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Antibiotics, Volume 6, Issue 4 (December 2017)

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Research

Jump to: Review, Other

Open AccessFeature PaperArticle Choline Kinase, A Novel Drug Target for the Inhibition of Streptococcus pneumoniae
Antibiotics 2017, 6(4), 20; doi:10.3390/antibiotics6040020
Received: 28 August 2017 / Revised: 18 September 2017 / Accepted: 19 September 2017 / Published: 25 September 2017
Cited by 2 | PDF Full-text (1384 KB) | HTML Full-text | XML Full-text
Abstract
Gram-positive pathogens, such as Streptococcus pneumoniae, can have deleterious effects on both human and animal health. Antibiotics and antimicrobials have been developed to treat infections caused by such pathogens and to prevent food contamination. However, these strategies have been increasingly thwarted
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Gram-positive pathogens, such as Streptococcus pneumoniae, can have deleterious effects on both human and animal health. Antibiotics and antimicrobials have been developed to treat infections caused by such pathogens and to prevent food contamination. However, these strategies have been increasingly thwarted by the emergence of resistant bacteria strains. Thus, new methods for controlling Gram-positive pathogen growth need to be continuously developed. Choline analogs, such as Hemicholinium-3 (HC-3), have been shown to be useful in blocking cell division in eukaryotic cells through the inhibition of choline kinase, an enzyme which catalyzes the production of phosphocholine from choline and ATP. In some Gram-positive pathogens, choline kinase is an important enzyme in the production of the cell wall element, lipoteichoic acid. However, it is not known if inhibiting this enzyme has any effect on cell division in Gram-positive bacteria. Using the R6 strain as a model, we tested the ability of HC-3 to block the activity of choline kinase in S. pneumoniae and inhibit cell growth. Mass-spectrometry measurements of crude extracts revealed that HC-3 blocked choline kinase activity. Turbidity measurements and population counts showed that HC-3 inhibited cell growth. Competition assays with choline suggested that HC-3 also blocked choline transporters. Western blots showed that lipoteichoic acid production was blocked in the presence of HC-3, and autolytic assays showed that this decrease in lipoteichoic acids caused cells to be more resistant to autolysis. Scanning electron microscopy revealed that HC-3 distorted the cell wall. This study thus establishes choline kinase as a novel drug target for S. pneumoniae. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
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Open AccessFeature PaperArticle Antibiotic Prescribing for Uncomplicated Acute Bronchitis Is Highest in Younger Adults
Antibiotics 2017, 6(4), 22; doi:10.3390/antibiotics6040022
Received: 11 September 2017 / Revised: 19 October 2017 / Accepted: 25 October 2017 / Published: 27 October 2017
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Abstract
Reducing inappropriate antibiotic prescribing is currently a global health priority. Current guidelines recommend against antibiotic treatment for acute uncomplicated bronchitis. We studied antibiotic prescribing patterns for uncomplicated acute bronchitis and identified predictors of inappropriate antibiotic prescribing. We used the Epic Clarity database (electronic
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Reducing inappropriate antibiotic prescribing is currently a global health priority. Current guidelines recommend against antibiotic treatment for acute uncomplicated bronchitis. We studied antibiotic prescribing patterns for uncomplicated acute bronchitis and identified predictors of inappropriate antibiotic prescribing. We used the Epic Clarity database (electronic medical record system) to identify all adult patients with acute bronchitis in family medicine clinics from 2011 to 2016. We excluded factors that could justify antibiotic use, such as suspected pneumonia, COPD or immunocompromising conditions. Of the 3616 visits for uncomplicated acute bronchitis, 2244 (62.1%) resulted in antibiotic treatment. The rates of antibiotic prescribing were similar across the years, p value for trend = 0.07. Antibiotics were most frequently prescribed in the age group of 18–39 years (66.9%), followed by the age group of 65 years and above (59.0%), and the age group of 40–64 years (58.7%), p value < 0.001. Macrolides were significantly more likely to be prescribed for younger adults, while fluoroquinolones were more likely to be prescribed for patients 65 years or older. Duration of antibiotic use was significantly longer in older adults. Sex and race were not associated with antibiotic prescribing. Our findings highlight the urgent need to reduce inappropriate antibiotic use for uncomplicated acute bronchitis, particularly in younger adults. Full article
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Open AccessArticle Exploring Patient Awareness and Perceptions of the Appropriate Use of Antibiotics: A Mixed-Methods Study
Antibiotics 2017, 6(4), 23; doi:10.3390/antibiotics6040023
Received: 7 September 2017 / Revised: 5 October 2017 / Accepted: 26 October 2017 / Published: 31 October 2017
