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Antibiotics, Volume 8, Issue 2 (June 2019)

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Cover Story (view full-size image) Antimicrobial resistance has jeopardized modern healthcare practices. Herein we describe the [...] Read more.
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Open AccessArticle
Qualitative Analysis of Primary Care Provider Prescribing Decisions for Urinary Tract Infections
Antibiotics 2019, 8(2), 84; https://doi.org/10.3390/antibiotics8020084
Received: 14 May 2019 / Revised: 13 June 2019 / Accepted: 14 June 2019 / Published: 19 June 2019
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Abstract
Inappropriate choices and durations of therapy for urinary tract infections (UTI) are a common and widespread problem. In this qualitative study, we sought to understand why primary care providers (PCPs) choose certain antibiotics or durations of treatment and the sources of information they [...] Read more.
Inappropriate choices and durations of therapy for urinary tract infections (UTI) are a common and widespread problem. In this qualitative study, we sought to understand why primary care providers (PCPs) choose certain antibiotics or durations of treatment and the sources of information they rely upon to guide antibiotic-prescribing decisions. We conducted semi-structured interviews with 18 PCPs in two family medicine clinics focused on antibiotic-prescribing decisions for UTIs. Our interview guide focused on awareness and familiarity with guidelines (knowledge), acceptance and outcome expectancy (attitudes), and external barriers. We followed a six-phase approach to thematic analysis, finding that many PCPs believe that fluoroquinolones achieve more a rapid and effective control of UTI symptoms than trimethoprim-sulfamethoxazole or nitrofurantoin. Most providers were unfamiliar with fosfomycin as a possible first-line agent for the treatment of acute cystitis. PCPs may be misled by advanced patient age, diabetes, and recurrent UTIs to make inappropriate choices for the treatment of acute cystitis. For support in clinical decision making, few providers relied on guidelines, preferring instead to have decision support embedded in the electronic medical record. Knowing the PCPs’ knowledge gaps and preferred sources of information will guide the development of a primary care-specific antibiotic stewardship intervention for acute cystitis. Full article
(This article belongs to the Special Issue Feature Paper in Antibiotics for 2019)
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Open AccessReview
Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis
Antibiotics 2019, 8(2), 83; https://doi.org/10.3390/antibiotics8020083
Received: 31 May 2019 / Revised: 10 June 2019 / Accepted: 14 June 2019 / Published: 18 June 2019
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Abstract
Discovering new antibiotics is vital to combat the growing threat of antimicrobial resistance. Most currently used antibiotics originate from the natural products of actinomycete bacteria, particularly Streptomyces species, that were discovered over 60 years ago. However, genome sequencing has revealed that most antibiotic-producing [...] Read more.
Discovering new antibiotics is vital to combat the growing threat of antimicrobial resistance. Most currently used antibiotics originate from the natural products of actinomycete bacteria, particularly Streptomyces species, that were discovered over 60 years ago. However, genome sequencing has revealed that most antibiotic-producing microorganisms encode many more natural products than previously thought. Biosynthesis of these natural products is tightly regulated by global and cluster situated regulators (CSRs), most of which respond to unknown environmental stimuli, and this likely explains why many biosynthetic gene clusters (BGCs) are not expressed under laboratory conditions. One approach towards novel natural product discovery is to awaken these cryptic BGCs by re-wiring the regulatory control mechanism(s). Most CSRs bind intergenic regions of DNA in their own BGC to control compound biosynthesis, but some CSRs can control the biosynthesis of multiple natural products by binding to several different BGCs. These cross-cluster regulators present an opportunity for natural product discovery, as the expression of multiple BGCs can be affected through the manipulation of a single regulator. This review describes examples of these different mechanisms, including specific examples of cross-cluster regulation, and assesses the impact that this knowledge may have on the discovery of novel natural products. Full article
(This article belongs to the Special Issue Mechanism and Regulation of Antibiotic Synthesis in Streptomyces)
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Open AccessArticle
A Topical Desiccant Agent in Association with Manual Debridement in the Initial Treatment of Peri-Implant Mucositis: A Clinical and Microbiological Pilot Study
Antibiotics 2019, 8(2), 82; https://doi.org/10.3390/antibiotics8020082
Received: 27 May 2019 / Revised: 16 June 2019 / Accepted: 16 June 2019 / Published: 18 June 2019
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Abstract
In patients presenting mucositis, effective sub-gingival debridement is crucial to prevent peri-implantitis. The aim of this randomized study was to assess the three-month (T1) effects of a locally delivered liquid desiccant agent with molecular hygroscopic properties, in association with manual debridement, at sites [...] Read more.
In patients presenting mucositis, effective sub-gingival debridement is crucial to prevent peri-implantitis. The aim of this randomized study was to assess the three-month (T1) effects of a locally delivered liquid desiccant agent with molecular hygroscopic properties, in association with manual debridement, at sites with peri-implant mucositis. Twenty-three patients presenting at least one implant with no radiographically detectable bone loss, a pocket probing depth (PPD) ≥ 4 mm, and bleeding on probing (BOP), were included. At baseline (T0), patients were randomly assigned to receive the aforementioned desiccant agent before debridement (Test-Group), or a Chlorhexidine 1% disinfectant gel after debridement (Control-Group). Treatments were repeated after seven and 14 days. Peri-implant soft tissue assessment [PPD, BOP, Modified Bleeding Index (mBI), Visible Plaque Index (VPI), and Modified Plaque Index (mPLI)] and microbial sampling were performed at T0 and T1. At T1 the Test-Group presented significantly greater reductions for BOP, mBI, VPI, and mPLI. Concerning the deepest sites of the treated implants, both groups showed statistically significant reductions for BOP and mBI between T0 and T1. Furthermore, the Test-Group exhibited a significant decrease in anaerobic bacteria. Despite these valid outcomes, a complete resolution of the inflammatory conditions was not achieved by any of the groups. Full article
(This article belongs to the Special Issue Antibiotics and Antimicrobials in Dentistry)
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Open AccessArticle
Impact of Mobility on Methicillin-Resistant Staphylococcus aureus among Injection Drug Users
Antibiotics 2019, 8(2), 81; https://doi.org/10.3390/antibiotics8020081
Received: 9 May 2019 / Revised: 31 May 2019 / Accepted: 12 June 2019 / Published: 17 June 2019
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Abstract
In this study, we develop and present a deterministic model for the transmission dynamics of methicillin-resistant staphylococcus aureus (MRSA) among injection drug users. The model consists of non-injection drug users as well as low-and high-risk injection drug users (IDUs). The model further incorporates [...] Read more.
