Evaluation of Oral Amoxicillin/Clavulanate for Urinary Tract Infections Caused by Ceftriaxone Non-Susceptible Enterobacterales.

Urinary tract infections (UTIs) are one of the most common infections and are frequently caused by Gram-negative organisms. The rise of resistant isolates has prompted evaluation of alternative therapies, including amoxicillin-clavulanate which has potent activity against Ambler class A enzymes. This study sought to evaluate clinical outcomes of patients with ceftriaxone non-susceptible UTIs receiving amoxicillin-clavulanate or standard of care (SOC). This was a single-center, retrospective, cohort study of adult patients with urinary tract infections caused by a ceftriaxone non-susceptible pathogen who received amoxicillin-clavulanate or SOC. The primary outcome was clinical failure at 90 days. Secondary outcomes included time to failure, isolation of a resistant organism, and hospital length of stay. Fifty-nine patients met study inclusion: 26 received amoxicillin/clavulanate and 33 received SOC. Amoxicillin-clavulanate recipients did not have higher failure rates compared to SOC recipients. For patients requiring hospital admission, hospital length of stay was numerically shorter with amoxicillin-clavulanate. The frequency of amoxicillin-clavulanate and carbapenem-resistant organisms did not differ significantly between groups. Amoxicillin-clavulanate may be a useful alternative therapy for the treatment of ceftriaxone non-susceptible Enterobacterales UTIs.

Amoxicillin-clavulanate Breakpoints Against Enterobacterales: Rationale for Revision by the Clinical and Laboratory Standards Institute.

Amoxicillin-clavulanate (AMC) is among the most frequently prescribed antibiotics globally. It has broad antibacterial activity against gram-positive, gram-negative, and anaerobic bacteria, and has been utilized to treat infections caused by a broad range of pathogens. AMC breakpoints against Enterobacterales were initially set in the 1980s but since then increases in antibiotic resistance, advances in pharmacokinetic (PK)/pharmacodynamic (PD) analyses, and publication of additional clinical data prompted a reassessment by the Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing. Based on this contemporary reappraisal, the CLSI retained the Enterobacterales breakpoints but revised comments regarding dosing associated with use of the AMC breakpoints in the 2022 supplement of M100. This viewpoint provides insight into the CLSI breakpoint reevaluation process and summarizes the data and rationale used to support these revisions to the AMC Enterobacterales breakpoint.

Clostridioides difficile recovered in pleural fluid: Contamination or infection? A case report of a proven empyema and a literature review / Aislamiento de Clostridioides difficile en líquido pleural: ¿contaminación o infección? Presentación de un caso probado de empiema y revisión de la literatura

Introduction: Pleural empyema is an infrequent manifestation of extraintestinal Clostridioidesdifficile infection, with just eight cases reported in literature. Methods: We report a new case in a 70-year-old male without comorbidities or evidence of concomitant gastrointestinal disease, and review the previous cases reported in the literature. Results: The isolate was susceptible to all antimicrobial tested and was negative for A+B toxins. The patient fully recovered after drainages and antimicrobial therapy with amoxicillin–clavulanate and doxycycline. Conclusion: As in the previously reported cases, aspiration was the most plausible hypothesis of mechanism of infection in our patient. Empyema by Clostridioidesdifficile is a diagnostic challenge, since it is necessary to rule out that the isolation of this microorganism in pleural fluid is not a contamination. Furthermore, more evidence is needed for its treatment since data regarding this entity are still scarce.(AU)

Introducción: El empiema pleural es una manifestación infrecuente de la infección extraintestinal por Clostridioidesdifficile, con sólo ocho casos reportados en la literatura. Métodos: Documentamos un nuevo caso de un varón de 70 años sin comorbilidades ni evidencia de enfermedad gastrointestinal concomitante y revisamos los casos previamente descritos en la literatura. Resultados: El aislado fue sensible a todos los antibióticos testados y fue negativo para las toxinas A+B. El paciente se recuperó totalmente tras la realización de drenajes y terapia antimicrobiana con amoxicilina-clavulánico y doxiciclina. Conclusión: Al igual que en los casos previamente documentados, la broncoaspiración fue la hipótesis más plausible del mecanismo de infección en nuestro paciente. El empiema por Clostridioidesdifficile constituye un reto diagnóstico, ya que es necesario descartar que su aislamiento en líquido pleural no se deba a una contaminación. Además, se necesita más evidencia científica para el tratamiento de esta entidad, ya que los datos sobre la misma aún son escasos.(AU)

Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) in Canada: treatment update and the role of new IV antimicrobials.

