Global Antimicrobial Resistance: What Are the Current Emerging Threats?

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotics Use and Antimicrobial Stewardship".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 54930

Special Issue Editor


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Guest Editor
Case Western Reserve University School of Medicine - Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA
Interests: antimicrobial resistance; carbapenemases; bacterial genomics; molecular epidemiology; multidrug resistant Gram-negative bacteria; Klebsiella pneumoniae

Special Issue Information

Antimicrobial resistance (AMR) is a complex public health challenge impacting all regions of the world. In addition to being a natural evolutionary phenomenon, AMR is increasingly being accelerated by selective pressure exerted as a result of the use and misuse of antibiotics in humans and animals. Fighting this threat is a priority that requires a global approach across multiple sectors beyond healthcare, including the food supply chain (e.g., antibiotics are known to be used for growth promotion) and the environment (e.g., interconnection through medical and agricultural waste that ultimately permeates water and soil). 

The scientific community has made significant advances in increasing their knowledge about the most urgent threats, primarily in clinical settings (e.g., ESKAPE organisms, high-risk clones, etc.); however new mechanisms and new emerging bacterial threats are constantly being discovered within these as well as other settings. 

With this global approach in mind, this Special Issue seeks submissions highlighting the new threats that we need to be on the lookout for: novel antibiotic resistance mechanisms, emerging pathogens, novel ‘high-risk clones’, or increasing rates of resistance in organisms previously considered less of a concern, especially from regions of the world where epidemiological data are scarce.

Dr. Laura J. Rojas
Guest Editor

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Keywords

  • emerging antimicrobial resistance mechanisms
  • emerging pathogens
  • molecular epidemiology
  • low- and middle-income countries

Published Papers (13 papers)

