Antimicrobials and Antimicrobial Resistance: Current and Future Prospects

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 (30 April 2022) | Viewed by 22662

Special Issue Editor


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Guest Editor
Institute of Antimicrobial Chemotherapy, Smolensk State Medical University, 214019 Smolensk, Russia
Interests: antibiotics; antimicrobial resistance; mechanism of resistance; epidemiology of resistance

Special Issue Information

Dear Colleagues,

As everyone is aware, antimicrobial resistance (AMR) is one of the biggest public health challenges of our time. It has been estimated that each year, at least 700,000 people across the world died from antibiotic-resistant infections. If nothing is done to combat this problem, the figure might reach 10 million people a year by 2050. Fighting this threat is a public health priority that requires a global collaborative approach across different sectors, including medicine, agriculture, and the veterinary sector.

The World Health Organization (WHO) has declared that AMR is one of the top 10 global public health threats facing humanity. The misuse and overuse of antimicrobials are considered the main drivers of the development and spread of drug-resistant pathogens. In addition, lack of clean water and effective infection control measures lead to the further enumeration of microorganisms that are potentially resistant to different antimicrobials. Moreover, the direct and indirect economic losses associated with AMR are significant.

We need to understand that without effective antimicrobials, the success of modern medicine varying from simple interventions (e.g., cesarean section) to complicated ones (major surgery, organ transplantations, etc.) is under increasing risk. Therefore, this Special Issue welcomes submissions related to different aspects of AMR, including epidemiology, surveillance, and analysis of consumption data. Submissions of effective interventions to combat AMR are especially welcome.

Prof. Dr. Roman Kozlov
Guest Editor

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Keywords

  • antibiotics
  • antimicrobial resistance
  • surveillance
  • epediomoly
  • consumption data

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Published Papers (8 papers)

