Involvement of autologous myeloid dendritic cells in the evaluation of immediate hypersensitivity reactions to betalactams.

BACKGROUND: Amoxicillin (AX) and clavulanic acid (CLV) are the betalactam antibiotics (BLs) most used to treat bacterial infections, although they can trigger immediate hypersensitivity reactions (IDHRs). The maturation analysis of monocyte-derived dendritic cells (moDCs) and their capacity to induce proliferative response of lymphocytes are useful to test the sensitisation to a drug, although without optimal sensitivity. Nevertheless, this can be improved using directly isolated DCs such as myeloid DCs (mDCs). METHODS: mDCs and moDCs were obtained from 28 allergic patients (AP), 14 to AX, 14 to CLV and from 10 healthy controls (HC). The expression of CCR7, CD40, CD80, CD83, and CD86 was analysed after stimulation with both BLs. We measured the capacity of these pre-primed DCs to induce drug-specific activation of different lymphocyte subpopulations, CD3+, CD4+, CD8+, CD4+Th1, and CD4+Th2, by flow cytometry. RESULTS: Higher expression of CCR7, CD40, CD80, CD83, and CD86 was observed on mDCs compared to moDCs from AP after stimulating with the culprit BL. Similarly, mDCs induced higher proliferative response, mainly of CD4+Th2 cells, compared to moDCs, reaching up to 67% of positive results with AX, whereas of only 25% with CLV. CONCLUSIONS: mDCs from selective AP efficiently recognise the culprit drug which trigger the IDHR. mDCs also trigger proliferation of lymphocytes, mainly those with a Th2 cytokine pattern, although these responses depend on the nature of the drug, mimicking the patient's reaction.

Incidence of amoxycillin-clavulanic acid associated hepatotoxicity in an Australian children's hospital.

OBJECTIVES: Amoxycillin/clavulanic acid is the most common antimicrobial cause of drug-induced liver injury in adults. It is a less common cause of severe drug-related hepatotoxicity in children despite its frequent use. We studied the incidence, characteristics and predictive factors for amoxycillin/clavulanic acid hepatoxicity in children. DESIGN: Retrospective cohort study of children who received oral or intravenous amoxycillin/clavulanic acid at a quaternary children's hospital over a 5-year period. Children were included if they had liver function tests (LFTs) determined at baseline, during and within 3 months after the treatment course. Causality was assessed using the Naranjo criteria for adverse drug reactions and Roussel Uclaf Causality Assessment Method. RESULTS: Of 3271 children prescribed amoxycillin/clavulanic acid, 374 were included. Forty-nine (13%) had LFT abnormalities related to amoxycillin/clavulanic acid. Fourteen (3.6%) fulfilled Common Terminology Criteria for Adverse Events (CTCAE) grade 2 criteria with clinically significant hepatotoxicity. Age <2 years, sepsis, post-gastrointestinal surgical indications, prolonged treatment course of >7 days and higher cumulative amoxycillin (>10 g) and clavulanic acid dose (>1 g) were predictive of hepatotoxicity. The median time to resolution of LFT abnormalities was 4 weeks (range 3-7). CONCLUSIONS: The incidence of amoxycillin/clavulanic acid related LFT abnormalities (CTCAE Grade 2 or above) in children was 3.6%. A prolonged treatment course >7 days, high cumulative amoxycillin (10 g) and clavulanic acid (>1 g) doses, those aged <2 years, and patients with sepsis or post-gastrointestinal surgery were predictive of a higher likelihood of abnormal LFTs. LFT monitoring should be considered in children receiving ≥7 days of treatment, particularly in those with other predisposing factors.

Clavulanic Acid Improves Memory Dysfunction and Anxiety Behaviors through Upregulating Glutamatergic Transporters in the Nucleus Accumbens of Mice Repeatedly Exposed to Khat Extract.

Khat (Catha edulis) is an evergreen shrub whose buds and leaves give a state of delight and euphoria when chewed. Cathinone, an amphetamine-like stimulant that is among the active ingredients in khat, is able to downregulate glutamate transporter subtype I (GLT-1). Neurobehavioral dysfunctions such as altered locomotor activity, anorexia, and nociception have been observed in animals exposed to cathinone. Interestingly, treatment with a ß-lactam antibiotic such as ceftriaxone, which upregulates GLT-1, normalizes cathinone-induced conditioned place preference, and alters repetitive movements in rats. However, little is known about the role of the glutamatergic system in memory dysfunction and anxiety-like behaviors in mice exposed to khat. We found here that clavulanic acid, a ß-lactam-containing compound and GLT-1 upregulator, would modulate the neurobehavioral changes, including memory impairment and anxiety-like behaviors, associated with repeated exposure of mice to khat. Our data supported that clavulanic acid could improve memory impairment and anxiety-like behaviors through upregulating GLT-1 in the nucleus accumbens (NAc), an effect abolished with a selective GLT-1 blocker. This upregulation was associated with restored glutamate/cystine antiporter expression in the NAc using a Western blotting assay. Cathine and cathinone were identified in khat extract using the gas chromatography technique. Our work provides preclinical insight into the efficacy of ß-lactam-containing compounds for the attenuation of neurobehavioral changes induced by khat exposure.

