RÉSUMÉ
Salmonella enterica serovar Newport is a human pathogen underreported in most developing countries. It is known for causing gastroenteritis and extraintestinal infections. In this case report, we report the case of ceftriaxone-resistant Salmonella enterica serovar Newport from South India, causing acute gastroenteritis in a sixty-year-old female patient having a history of antimicrobial therapy and recent hospital admission. Serovar Newport, especially among antibiotic-exposed patients, poses a significant public health threat due to its ability to acquire multidrug resistance. This emphasizes the necessity for robust surveillance and monitoring of nontyphoidal Salmonella infections, particularly given the limited data on serovar Newport in India. Vigilance in clinical practice and public health initiatives is crucial to effectively address the emergence and spread of multidrug-resistant strains.
Sujet(s)
Antibactériens , Ceftriaxone , Salmonelloses , Salmonella enterica , Humains , Femelle , Ceftriaxone/pharmacologie , Ceftriaxone/usage thérapeutique , Inde , Salmonelloses/traitement médicamenteux , Salmonelloses/microbiologie , Salmonella enterica/effets des médicaments et des substances chimiques , Salmonella enterica/isolement et purification , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Adulte d'âge moyen , Multirésistance bactérienne aux médicaments , Gastroentérite/microbiologie , Gastroentérite/traitement médicamenteux , Sérogroupe , Tests de sensibilité microbienneRÉSUMÉ
Sortase-assembled pili contribute to virulence in many Gram-positive bacteria. In Enterococcus faecalis, the endocarditis and biofilm-associated pilus (Ebp) is polymerized on the membrane by sortase C (SrtC) and attached to the cell wall by sortase A (SrtA). In the absence of SrtA, polymerized pili remain anchored to the membrane (i.e. off-pathway). Here we show that the high temperature requirement A (HtrA) bifunctional chaperone/protease of E. faecalis is a quality control system that clears aberrant off-pathway pili from the cell membrane. In the absence of HtrA and SrtA, accumulation of membrane-bound pili leads to cell envelope stress and partially induces the regulon of the ceftriaxone resistance-associated CroRS two-component system, which in turn causes hyper-piliation and cell morphology alterations. Inactivation of croR in the OG1RF ΔsrtAΔhtrA background partially restores the observed defects of the ΔsrtAΔhtrA strain, supporting a role for CroRS in the response to membrane perturbations. Moreover, absence of SrtA and HtrA decreases basal resistance of E. faecalis against cephalosporins and daptomycin. The link between HtrA, pilus biogenesis and the CroRS two-component system provides new insights into the E. faecalis response to endogenous membrane perturbations.
Sujet(s)
Aminoacyltransferases , Protéines bactériennes , Biofilms , Cysteine endopeptidases , Enterococcus faecalis , Fimbriae bactériens , Chaperons moléculaires , Fimbriae bactériens/génétique , Fimbriae bactériens/métabolisme , Aminoacyltransferases/génétique , Aminoacyltransferases/métabolisme , Enterococcus faecalis/génétique , Cysteine endopeptidases/génétique , Cysteine endopeptidases/métabolisme , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Chaperons moléculaires/génétique , Chaperons moléculaires/métabolisme , Biofilms/croissance et développement , Membrane cellulaire/métabolisme , Régulation de l'expression des gènes bactériens , Virulence/génétique , Antibactériens/pharmacologie , Ceftriaxone/pharmacologieRÉSUMÉ
The increase in the resistance of mutant strains of Neisseria gonorrhoeae to the antibiotic ceftriaxone is pronounced in the decrease in the second-order acylation rate constant, k2/KS, by penicillin-binding protein 2 (PBP2). These changes can be caused by both the decrease in the acylation rate constant, k2, and the weakening of the binding affinity, i.e., an increase in the substrate constant, KS. A501X mutations in PBP2 affect second-order acylation rate constants. The PBP2A501V variant exhibits a higher k2/KS value, whereas for PBP2A501R and PBP2A501P variants, these values are lower. We performed molecular dynamic simulations with both classical and QM/MM potentials to model both acylation energy profiles and conformational dynamics of four PBP2 variants to explain the origin of k2/KS changes. The acylation reaction occurs in two elementary steps, specifically, a nucleophilic attack by the oxygen atom of the Ser310 residue and C-N bond cleavage in the ß-lactam ring accompanied by the elimination of the leaving group of ceftriaxone. The energy barrier of the first step increases for PBP2 variants with a decrease in the observed k2/KS value. Submicrosecond classic molecular dynamic trajectories with subsequent cluster analysis reveal that the conformation of the ß3-ß4 loop switches from open to closed and its flexibility decreases for PBP2 variants with a lower k2/KS value. Thus, the experimentally observed decrease in the k2/KS in A501X variants of PBP2 occurs due to both the decrease in the acylation rate constant, k2, and the increase in KS.
