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Veterinary Medicine and Science Jul 2023Resistance to multiple drugs in Klebsiella pneumoniae (KPN) is an important issue in human and animal medicine. KPN phenotypic and genotypic aspects in poultry samples...
BACKGROUND
Resistance to multiple drugs in Klebsiella pneumoniae (KPN) is an important issue in human and animal medicine. KPN phenotypic and genotypic aspects in poultry samples have not been comprehensively explored in Bangladesh.
METHODS
This research focused on the prevalence of antibiotic resistance and the characterization of KPN in Bangladeshi poultry isolates using both phenotypic and genotypic approaches.
RESULTS
A total of 32 poultry samples were randomly obtained from a commercial poultry farm in Narsingdi, Bangladesh, and 43.90% (18/41) of the isolates were confirmed to be KPN, whereas all isolates were biofilm producers. The antibiotic sensitivity test revealed the most remarkable (100%) antibiotic resistance level against Ampicillin, Doxycycline and Tetracycline while remaining susceptible to Doripenem, Meropenem, Cefoxitin and Polymyxin B. Resistance to Nalidixic acid, Nitrofurantoin, Trimethoprim, Levofloxacin, Ciprofloxacin, Cefuroxime and Chloramphenicol ranges from 18% to 70%. Minimum inhibitory concentrations for carbapenem-resistant KPN ranged from 128 to 512 mg/mL for Meropenem, Imipenem, Gentamycin and Ciprofloxacin, respectively. [Correction added on 15 June 2023, after first online publication: 512 g/mL was corrected to 512 mg/mL in the preceding sentence]. Carbapenemase-producing KPN isolates harboured a single or multiple β-lactamase genes, bla , bla and bla as well as one ESBL gene (bla ) and plasmid-mediated quinolone resistance gene (qnrB). Furthermore, Cr and Co outperformed Cu and Zn in antibacterial effectiveness.
CONCLUSIONS
The results of this investigation showed that the high prevalence of multidrug-resistant pathogenic KPN in our chosen geographic location had displayed sensitivity to FOX/PB/Cr/Co, which might be regarded as an alternate treatment to reduce pressure of use on carbapenems.
Topics: Humans; Animals; Klebsiella pneumoniae; Meropenem; Bangladesh; Poultry; Anti-Bacterial Agents; beta-Lactamases; Ciprofloxacin; Metals, Heavy
PubMed: 37252894
DOI: 10.1002/vms3.1168 -
Foods (Basel, Switzerland) May 2023Farming seabass () is an essential activity in the Mediterranean basin including the Aegean Sea. The main seabass producer is Turkey accounting for 155,151 tons of...
Farming seabass () is an essential activity in the Mediterranean basin including the Aegean Sea. The main seabass producer is Turkey accounting for 155,151 tons of production in 2021. In this study, skin swabs of seabass farmed in the Aegean Sea were analysed with regard to the isolation and identification of . Bacterial microbiota of skin samples ( = 96) from 12 fish farms were investigated using next-generation sequencing (NGS) and metabarcoding analysis. The results demonstrated that Proteobacteria was the dominant bacterial phylum in all samples. At the species level, was identified in all samples. , and were identified using conventional methods and a total of 46 viable (48% of all NGS+) were isolated in seabass swab samples. Additionally, antibiotic susceptibility was determined according to standards of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) in psychrotrophic . strains were tested for susceptibility to 11 antibiotics (piperacillin-tazobactam, gentamicin, tobramycin, amikacin, doripenem, meropenem, imipenem, levofloxacin, ciprofloxacin, norfloxacin, and tetracycline) from five different groups of antibiotics (penicillins, aminoglycosides, carbapenems, fluoroquinolones, and tetracyclines). The antibiotics chosen were not specifically linked to usage by the aquaculture industry. According to the EUCAST and CLSI, three and two strains were found to be resistant to doripenem and imipenem (E-test), respectively. All strains were susceptible to piperacillin-tazobactam, amikacin, levofloxacin, and tetracycline. Our data provide insight into different bacteria that are prevalent in the skin microbiota of seabass sampled from the Aegean Sea in Turkey, and into the antibiotic resistance of psychrotrophic spp.
