An Evaluation of Amoxicillin/Clavulanate Stability in Aqueous Systems, Including Its Suitability for Outpatient Parenteral Antimicrobial Therapy (OPAT).

Purpose: Amoxicillin/clavulanate antibiotic combination is suitable for treating a range of infections, including some suited for Outpatient Parenteral Antimicrobial Therapy (OPAT). The aim of the study was to evaluate shelf-life values of amoxicillin at clinical concentrations in the presence of clavulanate for use in OPAT. Methods: A stability-indicating HPLC assay was developed and validated. Kinetic studies were performed at 1 mg/mL and 15 mg/mL amoxicillin at 40-60 °C. Studies in elastomeric infusers included the pH lowered from 8.73 to 6.52 for 1 mg/mL; 8.85 to 7.69 for 7.5 mg/mL and 8.68 to 8.40 for 15 mg/mL amoxicillin plus clavulanate and stored at 2.9 °C. Results: Amoxicillin and clavulanate eluted at 5.2 and 3.0 minutes, respectively, with linear concentration relationships. Forced degradation retained base-line separation of each component in the presence of degradation products. Amoxicillin 1 mg/mL had a shelf-life of 4.85 hours at pH 6.53 and 40 °C which on extrapolation to 25 °C was 22.8 h. Clavulanate was 1.38 h at 40 °C and 4.0 h at 25 °C. Amoxicillin 15 mg/mL at pH 8.34 gave a shelf-life of 0.11 h at 40 °C and clavulanate 0.41 h. In elastomeric infusers, amoxicillin 1 mg/mL, with lowering pH from 8.73 to 6.52, improved the shelf-life at 2.9 °C from 72 to >263.8 h and similarly for clavulanate. At 7.5 mg/mL amoxicillin, lowering pH from 8.85 to 7.69 improved the shelf-life from 4.2 to 51.8 h and clavulanate from 4.2 to 48.0 h. At 15 mg/mL amoxicillin, the shelf-life values at pH 8.68 or 8.40 were 3.8 h and 1.6 h and similarly for clavulanate. Conclusion: Amoxicillin and clavulanate showed adequate stability at 2.9 °C for OPAT storage at 1 mg/mL and possibly 7.5 mg/mL, but not 15 mg/mL. Low shelf-life values at 25 °C also limit administration times.

Antibiotic susceptibility of orofacial infections in Bratislava: a 10-year retrospective study.

OBJECTIVES: Aim of this study was to analyse causal microbiological agents and their bacterial resistance in orofacial infections requiring hospital admission. MATERIALS AND METHODS: Presented is a 10-year retrospective study of patients hospitalised at a single department in 2014-2023. 744 patients were involved. In the statistical analysis, following data was evaluated: causal microbes and their resistance to Penicillin, Amoxicillin-Clavulanate, Clindamycin and Metronidazole. RESULTS: Most frequent aetiology was odontogenic with causal tooth in socket (n = 468; 62,9%), followed by odontogenic - post extraction (n = 152; 20.4%), jaw fracture (n = 41; 5.5%), sialadenitis n = 31 (4.2%), osteonecrosis n = 22 (3.0%), oncological diagnosis in head and neck (n = 17; 2.3%), unknown (n = 10; 1.3%) and multiple factors (n = 3; 0.4%). 408 patients (54.8%) underwent extraoral abscess revision, 336 patients (45.2%) patients were treated locally without extraoral revision. In odontogenic group with tooth still present, superior CRP (m = 145.8 mg/l; SD = 117.7) and leukocyte values (m = 13.6*109l; SD = 6.6) were observed in comparison to other groups. There were 698 cultivated bacteria in 362 patients. Most frequent bacteria were Streptococci (n = 162; 23.2%), Prevotella (n = 83; 11.2%) and Parvimonas (n = 65; 9.3%). Clindamycin resistance was highest (n = 180 resistant bacteria; 25.8%), followed by Metronidazole (n = 178; 25.5%), Penicillin (n = 107; 15.3%) and Amoxicillin-Clavulanate (n = 34; 4.9%). CONCLUSIONS: Orofacial infections in head and neck region are mostly of odontogenic origin with causal tooth still in socket. Causal bacteria show a high antibiotic resistance rate, especially to Clindamycin and Metronidazole. CLINICAL RELEVANCE: Acquired data will be used to determine guidelines for empirical antibiotic prescription in cases of orofacial infections.

