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BMC Microbiology Jun 2022Ribosome stalling on ermBL at the tenth codon (Asp) and mRNA stabilization are believed to be mechanisms by which erythromycin (Ery) induces ermB expression. Expression...
BACKGROUND
Ribosome stalling on ermBL at the tenth codon (Asp) and mRNA stabilization are believed to be mechanisms by which erythromycin (Ery) induces ermB expression. Expression of ermB is also induced by 16-membered ring macrolides (tylosin, josamycin and spiramycin), but the mechanism underlying this induction is unknown.
METHODS
We introduced premature termination codons, alanine-scanning mutagenesis and amino acid mutations in ermBL and ermBL2.
RESULTS
In this paper, we demonstrated that 16-membered ring macrolides can induce ermB expression but not ermC expression. The truncated mutants of the ermB-coding sequence indicate that the regulatory regions of ermB whose expression is induced by Ery and 16-membered ring macrolides are different. We proved that translation of the N-terminal region of ermBL is key for the induction of ermB expression by Ery, spiramycin (Spi) and tylosin (Tyl). We also demonstrated that ermBL2 is critical for the induction of ermB expression by erythromycin but not by 16-membered ring macrolides.
CONCLUSIONS
The translation of ermBL and the RNA sequence of the C-terminus of ermBL are critical for the induction of ermB expression by Spi and Tyl.
Topics: Anti-Bacterial Agents; Erythromycin; Macrolides; Spiramycin; Tylosin
PubMed: 35681117
DOI: 10.1186/s12866-022-02565-3 -
MSphere Oct 2022Escherichia coli is intrinsically resistant to macrolides due to outer membrane impermeability, but may also acquire macrolide resistance genes by horizontal transfer....
Escherichia coli is intrinsically resistant to macrolides due to outer membrane impermeability, but may also acquire macrolide resistance genes by horizontal transfer. We evaluated the prevalence and types of acquired macrolide resistance determinants in pig clinical E. coli, and we assessed the ability of peptidomimetics to potentiate different macrolide subclasses against strains resistant to neomycin, a first-line antibiotic in the treatment of pig-enteric infections. The erythromycin MIC distribution was determined in 324 pig clinical E. coli isolates, and 62 neomycin-resistant isolates were further characterized by genome sequencing and MIC testing of azithromycin, spiramycin, tilmicosin, and tylosin. The impact on potency achieved by combining these macrolides with three selected peptidomimetic compounds was determined by checkerboard assays in six strains representing different genetic lineages and macrolide resistance gene profiles. Erythromycin MICs ranged from 16 to >1,024 μg/mL. Azithromycin showed the highest potency in wild-type strains (1 to 8 μg/mL), followed by erythromycin (16 to 128 μg/mL), tilmicosin (32 to 256 μg/mL), and spiramycin (128 to 256 μg/mL). Isolates with elevated MIC mainly carried (B), either alone or in combination with other acquired macrolide resistance genes, including (42), (C), (A), (B), and (G). All peptidomimetic-macrolide combinations exhibited synergy (fractional inhibitory concentration index [FICI] < 0.5) with a 4- to 32-fold decrease in the MICs of macrolides. Interestingly, the MICs of tilmicosin in wild-type strains were reduced to concentrations (4 to 16 μg/mL) that can be achieved in the pig intestinal tract after oral administration, indicating that peptidomimetics can potentially be employed for repurposing tilmicosin in the management of E. coli enteritis in pigs. Acquired macrolide resistance is poorly studied in Escherichia coli because of intrinsic resistance and limited antimicrobial activity in Gram-negative bacteria. This study reveals new information on the prevalence and distribution of macrolide resistance determinants in a comprehensive collection of porcine clinical E. coli from Denmark. Our results contribute to understanding the correlation between genotypic and phenotypic macrolide resistance in E. coli. From a clinical standpoint, our study provides an initial proof of concept that peptidomimetics can resensitize E. coli to macrolide concentrations that may be achieved in the pig intestinal tract after oral administration. The latter result has implications for animal health and potential applications in veterinary antimicrobial drug development in view of the high rates of antimicrobial-resistant E. coli isolated from enteric infections in pigs and the lack of viable alternatives for treating these infections.