Sujet(s)
Ceftriaxone , Simulation de dynamique moléculaire , Neisseria gonorrhoeae , Protéines de liaison aux pénicillines , Ceftriaxone/pharmacologie , Neisseria gonorrhoeae/génétique , Neisseria gonorrhoeae/effets des médicaments et des substances chimiques , Neisseria gonorrhoeae/métabolisme , Protéines de liaison aux pénicillines/génétique , Protéines de liaison aux pénicillines/composition chimique , Protéines de liaison aux pénicillines/métabolisme , Antibactériens/pharmacologie , Mutation , Résistance bactérienne aux médicaments/génétique , Acylation , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Protéines bactériennes/composition chimique , Serine-type D-Ala-D-Ala carboxypeptidaseRÉSUMÉ
BACKGROUND: The increased resistance rate of Salmonella to third-generation cephalosporins represented by ceftriaxone (CRO) may result in the failure of the empirical use of third-generation cephalosporins for the treatment of Salmonella infection in children. The present study was conducted to evaluate a novel method for the rapid detection of CRO-resistant Salmonella (CRS). METHODS: We introduced the concept of the ratio of optical density (ROD) with and without CRO and combined it with matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) to establish a new protocol for the rapid detection of CRS. RESULTS: The optimal incubation time and CRO concentration determined by the model strain test were 2 h and 8 µg/ml, respectively. We then conducted confirmatory tests on 120 clinical strains. According to the receiver operating characteristic curve analysis, the ROD cutoff value for distinguishing CRS and non-CRS strains was 0.818 [area under the curve: 1.000; 95% confidence interval: 0.970-1.000; sensitivity: 100.00%; specificity: 100%; P < 10- 3]. CONCLUSIONS: In conclusion, the protocol for the combined ROD and MALDI-TOF MS represents a rapid, accurate, and economical method for the detection of CRS.
Sujet(s)
Antibactériens , Ceftriaxone , Tests de sensibilité microbienne , Salmonelloses , Salmonella , Spectrométrie de masse MALDI , Spectrométrie de masse MALDI/méthodes , Ceftriaxone/pharmacologie , Humains , Antibactériens/pharmacologie , Salmonella/effets des médicaments et des substances chimiques , Salmonelloses/microbiologie , Tests de sensibilité microbienne/méthodes , Résistance bactérienne aux médicaments , Sensibilité et spécificité , Courbe ROCRÉSUMÉ
Objective: This study aims to examine the frequency of Salmonella Paratyphi found in blood cultures and evaluate the antibiotic susceptibility pattern of Salmonella isolates to different antibiotics. Additionally, the study aims to assess the paradigm shift in the trend of enteric fever caused by Salmonella Typhi (S. Typhi) to Salmonella Paratyphi(S. Paratyphi) . Study Design: Retrospective study. Participant: The study enrolled patients aged 12 years and above diagnosed with enteric fever (positive blood culture) and admitted to Peelamedu Samanaidu Govindasamy Naidu (PSG) Hospital. Interventions: The study analyzed demographic and antibiotic susceptibility profiles of Salmonella isolates collected from 106 enteric fever patients in the hospital between 2010 and 2022. The susceptibility profiles of Salmonella isolates to multiple antibiotics were assessed. Results: There were 106 participants, and 95 (89.62%) of them had enteric fever linked to Salmonella Typhi, while only 11 (10.38%) had enteric fever linked to Salmonella Paratyphi A. From 2010 to 2022, the study discovered a general decline in the prevalence of enteric fever caused by Salmonella species. But between 2014 and 2022, the incidence of enteric fever linked to S. Typhi rapidly increased. Azithromycin (100% , n = 106) and ceftriaxone (99% , n = 105) were highly effective against the Salmonella isolates, whereas nalidixic acid was resisted by 3 isolates (4.72%, n = 3). Conclusion: The study observed a higher incidence of Salmonella Typhi in comparison to Paratyphi A and a greater susceptibility of males to enteric fever. Funding: None declared.