Adverse Drug Reactions Resulting From the Use of Chiral Medicines Amoxicillin, Amoxicillin-Clavulanic Acid, and Ceftriaxone: A Mixed Prospective-Retrospective Cohort Study.

The use of chiral medicines (possessing center(s) of asymmetric carbon) may cause adverse drug reactions (ADRs). The safety assurance of these medicines is critical. We aimed to evaluate registered and commonly used anti-infective chiral medicines circulating in the Tanzanian market to establish their safety profile to protect public health. A mixed prospective-retrospective cohort study was conducted to assess the safety profile of amoxicillin, amoxicillin-clavulanic acid and ceftriaxone injection. ADRs causality assessment was conducted by using World Health Organization (WHO)-Algorithm criteria. Data were collected from 7 tertiary hospitals: Muhimbili National Hospital (MNH), Kilimanjaro Christian Medical Centre (KCMC), Bugando Medical Centre (BMC), Ligula Referral-Regional Hospital (LRRH), Kitete Referral-Regional Hospital (KRRH), Dodoma Referral-Regional Hospital (DRRH), and Mbeya Zonal-Referral Hospital (MZRH). Data were supplemented by those recorded in the WHO-Vigiflow/VigiLyze database within the same monitoring period. Data were analyzed using STATA version-15. The results were considered statistically significant when P < .05. A total of 2522 patients were enrolled in hospitals: MNH (499), KCMC (407), BMC (396), LRRH (387), KRRH (345), DRRH (249), and MZRH (239). Among those, 1197 (47.5%) were treated with ceftriaxone, 585 (23.2%) amoxicillin and 740(29.3%) amoxicillin-clavulanic acid. Out of those, 102 (4.5%) experienced adverse events (AEs), 49 (48%) were due to ceftriaxone, 37 (36.3%) amoxicillin-clavulanic acid and 16 (15.7%) amoxicillin (P-value .012). A total of 443 participants from the enrolled and WHO-Vigiflow/VigiLyze database were experienced with ADRs. The ADRs affected mainly gastro-intestinal system 234 (53%), skin and subcutaneous tissue 85 (19%), nervous system 49 (11%), respiratory thoracic 22 (5%), and general disorders 18(4%). In this study, approximately 90% of reported AEs were ADRs possible-related to the monitored medicines, with few plausible and certain. Ceftriaxone injection caused more ADRs. Amoxicillin-clavulanic acid was associated with more ADRs than amoxicillin alone. The safety profile of these medicines is still maintained; however, comprehensive monitoring of ADRs is recommended to improve patient safety and enhance overall treatment outcomes.

The efficacy of nebulized budesonide and ambroxol hydrochloride in treating pediatric community-acquired pneumonia and their impact on clinical characteristics and inflammatory markers.

PURPOSE: To evaluate the therapeutic efficacy of intravenous amoxicillin clavulanate potassium combined with nebulized budesonide and ambroxol hydrochloride in pediatric community-acquired pneumonia (CAP) and its impact across various microbial strains and clinical symptoms. The primary objective of this study is to evaluate the efficacy of intravenous amoxicillin-clavulanate combined with nebulized budesonide and ambroxol hydrochloride in the treatment of pediatric community-acquired pneumonia (CAP), and to analyze their impact on different microbial strains and clinical symptoms. Secondary objectives include assessing the treatment's effect on the improvement of clinical symptoms, hospital stay duration, and the levels of inflammatory markers. DESIGN: Prospective, single-center study. METHODS: Fifty-six children with CAP, aged under 6 years, from Affiliated Maternity and Child Health Care Hospital of Nantong University were included. Patients were treated with conventional therapy and the study medication. Clinical characteristics, microbiological data, symptom improvement, and hospitalization times were analyzed. FINDINGS: Young children, particularly under 1 year, exhibited a higher incidence of multiple microbial infections and severe clinical manifestations. Treatment with budesonide and ambroxol hydrochloride led to significant clinical improvement across all age groups, with notable efficacy against various pathogens. CONCLUSIONS: Nebulized budesonide and ambroxol hydrochloride are effective in treating pediatric CAP, offering a promising therapeutic option, particularly for young children with severe presentations.

