Toxin inhibition: Examining tetracyclines, clindamycin, and linezolid.

PURPOSE: The purpose of this review is to discuss the role of toxin inhibition in select infections and to provide recommendations for appropriate antimicrobial selection when toxin inhibition is indicated. SUMMARY: For select organisms, specifically Clostridioides difficile, Staphylococcus aureus, and Streptococcus pyogenes, toxin production plays an integral role in overall disease pathogenesis and progression. Some expert recommendations include utilization of an antimicrobial with toxin inhibition properties as primary or adjunctive therapy for certain infections due to these organisms, but evolving data have made the choice of antitoxin agent less clear. Clindamycin has been the long-standing standard of care agent for toxin inhibition in necrotizing S. aureus and S. pyogenes infections, but linezolid shows promise as an alternative either in the setting of drug shortages or simply when clindamycin is not optimal, while tetracyclines require further study for this indication. The role for adjunctive toxin inhibition in C. difficile infection (CDI) is less defined, as current first-line therapies already have antitoxin properties. CONCLUSION: Toxin inhibition plays a key role in successful management of patients with infections due to toxin-producing organisms. Adjunctive therapy with a tetracycline could be considered in severe, fulminant CDI, but the associated benefit is variable. The benefit of antitoxin treatment for necrotizing S. aureus and S. pyogenes has been more consistently documented. Recent studies support linezolid as an alternative to clindamycin as an adjunctive S. aureus treatment or as monotherapy when appropriate.

Modified minimally invasive surgical technique with clindamycin-augmented or non-augmented platelet-rich fibrin in periodontal regeneration: A randomized clinical trial.

AIM: Injectable platelet-rich fibrin (I-PRF), a second-generation platelet concentrate, is widely used to enhance soft and hard tissue healing alone or in combination with biomaterials, relying on its harboring of various pivotal growth/differentiation factors. This randomized trial assessed the effect of clindamycin (CLN) augmented injectable platelet-rich fibrin (I-PRF) with modified minimally invasive surgical technique (M-MIST) versus I-PRF alone with M-MIST on the clinical and radiographic parameters in the management of periodontal intra-bony defects in patients with stage-III grade B periodontitis. METHODS: This is a 9-month parallel-grouped, two arm, double-blinded, randomized controlled trial (RCT) that included 28 patients (n = 28) with stage-III grade B periodontitis, who were allocated randomly to test- (CLN/I-PRF + M-MIST, 50 µL of CLN per 1 mL of I-PRF; n = 14) or control-group (I-PRF + M-MIST; n = 14). Clinical attachment level (CAL; primary outcome), probing depth (PD), gingival margin level (GML), plaque index (PI), and gingival index (GI) were recorded at baseline, 3, 6, and 9 months, whereas radiographic parameters radiographic linear defect depth (RLDD), and radiographic defect area (RDA) were recorded at baseline, 6, and 9 months. The CLN release kinetics from the I-PRF were further characterized. RESULTS: Compared to baseline, both groups independently demonstrated significant improvements in CAL, PD, GML, GI, PI, RLDD and BDA at 3, 6 and 9 months (p < .05). A significant reduction in CAL measurements was noticeable in the CLN/I-PRF + M-MIST and I-PRF + M-MIST group independently over time (p < .05). CLN/I-PRF + M-MIST showed significantly lower CAL than PRF + M-MIST group at baseline, after three as well as 9 months (p < .05). Intergroup comparisons at 9 months demonstrated that CAL-gain was non-significant between groups (p > .05), GI significantly lower in CLN/I-PRF + M-MIST, whereas PD-reduction significantly higher I-PRF + M-MIST group (p < .05). CLN was steadily released for the I-PRF for up to 48 h, with a peak concentration at 24 h, which then gradually declined till the seventh day. CONCLUSIONS: I-PRF with M-MIST provided significant clinical and radiographic improvement up to 9 months postoperatively in stage-III grade B periodontitis. CLN, at the applied concentration and release duration, does not appear to further positively impact these observed I-PRF effects.

An Overview of the Analytical Methods for Products based on Clindamycin and Eco-efficiency Perspectives.