Non-operative treatment of acute appendicitis in children: clinical efficacy of amoxicillin-clavulanic acid in a retrospective single-centre study.

BACKGROUND: The success rate of non-operative treatment (NOT) of acute uncomplicated appendicitis (AUA) in children varies from 65% to 95%. There are no recommendations on the appropriate antibiotic therapy. OBJECTIVE: To determine the clinical efficacy of amoxicillin-clavulanic acid for NOT of AUA in children. METHODS: Design: Cross-sectional study in a single medical centre. SETTINGS: Emergency department and Paediatric Visceral Surgery department of the Children Hospital in Toulouse, France. PATIENTS: Patients 5-15 years old who were diagnosed with appendicitis, (1) With abdominal pain and a first episode of acute appendicitis, (2) With no radiological or ultrasound evidence of appendicolith, appendiceal perforation, pelvic abscess nor peritonitis, and (3) With non-septic general aspect, were included. INTERVENTIONS: NOT consisted of hospital admission. The antibiotic treatment was a combination of amoxicillin and clavulanic acid (80 mg/kg/day of amoxicillin): intravenous regimen during 48 hours followed by oral route during 7 days. MAIN OUTCOME MEASURE: Success rate of amoxicillin-clavulanic acid NOT in children with AUA at 2 years. RESULTS: The initial success rate of amoxicillin-clavulanic acid NOT in children with AUA was 100% (104/104 patients). The success rate at 2 years was 85.6% (89/104) at discharge. None of the 15 patients who underwent surgery after recurrence of appendicitis presented with peritonitis, appendiceal perforation nor pelvic abscess. CONCLUSION: Narrowed antibiotic therapy with amoxicillin and clavulanic acid seems to be an alternative to surgery in children with AUA. It is necessary to wait for the results of ongoing studies to confirm these results.

Inhibition of ß-lactamase function by de novo designed peptide.

Antimicrobial resistance is a great public health concern that is now described as a "silent pandemic". The global burden of antimicrobial resistance requires new antibacterial treatments, especially for the most challenging multidrug-resistant bacteria. There are various mechanisms by which bacteria develop antimicrobial resistance including expression of ß-lactamase enzymes, overexpression of efflux pumps, reduced cell permeability through downregulation of porins required for ß-lactam entry, or modifications in penicillin-binding proteins. Inactivation of the ß-lactam antibiotics by ß-lactamase enzymes is the most common mechanism of bacterial resistance to these agents. Although several effective small-molecule inhibitors of ß-lactamases such as clavulanic acid and avibactam are clinically available, they act only on selected class A, C, and some class D enzymes. Currently, none of the clinically approved inhibitors can effectively inhibit Class B metallo-ß-lactamases. Additionally, there is increased resistance to these inhibitors reported in several bacteria. The objective of this study is to use the Resonant Recognition Model (RRM), as a novel strategy to inhibit/modulate specific antimicrobial resistance targets. The RRM is a bio-physical approach that analyzes the distribution of energies of free electrons and posits that there is a significant correlation between the spectra of this energy distribution and related protein biological activity. In this study, we have used the RRM concept to evaluate the structure-function properties of a group of 22 ß-lactamase proteins and designed 30-mer peptides with the desired RRM spectral periodicities (frequencies) to function as ß-lactamase inhibitors. In contrast to the controls, our results indicate 100% inhibition of the class A ß-lactamases from Escherichia coli and Enterobacter cloacae. Taken together, the RRM model can likely be utilized as a promising approach to design ß-lactamase inhibitors for any specific class. This may open a new direction to combat antimicrobial resistance.

Use or abuse of antibiotics as prophylactic therapy in oral surgery: A systematic review.

