Antibiotics

13 pages, 1998 KiB

Open AccessArticle

Prevalence of Virulence Genes and Antimicrobial Resistances in E. coli Associated with Neonatal Diarrhea, Postweaning Diarrhea, and Edema Disease in Pigs from Austria

by René Renzhammer, Igor Loncaric, Franz-Ferdinand Roch, Beate Pinior, Annemarie Käsbohrer, Joachim Spergser, Andrea Ladinig and Christine Unterweger

Antibiotics 2020, 9(4), 208; https://doi.org/10.3390/antibiotics9040208 - 24 Apr 2020

Cited by 23 | Viewed by 4756

Abstract

Increasing numbers of multi-resistant Escherichia (E.) coli from clinical specimens emphasize the importance of monitoring of their resistance profiles for proper treatment. Furthermore, knowledge on the presence of virulence associated genes in E. coli isolates from European swine stocks is scarce. Consequently, a [...] Read more.

Increasing numbers of multi-resistant Escherichia (E.) coli from clinical specimens emphasize the importance of monitoring of their resistance profiles for proper treatment. Furthermore, knowledge on the presence of virulence associated genes in E. coli isolates from European swine stocks is scarce. Consequently, a total of 694 E. coli isolated between 2016 and 2018 from diarrheic piglets of Austrian swine herds were investigated. The isolates were tested for their susceptibility to twelve antibiotics using agar disk diffusion test and for the presence of 22 virulence associated genes via PCR. Overall, 71.9, 67.7, and 49.5% of all isolates were resistant to ampicillin, tetracycline, and trimethoprim-sulfamethoxazole, while resistance levels to gentamicin and fosfomycin were 7.7 and 2.0%, respectively. Resistance frequency to ciprofloxacin was higher than in previous studies. Isolates were more likely to be resistant to ampicillin if they were also resistant to ciprofloxacin. No isolate was resistant to meropenem or amikacin. Virulence genes were detected more frequently in isolates expressing hemolytic activity on blood agar plates. The detection rate of faeG was increased in fimH negative isolates. We assume, that hemolytic activity and absence of fimH could be considered as potential indicators for the virulence of E. coli in piglets. Full article

(This article belongs to the Special Issue Pathogenic Escherichia coli: Infections and Therapies)

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12 pages, 264 KiB

Open AccessArticle

Biological Activities of Essential Oils from Leaves of Paramignya trimera (Oliv.) Guillaum and Limnocitrus littoralis (Miq.) Swingle

by Nhan Trong Le, Duc Viet Ho, Tuan Quoc Doan, Anh Tuan Le, Ain Raal, Donatella Usai, Giuseppina Sanna, Antonio Carta, Paola Rappelli, Nicia Diaz, Piero Cappuccinelli, Stefania Zanetti, Hoai Thi Nguyen and Matthew Gavino Donadu

Antibiotics 2020, 9(4), 207; https://doi.org/10.3390/antibiotics9040207 - 24 Apr 2020

Cited by 43 | Viewed by 4646

Abstract

The present study aimed to determine the bioactivities of essential oils extracted from the leaves of Paramignya trimera and Limnocitrus littoralis, including cytotoxicity, antiviral, antibacterial, antimycotic, and antitrichomonas effects. Herein, it was indicated that P. trimera and L. littoralis oils showed no [...] Read more.

The present study aimed to determine the bioactivities of essential oils extracted from the leaves of Paramignya trimera and Limnocitrus littoralis, including cytotoxicity, antiviral, antibacterial, antimycotic, and antitrichomonas effects. Herein, it was indicated that P. trimera and L. littoralis oils showed no cytotoxicity on normal cells, namely MT-4, BHK-21, MDBK, and Vero-76. P. trimera oil (i) exhibited the strongest inhibition against Staphylococcus aureus with MIC and MLC values of 2% (v/v); (ii) showed MIC and MLC values of 8% (v/v) in Candida parapsilosis; and (iii) in the remaining strains, showed MIC and MLC values greater than or equal to 16% (v/v). On the other hand, L. littoralis oil (i) displayed the strongest inhibition against Candida tropicalis and Candida parapsilosis with 2% (v/v) of MIC and MLC; and (ii) in the remaining strains, possessed MIC and MLC greater than or equal to 16% (v/v). In addition, antitrichomonas activities of the oils were undertaken, showing IC₅₀, IC₉₀, MLC values, respectively, at 0.016%, 0.03%, and 0.06% (v/v) from P. trimera, and 0.03%, 0.06%, 0.12% (v/v) from L. littoralis, after 48 h of incubation. The oils were completely ineffective against ssRNA+ (HIV-1, YFV, BVDV, Sb-1, CV-B4), ssRNA- (RSV, VSV), dsRNA (Reo-1), and dsDNA (HSV-1, VV) viruses. This is the first report describing the cytotoxicity, antiviral, antibacterial, antimycotic, and antitrichomonas activities of the essential oils of P. trimera and L. littoralis. Full article

(This article belongs to the Special Issue Antibacterial and Antibiofilm Activity of Plant Extracts)

3 pages, 171 KiB

Open AccessEditorial

Stewardship of Antibiotics for Multidrug-Resistant Gram-Negative Bacteria

by Daniele Roberto Giacobbe and Ilias Karaiskos

Antibiotics 2020, 9(4), 206; https://doi.org/10.3390/antibiotics9040206 - 24 Apr 2020

Cited by 3 | Viewed by 2384

Abstract

Nearly one year ago, we wrote the following introductory note for authors willing to submit their paper to our Special Issue entitled “Stewardship of Antibiotics for Multidrug-Resistant Gram-Negative Bacteria” in Antibiotics: [...] Full article

(This article belongs to the Special Issue Stewardship of Antibiotics for Multidrug-Resistant Gram-Negative Bacteria)

22 pages, 343 KiB

Open AccessReview

Acinetobacter baumannii Resistance: A Real Challenge for Clinicians

by Rosalino Vázquez-López, Sandra Georgina Solano-Gálvez, Juan José Juárez Vignon-Whaley, Jorge Andrés Abello Vaamonde, Luis Andrés Padró Alonzo, Andrés Rivera Reséndiz, Mauricio Muleiro Álvarez, Eunice Nabil Vega López, Giorgio Franyuti-Kelly, Diego Abelardo Álvarez-Hernández, Valentina Moncaleano Guzmán, Jorge Ernesto Juárez Bañuelos, José Marcos Felix, Juan Antonio González Barrios and Tomás Barrientos Fortes

Antibiotics 2020, 9(4), 205; https://doi.org/10.3390/antibiotics9040205 - 23 Apr 2020

Cited by 173 | Viewed by 16300

Abstract

Acinetobacter baumannii (named in honor of the American bacteriologists Paul and Linda Baumann) is a Gram-negative, multidrug-resistant (MDR) pathogen that causes nosocomial infections, especially in intensive care units (ICUs) and immunocompromised patients with central venous catheters. A. baumannii has developed a broad spectrum [...] Read more.

