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The Annals of Pharmacotherapy Jan 2015To review the literature on the pharmacotherapy of bloodstream infections (BSI) caused by vancomycin-resistant enterococci (VRE). (Review)
Review
OBJECTIVE
To review the literature on the pharmacotherapy of bloodstream infections (BSI) caused by vancomycin-resistant enterococci (VRE).
DATA SOURCES
A MEDLINE literature search was performed for the period 1946 to May 2014 using the search terms Enterococcus, enterococci, vancomycin-resistant, VRE, bacteremia, and bloodstream infection. References were also identified from selected review articles.
STUDY SELECTION AND DATA EXTRACTION
English-language case series, cohort studies, and meta-analyses assessing the options in the pharmacotherapy of VRE BSIs in adult patients were evaluated.
DATA SYNTHESIS
Studies were identified that utilized linezolid, quinupristin/dalfopristin (Q/D), and daptomycin. In all, 8 comparative retrospective cohort studies, 2 meta-analyses of daptomycin and linezolid, and 3 retrospective comparisons of linezolid and Q/D were included for review. Mortality associated with VRE BSIs was high across studies, and the ability to determine differences in outcomes between agents was confounded by the complex nature of the patients included. Two meta-analyses comparing daptomycin with linezolid for VRE BSIs found modest advantages for linezolid, but these conclusions may be hampered by heterogeneity within the included studies.
CONCLUSIONS
VRE BSIs remain a difficult-to-treat clinical situation. Differences in toxicity between the agents used to treat it are clear, but therapeutic differences are more difficult to discern. Meta-analyses suggest that a moderate advantage for linezolid over daptomycin may exist, but problems with the nature of studies that they included make definitive conclusions difficult.
Topics: Acetamides; Anti-Bacterial Agents; Bacteremia; Daptomycin; Gram-Positive Bacterial Infections; Humans; Linezolid; Oxazolidinones; Vancomycin; Vancomycin-Resistant Enterococci; Virginiamycin
PubMed: 25352037
DOI: 10.1177/1060028014556879 -
Translational Animal Science Oct 2022Monensin and virginiamycin are included in beef cattle finishing diets as prophylaxis to minimize the incidence of ruminal acidosis and liver abscesses. Due to different...
Monensin and virginiamycin are included in beef cattle finishing diets as prophylaxis to minimize the incidence of ruminal acidosis and liver abscesses. Due to different and probably complementary modes of action, this study aimed to determine the effects of a combination of monensin and virginiamycin, both included in the diet at recommended doses, on ruminal health, the occurrence of liver abscesses, and growth performance of feedlot-finished cattle. One hundred and forty-four steers (6 animals/pen) were fed 1 of 3 corn-based finishing diets containing 30 mg of monensin (), 25 mg of virginiamycin (), or 30 and 25 mg of monensin and virginiamycin (), respectively, per kilogram of dry matter. Ruminal pH probes were inserted into two animals per pen and set to record pH every 10 min. On d 100, animals were slaughtered, and rumens and livers were recovered, on which occurrence and degree of ruminal damage, prevalence and number of liver abscesses, and liver scores (A-: livers with no more than two small abscesses; A+: livers with at least one large abscess or more than four medium abscesses; A: any other abscessed liver) were determined. Simultaneous inclusion of monensin and virginiamycin resulted in a 4.3% decrease ( < 0.04) in dry matter intake (; 8.8, 9.2, and 9.2 ± 0.19 kg/d for MN + VM, MN, and VM-fed animals, respectively) and similar ( > 0.13) average daily body weight gain (; 1.49 ± 0.021 kg/d) and hot carcass weight (; 269 ± 1.7 kg), compared with feeding diets containing one additive or the other. Therefore, in terms of ADG, a 9.4% improvement ( < 0.01) in feed efficiency was observed in MN + VM-fed animals. Backfat thickness (5.6 ± 0.08 mm) and ribeye area (69.9 ± 0.53 cm) remained unaffected ( ≥ 0.74), as well as the minimum (4.98 ± 0.047), mean (6.11 ± 0.037), and maximum ruminal pH (7.23 ± 0.033) values and the time (125 ± 22.3 min/d), area (57.67 ± 12.383 pH × h), and episodes (22 ± 3.8 bouts) of pH below 5.6 ( ≥ 0.12). Overall, prevalence (24 ± 3.4%) and the number of liver abscesses (1.6 ± 0.14 abscesses/abscessed liver), liver scores (20 ± 3.1% of A- and 4 ± 1.8% of A livers), and prevalence (67 ± 3.5%) and degree of damage to the ruminal epithelium (2.5 ± 0.22% affected surface) were similar ( ≥ 0.18) across treatments; however, the occurrence of ruminal lesions tended ( ≤ 0.07) to be associated with that of liver abscesses and reduced ADG when feeding monensin alone.
