate (R²) was 0.72 and 0.65, respectively, whereas the time at which the free drug concentration remained above the MIC (R² = 0.28). The target value of pazufloxacin fAUC₂₄/MIC for stasis was 46.1, for 1 log₁₀ it was 63.8, and for 2 log₁₀ it was 100.8. Moreover, fC_max/MIC for stasis was 5.5, for 1 log₁₀ it was 7.1, and for 2 log₁₀ it was 10.8. We demonstrated that the in vivo concentration-dependent activity of pazufloxacin was effective against the P. aeruginosa infection, and successfully made the PK/PD model sufficiently bactericidal. The PK/PD model will be beneficial in preventing the spread of nosocomial infections. Full article

(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)

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15 pages, 1814 KiB

Open AccessArticle

Early Life Antimicrobial Exposure: Impact on Clostridioides difficile Colonization in Infants

by Chinwe Vivien Obiakor, Jaclyn Parks, Tim K. Takaro, Hein M. Tun, Nadia Morales-Lizcano, Meghan B. Azad, Piushkumar J. Mandhane, Theo J. Moraes, Elinor Simons, Stuart E. Turvey, Padmaja Subbarao, James A. Scott and Anita L. Kozyrskyj

Antibiotics 2022, 11(7), 981; https://doi.org/10.3390/antibiotics11070981 - 21 Jul 2022

Cited by 2 | Viewed by 2525

Abstract

The relationship between antibiotic use and Clostridioides difficile (C. difficile) has been well established in adults and older children but remains unclear and is yet to be fully examined in infant populations. This study aimed to determine the separate and cumulative [...] Read more.

The relationship between antibiotic use and Clostridioides difficile (C. difficile) has been well established in adults and older children but remains unclear and is yet to be fully examined in infant populations. This study aimed to determine the separate and cumulative impact from antibiotics and household cleaning products on C. difficile colonization in infants. This study included 1429 infants at 3–4 months of age and 1728 infants at 12 months of age from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. The levels of infant antimicrobial exposure were obtained from hospital birth charts and standardized questionnaires. Infant gut microbiota was characterized by Illumina 16S ribosomal ribonucleic acid (rRNA) gene sequencing. Analysis of C. difficile was performed using a quantitative polymerase chain reaction (qPCR). Overall, C. difficile colonized 31% and 46% of infants at 3–4 months and 12 months, respectively. At 3–4 months, C. difficile colonization was significantly higher in infants exposed to both antibiotics and higher (above average) usage of household cleaning products (adjusted odds ratio (aOR) 1.50, 95% CI 1.03–2.17; p = 0.032) than in infants who had the least antimicrobial exposure. This higher colonization persisted up to 12 months of age. Our study suggests that cumulative exposure to systemic antibiotics and higher usage of household cleaning products facilitates C. difficile colonization in infants. Further research is needed to understand the future health impacts. Full article

(This article belongs to the Special Issue Antibiotics in Health and Diseases)

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8 pages, 2424 KiB

Open AccessViewpoint

Advocacy for Responsible Antibiotic Production and Use

by Véronique Mondain, Nicolas Retur, Benjamin Bertrand, Florence Lieutier-Colas, Philippe Carenco and Sylvain Diamantis

Antibiotics 2022, 11(7), 980; https://doi.org/10.3390/antibiotics11070980 - 20 Jul 2022

Viewed by 2260

Abstract

Antibiotic-resistant bacteria have become one of humankind’s major challenges, as testified by the UN’s Call to Action on Antimicrobial Resistance in 2021. Our knowledge of the underlying processes of antibiotic resistance is steadily improving. Beyond the inappropriate use of antimicrobials in human medicine, [...] Read more.

Antibiotic-resistant bacteria have become one of humankind’s major challenges, as testified by the UN’s Call to Action on Antimicrobial Resistance in 2021. Our knowledge of the underlying processes of antibiotic resistance is steadily improving. Beyond the inappropriate use of antimicrobials in human medicine, other causes have been identified, raising ethical issues and requiring an approach to the problem from a “One Health” perspective. Indeed, it is now clear that the two main issues regarding the subject of antibiotics are their misuse in the global food industry and their method of production, both leading to the emergence and spread of bacterial resistance. Full article

(This article belongs to the Special Issue New Paradigms Concerning the Production of Antibiotics: Between Ecological Responsibility and Revalorization of Narrow Spectrums)

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13 pages, 1538 KiB

Open AccessArticle

Antimicrobial Activity of Essential Oils Evaluated In Vitro against Escherichia coli and Staphylococcus aureus

by Michela Galgano, Paolo Capozza, Francesco Pellegrini, Marco Cordisco, Alessio Sposato, Sabina Sblano, Michele Camero, Gianvito Lanave, Giuseppe Fracchiolla, Marialaura Corrente, Francesco Cirone, Adriana Trotta, Maria Tempesta, Domenico Buonavoglia and Annamaria Pratelli

Antibiotics 2022, 11(7), 979; https://doi.org/10.3390/antibiotics11070979 - 20 Jul 2022

Cited by 28 | Viewed by 5165

Abstract

The spread of extended-spectrum β-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus has caused a reduction in antibiotic effectiveness and an increase in mortality rates. Essential oils (EOs), known for their therapeutic efficacy, can be configured as novel broad-spectrum biocides. Accordingly, the bacteriostatic–bactericidal activity [...] Read more.

The spread of extended-spectrum β-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus has caused a reduction in antibiotic effectiveness and an increase in mortality rates. Essential oils (EOs), known for their therapeutic efficacy, can be configured as novel broad-spectrum biocides. Accordingly, the bacteriostatic–bactericidal activity of Citrus Lemon (LEO), Pinus Sylvestris (PEO), Foeniculum Vulgaris (FEO), Ocimum Basilicum (BEO), Melissa Officinalis (MEO), Thymus Vulgaris (TEO), and Zingiber Officinalis Rosc. (GEO), at concentrations ranging from 1.25 to 40% (v/v), were tested in vitro against different E. coli and S. aureus strains using minimal inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). The chemical compositions of the EOs were analyzed using GC/MS. The major components of all seven tested oils were limonene, α-pinene, anethole, estragole, citral, thymol, and zingiberene, respectively. We found that the bacteriostatic–bactericidal activity of the EOs was related to their chemotypes and concentrations, as well as the strain of the bacteria. A dose–effect correlation was found when testing GEO against S. aureus strains, whilst FEO was found to have no activity regardless of concentration. PEO, MEO, and BEO were found to have bactericidal effect with a MIC and MBC of 1.25% (v/v) against S. aureus strains, and LEO was found to have values of 1.25% (v/v) and 5% (v/v) against ATCC and clinical isolate, respectively. Interestingly, the antimicrobial activity of TEO was not related to oil concentration and the complete inhibition of growth across all E. coli and S. aureus was observed. Although preliminary, our data demonstrate the efficacy of EOs and pave the way for further investigations on their potential synergistic use with traditional drugs in the human and veterinary fields. Full article

(This article belongs to the Special Issue What’s New: Natural and Synthetic Antibacterials and/or Agents with Multiple Activities? 2nd Volume)

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10 pages, 1307 KiB

Open AccessArticle

Profiling Antibiotic Resistance in Acinetobacter calcoaceticus

by Janiece S. Glover, Taylor D. Ticer and Melinda A. Engevik

Antibiotics 2022, 11(7), 978; https://doi.org/10.3390/antibiotics11070978 - 20 Jul 2022

Cited by 6 | Viewed by 6469

Abstract

Background: Acinetobacter spp. have emerged as troublesome pathogens due to their multi-drug resistance. The majority of the work to date has focused on the antibiotic resistance profile of Acinetobacter baumannii. Although A. calcoaceticus strains are isolated in the hospital setting, limited [...] Read more.

