RESUMEN

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.

Asunto(s)

Ceftriaxona , Simulación de Dinámica Molecular , Neisseria gonorrhoeae , Proteínas de Unión a las Penicilinas , Ceftriaxona/farmacología , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/metabolismo , Proteínas de Unión a las Penicilinas/genética , Proteínas de Unión a las Penicilinas/química , Proteínas de Unión a las Penicilinas/metabolismo , Antibacterianos/farmacología , Mutación , Farmacorresistencia Bacteriana/genética , Acilación , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , D-Ala-D-Ala Carboxipeptidasa de Tipo Serina

RESUMEN

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.

Asunto(s)

Antibacterianos , Ceftriaxona , Pruebas de Sensibilidad Microbiana , Infecciones por Salmonella , Salmonella , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Ceftriaxona/farmacología , Humanos , Antibacterianos/farmacología , Salmonella/efectos de los fármacos , Infecciones por Salmonella/microbiología , Pruebas de Sensibilidad Microbiana/métodos , Farmacorresistencia Bacteriana , Sensibilidad y Especificidad , Curva ROC

RESUMEN

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.

Asunto(s)

Antibacterianos , Ceftriaxona , Infecciones por Salmonella , Salmonella enterica , Humanos , Femenino , Ceftriaxona/farmacología , Ceftriaxona/uso terapéutico , India , Infecciones por Salmonella/tratamiento farmacológico , Infecciones por Salmonella/microbiología , Salmonella enterica/efectos de los fármacos , Salmonella enterica/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Farmacorresistencia Bacteriana Múltiple , Gastroenteritis/microbiología , Gastroenteritis/tratamiento farmacológico , Serogrupo , Pruebas de Sensibilidad Microbiana

RESUMEN

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.

Asunto(s)

Aminoaciltransferasas , Proteínas Bacterianas , Biopelículas , Cisteína Endopeptidasas , Enterococcus faecalis , Fimbrias Bacterianas , Chaperonas Moleculares , Fimbrias Bacterianas/genética , Fimbrias Bacterianas/metabolismo , Aminoaciltransferasas/genética , Aminoaciltransferasas/metabolismo , Enterococcus faecalis/genética , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Biopelículas/crecimiento & desarrollo , Membrana Celular/metabolismo , Regulación Bacteriana de la Expresión Génica , Virulencia/genética , Antibacterianos/farmacología , Ceftriaxona/farmacología

RESUMEN

Superficial skin injuries especially burn injuries and unhealed diabetic foot open wounds remain troubling for public health. The healing process is often interrupted by the invasion of resistant pathogens that results in the failure of conventional procedures outside the clinical settings. Herein, we designed nanofibers dressing with intrinsic antibacterial potential of poly(vinyl-pyrrolidone)-iodine/ poly (vinyl)-alcohol by electrospinning with chitosan encapsulating ceftriaxone (CPC/NFs). The optimized electrospun CPC/NFs exhibited smooth surface morphology with average diameter of 165 ± 7.1 nm, drug entrapment and loading efficiencies of 76.97 ± 4.7 % and 8.32 ± 1.73 %, respectively. The results displayed smooth and uniformed fibers with adequate thermal stability and ensured chemical doping. The enhanced in vitro antibacterial efficacy of CPC/NFs against resistant E. coli isolates and biosafety studies encourage the use of designed nanofibers dressing for burn injuries and diabetic foot injuries. In vivo studies proved the healing power of dressing for burn wounds model and diabetic infected wounds model. Immunofluorescence investigation of the wound tissue also suggested promising healing ability of CPC/NFs. The designed approach would be helpful to treat these infected skin open wounds in the hospitals and outside the clinical settings.

