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1.
Nat Commun ; 15(1): 6969, 2024 Aug 14.
Article de Anglais | MEDLINE | ID: mdl-39138200

RÉSUMÉ

Bloodstream infections caused by the opportunistic pathogen Klebsiella pneumoniae are associated with adverse health complications and high mortality rates. Antimicrobial resistance (AMR) limits available treatment options, thus exacerbating its public health and clinical burden. Here, we aim to elucidate the population structure of K. pneumoniae in bloodstream infections from a single medical center and the drivers that facilitate the dissemination of AMR. Analysis of 136 short-read genome sequences complemented with 12 long-read sequences shows the population consisting of 94 sequence types (STs) and 99 clonal groups, including globally distributed multidrug resistant and hypervirulent clones. In vitro antimicrobial susceptibility testing and in silico identification of AMR determinants reveal high concordance (90.44-100%) for aminoglycosides, beta-lactams, carbapenems, cephalosporins, quinolones, and sulfonamides. IncF plasmids mediate the clonal (within the same lineage) and horizontal (between lineages) transmission of the extended-spectrum beta-lactamase gene blaCTX-M-15. Nearly identical plasmids are recovered from isolates over a span of two years indicating long-term persistence. The genetic determinants for hypervirulence are carried on plasmids exhibiting genomic rearrangement, loss, and/or truncation. Our findings highlight the importance of considering both the genetic background of host strains and the routes of plasmid transmission in understanding the spread of AMR in bloodstream infections.


Sujet(s)
Antibactériens , Infections à Klebsiella , Klebsiella pneumoniae , Tests de sensibilité microbienne , Plasmides , bêta-Lactamases , Klebsiella pneumoniae/génétique , Klebsiella pneumoniae/effets des médicaments et des substances chimiques , Klebsiella pneumoniae/isolement et purification , Klebsiella pneumoniae/pathogénicité , Plasmides/génétique , Humains , Infections à Klebsiella/microbiologie , Infections à Klebsiella/transmission , Infections à Klebsiella/épidémiologie , Antibactériens/pharmacologie , bêta-Lactamases/génétique , Multirésistance bactérienne aux médicaments/génétique , Bactériémie/microbiologie , Bactériémie/transmission , Virulence/génétique , Carbapénèmes/pharmacologie
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(8): 1242-1246, 2024 Aug 06.
Article de Chinois | MEDLINE | ID: mdl-39142895

RÉSUMÉ

To investigate the strain composition and drug resistance characteristics of G+(Gram positive cocci) cocci causing bloodstream infections in the People's Hospital of Inner Mongolia Autonomous Region in recent years and provide a basis for the empirical and rational use of drugs for the prevention and treatment of bloodstream infections caused by G+cocci. The strain composition and drug-resistant characteristics of G+cocci isolated from positive blood culture specimens sent to various departments of the Inner Mongolia Autonomous Region People's Hospital from January 2015 to December 2022 were retrospectively analyzed, and the higher detection rates of Staphylococcus hominis and Staphylococcus epidermidis, Enterococcus faecium and Enterococcus faecalis, and methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) were examined. MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) were comparatively analyzed for resistance. The resistance data were analyzed by Whonet 5.6 statistical software, the significance of difference was analyzed by SPSS 22.0 software, and the resistance rate was compared by χ2 test. The results showed that 1 209 strains of G+cocci, in terms of the composition ratio, from high to low, were mainly human staphylococci (32.5%,393/1 209), Staphylococcus epidermidis (27.8%, 336/1 209), Staphylococcus aureus (14.9%,180/1 209) and Enterococcus faecalis (10.6%, 128/1 209). Among them, the detection rate of methicillin-resistant Staphylococcus aureus (MRSA) (42.8%, 77/180) was lower than that of methicillin-resistant coagulase-negative staphylococcus (MRCNS) (71.5%, 608/850); and among enterococci, the detection rate of Enterococcus faecalis (71.5%, 128/179) was much higher than that of Enterococcus faecalis (28.5%, 51/179). For drug resistance, the resistance rate to five commonly used antimicrobial drugs, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin and tetracycline, was higher in Staphylococcus hominis than in Staphylococcus epidermidis (χ2=7.152-64.080, P<0.05); however, for the aminoglycoside antimicrobial drug gentamicin, the rate of resistance in Staphylococcus humanus was lower than in Staphylococcus epidermidis, and the difference was statistically significant (χ2=11.895, P<0.05); no strains resistant to linezolid and vancomycin were found in both. Comparison of the resistance rates to seven antimicrobial drugs, gentamicin, rifampicin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin and tetracycline, was significantly higher in MRSA than in MSSA (χ2=6.169-56.941, P<0.05); however, the resistance rate to cotrimoxazole, MRSA (15.6%, 12/77) was significantly lower than that of MSSA (35.3%, 36/102), and the difference was statistically significant (χ2=5.155, P<0.05); MRSA and MSSA resistant to linezolid and vancomycin were not found. The resistance rate of Enterococcus faecalis to penicillin G and ampicillin was much higher than that of Enterococcus faecalis, and the difference was statistically significant (χ2=22.965, P<0.05), and vancomycin-resistant enterococci (VRE) were not found. In conclusion, for staphylococci, except for individual antibiotics, S.hominis and MRSA were more resistant to most antimicrobial drugs than S. epidermidis and MSSA, showing a multidrug-resistant pattern. For enterococci, except for penicillin G and ampicillin resistance rate, Enterococcus faecalis is much higher than Enterococcus faecalis, the rest of the antimicrobial drugs did not see a significant difference, in addition to vancomycin-resistant enterococci were not detected. Clinicians should pay great attention to the monitoring data of multidrug-resistant G+cocci isolated from blood cultures to provide a basis for empirical and rational use of drugs in the clinic, to effectively prevent and reduce the incidence of bloodstream infections caused by G+cocci.