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Abstract
In the outpatient setting, estimates suggest that 30% of the antibiotics prescribed are unnecessary. This study explores patient knowledge and awareness of appropriate use of antibiotics and expectations regarding how antibiotics are used for their treatment in outpatient settings. A survey was administered
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In the outpatient setting, estimates suggest that 30% of the antibiotics prescribed are unnecessary. This study explores patient knowledge and awareness of appropriate use of antibiotics and expectations regarding how antibiotics are used for their treatment in outpatient settings. A survey was administered to a convenience sample of patients, parents, and caregivers (n = 190) at seven primary care clinics and two urgent care locations. Fisher’s exact tests compared results by patient characteristics. Although 89% of patients correctly believed that antibiotics work well for treating infections from bacteria, 53% incorrectly believed that antibiotics work well for treating viral infections. Patients who incorrectly believed that antibiotics work well for treating viral infections were more than twice as likely to expect a provider to give them an antibiotic when they have a cough or common cold. Patients who completed the survey also participated in semi-structured interviews (n = 4), which were analyzed using thematic analysis. Patients reported experiencing confusion about which illnesses may be treated by antibiotics and unclear communication from clinicians about the appropriate use of antibiotics. Development of easy to understand patient educational materials can help address patients’ incorrect perceptions of appropriate antibiotic use and facilitate patient-provider communication. Full article
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Open AccessArticle Activity In Vitro of Clotrimazole against Canine Methicillin-Resistant and Susceptible Staphylococcus pseudintermedius
Antibiotics 2017, 6(4), 29; doi:10.3390/antibiotics6040029
Received: 26 October 2017 / Revised: 17 November 2017 / Accepted: 18 November 2017 / Published: 22 November 2017
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Abstract
Emergence of multidrug-resistance in Staphylococcus pseudintermedius (SP) has increased interest in topical therapy as an alternative to systemic antibiotics in canine pyoderma. The antifungal imidazole, clotrimazole, is contained in numerous licensed canine ear preparations. Its in vitro activity against SP has not been
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Emergence of multidrug-resistance in Staphylococcus pseudintermedius (SP) has increased interest in topical therapy as an alternative to systemic antibiotics in canine pyoderma. The antifungal imidazole, clotrimazole, is contained in numerous licensed canine ear preparations. Its in vitro activity against SP has not been evaluated, although previous studies have shown that the related imidazole, miconazole, has significant anti-staphylococcal efficacy. We therefore determined minimum inhibitory concentrations (MICs) of clotrimazole amongst 50 SP isolates (25 methicillin-resistant [MR]SP and susceptible [MS]SP) collected from dogs in Germany during 2010–2011 using an agar dilution method (CLSI VET01-A4). MICs amongst MRSP and MSSP were comparable (MIC50 and MIC90 = 1mg/L for both groups, p = 0.317); overall, 49 isolates had MIC = 1 mg/L and one had MIC = 0.5 mg/L. The relatively low MICs obtained in this study are likely to be exceeded by topical therapy and thus further clinical evaluation of clotrimazole use in canine superficial pyoderma and otitis externa caused by MRSP and MSSP is now warranted. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
Open AccessArticle Antimicrobial Activity of Bee Venom and Melittin against Borrelia burgdorferi
Antibiotics 2017, 6(4), 31; doi:10.3390/antibiotics6040031
Received: 19 October 2017 / Revised: 21 November 2017 / Accepted: 22 November 2017 / Published: 29 November 2017
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Abstract
Lyme disease is a tick-borne, multi-systemic disease, caused by the bacterium Borrelia burgdorferi. Though antibiotics are used as a primary treatment, relapse often occurs after the discontinuation of antimicrobial agents. The reason for relapse remains unknown, however previous studies suggest the possible presence
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Lyme disease is a tick-borne, multi-systemic disease, caused by the bacterium Borrelia burgdorferi. Though antibiotics are used as a primary treatment, relapse often occurs after the discontinuation of antimicrobial agents. The reason for relapse remains unknown, however previous studies suggest the possible presence of antibiotic resistant Borrelia round bodies, persisters and attached biofilm forms. Thus, there is an urgent need to find antimicrobial agents suitable to eliminate all known forms of B. burgdorferi. In this study, natural antimicrobial agents such as Apis mellifera venom and a known component, melittin, were tested using SYBR Green I/PI, direct cell counting, biofilm assays combined with LIVE/DEAD and atomic force microscopy methods. The obtained results were compared to standalone and combinations of antibiotics such as Doxycycline, Cefoperazone, Daptomycin, which were recently found to be effective against Borrelia persisters. Our findings showed that both bee venom and melittin had significant effects on all the tested forms of B. burgdorferi. In contrast, the control antibiotics when used individually or even in combinations had limited effects on the attached biofilm form. These findings strongly suggest that whole bee venom or melittin could be effective antimicrobial agents for B. burgdorferi; however, further research is necessary to evaluate their effectiveness in vivo, as well as their safe and effective delivery method for their therapeutic use. Full article