Sujet(s)
Antibactériens , Tests de sensibilité microbienne , Salmonella paratyphi A , Salmonella typhi , Fièvre typhoïde , Humains , Mâle , Femelle , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Fièvre typhoïde/épidémiologie , Fièvre typhoïde/microbiologie , Fièvre typhoïde/traitement médicamenteux , Études rétrospectives , Salmonella typhi/effets des médicaments et des substances chimiques , Salmonella typhi/isolement et purification , Salmonella paratyphi A/effets des médicaments et des substances chimiques , Salmonella paratyphi A/isolement et purification , Adulte , Adolescent , Enfant , Adulte d'âge moyen , Jeune adulte , Fièvre paratyphoïde/épidémiologie , Fièvre paratyphoïde/microbiologie , Fièvre paratyphoïde/traitement médicamenteux , Incidence , Résistance bactérienne aux médicaments , Azithromycine/usage thérapeutique , Azithromycine/pharmacologie , Ceftriaxone/usage thérapeutique , Ceftriaxone/pharmacologie , Sujet âgé , PrévalenceRÉSUMÉ
BACKGROUND AND OBJECTIVES: There were 82.4 million new gonorrhoea cases worldwide in 2020. Dual treatment with ceftriaxone or cefixime and azithromycin or doxycycline is currently recommended for gonorrhoea in Indonesia. However, reduced susceptibility and resistance to cephalosporins and azithromycin are increasing. We evaluated the susceptibility pattern of Neisseria gonorrhoeae to cefixime, ceftriaxone, azithromycin and doxycycline. METHOD: N. gonorrhoeae isolates were obtained from 19 male participants with clinically and laboratory-confirmed gonorrhoea. Antibiotic susceptibility testing was conducted by disc diffusion and interpreted according to Clinical and Laboratory Standards Institute and Centers for Disease Control and Prevention criteria. RESULTS: Reduced susceptibility or resistance was observed against doxycycline in 19 isolates (100%), cefixime in six (31.6%), ceftriaxone in three (15.8%) and azithromycin in zero (0%) isolates. DISCUSSION: A dual treatment regimen with ceftriaxone and azithromycin can still be recommended as first-line therapy for gonorrhoea in Indonesia. Antibiotic susceptibility surveillance of N. gonorrhoeae should be routinely conducted.
Sujet(s)
Antibactériens , Azithromycine , Ceftriaxone , Doxycycline , Gonorrhée , Tests de sensibilité microbienne , Neisseria gonorrhoeae , Humains , Indonésie , Neisseria gonorrhoeae/effets des médicaments et des substances chimiques , Antibactériens/usage thérapeutique , Antibactériens/pharmacologie , Gonorrhée/traitement médicamenteux , Mâle , Tests de sensibilité microbienne/méthodes , Azithromycine/usage thérapeutique , Doxycycline/usage thérapeutique , Ceftriaxone/usage thérapeutique , Ceftriaxone/pharmacologie , Adulte , Céfixime/usage thérapeutique , Céfixime/pharmacologie , Soins de santé primaires/statistiques et données numériques , Résistance bactérienne aux médicaments/effets des médicaments et des substances chimiques , Association de médicaments/méthodesRÉSUMÉ
Since 2022, Europe has had 4 cases of extensively drug-resistant Neisseria gonorrhoeae, sequence type 16406, that is resistant to ceftriaxone and highly resistant to azithromycin. We report 2 new cases from France in 2023 involving strains genetically related to the 4 cases from Europe as well as isolates from Cambodia.
Sujet(s)
Antibactériens , Multirésistance bactérienne aux médicaments , Gonorrhée , Neisseria gonorrhoeae , Neisseria gonorrhoeae/effets des médicaments et des substances chimiques , Neisseria gonorrhoeae/génétique , Neisseria gonorrhoeae/isolement et purification , Humains , Gonorrhée/traitement médicamenteux , Gonorrhée/microbiologie , Gonorrhée/épidémiologie , France/épidémiologie , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Mâle , Multirésistance bactérienne aux médicaments/génétique , Tests de sensibilité microbienne , Adulte , Femelle , Azithromycine/pharmacologie , Azithromycine/usage thérapeutique , Ceftriaxone/pharmacologie , Ceftriaxone/usage thérapeutiqueRÉSUMÉ
Ceftriaxone-resistant Neisseria gonorrhoeae FC428-like strains have disseminated across the Asia-Pacific region, with a continuous rise in prevalence during 2015-2022. To mitigate the effect of these strains, we advocate for enhanced molecular diagnostics, expanded surveillance networks, and a regionally coordinated effort to combat the global spread of FC428-like strains.
Sujet(s)
Antibactériens , Ceftriaxone , Résistance bactérienne aux médicaments , Gonorrhée , Neisseria gonorrhoeae , Neisseria gonorrhoeae/effets des médicaments et des substances chimiques , Neisseria gonorrhoeae/génétique , Ceftriaxone/pharmacologie , Humains , Gonorrhée/microbiologie , Gonorrhée/épidémiologie , Gonorrhée/traitement médicamenteux , Asie/épidémiologie , Antibactériens/pharmacologie , Tests de sensibilité microbienne , Prévalence , Histoire du 21ème siècleRÉSUMÉ
OBJECTIVE: Monitoring the susceptibility patterns of Neisseria gonorrhoeae is essential for the continuing compliance with current treatment recommendations. Puerto Rico conducts susceptibility tests on N. gonorrhoeae; however, trends on antimicrobial resistance in the island have not been reported since the mid 80's. METHODS: We performed a secondary analysis of a national data repository on the antimicrobial susceptibility of N. gonorrhoeae isolates between 2012 and 2017; a period of time when the CDC recommended a single dose of ceftriaxone and azithromycin for the treatment of uncomplicated gonorrhea. Data on susceptibility to eight antibiotics using the standard disk diffusion method was obtained for 30.0% (84/276) of the samples collected from the Sexually Transmitted Disease clinics in Puerto Rico. We also performed patient demographic analyses linked to resistance. RESULTS: Rates of resistance to ceftriaxone and azithromycin were 0% and 4.0% (2/50), respectively. The percentage of isolates resistant to antimicrobials no longer recommended in Puerto Rico, such as tetracycline, ciprofloxacin, and penicillin, was 86.0% (43/50), 76.0% (38/50), and 38.0% (19/50), respectively. Prevalence of resistant N. gonorrhoeae was higher among men who have sex with men, MSM (79%, 37/47). DISCUSSION: Lack of resistance to ceftriaxone and slow emergence of azithromycin resistance was identified from 2012-2017. It is imperative to continue the surveillance for emerging patterns of resistance, especially for ceftriaxone, as it is part of the current treatment guidelines. Therefore, protocols for culture based surveillance, including sample transport and processing, should be strengthened to ensure quality assured epidemiology of gonococcal resistance in Puerto Rico.