Idiosyncratic Drug-Induced Liver Injury and Amoxicillin-Clavulanate: Spotlight on Gut Microbiota, Fecal Metabolome and Bile Acid Profile in Patients.

Several hepatic disorders are influenced by gut microbiota, but its role in idiosyncratic drug-induced liver injury (iDILI), whose main causative agent is amoxicillin-clavulanate, remains unknown. This pioneering study aims to unravel particular patterns of gut microbiota composition and associated metabolites in iDILI and iDILI patients by amoxicillin-clavulanate (iDILI-AC). Thus, serum and fecal samples from 46 patients were divided into three study groups: healthy controls (n = 10), non-iDILI acute hepatitis (n = 12) and iDILI patients (n = 24). To evaluate the amoxicillin-clavulanate effect, iDILI patients were separated into two subgroups: iDILI non-caused by amoxicillin-clavulanate (iDILI-nonAC) (n = 18) and iDILI-AC patients (n = 6). Gut microbiota composition and fecal metabolome plus serum and fecal bile acid (BA) analyses were performed, along with correlation analyses. iDILI patients presented a particular microbiome profile associated with reduced fecal secondary BAs and fecal metabolites linked to lower inflammation, such as dodecanedioic acid and pyridoxamine. Moreover, certain taxa like Barnesiella, Clostridia UCG-014 and Eubacterium spp. correlated with significant metabolites and BAs. Additionally, comparisons between iDILI-nonAC and iDILI-AC groups unraveled unique features associated with iDILI when caused by amoxicillin-clavulanate. In conclusion, specific gut microbiota profiles in iDILI and iDILI-AC patients were associated with particular metabolic and BA status, which could affect disease onset and progression.

Exploring therapeutic options for mild diabetic-related foot infections: a comparative in vitro study of cefditoren versus amoxicillin/clavulanic acid.

Skin and soft tissue infections (SSTIs), and particularly diabetic-related foot infections (DFI), present diagnostic and therapeutic complexities, often leading to severe complications. This study aims to evaluate the in vitro efficacy of cefditoren and amoxicillin/clavulanic acid against typical DFI pathogens. Clinical samples from 40 patients with mild SSTIs were analyzed, revealing a predominance of Staphylococcus spp. and Streptococcus spp. species. Cefditoren exhibited activity against 90% of isolates, with superior potency over amoxicillin/clavulanic acid. These findings underscore the utility of cefditoren in empirical treatment of DFI, although a larger sample size would be desirable for further validation.

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.

Ingestion of amoxicillin-clavulanic acid at therapeutic concentration during blood meal impacts Aedes aegypti microbiota and dengue virus transmission.

Dengue virus (DENV), mainly transmitted by Aedes aegypti mosquitoes, is the most prevalent arbovirus worldwide, representing a public health problem in tropical and subtropical countries. In these areas, antibiotic consumption rises which may impact both mosquito microbiota and dengue transmission. Here, we assessed how the ingestion by Ae. aegypti of therapeutic concentrations of amoxicillin-clavulanic Acid association (Amox/Clav), a broad-spectrum antibiotic used to treat febrile symptoms worldwide, impacted its microbiota. We also evaluated whether simultaneous ingestion of antibiotic and DENV impacted Ae. aegypti ability to transmit this virus. We found that Amox/Clav ingestion impacted microbiota composition in Ae. aegypti and we confirmed such impact in field-collected mosquitoes. Furthermore, we observed that Amox/Clav ingestion enhanced DENV dissemination and transmission by this mosquito at 21 days post-DENV exposure. These findings increase our understanding of factors linked to human hosts that may influence dengue transmission dynamics in regions with mass-drug administration programs.

Severe hepatic cholestasis after treatment with amoxicillin/clavulanic acid.

Amoxicillin/clavulanate is a commonly used antibiotic. Though relatively rare, amoxicillin/clavulanate carries the highest incidence of idiosyncratic drug-induced liver disease. This case report presents an 80-year-old woman treated for simple respiratory tract infection with amoxicillin/clavulanate who was subsequently hospitalized with malaise and icterus and a biochemical cholestatic pattern with high alkaline phosphatase and bilirubin. Diagnostically challenging, ultimately, liver biopsy revealed drug-induced liver injury with a fatal course after attempt of supportive, symptomatic treatment.