PubMed: 36601062
DOI: 10.1093/tas/txac154 -
Expert Review of Anti-infective Therapy May 2021Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially... (Review)
Review
INTRODUCTION
Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially multidrug-resistant isolates.
AREAS COVERED
This review provides an updated overview of structural and activity characteristics, mechanisms of action and resistance, pharmacokinetic/pharmacodynamic, and clinical use of streptogramins.
EXPERT OPINION
The streptogramin antibiotics act by inhibition of the bacterial protein synthesis. They are composed of two chemically distinct compounds, namely type A and type B streptogramins, which exert a rapid bactericidal activity against a wide range of Gram-positive bacteria (including methicillin-resistant staphylococci and vancomycin-resistant enterococci). Several mechanisms of resistance have been identified in staphylococci and enterococci but the prevalence of streptogramin resistance among clinical isolates remains very low. Even if only a few randomized clinical trials have been conducted, the efficacy of pristinamycin has been largely demonstrated with an extensive use for 50 years in France and some African countries. Despite its effectiveness in the treatment of severe Gram-positive bacterial infections demonstrated in several studies and the low rate of reported resistance, the clinical use of quinupristin-dalfopristin has remained limited, mainly due to its poor tolerance. Altogether, streptogramins (especially pristinamycin) can be considered as potential alternatives for the treatment of Gram-positive infections.
Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Pristinamycin; Randomized Controlled Trials as Topic; Streptogramins; Virginiamycin
PubMed: 33030387
DOI: 10.1080/14787210.2021.1834851 -
Synlett : Accounts and Rapid... Apr 2021Streptogramins are antibiotics produced by several species of bacteria that are used in both human and veterinary medicine. Group A streptogramins comprise 23-membered...
Streptogramins are antibiotics produced by several species of bacteria that are used in both human and veterinary medicine. Group A streptogramins comprise 23-membered macrocyclic polyketide/nonribosomal peptide hybrids for which several innovative, fully synthetic routes have been developed. Herein we describe in detail our scalable routes to natural group A streptogramins and compare these routes to other reported syntheses.
PubMed: 34113063
DOI: 10.1055/a-1293-9655 -
Microbiology Spectrum Jun 2023Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 (CC398) isolates ( = 178) collected in the national resistance...
Genomic Diversity of Methicillin-Resistant Staphylococcus aureus CC398 Isolates Collected from Diseased Swine in the German National Resistance Monitoring Program GE-Vet from 2007 to 2019.