Background: Acinetobacter spp. have emerged as troublesome pathogens due to their multi-drug resistance. The majority of the work to date has focused on the antibiotic resistance profile of Acinetobacter baumannii. Although A. calcoaceticus strains are isolated in the hospital setting, limited information is available on these closely related species. Methods & Results: The computational analysis of antibiotic resistance genes in 1441 Acinetobacter genomes revealed that A. calcoaceticus harbored a similar repertoire of multi-drug efflux pump and beta-lactam resistance genes as A. baumannii, leading us to speculate that A. calcoaceticus would have a similar antibiotic resistance profile to A. baumannii. To profile the resistance patterns of A. calcoaceticus, strains were examined by Kirby–Bauer disk diffusion and phenotypic microarrays. We found that Acinetobacter strains were moderately to highly resistant to certain antibiotics within fluoroquinolones, aminoglycosides, tetracyclines, and other antibiotic classes. These data indicate that A. calcoaceticus has a similar antibiotic resistance profile as A. baumannii ATCC 19606. We also identified that all Acinetobacter species were sensitive to 5-fluoroorotic acid, novobiocin, and benzethonium chloride. Conclusion: Collectively, these data provide new insights into the antibiotic resistance in A. calcoaceticus and identify several antibiotics that could be beneficial in treating Acinetobacter infections. Full article

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9 pages, 1983 KiB

Open AccessArticle

Essential Oils as a Good Weapon against Drug-Resistant Candida auris

by Liliana Fernandes, Rita Ribeiro, Raquel Costa, Mariana Henriques and M. Elisa Rodrigues

Antibiotics 2022, 11(7), 977; https://doi.org/10.3390/antibiotics11070977 - 20 Jul 2022

Cited by 15 | Viewed by 4143

Abstract

Candida auris is a recently found Candida species, mainly associated with nosocomial outbreaks in intensive care hospital settings, and unlike other Candida species, it can be transmitted through person-to-person or by contact with surfaces. C. auris is described as resistant to first-line antifungals [...] Read more.

Candida auris is a recently found Candida species, mainly associated with nosocomial outbreaks in intensive care hospital settings, and unlike other Candida species, it can be transmitted through person-to-person or by contact with surfaces. C. auris is described as resistant to first-line antifungals and, consequently, associated with high mortality. Nowadays, essential oils (EOs) are known to be effective against fungal and bacterial infections. This work aimed to evaluate the effect of four EOs (tea tree, niaouli, white thyme and cajeput) against C. auris. The EO’s effect on C. auris planktonic growth was evaluated by the minimum inhibitory concentration determination and by the agar disc diffusion method. Then, the same effect was evaluated on biofilm by colony-forming units’ enumeration. The results showed that EOs were able to inhibit the C. auris planktonic growth, with an MIC50 between 0.78 and 1.56% and halos of 20–21 mm for white thyme and tea tree and 13–14 mm for cajeput and niaouli. In addition, the EOs were also able to completely inhibit biofilm formation. Moreover, white thyme and cajeput completely eradicate pre-formed biofilms, while tea tree and niaouli significantly reduce it. Thus, this work demonstrates that EOs are a possible therapeutic alternative and a future perspective for the hard fight against C. auris. Full article

(This article belongs to the Special Issue Microbial Biofilms, Antimicrobials, and Virulence Determinants)

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13 pages, 2776 KiB

Open AccessArticle

Assessment of the Compliance of Cystitis Management According to French Recommendations through the Analysis of Prescriptions Collected in Community Pharmacies

by Arthur Piraux, Ramy Hammoud, Jérémie Riou, Souhil Lebdai and Sébastien Faure

Antibiotics 2022, 11(7), 976; https://doi.org/10.3390/antibiotics11070976 - 20 Jul 2022

Cited by 5 | Viewed by 2731

Abstract

Urinary tract infections, especially cystitis, are common infections; they are the second most prevalent cause of antibiotic prescriptions in community pharmacies. To reduce antimicrobial resistance, guidelines are revised regularly. This study aims to assess compliance between prescriptions collected in community pharmacies and French [...] Read more.

Urinary tract infections, especially cystitis, are common infections; they are the second most prevalent cause of antibiotic prescriptions in community pharmacies. To reduce antimicrobial resistance, guidelines are revised regularly. This study aims to assess compliance between prescriptions collected in community pharmacies and French cystitis guidelines. A treatment is considered compliant if the nature, dosage, and duration of the antibiotics are correct. Only women aged 18–65 years with a diagnosis of cystitis were eligible. The participation of 16 pharmacies resulted in 303 prescriptions. Most infections were classified as uncomplicated cystitis (79.2%), general practitioners were the prescribers in more than 9 out of 10 cases, and fosfomycin trometamol was the antibiotic dispensed for 1 in 2 women. An average compliance of 66% was observed, but with disparities according to the type of cystitis. Two-thirds of cases of uncomplicated cystitis and recurrent cystitis followed the recommendations, whereas only 15% of cystitis cases that were at risk of complication did so. The inclusion of a urine examination in uncomplicated cystitis decreased the overall compliance rate to 5.8%. These results show the essential role played by pharmacists; they are the last line of defence before dispensing antibiotics. They must know the recommendations in order to apply them. Full article

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17 pages, 1809 KiB

Open AccessReview

A Review of Commonly Used Methodologies for Assessing the Antibacterial Activity of Honey and Honey Products

by Md Lokman Hossain, Lee Yong Lim, Katherine Hammer, Dhanushka Hettiarachchi and Cornelia Locher

Antibiotics 2022, 11(7), 975; https://doi.org/10.3390/antibiotics11070975 - 20 Jul 2022

Cited by 45 | Viewed by 17501

Abstract

Honey, a naturally sweet and viscous substance is mainly produced by honeybees (Apis mellifera) from flower nectar. Honey exerts a plethora of biological and pharmacological activities, namely, antioxidant, antimicrobial and anti-inflammatory activity, because of the presence of an extensive variety of [...] Read more.

Honey, a naturally sweet and viscous substance is mainly produced by honeybees (Apis mellifera) from flower nectar. Honey exerts a plethora of biological and pharmacological activities, namely, antioxidant, antimicrobial and anti-inflammatory activity, because of the presence of an extensive variety of bioactive compounds. The antibacterial activity is one of the most reported biological properties, with many studies demonstrating that honey is active against clinically important pathogens. As a result, beside honey’s widespread utilization as a common food and flavouring agent, honey is an attractive natural antimicrobial agent. However, the use of neat honey for therapeutic purposes poses some problems, for instance, its stickiness may hamper its appeal to consumers and health care professionals, and the maintenance of an adequate therapeutic concentration over a sufficient timeframe may be challenging due to honey liquidity and leakage. It has motivated researchers to integrate honey into diverse formulations, for example, hydrogels, dressings, ointments, pastes and lozenges. The antibacterial activity of these formulations should be scientifically determined to underscore claims of effectiveness. Some researchers have made efforts to adapt the disc carrier and suspension test to assess the antimicrobial activity of topical products (e.g., silver-based wound dressings). However, there is currently no established and validated method for determining the in vitro antimicrobial potential of natural product-based formulations, including those containing honey as the active principle. Against the backdrop of a brief discussion of the parameters that contribute to its antibacterial activity, this review provides an outline of the methods currently used for investigating the antibacterial activity of neat honey and discusses their limitations for application to honey-based formulations. Full article

(This article belongs to the Special Issue Antioxidant and Antibacterial Properties of Honey)

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18 pages, 989 KiB

Open AccessPerspective

Antimicrobial Resistance in the Environment: Towards Elucidating the Roles of Bioaerosols in Transmission and Detection of Antibacterial Resistance Genes

by Paul B. L. George, Florent Rossi, Magali-Wen St-Germain, Pierre Amato, Thierry Badard, Michel G. Bergeron, Maurice Boissinot, Steve J. Charette, Brenda L. Coleman, Jacques Corbeil, Alexander I. Culley, Marie-Lou Gaucher, Matthieu Girard, Stéphane Godbout, Shelley P. Kirychuk, André Marette, Allison McGeer, Patrick T. O’Shaughnessy, E. Jane Parmley, Serge Simard, Richard J. Reid-Smith, Edward Topp, Luc Trudel, Maosheng Yao, Patrick Brassard, Anne-Marie Delort, Araceli D. Larios, Valérie Létourneau, Valérie E. Paquet, Marie-Hélène Pedneau, Émilie Pic, Brooke Thompson, Marc Veillette, Mary Thaler, Ilaria Scapino, Maria Lebeuf, Mahsa Baghdadi, Alejandra Castillo Toro, Amélia Bélanger Cayouette, Marie-Julie Dubois, Alicia F. Durocher, Sarah B. Girard, Andrea Katherín Carranza Diaz, Asmaâ Khalloufi, Samantha Leclerc, Joanie Lemieux, Manuel Pérez Maldonado, Geneviève Pilon, Colleen P. Murphy, Charly A. Notling, Daniel Ofori-Darko, Juliette Provencher, Annabelle Richer-Fortin, Nathalie Turgeon and Caroline Duchaine Show full author list Hide full author list

Antibiotics 2022, 11(7), 974; https://doi.org/10.3390/antibiotics11070974 - 19 Jul 2022

Cited by 8 | Viewed by 5980

Abstract

Antimicrobial resistance (AMR) is continuing to grow across the world. Though often thought of as a mostly public health issue, AMR is also a major agricultural and environmental problem. As such, many researchers refer to it as the preeminent One Health issue. Aerial [...] Read more.