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13 pages, 252 KiB  
Article
Antimicrobial Dispensing Practice in Community Pharmacies in Russia during the COVID-19 Pandemic
by Svetlana Rachina, Roman Kozlov, Anastasiya Kurkova, Ulyana Portnyagina, Shamil Palyutin, Aleksandr Khokhlov, Olga Reshetko, Marina Zhuravleva, Ivan Palagin and on behalf of Russian Working Group of the Project
Antibiotics 2022, 11(5), 586; https://doi.org/10.3390/antibiotics11050586 - 27 Apr 2022
Cited by 8 | Viewed by 2438
Abstract
COVID-19 has had a significant impact on health care systems, including drug use. The present study aimed to evaluate the patterns of community supply of antimicrobials from community pharmacies during the COVID-19 pandemic in five cities of Russia. In a cross-sectional study, a [...] Read more.
COVID-19 has had a significant impact on health care systems, including drug use. The present study aimed to evaluate the patterns of community supply of antimicrobials from community pharmacies during the COVID-19 pandemic in five cities of Russia. In a cross-sectional study, a random sample of pharmacies reported all episodes of antimicrobials supply during a one-week period. Patterns of supply (age and gender of customer, drug name and formulation, prescription availability, indication, etc.) were analyzed. Altogether, 71 pharmacies took part in the study and 5270 encounters were recorded. In total, 4.2% of visits resulted in supply of more than one antimicrobial agent and 5.2% were for parenteral formulations. The rate of prescription-based purchase in participated cities varied from 40.5 to 99.1%. Systemic antibiotics and antivirals accounted for the majority of supplies (60.5 and 26.3%, respectively). Upper respiratory tract infections were reported as the indication for antimicrobials usage in 36.9% of cases, followed by skin and soft tissue infections (12.1%) and urinary tract infections (8.7%); COVID-19 accounted for 8.4% of all supplies. Amoxicillin with clavulanic acid, azithromycin and amoxicillin were indicated as the top three antimicrobials purchased for upper respiratory tract infections, and azithromycin, umifenovir and levofloxacin were the top three for COVID-19. In general, a high rate of drugs dispensing without prescription was revealed. Antibiotics for systemic use remained the most common antimicrobials, whereas presumably viral upper respiratory tract infections were the main reason for their purchase. COVID-19 infection itself was responsible for a small proportion of the supply of antimicrobial agents, but systemic antibiotics accounted for more than a half of supplies. Full article
10 pages, 1727 KiB  
Article
Influence of Sub-Inhibitory Dosage of Cefotaxime on Multidrug Resistant Staphylococcus haemolyticus Isolated from Sick Neonatal Care Unit
by Madhurima Chakraborty, Taniya Bardhan, Manjari Basu and Bornali Bhattacharjee
Antibiotics 2022, 11(3), 360; https://doi.org/10.3390/antibiotics11030360 - 8 Mar 2022
Cited by 3 | Viewed by 3047
Abstract
Staphylococcus haemolyticus has emerged to be a frequently encountered late-onset sepsis pathogen among newborn infants. Critical care of neonates involves substantial usage of antibiotics and these pathogens are often exposed to sub-optimal doses of antibiotics which can augment maintenance of selection determinants and [...] Read more.
Staphylococcus haemolyticus has emerged to be a frequently encountered late-onset sepsis pathogen among newborn infants. Critical care of neonates involves substantial usage of antibiotics and these pathogens are often exposed to sub-optimal doses of antibiotics which can augment maintenance of selection determinants and a range of physiological effects, prime among them being biofilm formation. Therefore, in this study, the outcome of a sub-inhibitory dosage of a commonly prescribed third-generation antibiotic, cefotaxime (CTX), on multidrug resistant (MDR) S. haemolyticus, was investigated. A total of 19 CTX-resistant, MDR and 5 CTX-susceptible strains isolated from neonates were included. Biofilm-forming abilities of S. haemolyticus isolates in the presence of sub-optimal CTX (30 μg/mL) were determined by crystal violet assays and extracellular DNA (eDNA) quantitation. CTX was found to significantly enhance biofilm production among the non-susceptible isolates (p-valueWilcoxintest—0.000008) with an increase in eDNA levels (p-valueWilcoxintest—0.000004). Further, in the absence of antibiotic selection in vitro, populations of MDR isolates, JNM56C1 and JNM60C2 remained antibiotic non-susceptible after >500 generations of growth. These findings demonstrate that sub-optimal concentration of CTX induces biofilm formation and short-term non-exposure to antibiotics does not alter non-susceptibility among S. haemolyticus isolates under the tested conditions. Full article
