scholarly journals Emergence of clonally related multidrug resistant Haemophilus influenzae with penicillin-binding protein 3-mediated resistance to extended-spectrum cephalosporins, Norway, 2006 to 2013

2014 ◽  
Vol 19 (49) ◽  
Author(s):  
D Skaare ◽  
I L Anthonisen ◽  
G Kahlmeter ◽  
E Matuschek ◽  
O B Natås ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Binding Protein ◽  
Empiric Therapy ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Blood Isolate ◽  
Extended Spectrum ◽  
High Level

Resistance to cephalosporins in Haemophilus influenzae is usually caused by characteristic alterations in penicillin-binding protein 3 (PBP3), encoded by the ftsI gene. Resistance to extended-spectrum cephalosporins is associated with high-level PBP3-mediated resistance (high-rPBP3), defined by the second stage S385T substitution in addition to a first stage substitution (R517H or N526K). The third stage L389F substitution is present in some high-rPBP3 strains. High-rPBP3 H. influenzae are considered rare outside Japan and Korea. In this study, 30 high-rPBP3 isolates from Norway, collected between 2006 and 2013, were examined by serotyping, multilocus sequence typing (MLST), ftsI sequencing, detection of beta-lactamase genes and minimum inhibitory concentration (MIC) determination. MICs were interpreted according to clinical breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Respiratory isolates predominated (proportion: 24/30). The 30 isolates included one serotype f isolate, while the remaining 29 lacked polysaccharide capsule genes. Resistance to extended-spectrum cephalosporins (cefixime, 29 isolates/30 isolates; cefepime, 28/30; cefotaxime, 26 /30; ceftaroline, 26/30; ceftriaxone, 14/30), beta-lactamase production (11/30) and co-resistance to non-beta-lactams (trimethoprim-sulfamethoxazole, 13/30; tetracycline, 4/30; chloramphenicol, 4/30; ciprofloxacin, 3/30) was frequent. The N526K substitution in PBP3 was present in 23 of 30 isolates; these included a blood isolate which represents the first invasive S385T?+?N526K isolate reported from Europe. The L389F substitution, present in 16 of 30 isolates, coincided with higher beta-lactam MICs. Non-susceptibility to meropenem was frequent in S385T?+?L389F?+?N526K isolates (8/12). All 11 beta-lactamase positive isolates were TEM-1. Five clonal groups of two to 10 isolates with identical MLST-ftsI allelic profiles were observed, including the first reported high-rPBP3 clone with TEM-1 beta-lactamase and co-resistance to ciprofloxacin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole. Prior to this study, no multidrug resistant high-rPBP3 H. influenzae had been reported in Norway. Intensified surveillance of antimicrobial resistance is needed to guide empiric therapy.

scholarly journals A TEM-derived extended-spectrum beta-lactamase in Pseudomonas aeruginosa.

1996 ◽  
Vol 40 (11) ◽  
pp. 2488-2493 ◽  
Author(s):  
P Mugnier ◽  
P Dubrous ◽  
I Casin ◽  
G Arlet ◽  
E Collatz
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Strain ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Aminoglycoside Resistance ◽  
Double Mutation ◽  
Extended Spectrum Beta Lactamase ◽  
Beta Lactam Antibiotics ◽  
Extended Spectrum ◽  
High Level

A clinical strain of Pseudomonas aeruginosa, PAe1100, was found to be resistant to all antipseudomonal beta-lactam antibiotics and to aminoglycosides, including gentamicin, amikacin, and isepamicin. PAe1100 produced two beta-lactamases, TEM-2 (pI 5.6) and a novel, TEM-derived extended-spectrum beta-lactamase called TEM-42 (pI 5.8), susceptible to inhibition by clavulanate, sulbactam, and tazobactam. Both enzymes, as well as the aminoglycoside resistance which resulted from AAC(3)-IIa and AAC(6')-I production, were encoded by an 18-kb nonconjugative plasmid, pLRM1, that could be transferred to Escherichia coli by transformation. The gene coding for TEM-42 had four mutations that led to as many amino acid substitutions with respect to TEM-2: Val for Ala at position 42 (Ala42), Ser for Gly238, Lys for Glu240, and Met for Thr265 (Ambler numbering). The double mutation Ser for Gly238 and Lys for Glu240, which has so far only been described in SHV-type but not TEM-type enzymes, conferred concomitant high-level resistance to cefotaxime and ceftazidime. The novel, TEM-derived extended-spectrum beta-lactamase appears to be the first of its class to be described in P. aeruginosa.

