Antibiotics

12 pages, 2285 KiB

Open AccessArticle

Characterization of LysBC17, a Lytic Endopeptidase from Bacillus cereus

by Steven M. Swift, Irina V. Etobayeva, Kevin P. Reid, Jerel J. Waters, Brian B. Oakley, David M. Donovan and Daniel C. Nelson

Antibiotics 2019, 8(3), 155; https://doi.org/10.3390/antibiotics8030155 - 19 Sep 2019

Cited by 10 | Viewed by 4933

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

(This article belongs to the Special Issue Updates on Novel Antimicrobial Agents and Strategies Against Pathogenic Bacteria)

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Schematics, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and zymogram of LysBC17, and its recombinant derivatives. (A) Schematics showing predicted domains of LysBC17, CAT (catalytic domain), cell wall binding domain (CWB), and the green fluorescent protein (GFP)-CWB proteins. (B) Coomassie-stained SDS-PAGE gel. Arrows indicate the purified proteins. (C) Zymogram gel with embedded B. cereus ATCC 14579 cells. Black triangle marks the clearing from LysBC17 activity on the embedded cells. Lanes for gels: lane 1, markers; lane 2, LysBC17 (32.5 kDa); lane 3, CAT (15.3 kDa); lane 4, CWB (19.0 kDa); lane 5, GFP-CWB (46.9 kDa). Full article ">Figure 2
Lytic activity of LysBC17 and its derivatives. (A) Dose-response of LysBC17 activity by turbidity reduction assay (TRA). Activity velocity is measured as the drop in milli-optical density at λ600 nm (-mOD600) per minute. (B) Activity of full-length LysBC17 by TRA compared to its CAT, CWB, and a GFP-CWB fusion; each at 80 µg/mL. Experiments run, N = 3. Relative activity of 100% assigned to the maximum value in the data set. (C) Spot lysis assay of LysBC17 and its derivatives. B. cereus cells were embedded in BHI semisolid agar, and 10 µL of 0.01, 0.1, or 1.0 mg/mL endolysin or buffer control (“0”) were spotted on the top. The plate was incubated at 37 °C for 2 h. Error bars represent the standard deviation. Full article ">Figure 3
Determination of pH and NaCl optima for LysBC17 by TRA. (A) pH range for LysBC17 activity (5 µg/mL) was tested in borate-phosphate buffer versus B. cereus cells. (B) Range of NaCl for LysBC17 activity (5 µg/mL) was tested in 50 mM NaH2PO4, pH 7.0 versus B. cereus cells. N = 3 for all experiments. Relative activity of 100% assigned to the maximum value in the data set. Error bars represent the standard deviation. Full article ">Figure 4
Thermostability of LysBC17. LysBC17 was incubated at the target temperature for 15 min, and then subjected to turbidity reduction assay to determine residual activity. Experiments run, N = 3. Relative activity of 100% assigned to the maximum value in the data set. Error bars represent the standard deviation. Full article ">Figure 5
The CWB of LysBC17 directs GFP (GFP-CWB) to the surface of bacteria. Selected bacterial cells and GFP-labeled LysBC17 CWB were mixed together, washed, and viewed by microscopy per the Methods. 1000× phase-contrast images (left panels) are shown with their corresponding fluorescent images (right panels). Exposure time for all fluorescent images was 100 ms. (A) B. cereus ATCC 4342, (B) B. cereus ATCC 11778, (C) B. cereus ATCC 14579, (D) B. thuringiensis ATCC 10792, (E) B. anthracis Ames 35, (F) B. anthracis UM23, (G) B. pumilus BJ0050, H) B. pumilus ATCC 700814. Scale bar = 5 µm. Full article ">

21 pages, 715 KiB

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

by Mainul Haque, Nor Azlina A. Rahman, Judy McKimm, Massimo Sartelli, Golam Mohammad Kibria, Md Zakirul Islam, Siti Nur Najihah Binti Lutfi, Nur Syamirah Aishah Binti Othman and Shahidah Leong Binti Abdullah

Antibiotics 2019, 8(3), 154; https://doi.org/10.3390/antibiotics8030154 - 19 Sep 2019

Cited by 17 | Viewed by 9206

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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15 pages, 692 KiB

Open AccessArticle

The Contribution of Efflux Pumps in Mycobacterium abscessus Complex Resistance to Clarithromycin

by Júlia S. Vianna, Diana Machado, Ivy B. Ramis, Fábia P. Silva, Dienefer V. Bierhals, Michael Andrés Abril, Andrea von Groll, Daniela F. Ramos, Maria Cristina S. Lourenço, Miguel Viveiros and Pedro E. Almeida da Silva