BACKGROUD: Antibiotics are a type of medication routinely prescribed by dental professionals; however, it is very common that the administration is not justified. Around 15% of dentists admit that they have administered antibiotics unnecessarily more than once a week. The objective of this project is to identify the effectiveness of the use of antibiotics as prophylactic therapy in oral surgery, and to carry out an analysis of the alternatives to pharmacological therapy. METHODS: The search strategy was carried out in the PubMed, Scopus, and ScienceDirect databases. For study selection, a first filter was carried out by title and abstract, which mentioned the use of prophylactic antibiotics in some type of oral surgery. To establish the risk of bias, the JBI Critical Appraisal Checklist for Randomized Controlled Trials was utilized. RESULTS: The type of antibiotics most prescribed as prophylactic therapy were beta-lactams, which were indicated in 100% of the studies. Penicillins predominated, observing amoxicillin as the most indicated drug in 54.1% of the studies (n = 13) followed by the use of amoxicillin in conjunction with clavulanic acid in 33.3% of the studies (n = 8). Of the 21 studies included, 17 mention that there is insufficient evidence to support the use of antibiotics as prophylactic therapy in patients who will undergo some type of oral surgery. CONCLUSIONS: Without a doubt, the biggest challenge is to develop academic update strategies aimed at dentists with active clinical practice and dental students from educational and government institutions to provide updated information about the correct use of prescription drugs.

The challenges of diagnosis and treatment of rare Prevotella-induced breast abscesses: A retrospective cohort study.

OBJECTIVE: Although the genus Prevotella is part of the general human microbiota, species of this anaerobic gram-negative bacterium have been described as causes of persisting nonpuerperal breast abscesses. Collecting punctate samples and testing these samples for anaerobic bacteria is not part of the common diagnostic workflow in atypical breast abscesses. The causative anaerobic micro-organism can remain unclear and patients can be treated with multiple inadequate antibiotics and/or extensive surgical procedures. The aim of this cohort study of Prevotella induced breast abscesses is to gain more insights into the diagnostic procedures and treatment. METHODS: Medical charts of patients with a Prevotella induced breast abscess between 2015 and 2021, were retrospectively reviewed on patient characteristics, diagnostic procedures, treatment and outcome. RESULTS: Twenty-one patients were included. Six subspecies of Prevotella were determined by culturing. High susceptibility was observed for amoxicillin/clavulanic acid (100%, n = 12). Nine patients (43%) were treated with antibiotics, eight patients (38%) with antibiotics and incision and drainage, and four patients (19%) with only incision and drainage. Recurrence was observed in nine patients (43%), of whom five patients were treated with antibiotics and three patients had surgery. The mean duration of antibiotic administration in patients with recurrence was significantly shorter compared to those without recurrence (5.6 days vs. 19.5 days, p = 0.039). CONCLUSION: Specific anaerobic culturing should be common practice in atypical breast abscesses to confirm Prevotella species. The high recurrence rate emphasizes the need of further research for optimal treatment. Prolonged duration of antibiotics could be considered and amoxicillin/clavulanic acid seems to be the first choice.

Feline urinary tract pathogens in western Canada: Prevalence of bacterial species and antimicrobial resistance from 2012 to 2018.

Objective: The aim of this study was to investigate the bacterial population and antimicrobial resistance of bacteria isolated from feline urine from 2012 to 2018 in the Canadian provinces of Alberta and British Columbia. Animals and procedure: IDEXX Reference Laboratories provided data from urine samples submitted from Alberta and British Columbia for aerobic culture and susceptibility testing from January 1, 2012 to December 31, 2018. The analysis included 8084 bacterial isolates from 7522 cystocentesis samples, with at least 1000 colony-forming units per mL. Results: Escherichia coli, Enterococcus species, and Staphylococcus species were the most commonly isolated bacteria, at 60.0%, 22.7%, and 11.8%, respectively. The proportions did not vary significantly throughout the study period or between British Columbia and Alberta. Apart from an increase in the resistance of Staphylococcus species to clindamycin, there was minimal change in the antimicrobial susceptibility of the 3 most commonly isolated bacteria over the study period. More than 85% of Gram-positive organisms were susceptible to amoxicillin with or without clavulanic acid, and > 85% of Gram-negative organisms were susceptible to amoxicillin with clavulanic acid and trimethoprim with sulfamethoxazole. Conclusion and clinical relevance: Treatment with amoxicillin, with or without clavulanic acid, may be considered for bacterial feline lower urinary tract disease in Alberta and British Columbia while awaiting culture results.