scholarly journals Molecular characterization of extended-spectrum beta-lactamase producing Enterobacteriaceae in a Saudi Arabian tertiary hospital

2014 ◽  
Vol 8 (03) ◽  
pp. 282-288 ◽  
Author(s):  
Hoda Hassan ◽  
Baha Abdalhamid
Keyword(s):  
Tertiary Hospital ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
M Gene ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Vitek 2 ◽  
High Level

Introduction: The aim of this study was to determine the prevalence of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Proteus mirabilis (P. mirabilis). In addition, different methods for detection of these enzymes, including the newly introduced CHROMagar ESBL, were evaluated. Methodology: A total of 382 Enterobacteriaceae clinical isolates were obtained from King Fahad Specialist Hospital – Dammam, during 2011 and screened for production of ESBL using advanced expert system of Vitek 2, CHROMagar and ESBL-E-strips. PCR assay was used to detect blaTEM, blaSHV, and blaCTX-M genes. Susceptibility to a panel of antibiotics was determined. Results: The overall proportion of ESBL-producing enterobacterial isolates was 30.6%, which was higher in E. coli (35.8%) than in K. pneumoniae (25.7%). ESBL genotypes showed remarkable increase in the CTX-M (97.4%) compared to SHV (23.1%). The predominant ESBL was CTX-M- 15 (92.1 %). No TEM ESBL was detected in this study. The Vitek2 showed the highest sensitivity (100%), and the CHROMagar had the lowest specificity (97.3%) compared to the molecular method. All isolates were susceptible to imipenem and meropenem. Conclusions: This study confirms a high level of blaCTX-M positive ESBL isolates are circulating in the Eastern Province of Saudi Arabia. The trend of a multidrug-resistant profile associated with the recovery of the blaCTX-M gene is alarming.

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.

scholarly journals Characterization of Multidrug Resistant Extended-Spectrum Beta-Lactamase-ProducingEscherichia coliamong Uropathogens of Pediatrics in North of Iran

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Mohammad Sadegh Rezai ◽  
Ebrahim Salehifar ◽  
Alireza Rafiei ◽  
Taimour Langaee ◽  
Mohammadreza Rafati ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Beta Lactam Antibiotics ◽  
Extended Spectrum ◽  
Extended Spectrum Beta Lactamases ◽  
North Of Iran

Escherichia coliremains as one of the most important bacteria causing infections in pediatrics and producing extended-spectrum beta-lactamases (ESBLs) making them resistant to beta-lactam antibiotics. In this study we aimed to genotype ESBL-producingE. coliisolates from pediatric patients for ESBL genes and determine their association with antimicrobial resistance. One hundred of theE. coliisolates were initially considered ESBL producing based on their MIC results. These isolates were then tested by polymerase chain reaction (PCR) for the presence or absence ofCTX,TEM,SHV,GES, andVEBbeta-lactamase genes. About 30.5% of isolatedE. coliwas ESBL-producing strain. TheTEMgene was the most prevalent (49%) followed bySHV(44%),CTX(28%),VEB(8%), andGES(0%) genes. The ESBL-producingE. coliisolates were susceptible to carbapenems (66%) and amikacin (58%) and showed high resistance to cefixime (99%), colistin (82%), and ciprofloxacin (76%). In conclusion, carbapenems were the most effective antibiotics against ESBl-producingE. coliin urinary tract infection in North of Iran. The most prevalent gene is the TEM-type, but the other resistant genes and their antimicrobial resistance are on the rise.

scholarly journals Haemophilus influenzae with Non-Beta-Lactamase-Mediated Beta-Lactam Resistance: Easy To Find but Hard To Categorize

2015 ◽  
Vol 53 (11) ◽  
pp. 3589-3595 ◽  
Author(s):  
Dagfinn Skaare ◽  
Astrid Lia ◽  
Anja Hannisdal ◽  
Yngvar Tveten ◽  
Erika Matuschek ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Disk Diffusion ◽  
High Dose ◽  
Beta Lactamase ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Content Type ◽  
Severe Infections ◽  
Clinical Breakpoints

