The changing nature of aminoglycoside resistance mechanisms and prevalence of newly recognized resistance mechanisms in Turkey

Introduction: Regardless of the country, advancements in medical care and infection prevention and control of bloodstream infections (BSIs) are an enormous burden of modern medicine. Objectives: The aim of our study was to describe the epidemiology and drug-resistance of laboratory-confirmed BSI (LC-BSIs) among adult patients of 16 hospitals in the south of Poland. Patients and methods: Data on 4218 LC-BSIs were collected between 2016–2019. The identification of the strains was performed using MALDI-TOF. Resistance mechanisms were investigated according to European Committee on Antimicrobial Susceptibility Testing, EUCAST recommendations. Results: Blood cultures were collected from 8899 patients, and LC-BSIs were confirmed in 47.4%. The prevalence of Gram-positive bacteria was 70.9%, Gram-negative 27.8% and yeast 1.4%. The most frequently isolated genus was Staphylococcus (50% of all LC-BSIs), with a domination of coagulase-negative staphylococci, while Escherichia coli (13.7%) was the most frequent Gram-negative bacterium. Over 4 years, 108 (2.6%) bacteria were isolated only once, including species from the human microbiota as well as environmental and zoonotic microorganisms. The highest methicillin resistant Staphylococcus aureus (MRSA) prevalence was in intensive care units (ICUs) (55.6%) but S. aureus with resistance to macrolides, lincosamides and streptogramins B (MLSB) in surgery was 66.7%. The highest prevalence of E. faecalis with a high-level aminoglycoside resistance (HLAR) mechanism was in ICUs, (84.6%), while E. faecium-HLAR in surgery was 83.3%. All cocci were fully glycopeptide-sensitive. Carbapenem-resistant Gram-negative bacilli were detected only in non-fermentative bacilli group, with prevalence 70% and more. Conclusions: The BSI microbiology in Polish hospitals was similar to those reported in other studies, but the prevalence of MRSA and enterococci-HLAR was higher than expected, as was the prevalence of carbapenem-resistant non-fermentative bacilli. Modern diagnostic techniques, such as MALDI-TOF, guarantee reliable diagnosis.

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Apramycin overcomes the inherent lack of antimicrobial bactericidal activity in Mycobacterium abscessus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01510-21 ◽

2021 ◽

Author(s):

Petra Selchow ◽

Diane J. Ordway ◽

Deepshikha Verma ◽

Nicholas Whittel ◽

Aline Petrig ◽

...

Keyword(s):

Bactericidal Activity ◽

Lung Infection ◽

Resistance Mechanisms ◽

Mycobacterium Abscessus ◽

Multi Drug Resistance ◽

Emerging Pathogen ◽

Aminoglycoside Resistance ◽

Treatment Regimens ◽

Distinct Structure ◽

Poor Therapeutic Outcome

Antibiotic therapy of infections caused by the emerging pathogen Mycobacterium abscessus is challenging due to the organism’s inherent resistance towards clinically available antimicrobials. The low bactericidal potency of currently available treatment regimens is of concern and testifies to the poor therapeutic outcome in pulmonary M. abscessus infections. Mechanistically, we here demonstrate that the acetyltransferase Eis2 is responsible for the lack of bactericidal activity of amikacin, the standard aminoglycoside used in combination treatment. In contrast, the distinct structure aminoglycoside apramycin is not modified by any of the pathogen’s innate aminoglycoside resistance mechanisms nor is it affected by the multi-drug resistance regulator WhiB7. As a consequence, apramycin uniquely shows potent bactericidal activity against M. abscessus . This favourable feature of apramycin is reflected in a mouse model of M. abscessus lung infection, which demonstrates superior activity over amikacin. These findings encourage the development of apramycin for the treatment of M. abscessus infections and suggest that M. abscessus eradication in lung pulmonary disease may be within therapeutic reach.

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Expected Plazomicin Susceptibility in India Based on the Prevailing Aminoglycoside Resistance Mechanisms in Gram-Negative Organisms Derived from Whole-Genome Sequencing

Indian Journal of Medical Microbiology ◽

10.4103/ijmm.ijmm_20_384 ◽

2020 ◽

Vol 38 (3-4) ◽

pp. 313-318

Author(s):

Agila Kumari Pragasam ◽

S.Lydia Jennifer ◽

Dhanalakshmi Solaimalai ◽

Dhiviya Prabaa Muthuirulandi Sethuvel ◽

Tanya Rachel ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Resistance Mechanisms ◽

Whole Genome ◽

Aminoglycoside Resistance ◽

Gram Negative ◽

Gram Negative Organisms

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Development and Persistence of Antimicrobial Resistance in Pseudomonas aeruginosa: a Longitudinal Observation in Mechanically Ventilated Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01278-06 ◽

