Special Issue "Antimicrobial Resistance: The Final Frontier"

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (31 October 2020).

Special Issue Editor

Dr. Matthaios Papadimitriou Olivgeris
E-Mail Website
Guest Editor
Department of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland
Interests: antimicrobial resistance; bloodstream infections; critically ill patients; carbapenemases; VRE; MRSA
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

The development of resistance after the discovery of a given antimicrobial is inevitable. The process of resistance development and its dissemination in the healthcare environment and the community are accelerated by misuse of such antimicrobials. The most important resistant bacterial pathogens are designated by the acronym “ESKAPE” that includes vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus, and multidrug-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species. During the last two decades, some Gram-negative bacteria have acquired genes that confer resistance to carbapenems, further restricting our limited armamentarium.

The constant rise of antimicrobial resistance constitutes one of the most important public health issues. According to some projections, in a matter of decades, infections due to antimicrobial-resistant pathogens will be responsible for more deaths than diabetes or cancer.

Therefore, this Special Issue seeks submissions concerning the mechanisms and evolution of resistance, the epidemiology and surveillance of resistance in the clinical setting and animal husbandry, clinical applications of existing and newer antimicrobials, and strategies to control the emergence and dissemination of resistance and improve the control of antimicrobials’ use.

Dr. Matthaios Papadimitriou Olivgeris
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antimicrobial resistance
  • MRSA
  • VRE
  • carbapenemases
  • infection control
  • multidrug resistance

Published Papers (14 papers)

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Research

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Article
Mortality of Pandrug-Resistant Klebsiella pneumoniae Bloodstream Infections in Critically Ill Patients: A Retrospective Cohort of 115 Episodes
Antibiotics 2021, 10(1), 76; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010076 - 15 Jan 2021
Viewed by 721
Abstract
Background: The increased frequency of bacteraemias caused by pandrug-resistant Klebsiella pneumoniae (PDR-Kp) has significant implications. The aim of the present study was to identify predictors associated with mortality of PDR-Kp bacteraemias. Methods: Patients with monomicrobial bacteraemia due to PDR-Kp were included. K. pneumoniae [...] Read more.
Background: The increased frequency of bacteraemias caused by pandrug-resistant Klebsiella pneumoniae (PDR-Kp) has significant implications. The aim of the present study was to identify predictors associated with mortality of PDR-Kp bacteraemias. Methods: Patients with monomicrobial bacteraemia due to PDR-Kp were included. K. pneumoniae was considered PDR if it showed resistance to all available groups of antibiotics. Primary outcome was 30-day mortality. Minimum inhibitory concentrations (MICs) of meropenem, tigecycline, fosfomycin, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. blaKPC, blaVIM, blaNDM, and blaOXA genes were detected by PCR. Results: Among 115 PDR-Kp bacteraemias, the majority of infections were primary bacteraemias (53; 46.1%), followed by catheter-related (35; 30.4%). All isolates were resistant to tested antimicrobials. blaKPC was the most prevalent carbapenemase gene (98 isolates; 85.2%). Thirty-day mortality was 39.1%; among 51 patients with septic shock, 30-day mortality was 54.9%. Multivariate analysis identified the development of septic shock, Charlson comorbidity index, and bacteraemia other than primary or catheter-related as independent predictors of mortality, while a combination of at least three antimicrobials was identified as an independent predictor of survival. Conclusions: Mortality of PDR-Kp bloodstream infections was high. Administration of at least three antimicrobials might be beneficial for infections in critically ill patients caused by such pathogens. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Article
Global Trends in Antimicrobial Use in Food Animals from 2017 to 2030
Antibiotics 2020, 9(12), 918; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120918 - 17 Dec 2020
Cited by 15 | Viewed by 1814
Abstract
Demand for animal protein is rising globally and has been facilitated by the expansion of intensive farming. However, intensive animal production relies on the regular use of antimicrobials to maintain health and productivity on farms. The routine use of antimicrobials fuels the development [...] Read more.