Antimicrobial resistance (AMR) is continuing to grow across the world. Though often thought of as a mostly public health issue, AMR is also a major agricultural and environmental problem. As such, many researchers refer to it as the preeminent One Health issue. Aerial transport of antimicrobial-resistant bacteria via bioaerosols is still poorly understood. Recent work has highlighted the presence of antibiotic resistance genes in bioaerosols. Emissions of AMR bacteria and genes have been detected from various sources, including wastewater treatment plants, hospitals, and agricultural practices; however, their impacts on the broader environment are poorly understood. Contextualizing the roles of bioaerosols in the dissemination of AMR necessitates a multidisciplinary approach. Environmental factors, industrial and medical practices, as well as ecological principles influence the aerial dissemination of resistant bacteria. This article introduces an ongoing project assessing the presence and fate of AMR in bioaerosols across Canada. Its various sub-studies include the assessment of the emissions of antibiotic resistance genes from many agricultural practices, their long-distance transport, new integrative methods of assessment, and the creation of dissemination models over short and long distances. Results from sub-studies are beginning to be published. Consequently, this paper explains the background behind the development of the various sub-studies and highlight their shared aspects. Full article

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

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18 pages, 2083 KiB

Open AccessArticle

Antibiotic Resistance of Bacterial Isolates from Smallholder Poultry Droppings in the Guinea Savanna Zone of Nigeria

by Oladeji Bamidele, Abdulmojeed Yakubu, Ehase Buba Joseph and Tunde Adegoke Amole

Antibiotics 2022, 11(7), 973; https://doi.org/10.3390/antibiotics11070973 - 19 Jul 2022

Cited by 5 | Viewed by 3023

Abstract

There is a growing risk of antibiotic resistance (AR) in smallholder poultry (SP). This study, therefore, aimed to investigate AR pattern of bacterial isolates from SP in the Guinea Savanna agro-ecological zone of Nigeria. A total of 120 fresh poultry droppings were aseptically [...] Read more.

There is a growing risk of antibiotic resistance (AR) in smallholder poultry (SP). This study, therefore, aimed to investigate AR pattern of bacterial isolates from SP in the Guinea Savanna agro-ecological zone of Nigeria. A total of 120 fresh poultry droppings were aseptically collected, randomly, from two tropically adapted (FUNAAB Alpha and Noiler) and local chickens. The chickens were raised either using ethnoveterinary medicines (n = 60) or antibiotics (n = 60). Bacterial isolates were characterized and analyzed using standard protocols, and appropriate statistical tools. Compared to Pseudomonas spp. (2.5%) and Klebsiella spp. (5.8%), Salmonella spp. (57.5%) and Escherichia coli (34.2%) were the most prevalent (χ² = 96.67; p < 0.001). Prevalence of bacterial species was significantly (p = 0.024; Odds Ratio = 2.552) influenced by antibiotics usage. All four species were multi-drug resistant. In total, 30% of the isolates had a multiple AR index ≥ 0.2. Bacterial isolates from FUNAAB Alpha (58.0%) and Noiler (44.0%) were highly resistant to quinolones, while isolates from the local chickens (22.6%) were most resistant to aminoglycosides. Bacterial species isolated from FUNAAB Alpha and local chickens exhibited the lowest and highest percentage of AR, respectively. Clustering of isolates with similar antibiogram revealed inter-species dependence with possibility for inter-species gene transfer. These findings provide a background to investigate the metagenomics of local and improved chickens for AR. Full article

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16 pages, 2278 KiB

Open AccessArticle

Nisin Mutant Prevention Concentration and the Role of Subinhibitory Concentrations on Resistance Development by Diabetic Foot Staphylococci

by Margarida Costa, Cláudia Meirinhos, Eva Cunha, Diana Gomes, Marcelo Pereira, Ricardo Dias, Luís Tavares and Manuela Oliveira

Antibiotics 2022, 11(7), 972; https://doi.org/10.3390/antibiotics11070972 - 19 Jul 2022

Viewed by 2167

Abstract

The most prevalent microorganism in diabetic foot infections (DFI) is Staphylococcus aureus, an important multidrug-resistant pathogen. The antimicrobial peptide nisin is a promising compound for DFI treatment, being effective against S. aureus. However, to avoid the selection of resistant mutants, correct [...] Read more.

The most prevalent microorganism in diabetic foot infections (DFI) is Staphylococcus aureus, an important multidrug-resistant pathogen. The antimicrobial peptide nisin is a promising compound for DFI treatment, being effective against S. aureus. However, to avoid the selection of resistant mutants, correct drug therapeutic doses must be established, being also important to understand if nisin subinhibitory concentrations (subMIC) can potentiate resistant genes transfer between clinical isolates or mutations in genes associated with nisin resistance. The mutant selection window (MSW) of nisin was determined for 23 DFI S. aureus isolates; a protocol aiming to prompt vanA horizontal transfer between enterococci to clinical S. aureus was performed; and nisin subMIC effect on resistance evolution was assessed through whole-genome sequencing (WGS) applied to isolates subjected to a MEGA-plate assay. MSW ranged from 5–360 μg/mL for two isolates, from 5–540 μg/mL for three isolates, and from 5–720 μg/mL for one isolate. In the presence of nisin subMIC values, no transconjugants were obtained, indicating that nisin does not seem to promote vanA transfer. Finally, WGS analysis showed that incubation in the presence of nisin subMIC did not promote the occurrence of significant mutations in genes related to nisin resistance, supporting nisin application to DFI treatment. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Virulence – 3rd Volume)

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11 pages, 1191 KiB

Open AccessArticle

Genetic Diversity and Virulence Profile of Methicillin and Inducible Clindamycin-Resistant Staphylococcus aureus Isolates in Western Algeria

by Zahoua Mentfakh Laceb, Seydina M. Diene, Rym Lalaoui, Mabrouk Kihal, Fella Hamaidi Chergui, Jean-Marc Rolain and Linda Hadjadj

Antibiotics 2022, 11(7), 971; https://doi.org/10.3390/antibiotics11070971 - 19 Jul 2022

Cited by 1 | Viewed by 2839

Abstract

Staphylococcus aureus causes a wide range of life-threatening infections. In this study, we determined its prevalence in the hospital environment and investigated nasal carriage among healthcare workers and patients admitted to a hospital in western Algeria. A total of 550 specimens were collected. [...] Read more.