INTRODUCTION: Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) continue to be common infections causing significant morbidity and mortality worldwide. The timely initiation of empiric antimicrobial therapy is essential. In this paper, we provide a focused expert opinion on the current and potential empiric antimicrobial treatment options in HABP and VABP in Canada influenced by antimicrobial resistance impacting the use of older agents as well as available new intravenous (IV) antimicrobials. AREAS COVERED: The authors discuss treatment options for HABP and VABP in Canada. In addition, we focus on the potential role of new IV antimicrobials recently introduced to Canada. A literature search of HABP and VABP treatments was performed via PubMed (up to March 2023), using the following key words: monotherapy, combination therapy, aminoglycosides, carbapenems, cephalosporins, fluoroquinolones, penicillins as well as amoxicillin/clavulanate, ceftobiprole, ceftolozane/tazobactam, dalbavancin, and fosfomycin. EXPERT OPINION: Empiric antimicrobial treatment for HABP and VABP in Canada continues to focus on both the severity of illness and the presence/absence of patient risk factors for antimicrobial resistance. The role of new IV antimicrobials in the empiric treatment for HABP and VABP depends on their antimicrobial activity and published data on efficacy and safety and influenced by Health Canada-approved indications.

Amoxicillin-induced aseptic meningitis: clinical features, diagnosis and management.

OBJECTIVES: The clinical features of aseptic meningitis associated with amoxicillin are unknown. The main objective of this study was to investigate the clinical characteristics of amoxicillin-induced aseptic meningitis (AIAM) and provide a reference for clinical diagnosis and treatment. METHODS: AIAM-related studies were collected by searching the relevant databases from inception to October 31, 2022. RESULTS: AIAM usually occurred 3 h to 7 days after amoxicillin administration in 13 males and 9 females. Twenty-one patients (95.5%) had recurrent AIAM with a total of 62 episodes. Fever (19 cases, 86.4%) and headache (18 cases, 81.8%) were the most common symptoms. Typical cerebrospinal fluid (CSF) findings were leukocytosis (100%) with lymphocytic predominance (14 cases, 63.6%), elevated protein (20 cases, 90.1%), normal glucose (21 cases, 95.5%) and negative culture (21 cases, 100%). Brain magnetic resonance imaging showed mild meningeal enhancement in one patient. The symptoms resolved mainly within 1-4 days after drug discontinuation in all patients. CONCLUSION: Clinical attention should be given to the adverse effects of AIAM. The medication history of patients with suspected meningitis should be investigated to avoid unnecessary examination and antibiotic treatment.

Antibiotic treatment failure of uncomplicated urinary tract infections in primary care.

BACKGROUND: Higher resistance rates of > 20% have been noted in Enterobacteriaceae urinary isolates towards ciprofloxacin and co-trimoxazole (C + C) in Singapore, compared with amoxicillin-clavulanate and nitrofurantoin (AC + N). This study examined if treatment failure varied between different antibiotics, given different resistant rates, for uncomplicated urinary tract infections (UTIs) managed in primary care. We also aimed to identify gaps for improvement in diagnosis, investigations, and management. METHODS: A retrospective cohort study was conducted from 2019 to 2021 on female patients aged 18-50 with uncomplicated UTIs at 6 primary care clinics in Singapore. ORENUC classification was used to exclude complicated UTIs. Patients with uncomplicated UTIs empirically treated with amoxicillin-clavulanate, nitrofurantoin, ciprofloxacin or co-trimoxazole were followed-up for 28 days. Treatment failure was defined as re-attendance for symptoms and antibiotic re-prescription, or hospitalisation for UTI complications. After 2:1 propensity score matching in each group, modified Poisson regression and Cox proportional hazard regression accounting for matched data were used to determine risk and time to treatment failure. RESULTS: 3194 of 4253 (75.1%) UTIs seen were uncomplicated, of which only 26% were diagnosed clinically. Urine cultures were conducted for 1094 (34.3%) uncomplicated UTIs, of which only 410 (37.5%) had bacterial growth. The most common organism found to cause uncomplicated UTIs was Escherichia coli (64.6%), with 92.6% and 99.4% of isolates sensitive to amoxicillin-clavulanate and nitrofurantoin respectively. Treatment failure occurred in 146 patients (4.57%). Among 1894 patients treated with AC + N matched to 947 patients treated with C + C, patients treated with C + C were 50% more likely to fail treatment (RR 1.49, 95% CI 1.10-2.01), with significantly higher risk of experiencing shorter time to failure (HR 1.61, 95% CI 1.12-2.33), compared to patients treated with AC + N. CONCLUSION: Treatment failure rate was lower for antibiotics with lower reported resistance rates (AC + N). We recommend treating uncomplicated UTIs in Singapore with amoxicillin-clavulanate or nitrofurantoin, based on current local antibiograms. Diagnosis, investigations and management of UTIs remained sub-optimal. Future studies should be based on updating antibiograms, highlighting its importance in guideline development.