Individual health insurance data of antibiotic delivery in previous months as a tool to predict bacterial resistance of urinary tract infection: A prospective cohort study.

OBJECTIVES: We aimed to quantify the individual risk of antimicrobial resistance among patients with community-acquired Escherichia coli urinary tract infection (UTI) according to their antibiotic exposure over the previous 18 months. PATIENTS AND METHODS: French patients were prospectively recruited in two centers in 2015-2017. Resistance of isolates to amoxicillin (AMX), amoxicillin-clavulanate (AMC), third-generation cephalosporins (3GC), trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones (FQ) and fosfomycin (FOS) was analysed according to previous intra-class and inter-class antibiotic exposure documented in health insurance files. RESULTS: Previous antibiotic exposure was found in 588 (81.4 %) of the 722 UTI cases analysed (564 patients). Recent exposure (three months before UTI) was associated with stronger intra-class impact on E. coli resistance compared to remote exposure (18 months before UTI) for AMX, AMC, FQ and TMP-SMX, with respective adjusted odds ratios [95 % confidence interval] of 1.63 [1.20-2.21], 1.59 [1.02-2.48], 3.01 [1.90-4.77], and 2.60 [1.75-3.87]. AMX, FQ, and TMP-SMX also showed significant inter-class impact. Resistance to 3GC was not significantly associated with intraclass exposure (adjusted OR: 0.88 [0.41-1.90]). FOS resistance was remarkably low (0.4 %). Duration of the antibiotic-free period required for resistance risk to drop below 10 %, the threshold for empirical use in UTI, was modelled as < 1 month for 3GC, >18 months for AMX and TMP-SMX and uncertain for AMC (5.2 months [2.3 to > 18]) and FQ (17.4 months [7.4 to > 18]). CONCLUSIONS: Resistance of E. coli causing UTI is partially predicted by previous personal antibiotic delivery.

Twenty-four Month Outcomes of Extended- Versus Standard-course Antibiotic Therapy in Children Hospitalized With Pneumonia in High-risk Settings: A Randomized Controlled Trial.

BACKGROUND: Pediatric community-acquired pneumonia (CAP) can lead to long-term respiratory sequelae, including bronchiectasis. We determined if an extended (13-14 days) versus standard (5-6 days) antibiotic course improves long-term outcomes in children hospitalized with CAP from populations at high risk of chronic respiratory disease. METHODS: We undertook a multicenter, double-blind, superiority, randomized controlled trial involving 7 Australian, New Zealand, and Malaysian hospitals. Children aged 3 months to ≤5 years hospitalized with radiographic-confirmed CAP who received 1-3 days of intravenous antibiotics, then 3 days of oral amoxicillin-clavulanate, were randomized to either extended-course (8-day oral amoxicillin-clavulanate) or standard-course (8-day oral placebo) arms. Children were reviewed at 12 and 24 months. The primary outcome was children with the composite endpoint of chronic respiratory symptoms/signs (chronic cough at 12 and 24 months; ≥1 subsequent hospitalized acute lower respiratory infection by 24 months; or persistent and/or new chest radiographic signs at 12-months) at 24-months postdischarge, analyzed by intention-to-treat, where children with incomplete follow-up were assumed to have chronic respiratory symptoms/signs ("worst-case" scenario). RESULTS: A total of 324 children were randomized [extended-course (n = 163), standard-course (n = 161)]. For our primary outcome, chronic respiratory symptoms/signs occurred in 97/163 (60%) and 94/161 (58%) children in the extended-courses and standard-courses, respectively [relative risk (RR) = 1.02, 95% confidence interval (CI): 0.85-1.22]. Among children where all sub-composite outcomes were known, chronic respiratory symptoms/signs between groups, RR = 1.10, 95% CI: 0.69-1.76 [extended-course = 27/93 (29%) and standard-course = 24/91 (26%)]. Additional sensitivity analyses also revealed no between-group differences. CONCLUSION: Among children from high-risk populations hospitalized with CAP, 13-14 days of antibiotics (versus 5-6 days), did not improve long-term respiratory outcomes.