Sujet(s)
Antibactériens , Tests de sensibilité microbienne , Humains , Antibactériens/pharmacologie , Chine , Cocci à Gram positif/effets des médicaments et des substances chimiques , Cocci à Gram positif/isolement et purification , Études rétrospectives , Staphylococcus aureus résistant à la méticilline/effets des médicaments et des substances chimiques , Enterococcus faecalis/effets des médicaments et des substances chimiques , Enterococcus faecalis/isolement et purification , Résistance bactérienne aux médicaments , Hôpitaux , Staphylococcus aureus/effets des médicaments et des substances chimiques , Staphylococcus epidermidis/effets des médicaments et des substances chimiques , Staphylococcus epidermidis/isolement et purification , Bactériémie/microbiologie , Bactériémie/épidémiologie
3.
Trop Biomed ; 41(2): 220-223, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-39154277

RÉSUMÉ

Vibrio vulnificus infection is associated with high morbidity and mortality in high-risk patients. Poor prognoses could lead to >50% mortality rate. The present report describes a case of V. vulnificus bacteremia in a cirrhotic patient with underlying hepatitis C. He presented with generalised abdominal pain associated with distention and could not ambulate for one week. He also complained of fever for six days and pruritus for 10 days. Tea-coloured urine was noted in continuous bag drainage. The abdomen was distended but soft, with mild tenderness palpated over the left lumbar and iliac region. Blood investigation indicated ongoing infection and inflammation. The aerobic blood culture was identified using the matrix-assisted laser desorption/ionisation-time of flight mass spectrometry and confirmed via 16S rDNA sequencing as V. vulnificus. Multilocus sequence typing of the isolated V. vulnificus revealed a novel sequence type, ST540. The patient responded well to the intravenous cefoperazone and was then discharged with a four day-course of oral ciprofloxacin, 500 mg twice daily after completing the intravenous cefoperazone for 10 days. Clinical history and physical examination are important for early antibiotic therapy initiation and appropriate surgical intervention. Furthermore, bacterial strain typing is also essential for epidemiological surveillance and potentially anticipating the pathogen's virulence traits, which are vital in controlling and preventing the spread of infection.


Sujet(s)
Infections à Vibrio , Vibrio vulnificus , Humains , Mâle , Vibrio vulnificus/isolement et purification , Infections à Vibrio/microbiologie , Bactériémie/microbiologie , Antibactériens/usage thérapeutique , ARN ribosomique 16S/génétique , Hépatite C/complications , Typage par séquençage multilocus , Adulte d'âge moyen , Cirrhose du foie/complications
4.
Trop Biomed ; 41(2): 206-208, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-39154274

RÉSUMÉ

Globally, Campylobacter spp. are responsible for most cases of bacterial gastrointestinal infections in humans and although rare, extraintestinal Campylobacter infections have been described. A 2-yearold neutropenic girl with underlying precursor B-cell acute lymphoblastic leukemia presented with a 3-day history of diarrhea. Her stool culture yielded no enteric bacterial pathogens. However, when her blood culture was flagged as positive for bacterial growth, no colonies could be observed on routine bacteriological isolation media. Nonetheless, gram-negative bacilli with seagull and spiral morphologies were seen when the surface of the isolation media used to subculture her blood was Gram-stained. Bacterial colonies were only visible when a subculture was attempted on a Campylobacter blood-free selective agar medium. The organism was identified as Campylobacter jejuni by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Since the organism was erythromycin-resistant and the patient's age precluded the use of tetracycline and ciprofloxacin, an antibiotic regimen consisting of piperacillin-tazobactam and gentamicin was commenced. Her C. jejuni bacteremia resolved following eight days of antibiotic therapy.


Sujet(s)
Antibactériens , Bactériémie , Infections à Campylobacter , Campylobacter jejuni , Humains , Femelle , Bactériémie/microbiologie , Bactériémie/traitement médicamenteux , Bactériémie/diagnostic , Campylobacter jejuni/isolement et purification , Infections à Campylobacter/traitement médicamenteux , Infections à Campylobacter/microbiologie , Infections à Campylobacter/diagnostic , Antibactériens/usage thérapeutique , Enfant d'âge préscolaire , Spectrométrie de masse MALDI , Leucémie-lymphome lymphoblastique à précurseurs B/diagnostic , Leucémie-lymphome lymphoblastique à précurseurs B/traitement médicamenteux
5.
PLoS One ; 19(8): e0308395, 2024.
Article de Anglais | MEDLINE | ID: mdl-39110739