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Open AccessArticle Dual Regulation of the Small RNA MicC and the Quiescent Porin OmpN in Response to Antibiotic Stress in Escherichia coli
Antibiotics 2017, 6(4), 33; doi:10.3390/antibiotics6040033
Received: 27 October 2017 / Revised: 27 November 2017 / Accepted: 3 December 2017 / Published: 6 December 2017
Cited by 1 | PDF Full-text (1314 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Antibiotic resistant Gram-negative bacteria are a serious threat for public health. The permeation of antibiotics through their outer membrane is largely dependent on porin, changes in which cause reduced drug uptake and efficacy. Escherichia coli produces two major porins, OmpF and OmpC. MicF
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Antibiotic resistant Gram-negative bacteria are a serious threat for public health. The permeation of antibiotics through their outer membrane is largely dependent on porin, changes in which cause reduced drug uptake and efficacy. Escherichia coli produces two major porins, OmpF and OmpC. MicF and MicC are small non-coding RNAs (sRNAs) that modulate the expression of OmpF and OmpC, respectively. In this work, we investigated factors that lead to increased production of MicC. micC promoter region was fused to lacZ, and the reporter plasmid was transformed into E. coli MC4100 and derivative mutants. The response of micC–lacZ to antimicrobials was measured during growth over a 6 h time period. The data showed that the expression of micC was increased in the presence of β-lactam antibiotics and in an rpoE depleted mutant. Interestingly, the same conditions enhanced the activity of an ompN–lacZ fusion, suggesting a dual transcriptional regulation of micC and the quiescent adjacent ompN. Increased levels of OmpN in the presence of sub-inhibitory concentrations of chemicals could not be confirmed by Western blot analysis, except when analyzed in the absence of the sigma factor σE. We suggest that the MicC sRNA acts together with the σE envelope stress response pathway to control the OmpC/N levels in response to β-lactam antibiotics. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
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Open AccessArticle Evaluation of Antibiotic Residues in Raw Meat Using Different Analytical Methods
Antibiotics 2017, 6(4), 34; doi:10.3390/antibiotics6040034
Received: 14 October 2017 / Revised: 30 November 2017 / Accepted: 1 December 2017 / Published: 7 December 2017
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Abstract
Antibiotic residue in meat is a serious public health concern due to its harmful effects on consumer health. This study aimed at estimating the residue levels of four commonly used antibiotics in meat samples using three analytical methods (ELISA, TLC and HPLC). A
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Antibiotic residue in meat is a serious public health concern due to its harmful effects on consumer health. This study aimed at estimating the residue levels of four commonly used antibiotics in meat samples using three analytical methods (ELISA, TLC and HPLC). A total of 150 samples of raw meat from sales points were analysed for ciprofloxacin, streptomycin, tetracycline, and sulphanilamide residues. Overall, ELISA analysis showed that 56, 34, 18, and 25.3% of the samples tested positive for ciprofloxacin, streptomycin, sulphanilamide and tetracycline residues respectively while TLC and HPLC detected 21.4, 29.4, 92.5, and 14.6%, and 8.3, 41.1, 88.8, and 14.6% of the samples as containing the residues, with ciprofloxacin and sulphanilamide having the lowest and highest occurrence, respectively. Furthermore, the concentrations of antibiotic residues were in the ranges of 19.8–92.8, 26.6–489.1, 14.2–1280.8, and 42.6–355.6 μg/kg with ELISA, while HPLC detected concentration ranges of 20.7–82.1, 41.8–320.8, 65.2–952.2 and 32.8–95.6 μg/kg for sulphanilamide, tetracycline, streptomycin, and ciprofloxacin, respectively. Mean ciprofloxacin and streptomycin residue levels were above the Codex/SA MRL recommended limit, while 3% of the samples contained multidrug residues. Although some of the mean residues levels were below the permissible limits, the co-occurrence of multidrug residues in some of the samples calls for concern. Full article
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Open AccessArticle Nisin in Combination with Cinnamaldehyde and EDTA to Control Growth of Escherichia coli Strains of Swine Origin
Antibiotics 2017, 6(4), 35; doi:10.3390/antibiotics6040035
Received: 14 November 2017 / Revised: 6 December 2017 / Accepted: 7 December 2017 / Published: 12 December 2017
