scholarly journals PRO: Carbapenems should be used for ALL infections caused by ceftriaxone-resistant Enterobacterales

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
David L Paterson ◽  
Burcu Isler ◽  
Patrick N A Harris
Keyword(s):  
Antibiotic Resistance ◽  
Observational Studies ◽  
Randomized Trials ◽  
Antibiotic Resistance Genes ◽  
Definitive Treatment ◽  
In Vitro Activity ◽  
Genes Encoding ◽  
Amoxicillin Clavulanate ◽  
Trial Outcomes

Abstract Ceftriaxone resistance in the Enterobacterales is typically the result of production of ESBLs or AmpC β-lactamases. The genes encoding these enzymes are often co-located with other antibiotic resistance genes leading to resistance to aminoglycosides, quinolones and trimethoprim/sulfamethoxazole. Carbapenems are stable to ESBLs and AmpC giving them reliable in vitro activity against producers of these β-lactamases. In contrast, piperacillin/tazobactam and amoxicillin/clavulanate are compromised by co-production of OXA-1, which is not inhibited by tazobactam or clavulanate. These in vitro findings provide an explanation for the MERINO trial outcomes, where 3.7% (7/191) randomized to meropenem died compared with 12.3% (23/187) randomized to piperacillin/tazobactam as definitive treatment of bloodstream infection due to ceftriaxone-resistant organisms. No randomized trials have yet put cefepime and carbapenems head to head, but some observational studies have shown worse outcomes with cefepime. We argue that carbapenems are the antibiotics of choice for ceftriaxone-resistant Enterobacterales.

scholarly journals Characterization of antibiotic resistance genes in the species of the rumen microbiota

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yasmin Neves Vieira Sabino ◽  
Mateus Ferreira Santana ◽  
Linda Boniface Oyama ◽  
Fernanda Godoy Santos ◽  
Ana Júlia Silva Moreira ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Animal Health ◽  
Antibiotic Resistance Genes ◽  
Tetracycline Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Ruminal Bacteria ◽  
Genes Encoding

AbstractInfections caused by multidrug resistant bacteria represent a therapeutic challenge both in clinical settings and in livestock production, but the prevalence of antibiotic resistance genes among the species of bacteria that colonize the gastrointestinal tract of ruminants is not well characterized. Here, we investigate the resistome of 435 ruminal microbial genomes in silico and confirm representative phenotypes in vitro. We find a high abundance of genes encoding tetracycline resistance and evidence that the tet(W) gene is under positive selective pressure. Our findings reveal that tet(W) is located in a novel integrative and conjugative element in several ruminal bacterial genomes. Analyses of rumen microbial metatranscriptomes confirm the expression of the most abundant antibiotic resistance genes. Our data provide insight into antibiotic resistange gene profiles of the main species of ruminal bacteria and reveal the potential role of mobile genetic elements in shaping the resistome of the rumen microbiome, with implications for human and animal health.

scholarly journals Inhibitory Impact of Bifidobacteria on the Transfer of β-Lactam Resistance among Enterobacteriaceae in the Gnotobiotic Mouse Digestive Tract

2006 ◽  
Vol 73 (3) ◽  
pp. 855-860 ◽  
Author(s):  
C. Moubareck ◽  
M. Lecso ◽  
E. Pinloche ◽  
M. J. Butel ◽  
F. Doucet-Populaire
Keyword(s):  
Antibiotic Resistance ◽  
Digestive Tract ◽  
Resistance Genes ◽  
Bifidobacterium Longum ◽  
Antibiotic Resistance Genes ◽  
Inhibitory Effect ◽  
Bifidobacterium Bifidum ◽  
Genes Encoding ◽  
Fourth Experiment