RÉSUMÉ

Allogeneic hematopoietic cell transplantation (HCT) is a crucial treatment for various diseases, including hematological malignancies, solid tumors, and genetic disorders. Despite its curative potential, HCT is associated with severe complications, notably infections, graft-versus-host disease, and organ damage. Infections, particularly bloodstream infections (BSIs), pose a significant threat in the initial weeks post-HCT, necessitating effective management strategies. This retrospective study aimed to clarify the incidence, pathogens, and risk factors associated with BSI within the first 30 days after allogeneic HCT in children/adolescents and young adults (AYAs). The study included 115 patients aged <31 years who underwent 121 allogeneic HCTs at the Department of Pediatrics, Nagoya University Hospital between January 1, 2018, and March 31, 2022. Data encompassed demographic characteristics, HCT details, and BSI information. Overall, 27 of 121 patients developed BSI with the cumulative incidence of 23.5% (95% confidence intervals [CI]: 17.0%-30.6%) at 30 days after HCT. The median onset time of BSI was 7 (range, 4-26 days) after HCT. Gram-positive bacteria accounted for 89% of pathogens isolated from blood cultures, with Streptococcus mitis/oralis being the most common. In multivariable analysis, tandem HCT (subdistribution hazard ratio [SHR]: 5.67, 95% CI: 2.74-11.7, p < 0.001) and peripherally inserted central catheters (SHR: 2.96, 95% CI: 1.34-6.55, p = 0.007) were identified as independent risk factors for BSI. In patients receiving tandem HCT, the pathogens isolated from blood cultures were all gram-positive bacteria, with Streptococcus mitis/oralis accounting for up to 67% of the isolated pathogens. Tandem HCT and PICCs were identified as independent risk factors for BSI after allogeneic HCT in children/AYAs. The pathogens were commonly gram-positive, and Streptococcus mitis/oralis is important in patients who received tandem HCT. These data can provide valuable information for future studies to consider effective interventions to reduce the risk of BSI in high-risk patients.


Sujet(s)
Transplantation de cellules souches hématopoïétiques , Humains , Transplantation de cellules souches hématopoïétiques/effets indésirables , Mâle , Femelle , Enfant , Adolescent , Facteurs de risque , Jeune adulte , Adulte , Enfant d'âge préscolaire , Études rétrospectives , Nourrisson , Transplantation homologue/effets indésirables , Incidence , Bactériémie/épidémiologie , Bactériémie/étiologie , Bactériémie/microbiologie
6.
BMC Infect Dis ; 24(1): 796, 2024 Aug 08.
Article de Anglais | MEDLINE | ID: mdl-39118021

RÉSUMÉ

BACKGROUND: Invasive Escherichia coli disease (IED), also known as invasive extraintestinal pathogenic E. coli disease, is a leading cause of sepsis and bacteremia in older adults that can result in hospitalization and sometimes death and is frequently associated with antimicrobial resistance. Moreover, certain patient characteristics may increase the risk of developing IED. This study aimed to validate a machine learning approach for the unbiased identification of potential risk factors that correlate with an increased risk for IED. METHODS: Using electronic health records from 6.5 million people, an XGBoost model was trained to predict IED from 663 distinct patient features, and the most predictive features were identified as potential risk factors. Using Shapley Additive predictive values, the specific relationships between features and the outcome of developing IED were characterized. RESULTS: The model independently predicted that older age, a known risk factor for IED, increased the chance of developing IED. The model also predicted that a history of ≥ 1 urinary tract infection, as well as more frequent and/or more recent urinary tract infections, and ≥ 1 emergency department or inpatient visit increased the risk for IED. Outcomes were used to calculate risk ratios in selected subpopulations, demonstrating the impact of individual or combinations of features on the incidence of IED. CONCLUSION: This study illustrates the viability and validity of using large electronic health records datasets and machine learning to identify correlating features and potential risk factors for infectious diseases, including IED. The next step is the independent validation of potential risk factors using conventional methods.


Sujet(s)
Infections à Escherichia coli , Apprentissage machine , Humains , Infections à Escherichia coli/épidémiologie , Infections à Escherichia coli/microbiologie , Facteurs de risque , Sujet âgé , Femelle , Mâle , Adulte d'âge moyen , Dossiers médicaux électroniques , Sujet âgé de 80 ans ou plus , Escherichia coli/effets des médicaments et des substances chimiques , Escherichia coli/isolement et purification , Escherichia coli/pathogénicité , Adulte , Infections urinaires/microbiologie , Infections urinaires/épidémiologie , Bactériémie/microbiologie , Bactériémie/épidémiologie
7.
Article de Anglais | MEDLINE | ID: mdl-39165021

RÉSUMÉ

Abstract: From 1 January 2020 to 31 December 2021, thirty-eight institutions across Australia submitted data to the Australian Group on Antimicrobial Resistance (AGAR) from patients aged < 18 years (AGAR-Kids). Over the two years, 1,679 isolates were reported from 1,611 patients. This AGAR-Kids report aims to describe the population of children and adolescents with bacteraemia reported to AGAR and the proportion of resistant isolates. Overall, there were 902 gram-negative isolates reported: 800 Enterobacterales, 61 Pseudomonas aeruginosa and 41 Acinetobacter spp. Among the Enterobacterales, 12.9% were resistant to third generation cephalosporins; 11.6% to gentamicin/tobramycin; and 11.2% to piperacillin-tazobactam. In total, 14.5% of Enterobacterales were multi-drug resistant (MDR). Only 3.3% of P. aeruginosa were resistant to carbapenems and 4.9% were MDR. Resistance in Acinetobacter spp was uncommon. Of 607 Staphylococcus aureus isolates, 12.9% were methicillin-resistant (MRSA). Almost half of S. aureus isolates from the Northern Territory were MRSA. In S. aureus, resistance to erythromycin was 13.2%; 12.4% to clindamycin; and 5.3% to ciprofloxacin. Resistance to all antibiotics tested was higher in MRSA. Overall, 6.5% of S. aureus were MDR, of which 65% were MRSA. Almost three-quarters of the 170 Enterococcus spp. reported were E. faecalis, and half were from patients < 1 year old. Ampicillin resistance in enterococci was 19.6%. Eight isolates were vancomycin resistant and three isolates were teicoplanin resistant. Five E. faecium isolates were classified as MDR. This AGAR-Kids report highlights clear differences in the geographic distribution of pathogens and resistance profiles across Australia.