Topics: Swine; Animals; Escherichia coli; Anti-Bacterial Agents; Azithromycin; Peptidomimetics; Macrolides; Tylosin; Drug Resistance, Bacterial; Spiramycin; Erythromycin; Escherichia coli Infections; Neomycin
PubMed: 36154672
DOI: 10.1128/msphere.00402-22 -
Cureus Jan 2024Introduction Congenital toxoplasmosis (CT), despite being mostly subclinical at birth, can cause disabling disease in the fetus and lead to long-term sequelae. It is an...
Introduction Congenital toxoplasmosis (CT), despite being mostly subclinical at birth, can cause disabling disease in the fetus and lead to long-term sequelae. It is an important cause of chorioretinitis in infants and adolescents. Data on postnatal treatment are controversial, and there is a lack of universal guidelines. Methods A cross-sectional study of newborns with suspected CT was conducted between January 2007 and December 2021. Results Seventy-one patients with suspected CT were included. During pregnancy, 64 (90.1%) of the mothers underwent therapy, of which 59 (83.1%) with spiramycin. Amniocentesis identified one positive polymerase chain reaction assay. Most newborns were asymptomatic with normal laboratory, ophthalmological, and hearing screening. There was one case of hyperproteinorrachia. Fifty-seven patients (80.3%) started treatment: 42 (73.7%) with spiramycin, seven (12.3%) with pyrimethamine, sulfadiazine, and folinic acid (P+S+FA), and eight (14%) with P+S+FA intercalated with spiramycin. Adverse effects were found in 11 (19.3%) cases, mainly neutropenia. After investigation, we found three confirmed CT cases corresponding to 4.2% of suspected cases and an incidence of 0.4 per 10,000 births. All had normal clinical and laboratory exams in the neonatal period and started P+S+FA, fulfilling 12 months of therapy. During the follow-up, all presented normal psychomotor development without any long-term sequelae. Conclusion The lower incidence in our study, compared to the incidence in Europe, may be related to the decline in the prevalence of toxoplasmosis as well as the effectiveness of measures to prevent primary infection and a well-established program of antenatal screening, followed by the early initiation of treatment during pregnancy to prevent vertical transmission.
PubMed: 38406029
DOI: 10.7759/cureus.52971 -
Infection and Drug Resistance 2023Toxoplasmosis is a parasitic disease caused by that infects humans and many types of mammals and birds.
BACKGROUND
Toxoplasmosis is a parasitic disease caused by that infects humans and many types of mammals and birds.
OBJECTIVE
To investigate the effect of selenium nanoparticles (SeNPs) and (Pd) extracts loaded on SeNPs as a new agent to combat chronic infections in murine model as an alternative method to standard Spiramycin drug therapy.
METHODS
A total of 64 female mice were randomly divided into eight groups: GI: Normal control, GII: Positive control, GIII: infected and treated with Spiramycin, GIV: infected and treated with SeNPs, GV: infected and treated with aqueous extract of Pd, GVI: infected and treated with methanolic extract of Pd, GVII: infected and treated with aqueous extract of Pd loaded on SeNPs, GVIII: infected and treated with methanolic extract of Pd loaded on SeNPs. Date palm () fruits were identified and collected from the farms of Saudi Arabia. Preparation and characterization of SeNPs were done. The parasitological, histopathological examinations and biochemical changes were evaluated in all groups.