Diagnostic Dilemma in a Case of Necrotizing Pneumonia With Negative Transbronchial Biopsy.

A 33-year-old male with a past medical history of asthma presented to the Emergency room with a three-day history of right-sided chest pain, productive cough with dark brown sputum, and shortness of breath. He was found to have right lower lobe consolidation consistent with acute pneumonia, and areas of non-homogenous density within the consolidation, suspicious of necrotizing pneumonia. Computed tomography (CT) of the chest with IV contrast revealed a large, irregular thick-walled cavitary mass involving the right middle lobe with surrounding ground glass cavitation. An extensive workup was negative, including a transbronchial biopsy. The case explains how a causative organism was detected.

Antibiotic associated diarrhea in outpatient pediatric antibiotic therapy.

BACKGROUND: Antibiotic-associated diarrhea is one of the most frequent side effects of antimicrobial therapy. We assessed the epidemiological data of antibiotic-associated diarrhea in pediatric patients in our region. METHODS: The prospective multi-center study included pediatric patients who were initiated an oral antibiotic course in outpatient clinics and followed in a well-established surveillance system. This follow-up system constituded inclusion of patient by the primary physician, supply of family follow-up charts to the family, passing the demographics and clinical information of patient to the Primary Investigator Centre, and a close telephone follow-up of patients for a period of eight weeks by the Primary Investigator Centre. RESULTS: A result of 758 cases were recruited in the analysis which had a frequency of 10.4% antibiotic-associated diarrhea. Among the cases treated with amoxicillin-clavulanate 10.4%, and cephalosporins 14.4% presented with antibiotic-associated diarrhea. In the analysis of antibiotic-associated diarrhea occurrence according to different geographical regions of Turkey, antibiotic-associated diarrhea episodes differed significantly (p = 0.014), particularly higher in The Eastern Anatolia and Southeastern Anatolia. Though most commonly encountered with cephalosporin use, antibiotic-associated diarrhea is not a frequent side effect. CONCLUSION: This study on pediatric antibiotic-associated diarrhea displayed epidemiological data and the differences geographically in our region.

Repurposing ß-Lactams for the Treatment of Mycobacterium kansasii Infections: An In Vitro Study.

Mycobacterium kansasii (Mkn) causes tuberculosis-like lung infection in both immunocompetent and immunocompromised patients. Current standard therapy against Mkn infection is lengthy and difficult to adhere to. Although ß-lactams are the most important class of antibiotics, representing 65% of the global antibiotic market, they have been traditionally dismissed for the treatment of mycobacterial infections, as they were considered inactive against mycobacteria. A renewed interest in ß-lactams as antimycobacterial agents has shown their activity against several mycobacterial species, including M. tuberculosis, M. ulcerans or M. abscessus; however, information against Mkn is lacking. In this study, we determined the in vitro activity of several ß-lactams against Mkn. A selection of 32 agents including all ß-lactam chemical classes (penicillins, cephalosporins, carbapenems and monobactams) with three ß-lactamase inhibitors (clavulanate, tazobactam and avibactam) were evaluated against 22 Mkn strains by MIC assays. Penicillins plus clavulanate and first- and third-generation cephalosporins were the most active ß-lactams against Mkn. Combinatorial time-kill assays revealed favorable interactions of amoxicillin-clavulanate and cefadroxil with first-line Mkn treatment. Amoxicillin-clavulanate and cefadroxil are oral medications that are readily available, and well tolerated with an excellent safety and pharmacokinetic profile that could constitute a promising alternative option for Mkn therapy.

