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Antibiotics, Volume 8, Issue 3 (September 2019)

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Cover Story (view full-size image) The discovery of new antibiotics has drastically decreased in the last 30 years. Finding new [...] Read more.
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Open AccessArticle
Characterization of LysBC17, a Lytic Endopeptidase from Bacillus cereus
Antibiotics 2019, 8(3), 155; https://doi.org/10.3390/antibiotics8030155 - 19 Sep 2019
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Abstract
Bacillus cereus, a Gram-positive bacterium, is an agent of food poisoning. B. cereus is closely related to Bacillus anthracis, a deadly pathogen for humans, and Bacillus thuringenesis, an insect pathogen. Due to the growing prevalence of antibiotic resistance in bacteria, [...] Read more.
Bacillus cereus, a Gram-positive bacterium, is an agent of food poisoning. B. cereus is closely related to Bacillus anthracis, a deadly pathogen for humans, and Bacillus thuringenesis, an insect pathogen. Due to the growing prevalence of antibiotic resistance in bacteria, alternative antimicrobials are needed. One such alternative is peptidoglycan hydrolase enzymes, which can lyse Gram-positive bacteria when exposed externally. A bioinformatic search for bacteriolytic enzymes led to the discovery of a gene encoding an endolysin-like endopeptidase, LysBC17, which was then cloned from the genome of B. cereus strain Bc17. This gene is also present in the B. cereus ATCC 14579 genome. The gene for LysBC17 encodes a protein of 281 amino acids. Recombinant LysBC17 was expressed and purified from E. coli. Optimal lytic activity against B. cereus occurred between pH 7.0 and 8.0, and in the absence of NaCl. The LysBC17 enzyme had lytic activity against strains of B. cereus, B. anthracis, and other Bacillus species. Full article
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Open AccessArticle
Antibiotic Use: A Cross-Sectional Study Evaluating the Understanding, Usage and Perspectives of Medical Students and Pathfinders of a Public Defence University in Malaysia
Antibiotics 2019, 8(3), 154; https://doi.org/10.3390/antibiotics8030154 - 19 Sep 2019
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Abstract
Background: Antimicrobial prescribing behaviors are often influenced by the local culture and prescribing appropriateness of medical doctors and other health care professionals. Globally, antimicrobial utilization practices have a profound impact on antimicrobial resistance and are a tremendous public health concern. The aim [...] Read more.
Background: Antimicrobial prescribing behaviors are often influenced by the local culture and prescribing appropriateness of medical doctors and other health care professionals. Globally, antimicrobial utilization practices have a profound impact on antimicrobial resistance and are a tremendous public health concern. The aim of this survey was to explore the knowledge and attitudes of medical students from the National Defence University of Malaysia regarding antimicrobial usage and antimicrobial resistance. Research design and methods: This was a cross-sectional study. The study population consisted of undergraduate medical students in each year group from the National Defence University of Malaysia. Students receive limited formal training on the use of antibiotics in their curriculum, and most of this learning is opportunistic whilst on clinical placement. Universal sampling was used as the study population was small. Data were collected utilizing a previously validated instrument regarding antibiotic use. Simple descriptive statistics were used to generate frequencies and percentages with SPSS V21. This research was approved by the Centre for Research and Innovation Management, National Defence University of Malaysia. Results: 206 questionnaires were distributed with a response rate of 99.03%, 54% (110) male, and 46% (94) female. Out of the respondents, 65% (132) had used antibiotics in the last year. Respondents displayed a moderate level of knowledge about antibiotics. Conclusions: This study revealed that the older the student was, or when the year of study and total knowledge score was higher, the students were less likely to stop antimicrobials when they felt better or use leftover antibiotics without consulting a doctor. Therefore, the nearer the students were to graduation, the better their knowledge and skills were, and this translated into their own behaviors regarding use of antimicrobials. This finding has clear implications for curriculum design and the inclusion of formal teaching throughout the medical program on antimicrobial use and antimicrobial resistance (AMR). However, more research is needed on this topic, including the prescribing habits and antibiotic use of practicing doctors. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessArticle
The Contribution of Efflux Pumps in Mycobacterium abscessus Complex Resistance to Clarithromycin
Antibiotics 2019, 8(3), 153; https://doi.org/10.3390/antibiotics8030153 - 18 Sep 2019
Viewed by 457
Abstract
The basis of drug resistance in Mycobacterium abscessus is still poorly understood. Nevertheless, as seen in other microorganisms, the efflux of antimicrobials may also play a role in M. abscessus drug resistance. Here, we investigated the role of efflux pumps in clarithromycin resistance [...] Read more.
The basis of drug resistance in Mycobacterium abscessus is still poorly understood. Nevertheless, as seen in other microorganisms, the efflux of antimicrobials may also play a role in M. abscessus drug resistance. Here, we investigated the role of efflux pumps in clarithromycin resistance using nine clinical isolates of M. abscessus complex belonging to the T28 erm(41) sequevar responsible for the inducible resistance to clarithromycin. The strains were characterized by drug susceptibility testing in the presence/absence of the efflux inhibitor verapamil and by genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. Efflux pump gene expression was studied by RT-qPCR upon exposure to clarithromycin. Verapamil increased the susceptibility to clarithromycin from 4- to ≥64-fold. The efflux pump genes MAB_3142 and MAB_1409 were found consistently overexpressed. The results obtained demonstrate that the T28 erm(41) polymorphism is not the sole cause of the inducible clarithromycin resistance in M. abscessus subsp. abscessus or bolletii with efflux activity providing a strong contribution to clarithromycin resistance. These data highlight the need for further studies on M. abscessus efflux response to antimicrobial stress in order to implement more effective therapeutic regimens and guidance in the development of new drugs against these bacteria. Full article
(This article belongs to the Special Issue Feature Paper in Antibiotics for 2019)
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Open AccessArticle
Decoding Antioxidant and Antibacterial Potentials of Malaysian Green Seaweeds: Caulerpa racemosa and Caulerpa lentillifera
Antibiotics 2019, 8(3), 152; https://doi.org/10.3390/antibiotics8030152 - 17 Sep 2019
Viewed by 468
Abstract
Seaweeds are gaining a considerable amount of attention for their antioxidant and antibacterial properties. Caulerpa racemosa and Caulerpa lentillifera, also known as ‘sea grapes’, are green seaweeds commonly found in different parts of the world, but the antioxidant and antibacterial potentials of [...] Read more.