Sujet(s)
Antibactériens , Résistance bactérienne aux médicaments , Gonorrhée , Tests de sensibilité microbienne , Neisseria gonorrhoeae , Porto Rico , Neisseria gonorrhoeae/effets des médicaments et des substances chimiques , Neisseria gonorrhoeae/isolement et purification , Humains , Mâle , Gonorrhée/traitement médicamenteux , Gonorrhée/microbiologie , Gonorrhée/épidémiologie , Femelle , Antibactériens/pharmacologie , Antibactériens/administration et posologie , Adulte , Jeune adulte , Azithromycine/pharmacologie , Azithromycine/administration et posologie , Ceftriaxone/pharmacologie , Adolescent , Adulte d'âge moyenRÉSUMÉ
BACKGROUND: This study tested the hypothesis that combined ceftriaxone (Cef) and human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) was better than either therapy for alleviating acute septic arthritis (ASA). METHODS AND RESULTS: Adult-male C57BL/6 mice were categorized into control group (Clt), group A (ASA only), group B [ASAâ +â Cef (5 mg/kg, IM per day, at days 2 to 16 after ASA induction)], group C [ASAâ +â HUCDMSCs (5â ×â 105 per mice at days 2, 3, 4 after ASA induction)], and group D (ASAâ +â Cefâ +â HUCDMSCs). Animals were euthanized by day 28. The result demonstrated that the body weight was significantly lower, whereas the ratio of kidney or spleen weight to WB, circulatory WBC count, bacterial colony-formation-unit from circulatory/kidney extraction were significantly higher in group A than in other groups (all Pâ <â .001). The proinflammatory cytokines (IL-6/TNF-α) of knee joint fluid were lowest in Clt and significantly and progressively reduced from groups A to D, whereas the circulatory levels of these 2 parameters at the time points of days 3/7/28 exhibited an identical pattern as knee joint fluid among the groups (all P-valueâ <â .0001). The scores of vertebral-bone destructions/inflamed synovium were lowest in Clt, highest in group A, significantly higher in group C than in groups B/D, and significantly higher in group C than in group D (all Pâ <â .0001). CONCLUSION: Combined antibiotics and Cef and HUCDMSCs was superior to just one therapy for suppressing circulatory and tissue levels of inflammation and knee joint destruction in ASA.
Sujet(s)
Arthrite infectieuse , Ceftriaxone , Transplantation de cellules souches mésenchymateuses , Cellules souches mésenchymateuses , Souris de lignée C57BL , Animaux , Ceftriaxone/pharmacologie , Arthrite infectieuse/traitement médicamenteux , Arthrite infectieuse/thérapie , Transplantation de cellules souches mésenchymateuses/méthodes , Mâle , Cellules souches mésenchymateuses/métabolisme , Souris , Humains , Antibactériens/pharmacologieSujet(s)
Antibactériens , Ceftriaxone , Gonorrhée , Neisseria gonorrhoeae , Neisseria gonorrhoeae/effets des médicaments et des substances chimiques , Neisseria gonorrhoeae/génétique , Ceftriaxone/usage thérapeutique , Ceftriaxone/pharmacologie , Humains , Vietnam , Gonorrhée/traitement médicamenteux , Gonorrhée/microbiologie , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Résistance bactérienne aux médicaments/génétique , Allèles , Tests de sensibilité microbienne , Mâle , FemelleRÉSUMÉ
OBJECTIVES: Antibiotic resistance in gonorrhoea is of significant public health concern with the emergence of resistance to last-line therapies such as ceftriaxone. Despite around half of Neisseria gonorrhoeae isolates tested in the UK being susceptible to ciprofloxacin, very little ciprofloxacin is used in clinical practice. Testing for the S91F mutation associated with ciprofloxacin resistance is now available in CE-marked assays and may reduce the requirement for ceftriaxone, but many patients are treated empirically, or as sexual contacts, which may limit any benefit. We describe the real-world impact of such testing on antimicrobial use and clinical outcomes in people found to have gonorrhoea in a large urban UK sexual health clinic. METHODS: Molecular ciprofloxacin resistance testing (ResistancePlus GC assay (SpeeDx)) was undertaken as an additional test after initial diagnosis (m2000 Realtime CT/NG assay (Abbott Molecular)) in those not already known to have had antimicrobial treatment. Data from a 6-month period (from March to September 2022) were analysed to determine treatment choice and treatment outcome. RESULTS: A total of 998 clinical samples tested positive for N.