Demand for animal protein is rising globally and has been facilitated by the expansion of intensive farming. However, intensive animal production relies on the regular use of antimicrobials to maintain health and productivity on farms. The routine use of antimicrobials fuels the development of antimicrobial resistance, a growing threat for the health of humans and animals. Monitoring global trends in antimicrobial use is essential to track progress associated with antimicrobial stewardship efforts across regions. We collected antimicrobial sales data for chicken, cattle, and pig systems in 41 countries in 2017 and projected global antimicrobial consumption from 2017 to 2030. We used multivariate regression models and estimated global antimicrobial sales in 2017 at 93,309 tonnes (95% CI: 64,443, 149,886). Globally, sales are expected to rise by 11.5% in 2030 to 104,079 tonnes (95% CI: 69,062, 172,711). All continents are expected to increase their antimicrobial use. Our results show lower global antimicrobial sales in 2030 compared to previous estimates, owing to recent reports of decrease in antimicrobial use, in particular in China, the world’s largest consumer. Countries exporting a large proportion of their production are more likely to report their antimicrobial sales data than countries with small export markets. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Article
Detection of Various Streptococcus spp. and Their Antimicrobial Resistance Patterns in Clinical Specimens from Austrian Swine Stocks
Antibiotics 2020, 9(12), 893; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120893 - 11 Dec 2020
Cited by 1 | Viewed by 568
Abstract
Knowledge of pathogenic potential, frequency and antimicrobial resistance patterns of porcine Streptococcus (S.) spp. other than S. suis is scarce. Between 2016 and 2020, altogether 553 S. spp. isolates were recovered from clinical specimens taken from Austrian swine stocks and [...] Read more.
Knowledge of pathogenic potential, frequency and antimicrobial resistance patterns of porcine Streptococcus (S.) spp. other than S. suis is scarce. Between 2016 and 2020, altogether 553 S. spp. isolates were recovered from clinical specimens taken from Austrian swine stocks and submitted for routine microbiological examination. Antimicrobial susceptibility testing towards eight antimicrobial substances was performed using disk diffusion test. All isolates from skin lesions belonged to the species S. dysgalactiae subspecies equisimilis (SDSE). S. hyovaginalis was mainly isolated from the upper respiratory tract (15/19) and S. thoraltensis from the genitourinary tract (11/15). The majority of S. suis isolates were resistant to tetracycline (66%), clindamycin (62%) and erythromycin (58%). S. suis isolates from the joints had the highest resistance rates. S. suis and SDSE isolates resistant to tetracycline were more likely to be resistant to erythromycin and clindamycin (p < 0.01). Results show that different species of Streptococcus tend to occur in specific body sites. Nevertheless, a statement whether these species are colonizers or potential pathogens cannot be given so far. High resistance rates of S. suis towards tetracyclines and erythromycin and high recovery rates of S. suis from lung tissue should be considered when treating pigs with respiratory diseases. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Article
Monitoring of Non-β-Lactam Antibiotic Resistance-Associated Genes in ESBL Producing Enterobacterales Isolates
Antibiotics 2020, 9(12), 884; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120884 - 09 Dec 2020
Viewed by 635
Abstract
Genetic context of extended spectrum β-Lactamase (ESBL) producing Enterobacterales and its association with plasmid mediated quinolone resistance (PMQR), aminoglycoside modifying enzymes (AME) and Trimethoprim/Sulfamethoxazole (TMP-SMX) resistance is little known from North India. Therefore, the current study was aimed to investigate the frequency of [...] Read more.