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Abstract
Post-weaning diarrhoea (PWD) due to enterotoxigenic Escherichia coli (ETEC) is an economically important disease in pig production worldwide. Although antibiotics have contributed significantly to mitigate the economic losses caused by PWD, there is major concern over the increased incidence of antimicrobial resistance among
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Post-weaning diarrhoea (PWD) due to enterotoxigenic Escherichia coli (ETEC) is an economically important disease in pig production worldwide. Although antibiotics have contributed significantly to mitigate the economic losses caused by PWD, there is major concern over the increased incidence of antimicrobial resistance among bacteria isolated from pigs. Consequently, suitable alternatives that are safe and effective are urgently required. Many naturally occurring compounds, including the antimicrobial peptide nisin and a number of plant essential oils, have been widely studied and are reported to be effective as antimicrobial agents against pathogenic microorganisms. Here, we evaluate the potential of nisin in combination with the essential oil cinnamaldehyde and ethylenediaminetetraacetic acid (EDTA) to control the growth of E. coli strains of swine origin including two characterized as ETEC. The results reveal that the use of nisin (10 μM) with low concentrations of trans-cinnamaldehyde (125 μg/mL) and EDTA (0.25–2%) resulted in extended lag phases of growth compared to when either antimicrobial is used alone. Further analysis through kill curves revealed that an approximate 1-log reduction in E. coli cell counts was observed against the majority of targets tested following 3 h incubation. These results highlight the potential benefits of combining the natural antimicrobial nisin with trans-cinnamaldehyde and EDTA as a new approach for the inhibition of E. coli strains of swine origin. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
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Open AccessArticle Adverse Effects of Amoxicillin for Acute Lower Respiratory Tract Infection in Primary Care: Secondary and Subgroup Analysis of a Randomised Clinical Trial
Antibiotics 2017, 6(4), 36; doi:10.3390/antibiotics6040036
Received: 30 October 2017 / Revised: 6 December 2017 / Accepted: 8 December 2017 / Published: 13 December 2017
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Abstract
A European placebo-controlled trial of antibiotic treatment for lower respiratory tract infection (LRTI) conducted in 16 primary care practices networks recruited participants between November 2007 and April 2010, and found adverse events (AEs) occurred more often in patients prescribed amoxicillin compared to placebo.
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A European placebo-controlled trial of antibiotic treatment for lower respiratory tract infection (LRTI) conducted in 16 primary care practices networks recruited participants between November 2007 and April 2010, and found adverse events (AEs) occurred more often in patients prescribed amoxicillin compared to placebo. This secondary analysis explores the causal relationship and estimates specific AEs (diarrhoea, nausea, rash) due to amoxicillin treatment for LRTI, and if any subgroup is at increased risk of any or a specific AE. A total of 2061 patients were randomly assigned to amoxicillin (1038) and placebo (1023); 595 (28%) were 60 and older. A significantly higher proportion of any AEs (diarrhoea or nausea or rash) (OR = 1.31, 95% CI 1.05–1.64, number needed to harm (NNH) = 24) and of diarrhoea (OR 1.43 95% CI 1.08–1.90, NNH = 29) was reported in the amoxicillin group during the first week after randomisation. Subgroup analysis showed rash was significantly more often reported in males prescribed amoxicillin (interaction term 3.72 95% CI 1.22–11.36; OR of amoxicillin in males 2.79 (95% CI 1.08–7.22). No other subgroup at higher risk was identified. Although the study was not powered for subgroup analysis, this analysis suggests that most patients are likely to be equally harmed when prescribed antibiotics. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
Open AccessArticle LC-MS/MS Tandem Mass Spectrometry for Analysis of Phenolic Compounds and Pentacyclic Triterpenes in Antifungal Extracts of Terminalia brownii (Fresen)
Antibiotics 2017, 6(4), 37; doi:10.3390/antibiotics6040037
Received: 30 October 2017 / Revised: 29 November 2017 / Accepted: 7 December 2017 / Published: 13 December 2017
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Abstract
Decoctions and macerations of the stem bark and wood of Terminalia brownii Fresen. are used in traditional medicine for fungal infections and as fungicides on field crops and in traditional granaries in Sudan. In addition, T. brownii water extracts are commonly used as
