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Antibiotics
Volume 9
Issue 2
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Antibiotics, Volume 9, Issue 2 (February 2020) – 59 articles

Cover Story (view full-size image): Staphylococcus aureus poses a significant and enduring challenge to both human and veterinary medicine. This challenge is exacerbated by the spread of antimicrobial-resistant strains, of particular note being methicillin-resistant S. aureus (MRSA). As a result, much effort is focussing on the development of alternative therapeutic approaches. One option being investigated is the exploitation of bacterocins and other inhibitory products made by the competing microflora. In our review, we present the current status of research investigating staphylococcal-produced bacteriocins and antimicrobial peptides as alternative treatments for S. aureus infections. A few show promising activity, including efficacy in animal models, but much work remains to be done if we are to fully explore and exploit this potentially useful source of new antimicrobials. View this paper
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14 pages, 236 KiB  
Article
Public Awareness and Practices towards Self-Medication with Antibiotics among the Malaysian Population. A Development of Questionnaire and Pilot-Testing
by Adeel Aslam, Márió Gajdács, Che Suraya Zin, Norny Syafinaz Binti Abd Rahman, Syed Imran Ahmed and Shazia Qasim Jamshed
Antibiotics 2020, 9(2), 97; https://doi.org/10.3390/antibiotics9020097 - 24 Feb 2020
Cited by 36 | Viewed by 7782
Abstract
It is well documented that injudicious antibiotic use and practicing self-medication with antibiotics (SMA) can lead to antibiotic resistance. The objective was to validate and develop an instrument in Bahasa Melayu to assess the awareness and practices towards SMA in the Malaysian population. [...] Read more.
It is well documented that injudicious antibiotic use and practicing self-medication with antibiotics (SMA) can lead to antibiotic resistance. The objective was to validate and develop an instrument in Bahasa Melayu to assess the awareness and practices towards SMA in the Malaysian population. A pilot study was conducted among 100 Malaysians participants. Reliability testing in terms of test-retest, internal consistency, and content validity was performed. One-way ANOVA and t-test were applied to determine significant differences between groups. A panel of nine experts evaluated the research instrument for content validity and it was found to have strong content item validity (Indices = 1). Each domain (level of knowledge and understanding about antibiotic use and antibiotic resistance: Practice towards self-medication) showed good internal consistency of Cronbach’s alpha 0.658 and 0.90. While test-retest reliability value for each domain was 0.773 (p = 0.009), and 0.891 (p = 0.001. The mean ± standard deviation (SD) for level of knowledge about antibiotic use and antibiotic resistance was 21.8 ± 7.02 and for practice scores (SMA) 6.03 ± 2.30. The instrument established sound reliability and validity and, therefore, can be an effective tool for assessing public awareness, and practices toward self-medication with antibiotics in the Malaysian population. Full article
(This article belongs to the Special Issue Antibiotic Resistance: From the Bench to Patients)
10 pages, 615 KiB  
Article
Excess Length of Acute Inpatient Stay Attributable to Acquisition of Hospital-Onset Gram-Negative Bloodstream Infection with and without Antibiotic Resistance: A Multistate Model Analysis
by Hiroyuki Suzuki, Eli N Perencevich, Rajeshwari Nair, Daniel J Livorsi and Michihiko Goto
Antibiotics 2020, 9(2), 96; https://doi.org/10.3390/antibiotics9020096 - 23 Feb 2020
Cited by 11 | Viewed by 3507
Abstract
Excess length of stay (LOS) is an important outcome when assessing the burden of nosocomial infection, but it can be subject to survival bias. We aimed to estimate the change in LOS attributable to hospital-onset (HO) Escherichia coli/Klebsiella spp. bacteremia using [...] Read more.
Excess length of stay (LOS) is an important outcome when assessing the burden of nosocomial infection, but it can be subject to survival bias. We aimed to estimate the change in LOS attributable to hospital-onset (HO) Escherichia coli/Klebsiella spp. bacteremia using multistate models to circumvent survival bias. We analyzed a cohort of all patients with HO E. coli/Klebsiella spp. bacteremia and matched uninfected control patients within the U.S. Veterans Health Administration System in 2003–2013. A multistate model was used to estimate the change in LOS as an effect of the intermediate state (HO-bacteremia). We stratified analyses by susceptibilities to fluoroquinolones (fluoroquinolone susceptible (FQ-S)/fluoroquinolone resistant (FQ-R)) and extended-spectrum cephalosporins (ESC susceptible (ESC-S)/ESC resistant (ESC-R)). Among the 5964 patients with HO bacteremia analyzed, 957 (16.9%) and 1638 (28.9%) patients had organisms resistant to FQ and ESC, respectively. Any HO E.coli/Klebsiella bacteremia was associated with excess LOS, and both FQ-R and ESC-R were associated with a longer LOS than susceptible strains, but the additional burdens attributable to resistance were small compared to HO bacteremia itself (FQ-S: 12.13 days vs. FQ-R: 12.94 days, difference: 0.81 days (95% CI: 0.56–1.05), p < 0.001 and ESC-S: 11.57 days vs. ESC-R: 16.56 days, difference: 4.99 days (95% CI: 4.75–5.24), p < 0.001). Accurate measurements of excess attributable LOS associated with resistance can help support the business case for infection control interventions. Full article
(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)
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4 pages, 195 KiB  
Editorial
Antibiotics and Antimicrobials for Treatment of the Oral Microbiota: Myths and Facts in Research and Clinical Practice
by Gaetano Isola
Antibiotics 2020, 9(2), 95; https://doi.org/10.3390/antibiotics9020095 - 22 Feb 2020
Cited by 5 | Viewed by 4363
Abstract
In the dental field, the most common oral diseases include periodontitis, apical periodontitis, abscesses, phlegmons and pulpits, all of which are determined by the same aetiological factor, bacterial infections. For these reasons, it is important to choose the right approach through a target [...] Read more.
In the dental field, the most common oral diseases include periodontitis, apical periodontitis, abscesses, phlegmons and pulpits, all of which are determined by the same aetiological factor, bacterial infections. For these reasons, it is important to choose the right approach through a target antibiotic therapy against oral bacteria. More specifically, during periodontitis, antibiotics are used, often in association with periodontal debridement, to reduce disease-associated periodontopathogens. However, international guidelines are not unanimous in recommending the use of local and/or systemic antimicrobials to reduce infection by oral bacteria, especially in cases in which there is a danger of spreading systemic infection such as cellulitis, diffuse swelling, and abscesses. The lack of consensus is mainly due to the side effects of antibiotic therapy in dentistry, maybe due to recent scientific evidence regarding the development of bacterial resistance to antibiotics. Therefore, the purpose of this editorial is to analyze the therapeutic effects of antibiotics against the main forms of oral and periodontal diseases, and whether there is a significant clinical benefit, especially in the long term, of antimicrobial therapies in dentistry. The most recent evidence regarding antimicrobial agents will also be discussed. Full article
(This article belongs to the Special Issue Antibiotics and Antimicrobials in Dentistry)
13 pages, 1271 KiB  
Concept Paper
Critical Parameters for the Development of Novel Therapies for Severe and Resistant Infections—A Case Study on CAL02, a Non-Traditional Broad-Spectrum Anti-Virulence Drug
by Samareh Azeredo da Silveira and Andrew F. Shorr
Antibiotics 2020, 9(2), 94; https://doi.org/10.3390/antibiotics9020094 - 21 Feb 2020
Cited by 6 | Viewed by 4726
Abstract
Background: Poor outcomes in severe and resistant infections, together with the economic struggles of companies active in the field of anti-infective development, call for new solutions and front runners with novel approaches. Among “non-traditional” approaches, blocking virulence could be a game changer. Objectives: [...] Read more.