PubMed: 37238774
DOI: 10.3390/foods12101956 -
Antibiotics (Basel, Switzerland) Apr 2023While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects,... (Review)
Review
While the relevance of inter-ethnic differences to the pharmacokinetic variabilities of antimicrobials has been reported in studies recruiting healthy subjects, differences in antimicrobial pharmacokinetics between Asian and non-Asian patients with severe pathologic conditions require further investigation. For the purpose of describing the potential differences in antimicrobial pharmacokinetics between Asian and non-Asian populations, a systematic review was performed using six journal databases and six theses/dissertation databases (PROSPERO record CRD42018090054). The pharmacokinetic data of healthy volunteers and non-critically ill and critically ill patients were reviewed. Thirty studies on meropenem, imipenem, doripenem, linezolid, and vancomycin were included in the final descriptive summaries. In studies recruiting hospitalised patients, inconsistent differences in the volume of distribution (V) and drug clearance (CL) of the studied antimicrobials between Asian and non-Asian patients were observed. Additionally, factors other than ethnicity, such as demographic (e.g., age) or clinical (e.g., sepsis) factors, were suggested to better characterise these pharmacokinetic differences. Inconsistent differences in pharmacokinetic parameters between Asian and non-Asian subjects/patients may suggest that ethnicity is not an important predictor to characterise interindividual pharmacokinetic differences between meropenem, imipenem, doripenem, linezolid, and vancomycin. Therefore, the dosing regimens of these antimicrobials should be adjusted according to patients' demographic or clinical characteristics that can better describe pharmacokinetic differences.
PubMed: 37237706
DOI: 10.3390/antibiotics12050803 -
Antimicrobial Agents and Chemotherapy Jun 2023The β-lactam antibiotics have been successfully used for decades to combat susceptible Pseudomonas aeruginosa, which has a notoriously difficult to penetrate outer...
The β-lactam antibiotics have been successfully used for decades to combat susceptible Pseudomonas aeruginosa, which has a notoriously difficult to penetrate outer membrane (OM). However, there is a dearth of data on target site penetration and covalent binding of penicillin-binding proteins (PBP) for β-lactams and β-lactamase inhibitors in intact bacteria. We aimed to determine the time course of PBP binding in intact and lysed cells and estimate the target site penetration and PBP access for 15 compounds in P. aeruginosa PAO1. All β-lactams (at 2 × MIC) considerably bound PBPs 1 to 4 in lysed bacteria. However, PBP binding in intact bacteria was substantially attenuated for slow but not for rapid penetrating β-lactams. Imipenem yielded 1.5 ± 0.11 log killing at 1h compared to <0.5 log killing for all other drugs. Relative to imipenem, the rate of net influx and PBP access was ~ 2-fold slower for doripenem and meropenem, 7.6-fold for avibactam, 14-fold for ceftazidime, 45-fold for cefepime, 50-fold for sulbactam, 72-fold for ertapenem, ~ 249-fold for piperacillin and aztreonam, 358-fold for tazobactam, ~547-fold for carbenicillin and ticarcillin, and 1,019-fold for cefoxitin. At 2 × MIC, the extent of PBP5/6 binding was highly correlated ( = 0.96) with the rate of net influx and PBP access, suggesting that PBP5/6 acted as a decoy target that should be avoided by slowly penetrating, future β-lactams. This first comprehensive assessment of the time course of PBP binding in intact and lysed P. aeruginosa explained why only imipenem killed rapidly. The developed novel covalent binding assay in intact bacteria accounts for all expressed resistance mechanisms.
Topics: Penicillin-Binding Proteins; Anti-Bacterial Agents; Pseudomonas aeruginosa; Bacterial Proteins; Network Pharmacology; Microbial Sensitivity Tests; beta-Lactams; Imipenem; Ceftazidime; beta-Lactamases
PubMed: 37199612
DOI: 10.1128/aac.01603-22 -
Journal of Clinical Medicine Apr 2023The high incidence of urinary tract infections (UTIs), often in nosocomial environments, is a major cause of antimicrobial resistance (AMR). The dissemination of...
PURPOSE
The high incidence of urinary tract infections (UTIs), often in nosocomial environments, is a major cause of antimicrobial resistance (AMR). The dissemination of antibiotic-resistant infections results in very high health and economic burdens for patients and healthcare systems, respectively. This study aims to determine and present the antibiotic resistance profiles of the most common pathogens in a urology department in Greece.
METHODS
During the period 2019-2020, we included 12,215 clinical samples of blood and urine specimens that tested positive for the following pathogens: , , , , , or , as these are the most commonly encountered microbes in a urology department.