â¯gonorrhoeae in 682 episodes of infection. Of the 560 (56%) samples eligible for resistance testing, 269 (48.0%) were reported as wild-type, 180 (32.1%) were predicted to be resistant, 63 (11.3%) had an indeterminate resistance profile, and in 48 (8.6%) samples, N.â¯gonorrhoeae was not detected. Ciprofloxacin was prescribed in 172 (75%) of 228 episodes in which the wild-type strain was detected. Four (2%) of those treated with ciprofloxacin had a positive test-of-cure sample by NAAT, with no reinfection risk. All four had ciprofloxacin-susceptible infection by phenotypic antimicrobial susceptibility testing. CONCLUSIONS: In routine practice in a large UK clinic, molecular ciprofloxacin resistance testing led to a significant shift in antibiotic use, reducing use of ceftriaxone. Testing can be targeted to reduce unnecessary additional testing. Longer term impact on antimicrobial resistance requires ongoing surveillance.
Sujet(s)
Antibactériens , Ciprofloxacine , Résistance bactérienne aux médicaments , Gonorrhée , Tests de sensibilité microbienne , Neisseria gonorrhoeae , Humains , Ciprofloxacine/usage thérapeutique , Ciprofloxacine/pharmacologie , Gonorrhée/traitement médicamenteux , Gonorrhée/diagnostic , Gonorrhée/microbiologie , Neisseria gonorrhoeae/effets des médicaments et des substances chimiques , Neisseria gonorrhoeae/génétique , Antibactériens/usage thérapeutique , Antibactériens/pharmacologie , Résistance bactérienne aux médicaments/génétique , Mâle , Femelle , Adulte , Royaume-Uni , Ceftriaxone/usage thérapeutique , Ceftriaxone/pharmacologie , Mutation , Jeune adulte , Adulte d'âge moyenRÉSUMÉ
BACKGROUND: Antibiotic exposure can occur in medical settings and from environmental sources. Long-term effects of brief antibiotic exposure in early life are largely unknown. RESULTS: Post a short-term treatment by ceftriaxone to C57BL/6 mice in early life, a 14-month observation was performed using 16S rRNA gene-sequencing technique, metabolomics analysis, and metagenomics analysis on the effects of ceftriaxone exposure. Firstly, the results showed that antibiotic pre-treatment significantly disturbed gut microbial α and ß diversities (P < 0.05). Both Chao1 indices and Shannon indices manifested recovery trends over time, but they didn't entirely recover to the baseline of control throughout the experiment. Secondly, antibiotic pre-treatment reduced the complexity of gut molecular ecological networks (MENs). Various network parameters were affected and manifested recovery trends over time with different degrees, such as nodes (P < 0.001, R2 = 0.6563), links (P < 0.01, R2 = 0.4543), number of modules (P = 0.0672, R2 = 0.2523), relative modularity (P = 0.6714, R2 = 0.0155), number of keystones (P = 0.1003, R2 = 0.2090), robustness_random (P = 0.79, R2 = 0.0063), and vulnerability (P = 0.0528, R2 = 0.28). The network parameters didn't entirely recover. Antibiotic exposure obviously reduced the number of key species in gut MENs. Interestingly, new keystones appeared during the recovery process of network complexity. Changes in network stability might be caused by variations in network complexity, which supports the ecological theory that complexity begets stability. Besides, the metabolism profiles of the antibiotic group and control were significantly different. Correlation analysis showed that antibiotic-induced differences in gut microbial metabolism were related to MEN changes. Antibiotic exposure also caused long-term effects on gut microbial functional networks in mice. CONCLUSIONS: These results suggest that short-term antibiotic exposure in early life will cause long-term negative impacts on gut microbial diversity, MENs, and microbial metabolism. Therefore, great concern should be raised about children's brief exposure to antibiotics if the results observed in mice are applicable to humans. Video Abstract.