Sujet(s)
Antibactériens , Bactériémie , Tests de sensibilité microbienne , Humains , Adolescent , Enfant , Australie/épidémiologie , Enfant d'âge préscolaire , Nourrisson , Antibactériens/pharmacologie , Bactériémie/microbiologie , Bactériémie/épidémiologie , Bactériémie/traitement médicamenteux , Mâle , Femelle , Multirésistance bactérienne aux médicaments , Nouveau-né , Bactéries à Gram négatif/effets des médicaments et des substances chimiques , Bactéries à Gram négatif/isolement et purification , Résistance bactérienne aux médicaments
8.
BMJ Case Rep ; 17(8)2024 Aug 03.
Article de Anglais | MEDLINE | ID: mdl-39097326

RÉSUMÉ

A man in his 70s was admitted to an intensive care unit with severe COVID-19 and treated with dexamethasone and tocilizumab. After recovery from COVID-19, he developed Clostridium butyricum bacteraemia and non-occlusive mesenteric ischaemia, with fatal outcome. He had been prescribed C. butyricum MIYAIRI 588 fine granules as probiotics for a month. The genome sequences of the C. butyricum isolate from the blood culture and C. butyricum MIYAIRI 588 fine granules were identical by single nucleotide polymorphism analysis. This is the first case of definitive probiotics-related C. butyricum bacteraemia after treatment of severe COVID-19.


Sujet(s)
Bactériémie , COVID-19 , Clostridium butyricum , Probiotiques , Séquençage du génome entier , Humains , Mâle , Clostridium butyricum/génétique , Probiotiques/usage thérapeutique , Bactériémie/traitement médicamenteux , Bactériémie/microbiologie , COVID-19/complications , Sujet âgé , Infections à Clostridium , Issue fatale , SARS-CoV-2 , Ischémie mésentérique
9.
J Drugs Dermatol ; 23(8): 680-682, 2024 08 01.
Article de Anglais | MEDLINE | ID: mdl-39093644

RÉSUMÉ

Erythroderma is characterized by diffuse erythema and scale covering over 90% body surface area that can affect individuals with inflammatory dermatoses such as psoriasis. Complications of erythrodermic psoriasis include infection and cardiovascular compromise. Here we present a case of a 68 year-old man who was hospitalized for erythrodermic psoriasis refractory to multiple immunosuppressive and immunomodulatory therapies, ultimately developing sepsis due to bacteremia and fungemia complicated by infective endocarditis and a mycotic aneurysm. Although the widespread loss of epidermal function in erythroderma increases the risk of infection by opportunistic pathogens, water loss, and electrolyte imbalances, there are very few reported cases of psoriatic erythroderma complicated by fungemia and mycotic aneurysm. Given the high mortality associated with widespread epidermal dysfunction, there is a great need for evidence-based treatment guidelines for psoriatic erythroderma. J Drugs Dermatol. 2024;23(8): doi:10.36849/JDD.7751.


Sujet(s)
Anévrysme infectieux , Dermatite exfoliatrice , Psoriasis , Choc septique , Humains , Mâle , Psoriasis/complications , Psoriasis/traitement médicamenteux , Psoriasis/diagnostic , Sujet âgé , Dermatite exfoliatrice/diagnostic , Dermatite exfoliatrice/étiologie , Dermatite exfoliatrice/thérapie , Dermatite exfoliatrice/traitement médicamenteux , Choc septique/diagnostic , Choc septique/microbiologie , Choc septique/thérapie , Choc septique/étiologie , Anévrysme infectieux/diagnostic , Anévrysme infectieux/thérapie , Anévrysme infectieux/microbiologie , Issue fatale , Fongémie/diagnostic , Fongémie/traitement médicamenteux , Fongémie/microbiologie , Fongémie/complications , Guides de bonnes pratiques cliniques comme sujet , Bactériémie/diagnostic , Bactériémie/traitement médicamenteux , Bactériémie/complications , Bactériémie/microbiologie
10.
BMC Pediatr ; 24(1): 526, 2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-39143544