ABSTRACT While looking for new means to limit the dissemination of antibiotic resistance, we evaluated the role of potentially probiotic bifidobacteria on the transfer of resistance genes between enterobacteria. Transfers of bla genes encoding extended-spectrum β-lactamases (SHV-5 and CTX-M-15) were studied in the absence or presence of bifidobacteria. In vitro, transfer frequencies of these bla genes decreased significantly in the presence of three of five tested strains, i.e., Bifidobacterium longum CUETM-89-215, Bifidobacterium bifidum CIP-56.7T, and Bifidobacterium pseudocatenulatum CIP-104168T. Four transfer experiments were conducted in the digestive tract of gnotobiotic mice, the first three observing the effect of B. longum CUETM-89-215, B. bifidum CIP-56.7T, and B. pseudocatenulatum CIP-104168T on bla SHV-5 transfer and the fourth experiment studying the effect of B. bifidum CIP-56.7T on bla CTX-M-15 transfer. These experiments revealed significant decreases in the transconjugant levels (up to 3 logs) in mice having received B. bifidum CIP-56.7T or B. pseudocatenulatum CIP-104168T compared to control mice. Bifidobacteria appear to have an inhibitory impact on the transfer of antibiotic resistance genes. The inhibitory effect is associated to specific bifidobacterial strains and may be related to the production of thermostable metabolites by these strains.

scholarly journals Cefepime/sulbactam as an enhanced antimicrobial combination therapy for the treatment of MDR Gram-negative infections

2019 ◽  
Author(s):  
David W Wareham ◽  
M H F Abdul Momin ◽  
Lynette M Phee ◽  
Michael Hornsey ◽  
Joseph F Standing
Keyword(s):  
Fixed Ratio ◽  
Vitro Activity ◽  
Definitive Treatment ◽  
High Dose ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Pharmacodynamic Modelling ◽  
Carbapenem Resistant ◽  
Combination Regimens

Abstract Background β-Lactam (BL)/β-lactamase inhibitor (BLI) combinations are widely used for the treatment of Gram-negative infections. Cefepime has not been widely studied in combination with BLIs. Sulbactam, with dual BL/BLI activity, has been partnered with very few BLs. We investigated the potential of cefepime/sulbactam as an unorthodox BL/BLI combination against MDR Gram-negative bacteria. Methods In vitro activity of cefepime/sulbactam (1:1, 1:2 and 2:1) was assessed against 157 strains. Monte Carlo simulation was used to predict the PTA with a number of simulated cefepime combination regimens, modelled across putative cefepime/sulbactam breakpoints (≤16/≤0.25 mg/L). Results Cefepime/sulbactam was more active (MIC50/MIC90 8/8–64/128 mg/L) compared with either drug alone (MIC50/MIC90 128 to >256 mg/L). Activity was enhanced when sulbactam was added at 1:1 or 1:2 (P < 0.05). Reduction in MIC was most notable against Acinetobacter baumannii and Enterobacterales (MIC 8/8–32/64 mg/L). Pharmacokinetic/pharmacodynamic modelling highlighted that up to 48% of all isolates and 73% of carbapenem-resistant A. baumannii with a cefepime/sulbactam MIC of ≤16/≤8 mg/L may be treatable with a high-dose, fixed-ratio (1:1 or 1:2) combination of cefepime/sulbactam. Conclusions Cefepime/sulbactam (1:1 or 1:2) displays enhanced in vitro activity versus MDR Gram-negative pathogens. It could be a potential alternative to existing BL/BLI combinations for isolates with a cefepime/sulbactam MIC of 16/8 mg/L either as a definitive treatment or as a carbapenem-sparing option.

scholarly journals Characterization of a Multiresistant Mosaic Plasmid from a Fish Farm Sediment Exiguobacterium sp. Isolate Reveals Aggregation of Functional Clinic-Associated Antibiotic Resistance Genes

2013 ◽  
Vol 80 (4) ◽  
pp. 1482-1488 ◽  
Author(s):  
Jing Yang ◽  
Chao Wang ◽  
Jinyu Wu ◽  
Li Liu ◽  
Gang Zhang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Mobile Elements ◽  
Fish Farms ◽  
Significant Similarity ◽  
Content Type ◽  
Genes Encoding ◽  
The Mean

