Antibiotic Treatment and Antibiotic Resistance of Enterococcus Infections

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 10775

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Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Salerno, Italy
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Dipartimento di Medicina, Chirurgia e Odontoiatria “Scuola Medica Salernitana”/DIPMED, Baronissi, Italy
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Department of Experimental Medicine, Section of University of Campania "Luigi Vanvitelli", 80138 Naples, Italy
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Special Issue Information

Dear Colleagues,

Among Enterococcus species, Enterococcus faecalis and Enterococcus faecium represent a major cause of human infections. In the last decade, available data from North American and European centers have indicated E. faecalis as the third causative agent of infective endocarditis. Overall, the incidence and the antibiotic resistance rate are increasing, and these species have been included among the ESCAPEs as the main pathogens associated with nosocomial infections. To date, epidemiological studies, reporting resistance antibiotic trends, or the isolation of new resistance genes, are crucial to understand and improve therapy and patient outcomes.

On the other hand, sanitization of the hospital environment, hygiene procedures, and monitoring of pathogenic microorganisms could be needed to prevent this phenomenon and improve management of these infections.

For this purpose, the Special Issue will collect original articles, reviews, clinical studies, and epidemiological studies focused on these Species.

Dr. Giovanni Boccia
Dr. Gianluigi Franci
Dr. Biagio Santella
Guest Editors

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Keywords

  • Enterococcus faecium
  • Enterococcus faecalis
  • drug resistance
  • epidemiologic studies
  • endocarditis

Published Papers (6 papers)

