Post-antibiotic Treatment Research Articles

Evaluation of protective potency of coconut oil-based probiotic against antibiotic-induced compromised gastrointestinal attributes and associated complications in Swiss albino mice

Background: Antibiotic-induced gastrointestinal toxicity is a major concern globally. The gut-organ axis has been explicitly studied, and hence, any damage to the gut ecosystem directly or indirectly manifests into compromised multi-organ functions. Therefore, the present study was designed to explore the protective potency of coconut oil-probiotic (C-PRO) against antibiotic-induced compromised gastrointestinal attributes and associated complications. Methods: Animals were divided into 5 groups (n=6). Normal saline was given to the control group; the antibiotic cocktail was given to the antibiotic group. In the treatment group, low and high doses of C-PRO were given post-antibiotic treatment. In the per se group, only a high dose of C-PRO was given. After 28 days, animals were studied for neurobehavioral parameters and scarified. Blood and organs were collected and stored for histopathological, immune histochemical, and biochemical analysis. Results: Antibiotic treatment reduced body weight, increased oxidative stress, and caused histopathological damage to the stomach, duodenum, colon, brain, heart, liver, lungs, kidney, spleen, and testis. It also altered biochemical parameters such as lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), albumin, creatinine, urea, uric acid, and blood urea nitrogen (BUN). Additionally, Antibiotic exposure in mice exhibited depressive-like behaviour and declined cognitive function. The treatment with a low dose of C-PROs showed negligible protective effect, whereas a high dose of C-PRO effectively reversed the structural, biochemical, and neurobehavioral attributes toward normal. Conclusions: We conclude that the synergistic effect of coconut oil and probiotics, which have potent antioxidant and anti-inflammatory effects, might be responsible for multidimensional protective effects against compromised gastrointestinal attributes and associated complications.

Changes in short-chain fatty acids affect brain development in mice with early life antibiotic-induced dysbacteriosis.

Early enteral nutrition and the gut microbiota profoundly influence neonatal brain development, with short-chain fatty acids (SCFAs) from the microbiota playing a pivotal role. Understanding the relationship between dysbiosis, SCFAs, and brain development is crucial. In this study, we investigated the impact of antibiotics on the concentration of SCFAs in neonatal feces. Additionally, we developed a model of gut dysbiosis in neonatal mice to examine the potential relationship between this imbalance, SCFAs production, and brain function development. We measured the SCFAs content in the feces of two groups of neonates, categorized based on whether antibiotics were used, and conducted the Neonatal Behavioral Neurological Assessment (NBNA) test on all neonates. Then we evaluated fecal SCFAs levels in neonates and neonatal mice post-antibiotic treatment using liquid chromatography-mass spectrometry (LC-MS) analysis. Morris water maze (MWM) tests assessed behavioral performance, and western blot analysis examined brain tissue-related proteins-neuron-specific enolase (NSE), ionized calcium binding adaptor molecule-1 (IBA1), and myelin basic proteins (MBP). The use of antibiotics did not affect the NBNA scores of the two groups of neonates, but it did reduce the SCFAs content in their feces. Antibiotic administration induced gut dysbiosis in mice, resulting in decreased IBA1 and MBP expression. Interventions to restore gut microbiota ameliorated these effects. Mice with dysbiosis displayed cognitive deficits in the MWM test. SCFAs levels decreased during dysbiosis, and increased upon microbiota recovery. Neonatal dysbiosis affects the microbiota-gut-brain axis, impairing cognitive function and nervous system development. Reduced SCFAs may contribute significantly to these alterations.

Role of glycogen metabolism in Clostridioides difficile virulence.