2007 ◽

Vol 51 (4) ◽

pp. 1341-1350 ◽

Cited By ~ 47

Author(s):

Anita Reinhardt ◽

Thilo Köhler ◽

Paul Wood ◽

Peter Rohner ◽

Jean-Luc Dumas ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Resistance ◽

Selective Pressure ◽

Resistance Mechanism ◽

Resistance Mechanisms ◽

Antimicrobial Treatment ◽

Aminoglycoside Resistance ◽

Prolonged Intubation ◽

Treatment Regimens ◽

Underlying Mechanisms

ABSTRACT Intubated patients frequently become colonized by Pseudomonas aeruginosa, which is subsequently responsible for ventilator-associated pneumonia. This pathogen readily acquires resistance against available antimicrobials. Depending on the resistance mechanism selected for, resistance might either be lost or persist after removal of the selective pressure. We investigated the rapidity of selection, as well as the persistence, of antimicrobial resistance and determined the underlying mechanisms. We selected 109 prospectively collected P. aeruginosa tracheal isolates from two patients based on their prolonged intubation and colonization periods, during which they had received carbapenem, fluoroquinolone (FQ), or combined β-lactam-aminoglycoside therapies. We determined antimicrobial resistance phenotypes by susceptibility testing and used quantitative real-time PCR to measure the expression of resistance determinants. Within 10 days after the initiation of therapy, all treatment regimens selected resistant isolates. Resistance to β-lactam and FQ was correlated with ampC and mexC gene expression levels, respectively, whereas imipenem resistance was attributable to decreased oprD expression. Combined β-lactam-aminoglycoside resistance was associated with the appearance of small-colony variants. Imipenem and FQ resistance persisted for prolonged times once the selecting antimicrobial treatment had been discontinued. In contrast, resistance to β-lactams disappeared rapidly after removal of the selective pressure, to reappear promptly upon renewed exposure. Our results suggest that resistant P. aeruginosa is selected in less than 10 days independently of the antimicrobial class. Different resistance mechanisms lead to the loss or persistence of resistance after the removal of the selecting agent. Even if resistant isolates are not evident upon culture, they may persist in the lung and can be rapidly reselected.

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Emergence of Multidrug-Resistant Uropathogens harboring ESBL, Carbapenem, Aminoglycosides and AmpC resistant genes from Northern India

10.1101/375501 ◽

2018 ◽

Author(s):

Varsha Rani Gajamer ◽

Amitabha Bhattacharjee ◽

Deepjyoti Paul ◽

Birson Ingti ◽

Arunabha Sarkar ◽

...

Keyword(s):

Resistance Gene ◽

Antibiotic Resistance Gene ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Aminoglycoside Resistance ◽

Antibiotic Resistant ◽

Northern India ◽

Carbapenem Resistant ◽

Resistant Genes ◽

Esbl Producers

ABSTRACTExtended-spectrum β-lactamase (ESBL) producing bacteria acts as a serious threat, and its co-existence with other antibiotic resistant gene makes the clinical scenario worse nowadays. Therefore in this study, we investigated the occurrence of ESBL genes coexisting with carbapenem, AmpC and aminoglycoside resistance gene in uropathogens. Out of 1516 urine samples, 454 showed significant bacteriuria with a prevalence rate of 29.94 %. Escherichia coli (n=340) were found to be the most predominant uropathogen followed by Klebsiella pneumoniae (n=92), Pseudomonas aeruginosa (n=10) and Proteus mirabilis (n=9). Among the total uropathogens, sixty-three ESBL-producers were identified which included blaCTX-M-15 (n=32), followed by blaCTX-M-15 + blaOXA-2 (n=15), blaCTX-M-15 + blaOXA-2 + blaTEM (n=6), blaOXA-2 (n=5), blaOXA-2 + blaSHV-76 (n=1), blaTEM+SHV-76 (n= 1) and blaTEM (n=1). All ESBL genes were found on plasmid incompatibility types: HI1, I1, FIA+FIB, FIA and Y and were horizontally transferable. Among 63 ESBL-producers, 59 isolates harboured carbapenem-resistant genes which included blaNDM-5 (n=48), blaNDM-5 + blaOXA-48 (n=5), blaNDM-5 + blaIMP (n=5) and blaNDM-5 + blaIMP + blaVIM (n=1). The ESBL producing uropathogens also harbored 16S rRNA methylase genes which included rmtB (n=9), rmtA (n=4), rmtC (n=1) and ArmA (n=1) followed by AmpC genes which includes CIT (n=8) and DHA-1 (n=1) genes. Imipenem and gentamicin were found to be more effective. We speculating, this is the first report showing the prevalence of multidrug-resistant uropathogens in this area demanding regular surveillance for such resistance mechanisms which will be useful for health personnel to treat ESBL infection and its co-existence with another antibiotic resistance gene.