BACKGROUND: Clindamycin (CLIN), an antibiotic sold in the form of capsules, injectable solution, gel, and lotion, is easily soluble in water and ethanol. However, it lacks eco-efficient methods for evaluating pharmaceutical products. OBJECTIVE AND METHOD: The objective of this review is to provide an overview of the analytical methods present both in the literature and in official compendia for evaluating pharmaceutical matrices based on CLIN in the context of Green Analytical Chemistry (GAC). RESULTS: Firstly, microbiological methods for evaluating the potency of CLIN final products were not found, which already shows the need to develop new methods. Among the methods found, which are all physicalchemical, the most used method is HPLC (71%) followed by UV-Vis (14%). Among the targets of the methods, capsules and raw materials were the most studied (33% each). Among the choices of analytical conditions for the methods, acetonitrile is the preferred solvent (27.7%), even though CLIN is easily soluble in ethanol. CONCLUSION: Thus, the gap in eco-friendly and sustainable analytical methods is a reality and an opportunity for analytical development centers to provide means for evaluating the quality of CLIN-based products.

Prevalence of antibiotic-resistant Cutibacterium acnes (formerly Propionibacterium acnes) isolates, A systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess the overall antibiotic susceptibility of Cutibacterium acnes (C. acnes), a bacterium implicated in acne vulgaris, with a particular focus on clindamycin and fluoroquinolones, which are commonly used in inflammatory acne treatment. METHODS: A systematic search of Scopus, PubMed, Web of Science, and EMBASE databases was conducted to identify relevant studies. Pooled prevalence estimates were calculated using a random-effects model, and additional analyses included quality assessment, evaluation of publication bias, meta-regression, and subgroup analyses based on antimicrobial susceptibility methods and year of publication. RESULTS: The analysis incorporated a total of 39 studies. The random-effects model revealed that the proportion of clindamycin-resistant isolates was 0.031 (95% CI: 0.014-0.071). Additionally, macrolides, including erythromycin (0.366; 95% CI, 0.302-0.434) and azithromycin (0.149; 95% CI, 0.061-0.322), exhibited distinct prevalence rates. Tetracyclines, including doxycycline (0.079; 95% CI, 0.014-0.071), tetracycline (0.062; 95% CI, 0.036-0.107), and minocycline (0.025; 95% CI, 0.012-0.051), displayed varying prevalence estimates. Fluoroquinolones, including ciprofloxacin (0.050; 95% CI, 0.017-0.140) and levofloxacin (0.061; 95% CI, 0.015-0.217), demonstrated unique prevalence rates. Additionally, the prevalence of the combination antibiotic trimethoprim/sulfamethoxazole (SXT) was estimated to be 0.087 (95% CI: 0.033-0.208). CONCLUSION: The study findings highlight a concerning increase in antimicrobial-resistant C. acnes with the use of antibiotics in acne treatment. The strategic utilization of appropriate antimicrobials has emerged as a crucial measure to mitigate the emergence of antimicrobial-resistant skin bacteria in acne management.

Clinical characteristics, treatment and outcome of clindamycin induced acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction to clindamycin. This study investigated the clinical features of clindamycin-induced AGEP and provided reference for the prevention and treatment of AGEP. Case reports, case series and clinical studies of clindamycin-induced AGEP were collected by retrieving English and Chinese database from inception until May 31, 2024. Of the 35 patients included, 25 (71.4%) were female, and the median age was 57 years (1.6-88 years). The duration of AGEP onset is 2 days (range 0.04,13) after initial administration. The main clinical morphology of AGEP is a non-follicular pustular on an erythematous base, which may be accompanied by fever (54.3%) and pruritus (40.0%). These lesions mainly involved extremities and trunk. The median elevated neutrophil count was 13.3 × 109/L (range 10.3, 31.4). Histologic features of AGEP are characterized by intracorneal, subcorneal, and/or intraepidermal pustules with papillary dermal edema containing neutrophilic, lymphocytic, andeosinophilic infiltrates. Patients gradually recovered after the withdrawal of clindamycin and supportive therapy with a median time of 9 days (range 2, 30). Clinicians should be aware of AGEP as a rare adverse effect of clindamycin. When clindamycin is prescribed, it should be stopped in time when AGEP occurs, and active systemic treatment should be given. AGEP is a self-limiting disease with a good prognosis.