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Decoctions and macerations of the stem bark and wood of Terminalia brownii Fresen. are used in traditional medicine for fungal infections and as fungicides on field crops and in traditional granaries in Sudan. In addition, T. brownii water extracts are commonly used as sprays for protecting wooden houses and furniture. Therefore, using agar disc diffusion and macrodilution methods, eight extracts of various polarities from the stem wood and bark were screened for their growth-inhibitory effects against filamentous fungi commonly causing fruit, vegetable, grain and wood decay, as well as infections in the immunocompromised host. Ethyl acetate extracts of the stem wood and bark gave the best antifungal activities, with MIC values of 250 µg/mL against Nattrassia mangiferae and Fusarium verticillioides, and 500 µg/mL against Aspergillus niger and Aspergillus flavus. Aqueous extracts gave almost as potent effects as the ethyl acetate extracts against the Aspergillus and Fusarium strains, and were slightly more active than the ethyl acetate extracts against Nattrassia mangiferae. Thin layer chromatography, RP-HPLC-DAD and tandem mass spectrometry (LC-MS/MS), were employed to identify the chemical constituents in the ethyl acetate fractions of the stem bark and wood. The stem bark and wood were found to have a similar qualitative composition of polyphenols and triterpenoids, but differed quantitatively from each other. The stilbene derivatives, cis- (3) and trans- resveratrol-3-O-β-galloylglucoside (4), were identified for the first time in T. brownii. Moreover, methyl-(S)-flavogallonate (5), quercetin-7-β-O-di-glucoside (8), quercetin-7-O-galloyl-glucoside (10), naringenin-4′-methoxy-7-pyranoside (7), 5,6-dihydroxy-3′,4′,7-tri-methoxy flavone (12), gallagic acid dilactone (terminalin) (6), a corilagin derivative (9) and two oleanane type triterpenoids (1) and (2) were characterized. The flavonoids, a corilagin derivative and terminalin, have not been identified before in T. brownii. We reported earlier on the occurrence of methyl-S-flavogallonate and its isomer in the roots of T. brownii, but this is the first report on their occurrence in the stem wood as well. Our results justify the traditional uses of macerations and decoctions of T. brownii stem wood and bark for crop and wood protection and demonstrate that standardized extracts could have uses for the eco-friendly control of plant pathogenic fungi in African agroforestry systems. Likewise, our results justify the traditional uses of these preparations for the treatment of skin infections caused by filamentous fungi. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
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Open AccessArticle Decreasing Inappropriate Use of Antibiotics in Primary Care in Four Countries in South America—Cluster Randomized Controlled Trial
Antibiotics 2017, 6(4), 38; doi:10.3390/antibiotics6040038
Received: 27 September 2017 / Revised: 5 December 2017 / Accepted: 11 December 2017 / Published: 14 December 2017
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Abstract
High antibiotic prescribing and antimicrobial resistance in patients attending primary care have been reported in South America. Very few interventions targeting general practitioners (GPs) to decrease inappropriate antibiotic prescribing have been investigated in this region. This study assessed the effectiveness of online feedback
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High antibiotic prescribing and antimicrobial resistance in patients attending primary care have been reported in South America. Very few interventions targeting general practitioners (GPs) to decrease inappropriate antibiotic prescribing have been investigated in this region. This study assessed the effectiveness of online feedback on reducing antibiotic prescribing in patients with suspected respiratory tract infections (RTIs) attending primary care. The aim was to reduce antibiotic prescribing in patients with acute bronchitis and acute otitis media. Both are RTIs for which antibiotics have a very limited effect. A cluster randomized two-arm control trial was implemented. Healthcare centres from Bolivia, Argentina, Paraguay and Uruguay participating in the quality improvement program HAPPY AUDIT were randomly allocated to either intervention or control group. During ten consecutive weeks, GPs in the intervention group received evidence-based online feedback on the management of suspected RTIs. In patients with acute bronchitis, the intervention reduced the antibiotic prescribing rate from 71.6% to 56% (control group from 61.2% to 52%). In patients with acute otitis media, the intervention reduced the antibiotic prescribing from 94.8% to 86.2% (no change in the control group). In all RTIs, the intervention reduced antibiotic prescribing rate from 37.4% to 28.1% (control group from 29% to 27.2%). Online evidence-based feedback is effective for reducing antibiotic prescribing in patients with RTIs attending primary care in South America. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
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Open AccessArticle Six-Year Retrospective Review of Hospital Data on Antimicrobial Resistance Profile of Staphylococcus aureus Isolated from Skin Infections from a Single Institution in Greece
Antibiotics 2017, 6(4), 39; doi:10.3390/antibiotics6040039
Received: 8 November 2017 / Revised: 14 December 2017 / Accepted: 19 December 2017 / Published: 20 December 2017
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Abstract