Staphylococcus aureus causes a wide range of life-threatening infections. In this study, we determined its prevalence in the hospital environment and investigated nasal carriage among healthcare workers and patients admitted to a hospital in western Algeria. A total of 550 specimens were collected. An antibiogram was performed and the genes encoding resistance to methicillin, inducible clindamycin and toxins were sought among the 92 S. aureus isolates. The spread of clones with a methicillin- and/or clindamycin-resistance phenotype between these ecosystems was studied using genomic analysis. A prevalence of 27%, 30% and 13% of S. aureus (including 2.7%, 5% and 1.25% of MRSA) in patients, healthcare workers and the hospital environment were observed, respectively. The presence of the mecA, erm, pvl and tsst-1 genes was detected in 10.9%, 17.4%, 7.6% and 18.5% of samples, respectively. Sequencing allowed us to identify seven sequence types, including three MRSA-IV-ST6, two MRSA-IV-ST80-PVL+, two MRSA-IV-ST22-TSST-1, two MRSA-V-ST5, and one MRSA-IV-ST398, as well as many virulence genes. Here, we reported that both the hospital environment and nasal carriage may be reservoirs contributing to the spread of the same pathogenic clone persisting over time. The circulation of different pathogenic clones of MRSA, MSSA, and iMLSB, as well as the emergence of at-risk ST398 clones should be monitored. Full article

(This article belongs to the Special Issue Diversity of Antimicrobial Resistance Genes in Clinical Settings)

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14 pages, 11304 KiB

Open AccessArticle

Activation of a Bacterial Mechanosensitive Channel, MscL, Underlies the Membrane Permeabilization of Dual-Targeting Antibacterial Compounds

by Robin Wray, Junmei Wang, Paul Blount and Irene Iscla

Antibiotics 2022, 11(7), 970; https://doi.org/10.3390/antibiotics11070970 - 19 Jul 2022

Cited by 5 | Viewed by 2308

Abstract

Resistance to antibiotics is a serious and worsening threat to human health worldwide, and there is an urgent need to develop new antibiotics that can avert it. One possible solution is the development of compounds that possess multiple modes of action, requiring at [...] Read more.

Resistance to antibiotics is a serious and worsening threat to human health worldwide, and there is an urgent need to develop new antibiotics that can avert it. One possible solution is the development of compounds that possess multiple modes of action, requiring at least two mutations to acquire resistance. Compound SCH-79797 both avoids resistance and has two mechanisms of action: one inhibiting the folate pathway, and a second described as “membrane permeabilization”; however, the mechanism by which membranes from bacterial cells, but not the host, are disrupted has remained mysterious. The opening of the bacterial mechanosensitive channel of large conductance, MscL, which ordinarily serves the physiological role of osmotic emergency release valves gated by hypoosmotic shock, has been previously demonstrated to affect bacterial membrane permeabilization. MscL allows the rapid permeabilization of both ions and solutes through the opening of the largest known gated pore, which has a diameter of 30 Å. We found that SCH-79797 and IRS-16, a more potent derivative, directly bind to the MscL channel and produce membrane permeabilization as a result of its activation. These findings suggest that possessing or adding an MscL-activating component to an antibiotic compound could help to lower toxicity and evade antibiotic resistance. Full article

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16 pages, 1927 KiB

Open AccessArticle

Lyophilized Human Bone Allograft as an Antibiotic Carrier: An In Vitro and In Vivo Study

by Débora C. Coraça-Huber, Stephan J. M. Steixner, Stevo Najman, Sanja Stojanovic, Ronja Finze, Denis Rimashevskiy, Dina Saginova, Mike Barbeck and Reinhard Schnettler

Antibiotics 2022, 11(7), 969; https://doi.org/10.3390/antibiotics11070969 - 19 Jul 2022

Cited by 2 | Viewed by 2713

Abstract

Background: Antibiotics delivered from implanted bone substitute materials (BSM) can potentially be used to prevent acute infections and biofilm formation, providing high concentrations of antibiotics at the surgical site without systemic toxicity. In addition, BSM should allow osteoconductivity supporting bone healing without [...] Read more.

Background: Antibiotics delivered from implanted bone substitute materials (BSM) can potentially be used to prevent acute infections and biofilm formation, providing high concentrations of antibiotics at the surgical site without systemic toxicity. In addition, BSM should allow osteoconductivity supporting bone healing without further surgery. Promising results have been achieved using lyophilized bone allografts mixed with antibiotics. Methods: In this study specially prepared human bone allografts were evaluated as an antibiotic carrier in vitro and in vivo. The efficacy of different antibiotic-impregnated bone allografts was measured by drug release tests in vitro and in vivo and bacterial susceptibility tests using four bacterial species usually responsible for implant-associated infections. Results: The loading procedures of allograft bone substitutes with antibiotics were successful. Some of the antibiotic concentrations exceeded the MIC90 for up to 7 days in vitro and for up to 72 h in vivo. The susceptibility tests showed that S. epidermidis ATCC 12228 was the most susceptible bacterial species in comparison to the other strains tested for all antibiotic substances. Vancomycin and rifampicin showed the best results against standard and patient-isolated strains in vitro. In vivo, new bone formation was comparable in all study groups including the control group without antibiotic loading. Conclusions: Human bone allografts showed the capacity to act as customized loaded antibiotic carriers to prevent acute infections and should be considered in the management of bone infections in combination with systemic antimicrobial therapy. Full article

(This article belongs to the Special Issue Strategies to Boost Antibiotic Activity)

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17 pages, 288 KiB

Open AccessArticle

Exploring Barriers to One Health Antimicrobial Stewardship in Sri Lanka: A Qualitative Study among Healthcare Professionals

by Yasodhara Deepachandi Gunasekara, Tierney Kinnison, Sanda Arunika Kottawatta, Ruwani Sagarika Kalupahana and Ayona Silva-Fletcher

Antibiotics 2022, 11(7), 968; https://doi.org/10.3390/antibiotics11070968 - 19 Jul 2022

Cited by 4 | Viewed by 2751

Abstract

Antimicrobial resistance (AMR) is a global health threat, but little is known about the perceptions regarding antimicrobials and AMR among healthcare professionals in Sri Lanka. This research aimed to take a One Health approach to explore the knowledge, attitudes and perceptions of antibiotic [...] Read more.

Antimicrobial resistance (AMR) is a global health threat, but little is known about the perceptions regarding antimicrobials and AMR among healthcare professionals in Sri Lanka. This research aimed to take a One Health approach to explore the knowledge, attitudes and perceptions of antibiotic stewardship and AMR among healthcare professionals in Sri Lanka. A qualitative study, using telephone interviews, allowing for an in-depth exploration of attitudes, beliefs and perspectives was conducted. Healthcare professionals from both the medical and veterinary sectors were included (n = 29). Interviews were conducted by an independent interviewer and were audio-recorded and transcribed. Conventional qualitative content analysis was undertaken. Four main categories were identified: (1) understanding of AMR and observing AMR, (2) barriers to antimicrobial stewardship, (3) personal factors in, and as a result of, inappropriate antibiotic usage and (4) how to tackle AMR. Healthcare professionals showed poor awareness regarding the spread of AMR and identified inappropriate prescribing behaviours by their inter- and intra-professional colleagues. Patient demands and the influence of pharmaceutical companies were factors contributing to poor prescribing behaviour. Suggestions for the future are stricter regulation of AMR control policy, effective government involvement, and awareness campaigns for healthcare professionals and the public. Full article

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

24 pages, 6663 KiB

Open AccessArticle

Synthesis, Spectroscopic, Chemical Characterizations, Anticancer Capacities against HepG-2, Antibacterial and Antioxidant Activities of Cefotaxime Metal Complexes with Ca(II), Cr(III), Zn(II), Cu(II) and Se(IV)

by Eman H. Al-Thubaiti, Samy M. El-Megharbel, Bander Albogami and Reham Z. Hamza

Antibiotics 2022, 11(7), 967; https://doi.org/10.3390/antibiotics11070967 - 19 Jul 2022

Cited by 10 | Viewed by 2712

Abstract

In this study, metal cefotaxime complexes of Ca(II), Cr(III), Cu(II), Zn(II), and Se(VI) were synthesized and characterized by elemental analysis, conductance measurements, IR, electronic spectra, magnetic measurements, ¹HNMR, and XRD, as well as by scanning electron microscopy (SEM) and transmission electron microscopy [...] Read more.