Glycogen plays a vital role as an energy reserve in various bacterial and fungal species. Clostridioides difficile possesses a glycogen metabolism operon that contains genes for both glycogen synthesis and utilization. In our investigation, we focused on understanding the significance of glycogen metabolism in the physiology and pathogenesis of C. difficile. To explore this, we engineered a C. difficile JIR8094 strain lacking glycogen synthesis capability by introducing a group II intron into the glgC gene, the operon's first component. Quantification of intracellular glycogen levels validated the impact of this modification. Interestingly, the mutant strain exhibited a 1.5-fold increase in toxin production compared with the parental strain, without significant changes in the sporulation rate. Our analysis also revealed that wild-type C. difficile spores contained glycogen, whereas spores from the mutant strain lacking stored glycogen showed increased sensitivity to physical and chemical treatments and had a shorter storage life. By suppressing glgP expression, the gene coding for glycogen-phosphorylase, via CRISPRi, we demonstrated that glycogen accumulation but not the utilization is needed for spore resilience in C. difficile. Transmission electron microscopy analysis revealed a significantly lower core/cortex ratio in glgC mutant strain spores. In hamster challenge experiments, both the parental and glgC mutant strains colonized hosts similarly; however, the mutant strain failed to induce infection relapse after antibiotic treatment cessation. These findings highlight the importance of glycogen metabolism in C. difficile spore resilience and suggest its role in disease relapse.IMPORTANCEThis study on the role of glycogen metabolism in Clostridioides difficile highlights its critical involvement in the pathogen's energy management, its pathogenicity, and its resilience. Our results also revealed that glycogen presence in spores is pivotal for their structural integrity and resistance to adverse conditions, which is essential for their longevity and infectivity. Importantly, the inability of the mutant strain to cause infection relapse in hamsters post-antibiotic treatment pinpoints a potential target for therapeutic interventions, highlighting the importance of glycogen in disease dynamics. This research thus significantly advances our understanding of C. difficile physiology and pathogenesis, offering new avenues for combating its persistence and recurrence.

Risk of emergency hospital admission related to adverse events after antibiotic treatment in adults with a common infection: impact of COVID-19 and derivation and validation of risk prediction models

BackgroundWith the global challenge of antimicrobial resistance intensified during the COVID-19 pandemic, evaluating adverse events (AEs) post-antibiotic treatment for common infections is crucial. This study aims to examines the changes in incidence rates of AEs during the COVID-19 pandemic and predict AE risk following antibiotic prescriptions for common infections, considering their previous antibiotic exposure and other long-term clinical conditions.MethodsWith the approval of NHS England, we used OpenSAFELY platform and analysed electronic health records from patients aged 18–110, prescribed antibiotics for urinary tract infection (UTI), lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), sinusitis, otitis externa, and otitis media between January 2019 and June 2023. We evaluated the temporal trends in the incidence rate of AEs for each infection, analysing monthly changes over time. The survival probability of emergency AE hospitalisation was estimated in each COVID-19 period (period 1: 1 January 2019 to 25 March 2020, period 2: 26 March 2020 to 8 March 2021, period 3: 9 March 2021 to 30 June 2023) using the Kaplan–Meier approach. Prognostic models, using Cox proportional hazards regression, were developed and validated to predict AE risk within 30 days post-prescription using the records in Period 1.ResultsOut of 9.4 million patients who received antibiotics, 0.6% of UTI, 0.3% of URTI, and 0.5% of LRTI patients experienced AEs. UTI and LRTI patients demonstrated a higher risk of AEs, with a noted increase in AE incidence during the COVID-19 pandemic. Higher comorbidity and recent antibiotic use emerged as significant AE predictors. The developed models exhibited good calibration and discrimination, especially for UTIs and LRTIs, with a C-statistic above 0.70.ConclusionsThe study reveals a variable incidence of AEs post-antibiotic treatment for common infections, with UTI and LRTI patients facing higher risks. AE risks varied between infections and COVID-19 periods. These findings underscore the necessity for cautious antibiotic prescribing and call for further exploration into the intricate dynamics between antibiotic use, AEs, and the pandemic.

Presepsin in Critical Illness: Current Knowledge and Future Perspectives.

The accurate identification of infections is critical for effective treatment in intensive care units (ICUs), yet current diagnostic methods face limitations in sensitivity and specificity, alongside cost and accessibility issues. Consequently, there is a pressing need for a marker that is economically feasible, rapid, and reliable. Presepsin (PSP), also known as soluble CD14 subtype (sCD14-ST), has emerged as a promising biomarker for early sepsis diagnosis. PSP, derived from soluble CD14, reflects the activation of monocytes/macrophages in response to bacterial infections. It has shown potential as a marker of cellular immune response activation against pathogens, with plasma concentrations increasing during bacterial infections and decreasing post-antibiotic treatment. Unlike traditional markers such as procalcitonin (PCT) and C-reactive protein (CRP), PSP specifically indicates monocyte/macrophage activation. Limited studies in critical illness have explored PSP's role in sepsis, and its diagnostic accuracy varies with threshold values, impacting sensitivity and specificity. Recent meta-analyses suggest PSP's diagnostic potential for sepsis, yet its standalone effectiveness in ICU infection management remains uncertain. This review provides a comprehensive overview of PSP's utility in ICU settings, including its diagnostic accuracy, prognostic value, therapeutic implications, challenges, and future directions.