Objective: To determine the prevalence of resistant strains of Staphylococcus aureus (S. aureus) isolated from Skin and soft tissue infections (SSTI) to various antibiotics. Material and Methods: All culture-positive results for S. aureus from swabs taken from patients presenting at one
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Objective: To determine the prevalence of resistant strains of Staphylococcus aureus (S. aureus) isolated from Skin and soft tissue infections (SSTI) to various antibiotics. Material and Methods: All culture-positive results for S. aureus from swabs taken from patients presenting at one Greek hospital with a skin infection between the years 2010–2015 were examined retrospectively. Bacterial cultures, identification of S. aureus and antimicrobial susceptibility testing were performed using the disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines and European Committee on Antimicrobial testing (EUCAST) breakpoints. EUCAST breakpoints were applied if no CLSI were available. Results: Of 2069 S. aureus isolates identified, 1845 (88%) were resistant to one or more antibiotics. The highest resistance was observed for benzylpenicillin (71.9%), followed by erythromycin (34.3%). Resistant strains to cefoxitin defined as MRSA (methicillin-resistant S. aureus) represented 21% of total isolates. Interestingly, resistance to fusidic acid was 22.9% and to mupirocin as high as 12.7%. Low rates were observed for minocycline, rifampicin and trimethoprim/sulfamethoxazole (SXT). Resistance to antibiotics remained relatively stable throughout the six-year period, with the exception of cefoxitin, fusidic acid and SXT. A high percentage of MRSA strains were resistant to erythromycin (60%), fusidic acid (46%), clindamycin (38%) and tetracycline (35.5%). Conclusions: Special attention is required in prescribing appropriate antibiotic therapeutic regimens, particularly for MRSA. These data on the susceptibility of S. aureus may be useful for guiding antibiotic treatment. Full article

Review

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Open AccessReview Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Outpatients—A Systematic Review and Meta-Analysis
Antibiotics 2017, 6(4), 21; doi:10.3390/antibiotics6040021
Received: 3 August 2017 / Revised: 6 October 2017 / Accepted: 10 October 2017 / Published: 12 October 2017
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Abstract
A common adverse effect of antibiotic use is diarrhea. Probiotics are living microorganisms, which, upon oral ingestion, may prevent antibiotic-associated diarrhea (AAD) by the normalization of an unbalanced gastrointestinal flora. The objective of this systematic review was to assess the benefits and harms
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A common adverse effect of antibiotic use is diarrhea. Probiotics are living microorganisms, which, upon oral ingestion, may prevent antibiotic-associated diarrhea (AAD) by the normalization of an unbalanced gastrointestinal flora. The objective of this systematic review was to assess the benefits and harms of probiotics used for the prevention of AAD in an outpatient setting. A search of the PubMed database was conducted and yielded a total of 17 RCTs with 3631 participants to be included in the review. A meta-analysis was conducted for the primary outcome: the incidence of AAD. The pooled results found that AAD was present in 8.0% of the probiotic group compared to 17.7% in the control group (RR 0.49, 95% CI 0.36 to 0.66; I2 = 58%), and the species-specific results were similar regarding the probiotic strains L. rhamnosus GG and S. boulardii. However, the overall quality of the included studies was moderate. A meta-analysis of the ten trials reporting adverse events demonstrated no statistically significant differences in the incidence of adverse events between the intervention and control group (RD 0.00, 95% CI −0.02 to 0.02, 2.363 participants). The results suggests that probiotic use may be beneficial in the prevention of AAD among outpatients. Furthermore, the use of probiotics appears safe. Full article
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Open AccessReview Fosfomycin: Pharmacological, Clinical and Future Perspectives
Antibiotics 2017, 6(4), 24; doi:10.3390/antibiotics6040024
Received: 30 May 2017 / Revised: 18 October 2017 / Accepted: 19 October 2017 / Published: 31 October 2017
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Abstract
Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimicrobial
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Fosfomycin is a bactericidal, low-molecular weight, broad-spectrum antibiotic, with putative activity against several bacteria, including multidrug-resistant Gram-negative bacteria, by irreversibly inhibiting an early stage in cell wall synthesis. Evidence suggests that fosfomycin has a synergistic effect when used in combination with other antimicrobial agents that act via a different mechanism of action, thereby allowing for reduced dosages and lower toxicity. Fosfomycin does not bind to plasma proteins and is cleared via the kidneys. Due to its extensive tissue penetration, fosfomycin may be indicated for infections of the CNS, soft tissues, bone, lungs, and abscesses. The oral bioavailability of fosfomycin tromethamine is <50%; therefore, oral administration of fosfomycin tromethamine is approved only as a 3-gram one-time dose for treating urinary tract infections. However, based on published PK parameters, PK/PD simulations have been performed for several multiple-dose regimens, which might lead to the future use of fosfomycin for treating complicated infections with multidrug-resistant bacteria. Because essential pharmacological information and knowledge regarding mechanisms of resistance are currently limited and/or controversial, further studies are urgently needed, and fosfomycin monotherapy should be avoided. Full article