Haemophilus influenzaeis a major pathogen, and beta-lactams are first-line drugs. Resistance due to altered penicillin-binding protein 3 (rPBP3) is frequent, and susceptibility testing of such strains is challenging. A collection of 154 beta-lactamase-negative isolates with a large proportion of rPBP3 (67.5%) was used to evaluate and compare Etest (Haemophilustest medium [HTM]) and disk diffusion (EUCAST method) for categorization of susceptibility to aminopenicillins and cefuroxime, using MICs generated with broth (HTM) microdilution and clinical breakpoints from CLSI and EUCAST as the gold standards. In addition, the proficiency of nine disks in screening for the rPBP3 genotype (N526K positive) was evaluated. By Etest, both essential and categorical agreement were generally poor (<70%), with high very major errors (VME) (CLSI, 13.0%; EUCAST, 34.3%) and falsely susceptible rates (FSR) (CLSI, 87.0%; EUCAST, 88.3%) for ampicillin. Ampicillin (2 μg) with adjusted (+2 mm) zone breakpoints was superior to Etest for categorization of susceptibility to ampicillin (agreement, 74.0%; VME, 11.0%; FSR, 28.3%). Conversely, Etest was superior to 30 μg cefuroxime for categorization of susceptibility to cefuroxime (agreement, 57.1% versus 60.4%; VME, 2.6% versus 9.7%; FSR, 7.1% versus 26.8%). Benzylpenicillin (1 unit) (EUCAST screening disk) and cefuroxime (5 μg) identified rPBP3 isolates with highest accuracies (95.5% and 92.2%, respectively). In conclusion, disk screening reliably detects rPBP3H. influenzae, but false ampicillin susceptibility is frequent with routine methods. We suggest adding a comment recommending high-dose aminopenicillin therapy or the use of other agents for severe infections with screening-positive isolates that are susceptible to aminopenicillins by gradient or disk diffusion.

scholarly journals Coproduction of Extended Spectrum, AmpC and Metallo β- Lactamases in Pseudomonas aeruginosa Isolates from a Super Speciality Center

2021 ◽  
Vol 10 (10) ◽  
pp. 176-184
Author(s):  
Ashna Bhasin Poonam Loomba ◽  
Abha Sharma Bibhabati Mishra ◽  
Ashish Bajaj
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Diffusion Method ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Disk Diffusion Method ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum

Pseudomonas aeruginosa (P. aeruginosa) is one of the leading causes of hospital as well as community acquired infections. They’re strenuous to treat as most of isolates exhibit various degrees of beta- lactamase mediated resistance to majority of the beta-lactam antibiotics. Single isolate can express multiple β- lactamase enzymes, further limiting the treatment options. Therefore, this study was outlined to research the coexistence of various beta-lactamase enzymes in clinical isolates of P. aeruginosa. The aim of the study was to detect the co-prevalence of Extended Spectrum Beta lactmases (ESBL), AmpC and Metallo β-Lactamases (MBL) in Pseudomonas aeruginosa isolates from a superspeciality center. Fifty clinical isolates of P. aeruginosa were tested for the presence of AmpC beta-lactamase, extended spectrum beta- lactamase (ESBL) and metallo beta-lactamase (MBL) enzyme. Discernment of AmpC beta-lactamase was performed by disk antagonism while ESBL detection was done by the combined disk diffusion method as per Clinical and Laboratory Standards Institute (CLSI) guidelines and MBL were detected by the Imipenem EDTA disk potentiation test. Eleven of 50 (22%) isolates were confirmed to be positive for AmpC and Extended spectrum beta lactamases. Co-production of AmpC along side ESBL and MBL was reported in 12 % isolates. The study shows the high prevalence of multidrug resistant P. aeruginosa producing beta-lactamase enzymes of diverse mechanisms. Consequently, formulation of a correct antibiotic policy and taking measures to restrict the indiscriminative use of cephalosporins and carbapenems should be taken to mitigate the emergence of this multiple beta-lactamase producing pathogens.

scholarly journals Impact of different amino acid substitutions in penicillin-binding protein 3 on beta-lactam susceptibility in Haemophilus influenzae