Asunto(s)

Antibacterianos , Quemaduras , Ceftriaxona , Quitosano , Pie Diabético , Nanofibras , Cicatrización de Heridas , Nanofibras/química , Pie Diabético/tratamiento farmacológico , Pie Diabético/microbiología , Quitosano/química , Quitosano/farmacología , Quemaduras/tratamiento farmacológico , Animales , Antibacterianos/farmacología , Antibacterianos/química , Cicatrización de Heridas/efectos de los fármacos , Ceftriaxona/farmacología , Ceftriaxona/química , Povidona Yodada/farmacología , Povidona Yodada/química , Povidona Yodada/administración & dosificación , Escherichia coli/efectos de los fármacos , Masculino , Vendajes , Ratones , Sistemas de Liberación de Medicamentos

RESUMEN

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.

Asunto(s)

Antibacterianos , Azitromicina , Ceftriaxona , Doxiciclina , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Humanos , Indonesia , Neisseria gonorrhoeae/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Gonorrea/tratamiento farmacológico , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Azitromicina/uso terapéutico , Doxiciclina/uso terapéutico , Ceftriaxona/uso terapéutico , Ceftriaxona/farmacología , Adulto , Cefixima/uso terapéutico , Cefixima/farmacología , Atención Primaria de Salud/estadística & datos numéricos , Farmacorresistencia Bacteriana/efectos de los fármacos , Quimioterapia Combinada/métodos

RESUMEN

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.

Asunto(s)

Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Gonorrea , Neisseria gonorrhoeae , Adulto , Femenino , Humanos , Masculino , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Azitromicina/farmacología , Azitromicina/uso terapéutico , Ceftriaxona/farmacología , Ceftriaxona/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Francia/epidemiología , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Gonorrea/epidemiología , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/aislamiento & purificación

RESUMEN

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.

Asunto(s)

Antibacterianos , Ceftriaxona , Farmacorresistencia Bacteriana , Gonorrea , Neisseria gonorrhoeae , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Ceftriaxona/farmacología , Humanos , Gonorrea/microbiología , Gonorrea/epidemiología , Gonorrea/tratamiento farmacológico , Asia/epidemiología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Prevalencia , Historia del Siglo XXI

RESUMEN

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.

Asunto(s)

Antibacterianos , Pruebas de Sensibilidad Microbiana , Salmonella paratyphi A , Salmonella typhi , Fiebre Tifoidea , Humanos , Masculino , Femenino , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Fiebre Tifoidea/epidemiología , Fiebre Tifoidea/microbiología , Fiebre Tifoidea/tratamiento farmacológico , Estudios Retrospectivos , Salmonella typhi/efectos de los fármacos , Salmonella typhi/aislamiento & purificación , Salmonella paratyphi A/efectos de los fármacos , Salmonella paratyphi A/aislamiento & purificación , Adulto , Adolescente , Niño , Persona de Mediana Edad , Adulto Joven , Fiebre Paratifoidea/epidemiología , Fiebre Paratifoidea/microbiología , Fiebre Paratifoidea/tratamiento farmacológico , Incidencia , Farmacorresistencia Bacteriana , Azitromicina/uso terapéutico , Azitromicina/farmacología , Ceftriaxona/uso terapéutico , Ceftriaxona/farmacología , Anciano , Prevalencia

RESUMEN

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 [ASA + Cef (5 mg/kg, IM per day, at days 2 to 16 after ASA induction)], group C [ASA + HUCDMSCs (5 × 105 per mice at days 2, 3, 4 after ASA induction)], and group D (ASA + Cef + 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 P < .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-value < .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 P < .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.

Asunto(s)

Artritis Infecciosa , Ceftriaxona , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Animales , Ceftriaxona/farmacología , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratones , Humanos , Antibacterianos/farmacología

RESUMEN

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.

Asunto(s)

Antibacterianos , Farmacorresistencia Bacteriana , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Puerto Rico , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/aislamiento & purificación , Humanos , Masculino , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Gonorrea/epidemiología , Femenino , Antibacterianos/farmacología , Antibacterianos/administración & dosificación , Adulto , Adulto Joven , Azitromicina/farmacología , Azitromicina/administración & dosificación , Ceftriaxona/farmacología , Adolescente , Persona de Mediana Edad

RESUMEN

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. 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. 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.