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Research

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12 pages, 590 KiB  
Article
Linezolid Resistance Genes and Mutations among Linezolid-Susceptible Enterococcus spp.—A Loose Cannon?
by Jennifer K. Bender, Carola Fleige, Finn Funk, Clara Moretó-Castellsagué, Martin A. Fischer and Guido Werner
Antibiotics 2024, 13(1), 101; https://doi.org/10.3390/antibiotics13010101 - 19 Jan 2024
Viewed by 1099
Abstract
The National Reference Centre for Enterococci receives an increasing number of linezolid-resistant Enterococcus isolates. Linezolid (LIN) resistance is mediated by G2576T 23S rDNA gene mutations and/or acquisition of resistance genes (cfr, optrA, poxtA). There are anecdotal reports that those resistance traits [...] Read more.
The National Reference Centre for Enterococci receives an increasing number of linezolid-resistant Enterococcus isolates. Linezolid (LIN) resistance is mediated by G2576T 23S rDNA gene mutations and/or acquisition of resistance genes (cfr, optrA, poxtA). There are anecdotal reports that those resistance traits may be present in phenotypically linezolid-susceptible isolates. We aimed to determine the prevalence of LIN resistance genes and mutations in enterococci with a LIN MIC of 4 mg/L in broth microdilution (EUCAST = susceptible) isolated from German hospital patients 2019–2021. LIN MICs were additionally determined by ETEST® and VITEK2. Selected strains were subjected to LIN selective pressure and growth was monitored with increasing antibiotic concentrations. We received 195 isolates (LIN MIC = 4 mg/L). In total, 78/195 (40%) isolates contained either a putative resistance gene, the G2576T mutation, or a combination thereof. Very major error was high for broth microdilution. The ability to predict phenotypic resistance from genotypic profile was highest for G2576T-mediated resistance. Selection experiments revealed that, in particular, E. faecium isolates with resistance gene mutations or poxtA rapidly adapt to MICs above the clinical breakpoint. In conclusion, LIN resistance genes and mutations can be observed in phenotypically linezolid-susceptible enterococci. Those isolates may rapidly develop resistance under LIN selective pressure potentially leading to treatment failure. Full article
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11 pages, 599 KiB  
Article
Comparison of Five Different Selective Agar for the Detection of Vancomycin-Resistant Enterococcus faecium
by Alessa L. Boschert, Franca Arndt, Axel Hamprecht, Martina Wolke and Sarah V. Walker
Antibiotics 2023, 12(4), 666; https://doi.org/10.3390/antibiotics12040666 - 29 Mar 2023
Cited by 2 | Viewed by 2053
Abstract
Five commercially available selective agar were evaluated regarding sensitivity and specificity to detect vancomycin-resistant Enterococcus (E.) faecium. Altogether 187 E. faecium strains were included, comprising 119 van-carrying strains (phenotypically vancomycin-resistant n = 105; phenotypically vancomycin-susceptible VVE-B n = 14) [...] Read more.
Five commercially available selective agar were evaluated regarding sensitivity and specificity to detect vancomycin-resistant Enterococcus (E.) faecium. Altogether 187 E. faecium strains were included, comprising 119 van-carrying strains (phenotypically vancomycin-resistant n = 105; phenotypically vancomycin-susceptible VVE-B n = 14) and 68 vancomycin-susceptible isolates. Limit of detection was calculated for each selective agar for pure cultures, stool suspensions and artificial rectal swabs. After 24-h incubation sensitivity ranged between 91.6% and 95.0%. It increased in 2 out of 5 agar after 48-h incubation. Specificity ranged between 94.1% and 100% and was highest after 24 h in 4 out of the 5 agar. Sensitivity of van-carrying phenotypically vancomycin-resistant strains was higher after 24 h (97.1–100%) and 48 h (99.1–100%) when compared to van-carrying strains that tested vancomycin-susceptible (50.0–57.1% after both incubation periods). Overall, chromID VRE, CHROMagar VRE and Brilliance VRE demonstrated the highest detection rates after 24 h. Detection rates of Chromatic VRE and VRESelect improved after 48 h. Adjustment of incubation time depending on the applied media may be advised. As detection of VVE-B was impeded with all selective agar, screening for vancomycin-resistant enterococci relying solely on selective media would not be recommended for critical clinical samples, but rather in combination with molecular methods to improve detection of these strains. Furthermore, stool samples were demonstrated to be superior to rectal swabs and should be favoured, if possible, in screening strategies. Full article
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19 pages, 2787 KiB  
Article
Clinical Resistant Strains of Enterococci and Their Correlation to Reduced Susceptibility to Biocides: Phenotypic and Genotypic Analysis of Macrolides, Lincosamides, and Streptogramins
by Amr Selim Abu Lila, Tareq Nafea Alharby, Jowaher Alanazi, Muteb Alanazi, Marwa H. Abdallah, Syed Mohd Danish Rizvi, Afrasim Moin, El-Sayed Khafagy, Shams Tabrez, Abdullah Ali Al Balushi and Wael A. H. Hegazy
Antibiotics 2023, 12(3), 461; https://doi.org/10.3390/antibiotics12030461 - 24 Feb 2023
Cited by 7 | Viewed by 1840
Abstract
Enterococci are troublesome nosocomial, opportunistic Gram-positive cocci bacteria showing enhanced resistance to many commonly used antibiotics. This study aims to investigate the prevalence and genetic basis of antibiotic resistance to macrolides, lincosamides, and streptogramins (MLS) in Enterococci, as well as the correlation [...] Read more.