The New Delhi metallo-β-lactamase-1 biosensor rapidly and accurately detected antibiotic plasma concentrations in cefuroxime-treated patients

ObjectivesTherapeutic drug monitoring (TDM) of β-lactam antibiotics in critically ill patients may benefit dose optimisation, thus improving therapeutic outcomes. However, rapidly and accurately detecting these antibiotics in blood remains a challenge. This research group recently developed a thermometric biosensor called the New Delhi metallo-β-lactamase-1 (NDM-1) biosensor, which detects multiple classes of β-lactam antibiotics in spiked plasma samples. MethodsThis study assessed the NDM-1 biosensor's effectiveness in detecting plasma concentrations of β-lactam antibiotics in treated patients. Seven patients receiving cefuroxime were studied. Plasma samples collected pre- and post-antibiotic treatment were analysed using the NDM-1 biosensor and compared with liquid chromatography coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). ResultsThe biosensor detected plasma samples without dilution, and a brief pre-treatment using a polyvinylidene fluoride filter significantly lowered matrix effects, reducing the running time to 5–8 minutes per sample. The assay's linear range for cefuroxime (6.25–200 mg/L) covered target concentrations during the trough phase of pharmacokinetics in critically ill patients. The pharmacokinetic properties of cefuroxime in treated patients determined by the NDM-1 biosensor and the UPLC-MS/MS were comparable, and the cefuroxime plasma concentrations measured by the two methods showed statistically good consistency. ConclusionThese data demonstrate that the NDM-1 biosensor assay is a fast, sensitive, and accurate method for detecting cefuroxime plasma concentrations in treated patients and highlights the NDM-1 biosensor as a promising tool for on-site TDM of β-lactam antibiotics in critically ill patients.

Ironing out Persisters? Revisiting the Iron Chelation Strategy to Target Planktonic Bacterial Persisters Harboured in Carbapenem-Resistant Escherichia coli.

Antibiotic resistance is a global health crisis. Notably, carbapenem-resistant Enterobacterales (CRE) pose a significant clinical challenge due to the limited effective treatment options. This problem is exacerbated by persisters that develop upon antibiotic exposure. Bacteria persisters can tolerate high antibiotic doses and can cause recalcitrant infections, potentially developing further antibiotic resistance. Iron is a critical micronutrient for survival. We aimed to evaluate the utility of iron chelators, alone and in combination with antibiotics, in managing persisters. We hypothesized that iron chelators eradicate CRE persisters in vitro, when administered in combination with antibiotics. Our screening revealed three clinical isolates with bacteria persisters that resuscitated upon antibiotic removal. These isolates were treated with both meropenem and an iron chelator (deferoxamine mesylate, deferiprone or dexrazoxane) over 24 h. Against our hypothesis, bacteria persisters survived and resuscitated upon withdrawing both the antibiotic and iron chelator. Pursuing our aim, we next hypothesized that iron chelation is feasible as a post-antibiotic treatment in managing and suppressing persisters' resuscitation. We exposed bacteria persisters to an iron chelator without antibiotics. Flow cytometric assessments revealed that iron chelators are inconsistent in suppressing persister resuscitation. Collectively, these results suggest that the iron chelation strategy may not be useful as an antibiotic adjunct to target planktonic bacteria persisters.

Gut microbiota dynamics in KK-Ay mice: restoration following antibiotic treatment.

