scholarly journals Analysis of Aminoglycoside Modifying Enzyme Genes Responsible for High-Level Aminoglycoside Resistance among Enterococcal Isolates

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Vishal Shete ◽  
Naveen Grover ◽  
Mahadevan Kumar
Keyword(s):  
Active Agent ◽  
Bactericidal Effect ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Aminoglycoside Resistance ◽  
Enzyme Gene ◽  
A Cell ◽  
Polymerase Chain ◽  
High Level ◽  
Level Resistance

Enzymatic modification results in high-level resistance to aminoglycoside (HLAR), which eliminates the synergistic bactericidal effect of combined exposure to a cell wall-active agent and an aminoglycoside. So aim of the study was to determine prevalence of HLAR enterococcal isolate and to study distribution of aminoglycoside modifying enzyme genes in them. A total of 100 nonrepeat isolates of enterococci from various clinical samples were analyzed. As per Clinical and Laboratory Standards Institute guidelines enterococci were screened for HLAR by Kirby-Bauer disc diffusion method. Minimum inhibitory concentration of all isolates for gentamicin and streptomycin was determined by E-test. Multiplex polymerase chain reaction (PCR) was carried out for HLAR enterococcal isolates to identify aminoglycoside modifying enzymes genes responsible for resistance. 60% isolates were found to be high-level gentamicin resistant (HLGR) whereas 45% isolates were found to be high-level streptomycin resistant (HLSR). By multiplex PCR 80% HLGR isolates carried bifunctional aminoglycoside modifying enzyme geneaac(6′)-Ie-aph(2′′)-Iawhereas 18 out of 45 high-level streptomycin resistant, that is, 40%, isolates carriedaph(3′)-IIIa.However,aph(2′′)-Ib, aph(2′′)-Ic, aph(2′′)-Id,andant(4′)-Iagenes which encode other aminoglycosides modifying enzymes were not detected. Bifunctional aminoglycoside modifying enzyme geneaac(6′)-Ie-aph(2′′)-Iais the predominant gene responsible for HLAR.

scholarly journals The life and times of the Enterococcus.

1990 ◽  
Vol 3 (1) ◽  
pp. 46-65 ◽  
Author(s):  
B E Murray
Keyword(s):  
Antimicrobial Agents ◽  
Acquired Resistance ◽  
Active Agent ◽  
Bactericidal Effect ◽  
Human Pathogens ◽  
A Cell ◽  
High Level ◽  
Tract Infections ◽  
Level Resistance ◽  
Resistance Traits

Enterococci are important human pathogens that are increasingly resistant to antimicrobial agents. These organisms were previously considered part of the genus Streptococcus but have recently been reclassified into their own genus, called Enterococcus. To date, 12 species pathogenic for humans have been described, including the most common human isolates, Enterococcus faecalis and E. faecium. Enterococci cause between 5 and 15% of cases of endocarditis, which is best treated by the combination of a cell wall-active agent (such as penicillin or vancomycin, neither of which alone is usually bactericidal) and an aminoglycoside to which the organism is not highly resistant; this characteristically results in a synergistic bactericidal effect. High-level resistance (MIC, greater than or equal to 2,000 micrograms/ml) to the aminoglycoside eliminates the expected bactericidal effect, and such resistance has now been described for all aminoglycosides. Enterococci can also cause urinary tract infections; intraabdominal, pelvic, and wound infections; superinfections (particularly in patients receiving expanded-spectrum cephalosporins); and bacteremias (often together with other organisms). They are now the third most common organism seen in nosocomial infections. For most of these infections, single-drug therapy, most often with penicillin, ampicillin, or vancomycin, is adequate. Enterococci have a large number of both inherent and acquired resistance traits, including resistance to cephalosporins, clindamycin, tetracycline, and penicillinase-resistant penicillins such as oxacillin, among others. The most recent resistance traits reported are penicillinase resistance (apparently acquired from staphylococci) and vancomycin resistance, both of which can be transferred to other enterococci. It appears likely that we will soon be faced with increasing numbers of enterococci for which there is no adequate therapy.

scholarly journals Vancomycin and high-level aminoglycoside resistance in Enterococcus species