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Research

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12 pages, 305 KiB  
Article
First Detection of Human ST131-CTX-M-15-O25-B2 Clone and High-Risk Clonal Lineages of ESBL/pAmpC-Producing E. coli Isolates from Diarrheic Poultry in Tunisia
by Ahlem Jouini, Amira Klibi, Imen Elarbi, Meriem Ben Chaabene, Safa Hamrouni, Oussema Souiai, Mariem Hanachi, Abdeljelil Ghram and Abderrazak Maaroufi
Antibiotics 2021, 10(6), 670; https://doi.org/10.3390/antibiotics10060670 - 04 Jun 2021
Cited by 10 | Viewed by 2406
Abstract
Circulation of a multi-resistance clone of bacteria associated with genetic elements in diseased animals constitutes a global public health problem. Our study focused on the characterization of the support of ESBL in cefotaxime resistant E. coli (CTXR) isolates recovered from poultry [...] Read more.
Circulation of a multi-resistance clone of bacteria associated with genetic elements in diseased animals constitutes a global public health problem. Our study focused on the characterization of the support of ESBL in cefotaxime resistant E. coli (CTXR) isolates recovered from poultry with diarrhea, analysis of their clonal lineage, and virulence-associated genes. The study was carried out on 130 samples of chickens with diarrhea, collected in 2015 from poultry farms in Tunisia. Isolates of 20 CTXR E. coli strains were identified as ESBL and AmpC β- lactamase producers. The following β-lactamase genes (number of isolates) were detected: blaCTX-M-15+ blaOXA1 (4), blaCTX-M-15 + blaOXA1 + blaTEM-1b (2), blaCTX-M-1 + blaTEM-1b (9), blaCTX-M-1 (2), blaCMY2 + blaTEM-1b (3). Six E. coli harboring blaCTXM-15 were allocated to ST131-B2-O25b-; six and three blaCTX-M-1 were grouped in ST155, ST10, and ST58, respectively, related to the phylogroup D and A. The qnrB gene, the variant aac(6′)-Ib-cr, and the class 1 integrons with different gene cassettes, were detected amongst our 20 isolated strains, which were classified as ExPEC and aEPEC. Our findings highlighted the emergence of the human pandemic ST131-CTX-M-15-O25-B2 clone and the high risk of such clonal lineage strains in diarrheic poultry, in Tunisia, which could constitute a risk of their transfer to healthy animals and humans. Full article
10 pages, 231 KiB  
Article
Epidemiological Characteristics and Predisposing Factors for Surgical Site Infections Caused by Bacterial Pathogens Exhibiting Multidrug-Resistant Patterns
by Abdikarim Hussein Mohamed, Hussein Ali Mohamud and Ebubekir Arslan
Antibiotics 2021, 10(6), 622; https://doi.org/10.3390/antibiotics10060622 - 24 May 2021
Cited by 2 | Viewed by 2264
Abstract
Background: Surgical site infection is the most common kind of nosocomial infection in developed and developing countries. Objectives: Our aim was to identify the prevalence of factors predisposing to multidrug resistance and the antimicrobial susceptibility profile of pathogens. Method: This retrospective study enrolled [...] Read more.
Background: Surgical site infection is the most common kind of nosocomial infection in developed and developing countries. Objectives: Our aim was to identify the prevalence of factors predisposing to multidrug resistance and the antimicrobial susceptibility profile of pathogens. Method: This retrospective study enrolled 10,878 patients who underwent operations in 2018–2020. Pathogens were identified using eosin methylene blue agar. Mueller–Hinton agar was used to assess antimicrobial sensitivity and resistance. In total, 382 patients with confirmed surgical site infection (SSI), whose culture showed growth, were included in the study. Results: The prevalence of SSI in the current study was 3.5%. Escherichia coli was the predominant pathogen (35.8%), followed by Staphylococcus aureus (21.8%). Antibiotic use, chronic renal failure, diabetes, and emergency operations were found to increase the likelihood of multidrug resistance (OR = 6.23, CI = 1.443–26.881, p = 0.014; OR = 5.67, CI = 1.837–19.64, p = 0.02; OR = 2.54, CI = 1.46–7.35, p = 0.03; OR = 1.885, CI = 1.067–3.332, p = 0.002, respectively). The pathogens showed different levels of antimicrobial resistance against ceftriaxone (72.7%), ciprofloxacin (46.6%), and gentamicin (34%). Antimicrobial resistance of about 1–3.4% was exhibited by linezolid, tigecycline, and teicoplanin. Conclusion: The study presented significantly increased multidrug-resistant (MDR) Enterobacteriaceae pathogens isolated from surgical sites. They involve significant morbidity and mortality rates and increased health-related costs. Full article
14 pages, 504 KiB  
Article
Molecular Epidemiology of Carbapenem-Resistant Acinetobacter baumannii Isolates from Northern Africa and the Middle East