Agents pathogènes des voies urinaires félines dans l'Ouest canadien: prévalence des espèces bactériennes et résistance aux antimicrobiens de 2012 à 2018. Objectif: Le but de cette étude était d'étudier la population bactérienne et la résistance antimicrobienne des bactéries isolées de l'urine féline de 2012 à 2018 dans les provinces canadiennes de l'Alberta et de la Colombie-Britannique. Animaux et procédure: Les Laboratoires de référence IDEXX ont fourni des données à partir d'échantillons d'urine soumis par l'Alberta et la Colombie-Britannique pour une culture aérobie et des tests de sensibilité du 1er janvier 2012 au 31 décembre 2018. L'analyse comprenait 8084 isolats bactériens provenant de 7522 échantillons d'urine obtenus par cystocentèse, avec au moins 1000 unités formant des colonies/mL. Résultats: Escherichia coli, les espèces appartenant aux genres Enterococcus et Staphylococcus étaient les bactéries les plus couramment isolées, à 60,0 %, 22,7 % et 11,8 %, respectivement. Les proportions n'ont pas varié de manière significative tout au long de la période d'étude ni entre la Colombie-Britannique et l'Alberta. Hormis une augmentation de la résistance des espèces de Staphylococcus à la clindamycine, il y a eu un changement minime de la sensibilité aux antimicrobiens des 3 bactéries les plus couramment isolées au cours de la période d'étude. Plus de 85 % des organismes à Gram positif étaient sensibles à l'amoxicilline avec ou sans acide clavulanique, et > 85 % des organismes à Gram négatif étaient sensibles à l'amoxicilline avec acide clavulanique et à la combinaison triméthoprime-sulfaméthoxazole. Conclusion et pertinence clinique: Un traitement à l'amoxicilline, avec ou sans acide clavulanique, peut être envisagé pour les infections bactérienne urinaires félines en Alberta et en Colombie-Britannique en attendant les résultats de la culture.(Traduit par Dr Serge Messier).

Antimicrobial susceptibility patterns from urinary isolates obtained from cats (2013-2020).

BACKGROUND: Bacterial urinary tract infections have been associated with comorbidities and increased antimicrobial resistance over time. OBJECTIVE: To identify bacterial species, antimicrobial susceptibility patterns and risk factors associated with antimicrobial resistance. ANIMALS: Three hundred sixty-three positive urine cultures from 308 cats. METHODS: Bacterial species and antimicrobial susceptibility data from positive aerobic bacterial urine cultures from cats with growth of ≥103 colony forming units per milliliter (cfu/ml) were included. Medical records were reviewed, and bacteriuria was classified as sporadic bacterial cystitis, recurrent bacterial cystitis or subclinical bacteriuria (SBU). Multivariable logistic regression analysis was used to evaluate antimicrobial resistance risk factors. RESULTS: A total of 444 bacterial isolates from 363 bacteriuric episodes were identified. Escherichia coli (52%) and SBU (59%) were the most common organism and classification, respectively. When compared to other classifications of bacteriuria, Enterococcus spp. were more likely to be isolated from SBU episodes (P < .001), whereas E. coli was more likely to be isolated from sporadic bacterial cystitis episodes (P < .001). Recurrent bacterial cystitis was associated with an increased risk of antimicrobial resistance to amoxicillin/clavulanic acid (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.3-11.3). The percent susceptibilities of all bacterial isolates to commonly prescribed antimicrobials were amoxicillin/clavulanic acid (72%), cefazolin (49%), enrofloxacin (61%), and trimethoprim/sulfamethoxazole (75%). Multidrug resistance was highest for Enterococcus faecium isolates (65%). CONCLUSIONS AND CLINICAL IMPORTANCE: No antimicrobial achieved >90% susceptible designation to all bacteria isolated highlighting the importance of performing urine culture and susceptibility testing, particularly for cats with recurrent bacterial cystitis.

Diagnosis of immediate reactions to amoxicillin: Comparison of basophil activation markers CD63 and CD203c in a prospective study.

BACKGROUND: Amoxicillin (AX) combined or not with clavulanic acid (CLV) is frequently involved in IgE-mediated reactions. Drug provocation test (DPT) is considered as the gold standard for diagnosis, although contraindicated in high-risk patients. Basophil activation test (BAT) can help diagnose immediate reactions to beta-lactams, although controversy exists regarding the best activation marker. We have performed a real-life study in a prospective cohort to analyze the real value of BAT as diagnostic tool and the best activation marker, CD63 and CD203c, for the evaluation of immediate reactions to these drugs. METHODS: We prospectively evaluated patients with a clinical suspicion of immediate reactions after AX or AX-CLV administration during a 6-year period. The allergological work-up was done following the EAACI recommendations. BAT was performed in all patients using CD63 and CD203c as activation markers. RESULTS: In AX-allergic patients, both activation markers, CD63 and CD203c, showed similar SE values (48.6% and 46.7%, respectively); however, specificity was of 81.1% and 94.6%, respectively, with CD203c showing good positive predictive value and like-hood ratio. In CLV-allergic patients, CD203c showed higher SE (50%) than CD63 (42.9%), maintaining the same value of SP (80%). Combining the results of both markers can slightly increase the sensitivity (51.4% for AX and 54.8% for CLV), although decreasing the specificity (79.7% and 73%, respectively). Interestingly, all patients with an anaphylactic shock showed a positive BAT to CLV using CD203c. CONCLUSIONS: BAT using CD203c showed a good confirmatory power, especially for AX allergy. Placing BAT as a first step in the diagnostic procedure can help reduce the need of performing a complete allergological work-up in 46.6% of patients, diminishing the risk of reinducing allergic reactions.

