Administration Of Oral Antibiotics Research Articles

Involvement of bacteria in the development of fungal infections in the Colorado potato beetle.

Entomopathogenic fungi may interact with insects' symbiotic bacteria during infection. We hypothesized that topical infection with Beauveria bassiana may alter the microbiota of the Colorado potato beetle (CPB) and that these modifications may alter the course of mycoses. We used a model with two concentrations of conidia: (1) high concentration that causes rapid (acute) pathogenesis with fast mortality followed by bacterial decomposition of insects; (2) lower concentration that leads to prolonged pathogenesis ending in conidiation on cadavers. The fungal infections increased loads of enterobacteria and bacilli on the cuticle surface and in hemolymph and midgut, and the greatest increase was detected during the acute mycosis. By contrast, stronger activation of IMD and JAK-STAT signaling pathways in integuments and fat body was observed during the prolonged mycosis. Relatively stable (nonpathogenic) conditions remained in the midgut during both scenarios of mycosis with slight changes in bacterial communities, the absence of mesh and stat expression, a decrease in reactive oxygen species production, and slight induction of Toll and IMD pathways. Oral administration of antibiotic and predominant CPB bacteria (Enterobacteriaceae, Lactococcus, Pseudomonas) led to minor and mainly antagonistic effects in survival of larvae infected with B. bassiana. We believe that prolonged mycosis is necessary for successful development of the fungus because such pathogenesis allows the host to activate antibacterial reactions. Conversely, after infection with high concentrations of the fungus, the host's resources are insufficient to fully activate antibacterial defenses, and this situation makes successful development of the fungus impossible.

Implementation of Outpatient Parenteral Antimicrobial Therapy (OPAT) in Patients with Complicated Periprosthetic Joint Infections.

Periprosthetic joint infections (PJI) are a serious complication of arthroplasty with high morbidity. With growing bacterial resistance and limited disposability of oral antibiotics with sufficient bioavailability, the need for intravenous antibiotic application is raising. This causes long-term hospital stays and rising costs. In the course of transferring procedures into an outpatient setting as well as coping with pressures on hospital capacity, outpatient parenteral antimicrobial therapy (OPAT) can build a bridge for the treatment of such infections.In a single centre analysis, 47 cases treated with OPAT were studied in relation to pathogen, antimicrobial resistance, indication for OPAT and follow up. Furthermore, the patients received an anonymised questionnaire with 4 clusters of interest in terms of internal quality assessment on the success and evaluation of this therapeutic procedure. Special attention was paid to the descriptive analysis of patients with periprosthetic joint infections (n=30).Between May 2021 and October 2022 out of 47 patients with OPAT, 30 cases with periprosthetic joint infections were identified. For infected hip- and knee arthroplasties, a remarkable spectrum of pathogens was found. In hip infections highly resistant strains of Staphylococcus epidermidis and Enterococci were detected. In knee infections, the pathogens were more susceptible, but however highly virulent Staphylococcus aureus and Streptococci. Difficult to treat, mixed infections were found in both locations. The indication for OPAT was based in half of the cases on the high level of antimicrobial resistance, with availability of only parenteral applicable antibiotics. Further indications were mixed infections and difficult to treat pathogens, with flucloxacillin therapy as well as OPAT as the last therapeutic option. The questionnaire showed 96% patient satisfaction in terms of organisation and acceptance of this kind of therapy. Complications or unexpected outpatient/ hospital treatments were very rare in connection with OPAT. Two thirds of patients reported completion of the treatment. In the clinical follow up (average of 5.7 months), 96.6% of cases were declared free of infection. In one patient the infection persisted.OPAT is a safe and reliable therapeutic option for outpatients to continue parenteral antimicrobial treatment in joint infections. Due to increasing pressure on hospitals in terms of costs and capacity, this therapy offers an alternative to inpatient treatment. The indication for OPAT should be set individually, risk adjusted and not generalised for all patients. The outpatient sector needs financial and structural support for comprehensive roll-out of this treatment in Germany. A further focus should be on the prevention of periprosthetic joint infections. With the knowledge of the expected pathogens and the surgical resources, the standards should be adapted. The choice of the antibiotic should be specified and the intervals of application be shortened, according to the surgical course, in order to yield high levels of agent concentration in the surgical area. Further investigations are required to test the superiority of OPAT versus the oral administration of antibiotics in long-term observations as well as to define the necessary duration of OPAT.