by Paul G. Higgins, Ralf Matthias Hagen, Bernd Kreikemeyer, Philipp Warnke, Andreas Podbielski, Hagen Frickmann and Ulrike Loderstädt
Antibiotics 2021, 10(3), 291; https://doi.org/10.3390/antibiotics10030291 - 11 Mar 2021
Cited by 21 | Viewed by 2590
Abstract
At the Bundeswehr Hospitals of Hamburg and Westerstede, patients repatriated from subtropical war and crisis zones of Northern Africa and the Middle East were medically treated, including microbiological assessment. Within a six-year interval, 16 Acinetobacter spp. strains, including 14 Acinetobacter baumannii (Ab) isolates [...] Read more.
At the Bundeswehr Hospitals of Hamburg and Westerstede, patients repatriated from subtropical war and crisis zones of Northern Africa and the Middle East were medically treated, including microbiological assessment. Within a six-year interval, 16 Acinetobacter spp. strains, including 14 Acinetobacter baumannii (Ab) isolates with resistance against carbapenems and origins in Afghanistan (n = 4), Iraq (n = 2), Libya (n = 2), and Syria (n = 8) were collected. While clonal relationships of Libyan and Syrian strains had been assessed by superficial next generation sequencing (NGS) and “DiversiLab” repetitive elements sequence-based (rep-)PCR so far, this study provides core genome-based sequence typing and thus more detailed epidemiological information. In detail, sequencing allowed a definitive species identification and comparison with international outbreak-associated Ab strains by core genome multi locus sequence typing (cgMLST) and the identification of MLST lineages, as well as the identification of known resistance genes. The sequence analysis allowed for the confirmation of outbreak-associated clonal clusters among the Syrian and Afghan Ab isolates, indicating likely transmission events. The identified acquired carbapenem resistance genes comprised blaOXA-23, blaOXA-58, blaNDM-1, and blaGES-11, next to other intrinsic and acquired, partly mobile resistance-associated genes. Eleven out of 14 Ab isolates clustered with the previously described international clonal lineages IC1 (4 Afghan strains), IC2 (6 Syrian strains), and IC7 (1 Syrian strain). Identified Pasteur sequence types of the 14 Ab strains comprised ST2 (Syrian), ST25 (Libyan), ST32 (Iraqi), ST81 (Afghan), ST85 (Libyan), and ST1112 (Syrian), respectively. In conclusion, the study revealed a broad spectrum of resistance genes in Ab isolated from war-injured patients from Northern Africa and the Middle East, thereby broadening the scarcely available data on locally abundant clonal lineages and resistance mechanisms. Full article
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11 pages, 1235 KiB  
Article
Molecular Analysis of Polymyxin Resistance among Carbapenemase-Producing Klebsiella pneumoniae in Colombia
by Elsa De La Cadena, María Fernanda Mojica, Juan Carlos García-Betancur, Tobías Manuel Appel, Jessica Porras, Christian José Pallares, Juan Sebastián Solano-Gutiérrez, Laura J. Rojas and María Virginia Villegas
Antibiotics 2021, 10(3), 284; https://doi.org/10.3390/antibiotics10030284 - 10 Mar 2021
Cited by 6 | Viewed by 2614
Abstract
Polymyxin resistance in Klebsiella pneumoniae has been attributed to mutations in mgrB, phoPQ, pmrAB, and crrAB and to the presence of mcr plasmid-mediated genes. Herein, we describe the molecular characteristics of 24 polymyxin- and carbapenem-resistant K. pneumoniae isolates recovered from [...] Read more.
Polymyxin resistance in Klebsiella pneumoniae has been attributed to mutations in mgrB, phoPQ, pmrAB, and crrAB and to the presence of mcr plasmid-mediated genes. Herein, we describe the molecular characteristics of 24 polymyxin- and carbapenem-resistant K. pneumoniae isolates recovered from six Colombian cities between 2009 and 2019. Minimum inhibitory concentrations (MICs) to polymyxin were confirmed by broth microdilution, and whole-genome sequencing was performed to determine sequence type, resistome, and mutations in the genes related to polymyxin resistance, as well the presence of mcr. The results showed high-level resistance to polymyxin (MICs ≥ 4 μg/mL). blaKPC-3 was present in the majority of isolates (17/24; 71%), followed by blaKPC-2 (6/24; 25%) and blaNDM-1 (1/24; 4%). Most isolates belonged to the CG258 (17/24; 71%) and presented amino acid substitutions in PmrB (22/24; 92%) and CrrB (15/24; 63%); mutations in mgrB occurred in only five isolates (21%). Additional mutations in pmrA, crrA, and phoPQ nor any of the mcr resistance genes were identified. In conclusion, we found clonal dissemination of polymyxin and carbapenem-resistant K. pneumoniae isolates in Colombia, mainly associated with CG258 and blaKPC-3. Surveillance of this multidrug-resistant clone is warranted due to the limited therapeutic options for the treatment of carbapenem-resistant K. pneumoniae infections. Full article
