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Microorganisms Feb 2023An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host...
An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies.
PubMed: 36838498
DOI: 10.3390/microorganisms11020533 -
Frontiers in Cellular and Infection... 2022The rapid emergence of carbapenem resistant (CRAB) has resulted in an alarming situation worldwide. Realizing the dearth of literature on susceptibility of CRAB in...
BACKGROUND
The rapid emergence of carbapenem resistant (CRAB) has resulted in an alarming situation worldwide. Realizing the dearth of literature on susceptibility of CRAB in genetic context in the developing region, this study was performed to determine the susceptibility profile against standard drugs/combinations and the association of drug synergy with the prevalent molecular determinants.
METHODS AND FINDINGS
A total of 356 clinical isolates of were studied. Confirmation of the isolates was done by amplifying and ITS region genes. Susceptibility against standard drugs was tested by Kirby Bauer disc diffusion. Minimum inhibitory concentration (MIC), MIC and MIC values against imipenem, meropenem, doripenem, ampicillin/sulbactam, minocycline, amikacin, polymyxin B, colistin and tigecycline was tested as per guidelines. Genes encoding enzymes classes A ( , , , ), B ( , , ) and D ( and ) were detected by multiplex polymerase chain reaction. Synergy against meropenem-sulbactam and meropenem-colistin combinations was done by checkerboard MIC method. Correlation of drug synergy and carbapenemase encoding genes was statistically analyzed.
RESULTS
Of the total, resistance above 90% was noted against gentamicin, ciprofloxacin, levofloxacin, ceftazidime, cefepime, ceftriaxone, cotrimoxazole and piperacillin/tazobactam. By MIC, resistance rates from highest to lowest was seen against imipenem 89.04% (n=317), amikacin 80.33% (n=286), meropenem 79.49% (n=283), doripenem 77.80% (n=277), ampicillin/sulbactam 71.62% (n=255), tigecycline 55.61% (n=198), minocycline 14.04% (n=50), polymyxin B 10.11% (n=36), and colistin 2.52% (n=9). CRAB was 317 (89.04%), 81.46% (n=290) were multidrug resistant and 13.48% (n=48) were extensively drug resistant. All the CRAB isolates harboured gene (100%) and 94% (n=298) gene. The gene was most prevalent 70.03% (n=222) followed by 59.62% (n=189). Majority (87.69%, 278) were co-producers of classes D and B carbapenemases, with and being the commonest. Synergy with meropenem-sulbactam and meropenem-colistin was 47% and 57% respectively. Reduced synergy (= <0.0001) was noted for those harbouring +blawith gene alone or co-producers.
CONCLUSION
Presence of gene was a significant cause of synergy loss in meropenem-sulbactam and meropenem-colistin. In endemic regions, tigecycline, minocycline and polymyxins could be viable options against CRAB isolates with more than one carbapenemase encoding genes.
Topics: Humans; Acinetobacter baumannii; Acinetobacter Infections; Amikacin; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Doripenem; Imipenem; Meropenem; Minocycline; Polymyxin B; Sulbactam; Tigecycline; beta-Lactam Resistance
PubMed: 36683677
DOI: 10.3389/fcimb.2022.1068840 -
ASAIO Journal (American Society For... Jan 2023Limited data exist to guide antimicrobial therapy commonly prescribed to patients undergoing extracorporeal membrane oxygenation (ECMO). This study aimed to describe the...
Limited data exist to guide antimicrobial therapy commonly prescribed to patients undergoing extracorporeal membrane oxygenation (ECMO). This study aimed to describe the kinetics of the cefazolin, doripenem, daptomycin, and levofloxacin in heparin-coated and Xcoating ECMO circuits. Circuits were primed with bovine whole blood and maintained at a physiological pH and temperature for 24 h. Each antimicrobial agent was added to the whole blood before priming. Equivalent doses of these drugs were added to glass jars containing fresh bovine whole blood as a control. Serial blood samples were collected from the ECMO circuits and controls over 24 h, and drug concentrations were quantified using validated assays. The concentrations of cefazolin, doripenem, daptomycin, and levofloxacin did not decrease significantly over 24 h. Collectively, these antimicrobial agents can be administered without the need to consider sequestration when using either heparin-coated or Xcoating circuits.