Evaluation Of Anti-Inflammatory Efficacy Of Ascorbic Acid After Third Molar Surgery.

BACKGROUND: Abstraction of wisdom teeth or impacted third molar under local anaesthesia is one of the most frequent interventions by an oral and maxillofacial surgeon. The abstraction of the third molar is usually followed by the release of liberation and consequent trismus, pain, and swelling due to the area of the third molar being highly vascularized and rich in loose connective tissue. Objective of the study was to evaluate the anti-inflammatory effect of ascorbic acid following surgical extraction of the third molar. METHODS: The current study was carried out Armed Forces Institute of Dentistry, Rawalpindi, from October to December 2022. This was a cross-sectional observational study. Fifty participants who required surgical extraction of the impacted third molar were included in the study via non-probability purposive sampling and were segregated equally into two groups, i.e., Group A and Group B, comprising twenty-five participants in each group. Group A received amoxicillin with clavulanic acid (625 mg) thrice a day and metronidazole (400 mg) twice daily. In comparison, Group B received amoxicillin with clavulanic acid (625 mg) thrice daily, ascorbic acid (500 mg) twice daily, and metronidazole (400 mg) twice daily. Both groups received naproxen sodium as per requirement (550 mg). Pain, facial swelling, and C reactive protein concentration were evaluated until the 7th postoperative day. RESULTS: There was a reduction in pain and facial swelling in both groups, but in the ascorbic acid group, there was more reduction in pain and facial swelling compared to the control group. However, the difference between the two groups in reducing pain and facial swelling was statistically significant (p<0.01). There was a reduction in CRP in both groups, but in the ascorbic acid group, there was more reduction in CRP 2.35 (1.60-5.30) compared to the control group 2.6 (0.86-5.03). However, the difference between the two groups in reducing C reactive protein concentration was statistically insignificant (p>0.05). CONCLUSIONS: Our study concluded that ascorbic acid significantly reduced inflammation and C reactive protein, so ascorbic acid should be used as an adjuvant supplement with other conventional drugs.

The Effect of Amoxicillin with Clavulanate on the Microbiota of Tonsillar Tissue in Disease: a Randomized Control Trial.

Despite antibiotics being the primary medical treatment for recurrent tonsillitis, the impact of antibiotics on the tonsillar microbiome is not well understood. This study aimed to determine the effect of amoxicillin with clavulanate on the composition and quantity of bacteria in the tonsils of children with recurrent tonsillitis. A multicenter randomized clinical trial in Auckland, New Zealand was undertaken between August 1, 2017, and June 30, 2018. Sixty children undergoing tonsillectomy for the indication of recurrent tonsillitis were recruited for this study. Following random allocation, 30 participants were prescribed amoxicillin with clavulanate for the week before surgery. The remaining 30 received no antibiotics. Immediately following surgery, the crypts of the right and left tonsils were swabbed. Bacterial 16S rRNA gene-targeted amplicon sequencing and histological techniques were utilized. In the control group, there were significantly higher relative abundances of Haemophilus, Streptococcus, Neisseria, and Porphyromonas. Members from the genera Fusobacterium and Treponema were found to be significantly more abundant in the antibiotic group. There were no significant differences in the absolute quantities of bacteria between the groups. Microscopic examination found fewer bacterial microcolonies present in the tonsillar crypts of participants in the antibiotic group. Streptococcus pyogenes was not present in these bacterial microcolonies. These results suggest that a single course of antibiotics has a significant impact on the tonsil microbiota composition. The duration of this effect and the effect that the altered microbiome has on the course of the condition need to be determined. IMPORTANCE Several studies have identified the presence of multiple pathogenic bacteria in hyperplastic adenoids and palatine tonsils. However, there are currently no studies that utilize this technology to investigate the effect of oral antibiotics in children with recurrent tonsillitis on the tonsillar microbiome. This is the first study to investigate the effect of antibiotics on the microbiome of tonsillar tissue in children with recurrent tonsillitis using molecular techniques. This study has shown that participants who received amoxicillin with clavulanate immediately before tonsillectomy had a significantly reduced number of bacterial taxa commonly associated with recurrent tonsillitis, as well as the number of bacterial microcolonies observed in the tonsillar crypts. This novel finding suggests that either the effect of antibiotics is not sustained or that they are not an effective treatment for recurrent tonsillitis.