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Open AccessReview Identification and Antimicrobial Susceptibility Testing of Anaerobic Bacteria: Rubik’s Cube of Clinical Microbiology?
Antibiotics 2017, 6(4), 25; doi:10.3390/antibiotics6040025
Received: 28 September 2017 / Revised: 30 October 2017 / Accepted: 3 November 2017 / Published: 7 November 2017
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Abstract
Anaerobic bacteria have pivotal roles in the microbiota of humans and they are significant infectious agents involved in many pathological processes, both in immunocompetent and immunocompromised individuals. Their isolation, cultivation and correct identification differs significantly from the workup of aerobic species, although the
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Anaerobic bacteria have pivotal roles in the microbiota of humans and they are significant infectious agents involved in many pathological processes, both in immunocompetent and immunocompromised individuals. Their isolation, cultivation and correct identification differs significantly from the workup of aerobic species, although the use of new technologies (e.g., matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, whole genome sequencing) changed anaerobic diagnostics dramatically. In the past, antimicrobial susceptibility of these microorganisms showed predictable patterns and empirical therapy could be safely administered but recently a steady and clear increase in the resistance for several important drugs (β-lactams, clindamycin) has been observed worldwide. For this reason, antimicrobial susceptibility testing of anaerobic isolates for surveillance purposes or otherwise is of paramount importance but the availability of these testing methods is usually limited. In this present review, our aim was to give an overview of the methods currently available for the identification (using phenotypic characteristics, biochemical testing, gas-liquid chromatography, MALDI-TOF MS and WGS) and antimicrobial susceptibility testing (agar dilution, broth microdilution, disk diffusion, gradient tests, automated systems, phenotypic and molecular resistance detection techniques) of anaerobes, when should these methods be used and what are the recent developments in resistance patterns of anaerobic bacteria. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
Open AccessReview Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities
Antibiotics 2017, 6(4), 26; doi:10.3390/antibiotics6040026
Received: 30 September 2017 / Revised: 26 October 2017 / Accepted: 3 November 2017 / Published: 7 November 2017
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Abstract
Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV), leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant
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Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV), leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant fluoroquinolones display a remarkable selectivity for prokaryotic topoisomerase II, with excellent safety records in humans. Typical agents that target human topoisomerases (such as etoposide, doxorubicin and mitoxantrone) are associated with significant toxicities and secondary malignancies, whereas clinically relevant fluoroquinolones are not known to exhibit such propensities. Although many fluoroquinolones have been shown to display topoisomerase-independent antiproliferative effects against various human cancer cells, those that are significantly active against eukaryotic topoisomerase show the same DNA damaging properties as other topoisomerase poisons. Empirical models also show that fluoroquinolones mediate some unique immunomodulatory activities of suppressing pro-inflammatory cytokines and super-inducing interleukin-2. This article reviews the extended roles of fluoroquinolones and their prospects as lead for the unmet needs of “small and safe” multimodal-targeting drug scaffolds. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
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Open AccessFeature PaperReview Bacteriophages in the Dairy Environment: From Enemies to Allies
Antibiotics 2017, 6(4), 27; doi:10.3390/antibiotics6040027
Received: 5 October 2017 / Revised: 3 November 2017 / Accepted: 6 November 2017 / Published: 8 November 2017
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Abstract
The history of dairy farming goes back thousands of years, evolving from a traditional small-scale production to the industrialized manufacturing of fermented dairy products. Commercialization of milk and its derived products has been very important not only as a source of nourishment but