Acinetobacter baumannii (named in honor of the American bacteriologists Paul and Linda Baumann) is a Gram-negative, multidrug-resistant (MDR) pathogen that causes nosocomial infections, especially in intensive care units (ICUs) and immunocompromised patients with central venous catheters. A. baumannii has developed a broad spectrum of antimicrobial resistance, associated with a higher mortality rate among infected patients compared with other non-baumannii species. In terms of clinical impact, resistant strains are associated with increases in both in-hospital length of stay and mortality. A. baumannii can cause a variety of infections; most involve the respiratory tract, especially ventilator-associated pneumonia, but bacteremia and skin wound infections have also been reported, the latter of which has been prominently observed in the context of war-related trauma. Cases of meningitis associated with A. baumannii have been documented. The most common risk factor for the acquisition of MDR A baumannii is previous antibiotic use, following by mechanical ventilation, length of ICU/hospital stay, severity of illness, and use of medical devices. Current efforts focus on addressing all the antimicrobial resistance mechanisms described in A. baumannii, with the objective of identifying the most promising therapeutic scheme. Bacteriophage- and artilysin-based therapeutic approaches have been described as effective, but further research into their clinical use is required Full article

(This article belongs to the Special Issue Bacterial Metabolic Reprograming and Antibiotic Susceptibility during Infection)

11 pages, 510 KiB

Open AccessArticle

Development of Antimicrobial Stewardship Programmes in Low and Middle-Income Countries: A Mixed-Methods Study in Nigerian Hospitals

by Eneyi E. Kpokiri, David G. Taylor and Felicity J. Smith

Antibiotics 2020, 9(4), 204; https://doi.org/10.3390/antibiotics9040204 - 23 Apr 2020

Cited by 27 | Viewed by 4923

Abstract

Antimicrobial resistance (AMR) is a major concern facing global health today, with the greatest impact in developing countries where the burden of infectious diseases is much higher. The inappropriate prescribing and use of antibiotics are contributory factors to increasing antibiotic resistance. Antimicrobial stewardship [...] Read more.

Antimicrobial resistance (AMR) is a major concern facing global health today, with the greatest impact in developing countries where the burden of infectious diseases is much higher. The inappropriate prescribing and use of antibiotics are contributory factors to increasing antibiotic resistance. Antimicrobial stewardship programmes (AMS) are implemented to optimise use and promote behavioural change in the use of antimicrobials. AMS programmes have been widely employed and proven to improve antibiotic use in many high-income settings. However, strategies to contain antimicrobial resistance have yet to be successfully implemented in low-resource settings. A recent toolkit for AMS in low- and middle-income countries by the World Health Organisation (WHO) recognizes the importance of local context in the development of AMS programmes. This study employed a bottom-up approach to identify important local determinants of antimicrobial prescribing practices in a low-middle income setting, to inform the development of a local AMS programme. Analysis of prescribing practices and interviews with prescribers highlighted priorities for AMS, which include increasing awareness of antibiotic resistance, development and maintenance of guidelines for antibiotic use, monitoring and surveillance of antibiotic use, ensuring the quality of low-cost generic medicines, and improved laboratory services. The application of an established theoretical model for behaviour change guided the development of specific proposals for AMS. Finally, in a consultation with stakeholders, the feasibility of the plan was explored along with strategies for its implementation. This project provides an example of the design, and proposal for implementation of an AMS plan to improve antibiotic use in hospitals in low-middle income settings. Full article

(This article belongs to the Special Issue Antibiotics Use and Antimicrobial Stewardship in Remote Areas – an One Health Perspective)

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13 pages, 389 KiB

Open AccessArticle

Risk Factors of Initial Inappropriate Antibiotic Therapy and the Impacts on Outcomes of Neonates with Gram-Negative Bacteremia

by Shih-Ming Chu, Jen-Fu Hsu, Mei-Yin Lai, Hsuan-Rong Huang, Ming-Chou Chiang, Ren-Huei Fu and Ming-Horng Tsai

Antibiotics 2020, 9(4), 203; https://doi.org/10.3390/antibiotics9040203 - 23 Apr 2020

Cited by 12 | Viewed by 3702

Abstract

Background: Timely appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. However, the relevant data and significant impacts have not been well studied in the neonatal intensive care unit (NICU). Methods: An 8-year (1 January 2007–31 December 2014) [...] Read more.

Background: Timely appropriate empirical antibiotic plays an important role in critically ill patients with gram-negative bacteremia. However, the relevant data and significant impacts have not been well studied in the neonatal intensive care unit (NICU). Methods: An 8-year (1 January 2007–31 December 2014) cohort study of all NICU patients with gram-negative bacteremia (GNB) in a tertiary-care medical center was performed. Inadequate empirical antibiotic therapy was defined when a patient did not receive any antimicrobial agent to which the causative microorganisms were susceptible within 24 h of blood culture sampling. Neonates with GNB treated with inadequate antibiotics were compared with those who received initial adequate antibiotics. Results: Among 376 episodes of Gram-negative bacteremia, 75 (19.9%) received inadequate empirical antibiotic therapy. The cause of inadequate treatment was mostly due to the pathogen resistance to prescribed antibiotics (88.0%). Bacteremia caused by Pseudomonas aeruginosa (Odds ratio [OR]: 20.8, P < 0.001) and extended spectrum β-lactamase (ESBL)-producing bacteria (OR: 18.4, P < 0.001) had the highest risk of inadequate treatment. Previous exposure with third generation cephalosporin was identified as the only independent risk factor (OR: 2.52, 95% CI: 1.18–5.37, P = 0.018). Empirically inadequately treated bacteremias were significantly more likely to have worse outcomes than those with adequate therapy, including a higher risk of major organ damage (20.0% versus 6.6%, P < 0.001) and infectious complications (25.3% versus 9.3%, P < 0.001), and overall mortality (22.7% versus 11.0%, P = 0.013). Conclusions: Inadequate empirical antibiotic therapy occurs in one-fifth of Gram-negative bacteremias in the NICU, and is associated with worse outcomes. Additional prospective studies are needed to elucidate the optimal timing and aggressive antibiotic regimen for neonates who are at risk of antibiotic-resistant Gram-negative bacteremia. Full article

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

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3 pages, 155 KiB

Open AccessEditorial

Antibiotics and Environment

by Rosa Alduina

Antibiotics 2020, 9(4), 202; https://doi.org/10.3390/antibiotics9040202 - 23 Apr 2020

Cited by 25 | Viewed by 5494

Abstract

Since the discovery of penicillin by Alexander Fleming in 1928, the use of antibiotics has become the golden standard in the treatment of bacterial infections of all kinds [...] Full article

(This article belongs to the Special Issue Antibiotics and Environment)

8 pages, 480 KiB

Open AccessCase Report

Hyponatremia Associated with Prophylactic Low-Dose Trimethoprim during Systemic Corticosteroid Therapy for AQP4-Positive Optic Neuritis in a Diabetic Patient

by Masahiro Takubo, Sho Tanaka, Masaru Kushimoto, Jin Ikeda, Katsuhiko Ogawa, Yutaka Suzuki, Masanori Abe, Hisamitsu Ishihara and Midori Fujishiro

Antibiotics 2020, 9(4), 201; https://doi.org/10.3390/antibiotics9040201 - 23 Apr 2020

Cited by 5 | Viewed by 4625

Abstract

Hyponatremia associated with low-dose trimethoprim in patients on concomitant systemic corticosteroid therapy has rarely been reported. Here, we describe a 57-year-old woman with a history of diabetes mellitus and hypertension treated with telmisartan, who presented with progressive visual impairment of the left eye [...] Read more.