RESULTS
Parasitological results showed significant differences in GVII in comparison to GII while GVIII showed significant differences in comparison to GII and GIII. The histopathological section of the cerebral cortex showed obvious alterations in the infected compared with untreated control groups. Aqueous and methanolic extracts of loaded on SeNPs treatment showed improvement that indicated by few perivascular cuffing with few inflammatory cell infiltrations. Few granule cells with mild intracellular vacuolation and edema few deformed neurons with deep pyknotic nuclei. Microglia cells expression of Iba-1 and inflammatory cytokines (IL-4, IL-10 and INF-γ) in serum of all groups was higher in GII and lowest in GVIII followed by GVII.
CONCLUSION
SeNPs and extracts loaded on SeNPs could be a potent agent to combat infections.
PubMed: 38144223
DOI: 10.2147/IDR.S443047 -
Journal of Chromatography. B,... Dec 2021A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of residues of spiramycin, a macrolide...
A liquid chromatography coupled to tandem mass spectrometry method for the quantification of spiramycin and its active metabolite neospiramycin in milk of major and minor species: Validation using the accuracy profile.
A liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of residues of spiramycin, a macrolide antibiotic, and its active metabolite neospiramycin in cow's milk as well as in minor species 'milk, goat and ewe. Spiramycin-d3 was used as internal standard for quantification of both analytes. This analytical method was validated using a global accuracy profile as a graphical decision tool built according to the trueness and the precision of the method. A unique and optimal linear model with logarithm transformation (with a determination coefficient of 0.9991) allowed the measurement of both analytes in the milks of the three animal species, in a wide range from 0.2 to 10 times the Maximal Residue Limit (MRL) (40-2000 µg.kg). The limits of detection and quantification were 13 µg.kg and 40 µg.kg, respectively. The accuracy profile was established to get 80% of future measurements in routine assays that will fall within the acceptance limits. Trueness of the method, expressed as relative bias, was comprised between -1.6% and 5.7% over the whole range of concentrations. The mean relative standard deviation for repeatability and intermediate precision were comprised between 1.1% and 2.7%; 2.5 and 4.2%, respectively, in all levels of concentration for the three milks. Moreover, a two-order polynomial function was used to model the relative expanded uncertainty with a determination coefficient of 0.834. This function aimed to determine the uncertainty of the future quantifications within the validated dosing range. Overall, the global accuracy profile highlighted the reliability of the method for the routine assays of spiramycin and neospiramycin even in milk from minor species (goat, ewe) by using the most accessible milk (often from cow), while guaranteeing a very high proportion of samples within the fixed acceptance limits. The applicability of this method was tested during a depletion study of spiramycin and neospiramycin in the milk of cow, goat and ewe. The developed analytical method will be useful to assess the distribution profile of the antibiotic and its metabolite in milk of minor species where few studies are available.
Topics: Animals; Chromatography, Liquid; Drug Residues; Limit of Detection; Linear Models; Milk; Reproducibility of Results; Spiramycin; Tandem Mass Spectrometry
PubMed: 34808577
DOI: 10.1016/j.jchromb.2021.123013 -
Experimental Parasitology May 2023Latent toxoplasmosis mostly reactivates which could result in acute encephalitis. Chronic toxoplasmosis treatments are severely constrained by Toxoplasma cyst...
UNLABELLED
Latent toxoplasmosis mostly reactivates which could result in acute encephalitis. Chronic toxoplasmosis treatments are severely constrained by Toxoplasma cyst resistance. Novel therapeutic approaches are therefore becoming more essential. In this study, the effects of levamisole (LEVA) and spiramycin on the early and late stages of experimental toxoplasmosis are investigated.
MATERIALS AND METHODS
Seventy-five Me49 Toxoplasma gondii infected Swiss albino mice were divided into five groups; (GI): noninfected control group; (GII): infected untreated control group; (GIII): infected- LEVA treated group; (GIV): infected and received combination of spiramycin and LEVA and (GV): infected-spiramycin treated group. The impact was assessed through brain cyst count by Quantitative Real-Time Polymerase Chain Reaction (PCR), interferon gamma (IFN-γ) assay, histopathological study, and total blood counts.
