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Canadian Journal of Physiology and... Jan 2024Augmented renal clearance (ARC) is commonly described in critically ill patients, making drug pharmacokinetics even harder to predict in this population. This case...
Augmented renal clearance (ARC) is commonly described in critically ill patients, making drug pharmacokinetics even harder to predict in this population. This case report displays the value of therapeutic drug monitoring (TDM) of piperacillin/tazobactam (PTZ) in this population. We identified two patients with ARC and intermittent administration of PTZ who took part in a prospective, descriptive study conducted at Hôpital du Sacré-Cœur de Montréal. Both had plasma samples drawn at peak, middle, and end of their dosing intervals of PTZ. Minimal inhibitory concentrations (MICs) of 4 and 8 mg/L were chosen to evaluate therapeutic target attainment at middle and end of dosing interval. The first patient was a 52-year-old male with a renal clearance rate estimated at 147 mL/min who received 3.375 g PTZ every 6 h. The second patient, a 49-year-old male, had an estimated renal clearance rate of 163 mL/min and received the same regimen. Both patients had piperacillin concentrations above the target MICs at middle of the dosing interval, but they failed to reach a trough concentration above 8 mg/L. The present case report showcases two patients with subtherapeutic PTZ concentrations despite strict following of local administration protocols. This suboptimal administration could not only lead to treatment failure, but also to the selection and growth of resistant pathogens. Implementing TDM would offer the possibility to adjust drug regimens in real-time and prevent situations like these from occurring.
Topics: Male; Humans; Middle Aged; Anti-Bacterial Agents; beta Lactam Antibiotics; Prospective Studies; Drug Monitoring; Piperacillin; Piperacillin, Tazobactam Drug Combination; Monobactams
PubMed: 37713726
DOI: 10.1139/cjpp-2023-0109 -
Infection Apr 2024Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections commonly cause hospital-acquired infections. The study aimed to compare the outcomes of CRKP infections...
Ceftazidime-avibactam alone or in combination with Aztreonam versus Polymyxins in the management of carbapenem-Resistant Klebsiella pneumoniae nosocomial Infections (CAPRI study): a retrospective cohort study from South India.
INTRODUCTION
Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections commonly cause hospital-acquired infections. The study aimed to compare the outcomes of CRKP infections between patients receiving ceftazidime avibactam +/- aztreonam and polymyxins in a hospital setting with a high prevalence of New Delhi Metallo Beta Lactamase production.
METHODS
We conducted a retrospective cohort study from January 2020 to September 2022 in critically ill adult patients admitted to a non-COVID-19 medical intensive care unit with CRKP infection. The patients were followed up for a total of 30 days or death, whichever was later.
RESULTS
Of a total of 106 patients included in the study, 65 patients received polymyxins and 41 patients received ceftazidime-avibactam +/- aztreonam. Higher 30-day mortality was noted in the polymyxin group (56.9% vs. 29.2%, P = 0.005). The mean time to event (mortality) in ceftazidime-avibactam +/- aztreonam was 23.9 + 1.5 days which was significantly higher compared to polymyxins (17.9 + 1.2 days, p = 0.006). On Cox regression analysis, after adjusting for the covariates, the hazard ratio for time to event with the use of polymyxin was 2.02 (95% CI: 1.03-3.9).
CONCLUSION
Ceftazidime-avibactam + aztreonam is possibly associated with better clinical outcomes in patients infected with CRKP.
Topics: Adult; Humans; Ceftazidime; Aztreonam; Anti-Bacterial Agents; Klebsiella pneumoniae; Polymyxins; Cross Infection; Retrospective Studies; Drug Combinations; beta-Lactamases; Carbapenems; Microbial Sensitivity Tests; Klebsiella Infections; Azabicyclo Compounds
PubMed: 37697224
DOI: 10.1007/s15010-023-02094-9 -
Frontiers in Microbiology 2023Agrobacterium-mediated soybean transformation is the simplest method of gene transfer. However, the low transformation due to the intractable nature of soybean genotypes...