Antibiotics 2019, 8(3), 153; https://doi.org/10.3390/antibiotics8030153 - 18 Sep 2019

Cited by 28 | Viewed by 5395

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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Accumulation and efflux of M. abscessus. The figure shows one representative assay for each subspecies, as follows: M. abscessus subsp. abscessus—MabPT1, M. abscessus subsp. massiliense—MabPT3, and M. abscessus subsp. bolletii—MabBR2. (A) Accumulation of increasing concentrations of ethidium bromide. The equilibrium concentration was determined for each strain as the concentration that promoted a plateau of no more than 10% of relative fluorescence units during the 60 min of the assay (black broken line) and is indicated in each graph by an arrow. The assays were performed in the presence of 0.4% of glucose. (B) Accumulation of ethidium bromide in the presence of verapamil. Each strain was tested at its equilibrium concentration (<a href="#antibiotics-08-00153-t004" class="html-table">Table 4</a>) in the presence and absence of ½ MIC of verapamil (see <a href="#antibiotics-08-00153-t001" class="html-table">Table 1</a> for MICs). The assays were performed in the presence of glucose. RFF, relative final fluorescence. (C) Efflux of ethidium bromide. The strains were loaded with ethidium bromide at the equilibrium concentration and efflux took place in the presence of glucose, which was inhibited by verapamil at ½ MIC. Full article ">Figure 2
Relative quantification of efflux pump gene mRNA levels in the M. abscessus strains exposed to clarithromycin. Strains were grown in MGIT medium for the MGIT 960 system in the presence of half MIC of clarithromycin (see <a href="#antibiotics-08-00153-t001" class="html-table">Table 1</a> for MICs). The relative expression of the efflux pump genes was evaluated comparing the relative quantity of the respective mRNA in the presence of clarithromycin to the respective unexposed strain. A level of relative expression equal to 1 indicates that the expression level is identical to the non-exposed parental strain. Genes showing expression levels above four were considered overexpressed (black dashed line in the graph). Full article ">

18 pages, 927 KiB

Open AccessArticle

Decoding Antioxidant and Antibacterial Potentials of Malaysian Green Seaweeds: Caulerpa racemosa and Caulerpa lentillifera

by Wing-Fai Yap, Vangene Tay, Sie-Hui Tan, Yoon-Yen Yow and Jactty Chew

Antibiotics 2019, 8(3), 152; https://doi.org/10.3390/antibiotics8030152 - 17 Sep 2019

Cited by 98 | Viewed by 13440

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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Dose-dependent antibacterial effect of C. racemosa chloroform extracts on MRSA. 1 × 106 bacterial cells were incubated with extract at 5 μg/mL, 10 μg/mL, 25 μg/mL, 50 μg/mL, 100 μg/mL, and 250 μg/mL for 2 h at 37 °C. Next, the samples were serially diluted (10-fold) and plated on Nutrient Agar followed by 18 h of incubation at 37 °C. Finally, bacterial colonies were enumerated and recorded to obtain the % of reduction of bacterial cells. Results represent three independent experiments performed in triplicates. * indicates p < 0.05, ** indicates p < 0.01, *** indicates p < 0.001. Full article ">Figure 2
Heat treatment of C. racemosa chloroform extract. C. racemosa chloroform extract at 250 μg/mL was heated at 95 °C for 30 min prior to use for antibacterial studies. 1 × 106 bacterial cells were then incubated with the heated and non-heated C. racemosa chloroform extract, respectively, for 2 h at 37 °C. Next, the samples were serially diluted (10-fold) and plated on Nutrient Agar followed by 18 h of incubation at 37 °C. Finally, bacterial colonies were enumerated and recorded to obtain the % of reduction of bacterial cells. Results represent three independent experiments performed in triplicates. * indicates p < 0.05, ** indicates p < 0.01, *** indicates p < 0.001. Full article ">

16 pages, 2997 KiB

Open AccessArticle

Isolation and Antibiotic Resistant Research of Tetragenococcus halophilus from Xuanwei Ham, A China High-Salt-Fermented Meat Products

by Yinjiao Li, Luying Shan, Chen Zhang, Zhan Lei and Ying Shang

Antibiotics 2019, 8(3), 151; https://doi.org/10.3390/antibiotics8030151 - 16 Sep 2019