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Seyda Ozarslan Kurtgoz ◽  
Burcin Ozer ◽  
Melek Inci ◽  
Nizami Duran ◽  
Erkan Yula
Keyword(s):  
Vancomycin Resistance ◽  
Automated System ◽  
Diffusion Method ◽  
Beta Lactamase ◽  
Aminoglycoside Resistance ◽  
Disk Diffusion Method ◽  
Gradient Diffusion ◽  
Gentamicin Resistance ◽  
Polymerase Chain ◽  
High Level

The aim of the study was to investigate vancomycin and high-level aminoglycoside resistance (HLAR) in <em>Enterococcus</em> species by phenotypic and genotypic methods. A hundred <em>Enterococcus</em> strains were included in the study. Antimicrobial susceptibilities of strains were investigated by automated system, betalactamase production was investigated by nitrocefin disks, vancomycin resistance and HLAR were investigated by gradient diffusion method (GDM) and disk diffusion method, respectively. For detection of vancomycin and high-level gentamicin resistance (HLGR) genes, polymerase chain reaction was used. Teicoplanin linezolid, vancomycin, ampicillin, penicillin are the most susceptible antibiotics and strains were detected not to produce beta lactamase. Vancomycin resistance was detected in ten isolates by automated system and in only five isolates by GDM. Five isolates carrying <em>VanA</em> gene were determined. The ratio of HLGR and high-level streptomycin resistance was found 40 and 63% respectively. <em>aac (6’)-1eaph (2’’)-1a</em> gene was detected in 58% of strains. <em>E. faecium</em> strains were found more resistant to the antibiotics than the other species. Beta lactamase was detected in none of strains. The automated system detected vancomycin resistance in more strains than GDM. Therefore it is concluded that strains, which were detected to be resistant to vancomycin, should be confirmed by GDM. The ratio of <em>VanA</em> gene in strains is consistent with other studies. The HLAR ratio was found in about half of strains. The ratio of<em> aac(6’)-1e-aph(2’’)-1a</em> gene, which is the most reported gene in our country and other countries and one of the HLGR genes investigated in our study, was detected 58%.

scholarly journals Vancomycin and High Level Aminoglycoside Resistance inEnterococcusspp. in a Tertiary Health Care Centre: A Therapeutic Concern

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Seema Mittal ◽  
Pooja Singla ◽  
Antariksha Deep ◽  
Kiran Bala ◽  
Rama Sikka ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Antibiotic Sensitivity ◽  
Vaginal Swab ◽  
Control Measures ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Aminoglycoside Resistance ◽  
Sensitivity Testing ◽  
Health Care Centre ◽  
High Level

Aims. This study was aimed at knowing the prevalence of vancomycin and high level aminoglycoside resistance in enterococcal strains among clinical samples.Study Design. It was an investigational study.Place and Duration of Study. It was conducted on 100Enterococcusisolates, in the Department of Microbiology, Pt. BDS PGIMS, Rohtak, over a period of six months from July to December 2014.Methodology. Clinical specimens including urine, pus, blood, semen, vaginal swab, and throat swab were processed andEnterococcusisolates were identified by standard protocols. Antibiotic sensitivity testing of enterococci was performed using Kirby-Bauer disc diffusion method.Results. High level gentamicin resistance (HLGR) was more common in urine samples (41.5%) followed by blood (36%) samples. High level streptomycin resistance (HLSR) was more common in pus samples (52.6%) followed by blood samples (36%). Resistance to vancomycin was maximum in blood isolates.Conclusion. Enterococci resistant to multiple antimicrobial agents have been recognized. Thus, it is crucial for laboratories to provide accurate antimicrobial resistance patterns for enterococci so that effective therapy and infection control measures can be initiated.

scholarly journals A Comparison of High-Level Aminoglycoside Resistance in Vancomycin-Sensitive and Vancomycin-Resistant Enterococcus Species

2002 ◽  
Vol 30 (5) ◽  
pp. 529-534 ◽  
Author(s):  
H Yazgi ◽  
M Ertek ◽  
S Erol ◽  
A Ayyildiz
Keyword(s):  
Brain Heart Infusion ◽  
Bactericidal Effect ◽  
Vancomycin Resistance ◽  
Glycopeptide Antibiotics ◽  
Aminoglycoside Resistance ◽  
Significant Difference ◽  
Vancomycin Resistant ◽  
High Level ◽  
Infusion Agar ◽  
Level Resistance