Enterococci are troublesome nosocomial, opportunistic Gram-positive cocci bacteria showing enhanced resistance to many commonly used antibiotics. This study aims to investigate the prevalence and genetic basis of antibiotic resistance to macrolides, lincosamides, and streptogramins (MLS) in Enterococci, as well as the correlation between MLS resistance and biocide resistance. From 913 clinical isolates collected from King Khalid Hospital, Hail, Saudi Arabia, 131 isolates were identified as Enterococci spp. The susceptibility of the clinical enterococcal isolates to several MLS antibiotics was determined, and the resistance phenotype was detected by the triple disk method. The MLS-involved resistance genes were screened in the resistant isolates. The current results showed high resistance rates to MLS antibiotics, and the constitutive resistance to all MLS (cMLS) was the most prevalent phenotype, observed in 76.8% of resistant isolates. By screening the MLS resistance-encoding genes in the resistant isolates, the erythromycin ribosome methylase (erm) genes that are responsible for methylation of bacterial 23S rRNA were the most detected genes, in particular, ermB. The ereA esterase-encoding gene was the most detected MLS modifying-encoding genes, more than lnuA (adenylation) and mphC (phosphorylation). The minimum inhibitory concentrations (MICs) of commonly used biocides were detected in resistant isolates and correlated with the MICs of MLS antibiotics. The present findings showed a significant correlation between MLS resistance and reduced susceptibility to biocides. In compliance with the high incidence of the efflux-encoding genes, especially mefA and mefE genes in the tolerant isolates with higher MICs to both MLS antibiotics and biocides, the efflux of resistant isolates was quantified, and there was a significant increase in the efflux of resistant isolates with higher MICs as compared to those with lower MICs. This could explain the crucial role of efflux in developing cross-resistance to both MLS antibiotics and biocides. Full article
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12 pages, 791 KiB  
Article
Molecular Rapid Diagnostics Improve Time to Effective Therapy and Survival in Patients with Vancomycin-Resistant Enterococcus Bloodstream Infections
by Sarah M. Bandy, Christopher B. Jackson, Cody A. Black, William Godinez, Gerard W. Gawrys and Grace C. Lee
Antibiotics 2023, 12(2), 210; https://doi.org/10.3390/antibiotics12020210 - 19 Jan 2023
Cited by 1 | Viewed by 1213
Abstract
Delays in appropriate antibiotic therapy are a key determinant for deleterious outcomes among patients with vancomycin-resistant Enterococcus (VRE) bloodstream infections (BSIs). This was a multi-center pre/post-implementation study, assessing the impact of a molecular rapid diagnostic test (Verigene® GP-BC, Luminex Corporation, Northbrook, IL, [...] Read more.
Delays in appropriate antibiotic therapy are a key determinant for deleterious outcomes among patients with vancomycin-resistant Enterococcus (VRE) bloodstream infections (BSIs). This was a multi-center pre/post-implementation study, assessing the impact of a molecular rapid diagnostic test (Verigene® GP-BC, Luminex Corporation, Northbrook, IL, USA) on outcomes of adult patients with VRE BSIs. The primary outcome was time to optimal therapy (TOT). Multivariable logistic and Cox proportional hazard regression models were used to determine the independent associations of post-implementation, TOT, early vs. delayed therapy, and mortality. A total of 104 patients with VRE BSIs were included: 50 and 54 in the pre- and post-implementation periods, respectively. The post- vs. pre-implementation group was associated with a 1.8-fold faster rate to optimized therapy (adjusted risk ratio, 1.841 [95% CI 1.234–2.746]), 6-fold higher likelihood to receive early effective therapy (<24 h, adjusted odds ratio, 6.031 [2.526–14.401]), and a 67% lower hazards for 30-day in-hospital mortality (adjusted hazard ratio, 0.322 [0.124–1.831]), after adjusting for age, sex, and severity scores. Inversely, delayed therapy was associated with a 10-fold higher risk of in-hospital mortality (aOR 10.488, [2.497–44.050]). Reduced TOT and in-hospital mortality were also observed in subgroups of immunosuppressed patients in post-implementation. These findings demonstrate that the addition of molecular rapid diagnostic tests (mRDT) to clinical microbiology and antimicrobial stewardship practices are associated with a clinically significant reduction in TOT, which is associated with lower mortality for patients with VRE BSIs, underscoring the importance of mRDTs in the management of VRE infections. Full article
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11 pages, 497 KiB  
Article
Clinical Impact of Vancomycin Treatment in Ampicillin-Susceptible Enterococci Bloodstream Infections
by Jatapat Hemapanpairoa, Dhitiwat Changpradub and Wichai Santimaleeworagun
Antibiotics 2022, 11(12), 1698; https://doi.org/10.3390/antibiotics11121698 - 25 Nov 2022
Cited by 5 | Viewed by 2149
Abstract
Enterococci are major causes of bacteremia. Although the mortality rate of ampicillin- susceptible enterococci (ASE) bloodstream infections (BSI) is lower, compared with that of ampicillin-resistant enterococci BSI, the role of treatment regimens in ASE BSI remains to be determined. This retrospective study aimed [...] Read more.
Enterococci are major causes of bacteremia. Although the mortality rate of ampicillin- susceptible enterococci (ASE) bloodstream infections (BSI) is lower, compared with that of ampicillin-resistant enterococci BSI, the role of treatment regimens in ASE BSI remains to be determined. This retrospective study aimed to evaluate the treatment outcomes and factors associated with mortality among patients with ASE BSI. The charts of 145 enrolled patients with ASE BSI between January 2013 and April 2022 at Phramongkutklao Hospital were reviewed. The 30-day and in-hospital mortality rates were 28.8 and 41.9%, respectively. The 30-day mortality rate was higher in the vancomycin treatment group than in the beta-lactam treatment group (61.5 vs. 26%; p = 0.02). Pitt bacteremia score (OR 1.44, 95% CI 1.20–1.71); age-adjusted Charlson Comorbidity Index (OR 1.34, 95% CI 1.14–1.58); and vancomycin treatment (OR 4.07, 95% CI 1.02–16.22) were independent factors associated with 30-day mortality. The severity of illness, comorbidity and definitive therapy with vancomycin increased the mortality rate of patients with ASE BSI. Anti-enterococcal beta-lactams remain the first line antibiotics for ASE bacteremia. Full article
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Review