Effects of Bifidobacterium animalis subsp. lactis BB-12 and yogurt on mice during oral antibiotic administration

Probiotics have the potential to prevent disruptions to normal gastrointestinal function caused by oral antibiotic use. In this study, we examined the capacity of Bifidobacterium animalis subspecies lactis BB-12 (BB-12) and yogurt, separately and combined, to mitigate the effects of the antibiotic amoxicillin-clavulanate (AMC) on the gut microbiota and metabolomes of C57BL/6 J mice. Male and female mice were administered either BB-12, yogurt, BB-12 in yogurt, or saline for 10 days concurrent with the inclusion of AMC in the drinking water. Male mice exposed to AMC exhibited significant reductions (p<0.05) in body weight over the course of the study compared to sham (no AMC) controls whereas no such effects were observed for female mice. AMC administration resulted in rapid alterations to the intestinal microbiota in both sexes irrespective of BB-12 or yogurt treatment, including significant (p<0.05) losses in bacterial cell numbers and changes in microbial alpha-diversity and beta-diversity in the feces and cecal contents. The effects of AMC on the gut microbiota were observed within one day of administration and the bacterial contents continued to change over time, showing a succession marked by rapid reductions in Muribaculaceae and Lachnospiraceae and temporal increases in proportions of Acholeplasmataceae (day 1) and Streptococcaceae and Leuconostocaceae (day 5). By day 10 of AMC intake, high proportions of Gammaproteobacteria assigned as Erwiniaceae or Enterobacteriaceae (average of 63 %), were contained in the stools and were similarly enriched in the cecum. The cecal contents of mice given AMC harbored significantly reduced concentrations of (branched) short-chain fatty acids (SCFA), aspartate, and other compounds, whereas numerous metabolites, including formate, lactate, and several amino acids and amino acid derivatives were significantly enriched. Despite the extensive impact of AMC, starting at day 7 of the study, the body weights of male mice given yogurt or BB-12 (in saline) with AMC were similar to the healthy controls. BB-12 (in saline) and yogurt intake was associated with increased Streptococcaceae and both yogurt and BB-12 resulted in lower proportions of Erwiniaceae in the fecal and cecal contents. The cecal contents of mice fed BB-12 in yogurt contained levels of formate, glycine, and glutamine that were equivalent to the sham controls. These findings highlight the potential of BB-12 and yogurt to mitigate antibiotic-induced gut dysbiosis.

The Safety of Glycopeptide-Impregnated Calcium Sulphate Following Debridement, Antibiotics and Implant Retention (DAIR) for Infected Total Knee Replacement.

Background and objective The impact of prosthetic joint infection (PJI) stretches far beyond the physical nature of the disease. It can result in psychological and social consequences, with significant morbidity and mortality for patients. Calcium sulphate-based delivery agents are effective in the management of PJI, yet with associated risks of systemic adverse events. This study aims to evaluate the risk of systemic adverse events when using calcium-sulphate-based local antibiotic delivery agents in the management of PJIs. Methodology We identified 43 patients who underwent debridement, antibiotics and implant retention (DAIR) for infected total knee arthroplasty (TKA) between 2008 and 2014. Patients in the control groupunderwent conventional intravenous and then oral antibiotic administration, while those in the intervention groupunderwent additional local antibiotic therapy via a calcium sulphate alpha hemihydrate matrix. Case notes and laboratory results data were compiled to establish the safety and efficacy of local glycopeptide delivery. Results Serum vancomycin levels were within the safe therapeutic range for all patients in the intervention group with no difference in serum assays between treatment groups (intervention 7.7 mg/L; control 8.0 mg/L; P = 0.85). Renal function for the study cohort improved at every time point post-operatively when referenced against pre-operative renal function (P < 0.05). There was no difference in renal function between intervention and control groups on day 1, one week, six weeks or 12 weeks post-operatively (P = 0.78, 0.89, 0.20 and 0.50). Conclusions Local glycopeptide delivery via a calcium sulphate alpha hemihydrate matrix did not result in systemic adverse consequences specifically not raising the systemic level of glycopeptide, nor reducing renal function. Implications for future research Although demonstrates a safety profile and potential therapeutic benefit, the long-term efficacy of this approach needs to be established. Importantly, selection bias may contribute to masking clinically significant differences in post-operative outcomes.