The aim of this study was to investigate whether there was a significant difference in high-level aminoglycoside resistance (HLAR) between vancomycin-sensitive enterococci (VSE) and vancomycin-resistant enterococci (VRE). Vancomycin resistance was determined in 116 Enterococcus isolates using brain-heart infusion agar containing 6 μg/ml vancomycin. HLAR was determined by both standard agar screening and disk diffusion methods. Streptomycin and gentamicin were used as predictors of HLAR. Vancomycin resistance and HLAR were found in 17 (14.7%) and 41 (35.3%) of the Enterococcus strains, respectively. HLAR was found in 11 of 17 VRE and 30 of 98 VSE strains. HLAR in VRE strains was significantly higher than in VSE. More enterococcal strains were found to be resistant to both gentamicin and streptomycin (29) than to gentamicin (one) or streptomycin (11) alone. The HLAR rate in VRE was two-fold higher than in VSE. The synergistic bactericidal effect of aminoglycosides and β-lactam or glycopeptide antibiotics is lost if there is high-level resistance to aminoglycosides.

scholarly journals Relationship between the Level of Acquired Resistance to Gentamicin and Synergism with Amoxicillin in Enterococcus faecalis

2005 ◽  
Vol 49 (10) ◽  
pp. 4144-4148 ◽  
Author(s):  
Elisabeth Aslangul ◽  
Raymond Ruimy ◽  
Françoise Chau ◽  
Louis Garry ◽  
Antoine Andremont ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Acquired Resistance ◽  
Bactericidal Effect ◽  
A Cell ◽  
Enzymatic Inactivation ◽  
High Level ◽  
The Impact ◽  
Level Resistance

ABSTRACT In enterococci, intrinsic low-level resistance to gentamicin does not abolish synergism with a cell wall-active antibiotic while high-level resistance due to acquired aminoglycoside-modifying enzymes does. To study the impact of intermediate levels of resistance to gentamicin (64 < MIC < 500 μg/ml), we selected in vitro three consecutive generations of mutants of Enterococcus faecalis JH2-2 with MICs of gentamicin at 128 μg/ml for G1-1477, 256 μg/ml for G2-1573, and 512 μg/ml for G3-1688. E. faecalis 102, which is highly resistant to gentamicin by enzymatic inactivation was used as control. In in vitro killing curves experiments, gentamicin concentrations allowing bactericidal activity and synergism in combination with amoxicillin increased from 4 μg/ml (1/16th the MIC), 16 μg/ml (one-eighth the MIC), 64 μg/ml (one-quarter the MIC), and 256 μg/ml (one-half the MIC) for strains JH2-2, G1-1477, G2-1573 and G3-1688, respectively. As expected, no bactericidal effect of the combination or synergism could be obtained with strain 102. In rabbits with aortic endocarditis caused by strain G1-1477 or G2-1573, combination therapy with amoxicillin and gentamicin was significantly more active than amoxicillin alone (P < 0.05) but not in those infected with the strains G3-1688 and 102. Thus, intermediate levels of resistance to gentamicin was not associated with a loss of a beneficial effect of the gentamicin-amoxicillin combination in vivo even though higher concentrations of gentamicin were necessary to achieve in vitro synergism. Therefore, the use of an MIC of 500 μg/ml as a clinical cutoff limit to predict in vivo benefit of the combination remains a simple and effective tool.

scholarly journals Detection of high-level aminoglycoside resistance by disc diffusion and e-test amongst the enterococcus species isolated from various clinical samples in a tertiary care hospital

2019 ◽  
Vol 7 (9) ◽  
pp. 3527
Author(s):  
Manisha Paul ◽  
Prem Singh Nirwan ◽  
Preeti Srivastava
Keyword(s):  
Antimicrobial Susceptibility ◽  
Tertiary Care ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Disc Diffusion ◽  
Enterococcus Species ◽  
Aminoglycoside Resistance ◽  
High Level ◽  
Multiple Drugs ◽  
Enterococcal Infections