Hyponatremia associated with low-dose trimethoprim in patients on concomitant systemic corticosteroid therapy has rarely been reported. Here, we describe a 57-year-old woman with a history of diabetes mellitus and hypertension treated with telmisartan, who presented with progressive visual impairment of the left eye due to anti-aquaporin-4 antibody-positive optic neuritis. The patient received pulsed intravenous methylprednisolone followed by oral prednisolone at 30 mg/day and trimethoprim–sulfamethoxazole prophylaxis (160 mg and 800 mg daily). Her serum sodium level steadily decreased, and the potassium level was slightly elevated despite well-preserved renal function. This state persisted even after telmisartan discontinuation. In addition to hypotonic hyponatremia (125 mEq/L) with natriuresis, hyperkalemic renal tubular acidosis was diagnosed based on normal anion gap metabolic acidosis and hyperkalemia with low urinary potassium excretion. After trimethoprim–sulfamethoxazole cessation, electrolytes and acid–base imbalances swiftly recovered. We can conclude that caution must be exercised when treating such patients, because even low-dose trimethoprim may cause hyponatremia concomitant with hyperkalemic renal tubular acidosis, despite the mineralocorticoid effects of systemic corticosteroids. Full article

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19 pages, 2208 KiB

Open AccessArticle

Investigating Bacteriophages Targeting the Opportunistic Pathogen Acinetobacter baumannii

by Kathryn M. Styles, Rapee Thummeepak, Udomluk Leungtongkam, Sophie E. Smith, Gabrielle S. Christie, Andrew Millard, John Moat, Christopher G. Dowson, Elizabeth M. H. Wellington, Sutthirat Sitthisak and Antonia P. Sagona

Antibiotics 2020, 9(4), 200; https://doi.org/10.3390/antibiotics9040200 - 22 Apr 2020

Cited by 27 | Viewed by 6054

Abstract

The multi-drug resistance of the opportunistic pathogen Acinetobacter baumannii is of growing concern, with many clinical isolates proving to be resistant to last resort as well as front line antibiotic treatments. The use of bacteriophages is an attractive alternative to controlling and treating [...] Read more.

The multi-drug resistance of the opportunistic pathogen Acinetobacter baumannii is of growing concern, with many clinical isolates proving to be resistant to last resort as well as front line antibiotic treatments. The use of bacteriophages is an attractive alternative to controlling and treating this emerging nosocomial pathogen. In this study, we have investigated bacteriophages collected from hospital wastewater in Thailand and we have explored their activity against clinical isolates of A. baumannii. Bacteriophage vB_AbaM_PhT2 showed 28% host range against 150 multidrug resistant (MDR) isolates and whole genome sequencing did not detect any known virulence factors or antibiotic resistance genes. Purified vB_AbaM_PhT2 samples had endotoxin levels below those recommended for preclinical trials and were not shown to be directly cytotoxic to human cell lines in vitro. The treatment of human brain and bladder cell lines grown in the presence of A. baumannii with this bacteriophage released significantly less lactate dehydrogenase compared to samples with no bacteriophage treatment, indicating that vB_AbaM_PhT2 can protect from A. baumannii induced cellular damage. Our results have also indicated that there is synergy between this bacteriophage and the end line antibiotic colistin. We therefore propose bacteriophage vB_AbaM_PhT2 as a good candidate for future research and for its potential development into a surface antimicrobial for use in hospitals. Full article

(This article belongs to the Special Issue Phage Therapy: A Biological Approach to Treatment of Bacterial Infections)

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10 pages, 1669 KiB

Open AccessArticle

Pharmacokinetics of Macrolide Antibiotics and Transport into the Interstitial Fluid: Comparison among Erythromycin, Clarithromycin, and Azithromycin

by Shinji Kobuchi, Teruhiko Kabata, Koki Maeda, Yukako Ito and Toshiyuki Sakaeda

Antibiotics 2020, 9(4), 199; https://doi.org/10.3390/antibiotics9040199 - 22 Apr 2020

Cited by 18 | Viewed by 8255

Abstract

Recent research has found higher levels and longer total exposure of azithromycin, a macrolide antibiotic agent, in the interstitial fluid of the skin than in the plasma. This unique distribution is expected to contribute to its antimicrobial activity at the primary infection site. [...] Read more.

Recent research has found higher levels and longer total exposure of azithromycin, a macrolide antibiotic agent, in the interstitial fluid of the skin than in the plasma. This unique distribution is expected to contribute to its antimicrobial activity at the primary infection site. However, it remains unclear whether this characteristic distribution in the extracellular tissue space is common to macrolide antibiotics or if it is azithromycin-specific, with most macrolides largely localized intracellularly. In this study, we investigated pharmacokinetic characteristics of erythromycin and clarithromycin in the interstitial fluid of the skin of rats after intravenous drug administration, and compared the results with our previously reported results on azithromycin. Interstitial fluid samples were directly collected from a pore on the skin using a dissolving microneedle array. We found that the total macrolide concentrations in the interstitial fluid were significantly different among three macrolides. The rank order of the interstitial fluid-plasma concentration ratio was azithromycin (3.8 to 4.9) > clarithromycin (1.2 to 1.5) > erythromycin (0.27 to 0.39), and this ratio was stable after dosing, whereas higher drug levels in the skin tissue than in the plasma were observed for all three macrolides. Our results suggest that lower erythromycin concentrations in the interstitial fluid than in the plasma contributes to the emergence of bacterial resistance in the extracellular tissue space. Monitoring of total macrolide concentrations in interstitial fluid may provide valuable information regarding antimicrobial effects and the emergence of bacterial resistance for the development of an appropriate pharmacokinetics–pharmacodynamics-based dosing strategy. Full article

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

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16 pages, 2150 KiB

Open AccessReview

Human Defensins: A Novel Approach in the Fight against Skin Colonizing Staphylococcus aureus

by Olga Scudiero, Mariarita Brancaccio, Cristina Mennitti, Sonia Laneri, Barbara Lombardo, Margherita G. De Biasi, Eliana De Gregorio, Chiara Pagliuca, Roberta Colicchio, Paola Salvatore and Raffaela Pero

Antibiotics 2020, 9(4), 198; https://doi.org/10.3390/antibiotics9040198 - 21 Apr 2020

Cited by 44 | Viewed by 9058

Abstract

Staphylococcus aureus is a microorganism capable of causing numerous diseases of the human skin. The incidence of S. aureus skin infections reflects the conflict between the host skin′s immune defenses and the S. aureus’ virulence elements. Antimicrobial peptides (AMPs) are small protein molecules [...] Read more.

Staphylococcus aureus is a microorganism capable of causing numerous diseases of the human skin. The incidence of S. aureus skin infections reflects the conflict between the host skin′s immune defenses and the S. aureus’ virulence elements. Antimicrobial peptides (AMPs) are small protein molecules involved in numerous biological activities, playing a very important role in the innate immunity. They constitute the defense of the host′s skin, which prevents harmful microorganisms from entering the epithelial barrier, including S. aureus. However, S. aureus uses ambiguous mechanisms against host defenses by promoting colonization and skin infections. Our review aims to provide a reference collection on host-pathogen interactions in skin disorders, including S. aureus infections and its resistance to methicillin (MRSA). In addition to these, we discuss the involvement of defensins and other innate immunity mediators (i.e., toll receptors, interleukin-1, and interleukin-17), involved in the defense of the host against the skin disorders caused by S. aureus, and then focus on the evasion mechanisms developed by the pathogenic microorganism under analysis. This review provides the “state of the art” on molecular mechanisms underlying S. aureus skin infection and the pharmacological potential of AMPs as a new therapeutic strategy, in order to define alternative directions in the fight against cutaneous disease. Full article

(This article belongs to the Special Issue Novel Strategies to Control Antimicrobial Resistance)

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8 pages, 738 KiB

Open AccessArticle

Assessment of the Usefulness of Cefapirin and Cefalonium Disks for Susceptibility Testing of Staphylococcus aureus Isolates from Bovine Mastitis

by Kazuki Harada, Shieri Irie, Mamoru Ohnishi and Yasushi Kataoka

Antibiotics 2020, 9(4), 197; https://doi.org/10.3390/antibiotics9040197 - 21 Apr 2020

Viewed by 2812

Abstract

Cefapirin (CEP) and cefalonium (CNM) are first-generation cephalosporins widely used to treat bovine mastitis caused by Gram-positive bacteria including staphylococci. However, disks for susceptibility testing of those drugs in causative bacteria are not available. This study evaluated the efficacy of 10 µg and [...] Read more.