ABSTRACTThe genusExiguobacteriumcan adapt readily to, and survive in, diverse environments. Our study demonstrated thatExiguobacteriumsp. strain S3-2, isolated from marine sediment, is resistant to five antibiotics. The plasmid pMC1 in this strain carries seven putative resistance genes. We functionally characterized these resistance genes inEscherichia coli, and genes encoding dihydrofolate reductase and macrolide phosphotransferase were considered novel resistance genes based on their low similarities to known resistance genes. The plasmid G+C content distribution was highly heterogeneous. Only the G+C content of one block, which shared significant similarity with a plasmid fromExiguobacterium arabatum, fit well with the mean G+C content of the host. The remainder of the plasmid was composed of mobile elements with a markedly lower G+C ratio than the host. Interestingly, five mobile elements located on pMC1 showed significant similarities to sequences found in pathogens. Our data provided an example of the link between resistance genes in strains from the environment and the clinic and revealed the aggregation of antibiotic resistance genes in bacteria isolated from fish farms.

scholarly journals Studies on Bd0934 and Bd3507, Two Secreted Nucleases from Bdellovibrio bacteriovorus, Reveal Sequential Release of Nucleases during the Predatory Cycle

2020 ◽  
Vol 202 (18) ◽  
Author(s):  
Ewa Bukowska-Faniband ◽  
Tilde Andersson ◽  
Rolf Lood
Keyword(s):  
Antibiotic Resistance ◽  
Life Cycle ◽  
Antibiotic Resistance Genes ◽  
Human Pathogens ◽  
Temporal Expression ◽  
Bdellovibrio Bacteriovorus ◽  
Exogenous Dna ◽  
Content Type ◽  
Genes Encoding ◽  
Predatory Bacteria

ABSTRACT Bdellovibrio bacteriovorus is an obligate predatory bacterium that invades and kills a broad range of Gram-negative prey cells, including human pathogens. Its potential therapeutic application has been the subject of increased research interest in recent years. However, an improved understanding of the fundamental molecular aspects of the predatory life cycle is crucial for developing this bacterium as a “living antibiotic.” During intracellular growth, B. bacteriovorus secretes an arsenal of hydrolases, which digest the content of the host cell to provide growth nutrients for the predator, e.g., prey DNA is completely degraded by the nucleases. Here, we have, on a genetic and molecular level, characterized two secreted DNases from B. bacteriovorus, Bd0934 and Bd3507, and determined the temporal expression profile of other putative secreted nucleases. We conclude that Bd0934 and Bd3507 are likely a part of the predatosome but are not essential for the predation, host-independent growth, prey biofilm degradation, and self-biofilm formation. The detailed temporal expression analysis of genes encoding secreted nucleases revealed that these enzymes are produced in a sequential orchestrated manner. This work contributes to our understanding of the sequential breakdown of the prey nucleic acid by the nucleases secreted during the predatory life cycle of B. bacteriovorus. IMPORTANCE Antibiotic resistance is a major global concern with few available new means to combat it. From a therapeutic perspective, predatory bacteria constitute an interesting tool. They not only eliminate the pathogen but also reduce the overall pool of antibiotic resistance genes through secretion of nucleases and complete degradation of exogenous DNA. Molecular knowledge of how these secreted DNases act will give us further insight into how antibiotic resistance, and the spread thereof, can be limited through the action of predatory bacteria.

scholarly journals Comparison of Culture- and Quantitative PCR-Based Indicators of Antibiotic Resistance in Wastewater, Recycled Water, and Tap Water

2019 ◽  
Vol 16 (21) ◽  
pp. 4217 ◽  
Author(s):  
Jaqueline Rocha ◽  
Telma Fernandes ◽  
Maria V. Riquelme ◽  
Ni Zhu ◽  
Amy Pruden ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Tap Water ◽  
Quantitative Polymerase Chain Reaction ◽  
Antibiotic Resistance Genes ◽  
Fecal Coliforms ◽  
Future Application ◽  
Strongly Correlated ◽  
Recycled Water ◽  
The Us ◽  
Genes Encoding

