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Clinical Infectious Diseases : An... Sep 2019Understanding the nuances of AmpC β-lactamase-mediated resistance can be challenging, even for the infectious diseases specialist. AmpC resistance can be classified... (Review)
Review
Understanding the nuances of AmpC β-lactamase-mediated resistance can be challenging, even for the infectious diseases specialist. AmpC resistance can be classified into 3 categories: (1) inducible chromosomal resistance that emerges in the setting of a β-lactam compound, (2) stable derepression due to mutations in ampC regulatory genes, or (3) the presence of plasmid-mediated ampC genes. This review will mainly focus on inducible AmpC resistance in Enterobacteriaceae. Although several observational studies have explored optimal treatment for AmpC producers, few provide reliable insights into effective management approaches. Heterogeneity within the data and inherent selection bias make inferences on effective β-lactam choices problematic. Most experts agree it is prudent to avoid expanded-spectrum (ie, third-generation) cephalosporins for the treatment of organisms posing the greatest risk of ampC induction, which has best been described in the context of Enterobacter cloacae infections. The role of other broad-spectrum β-lactams and the likelihood of ampC induction by other Enterobacteriaceae are less clear. We will review the mechanisms of resistance and triggers resulting in AmpC expression, the species-specific epidemiology of AmpC production, approaches to the detection of AmpC production, and treatment options for AmpC-producing infections.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; beta-Lactamases; beta-Lactams
PubMed: 30838380
DOI: 10.1093/cid/ciz173 -
Antimicrobial Agents and Chemotherapy Feb 2018Carbapenem-resistant (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a...
Carbapenem-resistant (CRE) infection is highly endemic in China, but estimates of the infection burden are lacking. We established the incidence of CRE infection from a multicenter study that covered 25 tertiary hospitals in 14 provinces. CRE cases defined as carbapenem-nonsusceptible , , , or infections during January to December 2015 were collected and reviewed from medical records. Antimicrobial susceptibility testing and carbapenemase gene identification were performed. Among 664 CRE cases, most were caused by (73.9%), followed by (16.6%) and (7.1%). The overall CRE infection incidence per 10,000 discharges was 4.0 and differed significantly by region, with the highest in Jiangsu (14.97) and the lowest in Qinghai (0.34). Underlying comorbidities were found in 83.8% of patients; the median patient age was 62 years (range, 45 to 74 years), and 450 (67.8%) patients were male. Lower respiratory tract infections (65.4%) were the most common, followed by urinary tract infection (16.6%), intra-abdominal infection (7.7%), and bacteremia (7.7%). The overall hospital mortality rate was 33.5%. All isolates showed nonsusceptibility to carbapenems and cephalosporins. The susceptibility rate of polymyxin B was >90%. Tigecycline demonstrated a higher susceptibility rate against than against (90.9% versus 40.2%). Of 155 clinical isolates analyzed, 89% produced carbapenemases, with a majority of isolates producing KPC (50%) or NDM (33.5%)-type beta-lactamases among and The incidence of CRE infection in China was 4.0 per 10,000 discharges. The patient-based disease burden in tertiary hospitals in China is severe, suggesting an urgent need to enhance infection control.
Topics: Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; China; Citrobacter freundii; Enterobacter cloacae; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Polymyxin B; Urinary Tract Infections; beta-Lactamases
PubMed: 29203488
DOI: 10.1128/AAC.01882-17 -
Cell Metabolism Jan 2024The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In...
The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In previous studies, we demonstrated that intestinal nitrogen-recycling bacteria are enriched in patients with MM. However, their role in MM relapse remains unclear. This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and curative effect scores. These findings provide new therapeutic targets and strategies for the intervention of MM progression and drug resistance.
Topics: Humans; Bortezomib; Multiple Myeloma; Gastrointestinal Microbiome; Cell Line, Tumor; Membrane Proteins; NIMA-Related Kinases; Solute Carrier Family 12, Member 2
PubMed: 38113887
DOI: 10.1016/j.cmet.2023.11.019 -
Acta Medica Indonesiana Jan 2022Urease is an enzyme produced by diverse bacterial species including normal flora, non pathogens, and pathogens such as Proteus mirabilis, Staphylococcus saprophyticus,...