RÉSUMÉ

INTRODUCTION: Early-onset neonatal sepsis (EONS) significantly impacts neonatal morbidity and mortality, with maternal bacteremia during the peripartum period being a potential risk factor. This study aims to explore the association between peripartum maternal bacteremia and EONS. METHODS: A retrospective cohort study at the Women's Wellness and Research Center in Doha, Qatar (2015-2019) compared women with and without bacteremia, based on blood cultures taken from up to seven days before to 48 h after delivery, examining the association with EONS. RESULTS: Among the 536 maternal blood cultures analyzed, 102 (19.0%) were positive. The most prevalent organisms were Group B streptococcus (GBS) (39.2%), followed by Escherichia coli (14.7%) and anaerobes (10.8%). Neonates from bacteremic mothers had lower birth weights (2913 ± 86 g vs. 3140 ± 745 g; MD 227.63 g; 95% CI 61.72 - 393.55; p = 0.007), required more resuscitation (27.5% vs. 13.2%; OR 2.48; 95% CI 1.48 - 4.17; p < 0.001), and received antibiotics for ≥ 7 days more frequently (41.2% vs. 16.6%; OR 3.51; 95% CI 2.20 - 5.62; p < 0.001) compared to those from non-bacteremic mothers. Maternal Gram-positive (GP) organisms were more commonly isolated in term gestation (67.9%) compared to Gram-negative (GN) (22.2%) and anaerobic bacteremias (9.9%). During intrapartum, GP bacteremia was predominant (67.1%) vs. GN (21.4%) and Anaerobes (11.4%), with GN bacteremia being more common in postpartum samples. Culture-proven EONS occurred in 0.75% of the cohort, affecting 3.9% of infants from bacteremic mothers vs. none in controls (OR 2.34; 95% CI 1.27 - 4.31; p < 0.001). Culture-negative EONS appeared in 14.7% of infants from bacteremic mothers vs. 7.8% in controls (OR 2.02; 95% CI, 1.05 - 3.88; p = 0.03). Among 40 cases of maternal GBS bacteremia, culture-proven GBS EONS occurred in 3 neonates (7.5%), all from mothers with negative GBS screening, compared to none in the control group. A strong association was found between EONS and maternal bacteremia due to any organism (aOR 2.34; 95% CI, 1.24 - 4.41; p = 0.009), GP bacteremia (aOR 3.66; 95% CI, 1.82 - 7.34; p < 0.001), or GBS (aOR 5.74; 95% CI, 2.57 - 12.81; p < 0.001). Bacteremia due to GN and Anaerobic organisms were not associated with EONS. Chorioamnionitis and antepartum fever were independent predictors for EONS associated with significant bacterial isolates. CONCLUSION: This study underscores the significant impact of maternal GP bacteremia, particularly from GBS, on EONS. The strong association highlights the need for vigilant monitoring and interventions in pregnancies complicated by bacteremia to reduce adverse neonatal outcomes.


Sujet(s)
Bactériémie , Sepsis néonatal , Période de péripartum , Complications infectieuses de la grossesse , Humains , Études rétrospectives , Femelle , Bactériémie/épidémiologie , Bactériémie/microbiologie , Sepsis néonatal/microbiologie , Sepsis néonatal/épidémiologie , Nouveau-né , Grossesse , Adulte , Complications infectieuses de la grossesse/épidémiologie , Complications infectieuses de la grossesse/microbiologie , Qatar/épidémiologie , Facteurs de risque , Infections à streptocoques/épidémiologie , Jeune adulte
11.
Nat Commun ; 15(1): 6040, 2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-39019927

RÉSUMÉ

The lack of new drugs that are effective against antibiotic-resistant bacteria has caused increasing concern in global public health. Based on this study, we report development of a modified antimicrobial drug through structure-based drug design (SBDD) and modular synthesis. The optimal modified compound, F8, was identified, which demonstrated in vitro and in vivo broad-spectrum antibacterial activity against drug-resistant bacteria and effectively mitigated the development of resistance. F8 exhibits significant bactericidal activity against bacteria resistant to antibiotics such as methicillin, polymyxin B, florfenicol (FLO), doxycycline, ampicillin and sulfamethoxazole. In a mouse model of drug-resistant bacteremia, F8 was found to increase survival and significantly reduce bacterial load in infected mice. Multi-omics analysis (transcriptomics, proteomics, and metabolomics) have indicated that ornithine carbamoyl transferase (arcB) is a antimicrobial target of F8. Further molecular docking, Isothermal Titration Calorimetry (ITC), and Differential Scanning Fluorimetry (DSF) studies verified arcB as a effective target for F8. Finally, mechanistic studies suggest that F8 competitively binds to arcB, disrupting the bacterial cell membrane and inducing a certain degree of oxidative damage. Here, we report F8 as a promising candidate drug for the development of antibiotic formulations to combat antibiotic-resistant bacteria-associated infections.


Sujet(s)
Antibactériens , Conception de médicament , Tests de sensibilité microbienne , Antibactériens/pharmacologie , Antibactériens/composition chimique , Animaux , Souris , Simulation de docking moléculaire , Résistance bactérienne aux médicaments/effets des médicaments et des substances chimiques , Protéines bactériennes/métabolisme , Protéines bactériennes/génétique , Bactériémie/traitement médicamenteux , Bactériémie/microbiologie , Multirésistance bactérienne aux médicaments/effets des médicaments et des substances chimiques , Femelle
12.
Antimicrob Agents Chemother ; 68(8): e0022024, 2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-38975753