RESULTS
The analysis revealed a 22.30% mean resistance rate of strains with a 76.42% resistance to ampicillin and a 54.76% resistance rate to ciprofloxacin in the two-year period. It also showed an approximately 19% resistance rate of strains and a mean resistance rate of 46.205% of strains, with a decreasing trend during the four semesters (-value < 0.001), which presented an 80% resistance rate to ampicillin/sulbactam and 73.33% to ciprofloxacin. The resistance to carbapenems was reported to be 39.82%. The analysis revealed a 24.17% mean resistance rate of with a declining rate over the two-year period (-value < 0.001). The strains were 38% resistant to fluoroquinolones and presented varying resistance against carbapenems (31.58% against doripenem and 19.79% against meropenem). Regarding the strains, a 46.91% mean resistance was noted for with 100% resistance to ampicillin, and a 24.247% mean resistance rate for strains that were 41% resistant to ciprofloxacin. Both types showed 100% sensitivity to linezolid.
CONCLUSIONS
The dissemination of antibiotic-resistant pathogens poses the need to implement surveillance programs and, consequently, to develop strategies to prevent the emergence of such pathogens in order to optimize patient outcomes.
PubMed: 37176622
DOI: 10.3390/jcm12093180 -
Data in Brief Jun 2023The dataset reported in this article describes the adsorption isotherms of amoxicillin, ampicillin, and doripenem onto bentonite. Batch adsorption experiments were...
The dataset reported in this article describes the adsorption isotherms of amoxicillin, ampicillin, and doripenem onto bentonite. Batch adsorption experiments were carried out on single antibiotic solutions with various dosage of bentonite across temperatures from 30 to 50 °C. The adsorbent loading dataset was later obtained by measuring the concentration of antibiotic solution at adsorption equilibrium UV-Vis spectrophotometer. The dataset was also fitted using various isotherm models including Freundlich, Langmuir, Toth, Hill, and Dubinin-Radushkevich models to further analyze the adsorption behavior. On top of that, orthogonal regression was applied to avoid fitting biasness, whereby the fitting results revealed the highest adsorption capacities of 82.259 mg g for amoxicillin, 78.851 mg g for ampicillin, and 93.278 mg g for doripenem using Langmuir model, which gave an accurate representation of the adsorption isotherm dataset that was consistent with the results of Toth and Hill model.
PubMed: 37168600
DOI: 10.1016/j.dib.2023.109159 -
Journal of Global Antimicrobial... Jun 2023Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing... (Meta-Analysis)
Meta-Analysis
Clinical efficacy of ertapenem vs. other carbapenems for the treatment of extended-spectrum-β-lactamase-producing Enterobacterales infection: A systematic review and meta-analysis.
OBJECTIVE
Both ertapenem and other carbapenems, including imipenem, meropenem, and doripenem, are recommended in the treatment of extended-spectrum-β-lactamase (ESBL)-producing Enterobacterales infection. However, whether ertapenem is as effective as other carbapenems for ESBL-producing Enterobacterales remains unclear. Therefore, this meta-analysis was conducted to compare the clinical efficacy of ertapenem versus other carbapenems in the treatment of ESBL-producing Enterobacterales infection.
METHODS
PubMed, Web of Science, and Cochrane Library were searched from their inception to 29 November 2022. Only studies comparing ertapenem and other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections were included.
RESULTS
A total of six studies meeting selection criteria were identified. Overall, ertapenem was associated with a significantly lower 30-d mortality when compared with other carbapenems (10.7% [46/431] vs. 17.7% [104/586]; risk ratio [RR], 0.61; 95% CI: 0.40-0.91). The ertapenem group exhibited a significantly shorter length of hospital stay than the other carbapenem groups (mean differences, -6.02 d; 95% CI, -9.39 to -2.64). No significant differences were noted between ertapenem and other carbapenem groups in terms of rates of clinical cure or improvement (RR, 1.11; 95% CI: 0.97-1.25) and microbiological eradication (RR, 1.01; 95% CI: 0.97-1.06).
CONCLUSIONS
Ertapenem could be as effective as other carbapenems in the treatment of patients with ESBL-producing Enterobacterales infections.
Topics: Humans; Ertapenem; Carbapenems; Anti-Bacterial Agents; beta-Lactams; beta-Lactamases; Treatment Outcome; Gammaproteobacteria
PubMed: 36944409
DOI: 10.1016/j.jgar.2023.03.003 -
The Journal of Biological Chemistry May 2023L1 is a dizinc subclass B3 metallo-β-lactamase (MBL) that hydrolyzes most β-lactam antibiotics and is a key resistance determinant in the Gram-negative pathogen...