Background: Poor outcomes in severe and resistant infections, together with the economic struggles of companies active in the field of anti-infective development, call for new solutions and front runners with novel approaches. Among “non-traditional” approaches, blocking virulence could be a game changer. Objectives: This review offers a perspective on parameters that have determined the development path of CAL02, a novel anti-virulence agent, with a view to steering clear of the obstacles and limitations that impede market sustainability for new anti-infective drugs. Conclusions and implications of key findings: This case study highlights four pillars that may support the development of other non-traditional drugs and, concurrently, provide a new model that could reshape the field. Therapeutic triggers, study designs, and economic parameters are discussed. Full article
(This article belongs to the Special Issue Nontraditional Antibiotics—Challenges and Triumphs)
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10 pages, 1738 KiB  
Article
Modified Aminoglycosides Bind Nucleic Acids in High-Molecular-Weight Complexes
by Lanqing Ying, Hongkun Zhu, Marina Y. Fosso, Sylvie Garneau-Tsodikova and Kurt Fredrick
Antibiotics 2020, 9(2), 93; https://doi.org/10.3390/antibiotics9020093 - 21 Feb 2020
Cited by 3 | Viewed by 3201
Abstract
Aminoglycosides represent a large group of antibiotics well known for their ability to target the bacterial ribosome. In studying 6”-substituted variants of the aminoglycoside tobramycin, we serendipitously found that compounds with C12 or C14 linear alkyl substituents potently inhibit reverse transcription [...] Read more.
Aminoglycosides represent a large group of antibiotics well known for their ability to target the bacterial ribosome. In studying 6”-substituted variants of the aminoglycoside tobramycin, we serendipitously found that compounds with C12 or C14 linear alkyl substituents potently inhibit reverse transcription in vitro. Initial observations suggested specific inhibition of reverse transcriptase. However, further analysis showed that these and related compounds bind nucleic acids with high affinity, forming high-molecular weight complexes. Stable complex formation is observed with DNA or RNA in single- or double-stranded form. Given the amphiphilic nature of these aminoglycoside derivatives, they likely form micelles and/or vesicles with surface-bound nucleic acids. Hence, these compounds may be useful tools to localize nucleic acids to surfaces or deliver nucleic acids to cells or organelles. 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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16 pages, 1828 KiB  
Article
A Rapid Fluorescence-Based Microplate Assay to Investigate the Interaction of Membrane Active Antimicrobial Peptides with Whole Gram-Positive Bacteria
by Gerard Boix-Lemonche, Maria Lekka and Barbara Skerlavaj
Antibiotics 2020, 9(2), 92; https://doi.org/10.3390/antibiotics9020092 - 19 Feb 2020
Cited by 38 | Viewed by 7106
Abstract
Background: Membrane-active antimicrobial peptides (AMPs) are interesting candidates for the development of novel antimicrobials. Although their effects were extensively investigated in model membrane systems, interactions of AMPs with living microbial membranes are less known due to their complexity. The aim of the present [...] Read more.
Background: Membrane-active antimicrobial peptides (AMPs) are interesting candidates for the development of novel antimicrobials. Although their effects were extensively investigated in model membrane systems, interactions of AMPs with living microbial membranes are less known due to their complexity. The aim of the present study was to develop a rapid fluorescence-based microplate assay to analyze the membrane effects of AMPs in whole Staphylococcus aureus and Staphylococcus epidermidis. Methods: Bacteria were exposed to bactericidal and sub-inhibitory concentrations of two membrane-active AMPs in the presence of the potential-sensitive dye 3,3′-dipropylthiadicarbocyanine iodide (diSC3(5)) and the DNA staining dye propidium iodide (PI), to simultaneously monitor and possibly distinguish membrane depolarization and membrane permeabilization. Results: The ion channel-forming gramicidin D induced a rapid increase of diSC3(5), but not PI fluorescence, with slower kinetics at descending peptide concentrations, confirming killing due to membrane depolarization. The pore-forming melittin, at sub-MIC and bactericidal concentrations, caused, respectively, an increase of PI fluorescence in one or both dyes simultaneously, suggesting membrane permeabilization as a key event. Conclusions: This assay allowed the distinction between specific membrane effects, and it could be applied in the mode of action studies as well as in the screening of novel membrane-active AMPs. Full article
(This article belongs to the Special Issue Antibacterial Peptides)
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14 pages, 1625 KiB  
Article
Marine Actinobacteria: Screening for Predation Leads to the Discovery of Potential New Drugs against Multidrug-Resistant Bacteria
by Manar Ibrahimi, Wassila Korichi, Mohamed Hafidi, Laurent Lemee, Yedir Ouhdouch and Souad Loqman
Antibiotics 2020, 9(2), 91; https://doi.org/10.3390/antibiotics9020091 - 19 Feb 2020
Cited by 15 | Viewed by 7036 | Correction
Abstract
Predatory bacteria constitute a heterogeneous group of prokaryotes able to lyse and feed on the cellular constituents of other bacteria in conditions of nutrient scarcity. In this study, we describe the isolation of Actinobacteria predator of other bacteria from the marine water of [...] Read more.
Predatory bacteria constitute a heterogeneous group of prokaryotes able to lyse and feed on the cellular constituents of other bacteria in conditions of nutrient scarcity. In this study, we describe the isolation of Actinobacteria predator of other bacteria from the marine water of the Moroccan Atlantic coast. Only 4 Actinobacteria isolates showing strong predation capability against native or multidrug-resistant Gram-positive or Gram-negative bacteria were identified among 142 isolated potential predatory bacteria. These actinobacterial predators were shown to belong to the Streptomyces genus and to inhibit the growth of various native or multidrug-resistant micro-organisms, including Micrococcus luteus, Staphylococcus aureus (native and methicillin-resistant), and Escherichia coli (native and ampicillin-resistant). Even if no clear correlation could be established between the antibacterial activities of the selected predator Actinobacteria and their predatory activity, we cannot exclude that some specific bio-active secondary metabolites were produced in this context and contributed to the killing and lysis of the bacteria. Indeed, the co-cultivation of Actinobacteria with other bacteria is known to lead to the production of compounds that are not produced in monoculture. Furthermore, the production of specific antibiotics is linked to the composition of the growth media that, in our co-culture conditions, exclusively consisted of the components of the prey living cells. Interestingly, our strategy led to the isolation of bacteria with interesting inhibitory activity against methicillin-resistant S. aureus (MRSA) as well as against Gram-negative bacteria. Full article
(This article belongs to the Special Issue Contexts of Biosynthesis and Functions of the Antibiotics for the Producing Bacteria)
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24 pages, 1829 KiB  
Perspective
Metal Complexes, an Untapped Source of Antibiotic Potential?
by Angelo Frei
Antibiotics 2020, 9(2), 90; https://doi.org/10.3390/antibiotics9020090 - 18 Feb 2020
Cited by 135 | Viewed by 11690
Abstract
With the widespread rise of antimicrobial resistance, most traditional sources for new drug compounds have been explored intensively for new classes of antibiotics. Meanwhile, metal complexes have long had only a niche presence in the medicinal chemistry landscape, despite some compounds, such as [...] Read more.
