Polymerized impurities in β-lactam antibiotics can induce allergic reaction, which seriously threaten the health of patients. In order to study the polymerized impurities in cefotaxime sodium and ...cefepime, a HPSEC method with TSK-gel G2000SWxl column and a RP-HPLC method with C18 column were established to replace the classical gel filtration chromatography with Sephadex G-10 gel as stationary phase. Two-dimensional (2D) liquid chromatography was employed to further investigate the HPSEC and RP-HPLC method and ion trap/time-of-flight mass spectrometry was applied to characterize the structures of polymerized impurities eluted from the two methods. The structures of the polymerized impurities in cefotaxime sodium and cefepime were deduced based on the MSn data, six of which were previously unknown. The corresponding relationship of impurities between the two methods was established, and the specificity of the two methods was compared. The results showed that the polymerized impurities in cefotaxime sodium and cefepime were co-eluted with other small molecular weight impurities with high polarity in HPSEC, leading to a poor specificity. The newly established RP-HPLC methods could effectively separate and detect polymerized impurities and were suitable for the quality control in daily analysis.
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•A HPSEC method with TSK-gel G2000SWxl column was developed.•A RP-HPLC method with C18 column was developed.•The structures of polymerized impurities were deduced by 2D LC-IT-TOF MS.•The corresponding relationship of polymerized impurities was established.•The specificity of the two methods was compared.
Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in a more pronounced impact on the intestinal microbiota. We performed a monocenter, randomized ...open-label clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for 3 days. We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling, and measurement of the antibiotic concentration and compared the groups for the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. The emergence of 3rd-generation-cephalosporin-resistant Gram-negative enteric bacilli (
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spp., or noncommensal microorganisms was not significantly different between the groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased the bacterial diversity, but the differences between the groups were not significant. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of the bacterial diversity of the gut. Both antibiotics markedly impacted the intestinal microbiota, but no significant differences were detected when standard clinical doses were administered for 3 days. This might be related to the similar daily amounts of antibiotics excreted through the bile using a clinical regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT02659033.).
To evaluate the effects of the replacement of ceftriaxone by cefotaxime on the incidence of third-generation cephalosporin-resistant Enterobacterales (3GC-RE).
We conducted a 24-month monocentric ...prospective, stepped-wedge cluster randomized controlled trial. During the control phase of the study, clinicians prescribed either ceftriaxone or cefotaxime. During the intervention phase, they systematically prescribed cefotaxime.
The cefotaxime/ceftriaxone ratio was inversely correlated with the incidence of 3GC-RE. All in all, 3GC-RE incidence was 1.05 (27/25,692) acquired cases/1000 hospitalization days during the control phase and 0.54 (11/20,419) acquired cases/1000 hospitalization days during the intervention phase (incidence rate ratio IRR = 0.51 0.22-1.07, p = 0.06). In multivariable analysis, intervention phase (versus control phase) (p = 0.007), cefotaxime/ceftriaxone ratio (p = 0.003) and imported 3GC-RE (p = 0.005) were associated with the incidence of acquired cases of 3GC-RE.
We found that replacing ceftriaxone with cefotaxime reduced the occurrence of 3GC-RE isolates. More studies are needed to confirm these results.
Workflow of the MBT-ASTRA approach. Display omitted
•Short, species dependent incubation time in the range between 1 and 4h.•Species dependent breakpoint concentrations provide resistance ...information.•Titration set ups provide susceptibility information (“ASTRA MIC”).•MBT-ASTRA results in concordance to routine methods.•Etest MIC and “ASTRA MIC” show a direct correlation.
The increasing resistance to antibiotics is an urgent health care problem. Detection of resistant microorganisms is the pre-requisite for initiating an adequate therapy and implementing respective hygiene measures. Depending on the species and the method employed for analysis, the time to result of antibiotic resistance testing ranges between five and 24h. As MALDI-TOF MS has become an established tool for the fast species identification in microbiological laboratories a time gap between the results of species identification and the information about antibiotic susceptibility arises. Here, we present a semi-quantitative MALDI-TOF MS-based approach for the detection of resistance in different species against different antibiotics.