Genetic context of extended spectrum β-Lactamase (ESBL) producing Enterobacterales and its association with plasmid mediated quinolone resistance (PMQR), aminoglycoside modifying enzymes (AME) and Trimethoprim/Sulfamethoxazole (TMP-SMX) resistance is little known from North India. Therefore, the current study was aimed to investigate the frequency of Non-β-Lactam antibiotic resistance associated genes in extended spectrum β-Lactamase producing Enterobacterales. For this study, Non-Duplicate phenotypically confirmed ESBL producing Enterobacterales isolates (N = 186) were analyzed for ESBLs, PMQRs, AMEs and TMP-SMX resistance genes using polymerase chain reaction (PCR). PCR detected presence of PMQR genes in 81.29% (N = 139) of ESBL isolates (N = 171), AME genes in 60.82% and TMP-SMX resistance genes in 63.74% of the isolates. Molecular characterization of ESBL producing Enterobacterales showed 84.79% blaTEM followed by 73.68% blaCTX-M, 43.86% blaSHV, 19.88% blaPER and 9.94% blaVEB, respectively. Analysis of PMQR genes revealed 77.7% aac(6′)-lb-cr the most commonly detected gene followed by 67.63% oqxB, 62.59% oqxA, 43.17% qnrB, 19.42% qnrD, 18.7% qnrS, 9.35% qnrA, 3.6% qepA and 2.88% qnrC, respectively. Analysis of AMEs gene profile demonstrated 81.73% aac(6′)-Ib, the most frequently encountered gene followed by 46.15% aph(3′)-Ia, 44.23% ant(3”)-Ia, respectively. A 100% prevalence of sul1, followed by dfrA (54.63%) and sul2 (15.74%) was observed. In summary, prevalence of ESBL-Producing genes (particularly blaTEM and blaCTX-M) along with PMQR, AMEs, and TMP-SMX resistant genes may potentially aid in the transfer of antimicrobial resistance among these strains. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
Communication
Impact of Tigecycline’s MIC in the Outcome of Critically Ill Patients with Carbapenemase-Producing Klebsiella pneumoniae Bacteraemia Treated with Tigecycline Monotherapy—Validation of 2019′s EUCAST Proposed Breakpoint Changes
Antibiotics 2020, 9(11), 828; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9110828 - 19 Nov 2020
Cited by 1 | Viewed by 693
Abstract
Background: Tigecycline is a therapeutic option for carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Our aim was to evaluate the impact of the tigecycline’s minimum inhibitory concentration (MIC) in the outcome of patients with CP-Kp bacteraemia treated with tigecycline monotherapy. Methods: Patients with monomicrobial bacteraemia due [...] Read more.
Background: Tigecycline is a therapeutic option for carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Our aim was to evaluate the impact of the tigecycline’s minimum inhibitory concentration (MIC) in the outcome of patients with CP-Kp bacteraemia treated with tigecycline monotherapy. Methods: Patients with monomicrobial bacteraemia due to CP-Kp that received appropriate targeted monotherapy or no appropriate treatment were included. Primary outcome was 30-day mortality. MICs of meropenem, tigecycline, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. PCR for blaKPC, blaVIM, blaNDM, and blaOXA genes was applied. Results: Among 302 CP-Kp bacteraemias, 32 isolates (10.6%) showed MICs of tigecycline ≤ 0.5 mg/L, whereas 177 (58.6%) showed MICs that were 0.75–2 mg/L. Colistin and aminoglycoside susceptibility was observed in 43.0% and 23.8% of isolates, respectively. The majority of isolates carried blaKPC (249; 82.5%), followed by blaVIM (26; 8.6%), both blaKPC and blaVIM (16; 5.3%), and blaNDM (11; 3.6%). Fifteen patients with tigecycline MIC ≤ 0.5 mg/L and 55 with MIC 0.75–2 mg/L were treated with tigecycline monotherapy; 30-day mortality was 20.0% and 50.9%, respectively (p = 0.042). Mortality of 150 patients that received other antimicrobials was 24.7%; among 82 patients that received no appropriate treatment, mortality was 39.0%. No difference in 30-day mortality was observed between patients that received tigecycline (MIC ≤ 0.5 mg/L) or other antimicrobials. Conclusion: Tigecycline monotherapy was as efficacious as other antimicrobials in the treatment of bloodstream infections due to CP-Kp isolates with a tigecycline’s MIC ≤ 0.5 mg/L. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
Article
Species Distribution, Antimicrobial Resistance, and Enterotoxigenicity of Non-aureus Staphylococci in Retail Chicken Meat
Antibiotics 2020, 9(11), 809; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9110809 - 13 Nov 2020
Cited by 2 | Viewed by 730
Abstract
Non-aureus staphylococci (NAS), including coagulase-negative staphylococci, have emerged as important causes of opportunistic infections in humans and animals and a potential cause of staphylococcal food poisoning. In this study, we investigated (i) the staphylococcal species profiles of NAS in in retail chicken [...] Read more.