Topics: Humans; Animals; Cattle; Extracorporeal Membrane Oxygenation; Heparin; Daptomycin; Doripenem; Cefazolin; Levofloxacin; Anti-Infective Agents
PubMed: 36583776
DOI: 10.1097/MAT.0000000000001842 -
The Yale Journal of Biology and Medicine Dec 2022: Antibiotic resistance in cystic fibrosis (CF) is a well-known phenomenon. However, the comprehensive epidemiological impact of antibiotic resistance in CF is not... (Meta-Analysis)
Meta-Analysis Review
: Antibiotic resistance in cystic fibrosis (CF) is a well-known phenomenon. However, the comprehensive epidemiological impact of antibiotic resistance in CF is not clearly documented. So, this meta-analysis evaluated the proportion rates of carbapenem resistance (imipenem, meropenem, and doripenem) in CF based on publication date (1979-2000, 2001-2010, and 2011-2021), continents, pathogens, and antimicrobial susceptibility testing (AST). : We searched studies in PubMed, Scopus, and Web of Science (until April 2021). Statistical analyses were conducted using STATA software (version 14.0). : The 110 studies included in the analysis were performed in 25 countries and investigated 13,324 pathogens associated with CF. The overall proportion of imipenem, meropenem, and doripenem resistance in CF were 43% (95% CI 36-49), 48% (95% CI 40-57), 28% (95% CI 23-33), and 45% (95% CI 32-59), respectively. Our meta-analysis showed that trends of imipenem, meropenem, and doripenem-resistance had gradual decreases over time (1979-2021). This could be due to the limited clinical effectiveness of these antibiotics to treat CF cases over time. Among the opportunistic pathogens associated with CF, the highest carbapenem resistance rates were shown in , spp., , and . The highest and lowest carbapenem resistance rates among in CF patients were shown against meropenem (23%) and doripenem (39%). : We showed that trends of carbapenem resistance had decreased over time (1979-2021). This could be due to the limited clinical effectiveness of these antibiotics to treat CF cases over time. Plans should be directed to fight biofilm-associated infections and prevent the emergence of mutational resistance. Systematic surveillance for carbapenemase-producing pathogens in CF by molecular surveillance is necessitated.
Topics: Humans; Meropenem; Doripenem; Carbapenems; Cystic Fibrosis; Microbial Sensitivity Tests; Anti-Bacterial Agents; Imipenem; Pseudomonas aeruginosa
PubMed: 36568834
DOI: No ID Found -
Journal of Clinical Laboratory Analysis Jan 2023Since severe infections frequently cause acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is often initiated for regulation of inflammatory...
UHPLC-MS/MS method for simultaneous quantification of doripenem, meropenem, ciprofloxacin, levofloxacin, pazufloxacin, linezolid, and tedizolid in filtrate during continuous renal replacement therapy.
BACKGROUND
Since severe infections frequently cause acute kidney injury (AKI), continuous renal replacement therapy (CRRT) is often initiated for regulation of inflammatory mediators and renal support. Thus, it is necessary to decide the antibiotic dosage considering the CRRT clearance in addition to residual renal function. Some of the hemofilters used in CRRT are known to adsorb antibiotics, and clearance of antibiotics may differ depending on the adsorptive characteristics of hemofilters. Although assay systems for blood and CRRT filtrate concentrations are required, no method for measuring antibiotics concentrations in filtrate has been reported. We developed a UHPLC-MS/MS method for simultaneous quantification of antibiotics commonly used in ICU, comprising carbapenems [doripenem (DRPM) and meropenem (MEPM)], quinolones [ciprofloxacin (CPFX), levofloxacin (LVFX) and pazufloxacin (PZFX)] and anti-MRSA agents [linezolid (LZD), and tedizolid (TZD)] in CRRT filtrate samples.
METHODS
Filtrate samples were pretreated by protein precipitation. The analytes were separated with an ACQUITY UHPLC CSH C18 column under a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid and 2 mM ammonium formate.
RESULTS
The method showed good linearity over wide ranges. Within-batch and batch-to-batch accuracy and precision for each drug fulfilled the criteria of the US Food and Drug Administration guidance. The recovery rate was more than 87.20%. Matrix effect ranged from 99.57% to 115.60%. Recovery rate and matrix effect did not differ remarkably between quality control samples at different concentrations.
CONCLUSION
This is the first report of a simultaneous quantification method of multiple antibiotics in filtrate of CRRT circuit.
Topics: Humans; Meropenem; Linezolid; Levofloxacin; Doripenem; Ciprofloxacin; Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Continuous Renal Replacement Therapy; Anti-Bacterial Agents
PubMed: 36525363
DOI: 10.1002/jcla.24815 -
BMC Microbiology Dec 2022Acinetobacter baumannii (A. baumannii) is one of the members of ESKAPE bacteria which is considered multidrug resistant globally. The objective of this study is to...