The primary aim of this study was to investigate the alterations in the microbial community of KK-Ay mice following antibiotic treatment. A comparative analysis of the gut microbiota was conducted between KK-Ay mice treated with antibiotics and those without treatment. The microbial community dynamics in antibiotic-treated KK-Ay mice were meticulously assessed over an eight-week period using 16S rDNA sequencing analysis. Simultaneously, dynamic renal function measurements were performed. The results demonstrated a marked decrease in bacterial DNA abundance following antibiotic intervention, coupled with a substantial reduction in bacterial diversity and a profound alteration in microbial composition. These observed microbiota changes persisted in the KK-Ay mice throughout the eight-week post-antibiotic treatment period. Particularly noteworthy was the reemergence of bacterial populations after two weeks or more, resulting in a microbiota composition resembling that of untreated KK-Ay mice. This transition was characterized by a significant increase in the abundance of clostridia at the class level, Lachnospirales and Oscillospirales at the order level, and Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae at the family level. Concurrently, there was a notable decrease in Clostridia_UCG-014. The observed alterations in the gut microbiota of antibiotic-treated KK-Ay mice suggest a dynamic response to antibiotic intervention and subsequent restoration towards the original untreated state.

A double-blind, randomized, placebo-controlled study assessing the impact of probiotic supplementation on antibiotic induced changes in the gut microbiome

The human gut microbiome, crucial for health, can be disrupted by antibiotic treatment, leading to various health issues and the rise of antimicrobial resistance (AMR). This study investigates the impact of a probiotic on the gut microbiome’s composition and antimicrobial resistance genes (ARGs) content following antibiotic treatment. Conducted as a single-centre, double-blind, randomized, placebo-controlled trial, adults taking oral antibiotics were allocated into a probiotic or placebo group. Evaluations included viable cell enumeration and shotgun metagenomic sequencing for microbiome analysis, along with ARG assessment. The probiotic maintained the numbers of lactobacilli, significantly increased the Bacteroides population and decreased numbers of enterobacteria. The lactobacilli and enterococci numbers decreased in the placebo. The alpha diversity remained stable in the probiotic group throughout the study, but significant reductions were observed in the placebo group post antibiotic treatment. There was significant spatial separation in beta diversities between groups at the end of the study. Compared to baseline levels, there was a significant reduction in the abundance of ARGs in the probiotic group at the end of the study, while ARG abundance in the placebo group was comparable with baseline levels at the end of the study. Co-occurrence network analysis observed consistent betweenness centrality and node degree within group in the probiotic group whereas scores decreased in the placebo group. This study suggests that the probiotic may minimize the disruption of antibiotic treatment on the gut microbiome by preserving microbial diversity and reducing ARG abundance.

Impact of Bacillus licheniformis from yaks following antibiotic therapy in mouse model.

Gut microorganism (GM) is an integral component of the host microbiome and health system. Abuse of antibiotics disrupts the equilibrium of the microbiome, affecting environmental pathogens and host-associated bacteria alike. However, relatively little research on Bacillus licheniformis alleviates the adverse effects of antibiotics. To test the effect of B. licheniformis as a probiotic supplement against the effects of antibiotics, cefalexin was applied, and the recovery from cefalexin-induced jejunal community disorder and intestinal barrier damage was investigated by pathology, real-time PCR (RT-PCR), and high-throughput sequencing (HTS). The result showed that A group (antibiotic treatment) significantly reduced body weight and decreased the length of jejunal intestinal villi and the villi to crypt (V/C) value, which also caused structural damage to the jejunal mucosa. Meanwhile, antibiotic treatment suppressed the mRNA expression of tight junction proteins ZO-1, claudin, occludin, and Ki67 and elevated MUC2 expression more than the other Groups (P < 0.05 and P < 0.01). However, T group (B. licheniformis supplements after antibiotic treatment) restored the expression of the above genes, and there was no statistically significant difference compared to the control group (P > 0.05). Moreover, the antibiotic treatment increased the relative abundance of 4 bacterial phyla affiliated with 16 bacterial genera in the jejunum community, including the dominant Firmicutes, Proteobacteria, and Cyanobacteria in the jejunum. B. licheniformis supplements after antibiotic treatment reduced the relative abundance of Bacteroidetes and Proteobacteria and increased the relative abundance of Firmicutes, Epsilonbacteraeota, Lactobacillus, and Candidatus Stoquefichus. This study uses mimic real-world exposure scenarios by considering the concentration and duration of exposure relevant to environmental antibiotic contamination levels. We described the post-antibiotic treatment with B. licheniformis could restore intestinal microbiome disorders and repair the intestinal barrier. KEY POINTS: • B. licheniformis post-antibiotics restore gut balance, repair barrier, and aid health • Antibiotics harm the gut barrier, alter structure, and raise disease risk • Long-term antibiotics affect the gut and increase disease susceptibility.