Cefapirin (CEP) and cefalonium (CNM) are first-generation cephalosporins widely used to treat bovine mastitis caused by Gram-positive bacteria including staphylococci. However, disks for susceptibility testing of those drugs in causative bacteria are not available. This study evaluated the efficacy of 10 µg and 30 µg pilot disks of CEP (CEP10 and CEP30) and CNM (CNM10 and CNM30) against 130 Staphylococcus aureus isolates from bovine mastitis. Scattergrams of minimum inhibitory concentrations (MICs) and zone diameters (ZDs) illustrated significant correlations between the MICs and ZDs of CEP10 (r = −0.912), CEP30 (r = −0.933), CNM10 (r = −0.847), and CNM30 (r = −0.807). The analysis by Normalized Resistance Interpretation indicated that the epidemiolocal cut-off value (ECV) of MIC for both cefapirin and cefalonium is ≤ 0.5 µg/mL, and the ECV of ZD for CEP10, CEP30, CNM10, and CNM30 were ≥ 22 mm, ≥ 25 mm, ≥ 22 mm, and ≥ 29 mm, respectively. We believe that both 10 μg and 30 μg CEP and CNM susceptibility disks will be helpful for guiding the appropriate use of these antibiotics for bovine mastitis. Further studies toward the establishment of clinical breakpoint of CEP and CNM would be needed for their routine use. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Pathogens Isolated from Animals)

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20 pages, 321 KiB

Open AccessReview

Trends, Epidemiology, and Management of Multi-Drug Resistant Gram-Negative Bacterial Infections in the Hospitalized Setting

by Sabrina Morris and Elizabeth Cerceo

Antibiotics 2020, 9(4), 196; https://doi.org/10.3390/antibiotics9040196 - 20 Apr 2020

Cited by 143 | Viewed by 13605

Abstract

The increasing prevalence of antibiotic resistance is a threat to human health, particularly within vulnerable populations in the hospital and acute care settings. This leads to increasing healthcare costs, morbidity, and mortality. Bacteria rapidly evolve novel mechanisms of resistance and methods of antimicrobial [...] Read more.

The increasing prevalence of antibiotic resistance is a threat to human health, particularly within vulnerable populations in the hospital and acute care settings. This leads to increasing healthcare costs, morbidity, and mortality. Bacteria rapidly evolve novel mechanisms of resistance and methods of antimicrobial evasion. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii have all been identified as pathogens with particularly high rates of resistance to antibiotics, resulting in a reducing pool of available treatments for these organisms. Effectively combating this issue requires both preventative and reactive measures. Reducing the spread of resistant pathogens, as well as reducing the rate of evolution of resistance is complex. Such a task requires a more judicious use of antibiotics through a better understanding of infection epidemiology, resistance patterns, and guidelines for treatment. These goals can best be achieved through the implementation of antimicrobial stewardship programs and the development and introduction of new drugs capable of eradicating multi-drug resistant Gram-negative pathogens (MDR GNB). The purpose of this article is to review current trends in MDR Gram-negative bacterial infections in the hospitalized setting, as well as current guidelines for management. Finally, new and emerging antimicrobials, as well as future considerations for combating antibiotic resistance on a global scale are discussed. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

9 pages, 715 KiB

Open AccessArticle

In Vitro Antimicrobial Activity of Frankincense Oils from Boswellia sacra Grown in Different Locations of the Dhofar Region (Oman)

by Vita Di Stefano, Domenico Schillaci, Maria Grazia Cusimano, Mohammed Rishan and Luay Rashan

Antibiotics 2020, 9(4), 195; https://doi.org/10.3390/antibiotics9040195 - 20 Apr 2020

Cited by 37 | Viewed by 7301

Abstract

Frankincense essential oils from Boswellia sacra have been commonly used to treat microbial infections from as early as the 11th century. The main feature of the plant is its gum resin, from which it is possible to obtain essential oils. In the present [...] Read more.

Frankincense essential oils from Boswellia sacra have been commonly used to treat microbial infections from as early as the 11th century. The main feature of the plant is its gum resin, from which it is possible to obtain essential oils. In the present study, we focused on the comparative study of the oils extracted from the resins of three different Boswellia sacra cultivars (Najdi, Sahli and Houjri). From each of frankincense resin three successive essential oil samples (Grade 1, Grade 2, Grade 3) were obtained. Houjri gum resin gave the lowest percentage (5%) of total essential oil content but showed the maximum number of volatile components in all three grades. Najdi Grade 2 essential oil showed a minimum inhibitory concentration (MIC) of 52 mg/mL toward relevant pathogens Staphylococcus aureus and Pseudomonas aeruginosa, and samples from Grade 2 of Sahily and Houjiri were particularly active against a dermatological strain Propionibacterium acnes, displaying MIC values of 0.264 and 0.66 mg/mL, respectively. Data obtained from in vitro studies showed that all essential oils had a significant antifungal effect against Candida albicans and Malassezia furfur, showing MIC values ranging from 54.56 to 0.246 mg/mL. This work aims to increase the number of substances available in the fight against pathogens and to combat the phenomenon of antibiotic resistance, encouraging the use of alternative resources, especially in non-clinical settings (farms, food processing, etc.). Full article

(This article belongs to the Special Issue Chemical Composition and Biological Activities of Essential Oils)

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12 pages, 231 KiB

Open AccessArticle

Teacher and Student Views on the Feasibility of Peer to Peer Education as a Model to Educate 16–18 Year Olds on Prudent Antibiotic Use—A Qualitative Study

by Cliodna A. M. McNulty, Carla L. Brown, Rowshonara B. Syeda, C. Verity Bennett, Behnaz Schofield, David G. Allison and Nick Francis

Antibiotics 2020, 9(4), 194; https://doi.org/10.3390/antibiotics9040194 - 19 Apr 2020

Cited by 3 | Viewed by 3430

Abstract

Peer education (PE) has been used successfully to improve young peoples’ health-related behaviour. This paper describes a qualitative evaluation of the feasibility of university healthcare students delivering PE, covering self-care and antibiotic use for infections, to biology students in three UK schools (16–18 [...] Read more.