With the widespread rise of antimicrobial resistance, most traditional sources for new drug compounds have been explored intensively for new classes of antibiotics. Meanwhile, metal complexes have long had only a niche presence in the medicinal chemistry landscape, despite some compounds, such as the anticancer drug cisplatin, having had a profound impact and still being used extensively in cancer treatments today. Indeed, metal complexes have been largely ignored for antibiotic development. This is surprising as metal compounds have access to unique modes of action and exist in a wider range of three-dimensional geometries than purely organic compounds. These properties make them interesting starting points for the development of new drugs. In this perspective article, the encouraging work that has been done on antimicrobial metal complexes, mainly over the last decade, is highlighted. Promising metal complexes, their activity profiles, and possible modes of action are discussed and issues that remain to be addressed are emphasized. Full article
(This article belongs to the Special Issue Nontraditional Antibiotics—Challenges and Triumphs)
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28 pages, 1022 KiB  
Review
Staphylococcus aureus Epidemiology in Wildlife: A Systematic Review
by Christina J. Heaton, Gracen R. Gerbig, Lucas D. Sensius, Vishwash Patel and Tara C. Smith
Antibiotics 2020, 9(2), 89; https://doi.org/10.3390/antibiotics9020089 - 18 Feb 2020
Cited by 64 | Viewed by 9442
Abstract
Staphylococcus aureus is a common bacterial colonizer of humans and a variety of animal species. Many strains have zoonotic potential, moving between humans and animals, including livestock, pets, and wildlife. We examined publications reporting on S. aureus presence in a variety of wildlife [...] Read more.
Staphylococcus aureus is a common bacterial colonizer of humans and a variety of animal species. Many strains have zoonotic potential, moving between humans and animals, including livestock, pets, and wildlife. We examined publications reporting on S. aureus presence in a variety of wildlife species in order to more cohesively review distribution of strains and antibiotic resistance in wildlife. Fifty-one studies were included in the final qualitative synthesis. The most common types documented included ST398, ST425, ST1, ST133, ST130, and ST15. A mix of methicillin-resistant and methicillin-susceptible strains were noted. A number of molecular types were identified that were likely to be found in wildlife species, including those that are commonly found in humans or other animal species (including livestock). Additional research should include follow-up in geographic areas that are under-sampled in this study, which is dominated by European studies. Full article
(This article belongs to the Special Issue Antibiotics and Environment)
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8 pages, 1238 KiB  
Review
Concerted Efforts Are Needed to Control and Mitigate Antibiotic Pollution in Coastal Waters of China
by Huaijun Xie, Jing Du and Jingwen Chen
Antibiotics 2020, 9(2), 88; https://doi.org/10.3390/antibiotics9020088 - 16 Feb 2020
Cited by 32 | Viewed by 4639
Abstract
Antibiotics have been applied for decades and antibiotic pollution is of great concern due to the risk for promoting resistant genes. Human activities such as mariculture and land-based discharge can lead to the antibiotic pollution in coastal area and it is of importance [...] Read more.
Antibiotics have been applied for decades and antibiotic pollution is of great concern due to the risk for promoting resistant genes. Human activities such as mariculture and land-based discharge can lead to the antibiotic pollution in coastal area and it is of importance to assess the pollution and risks of antibiotics in this area. In this mini-review, the pollution status of antibiotics in Chinese coastal waters is summarized and some perspectives are put forward for future efforts to mitigate the pollution. Full article
(This article belongs to the Special Issue Antibiotics and Environment)
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17 pages, 1037 KiB  
Article
Antimicrobial Usage and Resistance in Companion Animals: A Cross-Sectional Study in Three European Countries
by Philip Joosten, Daniela Ceccarelli, Evelien Odent, Steven Sarrazin, Haitske Graveland, Liese Van Gompel, Antonio Battisti, Andrea Caprioli, Alessia Franco, Jaap A. Wagenaar, Dik Mevius and Jeroen Dewulf
Antibiotics 2020, 9(2), 87; https://doi.org/10.3390/antibiotics9020087 - 16 Feb 2020
Cited by 84 | Viewed by 10657
Abstract
Companion animals have been described as potential reservoirs of antimicrobial resistance (AMR), however data remain scarce. Therefore, the objectives were to describe antimicrobial usage (AMU) in dogs and cats in three European countries (Belgium, Italy, and The Netherlands) and to investigate phenotypic AMR. [...] Read more.
Companion animals have been described as potential reservoirs of antimicrobial resistance (AMR), however data remain scarce. Therefore, the objectives were to describe antimicrobial usage (AMU) in dogs and cats in three European countries (Belgium, Italy, and The Netherlands) and to investigate phenotypic AMR. A questionnaire and one fecal sample per animal (n = 303) were collected over one year and AMU was quantified using treatment incidence (TI). Phenotypic resistance profiles of 282 Escherichia coli isolates were determined. Nineteen percent of the animals received at least one antimicrobial treatment six months preceding sampling. On average, cats and dogs were treated with a standard daily dose of antimicrobials for 1.8 and 3.3 days over one year, respectively. The most frequently used antimicrobial was amoxicillin-clavulanate (27%). Broad-spectrum antimicrobials and critically important antimicrobials for human medicine represented 83% and 71% of the total number of treatments, respectively. Resistance of E. coli to at least one antimicrobial agent was found in 27% of the isolates. The most common resistance was to ampicillin (18%). Thirteen percent was identified as multidrug resistant isolates. No association between AMU and AMR was found in the investigated samples. The issue to address, regarding AMU in companion animal, lies within the quality of use, not the quantity. Especially from a One-Health perspective, companion animals might be a source of transmission of resistance genes and/or resistant bacteria to humans. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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14 pages, 931 KiB  
Article
Use of Micellar Liquid Chromatography to Determine Mebendazole in Dairy Products and Breeding Waste from Bovine Animals
by Rajendra Prasad Pawar, Pooja Mishra, Abhilasha Durgbanshi, Devasish Bose, Jaume Albiol-Chiva, Juan Peris-Vicente, Daniel García-Ferrer and Josep Esteve-Romero
Antibiotics 2020, 9(2), 86; https://doi.org/10.3390/antibiotics9020086 - 14 Feb 2020
Cited by 12 | Viewed by 3475
Abstract
Mebendazole is an anthelmintic drug used in cattle production. However, residues may occur in produced food and in excretions, jeopardizing population health. A method based on micellar liquid chromatography (MLC) was developed to determine mebendazole in dairy products (milk, cheese, butter, and curd) [...] Read more.