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12 pages, 1392 KiB  
Article
Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic Analysis
by Mathilde Lescat, Mélanie Magnan, Sonia Kenmoe, Patrice Nordmann and Laurent Poirel
Antibiotics 2022, 11(1), 50; https://doi.org/10.3390/antibiotics11010050 - 31 Dec 2021
Cited by 5 | Viewed by 2091
Abstract
Bacterial adaptation to antiseptic selective pressure might be associated with decreased susceptibility to antibiotics. In Gram-negative bacteria, some correlations between reduced susceptibility to chlorhexidine (CHX) and polymyxins have been recently evidenced in Klebsiella pneumoniae. In the present study, four isolates belonging to [...] Read more.
Bacterial adaptation to antiseptic selective pressure might be associated with decreased susceptibility to antibiotics. In Gram-negative bacteria, some correlations between reduced susceptibility to chlorhexidine (CHX) and polymyxins have been recently evidenced in Klebsiella pneumoniae. In the present study, four isolates belonging to distinct enterobacterial species, namely K. pneumoniae, Escherichia coli, Klebsiella oxytoca and Enterobacter cloacae, were submitted to in-vitro selective adaptation to two antiseptics, namely CHX and octenidine (OCT), and to the antibiotic colistin (COL). Using COL as selective agent, mutants showing high MICs for that molecule were recovered for E. cloacae, K. pneumoniae and K. oxytoca, exhibiting a moderate decreased susceptibility to CHX, whereas OCT susceptibility remained unchanged. Using CHX as selective agent, mutants with high MICs for that molecule were recovered for all four species, with a cross-resistance observed for COL, while OCT susceptibility remained unaffected. Finally, selection of mutants using OCT as selective molecule allowed recovery of K. pneumoniae, K. oxytoca and E. cloacae strains showing only slightly increased MICs for that molecule, without any cross-elevated MICs for the two other molecules tested. No E. coli mutant with reduced susceptibility to OCT could be obtained. It was therefore demonstrated that in-vitro mutants with decreased susceptibility to CHX and COL may be selected in E. coli, K. pneumoniae, K. oxytoca and E. cloacae, showing cross-decreased susceptibility to COL and CHX, but no significant impact on OCT efficacy. On the other hand, mutants were difficult to obtain with OCT, being obtained for K. pneumoniae and E. cloacae only, showing only very limited decreased susceptibility in those cases, and with no cross effect on other molecules. Whole genome sequencing enabled deciphering of the molecular basis of adaptation of these isolates under the respective selective pressures, with efflux pumps or lipopolysaccharide biosynthesis being the main mechanisms of adaptation. Full article
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14 pages, 578 KiB  
Article
Genotypic Diversity of Ciprofloxacin Nonsusceptibility and Its Relationship with Minimum Inhibitory Concentrations in Nontyphoidal Salmonella Clinical Isolates in Taiwan
by Shiuh-Bin Fang, Tsai-Ling Yang Lauderdale, Chih-Hung Huang, Pei-Ru Chang, Yuan-Hung Wang, Katsumi Shigemura, Ying-Hsiu Lin, Wei-Chiao Chang, Ke-Chuan Wang, Tzu-Wen Huang and Yu-Chu Chang
Antibiotics 2021, 10(11), 1383; https://doi.org/10.3390/antibiotics10111383 - 11 Nov 2021
Cited by 4 | Viewed by 2844
Abstract
This study analyzed the genetic diversity of ciprofloxacin (CIP) nonsusceptibility and the relationship between two major mechanisms and minimum inhibitory concentrations (MICs) of CIP in nontyphoidal Salmonella (NTS). Chromosomal mutations in quinolone resistance-determining regions (QRDRs) and plasmid-mediated quinolone resistance (PMQR) genes were searched [...] Read more.
This study analyzed the genetic diversity of ciprofloxacin (CIP) nonsusceptibility and the relationship between two major mechanisms and minimum inhibitory concentrations (MICs) of CIP in nontyphoidal Salmonella (NTS). Chromosomal mutations in quinolone resistance-determining regions (QRDRs) and plasmid-mediated quinolone resistance (PMQR) genes were searched from ResFinder, ARG-ANNOT, and PubMed for designing the sequencing regions in gyrA, gyrB, parC, and parE, and the 13 polymerase chain reactions for PMQR genes. We found that QRDR mutations were detected in gyrA (82.1%), parC (59.0%), and parE (20.5%) but not in gyrB among the 39 isolates. Five of the 13 PMQR genes were identified, including oqxA (28.2%), oqxB (28.2%), qnrS (18.0%), aac(6′)-Ib-cr (10.3%), and qnrB (5.1%), which correlated with the MICs of CIP within 0.25–2 μg/mL, and it was found that oxqAB contributed more than qnr genes to increase the MICs. All the isolates contained either QRDR mutations (53.8%), PMQR genes (15.4%), or both (30.8%). QRDR mutations (84.6%) were more commonly detected than PMQR genes (46.2%). QRDR mutation numbers were significantly associated with MICs (p < 0.001). Double mutations in gyrA and parC determined high CIP resistance (MICs ≥ 4 μg/mL). PMQR genes contributed to intermediate to low CIP resistance (MICs 0.25–2 μg/mL), thus providing insights into mechanisms underlying CIP resistance. Full article