Seaweeds are gaining a considerable amount of attention for their antioxidant and antibacterial properties. Caulerpa racemosa and Caulerpa lentillifera, also known as ‘sea grapes’, are green seaweeds commonly found in different parts of the world, but the antioxidant and antibacterial potentials of Malaysian C. racemosa and C. lentillifera have not been thoroughly explored. In this study, crude extracts of the seaweeds were prepared using chloroform, methanol, and water. Total phenolic content (TPC) and total flavonoid content (TFC) were measured, followed by in vitro antioxidant activity determination using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Antibacterial activities of these extracts were tested against Methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Liquid chromatography–mass spectrometry (LCMS) analysis was then used to determine the possible compounds present in the extract with the most potent antioxidant and antibacterial activity. Results showed that C. racemosa chloroform extract had the highest TPC (13.41 ± 0.86 mg GAE/g), antioxidant effect (EC50 at 0.65 ± 0.03 mg/mL), and the strongest antibacterial effect (97.7 ± 0.30%) against MRSA. LCMS analysis proposed that the chloroform extracts of C. racemosa are mainly polyunsaturated and monounsaturated fatty acids, terpenes, and alkaloids. In conclusion, C. racemosa can be a great source of novel antioxidant and antibacterial agents, but isolation and purification of the bioactive compounds are needed to study their mechanism of action. Full article
(This article belongs to the Special Issue Antimicrobial Plant Extracts and Phytochemicals)
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Open AccessArticle
Isolation and Antibiotic Resistant Research of Tetragenococcus halophilus from Xuanwei Ham, A China High-Salt-Fermented Meat Products
Antibiotics 2019, 8(3), 151; https://doi.org/10.3390/antibiotics8030151 - 16 Sep 2019
Viewed by 404
Abstract
We assessed the prevalence of antibiotic resistant and antibiotic resistance genes for 49 Tetragenococcus halophilus (T. halophilus) strains isolated from Xuawei ham in China. The antibiotic resistance phenotype was detected by the Bauer–Kirby (K–B) method and the results showed that 49 [...] Read more.
We assessed the prevalence of antibiotic resistant and antibiotic resistance genes for 49 Tetragenococcus halophilus (T. halophilus) strains isolated from Xuawei ham in China. The antibiotic resistance phenotype was detected by the Bauer–Kirby (K–B) method and the results showed that 49 isolates can be considered completely susceptible to penicillin, ampicillin, amoxicillin, cefradine, cefotaxime, tetracyclines, minocycline, doxycycline, and vancomycin, but resistant to gentamicin, streptomycin, neomycin, polymyxinB, cotrimoxazole. This resistance was sufficiently high to consider the potential for acquisition of transmissible determinants. A total of 32 isolates were resistant to ofloxacin, 4 isolates were resistant to ciprofloxacin and chloramphenicol, and 2 isolates were resistant to ceftazidime and ticarcillin. The antibiotic resistance genes were detected by routine polymerase chain reaction (PCR). Among the 26 antibiotic resistance genes, 5 varieties of antibiotic resistance genes, including acrB, blaTEM, AAda1, SulII, and GyrB were detected and the detection rates were 89.79%, 47.7%, 16.33%, 77.55%, and 75.51%, respectively. The potential acquisition of transmissible determinants for antibiotic resistance and antibiotic resistance genes identified in this study necessitate the need for a thorough antibiotic resistance safety assessment of T. halophilus before it can be considered for use in food fermentation processes. Full article
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Open AccessCase Report
Frequent Klebsiella pneumoniae Urinary Tract Infections in a Patient Treated with Ruxolitinib
Antibiotics 2019, 8(3), 150; https://doi.org/10.3390/antibiotics8030150 - 16 Sep 2019
Viewed by 415
Abstract
Ruxolitinib is a targeted agent that inhibits Janus 2 Kinase and is approved for use in Polycythemia Vera and Primary Myelofibrosis. Its mechanism of action involves inhibition of cellular proliferation via the Janus kinase/signal transducer and activator of transcription proteins pathway. Ruxolitinib has [...] Read more.
Ruxolitinib is a targeted agent that inhibits Janus 2 Kinase and is approved for use in Polycythemia Vera and Primary Myelofibrosis. Its mechanism of action involves inhibition of cellular proliferation via the Janus kinase/signal transducer and activator of transcription proteins pathway. Ruxolitinib has different immune modulating effects that result in functional immunosuppression, leading to an increased susceptibility to certain infections. Klebsiella pneumoniae infections, in particular, were common among the reported pathogens contracted by ruxolitinib users. We report a 75-year-old male patient who had recurrent K. pneumoniae urinary tract infections while on ruxolitinib for Polycythemia Vera. This case is reported to add to the literature describing an increased susceptibility of patients to this often-resistant bacteria and to raise awareness about the immune modulating effects of JAK inhibitors. Full article
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Open AccessArticle
Characterization of a Carbapenem-Resistant Kluyvera Cryocrescens Isolate Carrying Blandm-1 from Hospital Sewage
Antibiotics 2019, 8(3), 149; https://doi.org/10.3390/antibiotics8030149 - 16 Sep 2019
Viewed by 401
Abstract
Carbapenem-resistant Enterobacteriaceae have been a global public health issue in recent years. Here, a carbapenem-resistant Kluyvera cryocrescens strain SCW13 was isolated from hospital sewage, and was then subjected to whole-genome sequencing (WGS). Based on WGS data, antimicrobial resistance genes were identified. Resistance plasmids [...] Read more.
Carbapenem-resistant Enterobacteriaceae have been a global public health issue in recent years. Here, a carbapenem-resistant Kluyvera cryocrescens strain SCW13 was isolated from hospital sewage, and was then subjected to whole-genome sequencing (WGS). Based on WGS data, antimicrobial resistance genes were identified. Resistance plasmids were completely circularized and further bioinformatics analyses of plasmids were performed. A conjugation assay was performed to identify a self-transmissible plasmid mediating carbapenem resistance. A phylogenetic tree was constructed based on the core genome of publicly available Kluyvera strains. The isolate SCW13 exhibited resistance to cephalosporin and carbapenem. blaNDM-1 was found to be located on a ~53-kb self-transmissible IncX3 plasmid, which exhibited high similarity to the previously reported pNDM-HN380, which is an epidemic blaNDM-1-carrying IncX3 plasmid. Further, we found that SCW13 contained a chromosomal blaKLUC-2 gene, which was the probable origin of the plasmid-born blaKLUC-2 found in Enterobacter cloacae. Phylogenetic analysis showed that K. cryocrescens SCW13 exhibited a close relationship with K. cryocrescens NCTC10483. These findings highlight the further dissemination of blaNDM through clonal IncX3 plasmids related to pNDM-HN380 among uncommon Enterobacteriaceae strains, including Kluyvera in this case. Full article
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Open AccessArticle
Carbapenemase Genes and Multidrug Resistance of Acinetobacter Baumannii: A Cross Sectional Study of Patients with Pneumonia in Southern Vietnam
Antibiotics 2019, 8(3), 148; https://doi.org/10.3390/antibiotics8030148 - 12 Sep 2019
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Abstract
Background: Acinetobacter baumannii (Ab) is an opportunistic bacterial pathogen found in hospital-acquired infections including nosocomial pneumonia, especially multidrug-resistant Ab. This study aims to survey the drug resistance profiles of Ab isolated from patients in Thong Nhat Dong Nai General Hospital and assess [...] Read more.