2019 ◽  
Author(s):  
Josiane Reist ◽  
Janina Linnik ◽  
Urs Schibli ◽  
Adrian Egli ◽  
Vladimira Hinić
Keyword(s):  
Amino Acid ◽  
Haemophilus Influenzae ◽  
Binding Site ◽  
Amino Acid Substitutions ◽  
Beta Lactamase ◽  
Penicillin Binding Protein ◽  
Wild Type ◽  
Beta Lactam ◽  
Group I ◽  
Group Ii

AbstractPurposeBeta-lactam antibiotics in combination with a beta-lactamase inhibitor are the first-line treatment option for Haemophilus influenzae infections. However, beta-lactamase-independent resistance to beta-lactams is increasing. This resistance mechanism has been linked to amino acid substitutions in the penicillin-binding protein 3 (PBP3), but how these substitutions lead to decreased binding affinities to certain beta-lactam antimicrobials remains unknown.MethodsWe investigated beta-lactam resistance and amino acid substitutions in PBP3 from fifty-three clinical isolates of H. influenzae collected in Switzerland from January to April 2016. Identification of key polymorphisms and classification of strains into PBP3 amino acid substitution groups I, II, and M was done as previously described. Based on published PBP3 crystal structures, we investigated how the group-specific amino acid substitutions impact the beta-lactam binding site.ResultsWe found that both group I and group II substitutions disrupt the Asn526-Arg517-Glu324 interaction, which might affect the configuration of the beta-lactam binding site. Amino acid substitutions in group M strains are distant from the active site and have most likely no impact on beta-lactam binding. In accordance with this observation, all group M strains showed minimal inhibitory concentrations (MICs) within the susceptible range for all tested antimicrobials and were not significantly different to the wild type (beta-lactamase producers excluded), while group I and group II strains showed significantly higher MICs for beta-lactam antimicrobials.ConclusionGroup M strains are phenotypically equal to the wild type, while amino acid substitutions of group I and group II might affect the beta-lactam binding through a common mechanism by disrupting the Asn526-Arg517-Glu324 interaction.

Molecular Characterization of Methicillin Resistant and Extended Spectrum β-Lactamase Staphylococcus aureus Isolated from Burn Patients

2020 ◽  
pp. 145-151
Author(s):  
Shawnm Ahmed Aziz
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Vancomycin Resistance ◽  
World Health ◽  
Molecular Technique ◽  
Burn Patients ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Extended Spectrum Beta Lactamase ◽  
Extended Spectrum

Antibiotic resistance has become a major world health challenge and has limited the ability of physician's treatment. Staphylococcus aureus the most notorious pathogens causes morbidity and mortality especially in burn patients. However, Staphylococcus aureus rapidly acquired resistance to multiple antibiotics. Vancomycin, a glycopeptide antibiotic remains a drug of choice for treatment of severe Methicillin Resistance S. aureus infections. This study aimed to detect the emergence of beta-lactam and glycopeptide resistance genes. 50 clinical specimens of S. aureus collected from burn patients in burn and plastic surgery units in Sulaimani-Iraq city. All specimens were confirmed to be positive for S. aureus. All the isolates were assessed for their susceptibility to different antibiotics depending on NCCL standards, followed by Extended Spectrum Beta Lactamase detection by double disk diffusion synergy test. The production of β- lactamases was evaluated in the isolated strains by several routine methods and polymerase chain reaction. Among the isolates 94% were Methicillin resistance and 34.28% were Extended Spectrum Beta Lactamase producer. PCR based molecular technique was done for the bla genes related to β- lactamase enzymes by the specific primers, as well as genes which related to reduced sensitivity to Vancomycin were detected. The results indicated that all isolated showed the PBP1, PBP2, PBP3, PBP4, trfA and trfB, graSR, vraS except the vraR gene and the prolonged therapy of Methicillin resistance infection with teicoplanin have been associated with progress of resistance and the rise of tecoplanin resistance may be a prologue to evolving Vancomycin resistance. In conclusion, beta-lactam over taking can rise Vancomycin- Intermediate S. aureus strains leading to appearance of Vancomycin resistance although the treatment of Vancomycin resistant infections is challenging.

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