Background: The emergence of Enterococcus species in causing nosocomial infections poses a therapeutic challenge to clinicians. Enterococci are intrinsically resistance to multiple antibiotics. Acquired resistance to commonly used antibiotics like Ampicillin, Vancomycin and Aminoglycosides have made the situation worse and difficult to treat serious Enterococcal infections. The present study aimed at detection of high-level aminoglycoside resistance by disc diffusion and E-test amongst the Enterococcus species isolated from various clinical samples in a tertiary care hospital.Methods: A total of 102 Enterococcus species isolated from various clinical samples and antimicrobial susceptibility was performed by Kirby Bauer disc diffusion method as per CLSI guidelines. E-test was done for all high level aminoglycoside resistance Enterococcus species isolated by disc diffusion test.Results: Among 102 isolates, 81 were E. faecalis, 18 were E. faecium and 3 were another Enterococcus. Their antimicrobial susceptibility pattern shows all isolates were sensitive to vancomycin, linezolid and teicoplanin with HLGR, HLSR detected in 40 and 38 isolates of E. faecalis, 17  and 13 isolates of E. faecium respectively by disc diffusion whereas by E-test it was detected in 44 and 40 in E. faecalis and 17 and 14 in E. faecium respectively. E. faecium is found to be more resistance to high level aminoglycoside than E. faecalis.Conclusions: Authors hereby conclude that Enterococci being the common cause of hospital acquired infections with their increasing resistance to multiple drugs and acquisition of HLAR; it must be routinely screened for various drugs to prevent drug resistance in hospital settings for serious Enterococcal infections.

High-Level Aminoglycoside Resistance in Enterococcus Faecalis and Enterococcus Faecium; as a Serious Threat in Hospitals

2020 ◽  
Vol 20 (2) ◽  
pp. 223-228 ◽  
Author(s):  
Mahmoud Khodabandeh ◽  
Mohsen Mohammadi ◽  
Mohammad Reza Abdolsalehi ◽  
Meysam Hasannejad-Bibalan ◽  
Mehrdad Gholami ◽  
...  
Keyword(s):  
Multiple Drug Resistance ◽  
High Rate ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Multiple Drug ◽  
Aminoglycoside Resistance ◽  
Antibiotic Resistance Profile ◽  
Antibiotic Susceptibility Test ◽  
High Level ◽  
Encoding Genes

Aims and Objectives: The present work aimed to evaluate the frequency of aminoglycoside- modifying enzymes encoding genes in the E. faecalis and E. faecium and their antibiotic resistance profile. Methods: A total of 305 different clinical samples were subjected for identification and antibiotic susceptibility test. The high-level aminoglycoside resistance was identified by MIC and Kirby Bauer disc diffusion method. The prevalence of aac (6')-Ie-aph (2'')-Ia, aph (3')-IIIa and ant (4')- Ia genes was determined by multiplex- PCR. In total, 100 enterococci strains were isolated. The prevalence of E. faecalis and E. faecium isolates was 78% and 22%, respectively. Results: All isolates were susceptible to linezolid. So, all E. faecalis were susceptible to vancomycin but, 36.4% of E. faecium were resistant to it. The prevalence of multiple drug resistance strains was 100% and 67.9% of E. faecium and E. faecalis, respectively. High-level-gentamicin and streptomycin resistant rates were as follows; 26.9% and 73.1% of E. faecalis and 77.3% and 90.1% of E. faecium. Conclusion: The results of the current study showed a high frequency of aac (6')-Ie-aph (2'')-Ia genes among enterococcal isolates. A high rate of resistance to antimicrobials in Enterococcus is obviously problematic, and a novel policy is needed to decrease resistance in these microorganisms.

scholarly journals Mutations in fbiD (Rv2983) as a Novel Determinant of Resistance to Pretomanid and Delamanid in Mycobacterium tuberculosis

2020 ◽  
Vol 65 (1) ◽  
pp. e01948-20
Author(s):  
Dalin Rifat ◽  
Si-Yang Li ◽  
Thomas Ioerger ◽  
Keshav Shah ◽  
Jean-Philippe Lanoix ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Evidence ◽  
Clinical Samples ◽  
Loss Of Function ◽  
Wild Type ◽  
Content Type ◽  
Solid Media ◽  
High Level ◽  
Level Resistance