Asunto(s)

Antibacterianos , Ciprofloxacina , Farmacorresistencia Bacteriana , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Humanos , Ciprofloxacina/uso terapéutico , Ciprofloxacina/farmacología , Gonorrea/tratamiento farmacológico , Gonorrea/diagnóstico , Gonorrea/microbiología , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Masculino , Femenino , Adulto , Reino Unido , Ceftriaxona/uso terapéutico , Ceftriaxona/farmacología , Mutación , Adulto Joven , Persona de Mediana Edad

Asunto(s)

Antibacterianos , Ceftriaxona , Gonorrea , Neisseria gonorrhoeae , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Ceftriaxona/uso terapéutico , Ceftriaxona/farmacología , Humanos , Vietnam , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Alelos , Pruebas de Sensibilidad Microbiana , Masculino , Femenino

RESUMEN

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 90 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 63 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 12.0 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.

Asunto(s)

Antibacterianos , Bacteriemia , Ceftriaxona , Infecciones por Escherichia coli , Escherichia coli , Infecciones por Klebsiella , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Combinación Piperacilina y Tazobactam , Humanos , Ceftriaxona/uso terapéutico , Ceftriaxona/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Persona de Mediana Edad , Masculino , Femenino , Estudios Retrospectivos , Anciano , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Combinación Piperacilina y Tazobactam/uso terapéutico , Combinación Piperacilina y Tazobactam/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Bacteriemia/mortalidad , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/mortalidad , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Resultado del Tratamiento

RESUMEN

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.

Asunto(s)

Antibacterianos , Bacterias , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , ARN Ribosómico 16S , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/efectos adversos , Ratones , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/efectos de los fármacos , Ceftriaxona/farmacología , Metagenómica/métodos , Masculino , Metabolómica , Heces/microbiología

RESUMEN

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 ∼150 (n = 8) or ∼138 (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.

Asunto(s)

Antibacterianos , Diarrea , Plásmidos , Salmonella enterica , Alimentos Marinos , Humanos , Plásmidos/genética , China , Antibacterianos/farmacología , Salmonella enterica/genética , Salmonella enterica/aislamiento & purificación , Salmonella enterica/efectos de los fármacos , Alimentos Marinos/microbiología , Diarrea/microbiología , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/genética , Estudios Retrospectivos , Farmacorresistencia Bacteriana Múltiple/genética , Ciprofloxacina/farmacología , Ceftriaxona/farmacología , Proteínas Bacterianas/genética , Serogrupo , Microbiología de Alimentos

RESUMEN

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.

Asunto(s)

Antibacterianos , Ceftriaxona , Infecciones por Haemophilus , Haemophilus influenzae , Pruebas de Sensibilidad Microbiana , beta-Lactamasas , Ceftriaxona/farmacología , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/aislamiento & purificación , Haemophilus influenzae/genética , Humanos , Antibacterianos/farmacología , República de Corea , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Niño , Infecciones por Haemophilus/microbiología , Infecciones por Haemophilus/tratamiento farmacológico , Proteínas de Unión a las Penicilinas/genética , Preescolar , Farmacorresistencia Bacteriana , Lactante , Femenino , Masculino , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo

RESUMEN

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.