Antibiotic Treatment Has No Influence on Anal Fistula Formation and Recurrent Perianal Abscess After Incision and Drainage of Cryptogenic Perianal Abscess: A Randomized Single-Blinded Prospective Study.

BACKGROUND: Anal fistula commonly appears after incision and drainage of a perianal abscess. Theoretically, a fistula develops as a consequence of the infection process. Antibiotic treatment was suggested to decrease the possibility of fistula development. OBJECTIVE: We hypothesized that antibiotic treatment has no influence on the development of anal fistula after surgical treatment of perianal abscess. DESIGN: A single-blinded randomized prospective study. SETTINGS: Patients with primary cryptogenic abscesses were eligible to participate. PATIENTS: Patients were divided into 2 groups. Patients in group I received amoxicillin 875 mg/clavulanic acid 125 mg during 7 days after surgery, and patients in group II received no antibiotics. The study database included demographics and clinical and laboratory data. MAIN OUTCOME MEASURES: Patients were examined in our outpatient clinic 2 weeks, 4 months, and 1 year after surgery, and a telephone questionnaire was performed 6 months after surgery. The primary outcome was the formation of anal fistula. The secondary outcome was recurrent perianal abscess. RESULTS: Overall, 98 patients completed the study. Groups were not different in inclusion. Anal fistula was diagnosed in 16 patients (16.3%) in group I (treatment group) and 10 patients (10.2%) in group II (control group; p = 0.67). Nine patients (9.2%) developed recurrent perianal abscess, 4 in the treatment group and 5 in the control group ( p = 0.73). LIMITATIONS: A relatively small number of patients were treated in a single medical center. CONCLUSION: Antibiotic therapy has no influence on anal fistula or recurrent perianal abscess formation after incision and drainage of perianal abscess. See Video Abstract . EL TRATAMIENTO CON ANTIBITICOS NO TIENE INFLUENCIA EN LA FORMACIN DE FSTULA ANAL Y EN EL ABSCESO PERIANAL RECURRENTE DESPUS DE LA INCISIN Y DRENAJE DE UN ABSCESO PERIANAL CRIPTOGNICO UN ESTUDIO PROSPECTIVO ALEATORIZADO, SIMPLE CIEGO: ANTECEDENTES:La fístula anal comúnmente aparece después de la incisión y drenaje de un absceso perianal. Teóricamente, la fístula se desarrolla como consecuencia del proceso infeccioso. Se sugirió tratamiento antibiótico para disminuir la posibilidad de desarrollo de fístula.OBJETIVO:Hipotetizamos que el tratamiento con antibióticos no tiene influencia en el desarrollo de fístula anal después del tratamiento quirúrgico del absceso perianal.DISEÑO:Estudio prospectivo, aleatorio, simple ciego.AJUSTE Y PACIENTES:Los pacientes con absceso criptogénico primario fueron elegibles para participar. Los pacientes se dividieron en dos grupos. Los pacientes del Grupo I recibieron amoxicilina 875 mg/ácido clavulánico 125 mg durante los 7 días posteriores a la cirugía y los pacientes del Grupo II no recibieron antibióticos. La base de datos del estudio incluyó datos demográficos, clínicos y de laboratorio.PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes fueron examinados en nuestra clínica ambulatoria 2 semanas, cuatro meses y 1 año después de la cirugía y se realizó un cuestionario telefónico 6 meses después de la cirugía. El resultado primario fue la formación de una fístula anal. El resultado secundario fue el absceso perianal recurrente.RESULTADOS:En total, 98 pacientes completaron el estudio. Los grupos no fueron diferentes en cuanto a la inclusión. Se diagnosticó fístula anal en 16 (16,3%) pacientes del Grupo I (grupo de tratamiento) y 10 (10,2%) pacientes del Grupo II (grupo control) (p = 0,67). Nueve pacientes (9,2%) desarrollaron absceso perianal recurrente, 4 en el grupo de tratamiento y 5 en el grupo control (p = 0,73).LIMITACIONES:Número relativamente pequeño de pacientes tratados en un solo centro médico.CONCLUSIÓN:La terapia con antibióticos no tuvo influencia sobre la fístula anal o la formación de absceso perianal recurrente después de la incisión y drenaje del absceso perianal. (Traducción - Dr. Fidel Ruiz Healy ).