Non-aureus staphylococci (NAS), including coagulase-negative staphylococci, have emerged as important causes of opportunistic infections in humans and animals and a potential cause of staphylococcal food poisoning. In this study, we investigated (i) the staphylococcal species profiles of NAS in in retail chicken meat, (ii) the phenotypic and genotypic factors associated with antimicrobial resistance in the NAS isolates, and (iii) the prevalence of classical and newer staphylococcal enterotoxin (SE) genes. A total of 58 NAS of nine different species were isolated from retail raw chicken meat samples. The occurrence of multidrug resistance in the NAS, particularly S. agnetis and S. chromogenes, with high resistance rates against tetracycline or fluoroquinolones were confirmed. The tetracycline resistance was associated with the presence of tet(L) in S. chromogenes and S. hyicus or tet(K) in S. saprophyticus. The occurrence of fluoroquinolone resistance in S. agnetis and S. chromogenes was usually associated with mutations in the quinolone resistance determining regions (QRDR) of gyrA and parC. In addition, the frequent presence of SE genes, especially seh, sej, and sep, was detected in S. agnetis and S. chromogenes. Our findings suggest that NAS in raw chicken meat can have potential roles as reservoirs for antimicrobial resistance and enterotoxin genes. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
Article
Development of Resistance in Escherichia coli ATCC25922 under Exposure of Sub-Inhibitory Concentration of Olaquindox
Antibiotics 2020, 9(11), 791; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9110791 - 10 Nov 2020
Cited by 1 | Viewed by 533
Abstract
Quinoxaline1,4-di-N-oxides (QdNOs) are a class of important antibacterial drugs of veterinary use, of which the drug resistance mechanism has not yet been clearly explained. This study investigated the molecular mechanism of development of resistance in Escherichia coli (E. coli) [...] Read more.
Quinoxaline1,4-di-N-oxides (QdNOs) are a class of important antibacterial drugs of veterinary use, of which the drug resistance mechanism has not yet been clearly explained. This study investigated the molecular mechanism of development of resistance in Escherichia coli (E. coli) under the pressure of sub-inhibitory concentration (sub-MIC) of olaquindox (OLA), a representative QdNOs drug. In vitro challenge of E. coli with 1/100× MIC to 1/2× MIC of OLA showed that the bacteria needed a longer time to develop resistance and could only achieve low to moderate levels of resistance as well as form weak biofilms. The transcriptomic and genomic profiles of the resistant E. coli induced by sub-MIC of OLA demonstrated that genes involved in tricarboxylic acid cycle, oxidation-reduction process, biofilm formation, and efflux pumps were up-regulated, while genes involved in DNA repair and outer membrane porin were down-regulated. Mutation rates were significantly increased in the sub-MIC OLA-treated bacteria and the mutated genes were mainly involved in the oxidation-reduction process, DNA repair, and replication. The SNPs were found in degQ, ks71A, vgrG, bigA, cusA, and DR76-4702 genes, which were covered in both transcriptomic and genomic profiles. This study provides new insights into the resistance mechanism of QdNOs and increases the current data pertaining to the development of bacterial resistance under the stress of antibacterials at sub-MIC concentrations. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Article
Pathogenic Escherichia coli Possess Elevated Growth Rates under Exposure to Sub-Inhibitory Concentrations of Azithromycin
Antibiotics 2020, 9(11), 735; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9110735 - 26 Oct 2020
Viewed by 804
Abstract
Antimicrobial resistance (AMR) has been identified by the World Health Organization (WHO) as one of the ten major threats to global health. Advances in technology, including whole-genome sequencing, have provided new insights into the origin and mechanisms of AMR. However, our understanding of [...] Read more.