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The history of dairy farming goes back thousands of years, evolving from a traditional small-scale production to the industrialized manufacturing of fermented dairy products. Commercialization of milk and its derived products has been very important not only as a source of nourishment but also as an economic resource. However, the dairy industry has encountered several problems that have to be overcome to ensure the quality and safety of the final products, as well as to avoid economic losses. Within this context, it is interesting to highlight the role played by bacteriophages, or phages, viruses that infect bacteria. Indeed, bacteriophages were originally regarded as a nuisance, being responsible for fermentation failure and economic losses when infecting lactic acid bacteria, but are now considered promising antimicrobials to fight milk-borne pathogens without contributing to the increase in antibiotic resistance. Full article
(This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond)
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Open AccessReview Interplay between Colistin Resistance, Virulence and Fitness in Acinetobacter baumannii
Antibiotics 2017, 6(4), 28; doi:10.3390/antibiotics6040028
Received: 30 October 2017 / Revised: 14 November 2017 / Accepted: 20 November 2017 / Published: 21 November 2017
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Abstract
Acinetobacter baumannii is an important opportunistic nosocomial pathogen often resistant to multiple antibiotics classes. Colistin, an “old” antibiotic, is now considered a last-line treatment option for extremely resistant isolates. In the meantime, resistance to colistin has been reported in clinical A. baumannii strains.
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Acinetobacter baumannii is an important opportunistic nosocomial pathogen often resistant to multiple antibiotics classes. Colistin, an “old” antibiotic, is now considered a last-line treatment option for extremely resistant isolates. In the meantime, resistance to colistin has been reported in clinical A. baumannii strains. Colistin is a cationic peptide that disrupts the outer membrane (OM) of Gram-negative bacteria. Colistin resistance is primarily due to post-translational modification or loss of the lipopolysaccharide (LPS) molecules inserted into the outer leaflet of the OM. LPS modification prevents the binding of polymyxin to the bacterial surface and may lead to alterations in bacterial virulence. Antimicrobial pressure drives the evolution of antimicrobial resistance and resistance is often associated with a reduced bacterial fitness. Therefore, the alterations in LPS may induce changes in the fitness of A. baumannii. However, compensatory mutations in clinical A. baumannii may ameliorate the cost of resistance and may play an important role in the dissemination of colistin-resistant A. baumannii isolates. The focus of this review is to summarize the colistin resistance mechanisms, and understand their impact on the fitness and virulence of bacteria and on the dissemination of colistin-resistant A. baumannii strains. Full article
Open AccessReview Establishing Genotype-to-Phenotype Relationships in Bacteria Causing Hospital-Acquired Pneumonia: A Prelude to the Application of Clinical Metagenomics
Antibiotics 2017, 6(4), 30; doi:10.3390/antibiotics6040030
Received: 29 September 2017 / Revised: 17 November 2017 / Accepted: 20 November 2017 / Published: 29 November 2017
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Abstract
Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the
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Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly, based on the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP. Full article
(This article belongs to the Special Issue Top 35 of Antibiotics Travel Awards 2017)
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Open AccessOpinion Is Genetic Mobilization Considered When Using Bacteriophages in Antimicrobial Therapy?
Antibiotics 2017, 6(4), 32; doi:10.3390/antibiotics6040032
Received: 5 September 2017 / Revised: 15 November 2017 / Accepted: 4 December 2017 / Published: 5 December 2017
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Abstract
The emergence of multi-drug resistant bacteria has undermined our capacity to control bacterial infectious diseases. Measures needed to tackle this problem include controlling the spread of antibiotic resistance, designing new antibiotics, and encouraging the use of alternative therapies. Phage therapy seems to be
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The emergence of multi-drug resistant bacteria has undermined our capacity to control bacterial infectious diseases. Measures needed to tackle this problem include controlling the spread of antibiotic resistance, designing new antibiotics, and encouraging the use of alternative therapies. Phage therapy seems to be a feasible alternative to antibiotics, although there are still some concerns and legal issues to overcome before it can be implemented on a large scale. Here we highlight some of those concerns, especially those related to the ability of bacteriophages to transport bacterial DNA and, in particular, antibiotic resistance genes. Full article
(This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond)
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