Exclusive oral antibiotic treatment for hospitalized community-acquired pneumonia: a post-hoc analysis of a randomized clinical trial.

OBJECTIVES: In this study, we aimed to assess the efficacy of different ways of administration and types of beta-lactams for hospitalized community-acquired pneumonia (CAP). METHODS: In this post-hoc analysis of randomized controlled trials (RCT) on patients hospitalized for CAP (pneumonia short treatment trial) comparing 3-day vs. 8-day durations of beta-lactams, which concluded to non-inferiority, we included patients who received either amoxicillin-clavulanate (AMC) or third-generation cephalosporin (3GC) regimens, and exclusively either intravenous or oral treatment for the first 3 days (followed by either 5 days of oral placebo or AMC according to randomization). The choice of route and molecule was left to the physician in charge. The main outcome was a failure at 15 days after the first antibiotic intake, defined as temperature >37.9°C, and/or absence of resolution/improvement of respiratory symptoms, and/or additional antibiotic treatment for any cause. The primary outcome according to the route of administration was evaluated through logistic regression. Inverse probability treatment weighting with a propensity score model was used to adjust for non-randomization of treatment routes and potential confounders. The difference in failure rates was also evaluated among several sub-populations (AMC vs. 3GC treatments, intravenous vs. oral AMC, patients with multi-lobar infection, patients aged ≥65 years old, and patients with CURB65 scores of 3-4). RESULTS: We included 200 patients from the original trial, with 93/200 (46.5%) patients only treated with intravenous treatment and 107/200 (53.5%) patients only treated with oral therapy. The failure rate at Day 15 was not significantly different among patients treated with initial intravenous vs. oral treatment [25/93 (26.9%) vs. 28/107 (26.2%), adjusted odds ratios (aOR) 0.973 (95% CI 0.519-1.823), p 0.932)]. Failure rates at Day 15 were not significantly different among the subgroup populations. DISCUSSION: Among hospitalized patients with CAP, there was no significant difference in efficacy between initial intravenous and exclusive oral treatment. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT01963442.

[Antibacterial therapy for acute streptococcal tonsillopharyngitis: results of a randomized comparative clinical trial with amoxicillin + clavulanic acid EXPRESS].

BACKGROUND: Acute tonsillopharyngitis is one of the most common types of respiratory tract infections. In case of bacterial etiologies of the disease, penicillin antibiotics are prescribed, in particular amoxicillin + clavulanic acid. Dispersible forms of antibiotics have a number of advantages over film-coated tablets and are characterized by better pharmacokinetic parameters that increase the effectiveness and safety of treatment, as well as patient compliance. AIM: To compare the effectiveness and safety of Amoxicillin + Clavulanic acid EXPRESS in the form of dispersible tablets and amoxicillin with clavulanic acid in film-coated tablets in the treatment of acute streptococcal tonsillopharyngitis. MATERIALS AND METHODS: A randomized comparative clinical study involved 60 adult patients diagnosed with acute streptococcal tonsillopharyngitis. Group 1 (n=30) received the Amoxicillin + Clavulanic acid EXPRESS, dispersible tablets, 875+125 mg 2 times a day at the beginning of meals. Group 2 (n=30) received Amoxiclav, film-coated tablets, 875+125 mg 2 times a day at the beginning of meals. The duration of the treatment was 10 days. The following procedures were performed to all participants: general clinical and otorhinolaryngological examinations, an express test to detect group A streptococcal antigens in a smear from the posterior pharyngeal wall (streptatest), assessment of symptoms of acute tonsillopharyngitis on the McIsaac scale, severity of sore throat, difficulty swallowing, swelling of the throat, measurement of body temperature, assessment of the clinical global impression of the therapy, adherence to treatment, frequency of the adverse reactions before treatment, 3 days after the beginning of therapy and after the course completion (day 10). RESULTS: Recovery occurred in 96.6% of patients in group 1 according to examination on the 10th day of treatment and in 93.3% of patients in group 2. The rate of fever regression was higher in group 1 - on the 3rd day of treatment, normalization of temperature was observed in 36.6% and 30% of patients in the comparison group. Pain syndrome, symptoms of throat swelling and difficulty swallowing significantly (p<0.01) regressed by the 10th day in patients of both treatment groups. The incidence of adverse reactions on the 10th day of treatment in group 1 was 10%, in group 2 - 33.3% (p=0.03). CONCLUSION: Amoxicillin + Clavulanic acid EXPRESS has high therapeutic efficacy in the treatment of acute streptococcal tonsillopharyngitis, comparable to the Amoxiclav in film-coated tablets. At the same time, dispersible tablets of Amoxicillin + Clavulanic acid EXPRESS demonstrated a significantly higher safety profile compared to the simple tablet form.