Background: Acinetobacter baumannii (Ab) is an opportunistic bacterial pathogen found in hospital-acquired infections including nosocomial pneumonia, especially multidrug-resistant Ab. This study aims to survey the drug resistance profiles of Ab isolated from patients in Thong Nhat Dong Nai General Hospital and assess the relationship between genotypes and antibiotic resistance; Methods: Ninety-seven Ab strains isolated from 340 lower respiratory tract specimens among pneumonia patients were used to screen the most common local carbapenemase genes. Antimicrobial susceptibility testing results and demographic data were collected and minimum inhibitory concentrations (MIC) of colistin were also determined; Results: Over 80% and 90% of Ab strains were determined as carbapenem-resistant and multidrug-resistant (MDR), respectively. Most of the strains carried carbapenemase genes, including blaOXA-51, blaOXA-23-like, blaOXA-58-like, and blaNDM-1, with proportions of 97 (100%), 76 (78.4%), 10 (10.3%), 6 (6.2%), respectively. Amongst these genes, blaOXA-23-like was the only gene which significantly influenced the resistance (p < 0.0001); and Conclusions: The severity of Ab antibiotic resistance is urgent and specifically related to carbapenemase encoding genes. Therefore, screening of MDR Ab and carbapenemase for better treatment options is necessary. Full article
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Open AccessArticle
Global Internet Data on the Interest in Antibiotics and Probiotics Generated by Google Trends
Antibiotics 2019, 8(3), 147; https://doi.org/10.3390/antibiotics8030147 - 12 Sep 2019
Viewed by 469
Abstract
Data from the Google search engine enables the assessment of Google users’ interest in a specific topic. We analyzed the world trends in searches associated with the topics “antibiotics” and “probiotics” from January 2004 to June 2019, using Google Trends. We analyzed the [...] Read more.
Data from the Google search engine enables the assessment of Google users’ interest in a specific topic. We analyzed the world trends in searches associated with the topics “antibiotics” and “probiotics” from January 2004 to June 2019, using Google Trends. We analyzed the yearly trends and seasonal variation. We performed an R-Spearman rank correlation analysis of the relative search volume (RSV) of the topics in 2015 with antibiotic consumption, health expenditure per capita, and the 2015 Human Development Index (HDI) of the country. The mean interest in the topic of antibiotics was equal to RSV = 57.5 ± 17.9, rising by 3.7 RSV/year (6.5%/year), while that of probiotics was RSV = 14.1 ± 7.9, which rose by 1.7 RSV/year (12.1%). The seasonal amplitude of antibiotics was equal to RSV = 9.8, while probiotics was RSV = 2.7. The seasonal peaks for both topics were observed in the cold months. The RSV of probiotics, but not antibiotics, was associated with antibiotic consumption (Rs = 0.35; p < 0.01), health expenditure (Rs = 0.41; p < 0.001), and HDI (Rs = 0.44; p < 0.001). Google users’ interest in antibiotic- and probiotic-related information increases from year to year, and peaks in cold months. The interest in probiotic-related information might be associated with antibiotic consumption, health expenditure, and the development status of the Google users’ country. Full article
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Open AccessCommunication
Carbapenemase-Producing Elizabethkingia Meningoseptica from Healthy Pigs Associated with Colistin Use in Spain
Antibiotics 2019, 8(3), 146; https://doi.org/10.3390/antibiotics8030146 - 11 Sep 2019
Viewed by 585
Abstract
Carbapenems are considered last-resort antimicrobials, especially for treating infections involving multidrug-resistant Gram-negative bacteria. In recent years, extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Gram-negative bacteria have become widespread in hospitals, community settings, and the environment, reducing the range of effective therapeutic alternatives. The use of [...] Read more.
Carbapenems are considered last-resort antimicrobials, especially for treating infections involving multidrug-resistant Gram-negative bacteria. In recent years, extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Gram-negative bacteria have become widespread in hospitals, community settings, and the environment, reducing the range of effective therapeutic alternatives. The use of colistin to treat infection caused by these multi-drug bacteria may favour the selection and persistence of carbapenem-resistant bacteria. In this study, it is described, for the first time to our knowledge, a carbapenemase-producing isolate of Elizabethkingia meningoseptica from healthy pigs in Spain. The isolate we report was recovered during a study to detect colistin-resistant bacteria from faecal samples of healthy food-production animals using a chromogenic selective medium. Unexpectedly, we found an isolate of Elizabethkingia meningoseptica with high Minimum Inhibitory Concentration (MIC) values for several antibiotics tested. Molecular analysis did not show any mcr family genes related with colistin resistance, but two carbapenemase genes, blaB-12_1 and blaGOB-17_1, were detected. This finding in healthy animals could suggest that colistin may favour the selection and persistence of carbapenem-resistant bacteria. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
Open AccessArticle
Structural Analysis of The OXA-48 Carbapenemase Bound to A “Poor” Carbapenem Substrate, Doripenem
Antibiotics 2019, 8(3), 145; https://doi.org/10.3390/antibiotics8030145 - 11 Sep 2019
Viewed by 444
Abstract
Carbapenem-resistant Enterobacteriaceae are a significant threat to public health, and a major resistance determinant that promotes this phenotype is the production of the OXA-48 carbapenemase. The activity of OXA-48 towards carbapenems is a puzzling phenotype as its hydrolytic activity against doripenem is non-detectable. [...] Read more.
Carbapenem-resistant Enterobacteriaceae are a significant threat to public health, and a major resistance determinant that promotes this phenotype is the production of the OXA-48 carbapenemase. The activity of OXA-48 towards carbapenems is a puzzling phenotype as its hydrolytic activity against doripenem is non-detectable. To probe the mechanistic basis for this observation, we determined the 1.5 Å resolution crystal structure of the deacylation deficient K73A variant of OXA-48 in complex with doripenem. Doripenem is observed in the Δ1R and Δ1S tautomeric states covalently attached to the catalytic S70 residue. Likely due to positioning of residue Y211, the carboxylate moiety of doripenem is making fewer hydrogen bonding/salt-bridge interactions with R250 compared to previously determined carbapenem OXA structures. Moreover, the hydroxyethyl side chain of doripenem is making van der Waals interactions with a key V120 residue, which likely affects the deacylation rate of doripenem. We hypothesize that positions V120 and Y211 play important roles in the carbapenemase profile of OXA-48. Herein, we provide insights for the further development of the carbapenem class of antibiotics that could render them less effective to hydrolysis by or even inhibit OXA carbapenemases. Full article
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Open AccessArticle
Antimicrobial Activity of Silver Camphorimine Complexes against Candida Strains
Antibiotics 2019, 8(3), 144; https://doi.org/10.3390/antibiotics8030144 - 10 Sep 2019
Viewed by 463
Abstract
Hydroxide [Ag(OH)L] (L = IVL, VL, VIL, VIIL), oxide [{AgL}2}(μ-O)] (L = IL, IIL, IIIL, VL, VIL) or chloride [AgIIL]Cl, [Ag(VIL)2]Cl complexes were obtained from reactions [...] Read more.