Standardization of quantitative PCR (qPCR) method to detect the level of parasitaemia in Babesia gibsoni infected dogs.

The present investigation aimed to quantitatively assess the level of parasitemia in dogs using qPCR.The dogs selected for this study were infected with the haemoprotozoan parasite Babesia gibsoni. In the study, dogs diagnosed with babesiosis were divided into two groups (n = 12) and subjected to distinct treatment strategies. The first group received clindamycin-metronidazole-doxycycline (CMD) therapy, while the second group was treated with a combination of buparvaquone-azithromycin (BPV-AZM). The level of parasitemia in the infected dogs was determined using an absolute quantification-based qPCR method. This assessment was conducted both prior to initiating the treatment and on the 10th day following the commencement of the treatment protocols. On the tenth day after the initiation of treatment, the CMD group exhibited a lower level of parasitemia in comparison to the BPV-AZM group. In the CMD treated groups, the mean parasitemia decreased from 4.9E + 06 to 3.4E + 06, indicating a reduction in parasitic load. Conversely, in the BPV-AZM treatment groups, the mean parasitemia increased from 1.62E + 06 to 2.87E + 06, suggesting an increase in parasitic load. On the 10th day, the CMD-treated group demonstrated a statistically significant decline in the level of parasitemia, with a P-value of ≤0.001. This indicates a strong and significant reduction in parasitic load following the CMD treatment. Therefore, the absolute quantification-based qPCR method could effectively assess the initial treatment response by measuring the level of parasitemia.

Antimicrobial Silk Fibroin Methacrylated Scaffolds for Regenerative Endodontics.

INTRODUCTION: Recognizing the necessity of novel disinfection strategies for improved bacterial control to ultimately favor tissue regeneration, this study developed and characterized antibiotics-laden silk fibroin methacrylated (SilkMA) scaffolds for regenerative endodontics. METHODS: SilkMA-based solutions (10% w/v) containing Clindamycin (CLI) or Tinidazole (TIN) (0 - control; 5, 10, or 15% w/w) or the combination of both drugs (BiMix CLI/TIN 10%) were electrospun and photocrosslinked. Morphology and composition were assessed using scanning electron microscopy and Fourier-transform infrared spectroscopy. Additionally, swelling and degradation profiles were also determined. Cytotoxicity was evaluated in stem cells from apical papilla. Antibacterial efficacy was tested using direct and indirect contact assays against Aggregatibacter actinomycetemcomitans/Aa, Actinomyces naeslundii/An, Enterococcus faecalis/Ef, and Fusobacterium nucleatum/Fn. E. faecalis biofilm inhibition on dentin discs was specifically evaluated for BiMix-laden scaffolds. Data were statistically analyzed with a significance level of 5%. RESULTS: Scanning electron microscopy revealed that all scaffolds had similar characteristics, including fiber morphology and bead absence. Fourier-transform infrared spectroscopy showed the incorporation of CLI and TIN into the fibers and in BiMix scaffolds. Antibiotic-laden scaffolds exhibited lower swelling capacity than the control and were degraded entirely after 45 days. Scaffolds laden with CLI, TIN, or BiMix throughout all time points did not reduce stem cells from apical papilla's viability. CLI-laden scaffolds inhibited the growth of Aa, An, and Ef, while TIN-laden scaffolds inhibited Fn growth. BiMix-laden scaffolds significantly inhibited Aa, An, Ef, and Fn in direct contact, and their aliquots inhibited An and Fn through indirect contact, with additional biofilm inhibition against Ef. CONCLUSIONS: BiMix-laden SilkMA scaffolds are cytocompatible and exhibit antimicrobial effects against endodontic pathogens, indicating their therapeutic potential as a drug delivery system for regenerative endodontics.

In vitro studies support clinical trials showing platelet-rich fibrin-mediated local delivery of antibiotics improves outcomes in impacted mandibular third molar surgery.