Porcine Monocyte DNA Traps Formed during Infection with Pathogenic Clostridioides difficile Strains.

Clostridioides (Clostridium) difficile is an enteric pathogen of several mammalian species including man, frequently involving nosocomial resurgence, following oral administration of broad-spectrum antibiotics, but also with human-to-human infection occurring, and neonatal pigs with zoonotic transmission. To date, the immune response to C. difficile has mostly focused on neutrophils and cytokine/chemokines, particularly in human infection. The neonatal pig is now recognized as a valuable model for human infection. We show that porcine monocytes respond to C. difficile differently compared with many other bacterial infections. Infection of porcine monocytes with human C. difficile strains CD630 (Ribotype 078) or R20291 (Ribotype 027) for 3 or 24 h post-infection (pi) resulted in a lack of oxidative burst or nitrite ion production when compared to uninfected controls (p > 0.05). The survival dynamics of both CD630 and R20291 in monocytes were similar with intracellular bacterial numbers being similar at 3 h pi and 24 h pi (p > 0.05). However, we show that porcine monocytes entrap C. difficile via extracellular DNA traps. This process began as early as 3 h pi, and at 24 h pi the nuclei appeared to be depleted of DNA, although extracellular DNA was associated with the cell membrane. Our preliminary study also suggests that entrapment of C. difficile by extracellular DNA may occur via a process of monocyte etosis.

The efficacy of vaginal treatment for non-Lactobacillus dominant endometrial microbiota-A case-control study.

Reduced Lactobacillus occupancy in the uterine microflora has been associated with implantation failure. This study aimed to evaluate a treatment for improving the uterine microflora. This study included patients diagnosed with repeated implantation failure-defined as failure to achieve pregnancy after two or more transfers of viable embryos-who were classified as non-Lactobacillus dominant. Treatment A comprised oral administration of antibiotics for 1 week, followed by oral probiotic butyrate tablets (3 g/day) for approximately 30 days. Treatment B comprised a 1-week course of oral (750 mg/day) and vaginal (250 mg/day) metronidazole, followed by a 1-week intravaginal administration of probiotic capsules (1 capsule/day) and continued oral administration of probiotics (1 capsule/day). Both treatments were compared in terms of efficacy in improving vaginal flora. Improvement was defined as Lactobacillus occupancy >90% or an increase in Lactobacillus occupancy >20%. Seven (41.2%) of 17 patients in the Treatment A group improved in response to the treatment. Contrastingly, 9 (90.0%) of 10 patients improved in the Treatment B group (p = 0.0127). Following treatment, Lactobacillus occupancy in the Treatment B group (62.9% ± 12.7%) was significantly higher than that in the Treatment A group (5.7% ± 9.8%) (p = 0.0242). This study demonstrates the effectiveness of combining antibiotics and probiotics in vaginal formulations for treating abnormal uterine microflora. However, its potential impact on in vitro fertilization outcomes remains unclear and warrants further investigation through larger, more comprehensive studies.

Gut microbiome alpha diversity decreases in relation to body weight, antibiotic exposure, and infection with multidrug-resistant organisms

The human gastrointestinal tract is home to a dense and diverse microbiome, predominated by bacteria. Despite the conservation of critical functionality across most individuals, the composition of the gut microbiome is highly individualized, leading to differential responses to perturbations such as oral antibiotics or multidrug-resistant organism (MDRO) infection. Herein, subject responses to these perturbations based on their body weight were evaluated. Fecal samples were collected from 45 subjects at the Detroit Medical Center to evaluate the effects of perturbations on subjects' gut microbiome composition. Bacterial profiling was completed using 16S rRNA gene sequencing. Subjects with multiple MDROs, subjects weighing greater than 80kg infected with MDRO E coli, and subjects weighing less than 80kg with exposure to vancomycin and carbapenem antibiotics during hospitalization had significantly decreased gut microbiome richness. Both administration of oral antibiotics and MDRO infections decreased gut microbiome alpha diversity, but the magnitude of these gut microbiome perturbations was body weight dependent.