Urease is an enzyme produced by diverse bacterial species including normal flora, non pathogens, and pathogens such as Proteus mirabilis, Staphylococcus saprophyticus, Klebsiella pneumonia, Citrobacter freundii, Enterobacter cloacae Helicobacter spp and Helicobacter pylori. Urease is central in Helicobacter pylori metabolism and virulence, important for colonization in the gastric mucosa. Urease catalyzes the hydrolysis of urea to ammonia and carbamate. This ammonia product can be examined by Urease biopsy test and Urea breath test such as 14C-Urea Breath Test or 13C-Urea Breath Test.Previously, the Urea breath test was intended to detect an increase in ammonia which is a urease product in the gastric mucosa produced by pathogenic gastric bacteria, such as Helicobacter pylori, etc.Acute and chronic gastritis caused by infection with these pathogenic bacteria infection turned out to be positive on Urea breath test. Indirectly, the results of the urea breath test are also related to the presence of inflammation in acute and chronic gastritis, regardless of whether the cause is Helicobacter pylori or other urease-producing pathogenic bacteria.The use of the urea breath test indirectly in diagnosing acute and chronic gastritis should be studied further. The use of the urea breath test is indeed very important to assist health services in countries and regions with limited endoscopic facilities, especially developing countries.We know that the prevalence of Helicobacter pylori infection in causing acute and chronic gastritis by examination of Urea breath test in Indonesia is not too high, ranging from 2-11.2%. So that is why more studies on non-Helicobacter pylori producing urease pathogens are needed, which can appear as a false positive urea breath test.
Topics: Ammonia; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Urea; Urease
PubMed: 35398819
DOI: No ID Found -
Journal of Microbiological Methods Sep 2022The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated proteins) system is a useful tool to edit genomes quickly and efficiently....
The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated proteins) system is a useful tool to edit genomes quickly and efficiently. However, the use of CRISPR/Cas9 to edit bacterial genomes has been limited to select microbial chassis primarily used for bioproduction of high value products. Thus, expansion of CRISPR/Cas9 tools to other microbial organisms is needed. Here, our aim was to assess the suitability of CRISPR/Cas9 for genome editing of the Citrobacter freundii type strain ATCC 8090. We evaluated the commonly used two plasmid pCas/pTargetF system to enable gene deletions and insertions in C. freundii and determined editing efficiency. The CRISPR/Cas9 based method enabled high editing efficiency (~91%) for deletion of galactokinase (galk) and enabled deletion with various single guide RNA (sgRNA) sequences. To assess the ability of CRISPR/Cas9 tools to insert genes, we used the fluorescent reporter mNeonGreen, an endopeptidase (yebA), and a transcriptional regulator (xylS) and found successful insertion with high efficiency (81-100%) of each gene individually. These results strengthen and expand the use of CRISPR/Cas9 genome editing to C. freundii as an additional microbial chassis.
Topics: CRISPR-Cas Systems; Citrobacter freundii; Gene Editing; Genome, Bacterial
PubMed: 35779647
DOI: 10.1016/j.mimet.2022.106533 -
Journal of Global Antimicrobial... Jun 2022Citrobacter freundii is an important opportunistic pathogen, and carbapenem-resistant strains pose a significant challenge to public health. Here we report the genetic...
OBJECTIVES
Citrobacter freundii is an important opportunistic pathogen, and carbapenem-resistant strains pose a significant challenge to public health. Here we report the genetic features of antimicrobial resistance genes of a carbapenem-resistant C. freundii SCLZS47 from hospital sewage by using whole genome sequencing.
METHODS
Antimicrobial susceptibility was determined by the broth microdilution method. Whole genomic sequences of SCLZS47 were obtained by using the HiSeq 2000 combined with PacBio RSII platforms. Plasmid incompatibility types, resistance genes, and insertion elements were identified using the PlasmidFinder, ResFinder, and ISfinder, respectively.