Peer education (PE) has been used successfully to improve young peoples’ health-related behaviour. This paper describes a qualitative evaluation of the feasibility of university healthcare students delivering PE, covering self-care and antibiotic use for infections, to biology students in three UK schools (16–18 years), who then educated their peers. Twenty peer educators (PEds) participated in focus groups and two teachers took part in interviews to discuss PE feasibility. Data were analysed inductively. All participants reported that teaching students about antibiotic resistance was important. PE was used by PEds to gain communication skills and experience for their CV. PEds confidence increased with practice and group delivery. Interactive activities and real-life illness scenarios facilitated enjoyment. Barriers to PE were competing school priorities, no antibiotic content in the non-biology curriculum, controlling disruptive behaviour, and evaluation consent and questionnaire completion. Participation increased PEds’ awareness of appropriate antibiotic use. This qualitative study supports the feasibility of delivering PE in schools. Maximising interactive and illness scenario content, greater training and support for PEds, and inclusion of infection self-care and antibiotics in the national curriculum for all 16–18-year olds could help facilitate greater antibiotic education in schools. Simplifying consent and data collection procedures would facilitate future evaluations. Full article

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

5 pages, 740 KiB

Open AccessCase Report

Management of a Case of Peritonitis Due to Neisseria gonorrhoeae Infection Following Pelvic Inflammatory Disease (PID)

by Maria A. De Francesco, Paola Stefanelli, Anna Carannante, Silvia Corbellini, Cinzia Giagulli, Giovanni Lorenzin, Maurizio Ronconi, Elisa Arici, Monica Cadei, Riccardo Campora and Arnaldo Caruso

Antibiotics 2020, 9(4), 193; https://doi.org/10.3390/antibiotics9040193 - 18 Apr 2020

Cited by 9 | Viewed by 3949

Abstract

Pelvic inflammatory disease (PID), a serious infection in sexually active women, is one of the reasons for which females seek care in emergency departments and therefore represents an important public health problem. PID is the result of an endocervical infection with different microorganisms, [...] Read more.

Pelvic inflammatory disease (PID), a serious infection in sexually active women, is one of the reasons for which females seek care in emergency departments and therefore represents an important public health problem. PID is the result of an endocervical infection with different microorganisms, which then ascend to the endometrium and fallopian tubes. Symptoms of PID may be mild and aspecific, making its diagnosis difficult. However, this clinical condition requires effective antibiotic treatment to reduce incidence of complications and late sequelae. We describe here a case of peritonitis as a complication of pelvic inflammatory disease (PID) due to Neisseria gonorrhoeae infection in a 49-year-old woman who presented at the Emergency Department with acute abdominal pain. Full article

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

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19 pages, 1444 KiB

Open AccessArticle

Genomic Characterization of Escherichia coli Isolates Belonging to a New Hybrid aEPEC/ExPEC Pathotype O153:H10-A-ST10 eae-beta1 Occurred in Meat, Poultry, Wildlife and Human Diarrheagenic Samples

by Dafne Díaz-Jiménez, Isidro García-Meniño, Alexandra Herrera, Vanesa García, Ana María López-Beceiro, María Pilar Alonso, Jorge Blanco and Azucena Mora

Antibiotics 2020, 9(4), 192; https://doi.org/10.3390/antibiotics9040192 - 17 Apr 2020

Cited by 28 | Viewed by 5062

Abstract

Different surveillance studies (2005–2015) in northwest Spain revealed the presence of eae-positive isolates of Escherichia coli O153:H10 in meat for human consumption, poultry farm, wildlife and human diarrheagenic samples. The aim of this study was to explore the genetic and genomic relatedness [...] Read more.

Different surveillance studies (2005–2015) in northwest Spain revealed the presence of eae-positive isolates of Escherichia coli O153:H10 in meat for human consumption, poultry farm, wildlife and human diarrheagenic samples. The aim of this study was to explore the genetic and genomic relatedness between human and animal/meat isolates, as well as the mechanism of its persistence. We also wanted to know whether it was a geographically restricted lineage, or whether it was also reported elsewhere. Conventional typing showed that 32 isolates were O153:H10-A-ST10 fimH54, fimAv_MT78, traT and eae-beta1. Amongst these, 21 were CTX-M-32 or SHV-12 producers. The PFGE XbaI-macrorestriction comparison showed high similarity (>85%). The plasmidome analysis revealed a stable combination of IncF (F2:A-:B-), IncI1 (STunknown) and IncX1 plasmid types, together with non-conjugative Col-like plasmids. The core genome investigation based on the cgMLST scheme from EnteroBase proved close relatedness between isolates of human and animal origin. Our results demonstrate that a hybrid MDR aEPEC/ExPEC of the clonal group O153:H10-A-ST10 (CH11-54) is circulating in our region within different hosts, including wildlife. It seems implicated in human diarrhea via meat transmission, and in the spreading of ESBL genes (mainly of CTX-M-32 type). We found genomic evidence of a related hybrid aEPEC/ExPEC in at least one other country. Full article

(This article belongs to the Special Issue Pathogenic Escherichia coli: Infections and Therapies)

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11 pages, 833 KiB

Open AccessArticle

Effects of Antibiotics on the Intestinal Microbiota of Mice

by Frederik Boetius Hertz, Andries E. Budding, Malieka van der Lugt-Degen, Paul H. Savelkoul, Anders Løbner-Olesen and Niels Frimodt-Møller

Antibiotics 2020, 9(4), 191; https://doi.org/10.3390/antibiotics9040191 - 17 Apr 2020

Cited by 23 | Viewed by 6259

Abstract

Studies on human and mouse gastrointestinal microbiota have correlated the composition of the microbiota to a variety of diseases, as well as proved it vital to prevent colonization with resistant bacteria, a phenomenon known as colonization resistance. Antibiotics dramatically modify the gut community [...] Read more.

Studies on human and mouse gastrointestinal microbiota have correlated the composition of the microbiota to a variety of diseases, as well as proved it vital to prevent colonization with resistant bacteria, a phenomenon known as colonization resistance. Antibiotics dramatically modify the gut community and there are examples of how antibiotic usage lead to colonization with resistant bacteria [e.g., dicloxacillin usage selecting for ESBL-producing E. coli carriage], as shown by Hertz et al. Here, we investigated the impact of five antibiotics [cefotaxime, cefuroxime, dicloxacillin, clindamycin, and ciprofloxacin] on the intestinal microbiota in mice. Five different antibiotics were each given to groups of five mice. The intestinal microbiotas were profiled by use of the IS-pro analysis; a 16S–23S rDNA interspace [IS]-region-based profiling method. For the mice receiving dicloxacillin and clindamycin, we observed dramatic shifts in dominating phyla from day 1 to day 5. Of note, diversity increased, but overall bacterial load decreased. For ciprofloxacin, cefotaxime, and cefuroxime there were few overall changes. We speculate that antibiotics with efficacy against the abundant anaerobes in the gut, particularly Bacteroidetes, can in fact be selected for resistant bacteria, disregarding the spectrum of activity. Full article

(This article belongs to the Special Issue Antibiotic-Resistance, Determinants, Prevention, Clinical Implications and Stewardship)

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10 pages, 4197 KiB

Open AccessArticle

Antibacterial Activities of Selected Pure Compounds Isolated from Gut Bacteria of Animals Living in Polluted Environments

by Noor Akbar, Ruqaiyyah Siddiqui, Mazhar Iqbal and Naveed Ahmed Khan

Antibiotics 2020, 9(4), 190; https://doi.org/10.3390/antibiotics9040190 - 17 Apr 2020

Cited by 28 | Viewed by 3753

Abstract

Antibiotic resistance is a global threat to public health, further accelerated by the misuse of antibiotics in humans and animals. Our recent studies have shown that gut bacteria of animals living in polluted environments are a potential source of antibacterials. Gut bacteria of [...] Read more.