Our previous clinical observations showed that platelet rich fibrin (PRF) can be used to deliver antibiotics to attenuate postoperative complications after unilaterally impacted mandibular third molar surgery (IMTMS). In order to begin understanding the mechanism involved in the beneficial in vivo effects of PRF-mediated delivery of antibiotics, in vitro studies were performed, which showed that PRF preparations containing amoxicillin/clavulanic acid or clindamycin significantly inhibited the growth of S. aureus bacteria. In our previous study, comparisons were made between control and treated groups. However, since variations among individual patients could possibly affect the results, the current study included patients with bilaterally symmetric impacted mandibular third molars, allowing us to compare control and antibiotic treatment within each patient. The effects of PRF preparations containing amoxicillin/clavulanic acid or clindamycin on IMTMS was tested in 60 clinical cases. Antibiotic-injected PRF treatment after bilaterally IMTMS resulted in significantly reduced pain, less use of analgesics, and reduced swelling and trismus compared to the control group (PRF without antibiotics) confirming our previous results after unilaterally IMTMS. The in vitro results support the hypothesis that in vivo delivery of antibiotics using PRF produces therapeutic effects after IMTMS by attenuating bacterial infection and inflammation.

IN VITRO ANTIMICROBIAL ACTIVITY OF Schinus terebinthifolia Raddi METRONIDAZOLE, CLINDAMYCIN AGAINST Lactobacillus gassari Lauer and Kandler AND ITS IMPLICATIONS IN RECURRENT BACTERIAL VAGINOSIS / ATIVIDADE ANTIMICROBIANA DE Schinus terebinthifolia Raddi METRONIDAZOL, CLINDAMICINA E CONTRA Lactobacillus gassari Lauer and Kandler, IN VITRO, E SUAS IMPLICAÇÕES NA VAGINOSE BACTERIANA RECIDIVANTE

Bacterial vaginosis (BV) is very prevalent and is the most common cause of vaginal discharge worldwide. It is a dysbiosis resulting from the replacement of hydrogen peroxide and lactic acid-producing lactobacilli by anaerobic bacteria in high concentrations, including Gardnerella vaginalis, Prevotella, Mobiluncus, Atopobium and other anaerobes. BV can be self-diagnosed when the patient presents the classic symptoms, or clinically and laboratory-based, following the Amsel criteria or by determining the Nugent score. The recommended treatments for BV are oral metronidazole, secnidazole and tinidazole, as well as vaginal metronidazole gel, clindamycin cream and Schinus terebinthifolia Raddi gel. The present study aimed to determine the ability of vaginal clindamycin cream, vaginal metronidazole gel and S. terebinthifolia Raddi vaginal gel to inhibit the growth or preserve the population of Lactobacillus gasseri ATCC 19992 microorganisms in vitro. The methodology used was perforation in plates, forming 6 mm wells, where the samples were inoculated. The plates were incubated for 48 hours at 30°C. After this period, by visual plates analysis, was observed that L. gasseri is resistant to S. terebinthifolia Raddi vaginal gel since no inhibition halo was observed. However, L. gasseri was moderately susceptible to Metronidazole vaginal gel and highly sensitive to Clindamycin vaginal cream. As lactobacilli, of which L. gasseri stands out, represent over 95% of the microorganisms 3/16 that inhabit the vaginal environment, maintaining the health of this microbiome, the action of Clindamycin and Metronidazole can lead to an imbalance in the vaginal microbiota, allowing relapses when these therapeutic agents are used to treat BV.