RESULTS
SCLZS47 has a circular chromosome and three resistance plasmids, and it carries 23 known ARGs. Among them, bla and three copies of bla are located on the chromosome. Sixteen ARGs are clustered in two accessory modules of a multidrug resistance (MDR) plasmid, and homologous recombination and transposition events contribute to the formation of these MDR regions. Carbapenemase genes bla and bla are carried by a pCKPC18-1-like plasmid and a pNDM-HN380-like plasmid, respectively. Conjugation experiments indicated that both KPC-2- and NDM-1-encoding plasmids are transmissible.
CONCLUSION
Analysis of the genetic features of resistance genes would help to better understand their transmission mechanisms and dynamics in bacterial community, which has significant clinical implications.
Topics: Carbapenems; Citrobacter freundii; Genomics; Plasmids; beta-Lactamases
PubMed: 35489677
DOI: 10.1016/j.jgar.2022.04.014 -
AMB Express Oct 2020Fenvalerate is a pyrethroid insecticide with rapid action, strong targeting, broad spectrum, and high efficiency. However, continued use of fenvalerate has resulted in...
Fenvalerate is a pyrethroid insecticide with rapid action, strong targeting, broad spectrum, and high efficiency. However, continued use of fenvalerate has resulted in its widespread presence as a pollutant in surface streams and soils, causing serious environmental pollution. Pesticide residues in the soil are closely related to food safety, yet little is known regarding the kinetics and metabolic behaviors of fenvalerate. In this study, a fenvalerate-degrading microbial strain, CD-9, isolated from factory sludge, was identified as Citrobacter freundii based on morphological, physio-biochemical, and 16S rRNA sequence analysis. Response surface methodology analysis showed that the optimum conditions for fenvalerate degradation by CD-9 were pH 6.3, substrate concentration 77 mg/L, and inoculum amount 6% (v/v). Under these conditions, approximately 88% of fenvalerate present was degraded within 72 h of culture. Based on high-performance liquid chromatography and gas chromatography-mass spectrometry analysis, ten metabolites were confirmed after the degradation of fenvalerate by strain CD-9. Among them, o-phthalaldehyde is a new metabolite for fenvalerate degradation. Based on the identified metabolites, a possible degradation pathway of fenvalerate by C. freundii CD-9 was proposed. Furthermore, the enzyme localization method was used to study CD-9 bacteria and determine that its degrading enzyme is an intracellular enzyme. The degradation rate of fenvalerate by a crude enzyme solution for over 30 min was 73.87%. These results showed that strain CD-9 may be a suitable organism to eliminate environmental pollution by pyrethroid insecticides and provide a future reference for the preparation of microbial degradation agents and environmental remediation.
PubMed: 33125615
DOI: 10.1186/s13568-020-01128-x -
Annals of Medicine and Surgery (2012) Nov 2023Vaccination against coronavirus disease 2019 (COVID-19) is essential for controlling the ongoing cases of this disease. Citrobacter infections of the bones and joints...
INTRODUCTION
Vaccination against coronavirus disease 2019 (COVID-19) is essential for controlling the ongoing cases of this disease. Citrobacter infections of the bones and joints are extremely uncommon. Thromboembolism and deep vein thrombosis (DVT) are very rare complications.
CASE PRESENTATION
The authors present a rare case of osteomyelitis, septic arthritis, deep venous thrombosis, and pulmonary embolism in a 15-year-old previously healthy boy occurring shortly after receiving the second dose of the Moderna COVID-19 vaccine. He experienced pain, swelling in the right leg, shortness of breath, and fever, followed by chest pain and leg edema. Treatment included anticoagulation, ketorolac for pain management, antipyretics, and intravenous antibiotics (Tazobactam/Piperacillin, Linezolid, Clindamycin) for osteomyelitis.
DISCUSSION
The risk of COVID-19 vaccine-related thrombotic events is minimal. Thrombotic events reported among mRNA is very rare. bone and joint infections are very rare, accounting for a small percentage of cases. Some documented cases include cefotaxime-resistant strains causing necrotizing fascitis and osteomyelitis, including postarthroplasty infections. Due to the diverse range of susceptibility patterns and the widespread occurrence of drug resistance, personalized treatment based on culture and sensitivity testing is recommended. However, in rare cases, severe complications like DVT and joint infections associated with Citrobacter infection may occur and should be reported to the vaccine adverse events reporting system.