Cited by 7 | Viewed by 4833

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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Partial electropherogram result of genomic DNA of isolated strains. M: DNA Maker DL2000; Lanes 5–49: DNA bands of 10 isolated strains. Full article ">Figure 2
The PCR (polymerase chain reaction) results of the screened T. halophilus strains. (A) The screened T. halophilus strains by amplification of groEL gene; Lane M: DNA Marker DL2000; Lane 0: negative; Lane 1–23: Candidate strain of T. halophilus; (B) Electrophoresis of amplification product; Lane M: DNA Maker; Lane 0: Negative control; Lanes 1–23: The band of PCR amplification products of DNA primer PCR. Full article ">Figure 3
Phylogenetic analysis of 49 strains of T halophilus based on 16S rRNA sequence. Full article ">Figure 4
Distribution of drug resistance of 49 strains of T. halophilus. (A) Number of bacterial strains —by type of antibiotic; (B) Number of bacterial strains —by categories of antibiotic. Full article ">Figure 5
PCR detection results of some T. halophilus resistance genes. (A) blaTEM gene; (B) GyrB gene; (C) SulII gene; (D) EmgrB gene; (E) acrB gene; (F) aadA1 gene; M: DL2000Marker, 0: Negative control. Full article ">Figure 6
Gene mechanism. (A) Inherent drug resistance. Resistance genes exist in bacteria and are passed on from generation to generation. (B) Gene mutation or acquisition of new genes. Pressure to increase antibiotic production causes bacteria to mutate genes into drug resistance and, at the same time, bacteria can easily acquire resistance by ingesting resistance genes released after the death of another drug-resistant bacteria. (C) Integrons mediate drug resistance. Under the catalysis of integrase, integrons can capture and express exogenous genes, especially drug-resistant genes, so that drug-resistant genes can be transmitted between different species. Full article ">Figure 7
Biochemical (protein) mechanism. (A) Production of inactivated or modified enzymes. (B) Change of target site or generation of new target site. This makes is difficult for antibiotics to bind to cells, thus reducing the inhibitory effect of antibiotics. (C) Changes of outer membrane protein. Long-term drug effects can stimulate adventitia proteins to alter the cell wall structure and reduce permeability, thus hindering the penetration of antibiotics. (D) Active efflux system. When energy is available, membrane proteins selectively or non-selectively expel antibiotics from the cell, reducing drug concentration and leading to drug resistance. Full article ">

4 pages, 396 KiB

Open AccessCase Report

Frequent Klebsiella pneumoniae Urinary Tract Infections in a Patient Treated with Ruxolitinib

by Ramy M. Hanna, Maham Khalid, Lama Abd El-Nour and Umut Selamet

Antibiotics 2019, 8(3), 150; https://doi.org/10.3390/antibiotics8030150 - 16 Sep 2019

Cited by 3 | Viewed by 6068

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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8 pages, 851 KiB

Open AccessArticle

Characterization of a Carbapenem-Resistant Kluyvera Cryocrescens Isolate Carrying Bla_ndm-1 from Hospital Sewage

by Ying Li, Li Luo, Zhijiao Xiao, Guangxi Wang, Chengwen Li, Zhikun Zhang, Yingshun Zhou and Luhua Zhang

Antibiotics 2019, 8(3), 149; https://doi.org/10.3390/antibiotics8030149 - 16 Sep 2019

Cited by 13 | Viewed by 4972

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. bla_NDM-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 bla_NDM-1-carrying IncX3 plasmid. Further, we found that SCW13 contained a chromosomal bla_KLUC-2 gene, which was the probable origin of the plasmid-born bla_KLUC-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 bla_NDM through clonal IncX3 plasmids related to pNDM-HN380 among uncommon Enterobacteriaceae strains, including Kluyvera in this case. Full article

