-
Scientific Reports Sep 2023Antibiotics are increasingly recognized as causing neuropsychiatric side effects including depression and anxiety. Alterations in central serotonin and 5-HT receptor...
Antibiotics are increasingly recognized as causing neuropsychiatric side effects including depression and anxiety. Alterations in central serotonin and 5-HT receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with gastrointestinal disorders. Nevertheless, it is still unclear how antibiotics can cause anxiety and depression. In this study, oral administration of cefaclor, a second-generation cephalosporin antibiotic, induced anxiety- and depression-like behaviors and colitis with gut microbiota alteration in mice. Cefaclor reduced serotonin levels and fluctuated 5-HT receptor mRNA expressions such as Htr1a, Htr1b, and Htr6 in the hippocampus. Vagotomy attenuated the cefaclor-induced anxiety- and depression-like symptoms, while the cefaclor-induced changes in gut bacteria alteration and colitis were not affected. Fluoxetine attenuated cefaclor-induced anxiety- and depression-like behaviors. Furthermore, fluoxetine decreased cefaclor-resistant Enterobacteriaceae and Enterococcaceae. Taken together, our findings suggest that the use of antibiotics, particularly, cefaclor may cause gut dysbiosis-dependent anxiety and depression through the microbiota-gut-blood-brain and microbiota-gut-vagus nerve-brain pathway. Targeting antibiotics-resistant pathogenic bacteria may be a promising therapeutic strategy for the treatment of anxiety and depression.
Topics: Animals; Mice; Cefaclor; Depression; Dysbiosis; Fluoxetine; Serotonin; Anti-Bacterial Agents; Vagus Nerve; Colitis
PubMed: 37726354
DOI: 10.1038/s41598-023-42690-1 -
Molecules (Basel, Switzerland) Jun 2023Copper (Cu) is an essential trace metal and its concentration in body plasma is tightly regulated. An increase in Cu concentration in body fluids is observed in numerous... (Review)
Review
Copper (Cu) is an essential trace metal and its concentration in body plasma is tightly regulated. An increase in Cu concentration in body fluids is observed in numerous pathological conditions, including infections caused by microorganisms. Evidence shows that Cu ions can impact the activity of antibiotics by increasing efficiency or diminishing/neutralizing antibiotic activity, forming complexes which may lead to antibiotic structure degradation. Herein, we represent the evidence available on Cu-antibiotic interactions and their possible impact on antimicrobial therapy efficiency. So far, in vitro studies described interactions between Cu ions and the majority of antibiotics in clinical use: penicillins, cephalosporins, carbapenems, macrolides, aminoglycosides, tetracyclines, fluoroquinolones, isoniazid, metronidazole. In vitro-described degradation or lower antimicrobial activity of amoxicillin, ampicillin, cefaclor, ceftriaxone, and meropenem in the presence of Cu ions suggest caution when using prescribed antibiotics in patients with altered Cu levels. On the other hand, several Cu-dependent compounds with antibacterial activity including the drug-resistant bacteria were discovered, such as thiosemicarbazones, disulfiram, dithiocarbamates, 8-hydroxiquinoline, phenanthrolines, pyrithione. Having in mind that the development of new antibiotics is already marked as inadequate and does not meet global needs, the potential of Cu-antibiotic interactions to change the efficiency of antimicrobial therapy requires further investigation.
Topics: Humans; Copper; Anti-Bacterial Agents; Meropenem; Ampicillin; Ions
PubMed: 37446795
DOI: 10.3390/molecules28135133 -
The World Allergy Organization Journal May 2024Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I...
BACKGROUND
Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity.
METHODS
Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site.
RESULTS
Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51-14.09], P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 [95% CI 1.09-13.67], P < 0.002).
CONCLUSION
LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.
PubMed: 38638799
DOI: 10.1016/j.waojou.2024.100901 -
Japanese Journal of Infectious Diseases Jan 2024All clinical isolates of Streptococcus dysgalactiae subsp. equisimilis (SDSE) are considered susceptible to β-lactams, the first-line drugs used for SDSE infections....