Mebendazole is an anthelmintic drug used in cattle production. However, residues may occur in produced food and in excretions, jeopardizing population health. A method based on micellar liquid chromatography (MLC) was developed to determine mebendazole in dairy products (milk, cheese, butter, and curd) and nitrogenous waste (urine and dung) from bovine animals. Sample treatment was expedited to simple dilution or solid-to-liquid extraction, followed by filtration and direct injection of the obtained solution. The analyte was resolved from matrix compounds in less than 8 min, using a C18 column and a mobile phase made up of 0.15 M sodium dodecyl sulfate (SDS)–6% 1-pentanol phosphate buffered at pH 7, and running at 1 mL/min under isocratic mode. Detection was performed by absorbance at 292 nm. The procedure was validated according to the guidelines of the EU Commission Decision 2002/657/EC in terms of: specificity, method calibration range (from the limit of quantification to 25–50 ppm), sensitivity (limit of detection 0.1–0.2 ppm; limit of quantification, 0.3–0.6 ppm), trueness (92.5–102.3%), precision (<7.5%, expressed at RSD), robustness, and stability. The method is reliable, sensitive, easy-to-handle, eco-friendly, safe, inexpensive, and provides a high sample-throughput. Therefore, it is useful for routine analysis as a screening or quantification method in a laboratory for drug-residue control. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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11 pages, 1577 KiB  
Article
Brevinin-2GHk from Sylvirana guentheri and the Design of Truncated Analogs Exhibiting the Enhancement of Antimicrobial Activity
by Guanzhu Chen, Yuxi Miao, Chengbang Ma, Mei Zhou, Zhanzhong Shi, Xiaoling Chen, James F. Burrows, Xinping Xi, Tianbao Chen and Lei Wang
Antibiotics 2020, 9(2), 85; https://doi.org/10.3390/antibiotics9020085 - 14 Feb 2020
Cited by 17 | Viewed by 3811
Abstract
Brevinins are an important antimicrobial peptide (AMP) family discovered in the skin secretions of Ranidae frogs. The members demonstrate a typical C-terminal ranabox, as well as a diverse range of other structural characteristics. In this study, we identified a novel brevinin-2 peptide from [...] Read more.
Brevinins are an important antimicrobial peptide (AMP) family discovered in the skin secretions of Ranidae frogs. The members demonstrate a typical C-terminal ranabox, as well as a diverse range of other structural characteristics. In this study, we identified a novel brevinin-2 peptide from the skin secretion of Sylvirana guentheri, via cloning transcripts, and identifying the expressed mature peptide, in the skin secretion. The confirmed amino acid sequence of the mature peptide was designated brevinin-2GHk (BR2GK). Moreover, as a previous study had demonstrated that the N-terminus of brevinin-2 is responsible for exerting antimicrobial activity, we also designed a series of truncated derivatives of BR2GK. The results show that the truncated derivatives exhibit significantly improved antimicrobial activity and cytotoxicity compared to the parent peptide, except a Pro14 substituted analog. The circular dichroism (CD) analysis of this analog revealed that it did not fold into a helical conformation in the presence of either lipopolysaccharides (LPS) or TFE, indicating that position 14 is involved in the formation of the α-helix. Furthermore, three more analogs with the substitutions of Ala, Lys and Arg at the position 14, respectively, revealed the influence on the membrane disruption potency on bacteria and mammalian cells by the structural changes at this position. Overall, the N-terminal 25-mer truncates demonstrated the potent antimicrobial activity with low cytotoxicity. Full article
(This article belongs to the Special Issue Development of Antimicrobial Peptides from Amphibian)
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11 pages, 1428 KiB  
Article
Tigecycline Interferes with Fibrinogen Polymerization Independent of Peripheral Interactions with the Coagulation System
by Anna Brandtner, Mirjam Bachler, Dietmar Fries, Martin Hermann, Jacqueline Ruehlicke, Vilmos Fux, Andrea Griesmacher, Christian Niederwanger, Tobias Hell and Benedikt Treml
Antibiotics 2020, 9(2), 84; https://doi.org/10.3390/antibiotics9020084 - 14 Feb 2020
Cited by 11 | Viewed by 3505
Abstract
Tigecycline offers broad anti-bacterial coverage for critically ill patients with complicated infections. A described but less researched side effect is coagulopathy. The aim of this study was to test whether tigecycline interferes with fibrinogen polymerization by peripheral interactions. To study the effect of [...] Read more.
Tigecycline offers broad anti-bacterial coverage for critically ill patients with complicated infections. A described but less researched side effect is coagulopathy. The aim of this study was to test whether tigecycline interferes with fibrinogen polymerization by peripheral interactions. To study the effect of unmetabolized tigecycline, plasma of healthy volunteers were spiked with increasing concentrations of tigecycline. In a second experimental leg, immortalized human liver cells (HepG2) were treated with the same concentrations to test an inhibitory effect of hepatic tigecycline metabolites. Using standard coagulation tests, only the activated thromboplastin time in humane plasma was prolonged with increasing concentrations of tigecycline. Visualization of the fibrin network using confocal live microscopy demonstrated a qualitative difference in tigecycline treated experiments. Thrombelastometry and standard coagulation tests did not indicate an impairment of coagulation. Although the discrepancy between functional and immunologic fibrinogen levels increased in cell culture assays with tigecycline concentration, fibrinogen levels in spiked plasma samples did not show significant differences determined by functional versus immunologic methods. In our in vitro study, we excluded a direct effect of tigecycline in increasing concentrations on blood coagulation in healthy adults. Furthermore, we demonstrated a rapid loss of mitochondrial activity in hepatic cells with supra-therapeutic tigecycline dosages. Full article
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6 pages, 519 KiB  
Concept Paper
A Challenging View: Antibiotics Play a Role in the Regulation of the Energetic Metabolism of the Producing Bacteria
by Marie-Joelle Virolle
Antibiotics 2020, 9(2), 83; https://doi.org/10.3390/antibiotics9020083 - 13 Feb 2020
Cited by 27 | Viewed by 5171
Abstract
Antibiotics are often considered as weapons conferring a competitive advantage to their producers in their ecological niche. However, since these molecules are produced in specific environmental conditions, notably phosphate limitation that triggers a specific metabolic state, they are likely to play important roles [...] Read more.