In this study, we develop and present a deterministic model for the transmission dynamics of methicillin-resistant staphylococcus aureus (MRSA) among injection drug users. The model consists of non-injection drug users as well as low-and high-risk injection drug users (IDUs). The model further incorporates the movement of these individuals between large metro, suburban and rural areas. The model parameters were estimated by fitting the model to the 2008–2013 disease prevalence data for non-IDUs obtained from the Agency for Healthcare and Research and Quality (AHRQ), as well as the 2009–2013 Census Bureau data for the number of individuals migrating between three different counties in Kansas. Sensitivity analysis was implemented to determine the parameters with the most significant impact on the total number of infected individuals; the transmission probability, recovery rates, and positive behavioral change parameter for the subgroup have the most significant effect on the number of infected individuals. Furthermore, the sensitivity of the parameters in the different areas was the same when the areas are disconnected. When the areas are connected, the parameters in large-metro areas were the most sensitive, and the rural areas were least sensitive. The result shows that to effectively control the disease across the large metro, suburban and rural areas, it is best to focus on controlling both behavior and disease in the large metro area as this has a trickle-down effect to the other places. However, controlling behavior and disease at the same time in all the areas will lead to the elimination of the disease. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Open AccessReview
Complement Evasion in Borrelia spirochetes: Mechanisms and Opportunities for Intervention
Antibiotics 2019, 8(2), 80; https://doi.org/10.3390/antibiotics8020080
Received: 15 May 2019 / Revised: 10 June 2019 / Accepted: 11 June 2019 / Published: 13 June 2019
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Abstract
Lyme disease (LD) is an increasingly prevalent, climate change-accelerated, vector-borne infectious disease with significant morbidity and cost in a proportion of patients who experience ongoing symptoms after antibiotic treatment, a condition known as post-treatment Lyme disease syndrome (PTLDS). Spirochetal bacteria of Borrelia species [...] Read more.
Lyme disease (LD) is an increasingly prevalent, climate change-accelerated, vector-borne infectious disease with significant morbidity and cost in a proportion of patients who experience ongoing symptoms after antibiotic treatment, a condition known as post-treatment Lyme disease syndrome (PTLDS). Spirochetal bacteria of Borrelia species are the causative agents of LD. These obligate parasites have evolved sophisticated immune evasion mechanisms, including the ability to defeat the innate immune system’s complement cascade. Research on complement function and Borrelia evasion mechanisms, focusing on human disease, is reviewed, highlighting opportunities to build on existing knowledge. Implications for the development of new antibiotic therapies having the potential to prevent or cure PTLDS are discussed. It is noted that a therapy enabling the complement system to effectively counter Borrelia might have lower cost and fewer side-effects and risks than broad-spectrum antibiotic use and could avert the need to develop and administer a vaccine. Full article
(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)
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Open AccessArticle
Antibiotic Prescribing Quality in Out-of-Hours Primary Care and Critical Appraisal of Disease-Specific Quality Indicators
Antibiotics 2019, 8(2), 79; https://doi.org/10.3390/antibiotics8020079
Received: 15 May 2019 / Revised: 5 June 2019 / Accepted: 7 June 2019 / Published: 12 June 2019
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Abstract
Outpatient antibiotic use in Belgium is among the highest in Europe. The most common reason for an encounter in out-of-hours (OOH) primary care is an infection. In this study, we assessed all consultations from July 2016 to June 2018 at five OOH services. [...] Read more.
Outpatient antibiotic use in Belgium is among the highest in Europe. The most common reason for an encounter in out-of-hours (OOH) primary care is an infection. In this study, we assessed all consultations from July 2016 to June 2018 at five OOH services. We described antibiotic prescribing by diagnosis, calculated disease-specific antibiotic prescribing quality indicators’ (APQI) values and critically appraised these APQI. We determined that 111,600 encounters resulted in 26,436 (23.7%) antibiotic prescriptions. The APQI diagnoses (i.e., bronchitis, upper respiratory infection, cystitis, tonsillitis, sinusitis, otitis media, and pneumonia) covered 14,927 (56.7%) antibiotic prescriptions. Erysipelas (1344 (5.1%)) and teeth/gum disease (982 (3.7%)) covered more prescriptions than sinusitis or pneumonia. Over 75% of patients with tonsillitis and over 50% with bronchitis, sinusitis, and otitis media were prescribed an antibiotic. Only for otitis media the choice of antibiotic was near the acceptable range. Over 10% of patients with bronchitis or pneumonia and over 25% of female patients with an acute cystitis received quinolones. The APQI cover the diagnoses for only 57% of all antibiotic prescriptions. As 5.1% and 3.7% of antibiotic prescriptions are made for erysipelas and teeth/gum disease, respectively, we propose to add these indications when assessing antibiotic prescribing quality in OOH primary care. Full article
(This article belongs to the Special Issue Feature Paper in Antibiotics for 2019)
Open AccessCase Report
Levofloxacin-Associated Neurotoxicity in a Patient with a High Concentration of Levofloxacin in the Blood and Cerebrospinal Fluid
Antibiotics 2019, 8(2), 78; https://doi.org/10.3390/antibiotics8020078
Received: 28 May 2019 / Revised: 10 June 2019 / Accepted: 10 June 2019 / Published: 12 June 2019
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Abstract
Neurotoxicity is a rare and intolerable adverse effect associated with levofloxacin therapy, whose diagnosis has mostly been reported based on medical history rather than quantitative measures in the blood. We report a 68-year-old man with levofloxacin-associated encephalopathy and myoclonus with high levels of [...] Read more.
Neurotoxicity is a rare and intolerable adverse effect associated with levofloxacin therapy, whose diagnosis has mostly been reported based on medical history rather than quantitative measures in the blood. We report a 68-year-old man with levofloxacin-associated encephalopathy and myoclonus with high levels of levofloxacin in the blood and cerebrospinal fluid. After hemodialysis, these decreased, and his symptoms rapidly improved. An electroencephalogram was also normal. This case showed the concentration of levofloxacin to be clearly related to levofloxacin-associated neurotoxicity. Therefore, an estimation of its concentration may contribute to accurate diagnosis. Full article
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Open AccessArticle
Inhibition of Bacterial and Fungal Biofilm Formation by 675 Extracts from Microalgae and Cyanobacteria
Antibiotics 2019, 8(2), 77; https://doi.org/10.3390/antibiotics8020077
Received: 13 May 2019 / Revised: 3 June 2019 / Accepted: 5 June 2019 / Published: 12 June 2019
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Abstract
Bacterial biofilms are complex biological systems that are difficult to eradicate at a medical, industrial, or environmental level. Biofilms confer bacteria protection against external factors and antimicrobial treatments. Taking into account that about 80% of human infections are caused by bacterial biofilms, the [...] Read more.