All clinical isolates of Streptococcus dysgalactiae subsp. equisimilis (SDSE) are considered susceptible to β-lactams, the first-line drugs used for SDSE infections. However, penicillin-non-susceptible SDSE has been reported from Denmark. In this study, we attempted to detect β-lactam-non-susceptible clinical isolates of SDSE in Japan. One hundred and fifty clinical isolates of S. dysgalactiae were collected in 2018, and species identification was performed using Rapid ID Strep API. The minimum inhibitory concentrations (MIC) of six β-lactams (penicillin G, oxacillin, ceftizoxime, ceftibuten, cefoxitin, and cefaclor) were determined for 85 clinical isolates of SDSE using the agar dilution method standardized by the Clinical Laboratory Standards Institute. For the 85 isolates identified as SDSE, the MIC ranges of penicillin G, oxacillin, ceftizoxime, ceftibuten, cefoxitin, and cefaclor were 0.007-0.06, 0.03-0.12, 0.015-0.06, 0.25-2, 0.12-2, and 0.06-0.5 μg/mL, respectively. None of the clinical isolates were non-susceptible to penicillin G, indicating that all 85 clinical isolates of SDSE were susceptible to β-lactams. Our findings indicate that almost all clinical isolates of SDSE in several prefectures of Japan remain susceptible to β-lactams. Nevertheless, there remains a need for continuous and careful monitoring of drug susceptibility among clinical isolates of SDSE in Japan.
PubMed: 38296542
DOI: 10.7883/yoken.JJID.2023.339 -
MBio Jun 2023Plasmids facilitate the vertical and horizontal spread of antimicrobial resistance genes between bacteria. The host range and adaptation of plasmids to new hosts...
Plasmids facilitate the vertical and horizontal spread of antimicrobial resistance genes between bacteria. The host range and adaptation of plasmids to new hosts determine their impact on the spread of resistance. In this work, we explore the mechanisms driving plasmid adaptation to novel hosts in experimental evolution. Using the small multicopy plasmid pB1000, usually found in , we studied its adaptation to a host from a different bacterial family, Escherichia coli. We observed two different mechanisms of adaptation. One mechanism is single nucleotide polymorphisms (SNPs) in the origin of replication () of the plasmid, which increase the copy number in E. coli cells, elevating the stability, and resistance profile. The second mechanism consists of two insertion sequences (ISs), IS and IS, which decrease the fitness cost of the plasmid by disrupting an uncharacterized gene on pB1000 that is harmful to E. coli. Both mechanisms increase the stability of pB1000 independently, but only their combination allows long-term maintenance. Crucially, we show that the mechanisms have a different impact on the host range of the plasmid. SNPs in prevent the replication in the original host, resulting in a shift of the host range. In contrast, the introduction of ISs either shifts or expands the host range, depending on the IS. While IS leads to expansion, IS cannot be reintroduced into the original host. This study gives new insights into the relevance of ISs in plasmid-host adaptation to understand the success in spreading resistance. ColE1-like plasmids are small, mobilizable plasmids that can be found across at least four orders of and are strongly associated with antimicrobial resistance genes. Plasmid pB1000 carries the gene , conferring high-level resistance to penicillins and cefaclor. pB1000 has been described in various species of the family , for example, in Haemophilus influenzae, which can cause diseases such as otitis media, meningitis, and pneumonia. To understand the resistance spread through horizontal transfer, it is essential to study the mechanisms of plasmid adaptation to novel hosts. In this work we identify that a gene from pB1000, which encodes a peptide that is toxic for E. coli, and the low plasmid copy number (PCN) of pB1000 in E. coli cells are essential targets in the described plasmid-host adaptation and therefore limit the spread of pB1000-encoded . Furthermore, we show how the interplay of two adaptation mechanisms leads to successful plasmid maintenance in a different bacterial family.