Challenging diagnosis and successful treatment of localised Mycobacterium avium subsp. hominissuis glossitis in a dog on long-term immunomodulatory therapy.

CASE HISTORY: A 3-year-old, intact female mixed-breed dog, weighing 7 kg, was presented with generalised swelling of the tongue, leading to impaired deglutition and episodes of dyspnoea. From the age of 2 years, the dog had been under immunosuppressive therapy due to atopic dermatitis. CLINICAL FINDINGS AND TREATMENT: Multiple nodular lesions at the apex of the tongue were noted as well as mandibular and retropharyngeal lymph node enlargement. Serum biochemistry results showed inflammatory changes. The results of several biopsies taken over 7 months indicated persistent pyogranulomatous and necrotising glossitis despite ongoing antimicrobial treatment, first with amoxicillin/clavulanic acid and then pradofloxacin. No foreign material, acid-fast bacteria or fungal hyphae were detected throughout. The final diagnosis of Mycobacterium avium subsp. hominissuis (Mah) was reached after PCR and bacterial culture were carried out on the third biopsy sample. Therapy was initiated with rifampicin, clarithromycin and doxycycline, leading to complete remission of the lesions. DIAGNOSIS: Severe chronic pyogranulomatous and necrotising glossitis associated with infection by Mah. CLINICAL RELEVANCE: This report describes challenges in the diagnosis and therapy of a localised Mah infection in an iatrogenically immunocompromised dog. Successful treatment was only achieved with a specific combination of antibiotics administered long-term. ABBREVIATIONS: AF: Acid-fast; ALP: Alkaline phosphatase; CT: Computed tomography; MAC: Mycobacterium avium complex; Mah: Mycobacterium avium subsp. hominissuis.

Systematic whole-genome sequencing reveals an unexpected diversity among actinomycetoma pathogens and provides insights into their antibacterial susceptibilities.

Mycetoma is a neglected tropical chronic granulomatous inflammatory disease of the skin and subcutaneous tissues. More than 70 species with a broad taxonomic diversity have been implicated as agents of mycetoma. Understanding the full range of causative organisms and their antibiotic sensitivity profiles are essential for the appropriate treatment of infections. The present study focuses on the analysis of full genome sequences and antibiotic inhibitory concentration profiles of actinomycetoma strains from patients seen at the Mycetoma Research Centre in Sudan with a view to developing rapid diagnostic tests. Seventeen pathogenic isolates obtained by surgical biopsies were sequenced using MinION and Illumina methods, and their antibiotic inhibitory concentration profiles determined. The results highlight an unexpected diversity of actinomycetoma causing pathogens, including three Streptomyces isolates assigned to species not previously associated with human actinomycetoma and one new Streptomyces species. Thus, current approaches for clinical and histopathological classification of mycetoma may need to be updated. The standard treatment for actinomycetoma is a combination of sulfamethoxazole/trimethoprim and amoxicillin/clavulanic acid. Most tested isolates had a high IC (inhibitory concentration) to sulfamethoxazole/trimethoprim or to amoxicillin alone. However, the addition of the ß-lactamase inhibitor clavulanic acid to amoxicillin increased susceptibility, particularly for Streptomyces somaliensis and Streptomyces sudanensis. Actinomadura madurae isolates appear to have a particularly high IC under laboratory conditions, suggesting that alternative agents, such as amikacin, could be considered for more effective treatment. The results obtained will inform future diagnostic methods for the identification of actinomycetoma and treatment.

Efficacy of amoxicillin or amoxicillin and clavulanic acid in reducing infection rates after third molar surgery: a systematic review and meta-analysis.