Bacterial biofilms are complex biological systems that are difficult to eradicate at a medical, industrial, or environmental level. Biofilms confer bacteria protection against external factors and antimicrobial treatments. Taking into account that about 80% of human infections are caused by bacterial biofilms, the eradication of these structures is a great priority. Biofilms are resistant to old-generation antibiotics, which has led to the search for new antimicrobials from different sources, including deep oceans/seas. In this study, 675 extracts obtained from 225 cyanobacteria and microalgae species (11 phyla and 6 samples belonging to unknown group) were obtained from different culture collections: The Blue Biotechnology and Ecotoxicology Culture Collection (LEGE-CC), the Coimbra Collection of Algae (ACOI) from Portugal, and the Roscoff Culture Collection (RCC) from France. The largest number of samples was made up of the microalgae phylum Chlorophyta (270) followed by Cyanobacteria (261). To obtain a large range of new bioactive compounds, a method involving three consecutive extractions (hexane, ethyl acetate, and methanol) was used. The antibiofilm activity of extracts was determined against seven different bacterial species and two Candida strains in terms of minimal biofilm inhibitory concentration (MBIC). The highest biofilm inhibition rates (%) were achieved against Candida albicans and Enterobacter cloacae. Charophyta, Chlorophyta, and Cyanobacteria were the most effective against all microorganisms. In particular, extracts of Cercozoa phylum presented the lowest MBIC50 and MBIC90 values for all the strains except C. albicans. Full article
(This article belongs to the Special Issue Marine Antimicrobials)
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Open AccessReview
The Link between Purine Metabolism and Production of Antibiotics in Streptomyces
Antibiotics 2019, 8(2), 76; https://doi.org/10.3390/antibiotics8020076
Received: 10 May 2019 / Revised: 30 May 2019 / Accepted: 3 June 2019 / Published: 6 June 2019
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Abstract
Stress and starvation causes bacterial cells to activate the stringent response. This results in down-regulation of energy-requiring processes related to growth, as well as an upregulation of genes associated with survival and stress responses. Guanosine tetra- and pentaphosphates (collectively referred to as (p)ppGpp) [...] Read more.
Stress and starvation causes bacterial cells to activate the stringent response. This results in down-regulation of energy-requiring processes related to growth, as well as an upregulation of genes associated with survival and stress responses. Guanosine tetra- and pentaphosphates (collectively referred to as (p)ppGpp) are critical for this process. In Gram-positive bacteria, a main function of (p)ppGpp is to limit cellular levels of GTP, one consequence of which is reduced transcription of genes that require GTP as the initiating nucleotide, such as rRNA genes. In Streptomycetes, the stringent response is also linked to complex morphological differentiation and to production of secondary metabolites, including antibiotics. These processes are also influenced by the second messenger c-di-GMP. Since GTP is a substrate for both (p)ppGpp and c-di-GMP, a finely tuned regulation of cellular GTP levels is required to ensure adequate synthesis of these guanosine derivatives. Here, we discuss mechanisms that operate to control guanosine metabolism and how they impinge on the production of antibiotics in Streptomyces species. Full article
(This article belongs to the Special Issue Mechanism and Regulation of Antibiotic Synthesis in Streptomyces)
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Open AccessArticle
Antimicrobial Drug Administration and Antimicrobial Resistance of Salmonella Isolates Originating from the Broiler Production Value Chain in Nigeria
Antibiotics 2019, 8(2), 75; https://doi.org/10.3390/antibiotics8020075
Received: 25 March 2019 / Revised: 19 May 2019 / Accepted: 21 May 2019 / Published: 6 June 2019
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Abstract
Salmonella is among the pathogens on the high global priority lists for monitoring for studies on the discovery of new antimicrobials and understanding of how antimicrobial resistance (AMR) develops. AMR in connection with antibiotic usage patterns has been considered as a strong factor [...] Read more.
Salmonella is among the pathogens on the high global priority lists for monitoring for studies on the discovery of new antimicrobials and understanding of how antimicrobial resistance (AMR) develops. AMR in connection with antibiotic usage patterns has been considered as a strong factor and contributor to the AMR pool. The purposes of use, pattern of antimicrobial drug administration, as well as the prevalence of AMR in Salmonella originating from the Nigeria broiler production value chain (NBPVC) was explored. A well-structured questionnaire on antimicrobial usage (n = 181) was used for sampling that focused on 21 antimicrobials from 151 locations. Simultaneously, AMR testing for 18 commonly used antimicrobials on Salmonella in humans was also carried out. Antimicrobial resistance Salmonella spp. were isolated in 23% of the samples (261 of 1135 samples from the broiler input, products, and the environment) using modified ISO 6579 and invA PCR protocols. Over 80% of the antimicrobials used in the NBPVC were administered without a veterinarian prescription. Prevalence of antimicrobial administration without prescription were as follows: live-bird-market (100%), hatchery (86.7%), grow-out-farm (75%), and breeder (66.7%). Widespread prophylactic and metaphylactic use of antimicrobials were recorded with the highest use seen for enrofloxacin (63% and 24%), tetracycline (58% and 33%), and erythromycin (50% and 17%). Antimicrobial resistance was highest for flumequine (100%), penicillin (95%), and perfloxacin (89%). High levels of use without laboratory support of a newer generation of a class of antibiotics suspected to confer high resistance on older generations of the same class (quinolones) was observed. Full article
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Open AccessArticle
Characterization of a Lytic Bacteriophage as an Antimicrobial Agent for Biocontrol of Shiga Toxin-Producing Escherichia coli O145 Strains
Antibiotics 2019, 8(2), 74; https://doi.org/10.3390/antibiotics8020074
Received: 20 April 2019 / Revised: 27 May 2019 / Accepted: 31 May 2019 / Published: 5 June 2019
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Abstract
Shiga toxin-producing Escherichia coli (STEC) O145 is one of the most prevalent non-O157 serogroups associated with foodborne outbreaks. Lytic phages are a potential alternative to antibiotics in combatting bacterial pathogens. In this study, we characterized a Siphoviridae phage lytic against STEC O145 strains [...] Read more.
Shiga toxin-producing Escherichia coli (STEC) O145 is one of the most prevalent non-O157 serogroups associated with foodborne outbreaks. Lytic phages are a potential alternative to antibiotics in combatting bacterial pathogens. In this study, we characterized a Siphoviridae phage lytic against STEC O145 strains as a novel antimicrobial agent. Escherichia phage vB_EcoS-Ro145clw (Ro145clw) was isolated and purified prior to physiological and genomic characterization. Then, in vitro antimicrobial activity against an outbreak strain, E. coli O145:H28, was evaluated. Ro145clw is a double-stranded DNA phage with a genome 42,031 bp in length. Of the 67 genes identified in the genome, 21 were annotated with functional proteins, none of which were stx genes. Ro145clw had a latent period of 21 min and a burst size of 192 phages per infected cell. The phage could sustain a wide range of pH (pH 3 to pH 10) and temperatures (−80 °C to −73 °C). Ro145clw was able to reduce E. coli O145:H28 in lysogeny broth by approximately 5 log at 37 °C in four hours. These findings indicate that the Ro145clw phage is a promising antimicrobial agent that can be used to control E. coli O145 in adverse pH and temperature conditions. Full article
(This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond)
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Open AccessArticle
Size and Flexibility Define the Inhibition of the H3N2 Influenza Endonuclease Enzyme by Calix[n]arenes
Antibiotics 2019, 8(2), 73; https://doi.org/10.3390/antibiotics8020073
Received: 4 April 2019 / Revised: 29 May 2019 / Accepted: 30 May 2019 / Published: 3 June 2019
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Abstract
Inhibition of H3N2 influenza PA endonuclease activity by a panel of anionic calix[n]arenes and β-cyclodextrin sulfate has been studied. The joint experimental and theoretical results reveal that the larger, more flexible and highly water-soluble sulfonato-calix[n]arenes have high inhibitory activity, with para-sulfonato-calix[8]arene, SC8, having [...] Read more.