L1 is a dizinc subclass B3 metallo-β-lactamase (MBL) that hydrolyzes most β-lactam antibiotics and is a key resistance determinant in the Gram-negative pathogen Stenotrophomonas maltophilia, an important cause of nosocomial infections in immunocompromised patients. L1 is not usefully inhibited by MBL inhibitors in clinical trials, underlying the need for further studies on L1 structure and mechanism. We describe kinetic studies and crystal structures of L1 in complex with hydrolyzed β-lactams from the penam (mecillinam), cephem (cefoxitin/cefmetazole), and carbapenem (tebipenem, doripenem, and panipenem) classes. Despite differences in their structures, all the β-lactam-derived products hydrogen bond to Tyr33, Ser221, and Ser225 and are stabilized by interactions with a conserved hydrophobic pocket. The carbapenem products were modeled as Δ-imines, with (2S)-stereochemistry. Their binding mode is determined by the presence of a 1β-methyl substituent: the Zn-bridging hydroxide either interacts with the C-6 hydroxyethyl group (1β-hydrogen-containing carbapenems) or is displaced by the C-6 carboxylate (1β-methyl-containing carbapenems). Unexpectedly, the mecillinam product is a rearranged N-formyl amide rather than penicilloic acid, with the N-formyl oxygen interacting with the Zn-bridging hydroxide. NMR studies imply mecillinam rearrangement can occur nonenzymatically in solution. Cephem-derived imine products are bound with (3R)-stereochemistry and retain their 3' leaving groups, likely representing stable endpoints, rather than intermediates, in MBL-catalyzed hydrolysis. Our structures show preferential complex formation by carbapenem- and cephem-derived species protonated on the equivalent (β) faces and so identify interactions that stabilize diverse hydrolyzed antibiotics. These results may be exploited in developing antibiotics, and β-lactamase inhibitors, that form long-lasting complexes with dizinc MBLs.
Topics: Humans; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Carbapenems; Crystallography; Kinetics; Stenotrophomonas maltophilia; Gram-Negative Bacterial Infections
PubMed: 36924941
DOI: 10.1016/j.jbc.2023.104606 -
Water Research Apr 2023Carbapenems are last-resort antibiotics used to treat bacterial infections unsuccessfully treated by most common categories of antibiotics in humans. Most of their...
Carbapenems are last-resort antibiotics used to treat bacterial infections unsuccessfully treated by most common categories of antibiotics in humans. Most of their dosage is secreted unchanged as waste, thereby making its way into the urban water system. There are two major knowledge gaps addressed in this study to gain a better understanding of the effects of their residual concentrations on the environment and environmental microbiome: development of a UHPLC-MS/MS method of detection and quantification from raw domestic wastewater via direct injection and study of their stability in sewer environment during the transportation from domestic sewers to wastewater treatment plants. The UHPLC-MS/MS method was developed for four carbapenems: meropenem, doripenem, biapenem and ertapenem, and validation was performed in the range of 0.5-10 μg/L for all analytes, with limit of detection (LOD) and limit of quantification (LOQ) values ranging from 0.2-0.5 μg/L and 0.8-1.6 μg/L respectively. Laboratory scale rising main (RM) and gravity sewer (GS) bioreactors were employed to culture mature biofilms with real wastewater as the feed. Batch tests were conducted in RM and GS sewer bioreactors fed with carbapenem-spiked wastewater to evaluate the stability of carbapenems and compared against those in a control reactor (CTL) without sewer biofilms, over a duration of 12 h. Significantly higher degradation was observed for all carbapenems in RM and GS reactors (60 - 80%) as opposed to CTL reactor (5 - 15%), which indicates that sewer biofilms play a significant role in the degradation. First order kinetics model was applied to the concentration data along with Friedman's test and Dunn's multiple comparisons analysis to establish degradation patterns and differences in the degradation observed in sewer reactors. As per Friedman's test, there was a statistically significant difference in the degradation of carbapenems observed depending on the reactor type (p = 0.0017 - 0.0289). The results from Dunn's test indicate that the degradation in the CTL reactor was statistically different from that observed in either RM (p = 0.0033 - 0.1088) or GS (p = 0.0162 - 0.1088), with the latter two showing insignificant difference in the degradation rates observed (p = 0.2850 - 0.5930). The findings contribute to the understanding about the fate of carbapenems in urban wastewater and the potential application of wastewater-based epidemiology.
Topics: Humans; Wastewater; Sewage; Carbapenems; Tandem Mass Spectrometry; Bioreactors; Biofilms; Anti-Bacterial Agents
PubMed: 36863281
DOI: 10.1016/j.watres.2023.119796 -
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