OBJECTIVE: The current review was designed to assess the efficacy of amoxicillin (AMX) and amoxicillin-clavulanic acid (AMX-CLA) for reducing infection rates after third molar surgery. MATERIALS AND METHODS: PubMed, Embase, ScienceDirect, and Google Scholar were searched for double-blind randomized controlled trials (RCTs) assessing the efficacy of AMX/AMX-CLA for infection control after third molar surgery. RESULTS: 13 RCTs were included. Our meta-analysis demonstrated a statistically significant reduced risk of infections with AMX/AMX-CLA (RR: 0.29, 95% CI: 0.18, 0.45 I2=0% p<0.00001). The meta-analysis demonstrated that the risk of infections was significantly reduced only in parallel-arm trials but not in split-mouth trials. Sub-group analysis based on antibiotic type indicated that the risk of infections was reduced with both AMX and AMX-CLA. A subgroup analysis based on the timing of AMX/AMX-CLA administration indicated that the risk of infections was significantly reduced with both preoperative (RR: 0.41, 95% CI: 0.21, 0.81 I2=0% p=0.01) and postoperative (RR: 0.18, 95% CI: 0.09, 0.35 I2=0% p<0.00001) administration of AMX/AMX-CLA. Meta-analysis indicated no increased risk of adverse events with the use of AMX/AMX-CLA (RR: 1.47, 95% CI: 0.41, 5.22 I2=77% p=0.55). CONCLUSIONS: The use of AMX/AMX-CLA is associated with a significant reduction in the risk of infections after impacted third molar surgery. The risk of infections is reduced with both AMX and AMX-CLA. Our results also indicated that the infection risk was reduced with preoperative and postoperative antibiotic administration and there is no significant increase in the risk of antibiotic-related adverse events.

Urinary Tract Infections in Long-term Care: Evaluation of Uropathogens, Antibiotic Susceptibility, and Empiric Treatment.

Objective To devise a residential empiric treatment algorithm, describe common uropathogens associated with urinary tract infections (UTIs) in residential care, assess all-pathogen and non-ESBL (extended-spectrum beta-lactamase) Escherichia coli antibiotic susceptibilities, and report the percentage of antibiotic use. Design A retrospective chart review of 198 residents with positive urine cultures from September 2019 to September 2020. Setting Institutional long-term care facility. Participants The exclusion criteria were negative urine culture, mixed organisms on urine culture, no antibiotic treatment, signs and symptoms of systemic infection, hospitalization because of systemic infection, and intravenous antibiotic treatment. The entire population was screened. Results The most prevalent pathogens were non-ESBL E. coli (29%), Proteus mirabilis (12%), Klebsiella pneumoniae (8%), and ESBL E. coli (8%). All-pathogen susceptibilities were 79.6% (amoxicillin/clavulanate), 64.1% (nitrofurantoin), 50.5% (sulfamethoxazole/trimethoprim), 43.7% (cephalexin), 42.7% (amoxicillin), and 41.8% (ciprofloxacin). Amoxicillin/clavulanate (96.7%), nitrofurantoin (90.0%) and sulfamethoxazole/trimethoprim (83.3%) demonstrated the highest non-ESBL E. coli susceptibilities. Nitrofurantoin was the most prescribed antibiotic (21%), followed by amoxicillin/clavulanate (19%) and ciprofloxacin (17%). Conclusion Based on the data, amoxicillin/clavulanate and nitrofurantoin are appropriate first-line options for empiric treatment of symptomatic cystitis in this long-term care facility, with sulfamethoxazole/trimethoprim as an alternative. Ciprofloxacin was overprescribed despite its low susceptibilities to commonly encountered pathogens, which emphasizes the need for a UTI empiric treatment algorithm tailored towards residential care.

Characteristics of Stenotrophomonas maltophilia isolates from cystic fibrosis patients in Russia.

Stenotrophomonas maltophilia is a common opportunistic microorganism and an important respiratory pathogen in cystic fibrosis (CF). The aim of this study was to determine antimicrobial resistance phenotypes, sequence-types (ST) and genetic determinants of antibiotic resistance in S. maltophilia strains recovered from CF patients in Russia. S. maltophilia isolates recovered from 170 CF patients were analyzed. Minimum inhibitory concentrations of antibacterial agents were determined using Sensititre Gram Negative GNX2F plates and the results were interpreted according to Clinical and Laboratory Standards Institute (CLSI) criteria. Whole-genome sequencing (WGS) was performed on MGISEQ-2000 platform. SPAdes software, Galaxy, ResFinder, Integrall and PubMLST were used for analysis of WGS data. S. maltophilia strains were identified from 24/170 (14%) CF patients. In total, 25 isolates were detected, two strains were isolated from the same patient. The isolates belonged to 17 different STs, including 5 new STs; ST4 was the most prevalent ST. Resistance to ceftazidime was observed in 60% of strains, to ticarcillin-clavulanate - in 32%, to levofloxacin - in 24%, to trimethoprim/sulfamethoxazole - in 12% of strains. All isolates were susceptible to minocycline. All ST4 isolates were resistant or intermediate to ceftazidime and ticarcillin-clavulanate. In two isolates, the sul1 gene was detected. In one isolate, sul1 was part of a class 1 integron. The detected integron also contained the blaGES-7 and aac(6')-Ib-cr genes. The ST4 sequence-type was the most prevalent ST among S. maltophilia strains recovered from CF patients in Russia. Antibiotic resistance genes, including sul1, blaGES-7, aac(6')-Ib-cr, were detected in single strains.