Strain- and sex-specific differences in intestinal microhemodynamics and gut microbiota composition.

Intestinal microcirculation is a critical interface for nutrient exchange and energy transfer, and is essential for maintaining physiological integrity. Our study aimed to elucidate the relationships among intestinal microhemodynamics, genetic background, sex, and microbial composition. To dissect the microhemodynamic landscape of the BALB/c, C57BL/6J, and KM mouse strains, laser Doppler flowmetry paired with wavelet transform analysis was utilized to determine the amplitude of characteristic oscillatory patterns. Microbial consortia were profiled using 16S rRNA gene sequencing. To augment our investigation, a broad-spectrum antibiotic regimen was administered to these strains to evaluate the impact of gut microbiota depletion on intestinal microhemodynamics. Immunohistochemical analyses were used to quantify platelet endothelial cell adhesion molecule-1 (PECAM-1), estrogen receptor α (ESR1), and estrogen receptor β (ESR2) expression. Our findings revealed strain-dependent and sex-related disparities in microhemodynamic profiles and characteristic oscillatory behaviors. Significant differences in the gut microbiota contingent upon sex and genetic lineage were observed, with correlational analyses indicating an influence of the microbiota on microhemodynamic parameters. Following antibiotic treatment, distinct changes in blood perfusion levels and velocities were observed, including a reduction in female C57BL/6J mice and a general decrease in perfusion velocity. Enhanced erythrocyte aggregation and modulated endothelial function post-antibiotic treatment indicated that a systemic response to microbiota depletion impacted cardiac amplitude. Immunohistochemical data revealed strain-specific and sex-specific PECAM-1 and ESR1 expression patterns that aligned with observed intestinal microhemodynamic changes. This study highlights the influence of both genetic and sex-specific factors on intestinal microhemodynamics and the gut microbiota in mice. These findings also emphasize a substantial correlation between intestinal microhemodynamics and the compositional dynamics of the gut bacterial community.

ResR/McdR-regulated protein translation machinery contributes to drug resilience in Mycobacterium tuberculosis

Survival response of the human tuberculosis pathogen, Mycobacterium tuberculosis (Mtb) to a diverse environmental cues is governed through its versatile transcription regulatory mechanisms with the help of a large pool of transcription regulators (TRs). Rv1830 is one such conserved TR, which remains uncharacterized in Mtb. It was named as McdR based on an effect on cell division upon its overexpression in Mycobacterium smegmatis. Recently, it has been implicated in antibiotic resilience in Mtb and reannotated as ResR. While Rv1830 affects cell division by modulating the expression of M. smegmatis whiB2, the underlying cause of its essentiality and regulation of drug resilience in Mtb is yet to be deciphered. Here we show that ResR/McdR, encoded by ERDMAN_2020 in virulent Mtb Erdman, is pivotal for bacterial proliferation and crucial metabolic activities. Importantly, ResR/McdR directly regulates ribosomal gene expression and protein synthesis, requiring distinct disordered N-terminal sequence. Compared to control, bacteria depleted with resR/mcdR exhibit delayed recovery post-antibiotic treatment. A similar effect upon knockdown of rplN operon genes further implicates ResR/McdR-regulated protein translation machinery in attributing drug resilience in Mtb. Overall, findings from this study suggest that chemical inhibitors of ResR/McdR may be proven effective as adjunctive therapy for shortening the duration of TB treatment.

Antibiotic-Induced Dysbiosis of the Gut Microbiota Impairs Gene Expression in Gut-Liver Axis of Mice.