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13 pages, 1343 KiB  
Article
Whole-Genome Sequencing Reveals the Presence of the blaCTX-M-65 Gene in Extended-Spectrum β-Lactamase-Producing and Multi-Drug-Resistant Clones of Salmonella Serovar Infantis Isolated from Broiler Chicken Environments in the Galapagos Islands
by Elton Burnett, Maria Ishida, Sofia de Janon, Sohail Naushad, Marc-Olivier Duceppe, Ruimin Gao, Armando Jardim, Jessica C. Chen, Kaitlin A. Tagg, Dele Ogunremi and Christian Vinueza-Burgos
Antibiotics 2021, 10(3), 267; https://doi.org/10.3390/antibiotics10030267 - 05 Mar 2021
Cited by 15 | Viewed by 3705
Abstract
Salmonella Infantis, a common contaminant of poultry products, is known to harbor mobile genetic elements that confer multi-drug resistance (MDR) and have been detected in many continents. Here, we report four MDR S. Infantis strains recovered from poultry house environments in Santa [...] Read more.
Salmonella Infantis, a common contaminant of poultry products, is known to harbor mobile genetic elements that confer multi-drug resistance (MDR) and have been detected in many continents. Here, we report four MDR S. Infantis strains recovered from poultry house environments in Santa Cruz Island of the Galapagos showing extended-spectrum β-lactamase (ESBL) resistance and reduced fluoroquinolone susceptibility. Whole-genome sequencing (WGS) revealed the presence of the ESBL-conferring blaCTX-M-65 gene in an IncFIB-like plasmid in three S. Infantis isolates. Multi-locus sequence typing (MLST) and single nucleotide variant/polymorphism (SNP) SNVPhyl analysis showed that the S. Infantis isolates belong to sequence type ST32, likely share a common ancestor, and are closely related (1–3 SNP difference) to blaCTX-M-65-containing clinical and veterinary S. Infantis isolates from the United States and Latin America. Furthermore, phylogenetic analysis of SNPs following core-genome alignment (i.e., ParSNP) inferred close relatedness between the S. Infantis isolates from Galapagos and the United States. Prophage typing confirmed the close relationship among the Galapagos S. Infantis and was useful in distinguishing them from the United States isolates. This is the first report of MDR blaCTX-M-65-containing S. Infantis in the Galapagos Islands and highlights the need for increased monitoring and surveillance programs to determine prevalence, sources, and reservoirs of MDR pathogens. Full article
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18 pages, 1402 KiB  
Article
Distribution of Extended-Spectrum β-Lactamase (ESBL)-Encoding Genes among Multidrug-Resistant Gram-Negative Pathogens Collected from Three Different Countries
by Khaled S. M. Azab, Mohamed Ali Abdel-Rahman, Hussien H. El-Sheikh, Ehab Azab, Adil A. Gobouri and Mohamed M. S. Farag
Antibiotics 2021, 10(3), 247; https://doi.org/10.3390/antibiotics10030247 - 02 Mar 2021
Cited by 10 | Viewed by 2594
Abstract
The incidence of Extended-spectrum β-lactamase (ESBL)-encoding genes (blaCTX-M and blaTEM) among Gram-negative multidrug-resistant pathogens collected from three different countries was investigated. Two hundred and ninety-two clinical isolates were collected from Egypt (n = 90), Saudi Arabia (n [...] Read more.
The incidence of Extended-spectrum β-lactamase (ESBL)-encoding genes (blaCTX-M and blaTEM) among Gram-negative multidrug-resistant pathogens collected from three different countries was investigated. Two hundred and ninety-two clinical isolates were collected from Egypt (n = 90), Saudi Arabia (n = 162), and Sudan (n = 40). Based on the antimicrobial sensitivity against 20 antimicrobial agents from 11 antibiotic classes, the most resistant strains were selected and identified using the Vitek2 system and 16S rRNA gene sequence analysis. A total of 85.6% of the isolates were found to be resistant to more than three antibiotic classes. The ratios of the multidrug-resistant strains for Egypt, Saudi Arabia, and Sudan were 74.4%, 90.1%, and 97.5%, respectively. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa showed inconstant resistance levels to the different classes of antibiotics. Escherichia coli and Klebsiella pneumoniae had the highest levels of resistance against macrolides followed by penicillins and cephalosporin, while Pseudomonas aeruginosa was most resistant to penicillins followed by classes that varied among different countries. The isolates were positive for the presence of the blaCTX-M and blaTEM genes. The blaCTX-M gene was the predominant gene in all isolates (100%), while blaTEM was detected in 66.7% of the selected isolates. This work highlights the detection of multidrug-resistant bacteria and resistant genes among different countries. We suggest that the medical authorities urgently implement antimicrobial surveillance plans and infection control policies for early detection and effective prevention of the rapid spread of these pathogens. Full article