Sujet(s)
Antibactériens , Bactéries , Microbiome gastro-intestinal , Souris de lignée C57BL , ARN ribosomique 16S , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Animaux , Antibactériens/pharmacologie , Antibactériens/effets indésirables , Souris , ARN ribosomique 16S/génétique , Bactéries/génétique , Bactéries/classification , Bactéries/métabolisme , Bactéries/effets des médicaments et des substances chimiques , Ceftriaxone/pharmacologie , Métagénomique/méthodes , Mâle , Métabolomique , Fèces/microbiologieRÉSUMÉ
BACKGROUND: A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates. OBJECTIVES: We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic. METHODS: We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90â day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups. RESULTS: Sixty-two patients were included in our analysis. Overall, median age was 63â years (IQR 49.5-71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0â days (IQR 9.0-16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30-1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%. CONCLUSIONS: These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone.
Sujet(s)
Antibactériens , Bactériémie , Ceftriaxone , Infections à Escherichia coli , Escherichia coli , Infections à Klebsiella , Klebsiella pneumoniae , Tests de sensibilité microbienne , Association de pipéracilline et de tazobactam , Humains , Ceftriaxone/usage thérapeutique , Ceftriaxone/pharmacologie , Klebsiella pneumoniae/effets des médicaments et des substances chimiques , Klebsiella pneumoniae/isolement et purification , Adulte d'âge moyen , Mâle , Femelle , Études rétrospectives , Sujet âgé , Antibactériens/usage thérapeutique , Antibactériens/pharmacologie , Association de pipéracilline et de tazobactam/usage thérapeutique , Association de pipéracilline et de tazobactam/pharmacologie , Escherichia coli/effets des médicaments et des substances chimiques , Escherichia coli/isolement et purification , Bactériémie/traitement médicamenteux , Bactériémie/microbiologie , Bactériémie/mortalité , Infections à Klebsiella/traitement médicamenteux , Infections à Klebsiella/microbiologie , Infections à Klebsiella/mortalité , Infections à Escherichia coli/traitement médicamenteux , Infections à Escherichia coli/microbiologie , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: Haemophilus influenzae is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant H. influenzae at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in H. influenzae, with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and ß-lactamase production. METHODS: Among H. influenzae isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of ß-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via ftsI gene sequencing. RESULTS: Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant H. influenzae isolates, eighteen were non-typeable H. influenzae, and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L. CONCLUSION: The emergence of ceftriaxone-resistant H. influenzae with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in H. influenzae isolated from pediatric patients in Korea.
Sujet(s)
Antibactériens , Ceftriaxone , Infections à Haemophilus , Haemophilus influenzae , Tests de sensibilité microbienne , bêta-Lactamases , Ceftriaxone/pharmacologie , Haemophilus influenzae/effets des médicaments et des substances chimiques , Haemophilus influenzae/isolement et purification , Haemophilus influenzae/génétique , Humains , Antibactériens/pharmacologie , République de Corée , bêta-Lactamases/génétique , bêta-Lactamases/métabolisme , Enfant , Infections à Haemophilus/microbiologie , Infections à Haemophilus/traitement médicamenteux , Protéines de liaison aux pénicillines/génétique , Enfant d'âge préscolaire , Résistance bactérienne aux médicaments , Nourrisson , Femelle , Mâle , Protéines bactériennes/génétique , Protéines bactériennes/métabolismeRÉSUMÉ
OBJECTIVES: International travel combined with sex may contribute to dissemination of antimicrobial-resistant (AMR) Neisseria gonorrhoeae (Ng). To assess the role of travel in Ng strain susceptibility, we compared minimum inhibitory concentrations (MICs) for five antibiotics (ie, azithromycin, ceftriaxone, cefotaxime, cefixime and ciprofloxacin) in strains from clients with an exclusively Dutch sexual network and clients with an additional international sexual network. METHODS: From 2013 to 2019, we recorded recent residence of sexual partners of clients (and of their partners) with Ng at the Center for Sexual Health of Amsterdam. We categorised clients as having: (1) exclusively sexual partners residing in the Netherlands ('Dutch only') or (2) at least one partner residing outside the Netherlands. We categorised the country of residence of sexual partners by World Bank/EuroVoc regions. We analysed the difference of log-transformed MIC of Ng strains between categories using linear or hurdle regression for each antibiotic. RESULTS: We included 3367 gay and bisexual men who had sex with men (GBMSM), 516 women and 525 men who exclusively had sex with women (MSW) with Ng. Compared with GBMSM with a 'Dutch only' network, GBMSM with: (1) a Western European network had higher MICs for ceftriaxone (ß=0.19, 95% CI=0.08 to 0.29), cefotaxime (ß=0.19, 95% CI=0.08 to 0.31) and cefixime (ß=0.06, 95% CI=0.001 to 0.11); (2) a Southern European network had a higher MIC for cefixime (ß=0.10, 95% CI=0.02 to 0.17); and (3) a sub-Saharan African network had a lower MIC for ciprofloxacin (ß=-1.79, 95% CI=-2.84 to -0.74). In women and MSW, higher MICs were found for ceftriaxone in clients with a Latin American and Caribbean network (ß=0.26, 95% CI=0.02 to 0.51). CONCLUSIONS: For three cephalosporin antibiotics, we found Ng strains with slightly higher MICs in clients with partner(s) from Europe or Latin America and the Caribbean. International travel might contribute to the spread of Ng with lower susceptibility. More understanding of the emergence of AMR Ng is needed.