In this study, metal cefotaxime complexes of Ca(II), Cr(III), Cu(II), Zn(II), and Se(VI) were synthesized and characterized by elemental analysis, conductance measurements, IR, electronic spectra, magnetic measurements, ¹HNMR, and XRD, as well as by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The lower values for molar conductance refer to the nonelectrolyte nature of the complexes. The FTIR and ¹H-NMR spectra for the metal complexes of cefotaxime proved that the free cefotaxime antibiotic ligand acted as a monoanionic tridentate ligand through the oxygen atoms of lactam carbonyl, the carboxylate group, and the nitrogen atoms of the amino group. From the magnetic measurements and electronic spectral data, octahedral structures were proposed for the Cr(III) and Se(VI) complexes, while the Cu(II) complex had tetragonal geometry. This study aimed to investigate the effects of cefotaxime and cefotaxime metal complexes on oxidative stress using antioxidant assays including DPPH, ORAC, FARAB, and ABTS, a metal chelation assay, as well as the inhibition of the viability of cancer cells (HepG-2). Regarding the antibacterial activity, the cefotaxime metal complexes were highly effective against both Bacillus subtilis and Escherichia coli. In conclusion, the cefotaxime metal complexes exhibited highly antioxidant activities. The cefotaxime metal complexes with Zn and Se inhibited HepG-2 cellular viability. Thus, the cefotaxime metal complexes elicited promising results as potent antioxidant and anticancer agents against HepG-2, with potent antibacterial activities at a much lower concentration. Full article

(This article belongs to the Special Issue Synthetic Biology Brings New Opportunity for Antibiotics Discovery)

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12 pages, 2053 KiB

Open AccessArticle

Immunogenicity of Endolysin PlyC

by Marek Adam Harhala, Katarzyna Gembara, Daniel C. Nelson, Paulina Miernikiewicz and Krystyna Dąbrowska

Antibiotics 2022, 11(7), 966; https://doi.org/10.3390/antibiotics11070966 - 18 Jul 2022

Cited by 8 | Viewed by 2743

Abstract

Endolysins are bacteriolytic enzymes derived from bacteriophages. They represent an alternative to antibiotics, since they are not susceptible to conventional antimicrobial resistance mechanisms. Since non-human proteins are efficient inducers of specific immune responses, including the IgG response or the development of an allergic [...] Read more.

Endolysins are bacteriolytic enzymes derived from bacteriophages. They represent an alternative to antibiotics, since they are not susceptible to conventional antimicrobial resistance mechanisms. Since non-human proteins are efficient inducers of specific immune responses, including the IgG response or the development of an allergic response mediated by IgE, we evaluated the general immunogenicity of the highly active antibacterial enzyme, PlyC, in a human population and in a mouse model. The study includes the identification of molecular epitopes of PlyC. The overall assessment of potential hypersensitivity to this protein and PlyC-specific IgE testing was also conducted in mice. PlyC induced efficient IgG production in mice, and the molecular analysis revealed that PlyC-specific IgG interacted with four immunogenic regions identified within the PlyCA subunit. In humans, approximately 10% of the population demonstrated IgG reactivity to the PlyCB subunit only, which is attributed to cross-reactions since this was a naïve serum. Of note, in spite of being immunogenic, PlyC induced a normal immune response, without hypersensitivity, since both the animals challenged with PlyC and in the human population PlyC-specific IgE was not detected. Full article

(This article belongs to the Special Issue Antibiotics vs. Phage Therapy)

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37 pages, 3288 KiB

Open AccessReview

Marine Actinobacteria a New Source of Antibacterial Metabolites to Treat Acne Vulgaris Disease—A Systematic Literature Review

by Maria Clara De La Hoz-Romo, Luis Díaz and Luisa Villamil

Antibiotics 2022, 11(7), 965; https://doi.org/10.3390/antibiotics11070965 - 18 Jul 2022

Cited by 11 | Viewed by 4579

Abstract

Acne vulgaris is a multifactorial disease that remains under-explored; up to date it is known that the bacterium Cutibacterium acnes is involved in the disease occurrence, also associated with a microbial dysbiosis. Antibiotics have become a mainstay treatment generating the emergence of antibiotic-resistant [...] Read more.

Acne vulgaris is a multifactorial disease that remains under-explored; up to date it is known that the bacterium Cutibacterium acnes is involved in the disease occurrence, also associated with a microbial dysbiosis. Antibiotics have become a mainstay treatment generating the emergence of antibiotic-resistant bacteria. In addition, there are some reported side effects of alternative treatments, which indicate the need to investigate a different therapeutic approach. Natural products continue to be an excellent option, especially those extracted from actinobacteria, which represent a prominent source of metabolites with a wide range of biological activities, particularly the marine actinobacteria, which have been less studied than their terrestrial counterparts. Therefore, this systematic review aimed to identify and evaluate the potential anti-infective activity of metabolites isolated from marine actinobacteria strains against bacteria related to the development of acne vulgaris disease. It was found that there is a variety of compounds with anti-infective activity against Staphylococcus aureus and Staphylococcus epidermidis, bacteria closely related to acne vulgaris development; nevertheless, there is no report of a compound with antibacterial activity or quorum-sensing inhibition toward C. acnes, which is a surprising result. Since two of the most widely used antibiotics for the treatment of acne targeting C. acnes were obtained from actinobacteria of the genus Streptomyces, this demonstrates a great opportunity to pursue further studies in this field, considering the potential of marine actinobacteria to produce new anti-infective compounds. Full article

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

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14 pages, 679 KiB

Open AccessArticle

Should We Consider Them as a Threat? Antimicrobial Resistance, Virulence Potential and Genetic Diversity of Campylobacter spp. Isolated from Varsovian Dogs

by Małgorzata Murawska, Monika Sypecka, Justyna Bartosik, Ewelina Kwiecień, Magdalena Rzewuska and Agnieszka Sałamaszyńska-Guz

Antibiotics 2022, 11(7), 964; https://doi.org/10.3390/antibiotics11070964 - 18 Jul 2022

Cited by 2 | Viewed by 2016

Abstract

Campylobacteriosis seems to be a growing problem worldwide. Apart from the most common sources of numerous Campylobacter species, such as poultry and other farm animals, dogs may be an underrated reservoir of this pathogen. Our goal was to establish the frequency of occurrence, [...] Read more.

Campylobacteriosis seems to be a growing problem worldwide. Apart from the most common sources of numerous Campylobacter species, such as poultry and other farm animals, dogs may be an underrated reservoir of this pathogen. Our goal was to establish the frequency of occurrence, antimicrobial resistance, and detection of chosen virulence factor genes in genomes of canine Campylobacter isolates. Campylobacter isolates frequency in dogs from shelters, and private origin was 13%. All of the tested virulence factor genes were found in 28 of 31 isolates. We determined high resistance levels to the ciprofloxacin and ampicillin and moderate tetracycline resistance. For C. jejuni shelter isolates, genetic diversity was also determined using PFGE. Our results indicate that dogs may be the reservoir of potentially diverse, potentially virulent, and antimicrobial-resistant Campylobacter strains. Full article

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

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16 pages, 2117 KiB

Open AccessArticle

Effect of Intramammary Dry Cow Antimicrobial Treatment on Fresh Cow’s Milk Microbiota in California Commercial Dairies

by Carl Basbas, Sharif Aly, Emmanuel Okello, Betsy M. Karle, Terry Lehenbauer, Deniece Williams, Erika Ganda, Martin Wiedmann and Richard V. Pereira

Antibiotics 2022, 11(7), 963; https://doi.org/10.3390/antibiotics11070963 - 18 Jul 2022

Cited by 2 | Viewed by 3784

Abstract

This study used 16S rRNA sequencing to evaluate the effects of dry cow antimicrobial therapy on the udder milk microbiota by comparing the microbial populations in milk at dry-off (DRY) (~60 days before calving) and post-partum (FRESH) (4–11 days after calving) from cows [...] Read more.