Comparing Oral Versus Intravenous Antibiotics Administration for Cellulitis Infection: Protocol for a Systematic Review and Meta-Analysis

Background Cellulitis is defined as an infection of the skin that is usually characterized by localized but poorly demarcated areas of erythema, swelling, and pain. Erysipelas is a subtype of cellulitis that is characterized by a more superficial infection, often involving the face. Because gram-positive bacteria are the most common infective agent, beta-lactam antibiotics such as cephalosporins are commonly used. However, guidelines and physician preference vary widely as different antibiotic options and routes of administration exist, in addition to the fact that most cases are treated empirically without microbiological lab guidance. This lack of standardization in evidence, guidelines, and physician practice prompted this systematic review and meta-analysis of both randomized trial data and cohort studies to aggregate the currently available evidence for the optimal routes of antibiotic administration in cellulitis treatment. Objective The primary objective of our review is to compare the efficacy of oral versus intravenous antibiotic administration for cellulitis infections, thereby providing clinicians with evidence-based guidelines for treatment. Methods We will search MEDLINE, Embase, and CENTRAL through Ovid as well as Web of Science and CINAHL for all available literature comparing different routes of antibiotic administration in the treatment of cellulitis and erysipelas. We will perform title and abstract as well as full-text screening in duplicate according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines and then extract the relevant data using a prepiloted data sheet. The primary outcome for our review is the duration of infection resolution, and secondary outcomes such as incidence of sepsis, mortality, hospital admission, and Clostridium difficile infection. We will assess the risk of bias in our included studies using the RoB 2.0 (revised tool for Risk of Bias in randomized trials) and ROBINS-I (Risk of bias in non-randomized studies for interventions) tools, with a final quality assessment using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework and a sensitivity analysis to examine heterogeneity. Results We will publish the final results of our systematic review in a peer-reviewed academic journal. This project received no funding or financial assistance. Data analysis is currently underway, and the results are expected to be submitted for publication in late November 2023. Conclusions To our knowledge, this will be the most up-to-date review of the best available evidence comparing different routes of antibiotic administration for cellulitis. Because of the vast selection of antibiotic options available and the empirical nature of the treatment, we anticipate heterogeneity within our data but nonetheless hope to provide aggregated evidence on the efficacy of intravenous versus oral administration of antibiotics in cellulitis treatment. We hope the results from this study will better inform physician practices in the future for cellulitis infections. International Registered Report Identifier (IRRID) PRR1-10.2196/48342

Adverse Events Associated with Prolonged Antibiotic Therapy for Periprosthetic Joint Infections-A Prospective Study with a Special Focus on Rifampin.

Periprosthetic Joint Infection (PJI) is a significant contributor to patient morbidity and mortality, and it can be addressed through a range of surgical interventions coupled with antibiotic therapies. Following surgical intervention(s), prolonged administration of oral antibiotics is recommended to cure PJI. There is a lack of reports on the adverse events (AEs) associated with oral antibiotics, particularly rifampin. This investigation sought to elucidate the occurrence of antibiotic-related AEs after an initial regimen of intravenous antibiotic administration, supplemented by an extended course of oral antibiotics. A prospective study of patients diagnosed with PJI of the hip, knee, or shoulder who underwent single-stage exchange arthroplasty (SSE) (10%), two-stage exchange arthroplasty (TSE) (81%), or debridement, antibiotics, and implant retention (DAIR) (6%) was performed. The primary outcome of interest was the detection of AEs, the secondary outcome the detection of a correlation between rifampin use and the incidence of AEs, and the tertiary outcome was whether oral antibiotic treatment needed to be adjusted or discontinued due to AEs. In addition, subjective tolerability was monitored throughout the study. A total of 336 events were identified for 73 out of 80 patients. The most frequently used antibiotics were rifampin and co-trimoxazole. Most AEs occurred in the gastrointestinal tract (46%). The most frequent AEs were nausea, inappetence, diarrhea, and skin rash. In 6% of cases, the AEs led to antibiotic discontinuation, and in 29% of cases, a dose adjustment of the oral therapy occurred, mainly with amoxicillin or co-trimoxazole. The majority of patients (55%) rated the subjective tolerability as good. In conclusion, AEs during antibiotic treatment for PJI are common. They mainly affect the gastrointestinal tract. Rifampin use might be a reason for the higher incidence of AEs compared to non-rifampin antibiotic treatment.