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19 pages, 1523 KiB  
Article
High Risk Clone: A Proposal of Criteria Adapted to the One Health Context with Application to Enterotoxigenic Escherichia coli in the Pig Population
by Maud de Lagarde, Ghyslaine Vanier, Julie Arsenault and John Morris Fairbrother
Antibiotics 2021, 10(3), 244; https://doi.org/10.3390/antibiotics10030244 - 28 Feb 2021
Cited by 11 | Viewed by 2704
Abstract
The definition of a high risk clone for antibiotic resistance dissemination was initially established for human medicine. We propose a revised definition of a high risk clone adapted to the One Health context. Then, we applied our criteria to a cluster of enrofloxacin [...] Read more.
The definition of a high risk clone for antibiotic resistance dissemination was initially established for human medicine. We propose a revised definition of a high risk clone adapted to the One Health context. Then, we applied our criteria to a cluster of enrofloxacin non susceptible ETEC:F4 isolates which emerged in 2013 in diseased pigs in Quebec. The whole genomes of 183 ETEC:F4 strains isolated in Quebec from 1990 to 2018 were sequenced. The presence of virulence and resistance genes and replicons was examined in 173 isolates. Maximum likelihood phylogenetic trees were constructed based on SNP data and clones were identified using a set of predefined criteria. The strains belonging to the clonal lineage ST100/O149:H10 isolated in Quebec in 2013 or later were compared to ETEC:F4 whole genome sequences available in GenBank. Prior to 2000, ETEC:F4 isolates from pigs in Quebec were mostly ST90 and belonged to several serotypes. After 2000, the isolates were mostly ST100/O149:H10. In this article, we demonstrated the presence of a ETEC:F4 high risk clone. This clone (1) emerged in 2013, (2) is multidrug resistant, (3) has a widespread distribution over North America and was able to persist several months on farms, and (4) possesses specific virulence genes. It is crucial to detect and characterize high risk clones in animal populations to increase our understanding of their emergence and their dissemination. Full article
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12 pages, 1324 KiB  
Article
Susceptibility Testing of Colistin for Acinetobacter baumannii: How Far Are We from the Truth?
by Federica Sacco, Paolo Visca, Federica Runci, Guido Antonelli and Giammarco Raponi
Antibiotics 2021, 10(1), 48; https://doi.org/10.3390/antibiotics10010048 - 05 Jan 2021
Cited by 6 | Viewed by 2897
Abstract
Acinetobacter baumannii is involved in life-threatening nosocomial infections, mainly in the intensive care units (ICUs), and often colistin may represent the last therapeutic opportunity. The susceptibility to colistin of 51 epidemiologically typed A. baumannii strains isolated in 2017 from clinical samples of patients [...] Read more.
Acinetobacter baumannii is involved in life-threatening nosocomial infections, mainly in the intensive care units (ICUs), and often colistin may represent the last therapeutic opportunity. The susceptibility to colistin of 51 epidemiologically typed A. baumannii strains isolated in 2017 from clinical samples of patients hospitalized in the ICU of a tertiary care academic hospital was investigated. All isolates were carbapenem-resistant due to the presence of the blaOXA-23 gene in sequence group 1 (international clonal lineage II) and sequence group 4 (related to international clonal lineage II) isolates, and to the blaOXA-24/40 gene in sequence group 2 (international clonal lineage I) isolates. Vitek®2, agar diffusion, and broth microdilution tests showed major discordancy (≥2 dilution factors) in the minimum inhibitory concentration (MIC) values for colistin in 24 out of 51 isolates, resulting in erroneous reporting of qualitative susceptibility data for eight isolates. In growth kinetics experiments in the presence of colistin, five isolates grew with drug concentrations above the susceptibility breakpoint when incubated for >12 h, and three isolates showed the presence of heteroresistant subpopulations. This study highlights that the high frequency of isolation of carbapenem-resistant A. baumannii strains in high-risk infectious wards requires an accurate application of methods for detecting susceptibility to antibiotics, in particular to colistin, so as to ensure a correct therapeutic approach. Full article