ABSTRACTThe nitroimidazole prodrugs delamanid and pretomanid comprise one of only two new antimicrobial classes approved to treat tuberculosis (TB) in 50 years. Prior in vitro studies suggest a relatively low barrier to nitroimidazole resistance in Mycobacterium tuberculosis, but clinical evidence is limited to date. We selected pretomanid-resistant M. tuberculosis mutants in two mouse models of TB using a range of pretomanid doses. The frequency of spontaneous resistance was approximately 10−5 CFU. Whole-genome sequencing of 161 resistant isolates from 47 mice revealed 99 unique mutations, of which 91% occurred in 1 of 5 genes previously associated with nitroimidazole activation and resistance, namely, fbiC (56%), fbiA (15%), ddn (12%), fgd (4%), and fbiB (4%). Nearly all mutations were unique to a single mouse and not previously identified. The remaining 9% of resistant mutants harbored mutations in Rv2983 (fbiD), a gene not previously associated with nitroimidazole resistance but recently shown to be a guanylyltransferase necessary for cofactor F420 synthesis. Most mutants exhibited high-level resistance to pretomanid and delamanid, although Rv2983 and fbiB mutants exhibited high-level pretomanid resistance but relatively small changes in delamanid susceptibility. Complementing an Rv2983 mutant with wild-type Rv2983 restored susceptibility to pretomanid and delamanid. By quantifying intracellular F420 and its precursor Fo in overexpressing and loss-of-function mutants, we provide further evidence that Rv2983 is necessary for F420 biosynthesis. Finally, Rv2983 mutants and other F420H2-deficient mutants displayed hypersusceptibility to some antibiotics and to concentrations of malachite green found in solid media used to isolate and propagate mycobacteria from clinical samples.

scholarly journals 2493. Real-World Utilization of Ibalizumab (IBA) Without an Optimized Background Regimen (OBT)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S865-S865 ◽  
Author(s):  
Jeannette Bouchard ◽  
Caroline Derrick ◽  
Joseph Horvath
Keyword(s):  
Real World ◽  
Active Agent ◽  
Multidrug Resistant ◽  
Phase Iii ◽  
Hiv Virus ◽  
Oral Agents ◽  
Patient Table ◽  
Tenofovir Alafenamide ◽  
High Level ◽  
Level Resistance

Abstract Background It is difficult to treat multidrug-resistant (MDR) human immunodeficiency virus (HIV). Trogarzo® (ibalizumab) a novel monoclonal antibody was approved in 2018 for heavily treatment-experienced HIV patients. Data support IBA use with at least one fully active agent, an OBR. Real-world IBA data are lacking. We report a successful case of reaching and maintaining suppression with IBA in a patient without an OBR. Methods Mutations were reviewed for the patient, Table 1, and evaluated for treatment. The patient is a 52- year old male, diagnosed in 1994, with MDR HIV secondary to non-adherence. Upon re-presenting to care, the patient was non-compliant with ART. Genotypic interpretation via the Stanford/ANRS algorithm was performed and interpreted, resulting in the addition of IBA intravenous administration every other week. IBA was obtained through patient assistance and costs were covered by the institution for infusion. Results Evaluation of the resistance profile indicated varying resistance to all available ART. More specifically, high-level resistance to all FDA-approved INSTIs, PIs, and low to high-level resistance to all NNRTIs and NRTIs. Table 2 outlines the ART history and viral load (VL) trends. The patient was initiated on daruanvir/ritonavir twice daily, etravirine twice daily, emtricitabine/tenofovir alafenamide and did not reach suppression. IBA was added off-label to a failing regimen. The patient reached VS (VL < 200 copies/mL) at Week 4 and has had an undetectable VL for 8 weeks. Notably his CD4 count has risen to 46, first detectable number since re-presenting to care. Conclusion We describe a heavily treatment experienced patient with an MDR HIV virus who achieved an undetectable VL without an OBT and the addition of intravenous IBA. Fostemsavir, was utilized in IBA’s phase III trial for similar patients, however, it is not currently FDA-approved nor available. Further data are needed to ensure continued susceptibility to IBA without an OBT. This patient required high-level coordination to reach each visit and receive this therapy alongside his oral agents. We conclude, IBA has allowed this patient to reach and maintain VS. Disclosures All authors: No reported disclosures.

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