Topics: DNA Transposable Elements; Escherichia coli; Plasmids; Bacteria; Cefaclor; Anti-Bacterial Agents
PubMed: 37097157
DOI: 10.1128/mbio.03158-22 -
Antibiotics (Basel, Switzerland) Sep 2023Cephalexin is a first-generation β-lactam antibiotic used in adults and pediatrics to treat various streptococcal and staphylococcal infections. This review aims to... (Review)
Review
Cephalexin is a first-generation β-lactam antibiotic used in adults and pediatrics to treat various streptococcal and staphylococcal infections. This review aims to summarize and evaluate all the pharmacokinetic (PK) data on cephalexin by screening out all pertinent studies in human beings following the per oral (PO) route. By employing different online search engines such as Google Scholar, PubMed, Cochrane Central, and Science Direct, 23 studies were retrieved, among which nine were in healthy subjects, five in diseased ones, and the remaining were drug-drug, drug-food, and bioequivalence-related. These studies were included only based on the presence of plasma concentration-time profiles or PK parameters, i.e., maximum plasma concentration (C), half-life (t) area under the curve from time 0-infinity (AUC and clearance (CL/F). A dose-proportional increase in AUC and C can be portrayed in different studies conducted in the healthy population. In comparison to cefaclor, C was recorded to be 0.5 folds higher for cephalexin in the case of renal impairment. An increase in AUC was seen in cephalexin on administration with probenecid, i.e., 117 µg.h/mL vs. 68.1 µg.h/mL. Moreover, drug-drug interactions with omeprazole, ranitidine, zinc sulfate, and drug-food interactions for cephalexin and other cephalosporins have also been depicted in different studies with significant changes in all PK parameters. This current review has reported all accessible studies containing PK variables in healthy and diseased populations (renal, dental, and osteoarticular infections, continuous ambulatory peritoneal dialysis) that may be favorable for health practitioners in optimizing doses among the latter.
PubMed: 37760698
DOI: 10.3390/antibiotics12091402 -
Journal of Conservative Dentistry and... 2023Apexification procedure with Mineral trioxide aggregate (MTA) and Biodentine as apical plugs along with the incorporation of medicaments such as silver zeolite,...
Evaluation of calcium ion release from apical plugs formed by Biodentine and MTA with and without incorporation of triple antibiotic powder and modified triple antibiotic powder (cefaclor) using atomic absorption spectrophotometry - An study.
INTRODUCTION
Apexification procedure with Mineral trioxide aggregate (MTA) and Biodentine as apical plugs along with the incorporation of medicaments such as silver zeolite, chlorhexidine, and triple antibiotic powder (TAP) is a new area of research that is gradually gaining momentum in dentistry.
AIM
The study aimed to evaluate and compare the calcium released from the apical plugs formed by MTA and Biodentine with and without incorporation of 2% TAP and 2% modified triple antibiotic powder (mTAP).
MATERIALS AND METHODS
Ninety single-rooted teeth were randomly divided ( = 15) into two experimental groups with three subgroups (n = 5) each based on the composition of apical plugs (4 mm) as follows: Group A: Biodentine - Subgroup 1: Biodentine, Subgroup 2: Biodentine + 2% TAP, and Subgroup 3: Biodentine + 2% modified TAP and Group B: MTA - Subgroup 1: MTA, Subgroup 2: MTA + 2% TAP, and Subgroup 3: MTA + 2% modified TAP. Each sample tooth was then immersed in 10 mL of deionized water. Evaluation of calcium release was done on days 7, 15, and 30 using an atomic absorption spectrophotometer. Data were analyzed using a one-way analysis of variance and a Tukey's test.
RESULTS
Calcium ion release was maximum for Biodentine compared to MTA and was greater with materials incorporated with TAP and mTAP than materials alone at days 7, 15, and 30.
CONCLUSION
The incorporation of 2% TAP and 2% mTAP resulted in increased calcium ions released from MTA and Biodentine which helps in faster apexification.