Antibiotics can be a double-edged sword. The application of broad-spectrum antibiotics leads to the suppression of microorganisms in the human body without selective targeting, including numerous non-pathogenic microorganisms within the gut. As a result, dysbiosis of the gut microbiota can occur. The gut microbiota is a vast and intricate ecosystem that has been connected with various illnesses. Significantly, the gut and liver function in a closely coupled anatomical and physiological relationship referred to as the "gut-liver axis". Consequently, metabolites stemming from the gut microbiota migrate via the portal vein to the liver, thereby influencing gene expression and proper physiological activity within the liver. This study aimed to investigate the dysbiosis of gut microbiota ecology and the disruption of gene expression resulting from oral antibiotics and their subsequent recovery. In the experiment, mice were tube-fed neomycin (0.5 mg/mL) and ampicillin (1 mg/mL) for 21 days (ABX group) to conduct 16s rRNA sequencing. By simultaneously analyzing public datasets PRJDB6615, which utilized the same antibiotics, it was found that nearly 50% of the total microbiota abundance was attributed to the f__Lactobacillaceae family. Additionally, datasets GSE154465 and GSE159761, using the same antibiotics, were used to screen for differentially expressed genes pre-and post-antibiotic treatment. Quantitative real-time PCR was employed to evaluate gene expression levels before and after antibiotic treatment. It was discovered that oral antibiotics significantly disrupted gene expression in the gut and liver, likely due to the dysregulation of the gut microbiota ecology. Fecal microbiota transplantation (FMT) was found to be an effective method for restoring gut microbiota dysbiosis. To further enhance the restoration of gut microbiota and gene expression, an antioxidant, vitamin C, was added to the FMT process to counteract the oxidative effect of antibiotics on microorganisms. The results showed that FMTs with vitamin C were more effective in restoring gut microbiota and gene expression to the level of the fecal transplant donor.

Evaluation of Serum Levels of Cytokines in Acute Apical Abscess: A Longitudinal Observational Study

IntroductionCytokine levels are related to the aethiopathogenia of acute apical abscesses (AAA); however, the specific cytokine profiles in these cases are unclear. This study aimed to investigate the changes in systemic cytokine levels in patients with AAA and trismus onset, postantibiotic treatment, and postroot canal disinfection. MethodsIn total, 46 AAA patients with trismus and 32 control subjects were included. After seven days of antibiotic therapy, root canal disinfection was performed in the AAA patients. The serum levels of cytokines were evaluated at basal, seven, and 14 days after endodontic treatment. Quantification of cytokines from T helper (Th) 1, Th2, Th17, and regulatory T cells profiles was determined using the BioPlex MagPix system, and the obtained data were analyzed using SPSS statistical software (P < .05). ResultsAAA patients showed higher tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6, and IL-10 levels than control subjects, at basal measurement (P < .05); there were similar levels of interferon gamma, IL-1β, IL-4, and IL-17 between groups (P > .05). IL-6 and IL-10 levels decreased after antibiotic treatment (P < .05), which was also associated with clinical improvement in patients with AAA and trismus. Patients with AAA had a positive correlation with higher serum levels of IL-6 and IL-10. In addition, TNF-α levels decreased only after antibiotic and endodontic treatment. ConclusionsIn conclusion, patients with AAA had increased systemic serum levels of TNF-α, IL-6, and IL-10. Moreover, increased levels of IL-6 and IL-10 are associated with acute inflammatory symptoms. However, IL-6 and IL-10 levels decreased after antibiotic treatment, while TNF-α levels decreased after antibiotic and endodontic treatment.

Kidney abscess as a rare complication of the urinary tract infections in children - 20 years of single-center observations

