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.

scholarly journals ArmA Methyltransferase in a Monophasic Salmonella enterica Isolate from Food

2011 ◽  
Vol 55 (11) ◽  
pp. 5262-5266 ◽  
Author(s):  
Sophie A. Granier ◽  
Laura Hidalgo ◽  
Alvaro San Millan ◽  
Jose Antonio Escudero ◽  
Belen Gutierrez ◽  
...  
Keyword(s):  
16S Rrna ◽  
Salmonella Enterica ◽  
Multidrug Resistant ◽  
Broad Host Range ◽  
En Bloc ◽  
Content Type ◽  
Route Of Transmission ◽  
Amoxicillin Clavulanate ◽  
High Level ◽  
Level Resistance

ABSTRACTThe 16S rRNA methyltransferase ArmA is a worldwide emerging determinant that confers high-level resistance to most clinically relevant aminoglycosides. We report here the identification and characterization of a multidrug-resistantSalmonella entericasubspecies I.4,12:i:− isolate recovered from chicken meat sampled in a supermarket on February 2009 in La Reunion, a French island in the Indian Ocean. Susceptibility testing showed an unusually high-level resistance to gentamicin, as well as to ampicillin, expanded-spectrum cephalosporins and amoxicillin-clavulanate. Molecular analysis of the 16S rRNA methyltransferases revealed presence of thearmAgene, together withblaTEM-1,blaCMY-2, andblaCTX-M-3. All of these genes could be transferreden blocthrough conjugation intoEscherichia coliat a frequency of 10−5CFU/donor. Replicon typing and S1 pulsed-field gel electrophoresis revealed that thearmAgene was borne on an ∼150-kb broad-host-range IncP plasmid, pB1010. To elucidate howarmAhad integrated in pB1010, a PCR mapping strategy was developed for Tn1548, the genetic platform forarmA.The gene was embedded in a Tn1548-like structure, albeit with a deletion of the macrolide resistance genes, and an IS26was inserted within themelgene. To our knowledge, this is the first report of ArmA methyltransferase in food, showing a novel route of transmission for this resistance determinant. Further surveillance in food-borne bacteria will be crucial to determine the role of food in the spread of 16S rRNA methyltransferase genes worldwide.

scholarly journals Integrative and Conjugative Element-Mediated Azithromycin Resistance in Multidrug-Resistant Salmonella enterica Serovar Albany

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Yu-Ping Hong ◽  
Ying-Tsong Chen ◽  
You-Wun Wang ◽  
Bo-Han Chen ◽  
Ru-Hsiou Teng ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Salmonella Enterica ◽  
Multidrug Resistant ◽  
Content Type ◽  
Human Salmonellosis ◽  
High Level ◽  
Azithromycin Resistance ◽  
Level Resistance ◽  
Integrative And Conjugative Element

ABSTRACT We identified an erm42-carrying integrative and conjugative element, ICE_erm42, in 26.4% of multidrug-resistant Salmonella enterica serovar Albany isolates recovered from cases of human salmonellosis between 2014 and 2019 in Taiwan. ICE_erm42-carrying strains displayed high-level resistance to azithromycin, and the element could move into the phylogenetically distant species Vibrio cholerae via conjugation.

scholarly journals Antimicrobial Resistance of DiarrheagenicEscherichia coli Isolated from Children under the Age of 5 Years from Ifakara, Tanzania

1999 ◽  
Vol 43 (12) ◽  
pp. 3022-3024 ◽  
Author(s):  
Jordi Vila ◽  
Martha Vargas ◽  
Climent Casals ◽  
Honorato Urassa ◽  
Hassan Mshinda ◽  
...  
Keyword(s):  
Developing Countries ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Important Public Health Problem ◽  
Important Public Health ◽  
E Coli ◽  
High Level ◽  
Level Resistance ◽  
Children Under 5

ABSTRACT Diarrhea caused by multidrug-resistant bacteria is an important public health problem among children in developing countries. The prevalence and antimicrobial susceptibility of diarrheagenicEscherichia coli in 346 children under 5 years of age in Ifakara, Tanzania, were studied. Thirty-eight percent of the cases of diarrhea were due to multiresistant enterotoxigenic E. coli, enteroaggregative E. coli, or enteropathogenicE. coli. Strains of all three E. colicategories showed high-level resistance to ampicillin, tetracycline, co-trimoxazole, and chloramphenicol but were highly susceptible to quinolones. Guidelines for appropriate use of antibiotics in developing countries need updating.