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 (CC398) isolates ( = 178) collected in the national resistance monitoring program GE-Vet from diseased swine in Germany from 2007 to 2019 were investigated for their genomic diversity with a focus on virulence and antimicrobial resistance (AMR) traits. Whole-genome sequencing was followed by molecular typing and sequence analysis. A minimum spanning tree based on core-genome multilocus sequence typing was constructed, and antimicrobial susceptibility testing was performed. Most isolates were assigned to nine clusters. They displayed close phylogenetic relationships but a wide molecular variety, including 13 types and 19 known and four novel types. Several toxin-encoding genes, including , , , , and , were detected. The isolates harbored a wide range of AMR properties mirroring the proportions of the classes of antimicrobial agents applied in veterinary medicine in Germany. Multiple novel or rare AMR genes were identified, including the phenicol-lincosamide-oxazolidinone-pleuromutilin-streptogramin A resistance gene , the lincosamide-pleuromutilin-streptogramin A resistance gene (C), and the novel macrolide-lincosamide-streptogramin B resistance gene (54). Many AMR genes were part of small transposons or plasmids. Clonal and geographical correlations of molecular characteristics and resistance and virulence genes were more frequently observed than temporal relations. In conclusion, this study provides insight into population dynamics of the main epidemic porcine LA-MRSA lineage in Germany over a 13-year-period. The observed comprehensive AMR and virulence properties, most likely resulting from the exchange of genetic material between bacteria, highlighted the importance of LA-MRSA surveillance to prevent further dissemination among swine husbandry facilities and entry into the human community. The LA-MRSA-CC398 lineage is known for its low host specificity and frequent multiresistance to antimicrobial agents. Colonized swine and their related surroundings represent a considerable risk of LA-MRSA-CC398 colonization or infection for occupationally exposed people through which such isolates might be further disseminated within the human community. This study provides insight into the diversity of the porcine LA-MRSA-CC398 lineage in Germany. Clonal and geographical correlations of molecular characteristics and resistance and virulence traits were detected and may be associated with the spread of specific isolates through livestock trade, human occupational exposure, or dust emission. The demonstrated genetic variability underlines the lineage's ability to horizontally acquire foreign genetic material. Thus, LA-MRSA-CC398 isolates have the potential to become even more dangerous for various host species, including humans, due to increased virulence and/or limited therapeutic options for infection control. Full-scale LA-MRSA monitoring at the farm, community, and hospital level is therefore essential.
Topics: Animals; Humans; Swine; Methicillin-Resistant Staphylococcus aureus; Phylogeny; Streptogramin A; Staphylococcal Infections; Anti-Bacterial Agents; Genomics; Lincosamides; Livestock; Pleuromutilins
PubMed: 37154741
DOI: 10.1128/spectrum.00770-23 -
Current Opinion in Infectious Diseases Dec 2014Uncertainties exist regarding the optimal treatment for vancomycin-resistant enterococcal (VRE) bloodstream infections, particularly in settings in which ampicillin... (Review)
Review
PURPOSE OF REVIEW
Uncertainties exist regarding the optimal treatment for vancomycin-resistant enterococcal (VRE) bloodstream infections, particularly in settings in which ampicillin cannot be used.
RECENT FINDINGS
Quinupristin-dalfopristin, linezolid, and daptomycin, all approved between 1999 and 2003, represent the mainstays of therapy for VRE bacteremia, although only linezolid has been specifically approved by the United States Food and Drug Administration for this indication. The main objective of this review is to compare the relative efficacies, dosing strategies, and side-effect profiles of quinupristin-dalfopristin, linezolid, and daptomycin for VRE bacteremia in the pediatric population. A brief description of recently approved broad-spectrum Gram-positive agents that may have a role in the management of VRE bacteremia in upcoming years is also provided.
SUMMARY
Linezolid, despite its bacteriostatic activity against VRE, may be the most versatile of the available drugs. It has activity against both Enterococcus faecalis and E. faecium, can be administered orally, and resistance appears to be less of a concern with linezolid compared with the other agents. Additionally, the results of two recent meta-analyses demonstrate more favorable outcomes with linezolid compared with daptomycin for the treatment of VRE bacteremia. The clinical pharmacokinetics of linezolid have been well described in children. The most notable concern with linezolid, however, is toxicities associated with prolonged use. Until more prospective data are available, we favor linezolid as first-line therapy for the treatment of VRE bacteremia in children.