Population pharmacokinetics of enrofloxacin and florfenicol in the giant danio (Devario aequipinnatus) following oral administration of both antibiotics and bath administration of enrofloxacin

The lack of pharmacokinetic and drug exposure data, even for commonly utilized antibiotics, in freshwater ornamental teleost fish species magnifies the difficulties in treating bacterial pathogens. This study aimed to determine the population pharmacokinetics of enrofloxacin and florfenicol and to predict their probability of target attainment for giant danio (Devario aequipinnatus), a close relative of the commercially and biomedically important zebra danio (Danio rerio). Enrofloxacin was dosed orally at 8 mg/kg or via bath at 10 mg/L in 95 fish, and florfenicol orally at 60 mg/kg in 56 fish. Informative sampling times were identified by optimal design analysis. Drug concentrations in blood and muscle homogenate were quantified by LC-MS/MS and modelled by population pharmacokinetics. Monte Carlo simulations were used to predict the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment. The apparent total clearance was 1.17 mL/h (33.9% coefficient of variation [CV] for between animal variability) for enrofloxacin and 1.89 mL/h (20.9% CV) for florfenicol. The ratio of drug exposure in muscle homogenate compared to that in plasma was 1.61 (33.3% CV) for enrofloxacin and 0.782 (19.4% CV) for florfenicol. Oral florfenicol at 60 mg/kg robustly covered MICs up to 2 to 4 mg/L, depending on the PK/PD target. While oral enrofloxacin (8 mg/kg) robustly covered MICs up to 0.125 to 0.5 mg/L, bath dosing at 10 mg/L for 5 or 10 h only covered MICs up to 0.0156 to 0.125 mg/L. These Monte Carlo simulations provided guidance on the range of MICs that result in high probabilities of successful treatment.

Preoperative oral antibiotic administration in patients undergoing curative resection with stoma creation for colorectal cancer: effectiveness in preventing surgical site infection and the possibility of peristomal candidiasis induced by enterobacterial alteration.

There are many reports that preoperative oral antibiotics (OAs) are effective in preventing surgical site infections (SSIs) in colorectal surgery. However, there is no consensus on the optimal dose of OAs. In this study, we investigated the efficacy of OAs in preventing SSIs and the possibility that OAs induce enterobacterial alteration in the intestinal tract. We performed a retrospective cross-sectional analysis of 389 patients who underwent R0 resection and stoma creation for colorectal cancer in our department between 2009 and 2020. We focused on the incidence of peristomal candidiasis (PSC) as an indicator of enterobacterial alteration and used kanamycin (KM) and metronidazole (MNZ) as the OAs. A low-dose group received 1000 mg/day of both KM and MNZ, and a high-dose group received 2000 mg/day of both KM and MNZ. SSI occurred in 60 of the 389 cases (15.4%). Regardless of stoma type, SSI was significantly more common in the non-OA group, while PSC was significantly less common. When examined by OA dose, the incidence of SSI was not significantly different between the low-dose and high-dose groups. However, PSC was significantly more common in the high-dose group than in the non-OA and low-dose groups. Analysis of bacterial and fungal levels in stool samples showed that bacterial levels after OAs were significantly lower than before OAs, while fungal levels increased. OAs significantly reduce SSI in colorectal cancer surgery. However, excess OAs were significantly associated with the occurrence of PSC without contributing to further reduction in SSI.