scholarly journals Genetic Analyses of Penicillin Binding Protein Determinants in Multidrug-Resistant Streptococcus pneumoniae Serogroup 19 CC320/271 Clone with High-Level Resistance to Third-Generation Cephalosporins

2015 ◽  
Vol 59 (7) ◽  
pp. 4040-4045 ◽  
Author(s):  
Margaret Ip ◽  
Irene Ang ◽  
Veranja Liyanapathirana ◽  
Helen Ma ◽  
Raymond Lai
Keyword(s):  
Hong Kong ◽  
Amino Acid ◽  
Amino Acid Substitution ◽  
Binding Protein ◽  
Multidrug Resistant ◽  
Penicillin Binding Protein ◽  
Unique Amino Acid Substitution ◽  
High Level ◽  
Unique Amino Acid ◽  
Level Resistance

ABSTRACTWe describe the dissemination of a multidrug-resistant (MDR) serogroup 19 pneumococcal clone of representative multilocus sequence type 271 (ST271) with high-level resistance to cefotaxime in Hong Kong and penicillin binding protein (pbp) genes and its relationships to Taiwan19F-14 and the prevalent multidrug-resistant 19A clone (MDR19A-ST320). A total of 472 nonduplicate isolates from 2006 and 2011 were analyzed. Significant increases in the rates of nonsusceptibility to penicillin (PEN) (MIC ≥ 4.0 μg/ml; 9.9 versus 23.3%;P= 0.0005), cefotaxime (CTX) (MIC ≥ 2.0 μg/ml; 12.2 versus 30.3%;P< 0.0001 [meningitis MIC ≥ 1.0 μg/ml; 30.2 versus 48.7%;P= 0.0001]), and erythromycin (ERY) (69.2 versus 84.0%;P= 0.0003) were noted when rates from 2006 and 2011 were compared. The CTX-resistant isolates with MICs of 8 μg/ml in 2011 were of serotype 19F, belonging to ST271. Analyses of the penicillin binding protein 2x (PBP2x) amino acid sequences in relation to the corresponding sequences of the R6 strain revealed M339F, E378A, M400T, and Y595F substitutions found within the ST271 clone but not present in Taiwan19F-14 or MDR19A. In addition, PBP2bs of ST271 strains and that of the Taiwan19F-14 clone were characterized by a unique amino acid substitution, E369D, while ST320 possessed the unique amino acid substitution K366N, as does that of MDR19A in the United States. We hypothesize that ST271 originated from the Taiwan19F-14 lineage, which had disseminated in Hong Kong in the early 2000s, and conferred higher-level β-lactam and cefotaxime resistance through acquisitions of 19 additional amino acid substitutions in PBP2b (amino acid [aa] positions 538 to 641) and altered PBP2x via recombination events. The serogroup 19 MDR CC320/271 clone warrants close monitoring to evaluate its effect after the switch to expanded conjugate vaccines.

Multiple-Antibiotic Resistance of Enterococcus faecalis and Enterococcus faecium from Cecal Contents in Broiler Chicken and Turkey Flocks Slaughtered in Canada and Plasmid Colocalization of tetO and ermB Genes

2011 ◽  
Vol 74 (10) ◽  
pp. 1639-1648 ◽  
Author(s):  
CINDY-LOVE TREMBLAY ◽  
ANN LETELLIER ◽  
SYLVAIN QUESSY ◽  
MARTINE BOULIANNE ◽  
DANIELLE DAIGNAULT ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Enterococcus Faecalis ◽  
Resistance Genes ◽  
Enterococcus Faecium ◽  
Broiler Chicken ◽  
Multidrug Resistant ◽  
Poultry Meat ◽  
Antimicrobial Resistance Genes ◽  
High Level ◽  
Level Resistance

