-
Frontiers in Microbiology 2024() is an important opportunistic pathogen causing nosocomial infection in the clinic. The occurrence rate of antibiotic resistance is increasing year by year, resulting...
INTRODUCTION
() is an important opportunistic pathogen causing nosocomial infection in the clinic. The occurrence rate of antibiotic resistance is increasing year by year, resulting in a highly serious situation of bacterial resistance.
METHODS
To better understand the local epidemiology of multidrug-resistant , an investigation was conducted on the antibiotic resistance of different types of and its relationship with the genes of . Furthermore, the molecular mechanism underlying antibiotic resistance in was investigated through transcriptome analysis.
RESULTS
These results showed that a total of 9 STs were detected. It was found that 99% of the strains isolated in the hospital belonged to the same STs, and the clone complex CC208 was widely distributed in various departments and all kinds of samples. Furthermore, these strains showed high resistance to ertapenem, biapenem, meropenem, and imipenem, among which the resistance to ertapenem was the strongest. The detection rate of gene in these carbapenem resistance (CRAB) reached 100%; Additionally, the transcriptome results showed that the resistance genes were up-regulated in resistance strains, and these genes involved in biofilm formation, efflux pumps, peptidoglycan biosynthesis, and chaperonin synthesis.
DISCUSSION
These results suggest that the CC208 STs were the main clonal complex, and showed high carbapenem antibiotic resistance. All these resistant strains were distributed in various departments, but most of them were distributed in intensive care units (ICU). The was the main antibiotic resistance genotype; In summary, the epidemic trend of clinical in Guiyang, China was analyzed from the molecular level, and the resistance mechanism of to carbapenem antibiotics was analyzed with transcriptome, which provided a theoretical basis for better control of .
PubMed: 38946905
DOI: 10.3389/fmicb.2024.1394775 -
The Journal of Antimicrobial... Jul 2024Successful use of carbapenems in combination with cefazolin or oxacillin for treatment of MSSA bacteraemia has been described; however, comparative data to standard...
BACKGROUND
Successful use of carbapenems in combination with cefazolin or oxacillin for treatment of MSSA bacteraemia has been described; however, comparative data to standard treatment approaches are lacking.
METHODS
This was a multicentre, retrospective study of adult patients with MSSA bacteraemia for >48 h. Standard treatment was considered monotherapy with cefazolin, oxacillin or nafcillin. Combination therapy was defined as the addition of ertapenem or meropenem to standard treatment for at least 24 h. The primary outcome was duration of bacteraemia defined as time from administration of an antibiotic with in vitro activity to first negative blood culture. Time to blood culture sterilization was compared through risk-set matching with aid of a propensity score.
RESULTS
Overall, 238 patients were included; 66% (157/238) received standard treatment and 34% (81/238) received combination therapy. The median (IQR) time to carbapenem initiation was 4.7 (3.63-6.5) days. Patients who received combination therapy were younger (P = 0.012), more likely to have endocarditis (P = 0.034) and had longer median duration of bacteraemia (P < 0.001). After applying risk-set matching, patients who received combination therapy experienced faster time to blood culture sterilization compared with control patients [HR = 1.618 (95% CI; 1.119-2.339) P = 0.011]. Using a paired hazard model, 90 day mortality rates were not statistically different among patients who received combination therapy versus matched controls [HR = 1.267 (95% CI; 0.610-2.678), P = 0.608].
DISCUSSION
Carbapenem combination therapy resulted in faster time to blood culture sterilization, but no differences in overall mortality rates. Randomized trials are critical to determine the utility of carbapenem combination therapy.
PubMed: 38946294
DOI: 10.1093/jac/dkae198 -
ChemMedChem Jun 2024Antibiotics, particularly the β-lactams, are a cornerstone of modern medicine. However, the rise of bacterial resistance to these agents, particularly through the...
Antibiotics, particularly the β-lactams, are a cornerstone of modern medicine. However, the rise of bacterial resistance to these agents, particularly through the actions of β-lactamases, poses a significant threat to our continued ability to effectively treat infections. Metallo-β-lactamases (MBLs) are of particular concern due to their ability to hydrolyze a wide range of β-lactam antibiotics including carbapenems. For this reason there is growing interest in the development of MBL inhibitors as well as novel antibiotics that can overcome MBL-mediated resistance. Here, we report the synthesis and evaluation of novel conjugates that combine a carbapenem (meropenem or ertapenem) with a recently reported MBL inhibiting indole carboxylate scaffold. These hybrids were found to display potent inhibition against MBLs including NDM-1 and IMP-1, with IC50 values in the low nanomolar range. However, their antibacterial potency was limited. Mechanistic studies suggest that despite maintaining effective MBL inhibiting activity in live bacteria, the new carbapenem/MBL inhibitor conjugates have a reduced ability to engage with the bacterial target of the β-lactams.