Sujet(s)
Anti-infectieux , Gonorrhée , Santé sexuelle , Mâle , Femelle , Humains , Neisseria gonorrhoeae , Ceftriaxone/pharmacologie , Ceftriaxone/usage thérapeutique , Céfixime/pharmacologie , Gonorrhée/traitement médicamenteux , Gonorrhée/épidémiologie , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Ciprofloxacine/pharmacologie , Ciprofloxacine/usage thérapeutique , Azithromycine/pharmacologie , Céfotaxime/pharmacologie , Tests de sensibilité microbienne , Anti-infectieux/pharmacologie , Résistance bactérienne aux médicamentsRÉSUMÉ
BACKGROUND: Neisseria gonorrhoeae (Ng) is a public health priority because of the rapid evolution of antimicrobial resistance, the emergence of antibiotic resistance, and the absence of a vaccine against Ng. The aim of this study was to investigate trends in the minimum inhibitory concentration and resistance (R) or reduced susceptibility (DS) of Ng cases to ceftriaxone (CRO), azithromycin (AZM), tetracycline (TET), benzylpenicillin (PenG), and ciprofloxacin (CIP) during a 10-year period. METHODS: We conducted a retrospective analysis on an open cohort of Ng cases diagnosed on rectal, urethral, and pharyngeal samples at San Raffaele Scientific Institute, between September 2012 and February 2023. Minimum inhibitory concentrations of antibiotics were determined by gradient-test strips. Bivariate linear regression models were applied on logarithmic minimum inhibitory concentrations values; Cochran-Armitage test was used to determine a linear trend in the proportions of resistant strains. RESULTS: A total of 436 Ng isolates from 352 individuals were analyzed. Minimum inhibitory concentrations of CRO and PenG reduced over time ( P < 0.001, P = 0.030), AZM increased ( P = 0.001), and CIP and TET did not change ( P = 0.473, P = 0.272). The percentages of resistant strains were as follows: PenG, 89.9%; TET, 90.8%; CIP, 48.2%; AZM, and 4.4%. CRO-DS strains were 8.7%, and only 1 case of CRO-R was identified. The proportion of resistant strains increased over time for AZM ( P = 0.007), TET ( P = 0.001), and CIP ( P < 0.001), whereas it decreased for PenG ( P < 0.001) and CRO-DS/R strains ( P < 0.001). CONCLUSIONS: Ng strains showed high susceptibility to CRO, although we identified cases of DS/R and observed high levels of susceptibility to AZM. Overall, the recommended primary regimen for Ng treatment was confirmed to be effective.
Sujet(s)
Antibactériens , Azithromycine , Gonorrhée , Tests de sensibilité microbienne , Neisseria gonorrhoeae , Tétracycline , Neisseria gonorrhoeae/effets des médicaments et des substances chimiques , Neisseria gonorrhoeae/isolement et purification , Humains , Gonorrhée/épidémiologie , Gonorrhée/microbiologie , Gonorrhée/traitement médicamenteux , Études rétrospectives , Antibactériens/pharmacologie , Mâle , Adulte , Femelle , Azithromycine/pharmacologie , Italie/épidémiologie , Tétracycline/pharmacologie , Résistance bactérienne aux médicaments , Ciprofloxacine/pharmacologie , Ceftriaxone/pharmacologie , Urètre/microbiologie , Adulte d'âge moyen , Jeune adulte , Benzylpénicilline/pharmacologie , Pharynx/microbiologie , Rectum/microbiologieRÉSUMÉ
Salmonella Thompson is a prevalent foodborne pathogen and a major threat to food safety and public health. This study aims to reveal the dissemination mechanism of S. Thompson with co-resistance to ceftriaxone and ciprofloxacin. In this study, 181 S. Thompson isolates were obtained from a retrospective screening on 2118 serotyped Salmonella isolates from foods and patients, which were disseminated in 12 of 16 districts in Shanghai, China. A total of 10 (5.5 %) S. Thompson isolates exhibited resistance to ceftriaxone (MIC ranging from 8 to 32 µg/mL) and ciprofloxacin (MIC ranging from 2 to 8 µg/mL). The AmpC ß-lactamase gene blaCMY-2 and plasmid-mediated quinolone resistance (PMQR) genes of qnrS and qepA were identified in the 9 isolates. Conjugation results showed that the co-transfer of blaCMY-2, qnrS, and qepA occurred on the IncC plasmids with sizes of â¼150 (n = 8) or â¼138 (n = 1) kbp. Three typical modules of ISEcp1-blaCMY-2-blc-sugE, IS26-IS15DIV-qnrS-ISKpn19, and ISCR3-qepA-intl1 were identified in an ST3 IncC plasmid pSH11G0791. Phylogenetic analysis indicated that IncC plasmids evolved into Lineages 1, 2, and 3. IncC plasmids from China including pSH11G0791 in this study fell into Lineage 1 with those from the USA, suggesting their close genotype relationship. In conclusion, to our knowledge, it is the first report of the co-existence of blaCMY-2, qnrS, and qepA in IncC plasmids, and the conjugational transfer contributed to their dissemination in S. Thompson. These findings underline further challenges for the prevention and treatment of Enterobacteriaceae infections posed by IncC plasmids bearing blaCMY-2, qnrS, and qepA.