Antibiotic resistance is a global threat to public health, further accelerated by the misuse of antibiotics in humans and animals. Our recent studies have shown that gut bacteria of animals living in polluted environments are a potential source of antibacterials. Gut bacteria of cockroaches, water monitor lizards and the turtle exhibited molecules such as curcumenol, docosanedioic acid, N-acyl-homoserine lactone, L-homotyrosine and Di-rhamnolipids. Using purified compounds, assays were performed to determine their antibacterial properties using serial dilution method, cytotoxic effects using lactate dehydrogenase release, and cell viability using MTT assay. The results revealed that the purified compounds exhibited significant antibacterial activities (p < 0.05) against selected Gram-negative (Pseudomonas aeruginosa) and Gram-positive bacteria (Streptococcus pyogenes) with effective MIC₅₀ and MIC₉₀ at µg concentrations, and with minimal effects on human cells as observed from LDH and MTT assays. These findings are significant and provide a basis for the rational development of therapeutic antibacterials. Future studies are needed to determine in vivo effects of the identified molecules together with their mode of action, which could lead to the development of novel antibacterial(s). Full article

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8 pages, 1104 KiB

Open AccessArticle

Impact of Reappraisal of Fluoroquinolone Minimum Inhibitory Concentration Susceptibility Breakpoints in Gram-Negative Bloodstream Isolates

by Stephanie C. Shealy, Matthew M. Brigmon, Julie Ann Justo, P. Brandon Bookstaver, Joseph Kohn and Majdi N. Al-Hasan

Antibiotics 2020, 9(4), 189; https://doi.org/10.3390/antibiotics9040189 - 17 Apr 2020

Cited by 5 | Viewed by 4184

Abstract

The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for Enterobacteriaceae and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk [...] Read more.

The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for Enterobacteriaceae and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk factors for antimicrobial resistance. Gram-negative bloodstream isolates collected from hospitalized adults at Prisma Health-Midlands hospitals in South Carolina, USA, from January 2010 to December 2014 were included. Matched pairs mean difference (MD) with 95% confidence intervals (CI) were calculated to examine the change in ciprofloxacin susceptibility after MIC breakpoint reappraisal. Susceptibility of Enterobacteriaceae to ciprofloxacin declined by 5.2% (95% CI: −6.6, −3.8; p < 0.001) after reappraisal. The largest impact was demonstrated among Pseudomonas aeruginosa bloodstream isolates (MD −7.8, 95% CI: −14.6, −1.1; p = 0.02) despite more conservative revision in ciprofloxacin MIC breakpoints. Among antimicrobial resistance risk factors, fluoroquinolone exposure within the previous 90 days was associated with the largest change in ciprofloxacin susceptibility (MD −9.3, 95% CI: −16.1, −2.6; p = 0.007). Reappraisal of fluoroquinolone MIC breakpoints has a variable impact on the susceptibility of bloodstream isolates by microbiology and patient population. Healthcare systems should be vigilant to systematically adopt this updated recommendation in order to optimize antimicrobial therapy in patients with bloodstream and other serious infections. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

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13 pages, 3113 KiB

Open AccessArticle

Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae

by Ayaz Anwar, Mohammad Ridwane Mungroo, Simal Khan, Itrat Fatima, Rafaila Rafique, Kanwal, Khalid Mohammed Khan, Ruqaiyyah Siddiqui and Naveed Ahmed Khan

Antibiotics 2020, 9(4), 188; https://doi.org/10.3390/antibiotics9040188 - 17 Apr 2020

Cited by 24 | Viewed by 5070

Abstract

Balamuthia mandrillaris and Naegleria fowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used [...] Read more.

Balamuthia mandrillaris and Naegleria fowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used drugs is a highly desirable approach that can lead to effective drug development against these devastating infections. In this regard, compounds belonging to the azole class possess wide range of antimicrobial properties and used clinically. In this study, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against brain-eating amoebae. These compounds were tested for their amoebicidal and static properties against N. fowleri and B. mandrillaris. Furthermore, the compounds were conjugated with silver nanoparticles and characterized. The synthetic heterocyclic compounds showed up to 72% and 65% amoebicidal activities against N. fowleri and B. mandrillaris respectively, while expressing up to 75% and 70% amoebistatic activities, respectively. Following conjugation with silver nanoparticles, amoebicidal activities of the drugs increased by up to 46 and 36% versus B. mandrillaris and N. fowleri. Minimal effects were observed when the compounds were evaluated against human cells using cytotoxicity assays. In summary, azole compounds exhibited potent activity against N. fowleri and B. mandrillaris. Moreover, conjugation of the azole compounds with silver nanoparticles further augmented the capabilities of the compounds against amoebae. Full article

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10 pages, 694 KiB

Open AccessCase Report

Isolation of Tetracycline-Resistant Chlamydia suis from a Pig Herd Affected by Reproductive Disorders and Conjunctivitis

by Christine Unterweger, Lukas Schwarz, Martina Jelocnik, Nicole Borel, René Brunthaler, Aleksandra Inic-Kanada and Hanna Marti

Antibiotics 2020, 9(4), 187; https://doi.org/10.3390/antibiotics9040187 - 17 Apr 2020

Cited by 13 | Viewed by 3724

Abstract

Due to various challenges in diagnosing chlamydiosis in pigs, antibiotic treatment is usually performed before any molecular or antibiotic susceptibility testing. This could increase the occurrence of tetracycline-resistant Chlamydia (C.) suis isolates in the affected pig population and potentiate the reoccurrence of clinical [...] Read more.

Due to various challenges in diagnosing chlamydiosis in pigs, antibiotic treatment is usually performed before any molecular or antibiotic susceptibility testing. This could increase the occurrence of tetracycline-resistant Chlamydia (C.) suis isolates in the affected pig population and potentiate the reoccurrence of clinical signs. Here, we present a case of an Austrian pig farm, where tetracycline resistant and sensitive C. suis isolates were isolated from four finishers with conjunctivitis. On herd-level, 10% of the finishers suffered from severe conjunctivitis and sows showed a high percentage of irregular return to estrus. Subsequent treatment of whole-herd using oxytetracycline led to a significant reduction of clinical signs. Retrospective antibiotic susceptibility testing revealed tetracycline resistance and decreased susceptibility to doxycycline in half of the ocular C. suis isolates, and all isolates were able to partially recover following a single-dose tetracycline treatment in vitro. These findings were later confirmed in vivo, when all former clinical signs recurred three months later. This case report raises awareness of tetracycline resistance in C. suis and emphasizes the importance of preventative selection of tetracycline resistant C. suis isolates. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Pathogens Isolated from Animals)

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34 pages, 946 KiB

Open AccessReview

The Current Burden of Carbapenemases: Review of Significant Properties and Dissemination among Gram-Negative Bacteria

by Dalal Hammoudi Halat and Carole Ayoub Moubareck

Antibiotics 2020, 9(4), 186; https://doi.org/10.3390/antibiotics9040186 - 16 Apr 2020

Cited by 140 | Viewed by 11083

Abstract

Carbapenemases are β-lactamases belonging to different Ambler classes (A, B, D) and can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, which hydrolyze a broad variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major [...] Read more.

Carbapenemases are β-lactamases belonging to different Ambler classes (A, B, D) and can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, which hydrolyze a broad variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are clinical due to compromising the activity of the last resort antibiotics used for treating serious infections, and epidemiological due to their dissemination into various bacteria across almost all geographic regions. Carbapenemase-producing Enterobacteriaceae have received more attention upon their first report in the early 1990s. Currently, there is increased awareness of the impact of nonfermenting bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, as well as other Gram-negative bacteria that are carbapenemase-producers. Outside the scope of clinical importance, carbapenemases are also detected in bacteria from environmental and zoonotic niches, which raises greater concerns over their prevalence, and the need for public health measures to control consequences of their propagation. The aims of the current review are to define and categorize the different families of carbapenemases, and to overview the main lines of their spread across different bacterial groups. Full article

(This article belongs to the Special Issue Targeting β-lactamases to Fight Bacterial Resistance to β-lactam Antibiotics)

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8 pages, 428 KiB

Open AccessArticle

Synergy between Florfenicol and Aminoglycosides against Multidrug-Resistant Escherichia coli Isolates from Livestock

by Shukho Kim, Jung Hwa Woo, So Hyun Jun, Dong Chan Moon, Suk-Kyung Lim and Je Chul Lee

Antibiotics 2020, 9(4), 185; https://doi.org/10.3390/antibiotics9040185 - 16 Apr 2020

Cited by 8 | Viewed by 3814

Abstract

The increasing prevalence of antimicrobial resistance and the laborious development of novel antimicrobial agents have limited the options for effective antimicrobial therapy. The combination of previously used antimicrobial agents represents an alternative therapy for multidrug-resistant (MDR) pathogens. The objective of this study was [...] Read more.