A vaginose bacteriana (VB) é muito prevalente e é a causa mais comum de corrimento vaginal em todo o mundo. Trata-se de uma disbiose resultante da substituição dos lactobacilos produtores de peróxido de hidrogênio e ácido lático por bactérias anaeróbicas em altas concentrações, incluindo Gardnerella vaginalis, Prevotella, Mobiluncus, Atopobium e outros anaeróbios. A VB pode ser autodiagnosticada, quando a paciente apresenta a sintomatologia clássica, ou clínica e laboratorialmente obedecendo aos critérios de Amsel ou pela determinação do escore de Nugent. Os tratamentos recomendados para a VB são o Metronidazol, o Secnidazol e o Tinidazol por via oral, bem como o metronidazol gel, a clindamicina creme e o gel de S. terebinthifolia Raddi por via vaginal. O presente estudo teve por objetivo determinar a capacidade da Clindamicina creme vaginal, do Metronidazol gel vaginal e do S. terebinthifolia Raddi gel vaginal em inibir o crescimento ou preservar a população dos microrganismos Lactobacillus gasseri ATCC 19992 in vitro. A metodologia utilizada foi de perfuração em placa, formando poços de 6mm, onde as amostras foram inoculadas. As placas foram incubadas por 48 horas à temperatura de 30°C. A análise visual das placas, após o período de incubação, evidenciou que L. gasseri é resistente ao gel vaginal de S. terenbithifolia Raddi gel, uma vez que não foi observado qualquer halo de inibição. Contudo, L. gasseri foi moderadamente susceptível ao gel vaginal de Metronidazol e altamente sensível ao creme vaginal de Clindamicina. Como os lactobacilos, dos quais se destaca L. gasseri, representam acima de 95% dos microrganismos que habitam o meio vaginal, mantendo a higidez desse microbioma, a ação da Clindamicina e do Metronidazol pode levar ao desequilíbrio da microbiota vaginal, permitindo as recidivas quando esses agentes terapêuticos são usados para o tratamento da VB.

Enhanced Antibacterial Activity of Clindamycin Using Molecularly Imprinted Polymer Nanoparticles Loaded with Polyurethane Nanofibrous Scaffolds for the Treatment of Acne Vulgaris.

Acne vulgaris, a prevalent skin condition, arises from an imbalance in skin flora, fostering bacterial overgrowth. Addressing this issue, clindamycin molecularly imprinted polymeric nanoparticles (Clin-MIP) loaded onto polyurethane nanofiber scaffolds were developed for acne treatment. Clin-MIP was synthesized via precipitation polymerization using methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), and azoisobutyronitrile (AIBN) as functional monomers, crosslinkers, and free-radical initiators, respectively. MIP characterization utilized Fourier-transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) before being incorporated into polyurethane nanofibers through electrospinning. Further analysis involved FTIR, scanning electron microscopy (SEM), in vitro release studies, and an ex vivo study. Clin-MIP showed strong antibacterial activity against S. aureus, with inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.39 and 6.25 µg/mL, respectively. It significantly dropped the bacterial count from 1 × 108 to 39 × 101 CFU/mL in vivo and has bactericidal activity within 180 min of incubation in vitro. The pharmacodynamic and histopathology studies revealed a significant decrease in infected animal skin inflammation, epidermal hypertrophy, and congestion upon treatment with Clin-MIP polyurethane nanofiber and reduced pro-inflammatory cytokines (NLRP3, TNF-α, IL-1ß, and IL-6) conducive to acne healing. Consequently, the recently created Clin-MIP polyurethane nanofibrous scaffold. This innovative approach offers insight into creating materials with several uses for treating infectious wounds caused by acne.

Development of Clindamycin-Releasing Polyvinyl Alcohol Hydrogel with Self-Healing Property for the Effective Treatment of Biofilm-Infected Wounds.

Self-healing hydrogels have good mechanical strength, can endure greater external force, and have the ability to heal independently, resulting in a strong bond between the wound and the material. Bacterial biofilm infections are life-threatening. Clindamycin (Cly) can be produced in the form of a self-healing hydrogel preparation. It is noteworthy that the antibacterial self-healing hydrogels show great promise as a wound dressing for bacterial biofilm infection. In this study, we developed a polyvinyl alcohol/borax (PVA/B) self-healing hydrogel wound dressing that releases Cly. Four ratios of PVA, B, and Cly were used to make self-healing hydrogels: F1 (4%:0.8%:1%), F2 (4%:1.2%:1%), F3 (1.6%:1%), and F4 (4%:1.6%:0). The results showed that F4 had the best physicochemical properties, including a self-healing duration of 11.81 ± 0.34 min, swelling ratio of 85.99 ± 0.12%, pH value of 7.63 ± 0.32, and drug loading of 98.34 ± 11.47%. The B-O-C cross-linking between PVA and borax caused self-healing, according to FTIR spectra. The F4 formula had a more equal pore structure in the SEM image. The PVA/B-Cly self-healing hydrogel remained stable at 6 ± 2 °C for 28 days throughout the stability test. The Korsmeyer-Peppas model released Cly by Fickian diffusion. In biofilm-infected mouse wounds, PVA/B-Cly enhanced wound healing and re-epithelialization. Our results indicate that the PVA/B-Cly produced in this work has reliable physicochemical properties for biofilm-infected wound therapy.