This study used 16S rRNA sequencing to evaluate the effects of dry cow antimicrobial therapy on the udder milk microbiota by comparing the microbial populations in milk at dry-off (DRY) (~60 days before calving) and post-partum (FRESH) (4–11 days after calving) from cows receiving an intramammary antibiotic infusion prior to dry-off (IMT) and cows that did not receive treatment (CTL). Milk was collected from 23 cows from the IMT group and 27 cows from the CTL group. IMT and DRY samples had a greater correlation with the genera Brevibacterium and Amaricoccus, and the family Micrococcaceae, when compared to IMT and FRESH samples. CTL group samples collected at DRY had a greater correlation with the genera Akkermansia and Syntrophus, when compared to FRESH samples; no bacterial taxa were observed to have a significant correlation with FRESH samples in the CTL group. DRY samples collected from the CTL group had a greater correlation with the genus Mogibacterium when compared to IMT and CTL samples. For DRY samples collected from the IMT group, a greater correlation with the genus Alkalibacterium when compared to DRY and CTL samples, was observed. The lack of a correlation for FRESH samples between the CTL and IMT treatment groups indicated that intramammary antimicrobial dry cow therapy had no significant effect on the udder milk microbiota post-partum. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Livestock)

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15 pages, 1256 KiB

Open AccessArticle

Co-Administration of Lactulose Crystals with Amoxicillin Followed by Prolonged Lactulose Treatment Promotes Recovery of the Human Gut Microbiome In Vitro

by Cindy Duysburgh, Pieter Van den Abbeele, Dennis Franckenstein, Martin Westphal, Angelika Kuchinka-Koch and Massimo Marzorati

Antibiotics 2022, 11(7), 962; https://doi.org/10.3390/antibiotics11070962 - 18 Jul 2022

Cited by 4 | Viewed by 2315

Abstract

The validated SHIME model was used to assess the effect of repeated administration of two different lactulose dosages (5 g/d and 10 g/d) on the human gut microbiome during and following amoxicillin–clavulanic acid treatment. First, antibiotic treatment strongly decreased Bifidobacteriaceae levels from 54.4% [...] Read more.

The validated SHIME model was used to assess the effect of repeated administration of two different lactulose dosages (5 g/d and 10 g/d) on the human gut microbiome during and following amoxicillin–clavulanic acid treatment. First, antibiotic treatment strongly decreased Bifidobacteriaceae levels from 54.4% to 0.6% and from 23.8% to 2.3% in the simulated proximal and distal colon, respectively, coinciding with a marked reduction in butyrate concentrations. Treatment with lactulose enhanced acetate and lactate levels during antibiotic treatment, likely through lactulose fermentation by Lachnospiraceae and Lactobacillaceae. One week after cessation of antibiotic treatment, Bifidobacteriaceae levels re-increased to 20.4% and 7.6% in the proximal and distal colon of the 5 g lactulose/d co-administered unit, as compared with 1.0% and 2.2% in the antibiotic-treated unit, and were even further stimulated upon extension of lactulose administration. Marked butyrogenic effects were observed upon prolonged lactulose supplementation, suggesting the establishment of cross-feeding interactions between Bifidobacteriaceae and butyrate producers. Furthermore, a limited Enterobacteriaceae outgrowth following antibiotic treatment was observed upon dosing with 10 g lactulose/d, indicating inhibition of pathogenic colonization by lactulose following antibiotic therapy. Overall, lactulose seems to be an interesting candidate for limiting the detrimental effects of amoxicillin–clavulanic acid on the human gut microbiome, though further studies are warranted to confirm these findings. Full article

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13 pages, 791 KiB

Open AccessArticle

Resveratrol Reverts Tolerance and Restores Susceptibility to Chlorhexidine and Benzalkonium in Gram-Negative Bacteria, Gram-Positive Bacteria and Yeasts

by Antonella Migliaccio, Maria Stabile, Maria Bagattini, Maria Triassi, Rita Berisio, Eliana De Gregorio and Raffaele Zarrilli

Antibiotics 2022, 11(7), 961; https://doi.org/10.3390/antibiotics11070961 - 18 Jul 2022

Cited by 6 | Viewed by 2132

Abstract

The spread of microorganisms causing health-care associated infection (HAI) is contributed to by their intrinsic tolerance to a variety of biocides, used as antiseptics or disinfectants. The natural monomeric stilbenoid resveratrol (RV) is able to modulate the susceptibility to the chlorhexidine digluconate (CHX) [...] Read more.

The spread of microorganisms causing health-care associated infection (HAI) is contributed to by their intrinsic tolerance to a variety of biocides, used as antiseptics or disinfectants. The natural monomeric stilbenoid resveratrol (RV) is able to modulate the susceptibility to the chlorhexidine digluconate (CHX) biocide in Acinetobacter baumannii. In this study, a panel of reference strains and clinical isolates of Gram-negative bacteria, Gram-positive bacteria and yeasts were analyzed for susceptibility to CHX and benzalkonium chloride (BZK) and found to be tolerant to one or both biocides. The carbonyl cyanide m-chlorophenylhydrazine protonophore (CCCP) efflux pump inhibitor reduced the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CHX and BZK in the majority of strains. RV reduced dose-dependently MIC and MBC of CHX and BZK biocides when used as single agents or in combination in all analyzed strains, but not CHX MIC and MBC in Pseudomonas aeruginosa, Candida albicans, Klebsiella pneumoniae, Stenotrophomonas maltophilia and Burkholderia spp. strains. In conclusion, RV reverts tolerance and restores susceptibility to CHX and BZK in the majority of microorganisms responsible for HAI. These results indicates that the combination of RV, CHX and BZK may represent a useful strategy to maintain susceptibility to biocides in several nosocomial pathogens. Full article

(This article belongs to the Special Issue Surveillance for Antimicrobial Resistance and Healthcare-Associated Infections in Hospital, 2nd Edition)

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11 pages, 1707 KiB

Open AccessArticle

In Vitro Growth-Inhibitory Synergistic Effect of Zinc Pyrithione in Combination with Gentamicin against Bacterial Skin Pathogens of Livestock

by Lucie Mala, Klara Lalouckova, Eva Skrivanova, Marketa Houdkova, Marie Strakova and Ladislav Kokoska

Antibiotics 2022, 11(7), 960; https://doi.org/10.3390/antibiotics11070960 - 17 Jul 2022

Viewed by 2594

Abstract

Bacterial skin diseases of livestock could be a serious global threat, especially in association with overcoming bacterial resistance. Combinatory action of antimicrobial agents proves to be an effective strategy to overcome the problem of increasing antibiotic resistance of microorganisms. In this study, the [...] Read more.

Bacterial skin diseases of livestock could be a serious global threat, especially in association with overcoming bacterial resistance. Combinatory action of antimicrobial agents proves to be an effective strategy to overcome the problem of increasing antibiotic resistance of microorganisms. In this study, the in vitro combined effect of zinc pyrithione with gentamicin against bacterial skin pathogens of livestock (Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus dysgalactiae) was evaluated according to the sum of fractional inhibitory concentration indices (FICI) obtained by checkerboard method. The results showed that a combination of zinc pyrithione with gentamicin produced a strong synergistic effect (p < 0.001) against all tested streptococcal strains (with FICI values ranging from 0.20 to 0.42). Compared to that, only three out of eight S. aureus strains were highly susceptible to the combination of antimicrobial agents at single concentration (0.25 µg/mL) of zinc pyrithione with range of FICI 0.35–0.43. These findings suggest that interference between agents tested in this study can be used for the development of future veterinary pharmaceutical preparations for the treatment of bacterial skin infections of livestock. Full article

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

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10 pages, 714 KiB

Open AccessArticle

Combatting Planktonic and Biofilm Populations of Carbapenem-Resistant Acinetobacter baumannii with Polymyxin-Based Combinations

by Marisol Wences, Elliot R. Wolf, Cindy Li, Nidhi Singh, Nene Bah, Xing Tan, Yanqin Huang and Zackery P. Bulman

Antibiotics 2022, 11(7), 959; https://doi.org/10.3390/antibiotics11070959 - 16 Jul 2022

Cited by 8 | Viewed by 2220

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) can cause serious infections that are associated with high mortality rates. During the course of an infection, many CRAB isolates are able to form biofilms, which are recalcitrant to several antibiotics and can be difficult to treat. Polymyxin-based regimens [...] Read more.