Hydroxide [Ag(OH)L] (L = IVL, VL, VIL, VIIL), oxide [{AgL}2}(μ-O)] (L = IL, IIL, IIIL, VL, VIL) or chloride [AgIIL]Cl, [Ag(VIL)2]Cl complexes were obtained from reactions of mono- or bicamphorimine derivatives with Ag(OAc) or AgCl. The new complexes were characterized by spectroscopic (NMR, FTIR) and elemental analysis. X-ray photoelectron spectroscopy (XPS), ESI mass spectra and conductivity measurements were undertaken to corroborate formulations. The antimicrobial activity of complexes and some ligands were evaluated towards Candida albicans and Candida glabrata, and strains of the bacterial species Escherichia coli, Burkholderia contaminans, Pseudomonas aeruginosa and Staphylococcus aureus based on the Minimum Inhibitory Concentrations (MIC). Complexes displayed very high activity against the Candida species studied with the lowest MIC values (3.9 µg/mL) being observed for complexes 9 and 10A against C. albicans. A significant feature of these redesigned complexes is their ability to sensitize C. albicans, a trait that was not found for the previously investigated [Ag(NO3)L] complexes. The MIC values of the complexes towards bacteria were in the range of those of [Ag(NO3)L] and well above those of the precursors Ag(OAc) or AgCl. The activity of the complexes towards normal fibroblasts V79 was evaluated by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Results showed that the complexes have a significant cytotoxicity. Full article
(This article belongs to the Special Issue Feature Paper in Antibiotics for 2019)
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Open AccessCommunication
Resistance Levels and Epidemiology of Non-Fermenting Gram-Negative Bacteria in Urinary Tract Infections of Inpatients and Outpatients (RENFUTI): A 10-Year Epidemiological Snapshot
Antibiotics 2019, 8(3), 143; https://doi.org/10.3390/antibiotics8030143 - 09 Sep 2019
Viewed by 470
Abstract
Background: Urinary tract infections (UTIs) are one of the most common infections in the human medicine, both among outpatients and inpatients. There is an increasing appreciation for the pathogenic role of non-fermenting Gram-negative bacteria (NFGNBs) in UTIs, particularly in the presence of underlying [...] Read more.
Background: Urinary tract infections (UTIs) are one of the most common infections in the human medicine, both among outpatients and inpatients. There is an increasing appreciation for the pathogenic role of non-fermenting Gram-negative bacteria (NFGNBs) in UTIs, particularly in the presence of underlying illnesses. Methods: The study was carried out using data regarding a 10-year period (2008–2017). The antimicrobial susceptibility testing was performed using the disk diffusion method, E-tests, and broth microdilution. Results: NFGNB represented 3.46% ± 0.93% for the outpatients, while 6.43% ± 0.81% of all positive urine samples for the inpatients (p < 0.001). In both groups, Pseudomonas spp. (78.7% compared to 85.1%) and Acinetobacter spp. (19.6% compared to 10.9%), were the most prevalent. The Acinetobacter resistance levels were significantly higher in inpatients isolates (p values ranging between 0.046 and <0.001), while the differences in the resistance levels of Pseudomonas was not as pronounced. The β-lactam-resistance levels were between 15–25% and 12–28% for the Acinetobacter and Pseudomonas spp., respectively. 4.71% of Acinetobacter and 1.67% of Pseudomonas were extensively drug resistant (XDR); no colistin-resistant isolates were recovered. Conclusions: Increasing resistance levels of the Acinetobacter spp. from 2013 onward, but not in the case of the Pseudomonas spp. Although rare, the drug resistant NFGNB in UTIs present a concerning therapeutic challenge to clinicians with few therapeutic options left. Full article
(This article belongs to the Special Issue Antibiotic Resistance: From the Bench to Patients)
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Open AccessArticle
Predictors of Appropriate Antibiotic Use in Bacteremia Patients Presenting at the Emergency Department
Antibiotics 2019, 8(3), 142; https://doi.org/10.3390/antibiotics8030142 - 09 Sep 2019
Viewed by 426
Abstract
Sepsis is a condition that requires appropriate antibiotic treatment at the emergency department (ED). Most previous studies conducted on inappropriate antibiotic use at the ED were conducted in developed countries with a low percentage of sepsis. This study aimed to find additional clinical [...] Read more.
Sepsis is a condition that requires appropriate antibiotic treatment at the emergency department (ED). Most previous studies conducted on inappropriate antibiotic use at the ED were conducted in developed countries with a low percentage of sepsis. This study aimed to find additional clinical predictors for appropriate antibiotic use in bacteremia patients presenting at the ED from a developing country, in which there is a higher proportion of patients with sepsis. We included adult patients who presented at the ED with clinical suspicion of infection and bacteremia. Patients allocated to the appropriate antibiotic group were those in whom the prescribed antibiotic was sensitive to the pathogen. Predictors and outcomes of appropriate antibiotic use were analyzed. A total of 3133 patients who met the study criteria presented at the ED during the study period. Of those, 271 patients were diagnosed with bacteremia, 48 of whom (17.71%) received inappropriate antibiotic prescriptions. Only pulse rate was an independent factor for appropriate antibiotic treatment, with an adjusted odds ratio of 1.019 (95% CI of 1.001, 1.036). In terms of clinical outcomes, the inappropriate antibiotic group had higher proportions of 28-day mortality (29.17% vs. 25.25%; p-value = 0.022) and longer hospitalization (14 vs. 9 days; p-value = 0.003). This study found that inappropriate antibiotics were prescribed in 17% of bacteremia patients presenting at the ED and that high pulse rate was an indicator for appropriate antibiotic prescription. Patients with inappropriate antibiotic administration had longer hospitalization and higher 28-day mortality than those who received appropriate antibiotic treatment. Full article
(This article belongs to the Special Issue Sepsis: Pathophysiology, Diagnosis and Therapy)
Open AccessArticle
Epidemiological Characteristics of Staphylococcus Aureus in Raw Goat Milk in Shaanxi Province, China
Antibiotics 2019, 8(3), 141; https://doi.org/10.3390/antibiotics8030141 - 08 Sep 2019
Viewed by 518
Abstract
Goat milk has been frequently implicated in staphylococcal food poisoning. The potential risk of raw goat milk contaminated by Staphylococcus aureus (S. aureus) in Shaanxi province of China is still not well documented. This study investigated the prevalence, antibiotic resistance, as [...] Read more.