Inhibition of H3N2 influenza PA endonuclease activity by a panel of anionic calix[n]arenes and β-cyclodextrin sulfate has been studied. The joint experimental and theoretical results reveal that the larger, more flexible and highly water-soluble sulfonato-calix[n]arenes have high inhibitory activity, with para-sulfonato-calix[8]arene, SC8, having an IC50 value of 6.4 μM. Molecular docking calculations show the SC8 can interact at both the polyanion binding site and also the catalytic site of H3N2 influenza PA endonuclease. Full article
(This article belongs to the Special Issue Supramolecular Anti-Infectives)
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Open AccessArticle
Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases
Antibiotics 2019, 8(2), 72; https://doi.org/10.3390/antibiotics8020072
Received: 28 March 2019 / Revised: 20 April 2019 / Accepted: 25 May 2019 / Published: 30 May 2019
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Abstract
Three patients, each of whom had required intensive open-ended antimicrobial therapy for control of the symptoms of chronic relapsing neurological Lyme disease and relapsing babesiosis, were able to discontinue treatment and remain clinically well for periods of observation of 6–23 months following the [...] Read more.
Three patients, each of whom had required intensive open-ended antimicrobial therapy for control of the symptoms of chronic relapsing neurological Lyme disease and relapsing babesiosis, were able to discontinue treatment and remain clinically well for periods of observation of 6–23 months following the completion of a finite course of treatment solely with disulfiram. One patient relapsed at six months and is being re-treated with disulfiram. Full article
(This article belongs to the Special Issue Antibiotics Resistance of Borrelia)
Open AccessReview
Phenotypic and Genotypic Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Related to Persistent Endovascular Infection
Antibiotics 2019, 8(2), 71; https://doi.org/10.3390/antibiotics8020071
Received: 1 May 2019 / Revised: 22 May 2019 / Accepted: 24 May 2019 / Published: 29 May 2019
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Abstract
Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus infection and correlates with poor clinical outcomes. MRSA isolates from patients with PB differ significantly from those of resolving bacteremia (RB) with regard to several in vitro phenotypic and [...] Read more.
Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus infection and correlates with poor clinical outcomes. MRSA isolates from patients with PB differ significantly from those of resolving bacteremia (RB) with regard to several in vitro phenotypic and genotypic profiles. For instance, PB strains exhibit less susceptibility to cationic host defense peptides and vancomycin (VAN) killing under in vivo-like conditions, greater damage to endothelial cells, thicker biofilm formation, altered growth rates, early activation of many global virulence regulons (e.g., sigB, sarA, sae and agr) and higher expression of purine biosynthesis genes (e.g., purF) than RB strains. Importantly, PB strains are significantly more resistant to VAN treatment in experimental infective endocarditis as compared to RB strains, despite similar VAN minimum inhibitory concentrations (MICs) in vitro. Here, we review relevant phenotypic and genotypic characteristics related to the PB outcome. These and future insights may improve our understanding of the specific mechanism(s) contributing to the PB outcome, and aid in the development of novel therapeutic and preventative measures against this life-threatening infection. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Open AccessArticle
Contributions of Net Charge on the PlyC Endolysin CHAP Domain
Antibiotics 2019, 8(2), 70; https://doi.org/10.3390/antibiotics8020070
Received: 29 April 2019 / Revised: 20 May 2019 / Accepted: 25 May 2019 / Published: 28 May 2019
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Abstract
Bacteriophage endolysins, enzymes that degrade the bacterial peptidoglycan (PG), have gained an increasing interest as alternative antimicrobial agents, due to their ability to kill antibiotic resistant pathogens efficiently when applied externally as purified proteins. Typical endolysins derived from bacteriophage that infect Gram-positive hosts [...] Read more.
Bacteriophage endolysins, enzymes that degrade the bacterial peptidoglycan (PG), have gained an increasing interest as alternative antimicrobial agents, due to their ability to kill antibiotic resistant pathogens efficiently when applied externally as purified proteins. Typical endolysins derived from bacteriophage that infect Gram-positive hosts consist of an N-terminal enzymatically-active domain (EAD) that cleaves covalent bonds in the PG, and a C-terminal cell-binding domain (CBD) that recognizes specific ligands on the surface of the PG. Although CBDs are usually essential for the EADs to access the PG substrate, some EADs possess activity in the absence of CBDs, and a few even display better activity profiles or an extended host spectrum than the full-length endolysin. A current hypothesis suggests a net positive charge on the EAD enables it to reach the negatively charged bacterial surface via ionic interactions in the absence of a CBD. Here, we used the PlyC CHAP domain as a model EAD to further test the hypothesis. We mutated negatively charged surface amino acids of the CHAP domain that are not involved in structured regions to neutral or positively charged amino acids in order to increase the net charge from -3 to a range from +1 to +7. The seven mutant candidates were successfully expressed and purified as soluble proteins. Contrary to the current hypothesis, none of the mutants were more active than wild-type CHAP. Analysis of electrostatic surface potential implies that the surface charge distribution may affect the activity of a positively charged EAD. Thus, we suggest that while charge should continue to be considered for future engineering efforts, it should not be the sole focus of such engineering efforts. Full article
(This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond)
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Open AccessArticle
Evaluation of Antibiotics Residues in Chicken Meat Samples in Lebanon
Antibiotics 2019, 8(2), 69; https://doi.org/10.3390/antibiotics8020069
Received: 19 April 2019 / Revised: 23 May 2019 / Accepted: 24 May 2019 / Published: 28 May 2019
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Abstract
Antibiotic residue in chicken is a human health concern due to its harmful effects on consumer health. This study aims at screening the antibiotic residues from 80 chicken samples collected from farms located in different regions of Lebanon. An optimized multi-class method for [...] Read more.