Asunto(s)

Antibacterianos , Azitromicina , Gonorrea , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae , Tetraciclina , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/aislamiento & purificación , Humanos , Gonorrea/epidemiología , Gonorrea/microbiología , Gonorrea/tratamiento farmacológico , Estudios Retrospectivos , Antibacterianos/farmacología , Masculino , Adulto , Femenino , Azitromicina/farmacología , Italia/epidemiología , Tetraciclina/farmacología , Farmacorresistencia Bacteriana , Ciprofloxacina/farmacología , Ceftriaxona/farmacología , Uretra/microbiología , Persona de Mediana Edad , Adulto Joven , Penicilina G/farmacología , Faringe/microbiología , Recto/microbiología

RESUMEN

BACKGROUND: Sepsis is a major health problem worldwide and is associated with high morbidity and mortality with every hour delay in initiation of therapy. A conventional method of blood culture and Antimicrobial Susceptibility Testing (AST) takes around 48-72 hours. Empirical antibiotics need to be administered until the sensitivity report is made available. It has been estimated that 20-50% of the empirical antibiotics are inappropriate, resulting in prolonged hospital stays, adverse effects, and emergence of drug resistance. Additionally, this also puts an extra financial burden on both the patients and healthcare settings. Performing direct Antimicrobial Sensitivity Testing (dAST) is an important tool to reduce turn-around time (TAT) by at least 18-24 hours, thus reducing morbidity and mortality among critically ill patients. METHODS: Direct AST (dAST) was performed from the positively flagged blood culture bottles received between December, 2021 to May, 2022 from Intensive Care Units (ICUs) on Mueller- Hinton Agar (MHA) using four drops of withdrawn blood. dAST was performed for six drugs: Ceftriaxone-30 µg (CTR), Piperacillin/Tazobactam-100/10 µg (PIT), Meropenem-10 µg (MRP), Ciprofloxacin-5 µg (CIP), Aztreonam-30 µg (AT), and Colistin (CL). The zone of inhibition was interpreted as per CLSI M100 ed32, 2022 guidelines. A parallel conventional method was also performed to examine for categorical agreement and disagreement. Identification was carried out using MALDI-TOF MS from the colonies that appeared on the dAST plate on the subsequent day. RESULTS: A total of 162 positively flagged blood culture bottles were included in the study. The majority of the Gram-negative organisms were from Enterobacterales (n=109), followed by Acinetobacter spp. (n=28) and Pseudomonas aeruginosa (n=25). Out of the 972 isolate-antimicrobial combinations, overall Categorical Agreement (CA) was seen in 936 (96.3%), whereas disagreement was observed in 36 with minor error (mE) in 21 (2.2%), major error (ME) in 7 (0.7%), and very major error (VME) in 8 (0.8%) when compared to the routine method. Categorical agreement (CA) of > 99% was seen in ceftriaxone (CTR) and ciprofloxacin (CIP). In comparison, the lowest CA was observed with meropenem (MRP) at 92%. Colistin dAST was performed using the E-strip method, and the result obtained was highly convincing, with an overall disagreement of only 1.2%. CONCLUSION: Rapid dAST from positively flagged blood culture bottles proved to significantly reduce the TAT from the time of sample collection to the first availability of antimicrobial susceptibility report with excellent categorical agreement of > 95% using the conventional disc diffusion method. Results obtained were within the acceptance criteria set by U. S. Food and Drug Administration (FDA) guidelines of > 90% categorical agreement for a new method. We were able to obtain excellent concordance for colistin using the E-strip method. Performing dAST not only saves a "day", but its proper implementation would save a "life".

Asunto(s)

Antibacterianos , Cultivo de Sangre , Unidades de Cuidados Intensivos , Pruebas de Sensibilidad Microbiana , Humanos , Cultivo de Sangre/métodos , Antibacterianos/farmacología , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Ciprofloxacina/farmacología , Meropenem/farmacología , Combinación Piperacilina y Tazobactam/farmacología , Combinación Piperacilina y Tazobactam/uso terapéutico , Bacterias Gramnegativas/efectos de los fármacos , Ceftriaxona/farmacología , Colistina/farmacología , Factores de Tiempo , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico

RESUMEN

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.

Asunto(s)

Microbiota , Pentoxifilina , Ratas , Animales , Analgésicos Opioides/efectos adversos , Ceftriaxona/farmacología , Ceftriaxona/uso terapéutico , Preparaciones Farmacéuticas , Pentoxifilina/farmacología , Pentoxifilina/uso terapéutico