Topics: Acetamides; Adolescent; Child; Child, Preschool; Daptomycin; Drug Resistance, Multiple, Bacterial; Enterococcus faecalis; Enterococcus faecium; Gram-Positive Bacterial Infections; Humans; Linezolid; Oxazolidinones; Risk Factors; Treatment Outcome; Vancomycin; Vancomycin-Resistant Enterococci; Virginiamycin
PubMed: 25313503
DOI: 10.1097/QCO.0000000000000115 -
Journal of AOAC International May 2023Antibiotics are used in ethanol production to discourage undesirable bacteria growth. To determine if antibiotic residues remain in the distillers grain (DG) byproduct,...
BACKGROUND
Antibiotics are used in ethanol production to discourage undesirable bacteria growth. To determine if antibiotic residues remain in the distillers grain (DG) byproduct, which is used as an animal food ingredient, the U.S. Food and Drug Administration/Center for Veterinary Medicine previously developed an LC-MS/MS method to detect residues of erythromycin A, penicillin G, virginiamycin M1, and virginiamycin S1 in DG to enable regulatory decision-making.
OBJECTIVE
Erythromycin and penicillin G were quantitated using the stable isotope dilution technique with their isotopically labeled compounds, which are considered optimal internal standards (ISTDs) for quantitative mass spectrometry. With the commercial availability of virginiamycin M1-d2 since then, the objectives of this study were to evaluate the feasibility of its use as it is only doubly deuterated, and to incorporate it in the method to enhance method performance.
METHOD
Antibiotic residues were solvent-extracted from DG; the extract was cleaned up by a hexane wash and solid phase extraction (SPE) and analyzed by LC-MS/MS.
RESULTS
We established suitability of virginiamycin M1-d2 as an ISTD and incorporated it in the method. For all analytes, accuracy and precision ranged 90 to 102% and 3.8 to 6.8, respectively.
CONCLUSIONS
We modified a previously developed LC-MS/MS method that uses virginiamycin M1-d2 as an ISTD to support surveillance studies to determine several drugs in DG.
HIGHLIGHTS
Virginiamycin M1-d2 was successfully incorporated into the method for better virginiamycin M1 quantitation. This addition also allowed calibration curves for all analytes to be constructed in solvent, thereby simplifying the method.
Topics: Animals; Anti-Bacterial Agents; Streptogramin A; Chromatography, Liquid; Tandem Mass Spectrometry; Penicillin G; Erythromycin; Solvents; Edible Grain; Solid Phase Extraction; Drug Residues
PubMed: 36975613
DOI: 10.1093/jaoacint/qsad032 -
Antimicrobial Resistance and Infection... Apr 2020Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCoNS) are among the main causes of nosocomial... (Meta-Analysis)
Meta-Analysis Review
The global prevalence of Daptomycin, Tigecycline, Quinupristin/Dalfopristin, and Linezolid-resistant Staphylococcus aureus and coagulase-negative staphylococci strains: a systematic review and meta-analysis.
OBJECTIVE
Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MRCoNS) are among the main causes of nosocomial infections, which have caused major problems in recent years due to continuously increasing spread of various antibiotic resistance features. Apparently, vancomycin is still an effective antibiotic for treatment of infections caused by these bacteria but in recent years, additional resistance phenotypes have led to the accelerated introduction of newer agents such as linezolid, tigecycline, daptomycin, and quinupristin/dalfopristin (Q/D). Due to limited data availability on the global rate of resistance to these antibiotics, in the present study, the resistance rates of S. aureus, Methicillin-resistant S. aureus (MRSA), and CoNS to these antibiotics were collected.
METHOD
Several databases including web of science, EMBASE, and Medline (via PubMed), were searched (September 2018) to identify those studies that address MRSA, and CONS resistance to linezolid, tigecycline, daptomycin, and Q/D around the world.