RÉSUMÉ

Data guiding the duration and route of streptococcal bloodstream infection (BSI) treatment are lacking. We conducted a retrospective cohort study of adults hospitalized with uncomplicated streptococcal BSI in a large integrated healthcare system from 2013 to 2020. The exposures of interest were antibiotic duration (5-10 days vs. 11-15 days) and antibiotic route (oral switch vs. entirely intravenous). The primary outcome was a composite 90-day outcome comprised of all-cause mortality, recurrent streptococcal BSI, or readmission. We performed non-inferiority analyses for each exposure. Separate multivariable Cox proportional hazards regression models were constructed for each exposure. The antibiotic duration analysis included 1,407 patients (5-10 days, n = 246; 11-15 days, n = 1,161). We found that 5-10-day courses were non-inferior to 11-15-day courses (P = 0.047). The antibiotic route analysis included 1,461 patients (oral switch, n = 1,112; entirely intravenous, n = 349). Oral step-down therapy did not meet the criteria for non-inferiority (P = 0.06). In the adjusted models, no significant difference was found in the primary outcome rate by antibiotic duration or antibiotic route at discharge. We found that 5-10-day courses were non-inferior to longer courses, and thus may be a safe and effective treatment option in the treatment of uncomplicated streptococcal bacteremia. Randomized controlled trials are needed to confirm the equivalent outcomes with shorter regimens and to definitively determine the optimal antibiotic route on discharge.


Sujet(s)
Antibactériens , Bactériémie , Infections à streptocoques , Humains , Antibactériens/usage thérapeutique , Infections à streptocoques/traitement médicamenteux , Infections à streptocoques/microbiologie , Études rétrospectives , Mâle , Femelle , Adulte d'âge moyen , Bactériémie/traitement médicamenteux , Bactériémie/microbiologie , Adulte , Sujet âgé , Administration par voie intraveineuse , Administration par voie orale , Modèles des risques proportionnels , Réadmission du patient/statistiques et données numériques
13.
Antimicrob Agents Chemother ; 68(8): e0066324, 2024 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-38990012

RÉSUMÉ

Non-carbapenemase-producing carbapenem-resistant Enterobacterales (non-CP CRE) may be associated with a grave outcome. The common underlying mechanism is beta-lactamases and mutations in outer membrane porins. We report a case of a deep-seated infection caused by Klebsiella pneumoniae ST395 not amenable to source control, involving recurrent bloodstream infection, resulting in in vivo selection of carbapenem resistance under therapy. Three consecutive K. pneumoniae blood isolates were studied using short- and long-read sequencing. The genomes were subject to resistome and virulome, phylogenetic, and plasmid analyses. ompK36 porins were analyzed at the nucleotide and amino acid levels. Genomes were compared to 297 public ST395 K. pneumoniae genomes using cgMLST, resistome, and porin analyses and the EuSCAPE project. Relevant ompK36 and micF sequences were extracted and analyzed as above. The three sequential K. pneumoniae blood isolates belonged to the same clone. Subsequent CR isolates revealed a new large deletion of the ompK36 gene also involving the upstream region (deletion of micF). Comparison with public ST395 genomes revealed the study isolates belonged to clade B, representing a separate clone. N-terminal large ompK36 truncations were uncommon in both public data sets. In vivo selection of non-CP CRE K. pneumoniae could have substantial clinical implications. Such selection should be scrutinized through repeated cultures and frequent susceptibility testing during antimicrobial treatment, especially in the context of persistent or recurrent bloodstream infections and when adequate source control cannot be achieved. The occurrence of an unusually large deletion involving the ompK36 locus and upstream micF should be further studied.


Sujet(s)
Antibactériens , Protéines bactériennes , Carbapénèmes , Infections à Klebsiella , Klebsiella pneumoniae , Tests de sensibilité microbienne , Porines , Klebsiella pneumoniae/génétique , Klebsiella pneumoniae/effets des médicaments et des substances chimiques , Klebsiella pneumoniae/isolement et purification , Humains , Infections à Klebsiella/traitement médicamenteux , Infections à Klebsiella/microbiologie , Carbapénèmes/pharmacologie , Carbapénèmes/usage thérapeutique , Porines/génétique , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Protéines bactériennes/génétique , Mâle , Bactériémie/microbiologie , Bactériémie/traitement médicamenteux , Phylogenèse , Génome bactérien/génétique , Plasmides/génétique , bêta-Lactamases/génétique
14.
Curr Microbiol ; 81(9): 286, 2024 Jul 29.
Article de Anglais | MEDLINE | ID: mdl-39073451

RÉSUMÉ

Streptococcus spp. are important opportunistic pathogen of bacteremia in both immunocompetent and immunosuppressed patients. A streptococcal strain, designated ST2T, was isolated from the blood specimen of a bacteremic patient. Comparative analyses of 16S rRNA, rpoB and groEL gene sequences demonstrated that the novel strain ST2T is a member of the genus Streptococcus. Based on of 16S rRNA gene sequence similarities, the type strains of Streptococcus (S.) parasanguinis (99.2%), S. ilei (98.8%), S. oralis subsp. oralis (97.6%), S. australis (97.5%) and S. sanguinis (97.5%) were the closest neighbours to strain ST2T. The housekeeping gene sequences (rpoB and groEL) similarities of strain ST2T to these closely related type strains were 80.4-97.4%, respectively. The complete draft genome of strain ST2T consisted of 2,155,906 bp with a G + C content of 42.0%. Strain ST2T has an average nucleotide identity (ANI) value of 94.1 and 81.3% with S. parasanguinis ATCC 15912T and S. ilei I-G2T, respectively. The highest in silico DNA-DNA hybridization value with respect to the closest species S. parasanguinis was 55.6%, below the species cut-off of 70% hybridization. The primary cellular fatty acids of strain ST2T were C16:0, C18:1 ω9c, C18:0 and C14:0. Based on biochemical criteria and molecular genetic evidence, it is proposed that strain ST2T be assigned to a new species of the genus Streptococcus as Streptococcus taoyuanensis sp. nov. The type strain of Streptococcus taoyuanensis is ST2T (=NBRC 115928T = BCRC 81374T) as the type strain.