Antibiotic residue in chicken is a human health concern due to its harmful effects on consumer health. This study aims at screening the antibiotic residues from 80 chicken samples collected from farms located in different regions of Lebanon. An optimized multi-class method for identification and quantification of 30 antibiotics from four different chemical classes (sulfonamides, tetracyclines, quinolones, and beta-lactams) has been developed by using liquid chromatography–mass spectrometry. The evaluation of antibiotics residues in 80 chicken muscles samples has shown that 77.5% of samples were at least contaminated with antibiotics residues, out of which 53.75% were exposed to co-occurrence of multidrug residues. The screening of the four antibiotics families has shown that ciprofloxacin (quinolones) represents the highest occurrence percentage (32.5%), followed by amoxicillin (β-lactams) (22.5%) and then tetracyclines (17.5%). Means of sarafloxacin, amoxicillin, and penicillin G residues levels were above the Maximum Residue Limit (MRL) recommended limit according to the European Union EC. This study revealed that chicken samples collected from Lebanese farms contain antibiotic residues. Guidelines for prudent use of antimicrobials agents for chicken should be adopted to reduce the prevalence of resistant Salmonella in chicken. Full article
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Open AccessArticle
Multiple Antibiotic Resistance (MAR), Plasmid Profiles, and DNA Polymorphisms among Vibrio vulnificus Isolates
Antibiotics 2019, 8(2), 68; https://doi.org/10.3390/antibiotics8020068
Received: 26 March 2019 / Revised: 19 May 2019 / Accepted: 19 May 2019 / Published: 28 May 2019
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Abstract
Sixty strains (n = 60) of Vibrio vulnificus were examined for their multiple antibiotic resistance (MAR) index, plasmid profiles, and DNA polymorphisms. Thirty-seven strains (n = 37) were isolated from cockles (Anadara granosa) in Malaysia, while 23 (n [...] Read more.
Sixty strains (n = 60) of Vibrio vulnificus were examined for their multiple antibiotic resistance (MAR) index, plasmid profiles, and DNA polymorphisms. Thirty-seven strains (n = 37) were isolated from cockles (Anadara granosa) in Malaysia, while 23 (n = 23) isolates were isolated from clams (Mercenaria mercenaria) in Qatar. All isolates were resistant to two or more of the antibiotics tested, with the most common resistances were demonstrated towards penicillin (93%), ampicillin (70%), cephalothin (65%), clindamycin (66%), vancomycin (64%), and erythromycin (51%). The antibiotic that experienced the least resistance was kanamycin (6%), and all isolates were susceptible to cefoperazone, streptomycin, and tetracycline. The MAR index for the V. vulnificus isolated from Malaysia and Qatar, possessed similar values which ranged from 0.2 to 0.7, respectively. Plasmid analysis demonstrated that 65% of V. vulnificus strains harbored plasmids, while 35% were not. Nineteen (P1–P19) plasmids profiles were observed. No specific cluster or group was observed although they were isolated from different sample sources and locations by phylogenetic analysis using GelCompar II software at an 80% similarity level. Results demonstrated the high MAR index and genomic heterogeneity of V. vulnificus, which are of great concern to the human health of those who have consumed cockles and clams from the study area. Full article
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Open AccessCase Report
Use of Ceftolozane/Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Pneumonia in a Pediatric Patient with Combined Immunodeficiency (CID): A Case Report from a Tertiary Hospital in Saudi Arabia
Antibiotics 2019, 8(2), 67; https://doi.org/10.3390/antibiotics8020067
Received: 1 April 2019 / Revised: 16 May 2019 / Accepted: 18 May 2019 / Published: 27 May 2019
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Abstract
Infections, with multidrug-resistant Pseudomonas aeruginosa, are a major concern in the pediatric intensive care unit, especially in immunocompromised patients. Some of these strains are resistant to all beta-lactams, including carbapenems, leaving very limited treatment options remaining. These options include aminoglycosides and colistin, [...] Read more.
Infections, with multidrug-resistant Pseudomonas aeruginosa, are a major concern in the pediatric intensive care unit, especially in immunocompromised patients. Some of these strains are resistant to all beta-lactams, including carbapenems, leaving very limited treatment options remaining. These options include aminoglycosides and colistin, both of which have poor pharmacokinetic profiles with significant toxicities. Newer beta-lactam/beta-lactamase inhibitor combinations offer additional novel options to treat such infections, given their good pharmacokinetic profiles and activity against multi-drug resistant strains. Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination approved in 2014. The drug demonstrates good activity against multidrug-resistant P. aeruginosa strains, including those resistant to all other antibiotics. Ceftolozane/tazobactam is currently approved in adult patients 18 years and older only. There are very limited data on its pharmacokinetic profile and clinical utility in the pediatric population. We report the use of ceftolozane/tazobactam to successfully treat pneumonia caused by multidrug-resistant P. aeruginosa in a pediatric patient with combined immunodeficiency syndrome. Full article
Open AccessArticle
Perceptions of Antibiotic Therapy Among Nursing Home Residents: Perspectives of Caregivers and Residents in a Mixed Exploratory Study
Antibiotics 2019, 8(2), 66; https://doi.org/10.3390/antibiotics8020066
Received: 10 April 2019 / Revised: 9 May 2019 / Accepted: 23 May 2019 / Published: 27 May 2019
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Abstract
Antimicrobial resistance is a major public health threat worldwide. Some authors have suggested that end-users of nursing homes have an influence on antibiotic prescribing. The objective of this study is to describe the views of end-users and professionals on residents’ behavior towards antibiotic [...] Read more.
Antimicrobial resistance is a major public health threat worldwide. Some authors have suggested that end-users of nursing homes have an influence on antibiotic prescribing. The objective of this study is to describe the views of end-users and professionals on residents’ behavior towards antibiotic therapy in terms of knowledge, beliefs, and attitudes towards this drug class and its prescribing process. This is a concurrent mixed methodology study using questionnaires and semi-directive individual interviews with nursing homes residents, nurses, and doctors practicing in these facilities. The questionnaires analyzed were collected from 35 residents (24.3%) and 109 nurses (75.7%). The qualitative interview involved 26 of total participants that agreed to be interviewed. We noticed misconceptions being held by the residents regarding the antibiotic resistance phenomenon. Additionally, nurses were not considered as a source of information about antibiotics. Nurses and residents had conflicting opinions about residents requesting antibiotics, and the findings depict a stereotypical view of the nurse profession as a reflection of a cognitive representation. The authors conclude that, despite many campaigns, further efforts are needed to tackle antimicrobial resistance. Initiatives could include raising awareness about antimicrobial resistance, clarifying the role of nurses, and communicating well with residents about their needs in nursing homes. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
Development of a High Throughput Screen for the Identification of Inhibitors of Peptidoglycan O-Acetyltransferases, New Potential Antibacterial Targets
Antibiotics 2019, 8(2), 65; https://doi.org/10.3390/antibiotics8020065
Received: 1 May 2019 / Revised: 22 May 2019 / Accepted: 22 May 2019 / Published: 27 May 2019
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Abstract
The O-acetylation of peptidoglycan occurs in many Gram-negative and most Gram-positive pathogens and this modification to the essential wall polymer controls the lytic activity of the autolysins, particularly the lytic transglycosylases, and inhibits that of the lysozymes of innate immunity systems. As [...] Read more.