RESULTS
The progression of chronic toxoplasmosis could only be partially controlled by using either levamisole or spiramycin as a separate drug. The combined spiramycin and levamisole treatment significantly decreased the burden of Toxoplasma brain cyst, increased IFN-γ level, total blood parameters and improved the histopathological features especially at the late stage of infection.
IN CONCLUSION
Levamisole effectively modulated Toxoplasma-induced immune responses, resulting in chronic toxoplasmosis remission. Further clinical trials will be needed to study the effect of these combination in HIV/AIDS (human immunodeficiency virus) patients with toxoplasmosis.
Topics: Animals; Mice; Humans; Spiramycin; Levamisole; Toxoplasmosis; Toxoplasma
PubMed: 36958594
DOI: 10.1016/j.exppara.2023.108515 -
Experimental Parasitology Sep 2019Spiramycin-metronidazole and spiramycin-loaded chitosan (CS) nanoparticles (NPs) were tested in comparison with the current spiramycin treatment of T.gondii concerning...
Spiramycin-metronidazole and spiramycin-loaded chitosan (CS) nanoparticles (NPs) were tested in comparison with the current spiramycin treatment of T.gondii concerning tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain and were divided into experimental and control groups. The experimental groups orally received CS NPs, spiramycin, spiramycin-metronidazole, spiramycin-loaded CS NPs 400 mg/kg and spiramycin-loaded CS NPs 100 mg/kg. Drug efficacy was assessed by mice survival time, mortality rate, parasite load in different organs and morphological study of the tachyzoites movement by light microscope and the ultra-structure by SEM. The results revealed that the maximum survival time of more than 200 days with no mortality on the sacrifice day (8th) was observed in mice receiving spiramycin-loaded NPs. Spiramycin-loaded NPs showed the highest significant percent reduction of tachyzoites (about 90% reduction) in liver, spleen and brain as compared to the other used drugs denoting successful bypass of BBB. Light microscopy of the treated peritoneal tachyzoites showed sluggish tachyzoites movement while the NPs caused loss of their movement. SEM of the treated tachyzoites were more mutilated and some of them appeared rupturing in those receiving CS NPs and spiramycin-loaded NPs. In conclusion, spiramycin-loaded NPs showed the highest efficiency in the treatment of acute toxoplasmosis. The non-toxic nature and the anti-parasitic effect of both CS and spiramycin make the use of spiramycin-loaded CS NPs a potential material for treatment of human toxoplasmosis.
Topics: Acute Disease; Animals; Ascitic Fluid; Biocompatible Materials; Blood-Brain Barrier; Brain; Chitosan; Coccidiostats; Drug Combinations; Drug Delivery Systems; Kaplan-Meier Estimate; Liver; Male; Metronidazole; Mice; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Nanoparticles; Particle Size; Pilot Projects; Spiramycin; Spleen; Survival Rate; Tablets; Toxoplasma; Toxoplasmosis, Animal
PubMed: 31228418
DOI: 10.1016/j.exppara.2019.107717 -
Pharmacological Research Dec 2023Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in... (Randomized Controlled Trial)
Randomized Controlled Trial
Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8 T cells than the placebo group at 3 (2.300P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8 T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).
Topics: Humans; CD8-Positive T-Lymphocytes; Biomarkers; HLA-DR Antigens; Sepsis; Inflammation; Immunity; Neoplasms; Double-Blind Method
PubMed: 37984505
DOI: 10.1016/j.phrs.2023.106991 -
Journal of Clinical and Experimental... Oct 2022Patients with odontogenic infections are commonly prescribed antimicrobials on an experiential base without knowing the precise microorganisms implicated. The aim of... (Review)
Review
BACKGROUND
Patients with odontogenic infections are commonly prescribed antimicrobials on an experiential base without knowing the precise microorganisms implicated. The aim of this systematic scoping review is to evaluate the prevalence and proportions of antimicrobial-resistant species in patients with odontogenic infections.