RESULT
Most studies that reported resistant staphylococci were from the United States, Canada, and the European continent, while African and Asian countries reported the least resistance to these antibiotics. Our results showed that linezolid had the best inhibitory effect on S. aureus. Although resistances to this antibiotic have been reported from different countries, however, due to the high volume of the samples and the low number of resistance, in terms of statistical analyzes, the resistance to this antibiotic is zero. Moreover, linezolid, daptomycin and tigecycline effectively (99.9%) inhibit MRSA. Studies have shown that CoNS with 0.3% show the lowest resistance to linezolid and daptomycin, while analyzes introduced tigecycline with 1.6% resistance as the least effective antibiotic for these bacteria. Finally, MRSA and CoNS had a greater resistance to Q/D with 0.7 and 0.6%, respectively and due to its significant side effects and drug-drug interactions; it appears that its use is subject to limitations.
CONCLUSION
The present study shows that resistance to new agents is low in staphylococci and these antibiotics can still be used for treatment of staphylococcal infections in the world.
Topics: Anti-Bacterial Agents; Coagulase; Cross Infection; Daptomycin; Drug Resistance, Multiple, Bacterial; Global Health; Humans; Linezolid; Prevalence; Staphylococcus; Staphylococcus aureus; Tigecycline; Virginiamycin
PubMed: 32321574
DOI: 10.1186/s13756-020-00714-9 -
Translational Animal Science Jan 2021The objective of this experiment was to determine the effects of narasin (NAR; Skycis®; Elanco Animal Health, Greenfield, IN) or virginiamycin (VIR; Stafac®; Phibro...
The objective of this experiment was to determine the effects of narasin (NAR; Skycis®; Elanco Animal Health, Greenfield, IN) or virginiamycin (VIR; Stafac®; Phibro Animal Health Corporation, Teaneck, NJ) on finishing pig growth performance and carcass characteristics. Two separate experiments were conducted at the same site in 2013 and 2014. A total of 576 pigs (initial BW = 23.2 ± 0.19 kg) were housed in 24 pens with 8 pigs per pen in Exp. 1. In Exp. 2, a total of 888 pigs (initial BW = 26.2 ± 0.12 kg) were housed in 39 pens with 8 pigs per pen. Treatments consisted of a series of unmedicated corn-soybean meal diets (CON), CON + NAR (15 mg/kg), or CON + VIR (11 mg/kg) fed for 108 d (Exp. 1) or 109 d (Exp. 2). Pen was the experimental unit in both studies. Data were analyzed as a randomized complete block design with the main effects of block and treatment (Exp. 1) and as an incomplete block design with the fixed effect of treatment and the random effects of barn and barn within block (Exp. 2). In Exp.1, NAR and VIR increased ( < 0.05) ADG and ADFI from days 0 to 28, and BW on days 28, 56, 76, and 97 as compared to pigs fed CON. During days 0-28, pigs fed NAR had a greater ( < 0.05) G:F than those fed CON or VIR. Also, during days 28-56 pigs fed VIR had a greater ( < 0.05) ADFI than pigs fed CON. Pigs fed NAR or VIR had greater ( < 0.05) carcass yield than those fed CON. In Exp.2, feeding NAR increased ( < 0.05) pig BW from days 54 through 96 compared to pigs fed CON or VIR. No differences ( > 0.05) in ADG were detected between pigs fed VIR and CON through the first 74 day, but ADG of pigs fed VIR was similar to ( > 0.05) those fed NAR from days 26 to 54. From day 0 to 109, NAR improved ADG compared to pigs fed VIR, which also had similar gain to those consuming CON ( = 0.04). Feed efficiency was similar between pigs fed NAR and VIR with pigs fed CON intermediate ( = 0.05). Pigs fed NAR had a greater ( < 0.05) HCW and loin depth than those fed CON or VIR. A subtherapeutic dose of VIR showed improvements in growth performance that were similar to NAR in one experiment. Although there were differences in the magnitude of growth and carcass effects of NAR between the two studies, pigs fed NAR showed at least a tendency to have greater G:F and in some cases increased carcass weight and yield compared to pigs consuming nonmedicated feed.
PubMed: 33748685
DOI: 10.1093/tas/txab020