Carbapenem-resistant Acinetobacter baumannii (CRAB) can cause serious infections that are associated with high mortality rates. During the course of an infection, many CRAB isolates are able to form biofilms, which are recalcitrant to several antibiotics and can be difficult to treat. Polymyxin-based regimens are a first-line treatment option for CRAB infections, but they have not been optimized against both planktonic and biofilm phases of growth. The objective of this study was to identify polymyxin-based combinations that are active against planktonic and biofilm populations of CRAB. Four CRAB isolates (meropenem MICs: 8–256 mg/L) capable of forming biofilms were used in each experiment. The activities of polymyxin B alone and in combination with ampicillin/sulbactam, meropenem, minocycline, and rifampin were assessed using time-kill assays, with the CRAB isolates grown in planktonic and biofilm phases. Viable colony counts were used to detect the bactericidal activity and synergy of the antibiotic combinations. Against the planktonic populations, polymyxin B combined with meropenem, minocycline, ampicillin/sulbactam, and rifampin caused 3.78, −0.15, 4.38, and 3.23 mean log₁₀ CFU/mL reductions against all isolates at 24 h, respectively. Polymyxin B combined with meropenem, ampicillin/sulbactam, or rifampin was synergistic against 75–100% (3/4 or 4/4) of CRAB isolates. Against biofilms, polymyxin B combined with meropenem, minocycline, ampicillin/sulbactam, and rifampin caused 1.86, 1.01, 0.66, and 3.55 mean log₁₀ CFU/mL reductions against all isolates at 24 h, respectively. Only the combination of polymyxin B and rifampin retained bactericidal activity or synergy against any of the isolates when grown as biofilms (50% of isolates). The combination of polymyxin B and rifampin may be promising for CRAB infections that have planktonic and biofilm populations present. Full article

(This article belongs to the Special Issue Novel Antimicrobial Strategies to Combat Biofilm Infections)

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12 pages, 1620 KiB

Open AccessArticle

Pharmacokinetics and Safety of Doripenem in Healthy Chinese Subjects and Monte Carlo Dosing Simulations

by Yu Wang, Xiaofen Liu, Kun Li, Yaxin Fan, Jicheng Yu, Hailan Wu, Yi Li, Xiaojie Wu, Beining Guo, Xin Li, Jiali Hu, Jufang Wu, Guoying Cao and Jing Zhang

Antibiotics 2022, 11(7), 958; https://doi.org/10.3390/antibiotics11070958 - 16 Jul 2022

Cited by 1 | Viewed by 2128

Abstract

The aim of this study was to investigate the pharmacokinetics (PK) of doripenem in healthy Chinese subjects and evaluate the optimal dosage regimens of doripenem. A randomized, single-dose, three-period, self-crossover controlled extended-infusion clinical trial was conducted with 12 healthy Chinese subjects. Plasma and [...] Read more.

The aim of this study was to investigate the pharmacokinetics (PK) of doripenem in healthy Chinese subjects and evaluate the optimal dosage regimens of doripenem. A randomized, single-dose, three-period, self-crossover controlled extended-infusion clinical trial was conducted with 12 healthy Chinese subjects. Plasma and urine samples were collected to determine doripenem concentrations. Non-compartmental and population PK analysis were performed to characterize the PK of doripenem. The Monte Carlo simulation was employed to optimize dosing regimens based on the probability of target attainment of doripenem against pathogens with different minimum inhibitory concentrations (MIC). All 12 healthy Chinese subjects completed the study, and the doripenem was well tolerated. The study showed linearity relationships in the peak plasma concentration and the area under the concentration-time curve after intravenous infusion of doripenem from 0.25 g to 1.0 g. The cumulative urinary recovery rate of doripenem was 68.1–72.0% within 24 h. PPK modeling showed a two-compartmental model, with first-order elimination presenting the best fit for doripenem PK. Monte Carlo simulation results showed that 1.0 g q12h or 0.5 g q8h was an optimal regimen for pathogens susceptible to doripenem (MIC ≤ 1 mg/L); while high dose and extended infusion (1 g, q8h, 4 h infusion) was proposed for unsusceptible pathogens (2 ≤ MIC ≤ 8 mg/L). In the dose range of 0.25 to 1.0 g, doripenem showed linear pharmacokinetics. Doripenem at 1.0 g with a prolonged infusion time of 4 h was predicted to be effective against pathogens with MICs as high as 8 mg/L. Full article

(This article belongs to the Section Pharmacokinetics and Pharmacodynamics of Drugs)

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12 pages, 1779 KiB

Open AccessArticle

Trends of Fixed-Dose Combination Antibiotic Consumption in Hospitals in China: Analysis of Data from the Center for Antibacterial Surveillance, 2013–2019

by Haishaerjiang Wushouer, Lin Hu, Yue Zhou, Yaoyao Yang, Kexin Du, Yanping Deng, Qing Yan, Xiaoqiang Yang, Zhidong Chen, Bo Zheng, Xiaodong Guan and Luwen Shi

Antibiotics 2022, 11(7), 957; https://doi.org/10.3390/antibiotics11070957 - 15 Jul 2022

Cited by 3 | Viewed by 2628

Abstract

Background: Fixed-dose combination (FDC) antibiotics can be clinically inappropriate and are concerning with regards to antimicrobial resistance, with little usage data available in low- and middle-income countries. Methods: Based on retrospective data from the Center for Antibacterial Surveillance, we investigated the consumption of [...] Read more.

Background: Fixed-dose combination (FDC) antibiotics can be clinically inappropriate and are concerning with regards to antimicrobial resistance, with little usage data available in low- and middle-income countries. Methods: Based on retrospective data from the Center for Antibacterial Surveillance, we investigated the consumption of FDC antibiotics in hospital inpatient settings in China from 1 January 2013 to 31 December 2019. The metric for assessing antibiotic consumption was the number of daily defined doses per 100 bed days (DDD/100BDs). FDC antibiotics were classified according to their composition and the Access, Watch, Reserve (AWaRe) classification of the World Health Organization. Results: A total of 24 FDC antibiotics were identified, the consumption of which increased sharply from 8.5 DDD/100BDs in 2013 to 10.2 DDD/100BDs in 2019 (p < 0.05) despite the reduction in the total antibiotic consumption in these hospitals. The increase was mainly driven by FDC antibiotics in the Not Recommended group of the AWaRe classification, whose consumption accounted for 63.0% (6.4 DDD/100BDs) of the overall FDC antibiotic consumption in 2019, while the consumption of FDC antibiotics in the Access group only accounted for 13.5% (1.4 DDD/100BDs). Conclusion: FDC antibiotic consumption significantly increased during the study period and accounted for a substantial proportion of all systemic antibiotic usage in hospitals in China. FDC antibiotics in the Not Recommended group were most frequently consumed, which raises concerns about the appropriateness of FDC antibiotic use. Full article

(This article belongs to the Special Issue Appropriateness of Antibiotics in China - 2nd Volume)

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14 pages, 924 KiB

Open AccessArticle

Antibacterial and Antifungal Management in Relation to the Clinical Characteristics of Elderly Patients with Infective Endocarditis: A Retrospective Analysis

by Camelia Melania Budea, Marius Pricop, Felix Bratosin, Iulia Bogdan, Miriam Saenger, Ovidiu Ciorica, Laurentiu Braescu, Eugenia Maria Domuta, Mirela Loredana Grigoras, Cosmin Citu, Mircea Mihai Diaconu and Iosif Marincu

Antibiotics 2022, 11(7), 956; https://doi.org/10.3390/antibiotics11070956 - 15 Jul 2022

Cited by 6 | Viewed by 2916

Abstract

Infective endocarditis (IE) is increasingly prevalent in the elderly, particularly due to the rising frequency of invasive procedures and intracardiac devices placed on these individuals. Several investigations have highlighted the unique clinical and echocardiographic characteristics, the microorganisms implicated, and the prognosis of IE [...] Read more.