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

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Comparison of linear maps of the blaNDM-1-carrying IncX3 plasmids. The complete sequence of pIncX-SHV was used as the reference. Open reading frames (ORFs) are shown as arrows to indicate the direction of transcription and are colored in accordance with their predicted gene functions. Homologous segments (representing ≥98% sequence identity) are indicated by light gray shading. Regions are drawn to scale from accession numbers pIncX-SHV (JN247852), pNDM-HN380 (JX104760), and pRJA274 (KF877335). The alignment is a pairwise BLASTn alignment performed using Easyfig. Full article ">Figure 2
Comparative analysis of the genetic context of blaKLUC-2 and blaKLUC-1. Genes and insertion sequences are indicated by arrows. Light gray shades denote shared regions with a high degree of homology. The construction of sequence comparison was performed using BLAST [<a href="#B29-antibiotics-08-00149" class="html-bibr">29</a>] and Easyfig version 2.2.3. Full article ">Figure 3
A phylogenetic analysis of the core genomes of K. cryocrescens strain SCW13 identified in this study (marked in bold) and 15 Kluyvera genomes deposited in the GenBank database (last accessed July 12, 2019). From left to right: (1) A maximum likelihood tree of Kluyvera spp strains. The phylogeny was inferred from the recombination-filtered single nucleotide polymorphism (SNP) alignment obtained by aligning a genome of Kluyvera isolate against the complete genome of K. cryocrescens NBRC 102467. (2) A heatmap of the antimicrobial resistance genes as determined by ABRicate. The presence or absence of antibiotic resistance genes is indicated by filled or empty squares, respectively. (3) The annotation of each Kluyvera isolate, including GenBank accession no., hosts of isolates, locations, and collection dates. -, not available. Full article ">

12 pages, 1336 KiB

Open AccessArticle

Carbapenemase Genes and Multidrug Resistance of Acinetobacter Baumannii: A Cross Sectional Study of Patients with Pneumonia in Southern Vietnam

by Cuong Hoang Quoc, Thao Nguyen Thi Phuong, Hai Nguyen Duc, Trung Tran Le, Hang Tran Thi Thu, Si Nguyen Tuan and Lan Phan Trong

Antibiotics 2019, 8(3), 148; https://doi.org/10.3390/antibiotics8030148 - 12 Sep 2019

Cited by 18 | Viewed by 6763

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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9 pages, 788 KiB

Open AccessArticle

Global Internet Data on the Interest in Antibiotics and Probiotics Generated by Google Trends

by Mikołaj Kamiński, Igor Łoniewski and Wojciech Marlicz

Antibiotics 2019, 8(3), 147; https://doi.org/10.3390/antibiotics8030147 - 12 Sep 2019

Cited by 27 | Viewed by 6196

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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4 pages, 209 KiB

Open AccessCommunication

Carbapenemase-Producing Elizabethkingia Meningoseptica from Healthy Pigs Associated with Colistin Use in Spain

by Pedro Miguela-Villoldo, Marta Hernández, Miguel Á. Moreno, David Rodríguez-Lázaro, Alberto Quesada, Lucas Domínguez and María Ugarte-Ruiz

Antibiotics 2019, 8(3), 146; https://doi.org/10.3390/antibiotics8030146 - 11 Sep 2019

Viewed by 4347

Abstract

Carbapenems are considered last-resort antimicrobials, especially for treating infections involving multidrug-resistant Gram-negative bacteria. In recent years, extended-spectrum ?-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 ?-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, bla_{B-12_1} and bla_{GOB-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)

14 pages, 2089 KiB

Open AccessArticle

Structural Analysis of The OXA-48 Carbapenemase Bound to A “Poor” Carbapenem Substrate, Doripenem

by Krisztina M. Papp-Wallace, Vijay Kumar, Elise T. Zeiser, Scott A. Becka and Focco van den Akker

Antibiotics 2019, 8(3), 145; https://doi.org/10.3390/antibiotics8030145 - 11 Sep 2019