Agrobacterium-mediated soybean transformation is the simplest method of gene transfer. However, the low transformation due to the intractable nature of soybean genotypes hinders this process. The use of biochemicals (acetosyringone, cinnamic acid, flavonoids, etc.) plays an important role in increasing soybean transformation. These biochemicals induce chemotaxis and virulence gene activation during the infection process. Here we identified a biochemical, aztreonam (a monobactam), for high agrobacterium-mediated transformation in soybean. The soybean explants from three genotypes were inoculated with (GV3101) harboring the pMDC32 vector containing during two separate events. High transient GUS expression was obtained during cotyledon explant culture on MS media supplemented with 2.5 mg/L aztreonam. The aztreonam-treated explants showed high efficiency in transient and stable transformation as compared to the untreated control. The transformation of aztreonam-treated explants during seed imbibition resulted in an average of 21.1% as compared to 13.2% in control by using the pMDC32 vector and 28.5 and 20.7% while using the GUS gene cassette, respectively. Based on these findings, the metabolic analysis of the explant after aztreonam treatment was assessed. The high accumulation of flavonoids was identified during an untargeted metabolic analysis. The quantification results showed a significantly high accumulation of the four compounds, i.e., genistein, apigenin, naringenin, and genistin, in cotyledon explants after 18 hours of aztreonam treatment. Alongside this, aztreonam also had some surprising effects on root elongation and lateral root formation when compared to indole-3-butyric acid (IBA). Our findings were limited to soybeans. However, the discovery of aztreonam and its effect on triggering flavonoids could lead to the potential role of aztreonam in the agrobacterium-mediated transformation of different crops.
PubMed: 37692409
DOI: 10.3389/fmicb.2023.1257270 -
Nature Communications Sep 2023There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases, which provide resistance by breaking down beta-lactam rings. We have...
There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases, which provide resistance by breaking down beta-lactam rings. We have observed that certain beta-lactamases tend to aggregate, which persists throughout their evolution under the selective pressure of antibiotics on their active sites. Interestingly, we find that existing beta-lactamase active site inhibitors can act as molecular chaperones, promoting the proper folding of these resistance factors. Therefore, we have created Pept-Ins, synthetic peptides designed to exploit the structural weaknesses of beta-lactamases by causing them to misfold into intracellular inclusion bodies. This approach restores sensitivity to a wide range of beta-lactam antibiotics in resistant clinical isolates, including those with Extended Spectrum variants that pose significant challenges in medical practice. Our findings suggest that targeted aggregation of resistance factors could offer a strategy for identifying molecules that aid in addressing the global antibiotic resistance crisis.
Topics: Anti-Bacterial Agents; Inclusion Bodies; Monobactams; R Factors; beta-Lactamase Inhibitors; beta-Lactamases
PubMed: 37689716
DOI: 10.1038/s41467-023-41191-z -
Antimicrobial Agents and Chemotherapy Oct 2023Novel antibacterial agents and strategies are urgently needed to fight against the ongoing global antibiotic resistance problem. While natural products remain the main...
Novel antibacterial agents and strategies are urgently needed to fight against the ongoing global antibiotic resistance problem. While natural products remain the main source in antibiotic discovery, synthetic antibacterials provide an attractive alternative and may evade the ancient antibiotic resistance. Herein, we report a small molecule that re-sensitizes methicillin-resistant to β-lactam antibiotics with extremely low potential for resistance development. It belongs to a new class of broad-spectrum antibacterials, trypyricins, which share similar structural characteristics and mechanism of action to the cationic antimicrobial peptides. Mechanistic studies indicated that trypyricins fluidize and disrupt bacterial cytoplasmic membrane. These results suggested that trypyricins represent a promising new class of antibacterials and may be further developed as antibiotic adjuvants to fight against resistant bacteria in the clinic.
Topics: Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Anti-Bacterial Agents; Monobactams; Drug Resistance, Microbial
PubMed: 37681969
DOI: 10.1128/aac.00051-23 -
Pakistan Journal of Medical Sciences 2023Molecular detection and co-presence of carbapenem-resistant genes in the isolates of are less commonly reported from Quetta. In the present study, we determined to...