Antibiotics are often considered as weapons conferring a competitive advantage to their producers in their ecological niche. However, since these molecules are produced in specific environmental conditions, notably phosphate limitation that triggers a specific metabolic state, they are likely to play important roles in the physiology of the producing bacteria that have been overlooked. Our recent experimental data as well as careful analysis of the scientific literature led us to propose that, in conditions of moderate to severe phosphate limitation—conditions known to generate energetic stress—antibiotics play crucial roles in the regulation of the energetic metabolism of the producing bacteria. A novel classification of antibiotics into types I, II, and III, based on the nature of the targets of these molecules and on their impact on the cellular physiology, is proposed. Type I antibiotics are known to target cellular membranes, inducing energy spilling and cell lysis of a fraction of the population to provide nutrients, and especially phosphate, to the surviving population. Type II antibiotics inhibit respiration through different strategies, to reduce ATP generation in conditions of low phosphate availability. Lastly, Type III antibiotics that are known to inhibit ATP consuming anabolic processes contribute to ATP saving in conditions of phosphate starvation. Full article
(This article belongs to the Special Issue Contexts of Biosynthesis and Functions of the Antibiotics for the Producing Bacteria)
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3 pages, 186 KiB  
Correction
Correction: Saeed, A., et al. Incidence of Vancomycin-Resistant Phenotype of the Methicillin-Resistant Staphylococcus aureus Isolated from a Tertiary Care Hospital in Lahore. Antibiotics 2020, 9, 3
by Aqib Saeed, Fatima Ahsan, Muhammad Nawaz, Khadeja Iqbal, Kashif Ur Rehman and Tayyaba Ijaz
Antibiotics 2020, 9(2), 82; https://doi.org/10.3390/antibiotics9020082 - 13 Feb 2020
Cited by 3 | Viewed by 2761
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue Methicillin-Resistant Staphylococci)
13 pages, 1281 KiB  
Article
Antibiotic Consumption and Microbiological Epidemiology in Surgery Departments: Results from a Single Study Center
by Dana Carmen Zaha, Simona Bungau, Diana Uivarosan, Delia Mirela Tit, Teodor Andrei Maghiar, Octavian Maghiar, Carmen Pantis, Ovidiu Fratila, Marius Rus and Cosmin Mihai Vesa
Antibiotics 2020, 9(2), 81; https://doi.org/10.3390/antibiotics9020081 - 13 Feb 2020
Cited by 25 | Viewed by 5026
Abstract
The spectrum and antibiotic sensitivity of isolated strains vary between departments, hospitals, countries; the discrepancies are related to the use and dosage of these antibiotics. The purpose of our research was to compare the type of pathogens and the susceptibility of the isolated [...] Read more.
The spectrum and antibiotic sensitivity of isolated strains vary between departments, hospitals, countries; the discrepancies are related to the use and dosage of these antibiotics. The purpose of our research was to compare the type of pathogens and the susceptibility of the isolated strains, as well as the use of antibiotics in the surgical departments of the Emergency Clinical County Hospital, Oradea, Romania; for one year, all the patients admitted to the mentioned sections were monitored. Antibiotic sensitivity of isolated strains was expressed using cumulative antibiogram. The total consumption of antibiotics was 479.18 DDD/1000 patient-days in the surgical sections. The most commonly used drugs were cephalosporins third and first generation, and clindamycin. Infections of wounds, urinary tract and fluids were most commonly diagnosed, and the most isolated was Escherichia coli, followed by Staphylococcus aureus and Enterococcus faecalis. The most commonly prescribed antimicrobial was ceftriaxone, but its sensitivity was low. This study revealed that the intake of antimicrobials in the surgical sections is increased and the comparison of antimicrobial prescriptions, sensitivity rates, and the spectrum of isolated pathogens showed differences between antimicrobials. Full article
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6 pages, 222 KiB  
Case Report
Genomic Characterization of New Variant of Hydrogen Sulfide (H2S)-Producing Escherichia coli with Multidrug Resistance Properties Carrying the mcr-1 Gene in China
by Silpak Biswas, Mohammed Elbediwi, Guimin Gu and Min Yue
Antibiotics 2020, 9(2), 80; https://doi.org/10.3390/antibiotics9020080 - 13 Feb 2020
Cited by 21 | Viewed by 3671
Abstract
Colistin is considered to be a ‘last-resort’ antimicrobial for the treatment of multidrug-resistant Gram-negative bacterial infections. Identification of Enterobacteriaceae, carrying the transferable colistin resistance gene mcr-1, has recently provoked a global health concern. This report presents the first detection of a [...] Read more.
Colistin is considered to be a ‘last-resort’ antimicrobial for the treatment of multidrug-resistant Gram-negative bacterial infections. Identification of Enterobacteriaceae, carrying the transferable colistin resistance gene mcr-1, has recently provoked a global health concern. This report presents the first detection of a hydrogen sulfide (H2S)-producing Escherichia coli variant isolated from a human in China, with multidrug resistance (MDR) properties, including colistin resistance by the mcr-1 gene, which could have great implications for the treatment of human infections. Full article
(This article belongs to the Special Issue Bacterial Pathogens Resistance and Virulence)
13 pages, 2415 KiB  
Article
Ib-M6 Antimicrobial Peptide: Antibacterial Activity against Clinical Isolates of Escherichia coli and Molecular Docking
by J. M. Flórez-Castillo, P. Rondón-Villareal, J. L. Ropero-Vega, S. Y. Mendoza-Espinel, J. A. Moreno-Amézquita, K. D. Méndez-Jaimes, A. E. Farfán-García, S. Y. Gómez-Rangel and Oscar Gilberto Gómez-Duarte
Antibiotics 2020, 9(2), 79; https://doi.org/10.3390/antibiotics9020079 - 12 Feb 2020
Cited by 11 | Viewed by 4778
Abstract
The Ib-M6 peptide has antibacterial activity against non-pathogenic Escherichia coli K-12 strain. The first part of this study determines the antibacterial activity of Ib-M6 against fourteen pathogenic strains of E. coli O157:H7. Susceptibility assay showed that Ib-M6 had values of Minimum Inhibitory Concentration [...] Read more.
The Ib-M6 peptide has antibacterial activity against non-pathogenic Escherichia coli K-12 strain. The first part of this study determines the antibacterial activity of Ib-M6 against fourteen pathogenic strains of E. coli O157:H7. Susceptibility assay showed that Ib-M6 had values of Minimum Inhibitory Concentration (MIC) lower than streptomycin, used as a reference antibiotic. Moreover, to predict the possible interaction between Ib-M6 and outer membrane components of E. coli, we used molecular docking simulations where FhuA protein and its complex with Lipopolysaccharide (LPS–FhuA) were used as targets of the peptide. FhuA/Ib-M6 complexes had energy values between −39.5 and −40.5 Rosetta Energy Units (REU) and only one hydrogen bond. In contrast, complexes between LPS–FhuA and Ib-M6 displayed energy values between −25.6 and −40.6 REU, and the presence of five possible hydrogen bonds. Hence, the antimicrobial activity of Ib-M6 peptide shown in the experimental assays could be caused by its interaction with the outer membrane of E. coli. Full article
(This article belongs to the Special Issue Antibacterial Peptides)
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13 pages, 2780 KiB  
Article
Characterization and Antimicrobial Activity of the Teleost Chemokine CXCL20b
by Xun Xiao, Yanqi Zhang, Zhiwei Liao and Jianguo Su
Antibiotics 2020, 9(2), 78; https://doi.org/10.3390/antibiotics9020078 - 12 Feb 2020
Cited by 12 | Viewed by 3139
Abstract
Fish are a potential source of diverse organic compounds with a broad spectrum of biological activities. Many fish-derived antimicrobial peptides and proteins are key components of the fish innate immune system. They are also potential candidates for development of new antimicrobial agents. CXCL20b [...] Read more.