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7 pages, 246 KiB  
Communication
Bacteriostatic and Bactericidal Effect of Tigecycline on Leptospira spp.
by Fabrizio Bertelloni, Giovanni Cilia and Filippo Fratini
Antibiotics 2020, 9(8), 467; https://doi.org/10.3390/antibiotics9080467 - 30 Jul 2020
Cited by 7 | Viewed by 4688
Abstract
Tigecycline is a relatively new antimicrobial, belonging to glycylcyclines with antimicrobial activity against a large spectrum of bacteria. Very few data are available on its effect on Leptospira spp., which consist in a bacteriostatic mechanism. The aim of this investigation was to evaluate [...] Read more.
Tigecycline is a relatively new antimicrobial, belonging to glycylcyclines with antimicrobial activity against a large spectrum of bacteria. Very few data are available on its effect on Leptospira spp., which consist in a bacteriostatic mechanism. The aim of this investigation was to evaluate the bacteriostatic and bactericidal effect of tigecycline on reference Leptospira strains belonging to 16 serovars. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined through the microdilutions method, and tetracycline was used as the control. Results showed that tigecycline had higher MIC and MBC values than tetracycline. Obtained MIC values were between 4 and 32 µg/mL, while MBC values between 16 and >128 µg/mL. Patoc (MIC: 4 µg/mL; MBC: 16 µg/mL) resulted in the most susceptible serovar, while the most resistant were Bataviae (MIC: 32 µg/mL; MBC: 64 µg/mL), Bratislava (MIC: 8 µg/mL; MBC 128 µg/mL), and Tarassovi (MIC: 8 µg/mL; MBC: >128 µg/mL). This is the first investigation focused on the effect of tigecycline against Leptospira spp. reference strains. Since tigecycline is used as a treatment for bacteremia and urinary tract disease, and these symptoms could be linked to Leptospira infection, the possibility of using this antibiotic as a treatment for leptospirosis should be evaluated. Further studies are needed to explore the possibility to use tigecycline for in vivo application against Leptospira. Full article
14 pages, 3775 KiB  
Article
Antimicrobial Susceptibility and Characterization of Resistance Mechanisms of Corynebacterium urealyticum Clinical Isolates
by Itziar Chapartegui-González, Marta Fernández-Martínez, Ana Rodríguez-Fernández, Danilo J. P. Rocha, Eric R. G. R. Aguiar, Luis G. C. Pacheco, José Ramos-Vivas, Jorge Calvo, Luis Martínez-Martínez and Jesús Navas
Antibiotics 2020, 9(7), 404; https://doi.org/10.3390/antibiotics9070404 - 13 Jul 2020
Cited by 8 | Viewed by 3530
Abstract
Corynebacterium urealyticum is a non-diphtherial urease-producing clinically relevant corynebacterial, most frequently involved in urinary tract infections. Most of the C. urealyticum clinical isolates are frequently resistant to several antibiotics. We investigated the susceptibility of 40 C. urealyticum isolated in our institution during the [...] Read more.
Corynebacterium urealyticum is a non-diphtherial urease-producing clinically relevant corynebacterial, most frequently involved in urinary tract infections. Most of the C. urealyticum clinical isolates are frequently resistant to several antibiotics. We investigated the susceptibility of 40 C. urealyticum isolated in our institution during the period 2005–2017 to eight compounds representative of the main clinically relevant classes of antimicrobial agents. Antimicrobial susceptibility was determined by the Epsilometer test. Resistance genes were searched by PCR. All strains were susceptible to vancomycin whereas linezolid and rifampicin also showed good activity (MICs90 = 1 and 0.4 mg/L, respectively). Almost all isolates (39/40, 97.5%) were multidrug resistant. The highest resistance rate was observed for ampicillin (100%), followed by erythromycin (95%) and levofloxacin (95%). Ampicillin resistance was associated with the presence of the blaA gene, encoding a class A β-lactamase. The two rifampicin-resistant strains showed point mutations driving amino acid replacements in conserved residues of RNA polymerase subunit β (RpoB). Tetracycline resistance was due to an efflux-mediated mechanism. Thirty-nine PFGE patterns were identified among the 40 C. urealyticum, indicating that they were not clonally related, but producing sporadic infections. These findings raise the need of maintaining surveillance strategies among this multidrug resistant pathogen. Full article
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Review