OBJECTIVE
Molecular detection and co-presence of carbapenem-resistant genes in the isolates of are less commonly reported from Quetta. In the present study, we determined to highlight the antibiotic sensitivity profile and genetic mechanism of carbapenem resistance.
METHODS
The cross-sectional study was conducted from May to September 2018 at the Hi-tech laboratory, Centre for Advance Studies in Vaccinology and Biotechnology, University of Baluchistan, Quetta. Biochemical and molecular methods were ascertained for the recognition of the isolates and minimum inhibitory concentration was performed using E-test and broth microdilution methods. The molecular basis of carbapenemase activity was determined by identifying carbapenemase genes in the isolates.
RESULTS
Of the (n=23) isolated from pus aspirates obtained from surgical/burn units, we have detected bla (n=7/8) 87.5%, bla (n=5/8) 62.5%, and bla (n=4/8) 50%. The co-existence of multiple antibiotic-resistant genes, bla, bla and bla was found in (n=2/8) 25% isolates. These isolates displayed resistance against a range of antimicrobials from β-lactams, tetracyclines, cephalosporins, quinolones, monobactams, aminoglycosides, sulphonamides, phosphoric acid, macrolides, and polypeptide groups, suggesting extensive-drug resistance.
CONCLUSION
The emergence of MBL and ESBL producers is an alarming threat in the region. It is of great importance to determine the resistance mechanism of bacterial bugs. The lack of new antimicrobials particularly against gram-negative bacteria is quite alarming worldwide.
PubMed: 37680816
DOI: 10.12669/pjms.39.5.7188 -
The Journal of Infection Jan 2024
Topics: Humans; Anti-Bacterial Agents; beta Lactam Antibiotics; beta-Lactams; Febrile Neutropenia; Monobactams; Systematic Reviews as Topic; Meta-Analysis as Topic
PubMed: 37678625
DOI: 10.1016/j.jinf.2023.08.015 -
Japanese Journal of Infectious Diseases Jan 2024Salmonella enterica subsp. enterica serovar Typhimurium has recently emerged worldwide as a producer of extended-spectrum β-lactamase (ESBL). However, drug-resistant...
Salmonella enterica subsp. enterica serovar Typhimurium has recently emerged worldwide as a producer of extended-spectrum β-lactamase (ESBL). However, drug-resistant clinical isolates are rare in Japan. The common types of ESBLs found are the CTX-M-type β-lactamases, including novel β-lactamases such as CTX-M-64. CTX-M-64 has a chimeric structure comprising a combination of the CTX-M-1 and CTX-M-9 groups. In 2017, S. Typhimurium was isolated from stool, blood, and urine cultures of an 82-year-old man. Herein, we describe the discovery of a clinical isolate of S. Typhimurium in Japan. Antimicrobial susceptibility testing revealed that the isolate was resistant to third- and fourth-generation cephalosporins, including ceftazidime and monobactam. The minimum inhibitory concentrations of ceftazidime and ceftriaxone were restored by administration of clavulanic acid. Whole-genome sequencing analysis revealed that the isolate harbored the bla gene on an IncHI2/IncHI2A-type plasmid, with an assembly length of 174,477 bp. The genetic structure of the region surrounding the bla gene, ISKpn26-ΔISEcp1-bla-orf477, was shared only with the chromosome sequence of S. Typhimurium detected in food-producing chickens in Guangdong, China. Although rare, S. Typhimurium can induce bloodstream infections and produce ESBL. To our knowledge, this is the first report of a CTX-M-64-producing Enterobacterales clinical isolate of domestic origin in Japan.