No evidence of difference in mortality with amoxicillin versus co-amoxiclav for hospital treatment of community-acquired pneumonia.

OBJECTIVES: Current guidelines recommend broad-spectrum antibiotics for high-severity community-acquired pneumonia (CAP), potentially contributing to antimicrobial resistance (AMR). We aim to compare outcomes in CAP patients treated with amoxicillin (narrow-spectrum) versus co-amoxiclav (broad-spectrum), to understand if narrow-spectrum antibiotics could be used more widely. METHODS: We analysed electronic health records from adults (≥16 y) admitted to hospital with a primary diagnosis of pneumonia between 01-January-2016 and 30-September-2023 in Oxfordshire, United Kingdom. Patients receiving baseline ([-12 h,+24 h] from admission) amoxicillin or co-amoxiclav were included. The association between 30-day all-cause mortality and baseline antibiotic was examined using propensity score (PS) matching and inverse probability treatment weighting (IPTW) to address confounding by baseline characteristics and disease severity. Subgroup analyses by disease severity and sensitivity analyses with missing covariates imputed were also conducted. RESULTS: Among 16,072 admissions with a primary diagnosis of pneumonia, 9685 received either baseline amoxicillin or co-amoxiclav. There was no evidence of a difference in 30-day mortality between patients receiving initial co-amoxiclav vs. amoxicillin (PS matching: marginal odds ratio 0.97 [0.76-1.27], p = 0.61; IPTW: 1.02 [0.78-1.33], p = 0.87). Results remained similar across stratified analyses of mild, moderate, and severe pneumonia. Results were also similar with missing data imputed. There was also no evidence of an association between 30-day mortality and use of additional macrolides or additional doxycycline. CONCLUSIONS: There was no evidence of co-amoxiclav being advantageous over amoxicillin for treatment of CAP in 30-day mortality at a population-level, regardless of disease severity. Wider use of narrow-spectrum empirical treatment of moderate/severe CAP should be considered to curb potential for AMR.

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 used to treat infections caused by a broad range of pathogens. AMC breakpoints against Enterobacterales were initially set in the 1980s. However, since that time, increases in antibiotic resistance, advances in pharmacokinetic/pharmacodynamic 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.

Paediatric Escherichia coli urinary tract infection: susceptibility trends and clinical management-a retrospective analysis of a 10-year period.

BACKGROUND: Escherichia coli is the predominant urinary pathogen in children. Irish and international studies have demonstrated increasing antimicrobial resistance (AMR) to antibiotics such as co-amoxiclav. AIMS: We aimed to (1) examine the AMR patterns of paediatric urinary E. coli isolates, from both hospital and community sources, over a 10-year period; (2) assess the effectiveness of Children's Health Ireland (CHI) antimicrobial guidance given local susceptibility data; and (3) review the clinical management of an admitted patient sub-set over a 6-year period. METHODS: Pure growth of urinary E. coli from patients aged ≤ 14 from 2012 to 2021 were analysed for AMR. Differences in susceptibility rates were assessed. A retrospective chart review conducted on inpatients aged ≥ 2 months to ≤ 14 years, 2016-2021. RESULTS: E. coli accounted for 70.8% of likely significant positive pure growth cultures (9314 isolates). Susceptibility to co-amoxiclav significantly increased over time, from 66.7% to 80.4% (2016-2021, p < 0.001). Nitrofurantoin and cefalexin had significantly higher susceptibility rates than trimethoprim (< 70% annually). 85.1% of isolates were susceptible to the combination of co-amoxiclav and gentamicin, recommended for those > 2months and systemically unwell. The additional gain in empiric susceptibility provided by gentamicin above that provided by co-amoxiclav alone has fallen from 16.4% to 6.7% (2016-2021). The 222 clinical cases reviewed showed improved antimicrobial guideline compliance over time. CONCLUSIONS: This study provides important regional AMR data. Co-amoxiclav susceptibility increased significantly over time, contrasting with previous studies. This was temporally associated with stewardship measures reducing co-amoxiclav prescribing. Decreasing utility of gentamicin supports recent CHI guideline updates reducing gentamicin use.

Antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) strains isolated at tertiary care hospital in Riyadh, Saudi Arabia.

Staphylococcus aureus is an important human pathogen that has a major impact on public health. The objective of the present work was to determine the prevalence and the pattern of antibiotic susceptibility in S aureus (MRSA) isolates from the King Khalid University Hospital (KKUH) in Riyadh, Saudi Arabia. The isolates were collected from different body sites of infection and the antibiotic susceptibility was confirmed on the Vitek 2 system. A total of 371 MRSA isolates from clinical samples were received over a 12-month period from January 2021 to December 2021. The results showed that infection was predominant among males (55.8%) and most of the isolates occurred in the older age groups, with a mean age of 43.7 years and an age span from <1 to 89 years old. The majority (34.5%) recovered from wound infection followed by (14.6%) from blood. We have observed peaks of MRSA infections during the autumn, especially in September and November. All MRSA isolates were resistant to Amoxicillin + clavulanic acid, Ampicillin, Imipenem, Oxacillin, Cloxacillin, and Penicillin while all isolates were sensitive to Daptomycin and Nitrofurantoin. Furthermore, Vancomycin was resistant in (0.3%) of MRSA isolates, and (2.9%) was resistant to Linezolid. The current study concluded that MRSA strains had developed resistance toward 24 tested antibiotics, including the previous effective drugs vancomycin and linezolid. Therefore, there is an urgent need for continuous review of infection control practices to prevent any further spread of resistant strains.

Amoxicillin/clavulanate in combination with rifampicin/clarithromycin is bactericidal against Mycobacterium ulcerans.

BACKGROUND: Buruli ulcer (BU) is a skin neglected tropical disease (NTD) caused by Mycobacterium ulcerans. WHO-recommended treatment requires 8-weeks of daily rifampicin (RIF) and clarithromycin (CLA) with wound care. Treatment compliance may be challenging due to socioeconomic determinants. Previous minimum Inhibitory Concentration and checkerboard assays showed that amoxicillin/clavulanate (AMX/CLV) combined with RIF+CLA were synergistic against M. ulcerans. However, in vitro time kill assays (TKA) are a better approach to understand the antimicrobial activity of a drug over time. Colony forming units (CFU) enumeration is the in vitro reference method to measure bacterial load, although this is a time-consuming method due to the slow growth of M. ulcerans. The aim of this study was to assess the in vitro activity of RIF, CLA and AMX/CLV combinations against M. ulcerans clinical isolates by TKA, while comparing four methodologies: CFU enumeration, luminescence by relative light unit (RLU) and optical density (at 600 nm) measurements, and 16S rRNA/IS2404 genes quantification. METHODOLOGY/PRINCIPAL FINDINGS: TKA of RIF, CLA and AMX/CLV alone and in combination were performed against different M. ulcerans clinical isolates. Bacterial loads were quantified with different methodologies after 1, 3, 7, 10, 14, 21 and 28 days of treatment. RIF+AMX/CLV and the triple RIF+CLA+AMX/CLV combinations were bactericidal and more effective in vitro than the currently used RIF+CLA combination to treat BU. All methodologies except IS2404 quantitative PCR provided similar results with a good correlation with CFU enumeration. Measuring luminescence (RLU) was the most cost-effective methodology to quantify M. ulcerans bacterial loads in in vitro TKA. CONCLUSIONS/SIGNIFICANCE: Our study suggests that alternative and faster TKA methodologies can be used in BU research instead of the cumbersome CFU quantification method. These results provide an in vitro microbiological support to of the BLMs4BU clinical trial (NCT05169554, PACTR202209521256638) to shorten BU treatment.