Introduction and objectiveKidney abscess is one of the complications of the urinary tract infection. Gram (-) intestinal flora is considered the most common etiological factor in development of kidney abscess. The spreading of bacteria usually occurs via an ascending route. Currently, in the era of antibiotic therapies, the kidney abscess is a relatively rare complication.Material and methodsThe study aimed to analyse the prevalence, risk factors, clinical course of the disease, results of treatment, and the long-term consequences in pediatric patients with kidney abscess diagnosis.ResultsThe renal abscess was diagnosed in 8 out of 32,000 hospitalized children (0.00025%) (5 girls, 3 boys, average age 6 years). In 7 cases, the association with urinary tract infection was confirmed (87.5%). In all patients, the abscess was limited to the renal parenchyma and its diameter was below 50 mm; two patients had multiple abscesses. Three children (37.5%) had a history of urinary tract disease. All patients had increased levels of the inflammation markers but the renal function parameters were within the reference values. Five children (62.5%) presented clinical symptoms (fever, pain, dysuria); in 2 children (25%) the clinical course was chronic and oligosymptomatic. The sensitivity and specificity of ultrasound examinations (US) were 100% accurate in the diagnosis and monitoring of treatment. In all cases, antibiotic therapy was effective. Post-antibiotic treatment renoscintigraphy showed persistent post-inflammatory scars in 62.5% of cases.ConclusionsDuring 20 years of observations, kidney abscess was a rare complication of urinary tract infection. Most patients did not have any underlying risk factors. Ultrasound examination had high sensitivity and specificity in the diagnosis and monitoring of the treatment. Broad-spectrum, prolonged antibiotic therapy proved to be an effective treatment in all patients. However, after the abscess has been successfully healed, most patients required permanent nephrology care due to the presence of the post-inflammatory scars.

Gut Microbiota as Well as Metabolomes of Wistar Rats Recover within Two Weeks after Doripenem Antibiotic Treatment.

An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies.

Detection of Chlamydia trachomatis inside spermatozoa using flow cytometry: Effects of antibiotic treatment (before and after) on sperm count parameters

There is increasing evidence that Chlamydia trachomatis (CT) infection can directly affect male fertility. However, only few have investigated the effects of CT on semen parameters, and mostly with inconclusive results. The main aims of this study were to identify CT inside spermatozoa, and the possible pre and post antibiotic treatment effects on the overall semen parameters. We developed a flow cytometric method for the detection of CT inside spermatozoa (SPI™). Briefly, sperm cells were fixed, membrane permeabilized and DNA was loosened using DNAse. Sperm cells were incubated with a primary monoclonal antibody against CT and with a secondary fluorescent antibody (vs primary), and analysed using a flow cytometer. Of 2415 infertile individuals, 48.61% were found positive for CT. 170 CT+ samples were included in the CT antibiotic treatment study. 78.82% (134/170) of the CT+ showed a significant reduction in the percentage of the iCT infected spermatozoa after the antibiotic treatment; 59.70% (80/134) decreased to non–detectable levels. Spermcount data were also recorded. Spermatozoa morphology (normal and teratozoospermia index, TZI) and motility (fast progressive and non–progressive spermatozoa) were statistically significant altered in CT+ pre–treatment vs control group. CT antibiotic treatment showed statistically significant effects on normal spermatozoa morphology, mid–piece and tail defects, and TZI. The study demonstrated that semen flow cytometric analysis of semen could be a valuable tool for faster and accurate identification of individuals with asymptomatic CT infection. It also identified a positive effect of antibiotic therapy on semen parameters, that could help males with infertility.

Assessing the clinical value of faecal bile acid profiling to predict recurrence in primary Clostridioides difficile infection.

Factors influencing recurrence risk in primary Clostridioides difficile infection (CDI) are poorly understood, and tools predicting recurrence are lacking. Perturbations in bile acids (BAs) contribute to CDI pathogenesis and may be relevant to primary disease prognosis. To define stool BA dynamics in patients with primary CDI and to explore signatures predicting recurrence METHODS: Weekly stool samples were collected from patients with primary CDI from the last day of anti-CDI therapy until recurrence or, otherwise, through 8 weeks post-completion. Ultra-high performance liquid chromatography-mass spectrometry was used to profile BAs. Stool bile salt hydrolase (BSH) activity was measured to determine primary BA bacterial deconjugation capacity. Multivariate and univariate models were used to define differential BA trajectories in patients with recurrence versus those without, and to assess faecal BAs as predictive markers for recurrence. Twenty (36%) of 56 patients (median age: 57, 64% male) had recurrence; 80% of recurrences occurred within the first 9 days post-antibiotic treatment. Principal component analysis of stool BA profiles demonstrated clustering by recurrence status and post-treatment timepoint. Longitudinal faecal BA trajectories showed recovery of secondary BAs and their derivatives only in patients without recurrence. BSH activity increased over time only among non-relapsing patients (β= 0.056; likelihood ratio test p= 0.018). A joint longitudinal-survival model identified five stool BAs with area under the receiver operating characteristic curve >0.73 for predicting recurrence within 9 days post-CDI treatment. Gut BA metabolism dynamics differ in primary CDI patients between those developing recurrence and those who do not. Individual BAs show promise as potential novel biomarkers to predict CDI recurrence.