Tracking trends in the Top End: clindamycin and erythromycin resistance in Group A Streptococcus in the Northern Territory, 2012-2023.

Abstract: This retrospective study reviewed the macrolide resistance rates of Group A Streptococcus (GAS) isolates in the Northern Territory from 2012 to 2023. Clindamycin and erythromycin resistance rates peaked in 2021, at 6.0% and 12.2% respectively, and then returned to near baseline at 1-2% in 2023. Increased resistance rates were identified in the Top End of Australia from mid-2020, followed 15 months later by high rates in central Australia in 2022. Factors associated with resistant isolates were living in a rural region and of age 18 years and older. Possible explanations include a transient clonal introduction of a resistant GAS strain to the Northern Territory from 2020 to 2022. Ongoing surveillance is required to monitor regional trends and identify temporal variations in resistant isolates.

Rising clindamycin resistance in group A Streptococcus in an Irish healthcare institution.

Group A streptococcus (GAS) can cause serious invasive disease in humans with a high mortality rate. An increase in GAS infections was reported in Ireland in 2022, and this increase has been sustained in 2023 and is paralleled by similar trends in Europe. Rising antimicrobial resistance is a global problem and presents significant challenges to clinicians treating GAS infection. There was a reported increase in clindamycin resistance in GAS isolates in Ireland in 2022. We examined antimicrobial susceptibility patterns of GAS isolates in our institution in 2022. Although all GAS isolates included in our study were susceptible to penicillin, we noted a high clindamycin resistance rate of 28 % in our invasive GAS isolates. We also noted high tetracycline and erythromycin resistance, 43 and 30 %, respectively. Our results could have implications for empiric antimicrobial prescribing guidelines for skin and soft tissue infections, which often include clindamycin as it inhibits the production of many virulence factors associated with GAS. In addition, macrolides are often the first line recommended antibiotic for patients with anaphylaxis to penicillin. This study emphasises the importance of continuous surveillance and antimicrobial susceptibility testing of invasive and non-invasive isolates in order to monitor trends in increasing antimicrobial resistance.

Updates on Topical Dyad and Triple Combination Therapies Approved for Acne Vulgaris.

Acne vulgaris is a multifaceted disease characterized by inflammatory and noninflammatory lesions. Topical combination therapies offer a multifaceted approach to acne treatment, with synergistic effects and a broad spectrum of action against multiple factors in acne pathogenesis in one single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene, a combination therapy consisting of clindamycin phosphate 1.2%, benzoyl peroxide (BPO) 3.1%, and adapalene 0.15%, is a novel treatment, the only FDA-approved triple combination drug that offers effective treatment of acne vulgaris. This review aims to provide information on clindamycin phosphate/benzoyl peroxide/adapalene and review the literature on combination topical acne medications approved in the United States. This search was conducted on topical combination therapies for acne, their efficacy, adverse effects, and impacts on quality of life with a specific focus on the newly approved clindamycin phosphate/benzoyl peroxide/adapalene and its sub-component dyads, along with other combinations. PubMed, SCOPUS, Embase, Cochrane, and Web of Science databases were searched for publications in 2018-2023. Primary sources were given priority, and secondary sources such as other reviews were considered to supplement any missing information. It was found that various topical dyad and triad combinations exist for acne vulgaris, including adapalene/BPO, tazarotene/clindamycin, clindamycin/BPO, adapalene/clindamycin, topical tretinoin/azelaic acid, topical tretinoin/BPO, and clindamycin phosphate/benzoyl peroxide/adapalene. Dyad and triple combinations represent a promising, convenient solution for acne management, potentially improving patient adherence due to its single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene exhibited significantly high efficacy in treating both inflammatory and noninflammatory lesions, a minimal side effect profile, although no significant changes in quality-of-life measures. Further research is indicated to assess its long-term efficacy and impact on other acne metrics such as cost, scarring, psychosocial implications, and impact on diverse patient populations.