Intestinal overgrowth of Candida albicans exacerbates bleomycin-induced pulmonary fibrosis in mice with dysbiosis.

Increasing evidence indicates an interaction between the intestinal microbiota and diseases in distal organs. However, the relationship between pulmonary fibrosis and the intestinal microbiota, especially intestinal fungal microbiota, is poorly understood. Thus, this study aimed to determine the effects of changes in the intestinal fungal microbiota on the pathogenesis of pulmonary fibrosis. Mice with intestinal overgrowth of Candida albicans, which was established by oral administration of antibiotics plus C. albicans, showed accelerated bleomycin-induced pulmonary fibrosis relative to the control mice (i.e. without C. albicans treatment). In addition, the mice with intestinal overgrowth of C. albicans showed enhanced Th17-type immunity, and treatment with IL-17A-neutralizing antibody alleviated pulmonary fibrosis in these mice but not in the control mice. This result indicates that IL-17A is involved in the pathogenesis of C. albicans-exacerbated pulmonary fibrosis. Even before bleomycin treatment, the expression of Rorc, the master regulator of Th17, was already upregulated in the pulmonary lymphocytes of the mice with intestinal overgrowth of C. albicans. Subsequent administration of bleomycin triggered these Th17-skewed lymphocytes to produce IL-17A, which enhanced endothelial-mesenchymal transition. These results suggest that intestinal overgrowth of C. albicans exacerbates pulmonary fibrosis via IL-17A-mediated endothelial-mesenchymal transition. Thus, it might be a potential therapeutic target in pulmonary fibrosis. This study may serve as a basis for using intestinal fungal microbiota as novel therapeutic targets in pulmonary fibrosis. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Comparison of Different Antibiotic Regimes for Preventive Tooth Extractions in Patients with Antiresorptive Intake-A Retrospective Cohort Study.

In the present study, the impacts on success rates between three different antibiotic regimes in patients receiving preventive tooth extraction during/after antiresorptive treatment were compared. For the retrospective analysis, we enrolled patients who had undergone tooth extraction from 2009 to 2019 according to the specified preventive conditions under antiresorptive therapy. Three antibiotic regimens were distinguished: (Group 1) intravenous for 7 days, (Group 2) oral for 14 days, and (Group 3) oral for 7 days of application. The primary endpoint was the occurrence of medication-related osteonecrosis of the jaw at 12 weeks after surgery. A total of 760 patients and 1143 extraction regions were evaluated (Group 1 n = 719; Group 2 n = 126; Group 3 n = 298). The primary endpoint showed no significant difference in the development of medication-related osteonecrosis of the jaw between the groups studied (Group 1 n = 50/669 (7%); Group 2 n = 9/117 (7%); Group 3 n = 17/281 (6%); p = 0.746). Overall, the success rate was 93% after intervention when preventive measures were followed. With the same success rate, a reduced, oral administration of antibiotics seems to be sufficient regarding the possible spectrum of side effects, the development of resistance and the health economic point of view.

Nafcillin-Loaded Photocrosslinkable Nanocomposite Hydrogels for Biomedical Applications.

Skin infections are frequently treated via intravenous or oral administration of antibiotics, which can lead to serious adverse effects and may sometimes contribute to the proliferation of resistant bacterial strains. Skin represents a convenient pathway for delivering therapeutic compounds, ensured by the high number of blood vessels and amount of lymphatic fluids in the cutaneous tissues, which are systematically connected to the rest of the body. This study provides a novel, straightforward method to obtain nafcillin-loaded photocrosslinkable nanocomposite hydrogels and demonstrates their performance as drug carriers and antimicrobial efficacy against Gram-positive bacteria. The novel formulations obtained, based on polyvinylpyrrolidone, tri(ethylene glycol) divinyl ether crosslinker, hydrophilic bentonite nanoclay, and/or two types of photoactive (TiO2 and ZnO) nanofillers, were characterized using various analytical methods (transmission electron microscopy (TEM), scanning electron microscopy-energy-dispersive X-ray analysis (SEM-EDX), mechanical tests (tension, compression, and shear), ultraviolet-visible spectroscopy (UV-Vis), swelling investigations, and via specific microbiological assays ("agar disc diffusion method" and "time-kill test"). The results reveal that the nanocomposite hydrogel possessed high mechanical resistance, good swelling abilities, and good antimicrobial activity, demonstrating a decrease in the bacteria growth between 3log10 and 2log10 after one hour of direct contact with S. aureus.