Teleocidin-producing genotype of Streptomyces clavuligerus ATCC 27064.

Streptomyces clavuligerus is an industrially important producer of clavulanic acid (CA), a ß-lactamase inhibitor which is used together with amoxicillin in one of the most widely prescribed antibacterial medicines, the co-amoxiclav. In a mid-eighties ATCC vial of S. clavuligerus ATCC 27064 culture, we have found a new genotype, which was apparently lost from the subsequent ATCC collection stocks, and has remained obscure to the scientific community. Most importantly, this genotype harbors teleocidin (lyngbyatoxin) biosynthetic genes, which are located on an enigmatic 138 kb chromosomal region and support accumulation of significant amounts of these highly toxic, tumor-promoting secondary metabolites in cultures of S. clavuligerus. While this genomic region is completely absent from all published sequences for S. clavuligerus ATCC strain, at least one of the industrial strains for commercial production of CA, originating from ATCC 27064, retained the genetic potential for production of teleocidins. The origin of teleocidin biosynthetic cluster can now be traced back to early S. clavuligerus stocks at the ATCC. Our work provides a genome sequence and a deposited monoisolate of this genotype. Given the scale of industrial use of S. clavuligerus world-wide and toxicity of teleocidins, we also discuss the environmental and safety implications and provide a method of abolishing teleocidin production without affecting productivity of CA. KEY POINTS: • Early stocks of S. clavuligerus ATCC 27064 produce toxic teleocidins • Teleocidin biosynthetic genes were found within a distinct S. clavuligerus genotype • The genotype has been passed on to some industrial clavulanic acid producer strains.

Drug-Induced Histiocytoid Sweet Syndrome: Two Cases With Levofloxacin and Amoxicillin-Clavulanate.

ABSTRACT: Histiocytoid Sweet syndrome (HSS) is an uncommon histologic variant of Sweet syndrome (SS). HSS can be distinguished from the classic SS with an infiltrate of histiocyte-like immature myeloid cells rather than dense neutrophilic infiltration, although the clinical features are similar. Previous studies have shown that the risk of hematologic malignancy is significantly higher in HSS compared with classic SS. To lesser extent, HSS is also associated with infections, inflammatory diseases, and drugs, particularly with antineoplastic agents as well. Here, we report a case of 2 patients with an abrupt onset of erythematous, tender plaques accompanied by fever, with that revealed similar histopathologic and immunohistochemical features, whom had a history of antibiotic use. Clinicopathologic correlation led to diagnosis of drug-induced HSS, associated with the use of levofloxacin and amoxicillin-clavulanate, respectively. Both patients were then successfully treated with systemic corticosteroid therapy, and neither of them had recurrence during the period of 24-month follow-up.

Statistical Optimizing of Medium for Clavulanic Acid Production by Streptomyces clavuligerus Using Response Surface Methodology.

Clavulanic acid (CA) is a naturally occurring antibiotic produced by Streptomyces clavuligerus. Statistical optimization of the fermentation medium for CA production by Streptomyces clavuligerus was carried out. Multiple carbon sources, glycerol, dextrin, and triolein, were considered simultaneously. A two-level fractional factorial design experiment was conducted to identify the significant components of medium on CA production. Statistical analysis of the results showed that soybean meal, dextrin, and triolein were the most significant medium ingredients on CA production. The optimal level of these screened components was obtained by RSM based on the result of a Box-Behnken design, in which the values of dextrin, soybean meal, and triolein in CA fermentation medium were 12.37 g/L, 39.75 g/L, and 26.98 ml/L, respectively. Using the proposed optimized medium, the model predicted 938 mg/L of CA level and via experimental rechecking the model, 946 mg/L of CA level was attained in shake flask fermentation, significantly high than 630 mg/L of original medium. The optimized medium was further verified in 50-L stirred fermenter, and compared with performance of original medium in parallel, CA titer was increased from 889 to 1310 mg/L; a 47% increase was achieved through medium optimization by statistical approaches.