Fish are a potential source of diverse organic compounds with a broad spectrum of biological activities. Many fish-derived antimicrobial peptides and proteins are key components of the fish innate immune system. They are also potential candidates for development of new antimicrobial agents. CXCL20b is a grass carp (Ctenopharyngodon idella) CXC chemokine strongly transcribed at the early stage of bacterial infections, for which the immune role had not been reported to date. In the present study, we found that CXCL20b is a cationic amphipathic protein that displays potent antimicrobial activity against both Gram-positive and Gram-negative bacteria. The results of DiOC2(3) and atomic force microscopy (AFM) assays indicated that CXCL20b could induce bacterial membrane depolarization and disruption in a short time. By performing further structure-activity studies, we found that the antimicrobial activity of CXCL20b was mainly relative to the N-terminal random coil region. The central part of this cytokine representing β-sheet region was insoluble in water and the C-terminal α-helical region did not show an antimicrobial effect. The results presented in this article support the poorly understood function of CXCL20b, which fulfills an important role in bony fish antimicrobial immunity. Full article
(This article belongs to the Section Antimicrobial Peptides)
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8 pages, 1127 KiB  
Article
In Vitro Antimicrobial Activity of Various Cefoperazone/Sulbactam Products
by Ming-Jen Sheu, Chi-Chung Chen, Ying-Chen Lu, Bo-An Su, Chun-Cheng Zhang, Shu-Shen Wang, Yin-Ching Chuang, Hung-Jen Tang and Chih-Cheng Lai
Antibiotics 2020, 9(2), 77; https://doi.org/10.3390/antibiotics9020077 - 12 Feb 2020
Cited by 9 | Viewed by 5123
Abstract
This study aims to assess the in vitro activity of different samples of cefoperazone/sulbactam (CFP/SUL) against multidrug-resistant organisms (MDROs). Clinical isolates of extended-spectrum β-lactamase (ESBL)-Escherichia coli, ESBL-Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii (CR-AB), and carbapenem-resistant Pseudomonas aeruginosa (CR-PA) were collected. [...] Read more.
This study aims to assess the in vitro activity of different samples of cefoperazone/sulbactam (CFP/SUL) against multidrug-resistant organisms (MDROs). Clinical isolates of extended-spectrum β-lactamase (ESBL)-Escherichia coli, ESBL-Klebsiella pneumoniae, carbapenem-resistant Acinetobacter baumannii (CR-AB), and carbapenem-resistant Pseudomonas aeruginosa (CR-PA) were collected. The minimum inhibitory concentration (MIC) and time-killing methods were used to assess and compare the in vitro activities of different samples of cefoperazone/sulbactam (CFP/SUL) against these MDROs. For ESBL-E. coli, ESBL-K. pneumoniae, and CR-PA, product C had smaller variations than product A and B (p < 0.05). For CR-AB, product B had the largest variation compared to the other two products (p < 0.05). In the time-killing studies, significant differences among the products when used at 16/16 µg/mL were noted for ESBL-E. coli, ESBL-K. pneumoniae, and CR-AB isolates. In conclusion, this study demonstrated the significantly different activity of different products of CFP/SUL against MDROs. Full article
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9 pages, 1503 KiB  
Article
Manure Compost Is a Potential Source of Tetracycline-Resistant Escherichia coli and Tetracycline Resistance Genes in Japanese Farms
by Nobuki Yoshizawa, Masaru Usui, Akira Fukuda, Tetsuo Asai, Hidetoshi Higuchi, Eiryu Okamoto, Kanako Seki, Hideshige Takada and Yutaka Tamura
Antibiotics 2020, 9(2), 76; https://doi.org/10.3390/antibiotics9020076 - 11 Feb 2020
Cited by 32 | Viewed by 4603
Abstract
Manure compost has been thought of as a potential important route of transmission of antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs) from livestock to humans. To clarify the abundance of ARB and ARGs, ARB and ARGs were quantitatively determined in tetracycline-resistant Escherichia [...] Read more.
Manure compost has been thought of as a potential important route of transmission of antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs) from livestock to humans. To clarify the abundance of ARB and ARGs, ARB and ARGs were quantitatively determined in tetracycline-resistant Escherichia coli (harboring the tetA gene)-spiked feces in simulated composts. In the simulated composts, the concentration of spiked E. coli decreased below the detection limit at day 7. The tetA gene remained in manure compost for 20 days, although the levels of the gene decreased. Next, to clarify the field conditions of manure compost in Japan, the quantities of tetracycline-resistant bacteria, tetracycline resistance genes, and residual tetracyclines were determined using field-manure-matured composts in livestock farms. Tetracycline-resistant bacteria were detected in 54.5% of tested matured compost (6/11 farms). The copy number of the tetA gene and the concentrations of residual tetracyclines in field manure compost were significantly correlated. These results suggest that the use of antimicrobials in livestock constitutes a selective pressure, not only in livestock feces but also in manure compost. The appropriate use of antimicrobials in livestock and treatment of manure compost are important for avoiding the spread of ARB and ARGs. Full article
(This article belongs to the Special Issue Antibiotics and Environment)
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17 pages, 668 KiB  
Review
Antimicrobial Activity of Host-Derived Lipids
by Carol L. Fischer
Antibiotics 2020, 9(2), 75; https://doi.org/10.3390/antibiotics9020075 - 11 Feb 2020
Cited by 55 | Viewed by 8209
Abstract
Host-derived lipids are increasingly recognized as antimicrobial molecules that function in innate immune activities along with antimicrobial peptides. Sphingoid bases and fatty acids found on the skin, in saliva and other body fluids, and on all mucosal surfaces, including oral mucosa, exhibit antimicrobial [...] Read more.
Host-derived lipids are increasingly recognized as antimicrobial molecules that function in innate immune activities along with antimicrobial peptides. Sphingoid bases and fatty acids found on the skin, in saliva and other body fluids, and on all mucosal surfaces, including oral mucosa, exhibit antimicrobial activity against a variety of Gram positive and Gram negative bacteria, viruses, and fungi, and reduce inflammation in animal models. Multiple studies demonstrate that the antimicrobial activity of lipids is both specific and selective. There are indications that the site of action of antimicrobial fatty acids is the bacterial membrane, while the long-chain bases may inhibit cell wall synthesis as well as interacting with bacterial membranes. Research in this area, although still sporadic, has slowly increased in the last few decades; however, we still have much to learn about antimicrobial lipid mechanisms of activity and their potential use in novel drugs or topical treatments. One important potential benefit for the use of innate antimicrobial lipids (AMLs) as antimicrobial agents is the decreased likelihood side effects with treatment. Multiple studies report that endogenous AML treatments do not induce damage to cells or tissues, often decrease inflammation, and are active against biofilms. The present review summarizes the history of antimicrobial lipids from the skin surface, including both fatty acids and sphingoid bases, in multiple human body systems and summarizes their relative activity against various microorganisms. The range of antibacterial activities of lipids present at the skin surface and in saliva is presented. Some observations relevant to mechanisms of actions are discussed, but are largely still unknown. Multiple recent studies examine the therapeutic and prophylactic uses of AMLs. Although these lipids have been repeatedly demonstrated to act as innate effector molecules, they are not yet widely accepted as such. These compiled data further support fatty acid and sphingoid base inclusion as innate effector molecules. Full article
(This article belongs to the Special Issue Innate Antimicrobial Defense of Skin and Oral Mucosa)
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13 pages, 511 KiB  
Review
Gram-Negative Bacterial Lysins
by Chandrabali Ghose and Chad W. Euler
Antibiotics 2020, 9(2), 74; https://doi.org/10.3390/antibiotics9020074 - 11 Feb 2020
Cited by 80 | Viewed by 9423
Abstract
Antibiotics have had a profound impact on human society by enabling the eradication of otherwise deadly infections. Unfortunately, antibiotic use and overuse has led to the rapid spread of acquired antibiotic resistance, creating a major threat to public health. Novel therapeutic agents called [...] Read more.