Goat milk has been frequently implicated in staphylococcal food poisoning. The potential risk of raw goat milk contaminated by Staphylococcus aureus (S. aureus) in Shaanxi province of China is still not well documented. This study investigated the prevalence, antibiotic resistance, as well as virulence-related genes of S. aureus from raw goat milk samples in Shaanxi, China. A total of 68 S. aureus isolates were cultured from 289 raw goat milk. Most of the isolates were resistant to penicillin and oxacillin, although 41.18%, 33.82%, and 29.41% of the isolates expressed resistance to piperacillin, trimethoprim-sulfamethoxazole, and ciprofloxacin, respectively. Our data demonstrated that 91.18% of the isolates produced biofilm, of which 54.41% isolates belonged to high-biofilm producers. In addition, genotypic analysis of biofilm related genes (fnbA, clfB, fnbB, cna) revealed that 91.18% of the isolates harbored at least one of the genes, in which the most prevalent genes were fnbA (66. 17%), clfB (48.53%), and fnbB (26.47%). 94.8% of the isolates contained at least one toxin-related gene, of which seb (76.47%), tsst (36.76%), and sea (23.53%) genes were the more frequently detected. Further analysis revealed a positive association between fnbA, clfB, fnbB, seb, tsst, and sea genes and certain antibiotic resistance. The results indicated that raw goat milk samples contaminated by S. aureus can be a potential risk to public health. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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Open AccessArticle
Tobramycin Promotes Melanogenesis by Upregulating p38 MAPK Protein Phosphorylation in B16F10 Melanoma Cells
Antibiotics 2019, 8(3), 140; https://doi.org/10.3390/antibiotics8030140 - 05 Sep 2019
Viewed by 558
Abstract
Tobramycin is an aminoglycoside-based natural antibiotic derived from Streptomyces tenebrarius, which is primarily used for Gram-negative bacterial infection treatment. Although tobramycin has been utilized in clinical practice for a long time, it has exhibited several side effects, leading to the introduction of [...] Read more.
Tobramycin is an aminoglycoside-based natural antibiotic derived from Streptomyces tenebrarius, which is primarily used for Gram-negative bacterial infection treatment. Although tobramycin has been utilized in clinical practice for a long time, it has exhibited several side effects, leading to the introduction of more effective antibiotics. Therefore, we conducted our experiments focusing on new possibilities for the clinical use of tobramycin. How tobramycin affects skin melanin formation is unknown. This study used B16F10 melanoma cells to assess the effect of tobramycin on melanin production. After cytotoxicity was assessed by MTT assay, melanin content and tyrosinase activity analyses revealed that tobramycin induces melanin synthesis in B16F10 cells. Next, Western blot analyses were performed to elucidate the mechanism by which tobramycin increases melanin production; phosphorylated p38 protein expression was upregulated. Protein inhibitors have been used to elucidate the mechanism of tobramycin. Kanamycin A and B are structurally similar to tobramycin, and 2-DOS represents the central structure of these antibiotics. The effects of these substances on melanogenesis were evaluated. Kanamycin A reduced melanin production, whereas kanamycin B and 2-DOS had no effect. Overall, our data indicated that tobramycin increases melanin production by promoting p38 protein phosphorylation in B16F10 melanoma cells. Full article
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Open AccessArticle
Antibiotic Prescribing by Informal Healthcare Providers for Common Illnesses: A Repeated Cross-Sectional Study in Rural India
Antibiotics 2019, 8(3), 139; https://doi.org/10.3390/antibiotics8030139 - 05 Sep 2019
Viewed by 592
Abstract
Informal healthcare providers (IHCPs) are predominant healthcare providers in rural India, who prescribe without formal training. Antibiotic prescription by IHCPs could provide crucial information for controlling antibiotic resistance. The aim of this study is to determine the practices and seasonal changes in antibiotic [...] Read more.
Informal healthcare providers (IHCPs) are predominant healthcare providers in rural India, who prescribe without formal training. Antibiotic prescription by IHCPs could provide crucial information for controlling antibiotic resistance. The aim of this study is to determine the practices and seasonal changes in antibiotic prescribing for common illnesses by IHCPs. A repeated cross-sectional study was conducted over 18 months, covering different seasons in the rural demographic surveillance site, at Ujjain, India. Prescriptions given to outpatients by 12 IHCPs were collected. In total, 15,322 prescriptions for 323 different complaint combinations were analyzed, of which 11,336 (74%) included antibiotics. The results showed that 14,620 (95%) of antibiotics prescribed were broad spectrum and the most commonly prescribed were fluoroquinolones (4771,31%), followed by penicillin with an extended spectrum (4119,27%) and third-generation cephalosporin (3069,20%). Antibiotics were prescribed more frequently in oral and dental problems (1126,88%), fever (3569,87%), and upper respiratory tract infections (3273, 81%); more during the monsoon season (2350,76%); and more frequently to children (3340,81%) than to adults (7996,71%). The study concludes that antibiotics were the more commonly prescribed drugs compared to other medications for common illnesses, most of which are broad-spectrum antibiotics, a situation that warrants further investigations followed by immediate and coordinated efforts to reduce unnecessary antibiotic prescriptions by IHCPs. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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Open AccessReview
Bacteriophages as Alternatives to Antibiotics in Clinical Care
Antibiotics 2019, 8(3), 138; https://doi.org/10.3390/antibiotics8030138 - 04 Sep 2019
Viewed by 1111
Abstract
Antimicrobial resistance is increasing despite new treatments being employed. With a decrease in the discovery rate of novel antibiotics, this threatens to take humankind back to a “pre-antibiotic era” of clinical care. Bacteriophages (phages) are one of the most promising alternatives to antibiotics [...] Read more.
Antimicrobial resistance is increasing despite new treatments being employed. With a decrease in the discovery rate of novel antibiotics, this threatens to take humankind back to a “pre-antibiotic era” of clinical care. Bacteriophages (phages) are one of the most promising alternatives to antibiotics for clinical use. Although more than a century of mostly ad-hoc phage therapy has involved substantial clinical experimentation, a lack of both regulatory guidance standards and effective execution of clinical trials has meant that therapy for infectious bacterial diseases has yet to be widely adopted. However, several recent case studies and clinical trials show promise in addressing these concerns. With the antibiotic resistance crisis and urgent search for alternative clinical treatments for bacterial infections, phage therapy may soon fulfill its long-held promise. This review reports on the applications of phage therapy for various infectious diseases, phage pharmacology, immunological responses to phages, legal concerns, and the potential benefits and disadvantages of this novel treatment. Full article
(This article belongs to the Special Issue Feature Paper in Antibiotics for 2019)
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Open AccessArticle
Tedizolid Versus Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infection: A Systematic Review and Meta-Analysis
Antibiotics 2019, 8(3), 137; https://doi.org/10.3390/antibiotics8030137 - 04 Sep 2019
Viewed by 562
Abstract
This meta-analysis aims to assess the efficacy and safety of tedizolid, compared to linezolid, in the treatment of acute bacterial skin and skin structure infection (ABSSSI). PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid Medline and Embase databases were [...] Read more.