Infective endocarditis (IE) is increasingly prevalent in the elderly, particularly due to the rising frequency of invasive procedures and intracardiac devices placed on these individuals. Several investigations have highlighted the unique clinical and echocardiographic characteristics, the microorganisms implicated, and the prognosis of IE in the elderly. In addition, the old population seems to be fairly diverse, ranging from healthy individuals with no medical history to patients with many ailments and those who are immobile. Furthermore, the therapy of IE in this group has not been well investigated, and worldwide recommendations do not propose tailoring the treatment approach to the patient’s functional state and comorbid conditions. A multicenter research study was designed as a retrospective study of hospitalized patients with infective endocarditis, aiming to examine the characteristics of elderly patients over 65 years old with infective endocarditis in relation to the antibiotic and antifungal treatments administered, as well as to quantify the incidence of treatment resistance, adverse effects, and mortality in comparison to patients younger than 65. Based on a convenience sampling method, we included in the analysis a total of 78 patients younger than 65 and 131 patients older than 65 years. A total of 140 patients had endocarditis on native valves and 69 patients had endocarditis on prosthetic valves. A significantly higher proportion of elderly patients had signs of heart failure on admission, and the mortality rate was significantly higher in the elderly population. A majority of infections had a vascular cause, followed by dental, maxillo-facial, and ENT interventions. The most common complications of IE were systemic sepsis (48.1% of patients older than 65 years vs. 30.8% in the younger group). The most frequent bacterium involved was Staphylococcus aureus, followed by Streptococcus spp. in a total of more than 50% of all patients. The most commonly used antibiotics were cephalosporins in 33.5% of cases, followed by penicillin in 31.2% and glycopeptides in 28.7%, while Fluconazole was the initial option of treatment for fungal endocarditis in 24.9% of cases. Heart failure at admission (OR = 4.07), the development of septic shock (OR = 6.19), treatment nephrotoxicity (OR = 3.14), severe treatment complications (OR = 4.65), and antibiotic resistance (OR = 3.24) were significant independent risk factors for mortality in the elderly patients. Even though therapeutic management was initiated sooner in the older patients, the associated complications and mortality rate remained significantly greater than those in the patients under 65 years old. Full article

(This article belongs to the Special Issue Combating Antibiotic Resistance with Precision Medicine: The Value of Diagnostic)

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10 pages, 281 KiB

Open AccessArticle

Whole-Genome Sequencing of ST2 A. baumannii Causing Bloodstream Infections in COVID-19 Patients

by Sabrina Cherubini, Mariagrazia Perilli, Bernardetta Segatore, Paolo Fazii, Giustino Parruti, Antonella Frattari, Gianfranco Amicosante and Alessandra Piccirilli

Antibiotics 2022, 11(7), 955; https://doi.org/10.3390/antibiotics11070955 - 15 Jul 2022

Cited by 19 | Viewed by 2452

Abstract

A total of 43 A. baumannii strains, isolated from 43 patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and by bacterial sepsis, were analyzed by antimicrobial susceptibility testing. All strains were resistant to almost three different classes of antibiotics, including carbapenems [...] Read more.

A total of 43 A. baumannii strains, isolated from 43 patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and by bacterial sepsis, were analyzed by antimicrobial susceptibility testing. All strains were resistant to almost three different classes of antibiotics, including carbapenems and colistin. The whole-genome sequencing (WGS) of eight selected A. baumannii isolates showed the presence of different insertion sequences (ISs), such as ISAba13, ISAba26, IS26, ISVsa3, ISEc29, IS6100 and IS17, giving to A. baumannii a high ability to capture and mobilize antibiotic resistance genes. Resistance to carbapenems is mainly mediated by the presence of OXA-23, OXA-66 and OXA-82 oxacillinases belonging to OXA-51-like enzymes. The presence of AmpC cephalosporinase, ADC-25, was identified in all A. baumannii. The pathogenicity of A. baumannii was exacerbated by the presence of several virulence factors. The multi-locus sequence typing (MLST) analysis showed that all strains belong to sequence type 2 (ST) international clone. Full article

(This article belongs to the Special Issue Bacterial Pathogenesis and Antimicrobial Strategy)

14 pages, 575 KiB

Open AccessArticle

Effectiveness of Intramammary Antibiotics, Internal Teat Sealants, or Both at Dry-Off in Dairy Cows: Clinical Mastitis and Culling Outcomes

by Sharif S. Aly, Emmanuel Okello, Wagdy R. ElAshmawy, Deniece R. Williams, Randall J. Anderson, Paul Rossitto, Karen Tonooka, Kathy Glenn, Betsy Karle and Terry W. Lehenbauer

Antibiotics 2022, 11(7), 954; https://doi.org/10.3390/antibiotics11070954 - 15 Jul 2022

Cited by 6 | Viewed by 2517

Abstract

Intramammary antibiotic (AB) and internal teat sealants (TS) infusion at dry-off have been used to prevent intramammary infections (IMI) in dairy cows during the dry period and reduce the risk of mastitis during the dry period and subsequent lactation. A randomized clinal trial [...] Read more.

Intramammary antibiotic (AB) and internal teat sealants (TS) infusion at dry-off have been used to prevent intramammary infections (IMI) in dairy cows during the dry period and reduce the risk of mastitis during the dry period and subsequent lactation. A randomized clinal trial was completed on eight California dairy herds to estimate the effects of different dry cow therapies (AB, TS, AB + TS or None) on clinical mastitis and culling. A total of 1273 cows were randomized to one of the four treatment groups over summer and winter seasons. For each enrolled cow, microbiological testing was done on quarter milk samples collected from the first detection of clinical mastitis within the first 150 days in milk (DIM) in the subsequent lactation. Statistical analysis was done using generalized linear mixed models. There were no significant differences in the odds of clinical mastitis or culling between cows treated with AB, TS, or AB + TS compared to the controls. Dry cow therapy with AB and/or TS had no statistically significant effect on clinical mastitis and cow culling during the first 150 DIM. Full article

(This article belongs to the Special Issue Antimicrobial Stewardship in Livestock)

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Open AccessArticle

Antibiotic Exposure during the Preceding Six Months Is Related to Intestinal ESBL-Producing Enterobacteriaceae Carriage in the Elderly

by Man Zhang, Xiaohua Qin, Baixing Ding, Zhen Shen, Zike Sheng, Shi Wu, Yang Yang, Xiaogang Xu, Fupin Hu, Xiaoqin Wang, Yu Zhang and Minggui Wang

Antibiotics 2022, 11(7), 953; https://doi.org/10.3390/antibiotics11070953 - 15 Jul 2022

Cited by 3 | Viewed by 1688

Abstract

Intestinal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE carriage) poses a health risk to the elderly. It was aimed to study the prevalence and the risk factors of intestinal ESBL-PE carriage in the elderly. An observational study of a 921-elderly cohort was examined at [...] Read more.

Intestinal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE carriage) poses a health risk to the elderly. It was aimed to study the prevalence and the risk factors of intestinal ESBL-PE carriage in the elderly. An observational study of a 921-elderly cohort was examined at health checkup for intestinal ESBL-PE carriage at a tertiary medical center in Shanghai. The prevalence and risk factors of intestinal ESBL-PE carriage, especially antimicrobial use in the preceding 9 months, were studied. The prevalence of intestinal ESBL-PE carriage was 53.3% (491/921) in community-dwelling elderly people. A total of 542 ESBL-producing isolates, including E. coli (n = 484) and K. pneumoniae (n = 58), were obtained. On genotyping, the CTX-M-9 ESBL was the most prevalent for 66.0% (358/542) of all isolates. Multivariate analysis showed that antibiotic exposure, age (61–70 years), and nursing home residence were independent risk factors of the ESBL-PE carriage. The analysis on the monthly use of antimicrobials showed that antibiotic exposure during the 6 months prior to sample collection contributed to the high prevalence of ESBL-PE carriage. A single exposure to an antimicrobial increased the risk of the carriage significantly, and the risk increased with the frequency of antimicrobial exposure (RR, 1.825 to 5.255). Prior use of second or third generation cephalosporins, fluoroquinolones, and macrolides increased the risk of the carriage. The results of this study indicate the importance of using antimicrobials judiciously in clinical settings to reduce antimicrobial resistance. Further studies with multiple center surveillance and with comparison of ESBL-PE carriage in the elderly and in the general population simultaneously are needed. Full article

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

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Antibiotics, Volume 11, Issue 7 (July 2022) – 153 articles

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