Acinetobacter baumannii (A. baumannii) is one of the members of ESKAPE bacteria which is considered multidrug resistant globally. The objective of this study is to determine the protein docking of different antibiotic resistance gene (ARGs) in A. baumannii. In silico analysis of antibiotic resistance genes against carbapenem are the blaOXA-51, blaOXA-23, blaOXA-58, blaOXA-24, blaOXA-143, NMD-1 and IMP-1 in A. baumannii. The doripenem, imipenem and meropenem were docked to blaOXA-51 and blaOXA-23 using PyRx. The top docking energy was -5.5 kcal/mol by imipenem and doripenem and meropenem showed a binding score of -5. 2 kcal/mol each and blaOXA-23 energy was -4.3 kcal/mol by imipenem and meropenem showed a binding score of -2.3 kcal/mol, while doripenem showed the binding score of -3.4 kcal/mol. Similarly, doripenem imipenem and meropenem were docked to blaOXA-58, IMP-1, Rec A and blaOXA-143, with docking energy was -8.8 kcal/mol by doripenem and meropenem each while imipenem showed a binding score of -4.2 kcal/mol and with IMP-1 demonstrated their binding energies. was -5.7 kcal/mol by meropenem and doripenem showed a binding score of -5.3 kcal/mol, while imipenem showed a binding score of -4.5 kcal/mol. And docking energy was -4.9 kcal/mol by imipenem and meropenem showed binding energy of -3.6 kcal/mol each while doripenem showed a binding score of -3.9 kcal/mol in RecA and with blaOXA-143 docking energy was -3.0 kcal/mol by imipenem and meropenem showed a binding score of -1.9 kcal/mol, while doripenem showed the binding score of -2.5 kcal/mol respectively. Doripenem, imipenem, and meropenem docking findings with blaOXA-24 confirmed their binding energies. Doripenem had the highest docking energy of -5.5 kcal/mol, meropenem had a binding score of -4.0 kcal/mol, and imipenem had a binding score of -3.9 kcal/mol. PyRx was used to dock the doripenem, imipenem, and meropenem to NMD-1. Docking energies for doripenem were all - 4.0 kcal/mol, whereas meropenem had docking energy of -3.3 kcal/mol and imipenem was -1.50 kcal/mol. To the best of our knowledge the underlying mechanism of phenotypic with genotypic resistance molecular docking regarding carbapenem resistance A. baumannii is unclear. Our molecular docking finds the possible protein targeting mechanism for carbapenem-resistant A.baumannii.
Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; Doripenem; Imipenem; Meropenem; Molecular Docking Simulation
PubMed: 36463105
DOI: 10.1186/s12866-022-02706-8 -
Antibiotics (Basel, Switzerland) Nov 2022Double-carbapenem combinations have shown synergistic potential against carbapenemase-producing but data remain inconclusive. This study evaluated the activity of...
Double-carbapenem combinations have shown synergistic potential against carbapenemase-producing but data remain inconclusive. This study evaluated the activity of double-carbapenem combinations against 51 clinical KPC-2-, OXA-48-, NDM-1, and NDM-5-producing and and against constructed strains harboring genes encoding KPC-2, OXA-48, or NDM-1 in an otherwise isogenic background. Two-drug combinations of ertapenem, meropenem, and doripenem were evaluated in 24 h time-lapse microscopy experiments with a subsequent spot assay and in static time-kill experiments. An enhanced effect in time-lapse microscopy experiments at 24 h and synergy in the spot assay was detected with one or more combinations against 4/14 KPC-2-, 17/17 OXA-48-, 2/17 NDM-, and 1/3 NDM-1+OXA-48-producing clinical isolates. Synergy rates were higher against meropenem- and doripenem-susceptible isolates and against OXA-48 producers. NDM production was associated with significantly lower synergy rates in . In time-kill experiments with constructed KPC-2-, OXA-48- and NDM-1-producing , 24 h synergy was not observed; however, synergy at earlier time points was found against the KPC-2- and OXA-48-producing constructs. Our findings indicate that the benefit of double-carbapenem combinations against carbapenemase-producing and is limited, especially against isolates that are resistant to the constituent antibiotics and produce NDM.
PubMed: 36421290
DOI: 10.3390/antibiotics11111646 -
Antibiotics (Basel, Switzerland) Oct 2022The aim of the study was to determine the efficacy of carbapenem-only combination treatments derived from four approved drugs (meropenem, doripenem, ertapenem and...