This meta-analysis aims to assess the efficacy and safety of tedizolid, compared to linezolid, in the treatment of acute bacterial skin and skin structure infection (ABSSSI). PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid Medline and Embase databases were accessed until 18 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of tedizolid with linezolid for adult patients with ABSSSIs were included. The outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of four RCTs involving 2056 adult patients with ABSSSI were enrolled. The early clinical response rate was 79.6% and 80.5% for patients receiving tedizolid and linezolid, respectively. The pooled analysis showed that tedizolid had a non-inferior early clinical response rate to linezolid (odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.77–1.19, I2 = 0%). The early response rate was similar between tedizolid and linezolid among patients with cellulitis/erysipelas (75.1% vs. 77.1%; OR = 0.90, 95% CI = 0.64–1.27, I2 = 25%), major cutaneous abscess (85.1% vs. 86.8%; OR = 0.93, 95% CI = 0.42–2.03, I2 = 37%) and wound infection (85.9% vs. 82.6%; OR = 1.29, 95% CI = 0.66–2.51, I2 = 45%). For methicillin-resistant Staphylococcus aureus patients, tedizolid had a favorable microbiological response rate of 95.2% which was comparable to linezolid (94%) (OR = 1.19, 95% CI = 0.49–2.90, I2 = 0%). In addition to the similar risk of treatment-emergent AEs (a serious event, the discontinuation of the study drug due to AEs and mortality between tedizolid and linezolid), tedizolid was associated with a lower risk of nausea, vomiting and abnormal neutrophil count than linezolid. In conclusion, once-daily tedizolid (200 mg for six days) compared to linezolid (600 mg twice-daily for 10 days) was non-inferior in efficacy in the treatment of ABSSSI. Besides, tedizolid was generally as well tolerated as linezolid, and had a lower incidence of gastrointestinal AEs and bone marrow suppression than linezolid. Full article
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Open AccessArticle
Longitudinal Shedding Patterns and Characterization of Antibiotic Resistant E. coli in Pastured Goats Using a Cohort Study
Antibiotics 2019, 8(3), 136; https://doi.org/10.3390/antibiotics8030136 - 02 Sep 2019
Viewed by 500
Abstract
There is a scarcity of information on antibiotic resistance in goats. To understand shedding of resistant Escherichia coli in pastured goats, we collected fecal samples from a mixed age cohort over a one-year period. No antibiotic had been used on the study animals [...] Read more.
There is a scarcity of information on antibiotic resistance in goats. To understand shedding of resistant Escherichia coli in pastured goats, we collected fecal samples from a mixed age cohort over a one-year period. No antibiotic had been used on the study animals one year prior to and during the study period. Resistant isolates were detected in all age groups and prevalence in goat kids was significantly higher than adults; 43–48% vs. 8–25% respectively. The proportion of resistant isolates was higher when animals were congregated near handling facility than on pasture. Most isolates were resistant to tetracycline (51%) and streptomycin (30%), but also to antibiotics that had never been used on the farm; ampicillin (19%). TetB, bla-TEM, (aadA and strpA/strpB) genes were detected in 70%, 43%, (44% and 24%) of tetracycline, ampicillin, and streptomycin resistant isolates respectively. Resistant isolates also harbored virulent genes and some belonged to D and B2 phylogenetic groups. Thus, pastured goats, despite minimal exposure to antibiotics, are reservoirs of resistant E. coli that may contaminate the environment and food chain and spread resistant genes to pathogenic bacteria and some that are potential animal and human pathogens. Environmental sources may play a role in acquisition of resistant bacteria in pastured goats. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Gram-negative Bacteria)
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Open AccessArticle
Investigating Understandings of Antibiotics and Antimicrobial Resistance in Diverse Ethnic Communities in Australia: Findings from a Qualitative Study
Antibiotics 2019, 8(3), 135; https://doi.org/10.3390/antibiotics8030135 - 02 Sep 2019
Viewed by 591
Abstract
This paper explores the understandings of antibiotics and antimicrobial resistance (AMR) among ethnically diverse informants in Melbourne, Australia. A total of 31 face-to-face semi-structured qualitative interviews were conducted with a sample of ethnic in-patients who were admitted with an acquired antimicrobial infection in [...] Read more.
This paper explores the understandings of antibiotics and antimicrobial resistance (AMR) among ethnically diverse informants in Melbourne, Australia. A total of 31 face-to-face semi-structured qualitative interviews were conducted with a sample of ethnic in-patients who were admitted with an acquired antimicrobial infection in a public hospital (n = 7); five hospital interpreters; and ethnic members of the general community (n = 19) as part of a broader study of lay understandings of AMR. Thematic analysis revealed there was poor understanding of AMR, even among informants being treated for AMR infections. Causes of the increasing incidence of AMR were attributed to: weather fluctuations and climate change; a lack of environmental cleanliness; and the arrival of new migrant groups. Asian informants emphasized the need for humoral balance. Antibiotics were viewed as ‘strong’ medicines that could potentially disrupt this balance and weaken the body. Travel back to countries of origin sometimes involved the use of medical services and informants noted that some community members imported antibiotics from overseas. Most used the internet and social media to source health information. There is a lack of information in their own languages. More attention needs to be given to migrant communities who are vulnerable to the development, transmission and infection with resistant bacteria to inform future interventions. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
Open AccessArticle
Female Asthmatic Patients Have Higher Risk to Develop Gemifloxacin-Associated Skin Rash, Highlighting Unique Delayed Onset Characteristics
Antibiotics 2019, 8(3), 134; https://doi.org/10.3390/antibiotics8030134 - 31 Aug 2019
Viewed by 558
Abstract
Gemifloxacin is a common oral antibiotic for lower respiratory tract infection worldwide. We noticed an uncommon delayed onset skin rash in patients who received Gemifloxacin. Therefore, we retrospectively reviewed all patients who received Gemifloxacin from 1 January 2011 to 31 May 2016 in [...] Read more.