Sex different effect of antibiotic and probiotic treatment on intestinal microbiota composition in chemically induced liver injury rats

Differences in the gut microbiota and metabolic processes between males and females may explain differences in the risk of liver injury; however, the sex-specific effects of antibiotics and probiotics on these relationships are not clear. We evaluated differences in the gut microbiota and the risk of liver injury between male and female rats after the oral administration of antibiotics or probiotics followed by a period of diethylnitrosamine treatment to chemically induce liver injuryusing high-throughput sequencing of fecal microbiota combined with histological analyses of liver and colon tissues. Our results suggest that the ratio of gram-positive to gram-negative bacteria in kanamycin-treated rats was significantly higher than that of other groups, and this difference persisted for the duration of the experiment. Antibiotics significantly changed the composition of the gut microbiota of experimental rats. Clindamycin caused more diethylnitrosamine-induced damage to livers of male rats. Probiotics did not influencethe gut microbiota; however, they hadprotective effects against liver injury induced by diethylnitrosamine, especially in female rats. These results strengthen our understanding of sex differences in the indirect effects of antibiotics or probiotics on metabolism and liver injury in hosts via the gut microbiota.

Microbiota-related metabolites fueling the understanding of ischemic heart disease.

Up-to-date knowledge of gut microbial taxa associated with ischemic heart disease (IHD). Microbial metabolites for mechanistic dissection of IHD pathology. Microbiome-based therapies in IHD prevention and treatment.

Frontal Sinus Mucosa Bacteriological Features: Evaluation after Unintentional Opening in Neurosurgery.

Objectives The bacteriological features of the frontal sinus mucosa may impose significant complications in neurosurgery, when breached unintentionally. This study aimed to investigate the bacterial flora in patients undergoing frontal craniotomy for cerebrovascular substrate surgery. Design This is a single-center prospective study. Setting When mucosal laceration occurred, the patients underwent frontal sinus reconstruction with mucosa reconstruction, preserving the nasofrontal duct. Participants We enrolled eight consecutive patients who underwent bifrontal craniotomy associated with frontal sinus mucosa laceration. Main Outcome Measures A portion of the mucosa was extracted during the reconstructive procedure and was sent for microbiological analysis. Results None of the patients presented with the bacterial flora in the mucosal cultures. No patient experienced postoperative cerebrospinal fluid leakage or meningitis. One patient with a clinical history of chronic maxillary sinusitis presented with a subcutaneous abscess around the forehead at 9 months postoperatively. The patient rapidly recovered after receiving oral administration of antibiotics. Conclusions Our findings demonstrated that the frontal sinuses were maintained in an aseptic environment in all cases. The results may encourage the development and wider use of transfrontal sinus approaches.

Oral vs. parenteral antibiotic therapy in adult patients with community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials

Antibiotic therapy is widely used for patients with community-acquired pneumonia (CAP), and yet whether the efficacy of antibiotics differs based on the treatment mode remains unclear. This study aimed to summarize the evidence regarding the efficacy and safety of oral vs. parenteral administration of antibiotic therapy for the treatment of patients with CAP. The databases of PubMed, EmBase, and the Cochrane Central Register of Controlled Trials were systematically searched for eligible randomized controlled trials (RCTs) from inception until 11 December 2021. The effectiveness of oral vs. parenteral administration of antibiotic therapy was estimated using a random-effects model. Additional sensitivity, subgroup, and publication bias analyses were performed. Of 912 identified articles, 12 RCTs involving 2158 patients with CAP were included in our pooled analysis. This mostly included trials with low certainty and some concerns regarding risk of bias, including lack of allocation concealment and blinding of participants and personnel. Overall, oral antibiotic therapy did not affect the incidence of clinical success at the end of treatment (relative risk [RR], 1.01; 95% confidence interval [CI], 0.98-1.05; P=0.417), clinical success at follow-up (RR, 1.02; 95% CI, 0.98-1.06; P=0.301), or adverse events (RR, 0.87; 95% CI, 0.56-1.35; P=0.527). Moreover, oral antibiotic therapy had a beneficial effect on the risk of all-cause mortality (RR, 0.58; 95% CI, 0.35-0.96; P=0.034). Oral administration of antibiotics is associated with a reduced risk of all-cause mortality compared with parenteral therapy based on RCTs with low to moderate quality. This finding should be verified in further large-scale RCTs.