Antimicrobial resistance (AMR) has been identified by the World Health Organization (WHO) as one of the ten major threats to global health. Advances in technology, including whole-genome sequencing, have provided new insights into the origin and mechanisms of AMR. However, our understanding of the short-term impact of antimicrobial pressure and resistance on the physiology of bacterial populations is limited. We aimed to investigate morphological and physiological responses of clinical isolates of E. coli under short-term exposure to key antimicrobials. We performed whole-genome sequencing on twenty-seven E. coli isolates isolated from children with sepsis to evaluate their AMR gene content. We assessed their antimicrobial susceptibility profile and measured their growth dynamics and morphological characteristics under exposure to varying concentrations of ciprofloxacin, ceftriaxone, tetracycline, gentamicin, and azithromycin. AMR was common, with all organisms resistant to at least one antimicrobial; a total of 81.5% were multi-drug-resistant (MDR). We observed an association between resistance profile and morphological characteristics of the E. coli over a three-hour exposure to antimicrobials. Growth dynamics experiments demonstrated that resistance to tetracycline promoted the growth of E. coli under antimicrobial-free conditions, while resistance to the other antimicrobials incurred a fitness cost. Notably, antimicrobial exposure heterogeneously suppressed bacterial growth, but sub-MIC concentrations of azithromycin increased the maximum growth rate of the clinical isolates. Our results outline complex interactions between organism and antimicrobials and raise clinical concerns regarding exposure of sub-MIC concentrations of specific antimicrobials. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Article
Prevalence and Epidemiology of Multidrug-Resistant Pathogens in the Food Chain and the Urban Environment in Northwestern Germany
Antibiotics 2020, 9(10), 708; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9100708 - 16 Oct 2020
Cited by 1 | Viewed by 790
Abstract
The surveillance of antimicrobial resistance among humans and food-producing animals is important to monitor the zoonotic transmission of multidrug-resistant bacteria (MDRB). We assessed the prevalence of four MDRB within the meat production chain, including extended-spectrum β-lactamase (ESBL)-producing, carbapenemase-producing Enterobacterales (CPE) and colistin-resistant Enterobacterales [...] Read more.
The surveillance of antimicrobial resistance among humans and food-producing animals is important to monitor the zoonotic transmission of multidrug-resistant bacteria (MDRB). We assessed the prevalence of four MDRB within the meat production chain, including extended-spectrum β-lactamase (ESBL)-producing, carbapenemase-producing Enterobacterales (CPE) and colistin-resistant Enterobacterales (Col-E), as well as vancomycin-resistant enterococci (VRE). In total, 505 samples from four stages of meat production, i.e., slaughterhouses, meat-processing plants, fresh food products and the urban environment, were collected in northwestern Germany in 2018/2019 and screened for the presence of MDRB using both culture-based and PCR-based techniques. We detected genes encoding for carbapenemases in 9–56% (blaOXA-48, blaKPC, blaNDM, blaVIM) and colistin resistance-encoding mcr genes in 9–26% of the samples from all stages. Culture-based analysis found CPE and VRE only in environmental samples (11% and 7%, respectively), but Col-E and ESBL-producers in 1–7% and 12–46% of samples from all stages, respectively. Overall, our results showed that ESBL-producers and mcr-carrying Col-E were common in food-producing animals at slaughterhouses, in meat-processing plants and in food items at retail, while CPE and VRE were only found in the environment. The discrepancy between detected carbapenemase genes and isolated CPE emphasizes the need for more sensitive detection methods for CPE monitoring. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Article
Changes in Clinical Characteristics of Community-Acquired Acute Pyelonephritis and Antimicrobial Resistance of Uropathogenic Escherichia coli in South Korea in the Past Decade
Antibiotics 2020, 9(9), 617; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9090617 - 18 Sep 2020
Cited by 2 | Viewed by 842
Abstract
This study examined changes in the clinical characteristics of community-acquired acute pyelonephritis (CA-APN) in South Korea between the period 2010–2011 and 2017–2018. We recruited all CA-APN patients aged ≥19 years who visited eight hospitals in South Korea from September 2017 to August 2018, [...] Read more.