VRE acquisition in hospital and its association with hospital antimicrobial usage -a non-linear analysis of an extended time series.

BACKGROUND: Vancomycin resistant enterococci (VRE) have become endemic pathogens in many Australian hospitals causing significant morbidity. There are few observational studies that have evaluated the effect of antibiotic usage on VRE acquisition. This study examined VRE acquisition and its association with antimicrobial use. The setting was a NSW tertiary hospital with 800 beds over a 63 month period up to March 2020, straddling piperacillin-tazobactam (PT) shortages that occurred from in September 2017. METHODS: The primary outcome was monthly inpatient hospital onset Vancomycin-resistant Enterococci (VRE) acquisitions. Multivariate adaptive regression splines (MARS) were used to estimate hypothetical thresholds, where antimicrobial use above threshold is associated with increased incidence of hospital onset VRE acquisition. Specific antimicrobials and categorised usage (broad, less broad and narrow spectrum) were modelled. RESULTS: There were 846 hospital onset VRE detections over the study period. Hospital onset vanB and vanA VRE acquisitions fell significantly by 64% and 36% respectively after the PT shortage. MARS modelling indicated that PT usage was the only antibiotic found to exhibit a meaningful threshold. PT usage greater than 17.4 defined daily doses/1000 occupied bed-days (95%C I: 13.4, 20.5) was associated with higher onset of hospital VRE. CONCLUSIONS: This paper highlights the large, sustained impact that reduced broad spectrum antimicrobial use had on VRE acquisition and showed that PT use in particular was a major driver with a relatively low threshold. It raises the question as to whether hospitals should be determining local antimicrobial usage targets based on direct evidence from local data analysed with non-linear methods.

Clostridioides difficile recovered in pleural fluid: Contamination or infection? A case report of a proven empyema and a literature review.

INTRODUCTION: Pleural empyema is an infrequent manifestation of extraintestinal Clostridioidesdifficile infection, with just eight cases reported in literature. METHODS: We report a new case in a 70-year-old male without comorbidities or evidence of concomitant gastrointestinal disease, and review the previous cases reported in the literature. RESULTS: The isolate was susceptible to all antimicrobial tested and was negative for A+B toxins. The patient fully recovered after drainages and antimicrobial therapy with amoxicillin-clavulanate and doxycycline. CONCLUSION: As in the previously reported cases, aspiration was the most plausible hypothesis of mechanism of infection in our patient. Empyema by Clostridioidesdifficile is a diagnostic challenge, since it is necessary to rule out that the isolation of this microorganism in pleural fluid is not a contamination. Furthermore, more evidence is needed for its treatment since data regarding this entity are still scarce.

Oral amoxicillin/clavulanate for the prevention of bacteremia following dental extractions.

This study aimed to evaluate the effectiveness of oral amoxicillin/clavulanate (AMX-CL) for the prevention of bacteremia following dental extractions. The study group (AMX-CLG) comprised 40 adults requiring dental extractions under general anesthesia who were administered a prophylactic regimen of 1875/125 mg of AMX-CL orally 1-2 h prior to the surgery. Venous blood samples were collected from each patient at baseline and at 30 s and 15 min after dental extractions. Samples were inoculated into BACTEC Plus culture bottles and processed in the BACTEC 9240. Conventional microbiological techniques were used for subcultures and further identification of the isolated bacteria. The results for the AMX-CLG were compared with those of a control group (CG; no prophylaxis) and an amoxicillin group (AMXG; 2 g of amoxicillin orally), consisting of randomly selected patients from among those participating in two clinical trials that we have previously published. The prevalence of bacteremia in the CG, AMXG, and AMX-CLG was 97%, 50%, and 15%, respectively, at 30 s after completing the extractions, and 67%, 10%, and 4% at 15 min, respectively, after the last extraction. The prevalence of bacteremia in the AMXG and the AMX-CLG at 30 s and at 15 min after completing the extractions was significantly lower than that in the CG (p < 0.001 and p < 0.001, respectively; Fisher's exact test). The prevalence of bacteremia in the AMX-CLG at 30 s after completing the extractions was significantly lower than that in the AMXG (p < 0.001; Fisher's exact test). Based in the results of this preliminary study, oral AMX-CL could be an excellent option for preventing bacteremia secondary to dental procedures in patients at risk.