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12 pages, 284 KiB  
Review
Antibiotic Resistance in Pediatric Infections: Global Emerging Threats, Predicting the Near Future
by Alessandra Romandini, Arianna Pani, Paolo Andrea Schenardi, Giulia Angela Carla Pattarino, Costantino De Giacomo and Francesco Scaglione
Antibiotics 2021, 10(4), 393; https://doi.org/10.3390/antibiotics10040393 - 06 Apr 2021
Cited by 55 | Viewed by 8844
Abstract
Antibiotic resistance is a public health threat of the utmost importance, especially when it comes to children: according to WHO data, infections caused by multidrug resistant bacteria produce 700,000 deaths across all ages, of which around 200,000 are newborns. This surging issue has [...] Read more.
Antibiotic resistance is a public health threat of the utmost importance, especially when it comes to children: according to WHO data, infections caused by multidrug resistant bacteria produce 700,000 deaths across all ages, of which around 200,000 are newborns. This surging issue has multipronged roots that are specific to the pediatric age. For instance, the problematic overuse and misuse of antibiotics (for wrong diagnoses and indications, or at wrong dosage) is also fueled by the lack of pediatric-specific data and trials. The ever-evolving nature of this age group also poses another issue: the partly age-dependent changes of a developing system of cytochromes determine a rather diverse population in terms of biochemical characteristics and pharmacokinetics profiles, hard to easily codify in an age- or weight-dependent dosage. The pediatric population is also penalized by the contraindications of tetracyclines and fluoroquinolones, and by congenital malformations which often require repeated hospitalizations and pharmacological and surgical treatments from a very young age. Emerging threats for the pediatric age are MRSA, VRSA, ESBL-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae and the alarming colistin resistance. Urgent actions need to be taken in order to step back from a now likely post-antibiotic era, where simple infections might cause infant death once again. Full article
21 pages, 576 KiB  
Review
Antimicrobial Resistance in Common Respiratory Pathogens of Chronic Bronchiectasis Patients: A Literature Review
by Riccardo Inchingolo, Chiara Pierandrei, Giuliano Montemurro, Andrea Smargiassi, Franziska Michaela Lohmeyer and Angela Rizzi
Antibiotics 2021, 10(3), 326; https://doi.org/10.3390/antibiotics10030326 - 20 Mar 2021
Cited by 8 | Viewed by 5189
Abstract
Non-cystic fibrosis bronchiectasis is a chronic disorder in which immune system dysregulation and impaired airway clearance cause mucus accumulation and consequent increased susceptibility to lung infections. The presence of pathogens in the lower respiratory tract causes a vicious circle resulting in impaired mucociliary [...] Read more.
Non-cystic fibrosis bronchiectasis is a chronic disorder in which immune system dysregulation and impaired airway clearance cause mucus accumulation and consequent increased susceptibility to lung infections. The presence of pathogens in the lower respiratory tract causes a vicious circle resulting in impaired mucociliary function, bronchial inflammation, and progressive lung injury. In current guidelines, antibiotic therapy has a key role in bronchiectasis management to treat acute exacerbations and chronic infection and to eradicate bacterial colonization. Contrastingly, antimicrobial resistance, with the risk of multidrug-resistant pathogen development, causes nowadays great concern. The aim of this literature review was to assess the role of antibiotic therapy in bronchiectasis patient management and possible concerns regarding antimicrobial resistance based on current evidence. The authors of this review stress the need to expand research regarding bronchiectasis with the aim to assess measures to reduce the rate of antimicrobial resistance worldwide. Full article
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29 pages, 7242 KiB  
Review
Drug-Resistant Fungi: An Emerging Challenge Threatening Our Limited Antifungal Armamentarium
by Amir Arastehfar, Toni Gabaldón, Rocio Garcia-Rubio, Jeffrey D. Jenks, Martin Hoenigl, Helmut J. F. Salzer, Macit Ilkit, Cornelia Lass-Flörl and David S. Perlin
Antibiotics 2020, 9(12), 877; https://doi.org/10.3390/antibiotics9120877 - 08 Dec 2020
Cited by 128 | Viewed by 9398
Abstract
The high clinical mortality and economic burden posed by invasive fungal infections (IFIs), along with significant agricultural crop loss caused by various fungal species, has resulted in the widespread use of antifungal agents. Selective drug pressure, fungal attributes, and host- and drug-related factors [...] Read more.
The high clinical mortality and economic burden posed by invasive fungal infections (IFIs), along with significant agricultural crop loss caused by various fungal species, has resulted in the widespread use of antifungal agents. Selective drug pressure, fungal attributes, and host- and drug-related factors have counteracted the efficacy of the limited systemic antifungal drugs and changed the epidemiological landscape of IFIs. Species belonging to Candida, Aspergillus, Cryptococcus, and Pneumocystis are among the fungal pathogens showing notable rates of antifungal resistance. Drug-resistant fungi from the environment are increasingly identified in clinical settings. Furthermore, we have a limited understanding of drug class-specific resistance mechanisms in emerging Candida species. The establishment of antifungal stewardship programs in both clinical and agricultural fields and the inclusion of species identification, antifungal susceptibility testing, and therapeutic drug monitoring practices in the clinic can minimize the emergence of drug-resistant fungi. New antifungal drugs featuring promising therapeutic profiles have great promise to treat drug-resistant fungi in the clinical setting. Mitigating antifungal tolerance, a prelude to the emergence of resistance, also requires the development of effective and fungal-specific adjuvants to be used in combination with systemic antifungals. Full article
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