Cited by 12 | Viewed by 6031

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

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

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Figure 1
Structures of doripenem, imipenem, ertapenem, and meropenem (A) Chemical structures of doripenem, imipenem, ertapenem, and meropenem; the left side of each carbapenem contains the R1 hydroxyethyl side chain that is present in all carbapenems, while the right side of the molecules is denoted as the R2 side chain, which varies in chemistry in different carbapenems. (B) Tautomerization states of the acyl intermediate of doripenem in Δ2 and Δ1R forms. Full article ">Figure 2
Electron density of doripenem bound in the active site of OXA-48 K73A. (A) Unbiased |Fo|-|Fc| electron density difference map of the active site of molecule A of OXA-48 K73 revealing the presence of a covalently bound doripenem (with cyan carbon atoms) attached to S70 (density contoured at 3 σ level). The sulfonamide moiety was observed in two conformations (labeled a and b). (B) Same as in (A) but for molecule B of OXA-48 K73A. The tail of doripenem attached to the 2 position of the pyrrolidine ring is observed in two conformations labeled a and b with occupancies of 0.7 and 0.3, respectively (difference density contoured at 2.75 σ level). (C) Same as in (B) but rotated ~90° to show the two conformations more clearly. Full article ">Figure 3
Stereo diagram of doripenem interactions in the active site of OXA-48 K73A molecule A. Hydrogen bonds are depicted as dashed black lines. Interacting water molecules are shown as red spheres. Full article ">Figure 4
Superposition of doripenem-bound molecules A and B of OXA-48 K73A. Molecules A and B are colored with white and magenta, respectively, carbon atoms; doripenem bound to molecule A is colored cyan. The active site of molecule B has a chloride ion bound (colored green, labeled ‘Cl1’). Full article ">Figure 5
Superposition of the doripenem-bound complexes of OXA-51 I129L/K83D and OXA-48 K73A. (A) OXA-51 I129L/K83D, OXA-48 K73A molecules A and B are superpositioned. Carbon atoms for the OXA-51 complex are colored light pink, molecules A and B of OXA-48 K73A are colored as in <a href="#antibiotics-08-00145-f003" class="html-fig">Figure 3</a>. Hydrogen bonds between the carboxyl moiety and R250 in the OXA-51 I129L/K83D structure are depicted as black dashed lines; hydrogen bonds between doripenem and that same R250 in the OXA-48 K73A molecule A structure are shown as grey dashed lines. The hydroxyethyl moiety of doripenem is highlighted by a blue dashed oval line; positions 1, 2, and 3 on the pyrrolidine ring are numbered. The rotation needed for doripenem’s pyrrolidine ring when bound to OXA-48 to achieve the binding mode as when bound to OXA-51 I129L/K83D is depicted by a small red dashed arrow. (B) Rotated such that view is perpendicular to that in (A). Van der Waals interaction between the methyl moiety of doripenem and Y211 in the OXA-48 K73A molecule A structure is depicted as a green dashed line. Full article ">Figure 6
Superposition of the doripenem-bound structures of OXA-24/40 K84D, OXA-51 I129L/K83D, and OXA-48 K73A. Carbon atoms for the OXA-24/40 K84D doripenem complex are colored green; molecule A of OXA-48 K73A and OXA-51 I129L/K83D are colored as in <a href="#antibiotics-08-00145-f005" class="html-fig">Figure 5</a>. The hydroxyethyl moiety of the doripenem’s pyrrolidine ring atom numbering and rotation are shown as in <a href="#antibiotics-08-00145-f005" class="html-fig">Figure 5</a>. The superpositioning involved the same set of 25 Cα atoms as in <a href="#antibiotics-08-00145-f005" class="html-fig">Figure 5</a> onto their equivalent residues in the OXA-24/40 K84D complex. Except for S70 and A71, all residues of their respective OXAs are labeled and color-coded. Full article ">

13 pages, 1410 KiB

Open AccessArticle

Antimicrobial Activity of Silver Camphorimine Complexes against Candida Strains

by Joana P. Costa, M. Joana F. Pinheiro, Sílvia A. Sousa, Ana M. Botelho do Rego, Fernanda Marques, M. Conceição Oliveira, Jorge H. Leitão, Nuno P. Mira and M. Fernanda N. N. Carvalho

Antibiotics 2019, 8(3), 144; https://doi.org/10.3390/antibiotics8030144 - 10 Sep 2019

Cited by 16 | Viewed by 4971

Abstract

Hydroxide [Ag(OH)L] (L = ^IVL, ^VL, ^VIL, ^VIIL), oxide [{AgL}₂}(μ-O)] (L = ^IL, ^IIL, ^IIIL, ^VL, ^VIL) or chloride [Ag^IIL]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 [Ag^IIL]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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13 pages, 1481 KiB

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

by Márió Gajdács, Katalin Burián and Gabriella Terhes

Antibiotics 2019, 8(3), 143; https://doi.org/10.3390/antibiotics8030143 - 9 Sep 2019

Cited by 51 | Viewed by 7259

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 ?-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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6 pages, 195 KiB

Open AccessArticle

Predictors of Appropriate Antibiotic Use in Bacteremia Patients Presenting at the Emergency Department

by Pariwat Phungoen, Areerat Kraisriwattana, Korakot Apiratwarakul, Lumyai Wonglakorn and Kittisak Sawanyawisuth

Antibiotics 2019, 8(3), 142; https://doi.org/10.3390/antibiotics8030142 - 9 Sep 2019

Cited by 4 | Viewed by 3928

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)