Salmonellosis is a major global foodborne infection, and strains that are resistant to a great variety of antibiotics have become a major public health concern. The aim of this study was to identify ...genes conferring resistance to fluoroquinolones and extended-spectrum β-lactams in nontyphoidal Salmonella (NTS) from patients and food-producing animals in China. In total, 133 and 21 NTS isolates from animals and humans, respectively, exhibiting concurrent resistance to ciprofloxacin and cefotaxime were cultured independently from 2009 to ∼2013. All of the isolates were identified, serotyped, and subjected to antimicrobial susceptibility testing. Importantly, the isolates with concurrent resistance to ciprofloxacin and cefotaxime all were confirmed as S. enterica serovar Indiana. The presence of fluoroquinolone resistance genes and extended-spectrum β-lactamases (ESBLs) was established by PCR and DNA sequencing. The occurrence and diversity of different genes conferring fluoroquinolone resistance qepA, oqxAB, and aac(6')-Ib-cr with mutations in topoisomerase-encoding genes (gyrA and parC) and several ESBLs (including CTX-M-65, CTX-M-27, CTX-M-15, CTX-M-14, and CTX-M-14/CTX-M-15) were noteworthy. Genes located on mobile genetic elements were identified by conjugation and transformation. Pulsed-field gel electrophoresis, used to determine the genetic relationships between these isolates, generated 91 pulsotypes from 133 chicken isolates and 17 pulsotypes from the 21 clinical isolates that showed considerable diversity. Analysis of the pulsotypes obtained with the isolates showed some clones appeared to have existed for several years and had been disseminating between humans and food-producing animals. This study highlights the emergence of ciprofloxacin- and cefotaxime-resistant S. enterica serovar Indiana, posing a threat to public health.
Background and purpose
Our aim was to evaluate the available evidence for pharmacological treatment of acute Lyme neuroborreliosis as a basis for evidence‐based clinical recommendations in a ...systematic review.
Methods
A systematic literature search of Medline, EMBASE, the Cochrane Library and three trial registries was performed. Randomized controlled trials (RCTs) and non‐randomized studies (NRS) were evaluated. Risk of bias was assessed using the Cochrane risk of bias tools. The primary outcome was ‘residual neurological symptoms’ whilst the secondary outcomes were disability, quality of life, pain, fatigue, depression, cognition, sleep, adverse events and cerebrospinal fluid pleocytosis. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Results
After screening 5779 records, eight RCTs and eight NRS were included. Risk of bias was generally high. No statistically significant difference was found between doxycycline and beta‐lactam antibiotics in a meta‐analysis regarding residual neurological symptoms at 4–12 months risk ratio (RR) 1.27, 95% confidence interval (CI) 0.98–1.63, P = 0.07 or adverse events (RR 0.82, 95% CI 0.54–1.25, P = 0.35). Significantly fewer neurological symptoms for cefotaxime compared with penicillin were found (RR 1.81, 95% CI 1.10–2.97, P = 0.02). Adverse events were significantly fewer for penicillin (RR 0.56, 95% CI 0.38–0.84, P = 0.005).
Conclusions
Evidence regarding pharmacological treatment of acute Lyme neuroborreliosis is scarce and therefore insufficient to recommend preference of beta‐lactam antibiotics over doxycycline or vice versa. However, due to considerable imprecision, relevant differences between treatments cannot be excluded. No evidence suggesting benefits of extended antibiotic treatments could be identified. Further well‐designed trials are needed. Individual treatment decisions should address patients' preferences and individual conditions like prior allergic reactions.
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Aims
Metal nanoparticles are promising materials for the management of infectious diseases as known to have various antimicrobial activities in pathogenic micro‐organisms. Among them, gold ...nanoparticles (AuNPs) are used in a wide range of fields such as photodynamic therapy, molecular diagnostics and drug delivery because of their unique physicochemical properties. However, little is known about the synergistic antibacterial activity and mechanism of AuNPs on pathogenic bacteria.