Standardized methods are needed to support monitoring of antibiotic resistance in environmental samples. Culture-based methods target species of human-health relevance, while the direct quantification of antibiotic resistance genes (ARGs) measures the antibiotic resistance potential in the microbial community. This study compared measurements of tetracycline-, sulphonamide-, and cefotaxime-resistant presumptive total and fecal coliforms and presumptive enterococci versus a suite of ARGs quantified by quantitative polymerase chain reaction (qPCR) across waste-, recycled-, tap-, and freshwater. Cross-laboratory comparison of results involved measurements on samples collected and analysed in the US and Portugal. The same DNA extracts analysed in the US and Portugal produced comparable qPCR results (variation <28%), except for blaOXA-1 gene (0%–57%). Presumptive total and fecal coliforms and cefotaxime-resistant total coliforms strongly correlated with blaCTX-M and intI1 (0.725 ≤ R2 ≤ 0.762; p < 0.0001). Further, presumptive total and fecal coliforms correlated with the Escherichia coli-specific biomarkers, gadAB, and uidA, suggesting that both methods captured fecal-sourced bacteria. The genes encoding resistance to sulphonamides (sul1 and sul2) were the most abundant, followed by genes encoding resistance to tetracyclines (tet(A) and tet(O)) and β-lactams (blaOXA-1 and, blaCTX-M), which was in agreement with the culture-based enumerations. The findings can help inform future application of methods being considered for international antibiotic resistance surveillance in the environment.

scholarly journals Diagnostic Microbiology: Present Status and Future Prospect

2017 ◽  
Vol 2 (2) ◽  
pp. 42-47
Author(s):  
Shahanara Begum ◽  
Md. Abdullah Yusuf ◽  
Bhuiyan Mohammad Mahtab Uddin
Keyword(s):  
Infectious Disease ◽  
Mass Spectrometry ◽  
Antibiotic Resistance ◽  
Historical Perspective ◽  
Future Prospect ◽  
Antibiotic Resistance Genes ◽  
Require Time ◽  
Prior Use ◽  
Diagnostic Microbiology

Diagnostic Microbiology is the tool that makes it possible to identify the exact pathogens of infectious diseases and the most optimal therapy at the level of individual patients. Conventional methods require time to grow the microbes in vitro under specific conditions and not all microbes can easily be cultured. This is followed by biochemical methods for identification which further makes the process lengthy. Transport of the specimens under less than ideal conditions, prior use of antibiotics and small number of organisms are among the factors that render culture-based methods less reliable. Newer methods depend on amplification of nucleic acids followed by use of probes for identification. This mitigates the need for higher microbial load, presence of metabolically active viable organisms and shortens the time. These methods can be used to detect antibiotic resistance genes directly from the specimen and help direct targeted therapy with efficacy. Since these methods will not fulfill all the diagnostic needs, a second approach is being used to shorten the time to identification after the organism has already grown. Mass spectrometry and bioinformatics are the tools making this possible. This review gives a historical perspective on diagnostic microbiology, discusses the pitfalls of current methodology and provides an overview of newer and future methods.Bangladesh Journal of Infectious Disease 2015;2(2):42-47

scholarly journals 598. In Vitro Activity of Aztreonam in Combination with Ceftazidime–Avibactam, Amoxicillin–Clavulanate, and Piperacillin–Tazobactam vs. NDM-Producing Escherichia coli and Klebsiella pneumoniae Clinical Isolates

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S281-S281
Author(s):  
Andrew Walkty ◽  
James Karlowsky
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Vitro Activity ◽  
Clinical Isolates ◽  
Disk Diffusion ◽  
In Vitro Activity ◽  
Zone Diameter ◽  
Amoxicillin Clavulanate ◽  
Lactamase Inhibitor