The O-acetylation of peptidoglycan occurs in many Gram-negative and most Gram-positive pathogens and this modification to the essential wall polymer controls the lytic activity of the autolysins, particularly the lytic transglycosylases, and inhibits that of the lysozymes of innate immunity systems. As such, the peptidoglycan O-acetyltransferases PatA/B and OatA are recognized as virulence factors. In this study, we present the high throughput screening of small compound libraries to identify the first known inhibitors of these enzymes. The fluorometric screening assay developed involved monitoring the respective O-acetyltransferases as esterases using 4-methylumbelliferylacetate as substrate. Pilot screens of 3921 compounds validated the usefulness of the HTS protocol. A number of potential inhibitors were identified amongst a total of 145,000 low molecular-weight compounds, some of which were common to both enzymes, while others were unique to each. After eliminating a number of false positives in secondary screens, dose response curves confirmed the apparent specificity of a benzothiazolyl-pyrazolo-pyridine as an inhibitor of Neisseria gonorrhoeae PatB, and several coumarin-based compounds as inhibitors of both this PatB and OatA from Staphylococcus aureus. The benzothiazolyl-pyrazolo-pyridine was determined to be a non-competitive inhibitor of PatB with a Ki of 126 µM. At 177 µg/mL and close to its solubility limit, this compound caused a 90% reduction in growth of N. gonorrhoeae, while growth of Escherichia coli, a bacterium that lacks PatB and, hence, does not produce O-acetylated peptidoglycan, was unaffected. These data provide preliminary proof of concept that peptidoglycan O-acetyltransferases would serve as useful antibacterial targets. Full article
(This article belongs to the Special Issue Novel Strategies against Pathogenic Bacteria)
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Open AccessArticle
Statin Use and the Point Prevalence of Antibiotics in Ambulatory Patients with Diabetes in the National Health and Nutrition Examination Survey (NHANES) 2003–2012
Antibiotics 2019, 8(2), 64; https://doi.org/10.3390/antibiotics8020064
Received: 1 February 2019 / Revised: 26 March 2019 / Accepted: 8 April 2019 / Published: 27 May 2019
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Abstract
In patients with diabetes, the risk of infections is increased, hypothesized to be due to alterations in the immune system, among other changes. The pleotropic effects of statins have been investigated to assess their role in reducing the risk of infection and infection-related [...] Read more.
In patients with diabetes, the risk of infections is increased, hypothesized to be due to alterations in the immune system, among other changes. The pleotropic effects of statins have been investigated to assess their role in reducing the risk of infection and infection-related outcomes with varying results. The aim of this study is to determine if the use of statins is associated with a decrease in the point prevalence of oral antibiotic use in ambulatory patients with diabetes. Using data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2012, all adult patients diagnosed with diabetes were analyzed. Patients were grouped into those who were prescribed statins and those who were not. Oral antibiotic use between the two groups was compared. Data were standardized to national estimates. A total of 3240 patients with diabetes were identified, with 1575 statin users and 1665 non-statin users. After controlling for baseline socio-demographic and clinical variables, the overall point prevalence of oral antibiotic use in diabetes population was 3.5% with no difference between statin users and non-statin users (2.9% vs. 4%, p = 0.116). Based on the results of this study, the use of statins in patients with diabetes was not associated with a reduction in the point prevalence of antibiotic use. Full article
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Open AccessArticle
Antibacterial Performance of Terpenoids from the Australian Plant Eremophila lucida
Antibiotics 2019, 8(2), 63; https://doi.org/10.3390/antibiotics8020063
Received: 13 March 2019 / Revised: 12 May 2019 / Accepted: 14 May 2019 / Published: 17 May 2019
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Abstract
Plants in the Australian genus Eremophila (Scrophulariaceae) have attracted considerable recent attention for their antimicrobial compounds, which possess a wide range of chemical structures. As they are typically associated with the oily-waxy resin layer covering leaves and green branchlets, and Eremophila lucida is [...] Read more.
Plants in the Australian genus Eremophila (Scrophulariaceae) have attracted considerable recent attention for their antimicrobial compounds, which possess a wide range of chemical structures. As they are typically associated with the oily-waxy resin layer covering leaves and green branchlets, and Eremophila lucida is prominent among the species containing a pronounced sticky resin layer, this species was considered of interest for assessing its antibacterial constituents. The n-hexane fraction of the crude acetone extract of the leaves exhibited antibacterial activity against Staphylococcus aureus. Isolation led to the known compounds cembratriene, (3Z, 7E, 11Z)-15-hydroxycembra-3,7,11-trien-19-oic acid (1), the sesquiterpenoid, farnesal (2) and the viscidane diterpenoid, 5α-hydroxyviscida-3,14-dien-20-oic acid (3). The purified compounds were tested for antibacterial activity with 2 and 3 showing moderate antibacterial activity against Gram-positive bacteria. Full article
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Open AccessArticle
A 2-Year Single-Centre Audit on Antibiotic Resistance of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae Strains from an Intensive Care Unit and Other Wards in a General Public Hospital in Greece
Antibiotics 2019, 8(2), 62; https://doi.org/10.3390/antibiotics8020062
Received: 26 March 2019 / Revised: 27 April 2019 / Accepted: 13 May 2019 / Published: 15 May 2019
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Abstract
Hospital-acquired infections, particularly in the critical care setting, are becoming increasingly common during the last decade, with Gram-negative bacterial infections presenting the highest incidence among them. Multi-drug-resistant (MDR) Gram-negative infections are associated with high morbidity and mortality, with significant direct and indirect costs [...] Read more.