PubMed: 38292368
DOI: 10.4103/jcd.jcd_250_23 -
Pharmaceutical Research Oct 2023Ovarian cancer is the most lethal cancer in gynaecology. Surgery, chemotherapy, and radiotherapy are the most often used cancer-fighting strategies. Post-surgery...
BACKGROUND
Ovarian cancer is the most lethal cancer in gynaecology. Surgery, chemotherapy, and radiotherapy are the most often used cancer-fighting strategies. Post-surgery infection is fairly prevalent, especially among people with insufficient immunity. Zinc oxide nanoparticles (ZnOnps) have amazing biomedical features as anticancer and antibacterial agents.
METHODS
We investigated the behaviour of ZnOnps synthesized by green methods on ovarian cancers using established human ovarian cancer cell lines, besides the antibacterial action toward models of gram + ve and gram -ve bacteria. The cytotoxic effect of ZnOnps was calculated using a Sulforhodamine B (SRB) trial. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were tested as models for gram + ve and gram -ve bacteria. The selected bacteria were subjected to concentrations of 20, 40, 80, and 100 μg/ml.
RESULTS
The synthesized ZnOnps induced 50% inhibitory concentration (IC50) at a concentration of 27.45 μg/ml. The diameter of inhibition ranged between 20.16 ± 0.16 and 27 ± 0.57 mm for S. aureus and 25.66 ± 0.33 to 31 ± 0.33 mm for E. coli. ZnOnps antagonistic effect statistically differed with neomycin, cefaclor, and cefadroxil.
CONCLUSIONS
Green synthesis of ZnOnps is easily prepared, low cost, non-toxic, and eco-friendly. Their cytotoxic action on SKOV3 cells and their antibacterial characteristics pave the way to be an alternative therapy for ovarian cancer and S. aureus and E. coli infection.
Topics: Humans; Female; Staphylococcus aureus; Zinc Oxide; Escherichia coli; Nanoparticles; Anti-Bacterial Agents; Antineoplastic Agents; Ovarian Neoplasms; Metal Nanoparticles
PubMed: 37016170
DOI: 10.1007/s11095-023-03505-0 -
Polish Journal of Microbiology Jun 2023The present study aimed to determine the capsular serotype distribution and antimicrobial drug resistance patterns of from children in the Kunming region of China. This...
The present study aimed to determine the capsular serotype distribution and antimicrobial drug resistance patterns of from children in the Kunming region of China. This information could guide policymakers in clinical treatment. In the present study, isolates were tested for their serotypes, antimicrobial susceptibility pattern, and presence of β-lactamases. One-hundred forty-eight strains isolated from children 0-2 years old were investigated for capsular types by glass slide agglutination and molecular methods, and biotyped by the biochemical reactions. The drug resistance-encoding genes , , and the gene mutations , and were detected with real-time quantitative polymerase chain reaction (qPCR). The prevalence of β-lactamase-producing strains (60.3%) was significantly higher ( < 0.05) than non-enzyme-producing strains. β-Lactamase-producing strains were multidrug resistant to various antibiotics such as ampicillin, tetracycline, sulfamethoxazole/trimethoprim, chloramphenicol, cefuroxime, and cefaclor. Among β-lactamase-producing strains, the detection rates of the , , , and were 54.1%, 18.9%, 11.8%, and 6.9%, respectively. The biotyping results show that most strains were of type II and III. Non-typeable e (NTHi) accounted for 89.3% of the strains. NTHi strains were the most prevalent in this region; most belonged to biological types II and III. β-Lactamase-positive ampi-cillin-resistant (BLPAR) strains were prevalent among isolates in this region.
Topics: Child; Humans; Infant, Newborn; Infant; Child, Preschool; Serogroup; Haemophilus influenzae; Haemophilus Infections; Anti-Bacterial Agents; beta-Lactamases; Microbial Sensitivity Tests; Drug Resistance
PubMed: 37144671
DOI: 10.33073/pjm-2023-006