Gemifloxacin is a common oral antibiotic for lower respiratory tract infection worldwide. We noticed an uncommon delayed onset skin rash in patients who received Gemifloxacin. Therefore, we retrospectively reviewed all patients who received Gemifloxacin from 1 January 2011 to 31 May 2016 in a university-affiliated hospital in Taiwan. A total of 1358 patients were enrolled, of whom 36 (2.65%) had skin eruptions. The female patients had a significantly higher odds ratio (OR) 2.24 (95% confidence interval (CI) 1.11–4.53, p = 0.021) of having skin eruptions. A history of asthma was also a significant risk factor (OR 2.04, 95% CI = 1.01–4.14, p = 0.043). Female asthmatic patients had the highest risk of skin eruptions (10/129, 7.2%) with an adjusted OR up to 4.45 (95% CI = 1.81–10.93, p < 0.001) compared to male and non-asthmatic patients. Of note, up to 58.3% (21/36) of the patients experienced a skin rash after they had completed and stopped Gemifloxacin. The median onset time was on the second day (ranging one to five days) after completing treatment. We reported that female asthmatic patients have the highest risk of Gemifloxacin-associated skin eruptions in Asia and that they highlighted a unique delayed onset skin rash. Full article
(This article belongs to the Special Issue Innate Antimicrobial Defense of Skin and Oral Mucosa)
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Open AccessReview
The Application of Ribosome Engineering to Natural Product Discovery and Yield Improvement in Streptomyces
Antibiotics 2019, 8(3), 133; https://doi.org/10.3390/antibiotics8030133 - 30 Aug 2019
Viewed by 655
Abstract
Microbial natural product drug discovery and development has entered a new era, driven by microbial genomics and synthetic biology. Genome sequencing has revealed the vast potential to produce valuable secondary metabolites in bacteria and fungi. However, many of the biosynthetic gene clusters are [...] Read more.
Microbial natural product drug discovery and development has entered a new era, driven by microbial genomics and synthetic biology. Genome sequencing has revealed the vast potential to produce valuable secondary metabolites in bacteria and fungi. However, many of the biosynthetic gene clusters are silent under standard fermentation conditions. By rational screening for mutations in bacterial ribosomal proteins or RNA polymerases, ribosome engineering is a versatile approach to obtain mutants with improved titers for microbial product formation or new natural products through activating silent biosynthetic gene clusters. In this review, we discuss the mechanism of ribosome engineering and its application to natural product discovery and yield improvement in Streptomyces. Our analysis suggests that ribosome engineering is a rapid and cost-effective approach and could be adapted to speed up the discovery and development of natural product drug leads in the post-genomic era. Full article
(This article belongs to the Special Issue Mechanism and Regulation of Antibiotic Synthesis in Streptomyces)
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Open AccessBrief Report
Reduced Incidence of Carbapenem-Resistant Klebsiella pneumoniae Infections in Cardiac Surgery Patients after Implementation of an Antimicrobial Stewardship Project
Antibiotics 2019, 8(3), 132; https://doi.org/10.3390/antibiotics8030132 - 28 Aug 2019
Viewed by 685
Abstract
Infections due to carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are associated with increased mortality in cardiac surgery patients. In this short communication, we report on the changes in the incidence of CR-Kp colonization and CR-Kp infection in cardiac surgery patients from 2014 to 2018 in [...] Read more.
Infections due to carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are associated with increased mortality in cardiac surgery patients. In this short communication, we report on the changes in the incidence of CR-Kp colonization and CR-Kp infection in cardiac surgery patients from 2014 to 2018 in a teaching hospital in Italy, after the implementation of an antimicrobial stewardship project in 2014. During the study period, 2261 patients underwent open-heart surgery. Of them, 130 were found to be colonized by CR-Kp (5.7%) and 52 developed a postoperative CR-Kp infection (2.3%). The crude in-hospital mortality in patients with CR-Kp infections was 48% (25/52). The incidences of both CR-Kp colonization (incidence rate ratio (IRR) 0.82, 95% confidence intervals (CI) 0.78–0.86, p < 0.001) and CR-Kp infection (IRR 0.76, 95% CI 0.69–0.83, p < 0.001) considerably decreased over the study period. This encouraging result should prompt further concerted efforts, directed towards retaining the positive impact of stewardship and infection-control interventions on CR-Kp-related morbidity in the long term. Full article
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Open AccessReview
Phage Therapy with a Focus on the Human Microbiota
Antibiotics 2019, 8(3), 131; https://doi.org/10.3390/antibiotics8030131 - 27 Aug 2019
Viewed by 1180
Abstract
Bacteriophages are viruses that infect bacteria. After their discovery in the early 1900s, bacteriophages were a primary cure against infectious disease for almost 25 years, before being completely overshadowed by antibiotics. With the rise of antibiotic resistance, bacteriophages are being explored again for [...] Read more.
Bacteriophages are viruses that infect bacteria. After their discovery in the early 1900s, bacteriophages were a primary cure against infectious disease for almost 25 years, before being completely overshadowed by antibiotics. With the rise of antibiotic resistance, bacteriophages are being explored again for their antibacterial activity. One of the critical apprehensions regarding bacteriophage therapy, however, is the possibility of genome evolution, development of phage resistance, and subsequent perturbations to our microbiota. Through this review, we set out to explore the principles supporting the use of bacteriophages as a therapeutic agent, discuss the human gut microbiome in relation to the utilization of phage therapy, and the co-evolutionary arms race between host bacteria and phage in the context of the human microbiota. Full article
(This article belongs to the Special Issue Bacteriophages: Alternatives to Antibiotics and Beyond)
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Open AccessArticle
Comparative In Vitro Activities of First and Second-Generation Ceragenins Alone and in Combination with Antibiotics Against Multidrug-Resistant Klebsiella pneumoniae Strains
Antibiotics 2019, 8(3), 130; https://doi.org/10.3390/antibiotics8030130 - 27 Aug 2019
Viewed by 621
Abstract
Objectives: The ceragenins, or CSAs, were designed to mimic the activities of antimicrobial peptides and represent a new class of antimicrobial agent. The aim of this study was to comparatively investigate the antimicrobial activities of first/second generation ceragenins and various antibiotics against multidrug-resistant [...] Read more.