Opioid-induced microbial dysbiosis disrupts irinotecan (CPT-11) metabolism and increases gastrointestinal toxicity in a murine model.

Opioids are commonly used for the management of cancer-associated pain and chemotherapy-induced diarrhoea. The chemotherapeutic irinotecan (CPT-11) causes severe gastrointestinal (GI) toxicity due to deconjugation of inactive metabolite SN-38 glucuronide (SN-38G) by bacterial β-glucuronidases to the active 7-ethyl-10-hydroxycamptothecin (SN-38). Opioids are known to cause gut microbial dysbiosis, this study evaluated whether CPT-11 anti-tumour efficacy and GI toxicity are exacerbated by opioid co-administration. Eight-week-old C57BL/6 male mice were co-administration with CPT-11 ± opioid. 16S rRNA sequencing was used for gut microbiome analysis. LC-MS analyses of plasma and intestinal extracts were performed to investigate the pharmacokinetic profile of CPT-11. Histological analysis and quantitative real-time polymerase chain reaction were used to determine the severity of intestinal tissue damage. Human liver microsome In vitro assay was performed to confirm the effects of opioids on CPT-11 metabolism. Gut microbiome analysis showed that morphine treatment induced enrichment of β-glucuronidase-producing bacteria in the intestines of CPT-11-treated mice, resulting in SN-38 accumulation and exacerbation of GI toxicity in the small intestine. Oral administration of both antibiotics and glucuronidase inhibitor protected mice against GI toxicity induced with CPT-11 and morphine co-administration, implicating a microbiome-dependent mechanism. Additionally, morphine and loperamide decreased the plasma concentration of SN-38 and compromised CPT-11 anti-tumour efficacy, this seemed to be microbiome independent. Gut microbiota play a significant role in opioid and chemotherapeutic agent drug-drug interactions. Inhibition of gut microbial glucuronidase may also prevent adverse GI effects of CPT-11 in patients on opioids.

Comparing the effectiveness of oral versus intravenous antibiotics in the prophylaxis of wound infection in hand laceration

Objective: Hand lacerations are among the most frequent causes of visiting emergency departments (EDs). Wound infection is one of its complications. There is still an ongoing disagreement on the administration of oral versus intravenous (IV) antibiotics (ABs). The objective of this study is to compare the effectiveness of oral versus IV ABs in preventing wound infection of hand lacerations. Methods: In this double-blind, randomized clinical trial, we enrolled all patients with hand lacerations (based on the inclusion criteria) during 6 months in the EDs of 2 tertiary referral centers. Convenient sampling was done. Finally, in the first group, 382 patients received oral AB (two 500 mg cephalexin capsules) and the other 382 patients in the second group received IV AB (1 gr IV cefazolin) before wound management. Both groups were followed and received oral cephalexin during 48 hours after suturing. Rates of wound infection and different complications were compared between the two groups. T-test, Mann-Whitney U test, Chi square and Fisher analysis were used. Results: Both groups had the same age and gender distribution rate (79.8% of males with the mean age of 30.8 years in the first group, and 83.5% of males with the mean age of 32.6 years in the second group (P=0.19 and 0.39, respectively). In our study, wound infection developed in 2.6% and 1.8% of patients in the first and second groups, respectively (P=0.46). Conclusion: Based on the results of this study, oral and IV ABs were not significantly different in terms of preventing wound infection.