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16 pages, 325 KiB  
Review
Evaluation of Enterococcal Probiotic Usage and Review of Potential Health Benefits, Safety, and Risk of Antibiotic-Resistant Strain Emergence
by Eric Jeeho Im, Harry Hyun-Yup Lee, Minzae Kim and Myo-Kyoung Kim
Antibiotics 2023, 12(8), 1327; https://doi.org/10.3390/antibiotics12081327 - 17 Aug 2023
Cited by 7 | Viewed by 1412
Abstract
Enterococci are often used in probiotics but can also cause nosocomial infections. As such, enterococcal consumption may have beneficial health effects, but a thorough evaluation of virulence absence and risk of antibiotic resistance spread is needed at the strain level. This article reviewed [...] Read more.
Enterococci are often used in probiotics but can also cause nosocomial infections. As such, enterococcal consumption may have beneficial health effects, but a thorough evaluation of virulence absence and risk of antibiotic resistance spread is needed at the strain level. This article reviewed ten online health product shopping websites in the US. On these websites, 23 probiotic products using enterococci were found across 12 companies. In addition, this article reviewed studies that demonstrated the probiotic potential of enterococcal consumption (e.g., gastrointestinal and respiratory disease, hyperlipidemia alleviation, as well as infection prevention). To investigate the safety aspects of enterococci, the present work examined studies evaluating virulence factors and antibiotic resistance. Furthermore, this article assessed research that explored these virulent factors, specifically in probiotics containing enterococci, as well as the potential transfer mechanism of their antibiotic resistance. Based on reviewed data, enterococcal probiotic consumption has been proven beneficial for conditions or symptoms of multiple diseases without any apparent adverse effects. However, due to the plasmid- or transposon-mediated gene transfer ability of enterococci, surveillance monitoring and further studies regarding enterococcal consumption are warranted. Future studies that identify enterococcal strains safe to use in probiotics without virulence factors and antibiotic resistance are imperative for evidence-based decisions by health organizations and government agencies. Full article
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