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23 pages, 2668 KiB  
Article
CRISPR Element Patterns vs. Pathoadaptability of Clinical Pseudomonas aeruginosa Isolates from a Medical Center in Moscow, Russia
by Marina Tyumentseva, Yulia Mikhaylova, Anna Prelovskaya, Konstantin Karbyshev, Aleksandr Tyumentsev, Lyudmila Petrova, Anna Mironova, Mikhail Zamyatin, Andrey Shelenkov and Vasiliy Akimkin
Antibiotics 2021, 10(11), 1301; https://doi.org/10.3390/antibiotics10111301 - 26 Oct 2021
Cited by 2 | Viewed by 2263
Abstract
Pseudomonas aeruginosa is a member of the ESKAPE opportunistic pathogen group, which includes six species of the most dangerous microbes. This pathogen is characterized by the rapid acquisition of antimicrobial resistance, thus causing major healthcare concerns. This study presents a comprehensive analysis of [...] Read more.
Pseudomonas aeruginosa is a member of the ESKAPE opportunistic pathogen group, which includes six species of the most dangerous microbes. This pathogen is characterized by the rapid acquisition of antimicrobial resistance, thus causing major healthcare concerns. This study presents a comprehensive analysis of clinical P. aeruginosa isolates based on whole-genome sequencing data. The isolate collection studied was characterized by a variety of clonal lineages with a domination of high-risk epidemic clones and different CRISPR/Cas element patterns. This is the first report on the coexistence of two and even three different types of CRISPR/Cas systems simultaneously in Russian clinical strains of P. aeruginosa. The data include molecular typing and genotypic antibiotic resistance determination, as well as the phylogenetic analysis of the full-length cas gene and anti-CRISPR genes sequences, predicted prophage sequences, and conducted a detailed CRISPR array analysis. The differences between the isolates carrying different types and quantities of CRISPR/Cas systems were investigated. The pattern of virulence factors in P. aeruginosa isolates lacking putative CRISPR/Cas systems significantly differed from that of samples with single or multiple putative CRISPR/Cas systems. We found significant correlations between the numbers of prophage sequences, antibiotic resistance genes, and virulence genes in P. aeruginosa isolates with different patterns of CRISPR/Cas-elements. We believe that the data presented will contribute to further investigations in the field of bacterial pathoadaptability, including antimicrobial resistance and the role of CRISPR/Cas systems in the plasticity of the P. aeruginosa genome. Full article
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14 pages, 1955 KiB  
Article
Current Antimicrobial Stewardship Practice and Education in Russian Hospitals: Results of a Multicenter Survey
by Ivan Palagin, Svetlana Rachina, Marina Sukhorukova, Irina Nizhegorodtseva, Ulyana Portnyagina, Svetlana Gordeeva, Elena Burasova, Vladimir Bagin, Olga Domanskaya, Dilip Nathwani and Roman Kozlov
Antibiotics 2021, 10(8), 892; https://doi.org/10.3390/antibiotics10080892 - 22 Jul 2021
Cited by 2 | Viewed by 2492
Abstract
Proper antibiotic usage education and training of medical students and healthcare professionals is the cornerstone to implement antimicrobial stewardship (AMS) programs worldwide. We conducted this voluntary and anonymous survey on current and preferred educational provision of AMS in Russia. Among 1358 polled respondents [...] Read more.