CONCLUSION
Administering the COVID-19 vaccine to enhance natural antibodies is crucial, despite the low risk of infection, thromboembolism, and DVT. Healthcare providers should stay vigilant about adverse effects postvaccination and promptly report those cases.
PubMed: 37915646
DOI: 10.1097/MS9.0000000000001351 -
AMB Express May 2022Citrobacter freundii CD-9 is a Gram-negative bacteria sourced from factory sludge that can use fenvalerate as its sole carbon source and has a broad degradation spectrum...
Citrobacter freundii CD-9 is a Gram-negative bacteria sourced from factory sludge that can use fenvalerate as its sole carbon source and has a broad degradation spectrum for pyrethroid pesticides. The whole genome of CD-9 sequenced using Illumina HiSeq PE150 was reported in this study. The CD-9 genome size was 5.33 Mb and the G + C content was 51.55%. A total of 5291 coding genes, 9 5s-rRNA, and 79 tRNA were predicted bioinformatically. 3586 genes annotated to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database that can be involved in 173 metabolic pathways, including various microbial metabolic pathways that degrade exogenous chemicals, especially those that degrade aromatic compounds, and also produce a variety of bioactive substances. Fifty genes related to pyrethroid degradation were identified in the C. freundii CD-9 genome, including 9 dioxygenase, 25 hydrolase, and 16 esterase genes. Notably, RT-qPCR results showed that from the predicted 13 genes related to fenvalerate degradation, the expression of six genes, including esterase, HAD family hydrolase, lipolytic enzyme, and gentisic acid dioxygenase, was induced in the presence of fenvalerate. In this study, the key genes and degradation mechanism of C. freundii CD-9 were analyzed and the results provide scientific evidence to support its application in environmental bioremediation. It can establish application models for different environmental pollution management by constructing genetically engineered bacteria for efficient fenvalerate or developing enzyme formulations that can be industrially produced.
PubMed: 35523901
DOI: 10.1186/s13568-022-01392-z -
Microbiology Spectrum Dec 2022With the globally prevailing carbapenemase-producing (CP) spp., polymyxin antibiotics have been reconsidered as one of the last-resort treatment options. Our study was...
With the globally prevailing carbapenemase-producing (CP) spp., polymyxin antibiotics have been reconsidered as one of the last-resort treatment options. Our study was conducted to investigate the prevalence of in species. From October to November 2021, 650 fecal samples and 215 isolates were collected from healthy individuals and infected patients, respectively. Isolates were screened for the presence of the gene by the PCR method. -carrying strains were identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Due to the susceptibility to colistin, spp. isolates were first induced to increase the expression of on China blue agar plates containing colistin and were then subjected to conjugation experiments. Whole-genome sequencing was performed on the Illumina NovaSeq PE150 system. The prevalence of in the genus from healthy guts and infected patients was 0.62% and 1.86%, respectively. In all -positive strains, MICs of polymyxin B were observed at ≤2 μg/mL, displaying a nonresistant phenotype. As for conjugation experiments, only one isolate successfully transferred the gene to Escherichia coli C600. Whole-genome sequencing showed that eight -positive isolates carried and genes encoding resistance to beta-lactam antibiotics, including , , , , and . We also discovered that could be located on the pKPC-CAV1321 plasmid. Our study investigated the prevalence of - in spp. in both healthy individuals and infected patients and described the carriage of on the pKPC-CAV1321 plasmid for the first time. The emergence of homologues posed a serious threat to the therapeutic efficiency of polymyxin antibiotics. Citrobacter freundii is generally regarded as an opportunistic pathogen associated with a variety of nosocomial infections. In this study, we investigated the prevalence of in spp. isolates from healthy individuals and infected patients and highlighted the importance of the rational use of antibiotics. In addition, this epidemiological investigation is the first to describe the carriage of on plasmid pKPC-CAV1321 and confirms the horizontal transfer of this plasmid. Our research may shed new light on further studies of dissemination in humans.
Topics: Humans; Anti-Bacterial Agents; beta-Lactamases; Citrobacter; Colistin; Drug Resistance, Bacterial; Escherichia coli; Microbial Sensitivity Tests; Plasmids
PubMed: 36374095
DOI: 10.1128/spectrum.01346-22