The increasing prevalence of antimicrobial resistance and the laborious development of novel antimicrobial agents have limited the options for effective antimicrobial therapy. The combination of previously used antimicrobial agents represents an alternative therapy for multidrug-resistant (MDR) pathogens. The objective of this study was to investigate the synergistic effect of a florfenicol (FFL)-based combination with other antimicrobial agents against MDR Escherichia coli isolates from livestock using checkerboard assays and murine infection models. The FFL/amikacin (AMK) and FFL/gentamicin (GEN) combinations showed synergy against 10/11 and 6/11 MDR E. coli isolates in vitro, respectively. The combination of FFL with aminoglycosides (AMK or GEN) exhibited a better synergistic effect against MDR E. coli isolates than the cephalothin (CEF)/GEN or FFL/CEF combinations. The combination of FFL with AMK or GEN could reduce the emergence of resistant mutants in vitro. The FFL/AMK combination showed a higher survival rate of mice infected with MDR E. coli isolates than FFL or AMK alone. In summary, the combination of FFL with aminoglycosides (AMK or GEN) is highly effective against MDR E. coli isolates both in vitro and in vivo. Our findings may contribute to the discovery of an effective combination regimen against MDR E. coli infections in veterinary medicine. Full article

(This article belongs to the Section The Global Need for Effective Antibiotics)

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12 pages, 380 KiB

Open AccessArticle

Knowledge, Attitude, and Practices of Antibiotics and Antibiotic Resistance Among Chinese Pharmacy Customers: A Multicenter Survey Study

by Pengchao Li, Khezar Hayat, Li Shi, Krizzia Lambojon, Amna Saeed, Muhammad Majid Aziz, Tao Liu, Shiyu Ji, Yilin Gong, Zhitong Feng, Minghuan Jiang, Wenjing Ji, Caijun Yang, Jie Chang and Yu Fang

Antibiotics 2020, 9(4), 184; https://doi.org/10.3390/antibiotics9040184 - 16 Apr 2020

Cited by 13 | Viewed by 6225

Abstract

Background: Resistance to antibiotics is one of the major global health challenges. An adequate understanding of the public regarding rational antibiotic use is a prerequisite to limit progression in antibiotic resistance. This study aimed to investigate the knowledge, attitude, and practices (KAP) of [...] Read more.

Background: Resistance to antibiotics is one of the major global health challenges. An adequate understanding of the public regarding rational antibiotic use is a prerequisite to limit progression in antibiotic resistance. This study aimed to investigate the knowledge, attitude, and practices (KAP) of antibiotics and antibiotic resistance among customers visiting community pharmacies. Methods: This study was undertaken in three capital cities in China during March 2019 and July 2019 by using a questionnaire of 28 items. The questionnaire had four parts, including sociodemographic characteristics, KAP about antibiotics, and antibiotic resistance. A systematic random sampling approach was used to recruit the participants. Kruskal–Wallis and Mann–Whitney tests were carried out for data analysis. Results: The response rate was 66.7% (1800/2700). Out of the total, only 9.7% of the customers had good knowledge about antibiotics. Nearly half of the participants were unable to differentiate between antibiotics, and anti-inflammatory drugs (n = 820, 45.6%, Median = 2, IQR = 1). Most of the customers were of the view that the use of over the counter antibiotics in pregnant women is unsafe (n = 1307, 72.6%, Median = 2, IQR = 0). Almost half of the participants disagreed that costly antibiotics are more effective and have fewer side effects (n = 897, 49.9%, Median = 3, IQR = 1). Only 22.3% of participants said that they always finish the course of antibiotic treatment (n = 401, 22.3%, Median = 3, IQR = 1). Conclusion: The knowledge of Chinese pharmacy consumers was inadequate, and a lack of good attitudes and practices in certain aspects of antibiotic use was observed. Educational interventions are needed to increase public knowledge of antibiotics. Full article

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

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5 pages, 634 KiB

Open AccessTechnical Note

Evaluation of Oxytetracycline Metabolites Cross-Reactivity with Oxytetracycline Enzyme-Linked Immunosorbent Assay (ELISA)

by Faraj Hijaz and Nabil Killiny

Antibiotics 2020, 9(4), 183; https://doi.org/10.3390/antibiotics9040183 - 15 Apr 2020

Cited by 5 | Viewed by 3328

Abstract

Antibiotics have been successfully used for the control of several plant diseases for many years. Recently, streptomycin and oxytetracycline have been approved for the treatment of Huanglongbing (HLB) in Florida. The enzyme-linked immunosorbent assay (ELISA) is the most commonly used assay for the [...] Read more.

Antibiotics have been successfully used for the control of several plant diseases for many years. Recently, streptomycin and oxytetracycline have been approved for the treatment of Huanglongbing (HLB) in Florida. The enzyme-linked immunosorbent assay (ELISA) is the most commonly used assay for the detection of these antibiotics because it is quick, simple, and can be used to analyze many samples at the same time. However, ELISA can react with the metabolites of the parent compound and its structurally related compounds. In this study, we investigated the cross-reactivity of the oxytetracycline ACCEL ELISA kit^TM with three of oxytetracycline metabolites (4-epi-oxytetracycline, α-apo-oxytetracycline, and β-apo-oxytetracycline). The α-apo-oxytetracycline and β-apo-oxytetracycline metabolite did not show any cross-reactivity in the linear range (1.5–50 ng mL⁻¹) of the assay. Whereas 4-epi-oxytetracycline showed high cross-reactivity, and its response was similar to oxytetracycline. Our results indicated that the oxytetracycline ELISA kits estimate the level of oxytetracycline as well as its main metabolite, 4-epi-oxytetracycline. Full article

(This article belongs to the Section Plant-Derived Antibiotics)

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11 pages, 2176 KiB

Open AccessArticle

Selective Modification of Streptozotocin at the C3 Position to Improve Its Bioactivity as Antibiotic and Reduce Its Cytotoxicity towards Insulin-Producing β Cells

by Ji Zhang, Liubov Yakovlieva, Bart J. de Haan, Paul de Vos, Adriaan J. Minnaard, Martin D. Witte and Marthe T. C. Walvoort

Antibiotics 2020, 9(4), 182; https://doi.org/10.3390/antibiotics9040182 - 15 Apr 2020

Cited by 8 | Viewed by 7785

Abstract

With the increasing resistance of bacteria to current antibiotics, novel compounds are urgently needed to treat bacterial infections. Streptozotocin (STZ) is a natural product that has broad-spectrum antibiotic activity, albeit with limited use because of its toxicity to pancreatic β cells. In an [...] Read more.