This study examined changes in the clinical characteristics of community-acquired acute pyelonephritis (CA-APN) in South Korea between the period 2010–2011 and 2017–2018. We recruited all CA-APN patients aged ≥19 years who visited eight hospitals in South Korea from September 2017 to August 2018, prospectively. Data collected were compared with those from the previous study in 2010–2012, with the same design and participation from 11 hospitals. A total of 617 patients were enrolled and compared to 818 patients’ data collected in 2010–2011. Escherichia coli was the most common causative pathogen of CA-APN in both periods (87.3% vs. 86.5%, p = 0.680). E. coli isolates showed significantly higher antimicrobial resistance against fluoroquinolone (32.0% vs. 21.6%, p < 0.001), cefotaxime (33.6% vs. 8.3%, p < 0.001), and trimethoprim/sulfamethoxazole (37.5% vs. 29.2%, p = 0.013) in 2017–2018 than in 2010–2011. Total duration of antibiotic treatment increased from 16.55 ± 9.68 days in 2010–2011 to 19.12 ± 9.90 days in 2017–2018 (p < 0.001); the duration of carbapenem usage increased from 0.59 ± 2.87 days in 2010–2011 to 1.79 ± 4.89 days in 2010–2011 (p < 0.001). The median hospitalization was higher for patients in 2017–2018 than in 2010–2011 (9 vs. 7 days, p < 0.001). In conclusion, antimicrobial resistance of E. coli to almost all antibiotic classes, especially third generation cephalosporin, increased significantly in CA-APN in South Korea. Consequently, total duration of antibiotic treatment, including carbapenem usage, increased. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Review

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Review
Use of Oral Tetracyclines in the Treatment of Adult Patients with Community-Acquired Bacterial Pneumonia: A Literature Review on the Often-Overlooked Antibiotic Class
Antibiotics 2020, 9(12), 905; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120905 - 14 Dec 2020
Cited by 1 | Viewed by 883
Abstract
Oral tetracyclines have been used in clinical practice for over 60 years. Overall, one of the most common indications for use of oral tetracyclines is for treatment of adult outpatients with lower respiratory tract infections, including community-acquired pneumonia (CAP). Despite the longstanding use [...] Read more.
Oral tetracyclines have been used in clinical practice for over 60 years. Overall, one of the most common indications for use of oral tetracyclines is for treatment of adult outpatients with lower respiratory tract infections, including community-acquired pneumonia (CAP). Despite the longstanding use of oral tetracyclines, practice patterns indicate that they are often considered after other guideline-concordant oral CAP treatment options (namely macrolides, fluoroquinolones, and β-lactams). However, there are growing resistance or safety concerns with the available oral agents listed for outpatients with CAP in the updated American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines, especially among patients with comorbidities or notable risk factors for resistant pathogens. Given the need for alternative oral agents to macrolides, fluoroquinolones, and beta-lactams for adult outpatients with CAP, this review summarizes the literature on the use of oral tetracyclines (i.e., doxycycline, minocycline, and omadacycline) for this indication. As part of this review, we described their mechanism of action, common mechanisms of resistance, susceptibility profiles against common CAP pathogens, pharmacokinetics, pharmacodynamics, clinical data, and safety. The intent of the review is to highlight the important considerations when deciding between doxycycline, minocycline, and omadacycline for an adult outpatient with CAP in situations in which use of an oral tetracycline is warranted. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
Review
Antibiotics in Food Chain: The Consequences for Antibiotic Resistance
Antibiotics 2020, 9(10), 688; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9100688 - 13 Oct 2020
Cited by 6 | Viewed by 1744
Abstract
Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant [...] Read more.
Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Other

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Brief Report
Fluoroquinolone Can Be an Effective Treatment Option for Acute Pyelonephritis When the Minimum Inhibitory Concentration of Levofloxacin for the Causative Escherichia coli Is ≤16 mg/L
Antibiotics 2021, 10(1), 37; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010037 - 02 Jan 2021
Viewed by 653
Abstract
The purpose of this study was to determine whether the fluoroquinolone (FQ) minimum inhibitory concentration (MIC) for the causative agent Escherichia coli influences the clinical response of FQ treatment at 72 h in patients with community-acquired acute pyelonephritis (CA-APN). We prospectively collected the [...] Read more.
The purpose of this study was to determine whether the fluoroquinolone (FQ) minimum inhibitory concentration (MIC) for the causative agent Escherichia coli influences the clinical response of FQ treatment at 72 h in patients with community-acquired acute pyelonephritis (CA-APN). We prospectively collected the clinical data of women with CA-APN from 11 university hospitals from March 2010 to February 2012 as well as E. coli isolates from the urine or blood. In total, 78 patients included in this study received FQ during the initial 72 h, and the causative E. coli was detected. The clinical response at 72 h was significantly higher in patients with a levofloxacin MIC ≤ 16 mg/L than in those with an MIC > 16 mg/L (70.4% vs. 28.6%, p = 0.038). No difference was observed in clinical response at 72 h based on ciprofloxacin MIC. To summarize, FQ can be an effective treatment option for CA-APN when levofloxacin MIC against E. coli is ≤16 mg/L. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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Brief Report
In Vitro Activity of Dalbavancin against Refractory Multidrug-Resistant (MDR) Staphylococcus aureus Isolates
Antibiotics 2020, 9(12), 865; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120865 - 03 Dec 2020
Cited by 2 | Viewed by 527
Abstract
The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections, always treated with vancomycin and daptomycin, has led to the emergence of vancomycin-intermediate (VISA), heteroresistant vancomycin-intermediate (hVISA) and daptomycin non-susceptible (DNS) S. aureus. Even if glycopeptides and daptomycin remain the keystone for treatment [...] Read more.
The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections, always treated with vancomycin and daptomycin, has led to the emergence of vancomycin-intermediate (VISA), heteroresistant vancomycin-intermediate (hVISA) and daptomycin non-susceptible (DNS) S. aureus. Even if glycopeptides and daptomycin remain the keystone for treatment of resistant S. aureus, the need for alternative therapies that target MRSA has now become imperative. The in vitro antibacterial and bactericidal activity of dalbavancin was evaluated against clinically relevant S. aureus showing raised antibiotic resistance levels, from methicillin-susceptible to Multidrug-Resistant (MDR) MRSA, including hVISA, DNS and rifampicin-resistant (RIF-R) strains. A total of 124 S. aureus strains were tested for dalbavancin susceptibility, by the broth microdilution method. Two VISA and 2 hVISA reference strains, as well as a vancomycin-resistant (VRSA) reference strain and a methicillin-susceptible Staphylococcus aureus (MSSA) reference strain, were included as controls. Time–kill curves were assayed to assess bactericidal activity. Dalbavancin demonstrated excellent in vitro antibacterial and bactericidal activity against all S. aureus resistance classes, including hVISA and DNS isolates. The RIF-R strains showed the highest percentage of isolates with non-susceptibility, reflecting the correlation between rpoB mutations and VISA/hVISA emergence. Our observations suggest that dalbavancin can be considered as an effective alternative for the management of severe MRSA infections also sustained by refractory phenotypes. Full article
(This article belongs to the Special Issue Antimicrobial Resistance: The Final Frontier)
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