Antibiotics have had a profound impact on human society by enabling the eradication of otherwise deadly infections. Unfortunately, antibiotic use and overuse has led to the rapid spread of acquired antibiotic resistance, creating a major threat to public health. Novel therapeutic agents called bacteriophage endolysins (lysins) provide a solution to the worldwide epidemic of antibiotic resistance. Lysins are a class of enzymes produced by bacteriophages during the lytic cycle, which are capable of cleaving bonds in the bacterial cell wall, resulting in the death of the bacteria within seconds after contact. Through evolutionary selection of the phage progeny to be released and spread, these lysins target different critical components in the cell wall, making resistance to these molecules orders of magnitude less likely than conventional antibiotics. Such properties make lysins uniquely suitable for the treatment of multidrug resistant bacterial pathogens. Lysins, either naturally occurring or engineered, have the potential of being developed into fast-acting, narrow-spectrum, biofilm-disrupting antimicrobials that act synergistically with standard of care antibiotics. This review focuses on newly discovered classes of Gram-negative lysins with emphasis on prototypical enzymes that have been evaluated for efficacy against the major antibiotic resistant organisms causing nosocomial infections. Full article
(This article belongs to the Special Issue Nontraditional Antibiotics—Challenges and Triumphs)
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15 pages, 1527 KiB  
Article
Molecular Characterization Of Pathogenic Salmonella Spp From Raw Beef In Karachi, Pakistan
by Muhammad Altaf Hussain, Wan Wang, Changbao Sun, Liya Gu, Zhijing Liu, Tong Yu, Yasin Ahmad, Zhanmei Jiang and Juncai Hou
Antibiotics 2020, 9(2), 73; https://doi.org/10.3390/antibiotics9020073 - 10 Feb 2020
Cited by 14 | Viewed by 4753
Abstract
The aim of the present study was to estimate the prevalence of Salmonella and investigate the dominant serovars distribution in raw beef and to screen the isolated serovars for the prescense of beta-lactamases and virulence genes. A total of 150 samples of raw [...] Read more.
The aim of the present study was to estimate the prevalence of Salmonella and investigate the dominant serovars distribution in raw beef and to screen the isolated serovars for the prescense of beta-lactamases and virulence genes. A total of 150 samples of raw beef sold at butcher shops (n = 75) and supermarkets (n = 75) in Karachi city were collected (50 samples each from muscles, lymph nodes, and minced beef). The samples were cultured according to the ISO-6579-1guidlines. The overall prevalence of Salmonella strains was found to be 21.34%. A total of 56 isolates of Salmonella belonging to four serogroups (Salmonella Pullorum, Salmonella Enteritidis, Salmonella Typhimurium and Salmonella Choleraesuis) were isolated from beef muscles (12%), lymph nodes (24%) and minced beef (28%) samples collected from butcher shops (av. 21.34%). No Salmonella was detected in beef samples collected from supermarkets. S. Enteritidis contamination was highest (37.5%), followed by S. Choleraesuis (30.4%), S. Pullorum (19.6%) and S. Typhimurium (12.5 %). Antibiotic susceptibility testing revealed that Salmonella isolates were highly resistant to Oxytetracycline (90%), Ampicillin (90.5%), Amoxicillin (81.1%), Tetracycline (76%), Neomycin, (79.8%) and Ciprofloxacin (61.4%). The Salmonella isolates examined were more susceptible to the Cephalosporin antibiotics such as Cefixime (43.2%), Cefepime (48.2) and Cefoxitin (49.8%). PCR based screening of blaTEM, blaCTX-M and blaSHV revealed that blaCTX-M and blaTEM were the dominant resistant genes in S. Enteritidis and S. Typhimurium followed by S. Pullorum and S. Choleraesuis whereas blaSHV was the least detected beta-lactamase in Salmonella isolates. Virulence genes screening revealed that at least five genes were present in all the serovars, highest being present in S. Enteritidis (12/17) and S. Typhimurium (12/17). S. Cholerasuis (5/17) carried the least number of virulence genes followed by S. Pullorum (6/17). The present data suggest that beef samples from butcher shops of Karachi city are heavily contaminated with MDR Salmonella. The presence of resistance and virulence genes in MDR strains of Salmonella may play a significant role in transmission and development of Salmonella infection in humans. Full article
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7 pages, 388 KiB  
Article
Rifabutin Suppresses Inducible Clarithromycin Resistance in Mycobacterium abscessus by Blocking Induction of whiB7 and erm41
by Dinah Binte Aziz, Mei Lin Go and Thomas Dick
Antibiotics 2020, 9(2), 72; https://doi.org/10.3390/antibiotics9020072 - 10 Feb 2020
Cited by 24 | Viewed by 4581
Abstract
Clarithromycin (CLR) is the corner stone in regimens for the treatment of lung disease caused by Mycobacterium abscessus (Mab). However, many strains harbor the CLR-inducible CLR resistance gene erm41, encoding a ribosome methylase. Induction of erm41 is mediated by the transcription factor [...] Read more.
Clarithromycin (CLR) is the corner stone in regimens for the treatment of lung disease caused by Mycobacterium abscessus (Mab). However, many strains harbor the CLR-inducible CLR resistance gene erm41, encoding a ribosome methylase. Induction of erm41 is mediated by the transcription factor whiB7. We hypothesized that an inhibitor of RNA synthesis should be able to block the whiB7–erm41 induction response to CLR exposure and thus suppress CLR resistance. Recently, we discovered that the rifampicin analog rifabutin (RFB) shows attractive potency against Mab. To determine whether RFB-CLR combinations are synergistic, a checkerboard analysis against a collection of erm41 positive and negative Mab strains was carried out. This revealed synergy of the two drugs for erm41 positive but not for erm41 negative strains. To determine whether RFB’s potentiation effect was due to inhibition of the transcriptional induction of the whiB7–erm41 resistance system, we measured the effect of CLR alone and in combination with RFB on whiB7 and erm41 mRNA levels. CLR alone strongly induced whiB7 and erm41 expression as expected. The synergistic, growth-inhibiting combination of RFB with CLR blocked induction of both genes. These results suggest that RFB suppresses inducible CLR resistance by preventing induction of whiB7 and erm41 expression. Full article
(This article belongs to the Special Issue Antibiotics against Tuberculosis)
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15 pages, 633 KiB  
Article
Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales
by Antonio Vena, Daniele Roberto Giacobbe, Nadia Castaldo, Annamaria Cattelan, Cristina Mussini, Roberto Luzzati, Francesco Giuseppe De Rosa, Filippo Del Puente, Claudio Maria Mastroianni, Antonio Cascio, Sergio Carbonara, Alessandro Capone, Silvia Boni, Chiara Sepulcri, Marianna Meschiari, Francesca Raumer, Alessandra Oliva, Silvia Corcione, Matteo Bassetti and for the Ceftabuse Study Group
Antibiotics 2020, 9(2), 71; https://doi.org/10.3390/antibiotics9020071 - 9 Feb 2020
Cited by 73 | Viewed by 7230
Abstract
Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram−negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who [...] Read more.
Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram−negative bacteria (GNB) other than carbapenem-resistant Enterobacterales (CRE) is very limited. Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≥72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events. Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were P. aeruginosa (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing Enterobacterales (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia (n = 20; 48.8%), primary bacteremia (n = 7; 17.1%), intra-abdominal infection (n = 4; 9.8%), and bone infection (n = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment (n = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population. Conclusions: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE. Full article
(This article belongs to the Special Issue Stewardship of Antibiotics for Multidrug-Resistant Gram-Negative Bacteria)
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7 pages, 722 KiB  
Article
IncI1 Plasmid Associated with blaCTX-M-2 Transmission in ESBL-Producing Escherichia coli Isolated from Healthy Thoroughbred Racehorse, Japan
by Eddy Sukmawinata, Ryoko Uemura, Wataru Sato, Shuya Mitoma, Takuya Kanda and Masuo Sueyoshi
Antibiotics 2020, 9(2), 70; https://doi.org/10.3390/antibiotics9020070 - 7 Feb 2020
Cited by 9 | Viewed by 3115
Abstract
In our previous study, extended spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBLEC) were isolated from healthy Thoroughbred racehorse feces samples in Japan. Some ESBL genes were predicted to be located on the conjugative plasmid. PCR-based replicon typing (PBRT) is a useful method to monitor [...] Read more.
In our previous study, extended spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBLEC) were isolated from healthy Thoroughbred racehorse feces samples in Japan. Some ESBL genes were predicted to be located on the conjugative plasmid. PCR-based replicon typing (PBRT) is a useful method to monitor and detect the association of replicons with specific plasmid-borne resistant genes. This study aimed to evaluate the plasmid replicon associated with ESBLEC isolated from healthy Thoroughbred racehorses at Japan Racing Association Training Centers in Japan. A total of 24 ESBLECs isolated from 23 (10.8%) individual Thoroughbred racehorse feces samples were used in this study. ESBL gene transfer was performed using a conjugation assay. Then, replicon types of ESBLEC isolates and their transconjugants were determined using PBRT. Pulsed-field gel electrophoresis (PFGE) was performed to look at the clonality of the ESBLECs isolates. ESBLECs were detected from 10.8% of healthy Thoroughbred racehorses. The blaCTX-M-2 was identified as the dominant type of ESBL gene, followed by blaCTX-M-1 and blaTEM-116. In this study, only the blaCTX-M-2 and the IncI1 plasmid were transferred to transconjugants. The PFGE results showed that ESBL genes were distributed in diversity of ESBLECs. This finding suggested that the IncI1 plasmid was associated with the dissemination of blaCTX-M-2 in Thoroughbred racehorses in Japan. Full article
(This article belongs to the Special Issue Antibiotics and Environment)
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28 pages, 2616 KiB  
Review
Targeting Bacterial Cell Division: A Binding Site-Centered Approach to the Most Promising Inhibitors of the Essential Protein FtsZ
by Andrea Casiraghi, Lorenzo Suigo, Ermanno Valoti and Valentina Straniero
Antibiotics 2020, 9(2), 69; https://doi.org/10.3390/antibiotics9020069 - 7 Feb 2020
Cited by 46 | Viewed by 6665
Abstract
Binary fission is the most common mode of bacterial cell division and is mediated by a multiprotein complex denominated the divisome. The constriction of the Z-ring splits the mother bacterial cell into two daughter cells of the same size. The Z-ring is formed [...] Read more.
Binary fission is the most common mode of bacterial cell division and is mediated by a multiprotein complex denominated the divisome. The constriction of the Z-ring splits the mother bacterial cell into two daughter cells of the same size. The Z-ring is formed by the polymerization of FtsZ, a bacterial protein homologue of eukaryotic tubulin, and it represents the first step of bacterial cytokinesis. The high grade of conservation of FtsZ in most prokaryotic organisms and its relevance in orchestrating the whole division system make this protein a fascinating target in antibiotic research. Indeed, FtsZ inhibition results in the complete blockage of the division system and, consequently, in a bacteriostatic or a bactericidal effect. Since many papers and reviews already discussed the physiology of FtsZ and its auxiliary proteins, as well as the molecular mechanisms in which they are involved, here, we focus on the discussion of the most compelling FtsZ inhibitors, classified by their main protein binding sites and following a medicinal chemistry approach. Full article
(This article belongs to the Special Issue Antibiotic Targets in Bacterial DNA Replication and Cell Division)
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11 pages, 230 KiB  
Article
Comparative In Vitro Resistance of Human Periodontal Bacterial Pathogens to Tinidazole and Four Other Antibiotics
by Thomas E. Rams, Jacqueline D. Sautter and Arie J. van Winkelhoff
Antibiotics 2020, 9(2), 68; https://doi.org/10.3390/antibiotics9020068 - 7 Feb 2020
Cited by 28 | Viewed by 4928
Abstract
The in vitro resistance of selected red/orange complex periodontal pathogens to tinidazole was compared with four other antibiotics. Subgingival biofilm samples from 88 adults with severe periodontitis were anaerobically incubated on enriched Brucella blood agar with and without supplementation with tinidazole (16 mg/L), [...] Read more.
The in vitro resistance of selected red/orange complex periodontal pathogens to tinidazole was compared with four other antibiotics. Subgingival biofilm samples from 88 adults with severe periodontitis were anaerobically incubated on enriched Brucella blood agar with and without supplementation with tinidazole (16 mg/L), metronidazole (16 mg/L), amoxicillin (8 mg/L), doxycycline (4 mg/L), or clindamycin (4 mg/L). Growth of Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia/nigrescens, Parvimonas micra, Fusobacterium nucleatum, Streptococcus constellatus, or Campylobacter rectus on antibiotic-supplemented plates indicated their in vitro antibiotic resistance. Tinidazole inhibited all test species, except P. intermedia/nigrescens, P. micra, and S. constellatus in 3.8%, 10.2%, and 88.9% of species-positive patients, respectively. Significantly fewer patients yielded tinidazole-resistant test species, and had significantly lower subgingival proportions of tinidazole-resistant organisms, than patients with amoxicillin, doxycycline, or clindamycin-resistant species, but not those with metronidazole-resistant strains. Joint in vitro species resistance to tinidazole and amoxicillin, or metronidazole and amoxicillin, was rare. Tinidazole performed in vitro similar to metronidazole, and markedly better than amoxicillin, doxycycline, or clindamycin, against fresh clinical isolates of red/orange complex periodontal pathogens. As a result of its similar antimicrobial spectrum, and more convenient once-a-day oral dosing, tinidazole should be considered in place of metronidazole for systemic periodontitis drug therapy. Full article
(This article belongs to the Special Issue Antibiotics and Antimicrobials in Dentistry)
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