12 pages, 2094 KiB

Open AccessArticle

Epidemiological Characteristics of Staphylococcus Aureus in Raw Goat Milk in Shaanxi Province, China

by Weidong Qian, Lanfang Shen, Xinchen Li, Ting Wang, Miao Liu, Wenjing Wang, Yuting Fu and Qiao Zeng

Antibiotics 2019, 8(3), 141; https://doi.org/10.3390/antibiotics8030141 - 8 Sep 2019

Cited by 15 | Viewed by 5101

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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13 pages, 3892 KiB

Open AccessArticle

Tobramycin Promotes Melanogenesis by Upregulating p38 MAPK Protein Phosphorylation in B16F10 Melanoma Cells

by Seung-Hyun Moon, You Chul Chung and Chang-Gu Hyun

Antibiotics 2019, 8(3), 140; https://doi.org/10.3390/antibiotics8030140 - 5 Sep 2019

Cited by 11 | Viewed by 8114

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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16 pages, 1371 KiB

Open AccessArticle

Antibiotic Prescribing by Informal Healthcare Providers for Common Illnesses: A Repeated Cross-Sectional Study in Rural India

by Shweta Khare, Manju Purohit, Megha Sharma, Ashok J. Tamhankar, Cecilia Stalsby Lundborg, Vishal Diwan and Ashish Pathak

Antibiotics 2019, 8(3), 139; https://doi.org/10.3390/antibiotics8030139 - 5 Sep 2019

Cited by 32 | Viewed by 7501

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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Relative distribution of proportion of prescribed antibiotics out of the total prescriptions in the respective seasons and percentage ofprescribed antibiotics for the individual complaint out of the total antibiotic prescriptions in the respective seasons in rural Ujjain, India. X axis represents the seasons (April–May 2015 Pre-monsoon 1, June–September 2015 Monsoon 1, October–December 2015 Post-monsoon, January–February 2016 Winter, March–May 2016 Pre-monsoon 2, June–September 2016 Monsoon 2); Primary Y axis on left represents the percentage of prescribed antibiotics out of total prescriptions in the respective season and secondary Y axis on right represents the percentage of prescribed antibiotics for the individual complaints (Fever, URTI—Upper respiratory tract infection, Gastro-intestinal disorders, Oral and dental problems, Skin infections, and Unspecified pain) out of the total antibiotic prescriptions in the respective seasons. Full article ">Figure 2
Relative distribution of defined daily doses/1000 prescriptions/presenting complaints (DDD/TPP) in rural Ujjain, India. X axis represents the defined daily doses/1000 prescriptions/presenting complaints (DDD/TPP); Y axis represents the complaints (URTI—Upper respiratory tract infection, Pain—Unspecified pain). Full article ">Figure 3
Geographical location of the selected informal healthcare providers. The maps show India, Madhya Pradesh, Ujjain district, and the location of participating informal healthcare providers within the sampling frame. Full article ">

20 pages, 1383 KiB

Open AccessReview

Bacteriophages as Alternatives to Antibiotics in Clinical Care

by Danitza Romero-Calle, Raquel Guimarães Benevides, Aristóteles Góes-Neto and Craig Billington

Antibiotics 2019, 8(3), 138; https://doi.org/10.3390/antibiotics8030138 - 4 Sep 2019

Cited by 154 | Viewed by 20629

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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11 pages, 2191 KiB

Open AccessArticle

Tedizolid Versus Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infection: A Systematic Review and Meta-Analysis

by Shao-Huan Lan, Wei-Ting Lin, Shen-Peng Chang, Li-Chin Lu, Chien-Ming Chao, Chih-Cheng Lai and Jui-Hsiang Wang

Antibiotics 2019, 8(3), 137; https://doi.org/10.3390/antibiotics8030137 - 4 Sep 2019

Cited by 28 | Viewed by 6529

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

(This article belongs to the Special Issue Updates on Novel Antimicrobial Agents and Strategies Against Pathogenic Bacteria)

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18 pages, 1478 KiB

Open AccessArticle

Longitudinal Shedding Patterns and Characterization of Antibiotic Resistant E. coli in Pastured Goats Using a Cohort Study

by Eunice Ndegwa, Hanin Almehmadi, Kim Chyer, Paul Kaseloo and Ankrah A. Ako

Antibiotics 2019, 8(3), 136; https://doi.org/10.3390/antibiotics8030136 - 2 Sep 2019