MATERIAL AND METHODS
A systematic scoping review of scientific evidence was accomplished involving different databases.
RESULTS
Eight randomized clinical trials and 13 prospective observational studies were included. These investigations analyzed 1506 patients. The species that showed higher levels of resistance included aerobic and facultative anaerobe such as , and . In obligate anaerobes sampled were Peptostreptococcos spp., Bacteroides spp., and Prevotella spp. Staphylococcus showed resistance to ampicillin, piperacillin, clindamycin, amoxicillin, metronidazole, and penicillin. Streptococcus had resistance to metronidazole, clindamycin, doxycycline, penicillin, and amoxicillin. Peptostreptococcus spp. presented resistance to penicillin, amoxicillin, erythromycin, and cefalexin. Gram-negative microorganisms had resistance to tetracycline, ciprofloxacin, azithromycin, amoxicillin, erythromycin, and penicillin. Bacteroides spp. exhibited resistance to penicillin, erythromycin, and gentamicin. Prevotella spp. showed resistance to penicillin, amoxicillin, erythromycin, clindamycin, levofloxacin, and imipenem. Finally, Klebsiella spp. displayed resistance to ampicillin, amoxicillin, moxifloxacin, and cefalexin. Interestingly, one clinical trial showed that after therapy there was a reduction in sensitivity of 18% for azithromycin and 26% for spiramycin.
CONCLUSIONS
Most of the microorganisms had resistance to diverse groups of antimicrobials. Suitable antimicrobials must be prescribed founded on the microbial samples, culture susceptibility, and clinical progression of the odontogenic infection. Furthermore, it was observed high levels of resistance to antimicrobials that have been used in local and systemic therapy of oral cavity infections. A preponderance of anaerobic microorganisms over aerobic ones was observed. Antibiotic resistance, odontogenic infections, efficacy, microorganisms, scoping review.
PubMed: 36320675
DOI: 10.4317/jced.59830 -
The Science of the Total Environment Feb 2022The emergence and pollution of antibiotics in surface water in various regions have drawn widespread concern because of the harm to aquatic ecosystems and human health....
Occurrence and distribution of antibiotics in groundwater, surface water, and sediment in Xiong'an New Area, China, and their relationship with antibiotic resistance genes.
The emergence and pollution of antibiotics in surface water in various regions have drawn widespread concern because of the harm to aquatic ecosystems and human health. In this study, we aim to first investigate contamination and ecological risks of 39 antibiotics in Xiong'an New Area (XANA), China, and then illuminate relative abundances of antibiotic resistance genes (ARGs) and their correlations with antibiotics. The sum of antibiotic concentrations in the water circulation system, including surface water, groundwater, and sediment was 12.71-260.56 ng/L, ND-196.12 ng/L, and 38.03-406.31 ng/g, respectively. In surface water and sediment, cephalosporins and quinolones were the primary antibiotics, accounting for 45% and 16% of the total antibiotic concentrations in surface water and for 62% and 32% of the total antibiotic concentrations in sediment; this suggests a significant interaction between the two media. The antibiotic concentration was the highest in shallow groundwater at depths of <50 m (mean concentration of 79.22 ± 56.46 ng/L), indicating that surface water was a possible source of antibiotic contamination in groundwater. AMX presented the highest risk in both surface and groundwater and should be controlled as a priority. Moreover, the selection pressure of antibiotics on ARGs was discovered in the sediment in XANA, because the enrichment of sulA was significantly correlated with spiramycin and lincomycin and the enrichment of bla was significantly correlated with roxithromycin, ciprofloxacin, ofloxacin, and sulfapyridine. Thus, our investigation revealed potential antibiotic contamination in multiple environmental media in XANA, which should be addressed to prevent more serious pollution.
Topics: Anti-Bacterial Agents; China; Drug Resistance, Microbial; Ecosystem; Groundwater; Humans; Water
PubMed: 34715223
DOI: 10.1016/j.scitotenv.2021.151011