Objectives: The ceragenins, or CSAs, were designed to mimic the activities of antimicrobial peptides and represent a new class of antimicrobial agent. The aim of this study was to comparatively investigate the antimicrobial activities of first/second generation ceragenins and various antibiotics against multidrug-resistant (MDR) Klebsiella pneumoniae, including colistin-resistant bacteria. Also, the synergistic effects of two ceragenins with colistin or meropenem were investigated with six K. pneumoniae strains presenting different resistant patterns. Methods: Minimal inhibition concentrations (MICs) were determined by the microdilution method according to the CLSI. Antibiotic combination studies were evaluated by the time–kill curve method. Results: MIC50 and MIC90 values of tested ceragenins ranged from 8 to 32 mg/L and 16 to 128 mg/L. Overall, among the ceragenins tested, CSA-131 showed the lowest MIC50 and MIC90 values against all microorganisms. The MICs of the ceragenins were similar or better than tested antibiotics, except for colistin. Synergistic activities of CSA-131 in combination with colistin was found for strains both at 1× MIC and 4× MIC. No antagonism was observed with any combination. Conclusions: First-generation ceragenins CSA-13 and CSA-44 and second-generation ceragenins CSA-131, CSA-138 and CSA-142 have significant antimicrobial effects on MDR K. pneumoniae. Mechanisms allowing resistance to clinical comparator antibiotics like colistin did not impact the activity of ceragenins. These results suggest that ceragenins may play a role in treating infections that are resistant to known antibiotics. Full article
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Open AccessEditorial
Antibiotic Resistance: From the Bench to Patients
Antibiotics 2019, 8(3), 129; https://doi.org/10.3390/antibiotics8030129 - 27 Aug 2019
Viewed by 651
Abstract
The discovery and subsequent clinical introduction of antibiotics is one of the most important game-changers in the history of medicine [...] Full article
(This article belongs to the Special Issue Antibiotic Resistance: From the Bench to Patients)
Open AccessReview
Staphylococcus aureus Infections in Malaysia: A Review of Antimicrobial Resistance and Characteristics of the Clinical Isolates, 1990–2017
Antibiotics 2019, 8(3), 128; https://doi.org/10.3390/antibiotics8030128 - 26 Aug 2019
Viewed by 697
Abstract
Staphylococcus aureus is an important nosocomial pathogen and its multidrug resistant strains, particularly methicillin-resistant S. aureus (MRSA), poses a serious threat to public health due to its limited therapeutic options. The increasing MRSA resistance towards vancomycin, which is the current drug of last [...] Read more.
Staphylococcus aureus is an important nosocomial pathogen and its multidrug resistant strains, particularly methicillin-resistant S. aureus (MRSA), poses a serious threat to public health due to its limited therapeutic options. The increasing MRSA resistance towards vancomycin, which is the current drug of last resort, gives a great challenge to the treatment and management of MRSA infections. While vancomycin resistance among Malaysian MRSA isolates has yet to be documented, a case of vancomycin resistant S. aureus has been reported in our neighboring country, Indonesia. In this review, we present the antimicrobial resistance profiles of S. aureus clinical isolates in Malaysia with data obtained from the Malaysian National Surveillance on Antimicrobial Resistance (NSAR) reports as well as various peer-reviewed published records spanning a period of nearly three decades (1990–2017). We also review the clonal types and characteristics of Malaysian S. aureus isolates, where hospital-associated (HA) MRSA isolates tend to carry staphylococcal cassette chromosome mec (SCCmec) type III and were of sequence type (ST)239, whereas community-associated (CA) isolates are mostly SCCmec type IV/V and ST30. More comprehensive surveillance data that include molecular epidemiological data would enable further in-depth understanding of Malaysian S. aureus isolates. Full article
(This article belongs to the Special Issue Staphylococci Antimicrobial Resistance)
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Open AccessReview
Direct Measurement of Performance: A New Era in Antimicrobial Stewardship
Antibiotics 2019, 8(3), 127; https://doi.org/10.3390/antibiotics8030127 - 24 Aug 2019
Viewed by 1041
Abstract
For decades, the performance of antimicrobial stewardship programs (ASPs) has been measured by incidence rates of hospital-onset Clostridioides difficile and other infections due to multidrug-resistant bacteria. However, these represent indirect and nonspecific ASP metrics. They are often confounded by factors beyond an ASP’s [...] Read more.
For decades, the performance of antimicrobial stewardship programs (ASPs) has been measured by incidence rates of hospital-onset Clostridioides difficile and other infections due to multidrug-resistant bacteria. However, these represent indirect and nonspecific ASP metrics. They are often confounded by factors beyond an ASP’s control, such as changes in diagnostic testing methods or algorithms and the potential of patient-to-patient transmission. Whereas these metrics remain useful for global assessment of healthcare systems, antimicrobial use represents a direct metric that separates the performance of an ASP from other safety and quality teams within an institution. The evolution of electronic medical records and healthcare informatics has made measurements of antimicrobial use a reality. The US Centers for Disease Control and Prevention’s initiative for reporting antimicrobial use and standardized antimicrobial administration ratio in hospitals is highly welcomed. Ultimately, ASPs should be evaluated based on what they do best and what they can control, that is, antimicrobial use within their own institution. This narrative review critically appraises existing stewardship metrics and advocates for adopting antimicrobial use as the primary performance measure. It proposes novel formulas to adjust antimicrobial use based on quality of care and microbiological burden at each institution to allow for meaningful inter-network and inter-facility comparisons. Full article
(This article belongs to the Special Issue Feature Paper in Antibiotics for 2019)
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Open AccessReview
The Perfect Bacteriophage for Therapeutic Applications—A Quick Guide
Antibiotics 2019, 8(3), 126; https://doi.org/10.3390/antibiotics8030126 - 23 Aug 2019
Viewed by 801
Abstract
The alarming spread of multiresistant infections has kick-started the quest for alternative antimicrobials. In a way, given the steady increase in untreatable infectious diseases, success in this endeavor has become a matter of life and death. Perhaps we should stop searching for an [...] Read more.
The alarming spread of multiresistant infections has kick-started the quest for alternative antimicrobials. In a way, given the steady increase in untreatable infectious diseases, success in this endeavor has become a matter of life and death. Perhaps we should stop searching for an antibacterial panacea and explore a multifaceted strategy in which a wide range of compounds are available on demand depending on the specific situation. In the context of this novel tailor-made approach to combating bacterial pathogens, the once forgotten phage therapy is undergoing a revival. Indeed, the compassionate use of bacteriophages against seemingly incurable infections has been attracting a lot of media attention lately. However, in order to take full advantage of this strategy, bacteria’s natural predators must be taken from their environment and then carefully selected to suit our needs. In this review, we have explored the vast literature regarding phage isolation and characterization for therapeutic purposes, paying special attention to the most recent studies, in search of findings that hint at the most efficient strategies to identify suitable candidates. From this information, we will list and discuss the traits that, at the moment, are considered particularly valuable in phages destined for antimicrobial therapy applications. Due to the growing importance given to biofilms in the context of bacterial infections, we will dedicate a specific section to those characteristics that indicate the suitability of a bacteriophage as an antibiofilm agent. Overall, the objective is not just to have a large collection of phages, but to have the best possible candidates to guarantee elimination of the target pathogens. Full article
(This article belongs to the Special Issue Feature Paper in Antibiotics for 2019)
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