Enhanced Carbonylation of Photosynthetic and Glycolytic Proteins in Antibiotic Timentin-Treated Tobacco In Vitro Shoot Culture.

Antibiotics are used in plant in vitro tissue culture to eliminate microbial contamination or for selection in genetic transformation. Antibiotic timentin has a relatively low cytotoxic effect on plant tissue culture; however, it could induce an enduring growth-inhibiting effect in tobacco in vitro shoot culture that persists after tissue transfer to a medium without antibiotic. The effect is associated with an increase in oxidative stress injury in plant tissues. In this study, we assessed changes of reactive oxygen species accumulation, protein expression, and oxidative protein modification response associated with enduring timentin treatment-induced growth suppression in tobacco (Nicotiana tabacum L.) in vitro shoot culture. The study revealed a gradual 1.7 and 1.9-fold increase in superoxide (O2•−) content at the later phase of the propagation cycle for treatment control (TC) and post-antibiotic treatment (PA) shoots; however, the O2•− accumulation pattern was different. For PA shoots, the increase in O2•− concentration occurred several days earlier, resulting in 1.2 to 1.4-fold higher O2•− concentration compared to TC during the period following the first week of cultivation. Although no protein expression differences were detectable between the TC and PA shoots by two-dimensional electrophoresis, the increase in O2•− concentration in PA shoots was associated with a 1.5-fold increase in protein carbonyl modification content after one week of cultivation, and protein carbonylation analysis revealed differential modification of 26 proteoforms involved in the biological processes of photosynthesis and glycolysis. The results imply that the timentin treatment-induced oxidative stress might be implicated in nontranslational cellular redox balance regulation, accelerates the development of senescence of the shoot culture, and contributes to the shoot growth-suppressing effect of antibiotic treatment.

Treating ‘Septic’ With Enhanced Antibiotics and ‘Arthritis’ by Mitigation of Excessive Inflammation

Bacterial infection within the synovial joint, commonly known as septic arthritis, remains a clinical challenge as it presents two concurrent therapeutic goals of reducing bacterial burden and preservation of articular cartilage from destructive host inflammation. We hypothesized that mitigation of MRSA-induced inflammatory signaling could diminish destruction of articular cartilage in the setting of septic arthritis when used in conjunction with antibiotics. Herein, we provide evidence which supports a new therapeutic notion that concurrent antimicrobial therapy to address the ‘septic’ component of the disease with inflammation mitigation to manage the destructive ‘arthritis’ component. We established a murine model to mimic septic knee arthritis, as well as a variety of other inflammatory joint conditions. This murine septic arthritis model, in conjunction with in vitro and ex-vivo models, was utilized to characterize the inflammatory profile seen in active septic arthritis, as well as post-antibiotic treatment, via transcriptomic and histologic studies. Finally, we provided the clinical rationale for a novel therapeutic strategy combining enhanced antibiotic treatment with rifampin and adjuvant immunomodulation to inhibit post-infectious, excess chondrolysis and osteolysis. We identified that septic arthritis secondary to MRSA infection in our murine model led to increased articular cartilage damage compared to various types of inflammatory arthritis. The activation of the pERK1/2 signaling pathway, which is implicated with the mounting of an immune response and generation of inflammation, was increased in intracellular MRSA-infected synovial tissue and persisted despite antibiotic treatment. Trametinib, an inhibitor of ERK signaling through suppression of MEK1/2, alleviated the inflammation produced by the addition of intra-articular, heat-killed MRSA. Further, when combined with vancomycin and rifampin, mitigation of inflammation by pERK1/2 targeting improved outcomes for MRSA septic arthritis by conferring chondroprotection to articular cartilage and diminishing inflammatory osteolysis within bone. Our results support a new therapeutic notion that cell/biofilm-penetrating antibiotics alongside adjuvant mitigation of excessive intra-articular inflammation accomplish distinct therapeutic goals: reduction of bacterial burden and preservation of articular cartilage integrity.