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Aminoglycoside Resistance Mechanisms

Frontiers in Antimicrobial Resistance ◽

10.1128/9781555817572.ch7 ◽

2014 ◽

pp. 85-100 ◽

Cited By ~ 2

Author(s):

David D. Boehr ◽

Ian F. Moore ◽

Gerard D. Wright

Keyword(s):

Resistance Mechanisms ◽

Aminoglycoside Resistance

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Assessment of Tedizolid In Vitro Activity and Resistance Mechanisms against a Collection of Enterococcus spp. Causing Invasive Infections, Including Isolates Requiring an Optimized Dosing Strategy for Daptomycin from U.S. and European Medical Centers, 2016 to 2018

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00175-20 ◽

2020 ◽

Vol 64 (4) ◽

Cited By ~ 1

Author(s):

Cecilia G. Carvalhaes ◽

Helio S. Sader ◽

Robert K. Flamm ◽

Jennifer M. Streit ◽

Rodrigo E. Mendes

Keyword(s):

The United States ◽

Resistance Mechanisms ◽

Aminoglycoside Resistance ◽

Content Type ◽

Medical Centers ◽

Enterococcus Spp ◽

Invasive Infections ◽

Dosing Strategy ◽

High Level

ABSTRACT High-level aminoglycoside resistance was noted in 30.0% of Enterococcus faecalis and 25.2% of Enterococcus faecium isolates. Only 3.3% and 2.1% of E. faecalis isolates had elevated daptomycin MIC (≥2 mg/liter) and vancomycin resistance, respectively. In contrast, 37.4% to 40.3% of E. faecium isolates exhibited these phenotypes. Tedizolid inhibited 98.9% to 100.0% of enterococci causing serious invasive infections, including resistant subsets. Oxazolidinone resistance was mainly driven by G2576T; however, optrA and poxtA genes were also detected, including poxtA in the United States and Turkey.

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Aminoglycoside resistance mechanism inference algorithm: Implication for underlying resistance mechanisms to aminoglycosides

EBioMedicine ◽

10.1016/j.ebiom.2019.07.045 ◽

2019 ◽

Vol 46 ◽

pp. 8

Author(s):

Abdelaziz Touati

Keyword(s):

Resistance Mechanism ◽

Resistance Mechanisms ◽

Inference Algorithm ◽

Aminoglycoside Resistance

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New Determinants of Aminoglycoside Resistance and Their Association with the Class 1 Integron Gene Cassettes in Trueperella pyogenes

International Journal of Molecular Sciences ◽

10.3390/ijms21124230 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4230

Author(s):

Ewelina Kwiecień ◽

Ilona Stefańska ◽

Dorota Chrobak-Chmiel ◽

Agnieszka Sałamaszyńska-Guz ◽

Magdalena Rzewuska

Keyword(s):

Resistance Genes ◽

Resistance Mechanisms ◽

Aminoglycoside Resistance ◽

Class 1 Integron ◽

Gene Cassettes ◽

Genetic Elements ◽

Trueperella Pyogenes ◽

Broth Microdilution Method ◽

Class 1 ◽

Aminoglycoside Resistance Genes

Trueperella pyogenes is an important opportunistic animal pathogen. Different antimicrobials, including aminoglycosides, are used to treat T. pyogenes infections. The aim of the present study was to evaluate aminoglycoside susceptibility and to detect aminoglycoside resistance determinants in 86 T. pyogenes isolates of different origin. Minimum inhibitory concentration of gentamicin, streptomycin, and kanamycin was determined using a standard broth microdilution method. Genetic elements associated with aminoglycoside resistance were investigated by PCR and DNA sequencing. All studied isolates were susceptible to gentamicin, but 32.6% and 11.6% of them were classified as resistant to streptomycin and kanamycin, respectively. A total of 30 (34.9%) isolates contained class 1 integrons. Class 1 integron gene cassettes carrying aminoglycoside resistance genes, aadA11 and aadA9, were found in seven and two isolates, respectively. Additionally, the aadA9 gene found in six isolates was not associated with mobile genetic elements. Moreover, other, not carried by gene cassettes, aminoglycoside resistance genes, strA-strB and aph(3’)-IIIa, were also detected. Most importantly, this is the first description of all reported genes in T. pyogenes. Nevertheless, the relevance of the resistance phenotype to genotype was not perfectly matched in 14 isolates. Therefore, further investigations are needed to fully explain aminoglycoside resistance mechanisms in T. pyogenes.

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