Cited by 9 | Viewed by 4755

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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Bar chart illustrating percentage of resistant E. coli isolates in pastured goat kids and the respective nursing does up to weaning. Proportions at the same sampling points with different number of asterisks ** vs. * are significantly different (P < 0.05). Full article ">Figure 2
Bar chart comparing percentage of resistant E. coli isolates in different age groups of pastured goat kids (only goat kids sampled at pasture are represented). Proportions with different number of asterisks ** vs. * are significantly different (P < 0.05). Full article ">Figure 3
Bar chart illustrating types of resistant (intermediate vs full resistance) in E. coli from pastured goat kids from 3 weeks of age to one year (PR-Intermediate resistance, FR-Full resistance, and NR-non-resistance). Full article ">Figure 4
Prevalence of virulence genes in 104 antibiotic resistant E. coli isolates from pastured meat goats. Full article ">Figure 5
Bar chart representing phylogenetic groups of 104 antibiotic resistant E. coli isolates from pastured meat goats. Full article ">

17 pages, 500 KiB

Open AccessArticle

Investigating Understandings of Antibiotics and Antimicrobial Resistance in Diverse Ethnic Communities in Australia: Findings from a Qualitative Study

by Andrea Whittaker, Davina Lohm, Chris Lemoh, Allen C. Cheng and Mark Davis

Antibiotics 2019, 8(3), 135; https://doi.org/10.3390/antibiotics8030135 - 2 Sep 2019

Cited by 14 | Viewed by 6531

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)

8 pages, 6277 KiB

Open AccessArticle

Female Asthmatic Patients Have Higher Risk to Develop Gemifloxacin-Associated Skin Rash, Highlighting Unique Delayed Onset Characteristics

by Chiou-Mei Wu, Po-Ju Wei, Yu-Ting Shen, Hsu-Liang Chang, Ying-Ming Tsai, Hung-Fang Pan, Yong-Chieh Chang, Yu-Ching Wei and Chih-Jen Yang

Antibiotics 2019, 8(3), 134; https://doi.org/10.3390/antibiotics8030134 - 31 Aug 2019

Cited by 3 | Viewed by 5043

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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16 pages, 1088 KiB

Open AccessReview

The Application of Ribosome Engineering to Natural Product Discovery and Yield Improvement in Streptomyces

by Saibin Zhu, Yanwen Duan and Yong Huang

Antibiotics 2019, 8(3), 133; https://doi.org/10.3390/antibiotics8030133 - 30 Aug 2019

Cited by 42 | Viewed by 8424

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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5 pages, 452 KiB

Open AccessBrief Report

Reduced Incidence of Carbapenem-Resistant Klebsiella pneumoniae Infections in Cardiac Surgery Patients after Implementation of an Antimicrobial Stewardship Project

by Daniele Roberto Giacobbe, Antonio Salsano, Filippo Del Puente, Francesco Campanini, Giovanni Mariscalco, Anna Marchese, Claudio Viscoli and Francesco Santini

Antibiotics 2019, 8(3), 132; https://doi.org/10.3390/antibiotics8030132 - 28 Aug 2019

Cited by 7 | Viewed by 5415

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

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

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19 pages, 1886 KiB

Open AccessReview

Phage Therapy with a Focus on the Human Microbiota

by Sharita Divya Ganeshan and Zeinab Hosseinidoust

Antibiotics 2019, 8(3), 131; https://doi.org/10.3390/antibiotics8030131 - 27 Aug 2019

Cited by 103 | Viewed by 11815

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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Graphical abstract