This study was conducted to characterize the antimicrobial resistance determinants and investigate plasmid colocalization of tetracycline and macrolide genes in Enterococcus faecalis and Enterococcus faecium from broiler chicken and turkey flocks in Canada. A total of 387 E. faecalis and E. faecium isolates were recovered from poultry cecal contents from five processing plants. The percentages of resistant E. faecalis and E. faecium isolates, respectively, were 88.1 and 94% to bacitracin, 0 and 0.9% to chloramphenicol, 0.7 and 14.5% to ciprofloxacin, 72.6 and 80.3% to erythromycin, 3.7 and 41% to flavomycin, 9.6 and 4.3% (high-level resistance) to gentamicin, 25.2 and 17.1% (high-level resistance) to kanamycin, 100 and 94% to lincomycin, 0 and 0% to linezolid, 2.6 and 20.5% to nitrofurantoin, 3 and 27.4% to penicillin, 98.5 and 89.7% to quinupristin-dalfopristin, 7 and 12.8% to salinomycin, 46.7 and 38.5% (high-level resistance) to streptomycin, 95.6 and 89.7% to tetracycline, 73 and 75.2% to tylosin, and 0 and 0% to vancomycin. One predominant multidrug-resistant phenotypic pattern was identified in both E. faecalis and E. faecium (bacitracin, erythromycin, lincomycin, quinupristin-dalfopristin, tetracycline, and tylosin). These isolates were further examined by PCR and sequencing for the genes encoding their antimicrobial resistance. Various combinations of vatD, vatE, bcrR, bcrA, bcrB, bcrD, ermB, msrC, linB, tetM, and tetO genes were detected, and ermB, tetM, and bcrB were the most common antimicrobial resistance genes identified. For the first time, plasmid extraction and hybridization revealed colocalization of tetO and ermB genes on a ca. 11-kb plasmid in E. faecalis isolates, and filter mating experiments demonstrated its transferability. Results indicate that the intestinal enterococci of healthy poultry, which can contaminate poultry meat at slaughter, could be a reservoir for quinupristin-dalfopristin, bacitracin, tetracycline, and macrolide resistance genes.

scholarly journals Susceptibility trends of zoliflodacin against multidrug-resistant Neisseria gonorrhoeae clinical isolates in Nanjing, China (2014-2018)

2020 ◽  
Author(s):  
Wenjing Le ◽  
Xiaohong Su ◽  
Xiangdi Lou ◽  
Xuechun Li ◽  
Xiangdong Gong ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Dna Sequencing ◽  
Multidrug Resistant ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Extended Spectrum ◽  
High Level ◽  
Level Resistance

ABSTRACTPreviously, we reported potent activity of a novel spiropyrimidinetrione, zoliflodacin, against N. gonorrhoeae isolates from symptomatic men in Nanjing, China, collected in 2013. Here, we investigated trends of susceptibilities of zoliflodacin in 986 gonococcal isolates collected from men between 2014 and 2018. N. gonorrhoeae isolates were tested for susceptibility to zoliflodacin and seven other antibiotics. Mutations in gyrA, gyrB, parC and parE genes were determined by PCR and DNA sequencing. The MIC of zoliflodacin for N. gonorrhoeae ranged from ≤0.002 to 0.25 mg/L; the overall MIC50s and MIC90s were 0.06 mg/L and 0.125mg/L in 2018, increasing two-fold from 2014. However, the percent of isolates with lower zoliflodacin MICs declined in each year sequentially while the percent with higher MICs increased yearly (P≤0.00001). All isolates were susceptible to spectinomycin but resistant to ciprofloxacin (MIC ≥1 μg/ml); 21.2% (209/986) were resistant to azithromycin (≥1 μg/ml), 43.4% (428/986) were penicillinase-producing (PPNG), 26.9% (265/986) tetracycline-resistant (TRNG) and 19.4% (191/986) were multi-drug resistant (MDR) isolates. Among 143 isolates with higher zoliflodacin MICs (0.125-0.25 mg/L), all had quinolone resistance associated double or triple mutations in gyrA; 139/143 (97.2%) also had mutations in parC. There were no D429N/A and/or K450T mutations in GyrB identified in the 143 isolates with higher zoliflodacin MICs; a S467N mutation in GyrB was identified in one isolate. We report that zoliflodacin has excellent in vitro activity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin and extended spectrum cephalosporins.

scholarly journals High-Level β-Lactam Resistance Associated with Acquired Multidrug Resistance in Helicobacter pylori

2003 ◽  
Vol 47 (7) ◽  
pp. 2169-2178 ◽  
Author(s):  
Dong H. Kwon ◽  
M. P. Dore ◽  
J. J. Kim ◽  
M. Kato ◽  
M. Lee ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Multidrug Resistance ◽  
Natural Transformation ◽  
Multidrug Resistant ◽  
Resistant Isolate ◽  
Terminal Portion ◽  
Nucleotide Substitutions ◽  
H Pylori ◽  
High Level ◽  
Level Resistance