PubMed: 38946213
DOI: 10.1002/cmdc.202400302 -
The Journal of Hospital Infection Jun 2024The global burden associated with antimicrobial resistance is of increasing concern. The aim of this study was to evaluate risk factors associated with...
Risk factors and clinical impact of multidrug resistance in healthcare-associated bacteremic urinary tract infections: a post-hoc analysis of a multicenter prospective cohort in Spain.
INTRODUCTION
The global burden associated with antimicrobial resistance is of increasing concern. The aim of this study was to evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated (HCA) bacteremic urinary tract infections (BUTI).
METHODS
This is a post-hoc analysis a prospective multicenter study of patients with HCA-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48-72h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression.
RESULTS
443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (OR 3.13, 95% CI 2.11-4.69, p<0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa etiology (OR 7.84, 95% CI 2.37-25.95; p=0.001). MDR was independently associated with prior use of fluoroquinolones (aOR 2.43; 95% CI 1.25-4.69), cephalosporins (aOR 2.14; 95% CI 1.35-3.41) and imipenem or meropenem (aOR 2.08; 95% CI 1.03-4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but with longer hospital stay.
CONCLUSIONS
MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although was independently associated with longer duration of hospital stay.
PubMed: 38945399
DOI: 10.1016/j.jhin.2024.05.020 -
The Journal of Antimicrobial... Jun 2024Mycobacterium abscessus has emerged as an opportunistic pathogen responsible for lung infections, especially in cystic fibrosis patients. In spite of the production of...
OBJECTIVES
Mycobacterium abscessus has emerged as an opportunistic pathogen responsible for lung infections, especially in cystic fibrosis patients. In spite of the production of the broad-spectrum β-lactamase BlaMab, the carbapenem imipenem is recommended in the initial phase of the treatment of pulmonary infections. Here, we determine whether the addition of vaborbactam, a second-generation β-lactamase inhibitor belonging to the boronate family, improves the activity of β-lactams against M. abscessus.
METHODS
The activity of β-lactams, alone or in combination with vaborbactam, was evaluated against M. abscessus CIP104536 by determining MICs, time-killing and intramacrophage activity. Kinetic parameters for the inhibition of BlaMab by vaborbactam were determined by spectrophotometry.
RESULTS
The combination of vaborbactam (8 mg/L) with β-lactams decreased more than 8 times the MIC of amoxicillin (from >1024 to 128 mg/L) and 2 times the MICs of meropenem (from 16 to 8 mg/L) and imipenem (from 4 to 2 mg/L). The reduction of the MICs was less than that obtained with avibactam at 4 mg/L for amoxicillin (from >1024 to 16 mg/L, more than 64 times less) and for meropenem (from 16 to 4 mg/L, 4 times less). In vitro and intracellularly, M. abscessus was not killed by the meropenem/vaborbactam combination, in spite of significant in vitro inhibition of BlaMab by vaborbactam.
CONCLUSIONS
Inhibition of BlaMab by vaborbactam decreases the MIC of β-lactams, including that of meropenem. As meropenem/vaborbactam is clinically available, this combination offers an alternative therapeutic option that should be evaluated for the treatment of pulmonary infections due to M. abscessus.
PubMed: 38943535
DOI: 10.1093/jac/dkae181 -
International Journal of Antimicrobial... Jun 2024Bacteroides fragilis is the most frequent cause of anaerobic bacteraemia. Although recent data suggest a rise in antimicrobial resistance (AMR) of this and other...
BACKGROUND
Bacteroides fragilis is the most frequent cause of anaerobic bacteraemia. Although recent data suggest a rise in antimicrobial resistance (AMR) of this and other anaerobic bacteria, surveillance remains limited due to a lack of both data availability and comparability. However, a newly introduced standardised method for antimicrobial susceptibility testing (AST) of anaerobic bacteria has made larger scale surveillance possible for the first time.
AIM
To investigate phenotypic AMR of Bacteroides fragilis isolates from bacteraemia across Europe in 2022.
METHODS
In a multicentre approach, clinical microbiology laboratories in Europe were invited to contribute results of AST for Bacteroides fragilis blood culture isolates (including only the first isolate per patient and year). AST of a selection of four antibiotics was performed locally by participating laboratories in a prospective or retrospective manner, using the new EUCAST disc diffusion method on fastidious anaerobe agar (FAA-HB).
RESULTS
A total of 16 European countries reported antimicrobial susceptibilities in 449 unique isolates of Bacteroides fragilis from blood cultures in 2022. Clindamycin demonstrated the highest resistance rates (20.9%, range 0 - 63.6%), followed by piperacillin-tazobactam (11.1%, 0 - 54.5%), meropenem (13.4%, 0 - 45.5%), and metronidazole (1.8%, 0 - 20.0%), all with wide variation between countries.