Proper antibiotic usage education and training of medical students and healthcare professionals is the cornerstone to implement antimicrobial stewardship (AMS) programs worldwide. We conducted this voluntary and anonymous survey on current and preferred educational provision of AMS in Russia. Among 1358 polled respondents from six participating Centers located in geographically remote Federal Districts of Russia, the majority were nurses (52.8%) and doctors (42.0%). Results of the survey demonstrated better coverage of education in AMS on an undergraduate level (57.1%). More than half of respondents in total (52.4%) stated they had not received any postgraduate training. Those 38.4% respondents who received postgraduate teaching in AMS stated that it had been provided substantially by an employing hospital (28.4%) or by a medical university/college (22.3%). According to the conducted survey, the methods of education in AMS in Russian Federation mainly include traditional face-to-face lectures, presentations and provision with clinical guidelines, recommendations and printed materials. The involvement of e-learning and web-based online approaches was lacking. The survey allowed us the identify the key problems associated with training of healthcare workers in this field, in particular the varying availability of under- and postgraduate education in different parts of Russia. Full article
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9 pages, 4881 KiB  
Case Report
A Clinical Case of Nosocomial Pneumonia as a Complication of COVID-19: How to Balance Benefits and Risks of Immunosuppressive Therapy?
by Svetlana Rachina, Gairat Kiyakbaev, Elena Antonova, Alexey Mescheryakov, Olga Kupryushina, Girindu Hewathanthirige, Ivan Palagin, Elena Kozhevnikova, Marina Sukhorukova and Daria Strelkova
Antibiotics 2023, 12(1), 53; https://doi.org/10.3390/antibiotics12010053 - 29 Dec 2022
Cited by 3 | Viewed by 3877
Abstract
We report a Russian case of a 61-year-old male patient with confirmed COVID-19 infection who developed nosocomial pneumonia complicated by lung abscess associated with multi-drug-resistant isolates of Klebsiella pneumoniae and Acinetobacter baumannii, which could have been provoked due to the immunosuppressive therapy. [...] Read more.
We report a Russian case of a 61-year-old male patient with confirmed COVID-19 infection who developed nosocomial pneumonia complicated by lung abscess associated with multi-drug-resistant isolates of Klebsiella pneumoniae and Acinetobacter baumannii, which could have been provoked due to the immunosuppressive therapy. We discuss the existing literature highlighting the issue of the prudent balance between benefits and risks when prescribing immunomodulators to hospitalized patients with COVID-19 due to the risk of difficult-to-treat nosocomial infections caused by MDR Gram-negative bacterial pathogens. Currently, there is evidence of a substantial positive effect of dexamethasone on the course of COVID-19 in patients requiring supplemental oxygen or anti-interleukin-6 drugs in individuals with prominent systemic inflammation. However, it seems that in real clinical practice, the proposed criteria for initiating treatment with immunomodulators are interpreted arbitrarily, and the doses of dexamethasone can significantly exceed those recommended. Full article
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12 pages, 1051 KiB  
Perspective
From Pathophysiological Hypotheses to Case–Control Study Design: Resistance from Antibiotic Exposure in Community-Onset Infections
by Salam Abbara, Didier Guillemot, Christian Brun-Buisson and Laurence Watier
Antibiotics 2022, 11(2), 201; https://doi.org/10.3390/antibiotics11020201 - 4 Feb 2022
Viewed by 2496
Abstract
Antimicrobial resistance is a global public health concern, at least partly due to the misuse of antibiotics. The increasing prevalence of antibiotic-resistant infections in the community has shifted at-risk populations into the general population. Numerous case–control studies attempt to better understand the link [...] Read more.
Antimicrobial resistance is a global public health concern, at least partly due to the misuse of antibiotics. The increasing prevalence of antibiotic-resistant infections in the community has shifted at-risk populations into the general population. Numerous case–control studies attempt to better understand the link between antibiotic use and antibiotic-resistant community-onset infections. We review the designs of such studies, focusing on community-onset bloodstream and urinary tract infections. We highlight their methodological heterogeneity in the key points related to the antibiotic exposure, the population and design. We show the impact of this heterogeneity on study results, through the example of extended-spectrum β-lactamases producing Enterobacteriaceae. Finally, we emphasize the need for the greater standardization of such studies and discuss how the definition of a pathophysiological hypothesis specific to the bacteria–resistance pair studied is an important prerequisite to clarify the design of future studies. Full article
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