ABSTRACT Four clinical Helicobacter pylori isolates with high-level resistance to β-lactams exhibited low- to moderate-level resistance to the structurally and functionally unrelated antibiotics ciprofloxacin, chloramphenicol, metronidazole, rifampin, and tetracycline. This pattern of multidrug resistance was transferable to susceptible H. pylori by natural transformation using naked genomic DNA from a clinical multidrug-resistant isolate. Acquisition of the multidrug resistance was also associated with a change in the genotype of the transformed multidrug-resistant H. pylori. DNA sequence analyses of the gene encoding penicillin binding protein 1A (PBP 1A) showed 36 nucleotide substitutions resulting in 10 amino acid changes in the C-terminal portion (the putative penicillin binding domain). Acquisition of β-lactam resistance was consistently associated with transfer of a mosaic block containing the C-terminal portion of PBP 1A. No changes of genes gyrA, rpoB, rrn16S, rdxA, and frxA, and nine other genes (ftsI, hcpA, llm, lytB, mreB, mreC, pbp2, pbp4, and rodA1) encoding putative PBPs or involved in cell wall synthesis were found among the transformed resistant H. pylori. Antibiotic accumulations of chloramphenicol, penicillin, and tetracycline were all significantly decreased in the natural and transformed resistant H. pylori compared to what was seen with susceptible H. pylori. Natural transformation also resulted in the outer membrane protein profiles of the transformed resistant H. pylori becoming similar to that of the clinical resistant H. pylori isolates. Overall, these results demonstrate that high-level β-lactam resistance associated with acquired multidrug resistance in clinical H. pylori is mediated by combination strategies including alterations of PBP 1A and decreased membrane permeability.

scholarly journals 1192. Identification of a Novel Enterobacter cloacae Isolate Producing an IMP-13 Metallo-β-Lactamase

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S360-S361
Author(s):  
Muhammad Bilal Abid ◽  
Blake Buchan ◽  
Nathan Ledeboer ◽  
L Silvia Munoz-Price ◽  
Mary Beth Graham
Keyword(s):  
Clinical Success ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Stage Iiic ◽  
Travel History ◽  
Healthcare Settings ◽  
High Level ◽  
Culture Positive ◽  
Broth Dilution ◽  
Level Resistance

Abstract Background Metallo-β-lactamases (MBLs) have been identified as emerging resistance determinants in Enterobacteriaceae, A. baumanii, and P. aeruginosa. Early identification of carbapenemase-producing organisms (CPOs) is essential to prevent dissemination within healthcare settings. We report a case of a patient who was blood culture positive for a multidrug-resistant E. cloacae which was subsequently found to be positive for the MBL blaIMP-13. Methods A 74-year-old female, with no significant past medical or travel history, developed sepsis 2 days after undergoing debulking surgery for stage IIIc ovarian carcinoma. Blood cultures were positive for Gram-negative bacilli and the organisms identified as Enterobacter spp. with blaIMP MBL (Verigene). Antimicrobial susceptibility testing demonstrated high-level resistance to all penicillins, ureidopenicillins, cephalosporins, and β-lactam/inhibitor antibiotics, and susceptibility to colistin, tigecycline, and monobactams. Results Further testing using micro-broth dilution, BD phoenix, and Etest, demonstrated susceptible MICs to meropenem and imipenem, with intermediate to resistant MICs to ertapenem. The patient was treated with a combination therapy of amikacin, aztreonam, and ceftazidime-avibactam and responded clinically. Per standard protocol, the organism was sent to WI Laboratory of Hygiene for further characterization. Phenotypic testing using the modified carbapenem inactivation test (mCIM) was positive, indicating the presence of a carbapenemase; however, results using Xpert CarbaR (Cepheid) were negative. Subsequent sequencing of the isolate confirmed the presence of blaIMP-13. Conclusion This was an important case for several reasons. First, blaIMP-13 is historically reported in Pseudomonas aeruginosa. Indeed, this was the first report of Enterobacteriaceae harboring blaIMP in WI. Second, it had unique susceptibility pattern to carbapenems and was not detected by the CarbaR. Third, these data demonstrate clinical success in treating an MBL CPO with a combination anti-microbial regimen, based on an understanding of resistance mechanisms involved. This report calls for more vigilant screening for CPO using both phenotypic and genotypic methods. Disclosures N. Ledeboer, Luminex: Consultant, Consulting fee.

scholarly journals High-level resistance to isoniazid and ethionamide in multidrug-resistant Mycobacterium tuberculosis of the Lisboa family is associated with inhA double mutations

2013 ◽  
Vol 68 (8) ◽  
pp. 1728-1732 ◽  
Author(s):  
Diana Machado ◽  
João Perdigão ◽  
Jorge Ramos ◽  
Isabel Couto ◽  
Isabel Portugal ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
High Level ◽  
Level Resistance

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.

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