Weak direct current exerts synergistic effect with antibiotics and reduces the antibiotic resistance: An in vitro subgingival plaque biofilm model.

BACKGROUND AND OBJECTIVE: Weak direct current (DC) exerts killing effect and synergistic killing effect with antibiotics in some specific bacteria biofilms. However, the potential of weak DC alone or combined with periodontal antibiotics in controlling periodontal pathogens and plaque biofilms remains unclear. The objective of this study was to investigate whether weak DC could exert the anti-biofilm effect or enhance the killing effect of metronidazole (MTZ) and/or amoxicillin-clavulanate potassium (AMC) on subgingival plaque biofilms, by constructing an in vitro subgingival plaque biofilm model. METHODS: The pooled subgingival plaque and saliva of patients with periodontitis (n = 10) were collected and cultured anaerobically on hydroxyapatite disks in vitro for 48 h to construct the subgingival plaque biofilm model. Then such models were stimulated with 0 µA DC alone (20 min/12 h), 1000 µA DC alone (20 min/12 h), 16 µg/ml MTZ, 16 µg/ml AMC or their combination, respectively. Through viable bacteria counting, metabolic activity assay, quantitative real-time PCR absolute quantification and 16S rDNA sequencing analysis, the anti-biofilm effect of 1000 µA DC and enhanced killing effects of 1000 µA DC combined with antibiotics (MTZ, AMC or MTZ+AMC) were explored. RESULTS: The old subgingival plaque model (48 h) had no significant difference in total bacterial loads from subgingival plaque in situ, which achieved a similarity of 80%. The 1000 µA DC plus MTZ or AMC for 12 h showed a stronger synergistic killing effect than the same combination for 20 min. The metabolic activity was reduced to the lowest by DC plus MTZ+AMC, as 37.4% of that in the control group, while average synergistic killing effect reached 1.06 log units and average total bacterial loads decreased to 0.87 log units. Furthermore, the relative abundance of the genera Porphyromonas, Prevotella, Treponema_2, and Tannerella were decreased significantly. CONCLUSION: The presence of weak DC (1000 µA) improved the killing effect of antibiotics on subgingival plaque biofilms, which might provide a novel strategy to reduce their antibiotic resistance.

Identification of Reduced ERAP2 Expression and a Novel HLA Allele as Components of a Risk Score for Susceptibility to Liver Injury Due to Amoxicillin-Clavulanate.

BACKGROUND & AIMS: Drug-induced liver injury (DILI) due to amoxicillin-clavulanate (AC) has been associated with HLA-A∗02:01, HLA-DRB1∗15:01, and rs2476601, a missense variant in PTPN22. The aim of this study was to identify novel risk factors for AC-DILI and to construct a genetic risk score (GRS). METHODS: Transcriptome-wide association study and genome-wide association study analyses were performed on 444 AC-DILI cases and 10,397 population-based controls of European descent. Associations were confirmed in a validation cohort (n = 133 cases and 17,836 population-based controls). Discovery and validation AC-DILI cases were also compared with 1358 and 403 non-AC-DILI cases. RESULTS: Transcriptome-wide association study revealed a significant association of AC-DILI risk with reduced liver expression of ERAP2 (P = 3.7 × 10-7), coding for an aminopeptidase involved in antigen presentation. The lead eQTL single nucleotide polymorphism, rs1363907 (G), was associated with AC-DILI risk in the discovery (odds ratio [OR], 1.68; 95% CI, 1.23-1.66; P = 1.7 × 10-7) and validation cohorts (OR, 1.2; 95% CI, 1.04-2.05; P = .03), following a recessive model. We also identified HLA-B∗15:18 as a novel AC-DILI risk factor in both discovery (OR, 4.19; 95% CI, 2.09-8.36; P = 4.9 × 10-5) and validation (OR, 7.78; 95% CI, 2.75-21.99; P = .0001) cohorts. GRS, incorporating rs1363907, rs2476601, HLA-B∗15:18, HLA-A∗02:01, and HLA-DRB1∗15:01, was highly predictive of AC-DILI risk when cases were analyzed against both general population and non-AC-DILI control cohorts. GRS was the most significant predictor in a regression model containing known AC-DILI clinical risk characteristics and significantly improved the predictive model. CONCLUSIONS: We identified novel associations of AC-DILI risk with ERAP2 low expression and with HLA-B∗15:18. GRS based on the 5 risk variants may assist AC-DILI causality assessment and risk management.