Sujet(s)
Bactériémie , Composition en bases nucléiques , ADN bactérien , Phylogenèse , ARN ribosomique 16S , Infections à streptocoques , Streptococcus , Bactériémie/microbiologie , Humains , ARN ribosomique 16S/génétique , Streptococcus/génétique , Streptococcus/isolement et purification , Streptococcus/classification , ADN bactérien/génétique , Infections à streptocoques/microbiologie , Analyse de séquence d'ADN , Techniques de typage bactérien , Génome bactérien , Acides gras , Hybridation d'acides nucléiques , Protéines bactériennes/génétique , Mâle
15.
Transpl Infect Dis ; 26(4): e14345, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39012614

RÉSUMÉ

INTRODUCTION: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture. RESULTS: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture. CONCLUSION: Among bacteremic AML patients in the post-HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low.


Sujet(s)
Bactériémie , Hémoculture , Neutropénie fébrile , Transplantation de cellules souches hématopoïétiques , Leucémie aigüe myéloïde , Transplantation homologue , Humains , Transplantation de cellules souches hématopoïétiques/effets indésirables , Bactériémie/microbiologie , Bactériémie/diagnostic , Bactériémie/étiologie , Leucémie aigüe myéloïde/complications , Leucémie aigüe myéloïde/thérapie , Études rétrospectives , Mâle , Femelle , Adulte d'âge moyen , Neutropénie fébrile/microbiologie , Neutropénie fébrile/sang , Adulte , Transplantation homologue/effets indésirables , Sujet âgé , Jeune adulte
16.
Acta Clin Belg ; 79(3): 168-173, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-39007879

RÉSUMÉ

PURPOSE: Blood culture (BC) is the standard for diagnosing bloodstream infections. Available blood culture (BC) systems have been developed to shorten the time to detection (TTD) of positive BCs. This study aimed to evaluate the performance of the Mindray TDR automatic BC system by comparing it with the BacT/ALERT®3D system. METHODS: Sixteen reference strains and 14 clinical isolates were used. Serial dilutions were prepared from all bacterial and yeast colonies with a final concentration of 100 CFU/ml and 10 CFU/ml. The prepared solutions were simultaneously inoculated into the bottles of both systems and placed in blood culture devices. RESULTS: Three hundred and fifty-two (176 BacT/ALERT®3D and 176 Mindray TDR-X060) blood culture bottles were evaluated, 336 aerobic and 16 anaerobic. At both 10 CFU/ml and 100 CFU/ml dilution, there was no significant difference between the two systems in terms of mean detection times for all isolates (p = 0.965, p = 0.245). When evaluated according to the type of organism, the detection time of gram-positive bacteria at 10 CFU/ml dilution was significantly shorter in the BacT/ALERT system (p = 0.019), whereas detection time for yeasts was significantly shorter with the Mindray system (p = 0.047). The number of anaerobic bacteria was too small to draw statistical conclusions, but we observed a trend of shorter detection times in the Mindray TDR-X060 system. CONCLUSION: Two systems with similar operating principles showed different concentrations-dependent performances in terms of positivity detection times depending on the type of microorganism. Mindray TDR-X060 system has been found to be safe to use at high concentrations with this at lower concentrations further comparative studies are needed on the newly introduced Mindray system.


Sujet(s)
Hémoculture , Hémoculture/méthodes , Hémoculture/instrumentation , Humains , Facteurs temps , Bactériémie/diagnostic , Bactériémie/microbiologie , Bactéries/isolement et purification
17.
Medicine (Baltimore) ; 103(29): e39017, 2024 Jul 19.
Article de Anglais | MEDLINE | ID: mdl-39029021

RÉSUMÉ

RATIONALE: Bacterascites are a rare complication of cesarean sections (C/S). Here, we report the case of a patient with bacterascites after an emergent C/S. PATIENT CONCERN: A 41-year-old female reported diffuse abdominal tightness and pain for a week after C/S, who received C/S at 38 4/7 weeks due to superimposed preeclampsia and prolonged labor. DIAGNOSES: Bacterascites caused by Salmonella species after C/S was diagnosed. INTERVENTIONS: Initial treatment included cefmetazole and metronidazole. On day 2, paracentesis was performed, followed by albumin and hydroxyethyl starch administration. By day 3, the patient developed pulmonary edema, necessitating Lasix administration. On day 6, ascites culture revealed Salmonella species resistant to third-generation cephalosporins, leading to meropenem therapy adjustment. This resulted in improved symptoms. Meropenem was continued for 14 days to complete the treatment regimen. OUTCOMES: Follow-up ultrasonography revealed a decrease in ascites. As the patient clinical condition improved, she was discharged on day 20 and scheduled for outpatient department follow-up. No recurrence of ascites was observed during the subsequent follow-up period of 3 months. No ascites were noted 8 days after discharge. LESSONS: Postoperative bacterascites with Salmonella were diagnosed. Antibiotic treatment and therapeutic paracentesis were effective for this condition.