Methods and Results
Combinations of AuNPs and cefotaxime and ciprofloxacin showed synergistic interaction against all Salmonella species, however the combination with kanamycin exhibited no interaction. We determined that AuNPs and in combinations with antibiotics exert its antibacterial effect through bacterial apoptosis‐like death. AuNPs caused collapse of intracellular divalent cation homeostasis, and conventional antibiotics caused accumulation of reactive oxygen species, which induced apoptotic hallmarks such as membrane depolarization, caspase‐like protein activation, cell filamentation and phosphatidylserine externalization.
Conclusions
The cation homeostasis disruption by AuNPs and the accumulation of reactive oxygen species by conventional antibiotics synergistically affected bacterial cell death and induced apoptosis‐like death in Salmonella cells.
Significance and Impact of the Study
The synergistic activity between AuNPs and antibiotics propose that the AuNPs are a potential antibacterial agent and adjuvant for antimicrobial chemotherapy.
Spherical agglomerates of pharmaceuticals are desired in the manufacturing process, however, the current selection of the wetting liquid is still determined in a trial-and-error way. This work ...reports a method that combines theoretical prediction and experimental validation to select the proper wetting liquid for spherical agglomeration of cefotaxime sodium (CTX). The theoretical prediction is realized by calculating the adhesion free energy between the solid surfaces and the liquid. Various solvents have been screened and candidates with a negative adhesion free energy such as water, chloroform, ethylene glycol, hexane and heptane are selected as wetting liquid candidates. Results show that the adhesion free energy is a feasible tool for selecting a suitable wetting liquid to produce spherical agglomerates. Better-shaped and uniformed spherical agglomerates are obtained with the suitable wetting liquid via orthogonal experiments. Finally, the spherical agglomeration process is visualized and possible mechanism is proposed.
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•The proper wetting liquid for spherical agglomeration of cefotaxime sodium (CTX) is decided by theoretical prediction.•Spherical agglomerates of CTX are produced by spherical agglomeration using the predicted wetting liquids.•A possible mechanism for the SA process of CTX is proposed.
Abstract
Background
The rapid and accurate detection of ESBL production in Gram-negative rod (GNR) bacteremia is critical as recent data suggest that carbapenem treatment decreases mortality. At the ...same time, avoiding widespread empiric carbapenem prescribing is an important goal of antimicrobial stewardship teams. The aim of this retrospective review was to determine the accuracy of a nucleic acid–based test, Luminex Verigene BC-GN panel, to detect ESBL-positive GNRs direct from blood cultures.
Methods
The Verigene BC-GN was performed on all first positive GNR blood cultures. In addition, routine antibiotic susceptibility testing was performed on all isolates by the disk-diffusion method and included phenotypic ESBL testing using cefotaxime and ceftazidime with and without clavulanate. Escherichia coli, Klebsiella spp., and Proteus mirabilis–positive blood cultures were identified as ESBL producers through either Verigene or phenotypic disk testing. Positive GNR blood cultures from February 2016 to July 2017 were included for review. The primary objective was to determine the sensitivity and specificity of Verigene for detection of ESBLs. The secondary objective was assessing the percent of community-onset and hospital-acquired ESBL-positive blood cultures.
Results
There were 83 positive blood cultures with ESBL producing GNR included in the primary review. A total of 82 of 83 positive GNR blood cultures were CTX-M gene positive via Verigene (sensitivity 98.8%). All 83 cultures were confirmed as ESBL producers via phenotypic tests. There were no positive Verigene cases with negative phenotypic results. All 68 ESBL E coli–positive cultures were detected by Verigene (100%), 10 ESBL K pneumoniae (100%), and four of the five ESBL P mirabilis–positive cultures (80%). Of the 73 results available for review in the secondary objectives, 68 were community onset (93%) and five were hospital acquired (7%).
Conclusion
The majority of ESBL-positive blood cultures in a low-prevalence setting were due to CTX-M producers. The Luminex Verigene BC-GN was accurate in detecting ESBL-producing Enterobacteriaceae from blood cultures and can be reliably used to guide antimicrobial therapy.
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