Clinical evaluation of the efficacy against helicobacter pylori by amoxicillin from volume-based procurement and potassium amoxicillin clavulanate / 中国临床药理学与治疗学

AIM: To evaluate the clinical efficacy of amoxicillin from volume-based procurement (VBP) and potassium amoxicillin clavulanate in the eradication of helicobacter pylori (Hp) infection, providing basis for the selection of treatment programs. METHODS: Data from the patients who received Hp eradication therapy from May 2021 to May 2022 were recruited from the rational drug use management system. The data from the patients treated by amoxicillin (amoxicillin 1.0 g bid + bismuth potassium citrate 220 mg bid + esomeprazole 20 mg bid + clarithromycin 0.5 g bid, for 14 days) and potassium amoxicillin clavulanate (potassium amoxicillin clavulanate 0.914 g bid + bismuth potassium citrate 220 mg bid + esomeprazole 20 mg bid + clarithromycin 0.5 g bid, for 14 days) were selected and compared. RESULTS: A total of 171 cases were collected in the group treated by Amoxicillin program, and the eradication rate was 87.8% (150/171). A total of 69 cases were collected in the group of potassium amoxicillin clavulanate, and the eradication rate was 76.8% (53/69). There was no significant difference in baseline data between the two groups (P>0.05). There was a significant difference in clinical efficacy between the two groups (P< 0.05). In addition, the cost-effectiveness ratio (C/E) of the Amoxicillin treatment program was lower than that of the potassium amoxicillin clavulanate program CONCLUSION: The clinical efficacy of VBP Amoxicillin program in eradicating Hp infection is better than that of the potassium amoxicillin clavulanate program, which is worthy of clinical recommendation.

Amoxicillin-clavulanate induced DRESS syndrome masquerading as red man syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity reaction carrying a mortality rate of up to 10%. We present a rare case of DRESS syndrome induced by amoxicillin-clavulanate, initially masquerading as red man syndrome. A 32-year-old male was admitted with flu-like symptoms and a maculopapular rash on the trunk and face that was exacerbated with vancomycin infusion, concerning for red man syndrome. He was receiving systemic antibiotics (vancomycin, ceftriaxone, and metronidazole) for infective endocarditis and previously took amoxicillin-clavulanate for a dental abscess. Despite the discontinuation of vancomycin, the exanthem continued to worsen, extending to involve >50% of his body surface area. Eosinophilia, hepatosplenomegaly, and acute kidney and liver injuries prompted consideration of DRESS syndrome. All antibiotics were discontinued, and systemic glucocorticoids were initiated. Punch biopsy revealed interface dermatitis with eosinophilic infiltrates; a high RegiSCAR score confirmed the diagnosis of DRESS. Amoxicillin-clavulanate was flagged as a severe allergy and deemed the culprit owing to the timing of exposure and personal/family history of hypersensitivity.

Evaluation of Amoxicillin and Amoxicillin-Clavulanate (Augmentin) for Antimicrobial Postexposure Prophylaxis Following Bacillus anthracis Inhalational Exposure in Cynomolgus Macaques.

Amoxicillin is a broad-spectrum antibiotic used to treat a variety of gram-positive and gram-negative infections, such as infections of the ear, nose, and throat, genitourinary tract, skin, and lower respiratory tract; gonorrhea; and Helicobacter pylori. The prophylactic benefit of both amoxicillin and Augmentin (amoxicillin-clavulanate for use against ß-lactamase-expressing bacteria) was evaluated for inhalation anthrax in cynomolgus macaques in 2 studies. A pilot study on amoxicillin-clavulanate that used a portion of the study animals demonstrated empirically that dosing twice a day was efficacious. In a subsequent study on both amoxicillin and amoxicillin-clavulanate that used the remaining study animals, the animals were treated orally every 12 hours on days 1-28 postchallenge and followed for an additional 60 days (total of 88 days from day of aerosol challenge to when the animals were culled). The animals from each treatment arm of the 2 studies were completely protected. All untreated animals succumbed to the infection. The degree of protection observed in this study suggests that both amoxicillin and amoxicillin-clavulanate, administered prophylactically over a period of 28 days after a lethal exposure to Bacillus anthracis spores, is sufficient for full protection.

Current Medical Treatment for Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.