Graphical abstract
Full article ">Figure 1
Schematic representation of major groups of bacteriophages. Reproduced with permission from reference [<a href="#B41-antibiotics-08-00131" class="html-bibr">41</a>]. Full article ">Figure 2
Introduction to lytic phage biology. (A) Shadowed Transition Electron Micrograph image of T4 phage (Mag 380,000×). This phage, a member in the Myoviridae family of the Caudovirales order, is one of the seven Escherichia coli phages (T1–T7) in this family. This image shows the icosahedral capsid head containing the genetic material, the contractile tail, and the long tail fibers of the phage. T4 head is approximately 90 nm, wide and the virion is 200 nm in length. This TEM was photographed at Wurtzbiozentrum at the University of Basel, reproduced with permission from references [<a href="#B42-antibiotics-08-00131" class="html-bibr">42</a>,<a href="#B43-antibiotics-08-00131" class="html-bibr">43</a>]. (B) Colorized scanning electron micrograph (SEM) images of multiple T4 bacteriophages infecting an E. coli cell reproduced with permission from reference [<a href="#B44-antibiotics-08-00131" class="html-bibr">44</a>]. (C) SEM images at different stages showing the infection of Synechococcus WH8102 by the S-TIM5 phage. 0 h-uninfected cells. 2 h-phage adsorption. 9-h cell lysis. 9-h viral release. These SEM images were collected from Sabehi. G., from the Israel Institute of Technology, reproduced with permission from reference [<a href="#B45-antibiotics-08-00131" class="html-bibr">45</a>]. (D) The lytic and lysogenic infection cycles. The first two stages are shared for both the cycles. Step 1- Attachment of the phage tail fibers to a specific receptor site on the bacterial cell wall and injection of the viral genome. Step 2- Phage DNA is then circularized and enters the lytic cycle or the lysogenic cycle. Lytic cycle: Step 3A- Synthesis of new viral proteins within the host. Step 4A- Virions are liberated as mature phages upon cell lysis. Lysogenic cycle: Step 3B- Phage DNA integrates within the bacterial chromosome by recombination, in turn becoming a prophage. Step 4B- Lysogenic bacterium reproduces normally and has the potential to do so over many cell divisions. The prophage may be released from the bacterial chromosome through external triggers, resulting in the initiation of the lytic cycle—reproduced with permission from reference [<a href="#B30-antibiotics-08-00131" class="html-bibr">30</a>]. (E) T7 bacteriophage infecting E. coli as seen with cryoelectron tomography at ~4 nm resolution. A/D- Adsorption of T7 phage into the outer membrane. B/E- Injection of the extended tail into the cell envelope. C/F- DNA ejection. These images are collected from Bo Hu, University of Texas—reproduced with permission from reference [<a href="#B31-antibiotics-08-00131" class="html-bibr">31</a>]. Full article ">Figure 3
Sextaphage pharmaceutical product from microgen. Image reproduced with permission form reference [<a href="#B103-antibiotics-08-00131" class="html-bibr">103</a>]. Full article ">

8 pages, 860 KiB

Open AccessArticle

Comparative In Vitro Activities of First and Second-Generation Ceragenins Alone and in Combination with Antibiotics Against Multidrug-Resistant Klebsiella pneumoniae Strains

by Berna Ozbek-Celik, Damla Damar-Celik, Emel Mataraci-Kara, Cagla Bozkurt-Guzel and Paul B. Savage

Antibiotics 2019, 8(3), 130; https://doi.org/10.3390/antibiotics8030130 - 27 Aug 2019

Cited by 14 | Viewed by 4469

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

(This article belongs to the Special Issue Updates on Novel Antimicrobial Agents and Strategies Against Pathogenic Bacteria)

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4 pages, 203 KiB

Open AccessEditorial

Antibiotic Resistance: From the Bench to Patients

by Márió Gajdács and Fernando Albericio

Antibiotics 2019, 8(3), 129; https://doi.org/10.3390/antibiotics8030129 - 27 Aug 2019

Cited by 115 | Viewed by 9672

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)

29 pages, 4826 KiB

Open AccessReview

Staphylococcus aureus Infections in Malaysia: A Review of Antimicrobial Resistance and Characteristics of the Clinical Isolates, 1990–2017

by Ainal Mardziah Che Hamzah, Chew Chieng Yeo, Suat Moi Puah, Kek Heng Chua and Ching Hoong Chew

Antibiotics 2019, 8(3), 128; https://doi.org/10.3390/antibiotics8030128 - 26 Aug 2019

Cited by 39 | Viewed by 8703

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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19 pages, 792 KiB

Open AccessReview

Direct Measurement of Performance: A New Era in Antimicrobial Stewardship

by Majdi N. Al-Hasan, Hana Rac Winders, P. Brandon Bookstaver and Julie Ann Justo

Antibiotics 2019, 8(3), 127; https://doi.org/10.3390/antibiotics8030127 - 24 Aug 2019

Cited by 21 | Viewed by 7964

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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16 pages, 1303 KiB

Open AccessReview

The Perfect Bacteriophage for Therapeutic Applications—A Quick Guide

by Lucía Fernández, Diana Gutiérrez, Pilar García and Ana Rodríguez

Antibiotics 2019, 8(3), 126; https://doi.org/10.3390/antibiotics8030126 - 23 Aug 2019

Cited by 116 | Viewed by 12246

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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