With the increasing resistance of bacteria to current antibiotics, novel compounds are urgently needed to treat bacterial infections. Streptozotocin (STZ) is a natural product that has broad-spectrum antibiotic activity, albeit with limited use because of its toxicity to pancreatic β cells. In an attempt to derivatize STZ through structural modification at the C3 position, we performed the synthesis of three novel STZ analogues by making use of our recently developed regioselective oxidation protocol. Keto-STZ (2) shows the highest inhibition of bacterial growth (minimum inhibitory concentration (MIC) and viability assays), but is also the most cytotoxic compound. Pre-sensitizing the bacteria with GlcNAc increased the antimicrobial effect, but did not result in complete killing. Interestingly, allo-STZ (3) revealed moderate concentration-dependent antimicrobial activity and no cytotoxicity towards β cells, and deoxy-STZ (4) showed no activity at all. Full article

(This article belongs to the Section Biosynthesis and Combinatorial Approaches in Antimicrobial Discovery)

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14 pages, 3600 KiB

Open AccessArticle

Antimicrobial Activity of Silver-Treated Bacteria against other Multi-Drug Resistant Pathogens in Their Environment

by Doaa Safwat Mohamed, Rehab Mahmoud Abd El-Baky, Tim Sandle, Sahar A. Mandour and Eman Farouk Ahmed

Antibiotics 2020, 9(4), 181; https://doi.org/10.3390/antibiotics9040181 - 15 Apr 2020

Cited by 57 | Viewed by 12474

Abstract

Silver is a potent antimicrobial agent against a variety of microorganisms and once the element has entered the bacterial cell, it accumulates as silver nanoparticles with large surface area causing cell death. At the same time, the bacterial cell becomes a reservoir for [...] Read more.

Silver is a potent antimicrobial agent against a variety of microorganisms and once the element has entered the bacterial cell, it accumulates as silver nanoparticles with large surface area causing cell death. At the same time, the bacterial cell becomes a reservoir for silver. This study aims to test the microcidal effect of silver-killed E. coli O104: H4 and its supernatant against fresh viable cells of the same bacterium and some other species, including E. coli O157: H7, Multidrug Resistant (MDR) Pseudomonas aeruginosa and Methicillin Resistant Staphylococcus aureus (MRSA). Silver-killed bacteria were examined by Transmission Electron Microscopy (TEM). Agar well diffusion assay was used to test the antimicrobial efficacy and durability of both pellet suspension and supernatant of silver-killed E. coli O104:H4 against other bacteria. Both silver-killed bacteria and supernatant showed prolonged antimicrobial activity against the tested strains that extended to 40 days. The presence of adsorbed silver nanoparticles on the bacterial cell and inside the cells was verified by TEM. Silver-killed bacteria serve as an efficient sustained release reservoir for exporting the lethal silver cations. This promotes its use as a powerful disinfectant for polluted water and as an effective antibacterial which can be included in wound and burn dressings to overcome the problem of wound contamination. Full article

(This article belongs to the Special Issue Nanoparticles-Based Antimicrobials)

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11 pages, 2317 KiB

Open AccessArticle

Polyphasic Validation of a Nisin-Biogel to Control Canine Periodontal Disease

by Eva Cunha, Ferdinando Bernardino Freitas, Berta São Braz, Jorge Moreira da Silva, Luís Tavares, Ana Salomé Veiga and Manuela Oliveira

Antibiotics 2020, 9(4), 180; https://doi.org/10.3390/antibiotics9040180 - 14 Apr 2020

Cited by 15 | Viewed by 3731

Abstract

Background: Periodontal disease (PD) is a highly prevalent inflammatory disease in dogs. This disease is initiated by a polymicrobial biofilm on the teeth surface, whose control includes its prevention and removal. Recently, it was shown that nisin displays antimicrobial activity against canine PD-related [...] Read more.

Background: Periodontal disease (PD) is a highly prevalent inflammatory disease in dogs. This disease is initiated by a polymicrobial biofilm on the teeth surface, whose control includes its prevention and removal. Recently, it was shown that nisin displays antimicrobial activity against canine PD-related bacteria. Moreover, guar gum biogel has shown to be a promising topical delivery system for nisin. Methods: In this study we aimed to evaluate the antimicrobial activity of the nisin-biogel in the presence of canine saliva and after a 24-month storage, at different conditions, using a canine oral enterococci collection. We also studied the nisin-biogel cytotoxicity using a Vero cell line and canine primary intestinal fibroblasts. Results: The presence of saliva hampers nisin-biogel antimicrobial activity, and higher nisin concentrations were required for an effective activity. A significant reduction (p ≤ 0.05) in inhibitory activity was observed for nisin-biogel solutions stored at 37 °C, over a 24-month period, which was not observed with the other conditions. The nisin-biogel showed no cytotoxicity against the cells tested at concentrations up to 200 µg/mL. Conclusions: Our results confirmed the potential of the nisin-biogel for canine PD control, supporting the development of an in vivo clinical trial. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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12 pages, 4272 KiB

Open AccessArticle

The Effectiveness of Chlorhexidine and Air Polishing System in the Treatment of Candida albicans Infected Dental Implants: An Experimental In Vitro Study

by Pier Carmine Passarelli, Marta De Leonardis, Giovan Battista Piccirillo, Viviana Desantis, Raffaele Papa, Edoardo Rella, Giuseppe Niccolò Mastandrea Bonaviri, Piero Papi, Giorgio Pompa, Guido Pasquantonio, Paolo Francesco Manicone and Antonio D’Addona

Antibiotics 2020, 9(4), 179; https://doi.org/10.3390/antibiotics9040179 - 14 Apr 2020

Cited by 12 | Viewed by 3904

Abstract

Background: Peri-implantitis is an inflammatory disease with an increasing diffusion rate which can affect the long-term survival of a prosthetic rehabilitation. The present study focused on the decontaminating efficacy of chlorhexidine and air polishing system with sodium bicarbonate powder against Candida albicans, a [...] Read more.

Background: Peri-implantitis is an inflammatory disease with an increasing diffusion rate which can affect the long-term survival of a prosthetic rehabilitation. The present study focused on the decontaminating efficacy of chlorhexidine and air polishing system with sodium bicarbonate powder against Candida albicans, a microorganism which seems to have a superinfecting opportunistic role in the pathology. The aim of the authors was to investigate and compare the effectiveness of these treatments, commonly used in clinical practice. Methods: An in vitro study was conducted to analyze the effects of two widely used therapeutic aids for the disinfection of affected titanium implants: chlorhexidine (CHX) and air polishing with sodium bicarbonate powder (P). A qualitative and quantitative comparative analysis of the residual biofilm was carried out using a colorimetric assay (XTT) and scanning electron microscopy (SEM) observation. The experiment was conducted both on machined titanium surfaces and on rough sandblasted ones with the aim of bringing out differences in the therapeutic outcomes concerning the superficial texture of the implant. The null hypothesis was that no difference could be detected between the samples, regarding both the treatments performed and the nano-structural features of titanium. Results: The best results (on both types of implant surfaces) were obtained when combining the use of chlorhexidine and air polishing (C + P). A linear decrease in the optical density (OD) values recorded at three different time points (30 s, 1 min, 5 min) was also observed passing from the first to the last one. When observed under scanning electron microscope rough surfaces showed an extensive and highly structured biofilm, more complex if compared to the one encountered when analyzing machined implants. Conclusions: the present pilot study showed that rough surfaces can promote fungal adhesion and eventually hinder the outcome of a decontaminating treatment. For this purpose, the physio-chemical technique is always more efficient if compared to a single-technique approach regardless of the surface characteristics. Full article

(This article belongs to the Special Issue Antibiotics and Antimicrobials in Dentistry)

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