The aim of the study was to determine the efficacy of carbapenem-only combination treatments derived from four approved drugs (meropenem, doripenem, ertapenem and imipenem) against a MDR strain of in a larvae infection model. larvae were infected with NCTC 13437 (carrying the VIM 10 carbapenamase) and the efficacy of the six possible dual, four triple, and one quadruple carbapenem combination(s) were compared to their constituent monotherapies. Four of these combinations showed significantly enhanced survival compared to monotherapies and reduced the bacterial burden inside infected larvae but without complete elimination. Bacteria that survived combination therapy were slower growing, less virulent but with unchanged carbapenem MICs-observations that are consistent with a persister phenotype. In vitro time-kill assays confirmed that the combinations were bactericidal and confirmed that a low number of bacteria survived exposure. Mass spectrometry was used to quantify changes in the concentration of carbapenems in the presence of carbapenemase-carrying . The rate of degradation of individual carbapenems was altered, and often significantly reduced, when the drugs were in combinations compared with the drugs alone. These differences may account for the enhanced inhibitory effects of the combinations against carbapenem-resistant and are consistent with a 'shielding' hypothesis. In conclusion, carbapenem combinations show promise in combating MDR and are worthy of additional study and development.
PubMed: 36358122
DOI: 10.3390/antibiotics11111467 -
Microbiology Insights 2022Antimicrobial resistance (AMR) remains a global health challenge, as bacteria display increasing resistance to last-resort antibiotics such as carbapenems. are evolving...
BACKGROUND
Antimicrobial resistance (AMR) remains a global health challenge, as bacteria display increasing resistance to last-resort antibiotics such as carbapenems. are evolving and developing high level of resistance to carbapenems. With increasing AMR, availability of antibiotics for treatment dwindles, hence a need to complement antibiotics to enhance activity or reduce the level of resistance. This study explored the use of calcium ions in attenuating bacterial resistance to carbapenems.
METHOD
strains isolated from hospital fomites and air were subjected to antimicrobial susceptibility testing with carbapenem antibiotics (imipenem, meropenem, doripenem and ertapenem) using the disc diffusion ( ATCC 25922 as control). Growth profile, Ca-Adjusted assay and time-kill curve of the strains was determined in the presence and absence of carbapenem antibiotics following a calcium stress assay.
RESULTS
Growth profile showed that all the strains grew markedly well at 37°C relative to ATCC 25922 and all strains displayed 80% to 100% level of resistance to tested antibiotics. The growth rate of the strains in the presence of the antibiotics was comparable to the growth rate in the absence of carbapenems. Conditional growth stress with calcium ions showed a 50% reduction in the level of resistance with doripenem displaying the lowest level of reduction and ertapenem, the highest.
DISCUSSION
The study showed that strains displayed high levels of resistance to carbapenems, increasing the possibility of treatment failure. Challenging strains with calcium prior to antibiotic treatment led to a significant reduction in level of resistance, indicating that calcium ions could affect bacterial strains during antibiotic activity leading to reduction in level of resistance.
CONCLUSION
Calcium supplement could potentiate carbapenem effectiveness and reduce bacterial AMR.
PubMed: 36325109
DOI: 10.1177/11786361221133728 -
Scientific Reports Oct 2022GBHs are the most widely used herbicides for weed control worldwide that potentially affect microorganisms, but the role of their sublethal exposure in the development...
GBHs are the most widely used herbicides for weed control worldwide that potentially affect microorganisms, but the role of their sublethal exposure in the development of antibiotic resistance of Pseudomonas aeruginosa is still not fully investigated. Here, the effects of glyphosate acid (GLY), five glyphosate-based herbicides (GBHs), and POE(15), a formerly used co-formulant, on susceptibility to imipenem, a potent carbapenem-type antibiotic, in one clinical and four non-clinical environmental P. aeruginosa isolates were studied. Both pre-exposure in broth culture and co-exposure in solid media of the examined P. aeruginosa strains with 0.5% GBHs resulted in a decreased susceptibility to imipenem, while other carbapenems (doripenem and meropenem) retained their effectiveness. Additionally, the microdilution chequerboard method was used to examine additive/antagonistic/synergistic effects between GLY/POE(15)/GBHs and imipenem by determining the fractional inhibitory concentration (FIC) indexes. Based on the FIC index values, glyphosate acid and Total demonstrated a potent antagonistic effect in all P. aeruginosa strains. Dominator Extra 608 SL and Fozat 480 reduced the activity of imipenem in only one strain (ATCC10145), while POE(15) and three other GBHs did not have any effect on susceptibility to imipenem. Considering the simultaneous presence of GBHs and imipenem in various environmental niches, the detected interactions between these chemicals may affect microbial communities. The mechanisms of the glyphosate and GBH-induced imipenem resistance in P. aeruginosa are yet to be investigated.
Topics: Pseudomonas aeruginosa; Imipenem; Herbicides; Glycine; Carbapenems; Anti-Bacterial Agents; Microbial Sensitivity Tests; Glyphosate
PubMed: 36309535
DOI: 10.1038/s41598-022-23117-9