Abstract Background There are limited options available for the treatment of infections caused by Enterobacteriaceae that produce an NDM metallo-β-lactamase. The purpose of this study was to compare the in vitro activity of aztreonam in combination with three different β-lactam/β-lactamase inhibitors (ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin–tazobactam) vs. NDM-positive Enterobacteriaceae clinical isolates. Methods Seven Escherichia coli and three Klebsiella pneumoniae clinical isolates (all NDM-positive by PCR) were included in this study. The in vitro activities of ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin–tazobactam, and aztreonam were determined by disk diffusion as described by CLSI. For synergy testing, disks containing a β-lactamase inhibitor (ceftazidime–avibactam, amoxicillin-clavulanate, piperacillin tazobactam) were applied to Mueller–Hinton agar plates inoculated with the test organisms, and the plates were incubated for 1 hour. The disks were then removed and aztreonam disks were dropped on the previous disk sites. The plates were then incubated as per standard CLSI recommendations for disk diffusion testing. Results All ten isolates demonstrated phenotypic resistance to aztreonam, amoxicillin-clavulanate, and piperacillin–tazobactam, and eight were resistant to ceftazidime–avibactam (CLSI breakpoints). The zone diameter observed for aztreonam in combination with ceftazidime–avibactam was greater than for either antimicrobial on its own for nine isolates. Seven isolates (70%) had susceptibility to aztreonam restored (zone diameter ≥21 mm) in the presence of avibactam. Aztreonam in combination with amoxicillin-clavulanate demonstrated in increase in zone diameter for all isolates relative to the zone for each antimicrobial alone, but only two (20%) had aztreonam susceptibility restored. Aztreonam susceptibility was not restored for any of the isolates in combination with piperacillin–tazobactam. Conclusion Of the three β-lactam/β-lactamase inhibitor-aztreonam combinations evaluated, ceftazidime–avibactam plus aztreonam demonstrated the greatest in vitro activity vs. NDM-producing Enterobacteriaceae. Disclosures All authors: No reported disclosures.

scholarly journals Removal of Antibiotic Resistance Gene-Carrying Plasmids from Lactobacillus reuteri ATCC 55730 and Characterization of the Resulting Daughter Strain, L. reuteri DSM 17938

2008 ◽  
Vol 74 (19) ◽  
pp. 6032-6040 ◽  
Author(s):  
Anna Rosander ◽  
Eamonn Connolly ◽  
Stefan Roos
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Lactobacillus Reuteri ◽  
Antibiotic Resistance Gene ◽  
Genetically Modify ◽  
Antibiotic Resistance Genes ◽  
Probiotic Strain ◽  
Probiotic Properties ◽  
Food Borne

ABSTRACT The spread of antibiotic resistance in pathogens is primarily a consequence of the indiscriminate use of antibiotics, but there is concern that food-borne lactic acid bacteria may act as reservoirs of antibiotic resistance genes when distributed in large doses to the gastrointestinal tract. Lactobacillus reuteri ATCC 55730 is a commercially available probiotic strain which has been found to harbor potentially transferable resistance genes. The aims of this study were to define the location and nature of β-lactam, tetracycline, and lincosamide resistance determinants and, if they were found to be acquired, attempt to remove them from the strain by methods that do not genetically modify the organism before subsequently testing whether the probiotic characteristics were retained. No known β-lactam resistance genes was found, but penicillin-binding proteins from ATCC 55730, two additional resistant strains, and three sensitive strains of L. reuteri were sequenced and comparatively analyzed. The β-lactam resistance in ATCC 55730 is probably caused by a number of alterations in the corresponding genes and can be regarded as not transferable. The strain was found to harbor two plasmids carrying tet(W) tetracycline and lnu(A) lincosamide resistance genes, respectively. A new daughter strain, L. reuteri DSM 17938, was derived from ATCC 55730 by removal of the two plasmids, and it was shown to have lost the resistances associated with them. Direct comparison of the parent and daughter strains for a series of in vitro properties and in a human clinical trial confirmed the retained probiotic properties of the daughter strain.

Sign in / Sign up

Export Citation Format

Share Document