CONCLUSION
Considering that the mean resistance rates across Europe were higher than expected for three of the four anti-anaerobic antibiotics under surveillance, both local AST of clinically relevant isolates of Bacteroides fragilis and continued surveillance on an international level is warranted.
PubMed: 38942247
DOI: 10.1016/j.ijantimicag.2024.107241 -
Case Reports in Infectious Diseases 2024Coadministering two different classes of antibiotics as empirical therapy can be critical in treating healthcare-associated infections in hospitals. Herein, we report a...
Coadministering two different classes of antibiotics as empirical therapy can be critical in treating healthcare-associated infections in hospitals. Herein, we report a case of acute kidney injury (AKI) caused by coadministration of vancomycin with high-dose meropenem that manifested as a rapid increase in serum creatinine levels and an associated increase in vancomycin trough concentrations. The patient was diagnosed with meningioma at 50 years and was followed up regularly. The patient underwent surgery and antibiotic treatment between 63 and 66 years for suspected meningitis and pneumonia. Coadministration of vancomycin with high-dose meropenem (6.0 g/day) caused AKI; however, no AKI occurred when vancomycin was administered alone or with a low dose of meropenem (1.5 or 3.0 g/day). To our knowledge, this report is the first to show that administering different dosages of meropenem in combination with vancomycin may contribute to the risk of developing AKI. We suggest that coadministered vancomycin and high-dose meropenem (6.0 g/day) may increase the risk of AKI. Our report adds to the limited literature documenting the coadministration of vancomycin with varying doses of meropenem and its impact on the risk of AKI and highlights the importance of investigating AKI risk in response to varying dosages of meropenem when it is coadministered with vancomycin.
PubMed: 38939108
DOI: 10.1155/2024/7956014 -
Open Veterinary Journal May 2024infections are considered the most common foodborne pathogens responsible for zoonotic infections and food poisoning in humans and animal species such as birds....
BACKGROUND
infections are considered the most common foodborne pathogens responsible for zoonotic infections and food poisoning in humans and animal species such as birds. Antimicrobial resistance is considered a global anxiety because it causes human public health repercussions, as well as leads to an increase in animal morbidity and death.
AIM
The aims of this study are the isolation and identification of , as well as to investigate the antimicrobial susceptibility test (AST) and the molecular characteristics using polymerase chain reaction (PCR) and sequences for isolates from chicken products (eggs, livers, and minced meat) and human in the Wasit Governorate of Iraq.
METHODS
A total of 300 samples (150 chicken product samples including eggs, livers, and minced meat, and 150 human fecal samples) were collected from the Wasit governorate of Iraq from January to December 2022. The bacterial isolation was done according to recommendations of ISO 6579 standard and the Global Foodborne Infections Network laboratory protocol. Serotyping test and AST were done by using 19 antibiotic agents according to the recommendations of the Clinical and Laboratory Standards Institute, 2022 by using disc diffusion susceptibility test and Vitik 2 test. Finally, the suspected isolates were confirmed using the conventional PCR method and sequencing for a unique gene.
RESULTS
The results showed that the isolation percentage of in chicken products was 8.66% (12% eggs, 6% livers, and 8% minced meat), while in humans it was 4.6%. Also, showed 100% of in humans. While, in chicken eggs , and were 50%, 33.33%, and 16.66%, respectively. Also, showed 100% of in both livers and minced meat. The AST in human isolates showed resistance to Ampicillin, Cefotaxime, Ceftazidime, Cefepime, Amikacin, Gentamicin, Ciprofloxacin, Norfloxacin, and Ceftriaxone, while no resistance to Amoxicillin, Pipracillin, Ertapenem, Imipenem, Meropenem, Fosfomycin, Nitrofurantoin, Trimethoprim, Azithromycin, and Tetracycline. In chicken products, isolates were resistant with different percentages to Amikacin, Gentamicin, Tetracycline, Ciprofloxacin, Norfloxacin, Nitrofurantoin, Ampicillin, Cefotaxime, Ceftazidime, Cefepime, and Trimethoprim; while no resistance to Amoxicillin, Pipracillin, Ertapenem, Imipenem, Meropenem, Fosfomycin, Azithromycin, and Ceftriaxone. Sequencing by using gene was done for four PCR products.
CONCLUSION
This study showed the presence of genetic mutations for which led to variations in the molecular characteristics, and antimicrobial drug resistance of isolated from chicken products and humans.
Topics: Animals; Salmonella enterica; Humans; Chickens; Iraq; Anti-Bacterial Agents; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Meat; Feces; Poultry Products; Salmonella Infections
PubMed: 38938436
DOI: 10.5455/OVJ.2024.v14.i5.5 -
Journal of Global Antimicrobial... Jun 2024Novel beta-lactams/beta-lactamase inhibitors (BIBLI) combinations are commercially available and they have been used for treating carbapenem-resistant Klebsiella...