Sujet(s)
Antibactériens , Diarrhée , Plasmides , Salmonella enterica , Produits de la mer , Humains , Plasmides/génétique , Chine , Antibactériens/pharmacologie , Salmonella enterica/génétique , Salmonella enterica/isolement et purification , Salmonella enterica/effets des médicaments et des substances chimiques , Produits de la mer/microbiologie , Diarrhée/microbiologie , Tests de sensibilité microbienne , bêta-Lactamases/génétique , Études rétrospectives , Multirésistance bactérienne aux médicaments/génétique , Ciprofloxacine/pharmacologie , Ceftriaxone/pharmacologie , Protéines bactériennes/génétique , Sérogroupe , Microbiologie alimentaireRÉSUMÉ
OBJECTIVE: Aim: To study changes of dental biofilm microbiota composition during experimental opioid exposure, after its withdrawal and when using of complex drug correction.. PATIENTS AND METHODS: Materials and Methods: Microbiological studies (48 rats) included microscopic and bacteriological methods, as well as determination of antibiotic susceptibility of microbial isolates. Ceftriaxone and pentoxifylline were used to correction the changes. RESULTS: Results: The action of opioid for 10 weeks caused considerable changes in the microbiocenosis, which was illustrated by a significant increasing of the opportunistic pathogens quantitative indicators and the emergence of pathogenic microbiota. Changes in the microbiocenosis at 6 weeks of opioid exposure and after its withdrawal for 4 weeks were expressed in the appearance of pathogenic microbiota and the absence of significant differences in quantitative indicators of saprophytic and opportunistic microflora compared to similar indicators in animals with 10 weeks opioid exposure. This indicated a slow progression of dysbiotic changes and the inflammatory process in the oral cavity of rats. CONCLUSION: Conclusions: After 10 weeks of experiment with opioid administration for 6 weeks and the use of ceftriaxone and pentoxifylline on the background of 4-week opioid withdrawal, a significant reduction of quantitative indicators of opportunistic bacteria and elimination of pathogenic species of microorganisms was determined. The use of complex drug correction on the background of 10 weeks of opioid exposure led to a significant reduction in the quantitative indicators of opportunistic pathogens and contributed to the elimination of most pathogenic species of microbiota under the action of ceftriaxone.
Sujet(s)
Microbiote , Pentoxifylline , Rats , Animaux , Analgésiques morphiniques/effets indésirables , Ceftriaxone/pharmacologie , Ceftriaxone/usage thérapeutique , Préparations pharmaceutiques , Pentoxifylline/pharmacologie , Pentoxifylline/usage thérapeutiqueRÉSUMÉ
Gonorrhea is a widespread sexually transmitted infection; in 2022, China reported 96,313 cases of gonorrhea, making it the fourth most common notifiable infectious disease in the country after viral hepatitis, pulmonary tuberculosis, and syphilis. The rise in prevalence in antimicrobial-resistant strains, particularly the international spread of ceftriaxone-resistant clones, poses a formidable challenge to gonorrhea control. The China Gonococcal Resistance Surveillance Program (China-GRSP), established in 1987 and covering 19 of 34 provincial-level administrative units, continuously monitors gonococcal antimicrobial resistance. In 2022, 13 China-GRSP sentinel sites collected 2,804 gonococcal isolates, representing 2.9% of all cases reported in China, and 4.1% of cases reported in the 13 participating provinces. The prevalence of Neisseria gonorrhoeae resistance to ceftriaxone was 8.1%, approximately three times the 2017 rate of 2.9%; five provinces reported >10% ceftriaxone resistance. Resistance prevalences to cefixime, azithromycin, tetracycline, penicillin, and ciprofloxacin were 16.0%, 16.9%, 77.1%, 77.8%, and 97.6%, respectively. Only one case of spectinomycin resistance was reported. These data highlight a substantial increase in ceftriaxone resistance from 2017 to 2022. Effective diagnosis and treatment and appropriate management of sex partners are essential to protect the health of infected persons and prevent ongoing transmission of gonorrhea, including transmission of resistant strains. Identifying reasons for the spread of ceftriaxone-resistant N. gonorrhoeae in China could guide strategies, such as antibiotic stewardship, to mitigate the rising resistance rate and curb the spread of resistant strains.