Hospital-acquired infections, particularly in the critical care setting, are becoming increasingly common during the last decade, with Gram-negative bacterial infections presenting the highest incidence among them. Multi-drug-resistant (MDR) Gram-negative infections are associated with high morbidity and mortality, with significant direct and indirect costs resulting from long hospitalization due to antibiotic failure. As treatment options become limited, antimicrobial stewardship programs aim to optimize the appropriate use of currently available antimicrobial agents and decrease hospital costs. Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae are the most common resistant bacteria encountered in intensive care units (ICUs) and other wards. To establish preventive measures, it is important to know the prevalence of Gram-negative isolated bacteria and antibiotic resistance profiles in each ward separately, compared with ICUs. In our single centre study, we compared the resistance levels per antibiotic of P. aeruginosa, A. baumannii and K.pneumoniae clinical strains between the ICU and other facilities during a 2-year period in one of the largest public tertiary hospitals in Greece. The analysis revealed a statistically significant higher antibiotic resistance of the three bacteria in the ICU isolates compared with those from other wards. ICU strains of P. aeruginosa presented the highest resistance rates to gentamycin (57.97%) and cefepime (56.67%), followed by fluoroquinolones (55.11%) and carbapenems (55.02%), while a sensitivity rate of 97.41% was reported to colistin. A high resistance rate of over 80% of A. baumannii isolates to most classes of antibiotics was identified in both the ICU environment and regular wards, with the lowest resistance rates reported to colistin (53.37% in ICU versus an average value of 31.40% in the wards). Statistically significant higher levels of resistance to most antibiotics were noted in ICU isolates of K. pneumoniae compared with non-ICU isolates, with the highest difference—up to 48.86%—reported to carbapenems. The maximum overall antibiotic resistance in our ICU was reported for Acinetobacter spp. (93.00%), followed by Klebsiella spp. (72.30%) and Pseudomonas spp. (49.03%). Full article
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Open AccessArticle
Solution-Mediated Modulation of Pseudomonas aeruginosa Biofilm Formation by a Cationic Synthetic Polymer
Antibiotics 2019, 8(2), 61; https://doi.org/10.3390/antibiotics8020061
Received: 18 April 2019 / Revised: 4 May 2019 / Accepted: 8 May 2019 / Published: 10 May 2019
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Abstract
Bacterial biofilms and their associated infections are a continuing problem in the healthcare community. Previous approaches utilizing anti-biofilm coatings suffer from short lifetimes, and their applications are limited to surfaces. In this research, we explored a new approach to biofilm prevention based on [...] Read more.
Bacterial biofilms and their associated infections are a continuing problem in the healthcare community. Previous approaches utilizing anti-biofilm coatings suffer from short lifetimes, and their applications are limited to surfaces. In this research, we explored a new approach to biofilm prevention based on the hypothesis that changing planktonic bacteria behavior to result in sub-optimal biofilm formation. The behavior of planktonic Pseudomonas aeruginosa exposed to a cationic polymer was characterized for changes in growth behavior and aggregation behavior, and linked to resulting P. aeruginosa biofilm formation, biomass, viability, and metabolic activity. The incubation of P. aeruginosa planktonic bacteria with a cationic polymer resulted in the aggregation of planktonic bacteria, and a reduction in biofilm development. We propose that cationic polymers may sequester planktonic bacteria away from surfaces, thereby preventing their attachment and suppressing biofilm formation. Full article
(This article belongs to the Special Issue Antimicrobial Peptides, Polymers and Surfaces)
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Open AccessArticle
A Pilot Study of the Synergy between Two Antimicrobial Peptides and Two Common Antibiotics
Antibiotics 2019, 8(2), 60; https://doi.org/10.3390/antibiotics8020060
Received: 26 March 2019 / Revised: 17 April 2019 / Accepted: 5 May 2019 / Published: 9 May 2019
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Abstract
Background: Frequent and unrestricted use of antibiotics has been associated with the development of antibiotic resistance by microorganisms. Thus, there is a need to find novel antibacterial agents or a combination of agents as the first line of treatment for various infections. This [...] Read more.
Background: Frequent and unrestricted use of antibiotics has been associated with the development of antibiotic resistance by microorganisms. Thus, there is a need to find novel antibacterial agents or a combination of agents as the first line of treatment for various infections. This study aimed to investigate the synergy between antimicrobial peptide (AMP) combinations or between AMP-antibiotics combinations using two common pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. Methods: The AMPs melimine, Mel4 and protamine, and antibiotics cefepime and ciprofloxacin were used in this study. The minimum inhibitory concentration (MIC) of each were evaluated against P. aeruginosa and S. aureus strains by a microtiter broth dilution. Based on the MIC of each antimicrobial agent, a checkerboard assay was performed to investigate the synergy between them, which was expressed as the fractional inhibitory concentration (FIC). Results: The combination of melimine and ciprofloxacin showed synergistic activity against antibiotic sensitive or resistant strains of P. aeruginosa and with FIC values ≤0.5. Conclusion: Combinations of AMPs and the fluoroquinolone ciprofloxacin is a promising method for reducing resistance to the fluoroquinolone of P. aeruginosa. Full article
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Open AccessArticle
Determination of Florfenicol, Thiamfenicol and Chloramfenicol at Trace Levels in Animal Feed by HPLC–MS/MS
Antibiotics 2019, 8(2), 59; https://doi.org/10.3390/antibiotics8020059
Received: 20 March 2019 / Revised: 26 April 2019 / Accepted: 30 April 2019 / Published: 7 May 2019
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Abstract
Administration of florfenicol and thiamfenicol through medicated feed is permitted within the European Union, always following veterinary prescription and respecting the withdrawal periods. However, the presence of low levels of florfenicol, thiamfenicol, and chloramfenicol in non-target feed is prohibited. Since cross-contamination can occur [...] Read more.
Administration of florfenicol and thiamfenicol through medicated feed is permitted within the European Union, always following veterinary prescription and respecting the withdrawal periods. However, the presence of low levels of florfenicol, thiamfenicol, and chloramfenicol in non-target feed is prohibited. Since cross-contamination can occur during the production of medicated feed and according to Annex II of the European Regulation 2019/4/EC, the control of residue levels of florfenicol and thiamfenicol in non-target feed should be monitored and avoided. Based on all the above, a sensitive and reliable method using liquid chromatography tandem mass spectrometry was developed for the simultaneous detection of chloramfenicol, florfenicol, and thiamfenicol at trace levels in animal feed. Analytes were extracted from minced feed with ethyl acetate. Then, the ethyl acetate was evaporated, the residue was resuspended in Milli-Q water and the extract filtered. The method was in-house validated at carryover levels, with concentration ranging from 100 to 1000 µg/kg. The validation was conducted following the European Commission Decision 2002/657/EC and all performance characteristics were successfully satisfied. The capability of the method to detect amfenicols at lower levels than any prior perspective regulation literature guarantees its applicability in official control activities. The developed method has been applied to non-compliant feed samples with satisfactory results. Full article
(This article belongs to the Special Issue Feature Paper in Antibiotics for 2019)
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Open AccessReview
Blue Light Disinfection in Hospital Infection Control: Advantages, Drawbacks, and Pitfalls
Antibiotics 2019, 8(2), 58; https://doi.org/10.3390/antibiotics8020058
Received: 19 March 2019 / Revised: 27 April 2019 / Accepted: 2 May 2019 / Published: 7 May 2019
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Abstract
Hospital acquired infections (HAIs) are a serious problem that potentially affects millions of patients whenever in contact with hospital settings. Worsening the panorama is the emergence of antimicrobial resistance by most microorganisms implicated in HAIs. Therefore, the improvement of the actual surveillance methods [...] Read more.