Sujet(s)
Antibactériens , Césarienne , Salmonelloses , Salmonella , Humains , Femelle , Adulte , Césarienne/effets indésirables , Antibactériens/usage thérapeutique , Antibactériens/administration et posologie , Salmonella/isolement et purification , Salmonelloses/diagnostic , Salmonelloses/traitement médicamenteux , Grossesse , Méropénème/usage thérapeutique , Méropénème/administration et posologie , Ascites/étiologie , Ascites/microbiologie , Bactériémie/microbiologie , Bactériémie/traitement médicamenteux , Complications postopératoires/microbiologie , Paracentèse/méthodes
18.
Curr Microbiol ; 81(8): 261, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38981918

RÉSUMÉ

A reliable and above all, rapid antimicrobial susceptibility test (AST) is required for the diganostics of blood stream infections (BSI). In this study, resistance testing using DxM MicroScan WalkAway (MicroScan) from a 4-h subculture is compared with the standard overnight culture (18-24 h). Randomly selected positive blood cultures (PBC, n = 102) with gram-negative bacteria were included in the study. PBC were sub-cultured onto appropriate agar plates and AST by MicroScan was performed after 4 h of incubation and repeated after incubation for 18-24 h as standard. In a total of 1909 drug-strain pairs, the 4-h subculture approach showed a very high essential agreement (EA) (98.6%) and categorical agreement (CA) (97.1%) compared with the standard. The incidence of minor error (mE), major error (ME), very major error (VME), and adjusted very major error (aVME) was 1.1%, 0.4%, 12.9%, and 5.3%, respectively. In summary, the use of 4-h subcultures for resistance testing with the MicroScan offers a very reliable and easy to realize time saving when testing positive blood cultures with gram-negative bacteria.


Sujet(s)
Antibactériens , Hémoculture , Bactéries à Gram négatif , Tests de sensibilité microbienne , Tests de sensibilité microbienne/méthodes , Humains , Hémoculture/méthodes , Antibactériens/pharmacologie , Bactéries à Gram négatif/effets des médicaments et des substances chimiques , Bactériémie/microbiologie , Facteurs temps , Infections bactériennes à Gram négatif/microbiologie
19.
Front Cell Infect Microbiol ; 14: 1359422, 2024.
Article de Anglais | MEDLINE | ID: mdl-39077434

RÉSUMÉ

Background: Aeromonas dhakensis is associated with soft tissue infection, bacteremia and gastroenteritis. Involvement of respiratory system in adults is extremely rare. We report a case of fulminant pneumonia and bacteremia due to A. dhakensis in a patient without underlying diseases. Case presentation: A 26-year-old man became ill suddenly with pneumonia after swimming in a river. Despite intensive support measures in the intensive care unit, he died 13 hours after admission and 4 days after his first symptoms. Autopsy showed abundant Gram-negative bacteria, massive inflammatory cell infiltration, edema, necrosis and hemorrhage in lung tissue. A. dhakensis was isolated from blood culture taken at admission and bronchoalveolar lavage fluid (BALF) after intubation. Moreover, A. dhakensis was also detected in lung tissue by metagenomic next-generation sequencing (mNGS) assay. The infection may have come from river water. Conclusion: In patients who develop a fulminant pneumonia after contacting an aquatic environment, A. dhakensis should be alerted and mNGS may aid in the detection of aquatic pathogens by being more sensitive and specific versus traditional bacterial culture.


Sujet(s)
Aeromonas , Bactériémie , Liquide de lavage bronchoalvéolaire , Infections bactériennes à Gram négatif , Humains , Mâle , Adulte , Aeromonas/isolement et purification , Aeromonas/génétique , Aeromonas/pathogénicité , Bactériémie/microbiologie , Bactériémie/diagnostic , Infections bactériennes à Gram négatif/microbiologie , Infections bactériennes à Gram négatif/diagnostic , Issue fatale , Liquide de lavage bronchoalvéolaire/microbiologie , Poumon/anatomopathologie , Poumon/microbiologie , Pneumopathie bactérienne/microbiologie , Pneumopathie bactérienne/diagnostic , Séquençage nucléotidique à haut débit , Métagénomique
20.
Sci Rep ; 14(1): 15472, 2024 07 05.
Article de Anglais | MEDLINE | ID: mdl-38969796

RÉSUMÉ

This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4+ T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4+ T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4+ T cells might play a pivotal role in SAB PB.


Sujet(s)
Bactériémie , Lymphocytes T CD4+ , Infections à staphylocoques , Staphylococcus aureus , Humains , Mâle , Femelle , Bactériémie/mortalité , Bactériémie/microbiologie , Bactériémie/immunologie , Lymphocytes T CD4+/immunologie , Infections à staphylocoques/mortalité , Infections à staphylocoques/immunologie , Infections à staphylocoques/microbiologie , Staphylococcus aureus/immunologie , Adulte d'âge moyen , Facteurs de risque , Sujet âgé , Études prospectives , Interféron gamma/sang , Interféron gamma/métabolisme , Interleukine-10/sang , Adulte , Cytokines/sang , Cytokines/métabolisme
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