Susceptibility evaluation of novel beta-lactam/beta-lactamase inhibitor combinations against carbapenem-resistant Klebsiella pneumoniae from bloodstream infections in hospitalized patients in Brazil.
Novel beta-lactams/beta-lactamase inhibitors (BIBLI) combinations are commercially available and they have been used for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Continuous surveillance of susceptibility profile and resistance mechanisms identification are necessary to monitor the evolution of resistance as these agents are used. The purpose of this study was to evaluate susceptibility rates to ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in CRKP isolates from patients with bloodstream infection screened for a randomized clinical trial in Brazil. Minimum inhibitory concentration (MIC) was determined by gradient diffusion strip method for meropenem, ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam. Carbapenemase genes were detected by multiplex qPCR. KPC-producing isolates showing resistance to any BLBLI and NDM-producing isolates showing susceptibility to any BLBLI were further submitted to whole genome sequencing. From a total of 69 CRKP isolates, 39 were positive for bla, 19 for bla and 11 for bla and bla. KPC-producing isolates demonstrated susceptibility rates above 94% for all BLBLI. Two isolates with resistance to meropenem/vaborbactam showed a Gly and Asp duplication at OmpK36 protein and truncated ompK35 genes. All NDM-producing isolates, including KPC and NDM coproducers, demonstrated susceptibility rates for ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam of 0%, 9.1 to 21.1% and 9.1 to 26.3%, respectively. Five NDM-producing isolates that presented susceptibility to BLBLI also demonstrated alterations in porins. This study demonstrated that, although high susceptibility rates to the BLBLI were found, KPC-2 isolates can also demonstrate resistance due to porin mutations. Additionally, NDM-1 isolates can demonstrate susceptibility in vitro to the BLBLI.
PubMed: 38936472
DOI: 10.1016/j.jgar.2024.06.007 -
Microbiology Spectrum Jun 2024New β-lactam-β-lactamase inhibitor combinations represent last-resort antibiotics to treat infections caused by multidrug-resistant . Carbapenemase gene acquisition...
UNLABELLED
New β-lactam-β-lactamase inhibitor combinations represent last-resort antibiotics to treat infections caused by multidrug-resistant . Carbapenemase gene acquisition can limit their spectrum of activity, and reports of resistance toward these new molecules are increasing. In this multi-center study, we evaluated the prevalence of resistance to ceftazidime-avibactam (CZA) and comparators among clinical isolates from bloodstream infections, hospital-acquired or ventilator-associated pneumonia, and urinary tract infections, circulating in Southern Italy. We also investigated the clonality and content of relevant β-lactam resistance mechanisms of CZA-resistant (CZA) isolates. A total of 120 . isolates were collected. CZA was among the most active β-lactams, retaining susceptibility in the 81.7% of cases, preceded by cefiderocol (95.8%) and followed by ceftolozane-tazobactam (79.2%), meropenem-vaborbactam (76.1%), imipenem-relebactam (75%), and aztreonam (69.6%). Among non-β-lactams, colistin and amikacin were active against 100% and 85.8% of isolates respectively. In CZA strains subjected to whole-genome sequencing ( = 18), resistance was mainly due to the expression of metallo-β-lactamases (66.6% VIM-type and 5.5% FIM-1), followed by PER-1 (16.6%) and GES-1 (5.5%) extended-spectrum β-lactamases, mostly carried by international high-risk clones (ST111 and ST235). Of note, two strains producing the PER-1 enzyme were resistant to all β-lactams, including cefiderocol. In conclusion, the CZA resistance rate among clinical isolates in Southern Italy remained low. CZA isolates were mostly metallo-β-lactamases producers and belonging to ST111 and ST253 epidemic clones. It is important to implement robust surveillance systems to monitor emergence of new resistance mechanisms and to limit the spread of high-risk clones.
IMPORTANCE
Multidrug-resistant infections are a growing threat due to the limited therapeutic options available. Ceftazidime-avibactam (CZA) is among the last-resort antibiotics for the treatment of difficult-to-treat infections, although resistance due to the acquisition of transferable β-lactamase genes is increasing. With this work, we report that CZA represents a highly active antipseudomonal β-lactam compound (after cefiderocol), and that metallo-β-lactamases (VIM-type) and extended-spectrum β-lactamases (GES and PER-type) production is the major factor underlying CZA resistance in isolates from Southern Italian hospitals. In addition, we reported that such resistance mechanisms were mainly carried by the international high-risk clones ST111 and ST235.
PubMed: 38934607
DOI: 10.1128/spectrum.04266-23