Topics: Male; Animals; Humans; Aged, 80 and over; Salmonella typhimurium; Anti-Bacterial Agents; Ceftazidime; Japan; Chickens; beta-Lactamases; Microbial Sensitivity Tests
PubMed: 37648488
DOI: 10.7883/yoken.JJID.2023.163 -
Journal of Global Antimicrobial... Dec 2023This work aimed to describe the in vitro performance of the combined activity of ceftazidime-avibactam (CZA) plus aztreonam (ATM) against carbapenemase-producing...
OBJECTIVE
This work aimed to describe the in vitro performance of the combined activity of ceftazidime-avibactam (CZA) plus aztreonam (ATM) against carbapenemase-producing Enterobacterales (CPE).
METHODS
We studied 44 CPE clinical isolates: NDM-1 (31), KPC-2 (5), KPC-3 (3), VIM-2 (2), NDM-1+KPC-2 (2), and OXA-48 (1). The efficacy of CZA in combination with were determined by two methods: (i) Kirby-Bauer's double disk synergy test and; (ii) Determination of the minimum inhibitory concentration to CZA by E-test, in either Mueller-Hinton agar alone or, supplemented with ATM 4 mg/L. Additionally, the Fractional inhibitory concentration index (FICI) was determined; values of ≤ 0.5 were interpreted as synergistic, while FICI > 0.5 were considered indifferent.
RESULTS
All isolates were carbapenem-resistant, 14 were resistant to CZA and ATM, 15 were only CZA resistant, 12 were only ATM resistant, and three were susceptible to both. 34/44 isolates presented positive double disk synergy tests between CZA and ATM regardless of their susceptibility profile, the isolates with negative synergy tests were susceptible to at least one of the agents. On the other hand, the 21 isolates selected to compare the MIC to CZA alone and CZA plus 4 mg/L ATM of exhibited FICI values between 0.016 and 0.125, indicating a synergistic effect.
CONCLUSIONS
This method is available to clinical laboratories and would provide valuable information to guide the treatment of infections with CZA and ATM. In this sense, the use of CZA together with ATM is a potentially suitable combination for the treatment of carbapenemase-producing microorganisms.
Topics: Aztreonam; Anti-Bacterial Agents; Ceftazidime
PubMed: 37611893
DOI: 10.1016/j.jgar.2023.08.010 -
Cureus Jul 2023Introduction Resistance due to AmpC and extended-spectrum beta (β)-lactamases (ESBLs) in is an emerging problem worldwide. AmpC enzymes are a subclass of β-lactamases...
Introduction Resistance due to AmpC and extended-spectrum beta (β)-lactamases (ESBLs) in is an emerging problem worldwide. AmpC enzymes are a subclass of β-lactamases that have a capacity to hydrolyze and deactivate a large range of β-lactam antibiotics, particularly cephalosporins, penicillins, and monobactams, although frequently being susceptible to carbapenems and fourth-generation cephalosporins. The prevalence of plasmid-mediated AmpC (pAmpC) genotypes in uropathogenic isolates were looked at a tertiary care teaching hospital of Western Uttar Pradesh. Materials and methods A total of 312 non-repeat clinical isolates among patients presented with urinary tract infections (UTIs) were investigated by standard microbiological methods. Isolates were screened for the presence of ampC using a cefoxitin (30 µg) disc and confirmed using an inhibitor-based assay. Using multiplex polymerase chain reaction (PCR), six AmpC genotypes, namely, CIT, DHA, EBC, ACC, FOX, and MOX, were genotypically identified. Results A total of 152 (48.72%) uropathogenic isolates tested positive on the cefoxitin screening. Out of which, AmpC production was confirmed in 118/152 (77.63%) using a phenotypic method. In particular, the pAmpC gene was found in 56/152 (36.84%) isolates. CIT was the most common gene detected in this geographical area (57.14 %). Multiple genes, i.e., CIT and FOX, were also detected in 14.29% of the isolates. Conclusion Identifying AmpC producers is important in routine microbiology laboratory as they are a nosocomial threat requiring strict adherence to infection control protocols. A confirmatory phenotypic test followed by genotypic tests will help in the correct and accurate identification of this resistance.
PubMed: 37565104
DOI: 10.7759/cureus.41551