Hospital acquired infections (HAIs) are a serious problem that potentially affects millions of patients whenever in contact with hospital settings. Worsening the panorama is the emergence of antimicrobial resistance by most microorganisms implicated in HAIs. Therefore, the improvement of the actual surveillance methods and the discovery of alternative approaches with novel modes of action is vital to overcome the threats created by the emergence of such resistances. Light therapy modalities represent a viable and effective alternative to the conventional antimicrobial treatment and can be preponderant in the control of HAIs, even against multidrug resistant organisms (MDROs). This review will initially focus on the actual state of HAIs and MDROs and which methods are currently available to fight them, which is followed by the exploration of antimicrobial photodynamic therapy (aPDT) and antimicrobial blue light therapy (aBLT) as alternative approaches to control microorganisms involved in HAIs. The advantages and drawbacks of BLT relatively to aPDT and conventional antimicrobial drugs as well as its potential applications to destroy microorganisms in the healthcare setting will also be discussed. Full article
(This article belongs to the Special Issue Photodynamic Therapy in the Inactivation of Microorganisms)
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Open AccessArticle
Pivmecillinam for Uncomplicated Lower Urinary Tract Infections Caused by Staphylococcus saprophyticus—Cumulative Observational Data from Four Recent Clinical Studies
Antibiotics 2019, 8(2), 57; https://doi.org/10.3390/antibiotics8020057
Received: 9 April 2019 / Revised: 24 April 2019 / Accepted: 30 April 2019 / Published: 7 May 2019
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Abstract
Objectives: To investigate pivmecillinam´s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus—considered non-susceptible to mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivmecillinam was empirically given to females [...] Read more.
Objectives: To investigate pivmecillinam´s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus—considered non-susceptible to mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivmecillinam was empirically given to females with symptoms of UTIs. The primary outcome was defined as a cumulative clinical effect—symptom resolution during the first eight days of therapy, without a recurrence of UTI symptoms in the long-term follow-up (approximately four weeks). Secondary outcomes included the bacteriological effect—elimination of the causative agent, with or without new uropathogenic bacteria present in the first control urine sample. Significant bacteriuria was defined as ≥103 bacteria/mL. The antibiotic susceptibility testing was done by disc diffusion methodology, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Seventy-four females (18–55 years) were empirically treated with pivmecillinam for UTIs caused by S. saphrophyticus (mean age 25 years; standard deviation (SD) 5.8). The cumulative clinical effect was 53/74 (72%), and the bacteriological effect was 51/59 (86%). Conclusion: Pivmecillinam showed a high clinical and bacteriological effect in UTIs caused by S. saprophyticus in these four clinical trials. The characterization of non-susceptibility for mecillinam regarding the treatment of UTIs caused by this common pathogen may need to be revised. Full article
(This article belongs to the Section Clinical Trials)
Open AccessReview
Current Issues and Perspectives in Patients with Possible Sepsis at Emergency Departments
Antibiotics 2019, 8(2), 56; https://doi.org/10.3390/antibiotics8020056
Received: 8 April 2019 / Revised: 24 April 2019 / Accepted: 25 April 2019 / Published: 7 May 2019
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Abstract
In the area of Emergency Room (ER), many patients present criteria compatible with a SIRS, but only some of them have an associated infection. The new definition of sepsis by the European Society of Intensive Care Medicine and the Society of Critical Care [...] Read more.
In the area of Emergency Room (ER), many patients present criteria compatible with a SIRS, but only some of them have an associated infection. The new definition of sepsis by the European Society of Intensive Care Medicine and the Society of Critical Care Medicine (2016), revolutionizes precedent criteria, overcoming the concept of SIRS and clearly distinguishing the infection with the patient’s physiological response from the symptoms of sepsis. Another fundamental change concerns the recognition method: The use of SOFA (Sequential-Sepsis Related-Organ Failure Assessment Score) as reference score for organ damage assessment. Also, the use of the qSOFA is based on the use of three objective parameters: Altered level of consciousness (GCS <15 or AVPU), systolic blood pressure ≤ 100 mmHg, and respiratory rate ≥ 22/min. If patients have at least two of these altered parameters in association with an infection, then there is the suspicion of sepsis. In these patients the risk of death is higher, and it is necessary to implement the appropriate management protocols, indeed the hospital mortality rate of these patients exceeds 40%. Patients with septic shock can be identified by the association of the clinical symptoms of sepsis with persistent hypotension, which requires vasopressors to maintain a MAP of 65 mmHg, and serum lactate levels >18 mg/dL in despite of an adequate volume resuscitation. Then, patient first management is mainly based on: (1) Recognition of the potentially septic patient (sepsis protocol-qSOFA); (2) Laboratory investigations; (3) Empirical antibiotic therapy in patients with sepsis and septic shock. With this in mind, the authors discuss the most important aspects of the sepsis in both adults and infants, and also consider the possible treatment according current guidelines. In addition, the possible role of some nutraceuticals as supportive therapy in septic patient is also discussed. Full article
(This article belongs to the Special Issue Sepsis: Pathophysiology, Diagnosis and Therapy)
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Open AccessArticle
Antimicrobial and Synergistic Effects of Commercial Piperine and Piperlongumine in Combination with Conventional Antimicrobials
Antibiotics 2019, 8(2), 55; https://doi.org/10.3390/antibiotics8020055
Received: 15 April 2019 / Revised: 29 April 2019 / Accepted: 2 May 2019 / Published: 4 May 2019
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Abstract
Microbial resistance to currently available antibiotics is a public health problem in the fight against infectious diseases. Most antibiotics are characterized by numerous side effects that may be harmful to normal body cells. To improve the efficacy of these antibiotics and to find [...] Read more.
Microbial resistance to currently available antibiotics is a public health problem in the fight against infectious diseases. Most antibiotics are characterized by numerous side effects that may be harmful to normal body cells. To improve the efficacy of these antibiotics and to find an alternative way to minimize the adverse effects associated with most conventional antibiotics, piperine and piperlongumine were screened in combination with conventional rifampicin, tetracycline, and itraconazole to evaluate their synergistic, additive, or antagonistic interactions against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The fractional inhibitory concentration index was used to estimate the synergistic effects of various combination ratios of the piperamides and antibiotics against the bacterial and fungal strains. Both piperine and piperlongumine showed synergistic effects against S. aureus when combined at various ratios with rifampicin. Synergistic interaction was also observed with piperine in combination with tetracycline against S. aureus, while antagonistic interaction was recorded for piperlongumine and tetracycline against S. aureus. All the piperamide/antibacterial combinations tested against P. aeruginosa showed antagonistic effects, with the exception of piperine and rifampicin, which recorded synergistic interaction at a ratio of 9:1 rifampicin/piperine. No synergistic interaction was observed when the commercial compounds were combined with itraconazole and tested against C. albicans. The results showed that piperine and piperlongumine are capable of improving the effectiveness of rifampicin and tetracycline. Dosage combinations of these bioactive compounds with the antibiotics used may be a better option for the treatment of bacterial infections that aims to minimize the adverse effects associated with the use of these conventional antibacterial drugs. Full article
(This article belongs to the Special Issue Feature Paper in Antibiotics for 2019)
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