Does adjunctive clindamycin have a role in Staphylococcus aureus bacteremia? A protocol for the adjunctive treatment domain of the S. aureus Network Adaptive Platform (SNAP) randomized controlled trial.

INTRODUCTION: The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and is recommended in many guidelines, but there is limited evidence underpinning this. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leucocidins (e.g., Panton-Valentine Leucocidin (PVL), toxic shock syndrome toxin 1 (TSST-1), exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question. METHODS AND ANALYSIS: The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multi-center adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either five days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard of care antibiotics. Most participants with SAB (within 72hr of index blood culture and not contraindicated) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and PVL-positive isolate.

Co-resistance to methicillin and clindamycin among coagulase-negative staphylococci isolates recovered from pet food in Brazil.

Pet food have been considered as possible vehicles of bacterial pathogens. The sudden boom of the pet food industry due to the worldwide increase in companion animal ownership calls for pet food investigations. Herein, this study aimed to determine the frequency, antimicrobial susceptibility profile, and molecular characteristics of coagulase-negative staphylococci (CoNS) in different pet food brands in Brazil. Eighty-six pet food packages were screened for CoNS. All isolates were identified at species level by MALDI-TOF MS and species-specific PCR. Antimicrobial susceptibility testing was performed by disc diffusion and broth microdilution (vancomycin and teicoplanin only) methods. The D-test was used to screen for inducible clindamycin phenotype (MLS-B). SCCmec typing and detection of mecA, vanA, vanB, and virulence-encoding genes were done by PCR. A total of 16 (18.6 %) CoNS isolates were recovered from pet food samples. Isolates were generally multidrug-resistant (MDR). All isolates were completely resistant (100 %) to penicillin. Resistances (12.5 % - 75 %) were also observed for fluoroquinolones, sulfamethoxazole-trimethoprim, tetracycline, rifampicin, erythromycin, and tobramycin. Isolates were susceptible to vancomycin (MICs <0.25-1 µg/mL) and teicoplanin (MICs <0.25-4 µg/mL). Intriguingly, 3/8 (37.5 %) CoNS isolates with the ERYRCLIS antibiotype expressed MLS-B phenotype. All isolates harboured blaZ gene. Seven (43.8 %) isolates carried mecA; and among them, the SCCmec Type III was the most frequent (n = 5/7; 71.4 %). Isolates also harboured seb, see, seg, sej, sem, etb, tsst, pvl, and hla toxin virulence-encoding genes (6.3 % - 25 %). A total of 12/16 (75 %) isolates were biofilm producers, while the icaAB gene was detected in an S. pasteuri isolate. Herein, it is shown that pet food is a potential source of clinically important Gram-positive bacterial pathogens. To the best of our knowledge, this is the first report of MLS-B phenotype and MR-CoNS in pet food in Latin America.

The Effect of Adding Various Antibiotics on the Push-out Bond Strength of a Resin-based Sealer: An In Vitro Study.

AIM: This study aimed to compare the bond strength of AH Plus sealer to root canal dentin when used with or without various antibiotics including amoxicillin, clindamycin, and triple antibiotic mixture (TAM). MATERIALS AND METHODS: A total of 80 single-rooted extracted human teeth were instrumented and obturated with gutta-percha and four different sealer-antibiotic combinations (n = 20). Group I: AH Plus without any antibiotics, Group II: AH Plus with amoxicillin, Group III: AH Plus with clindamycin, and Group IV: AH Plus with TAM. After seven days, the roots were sectioned perpendicular to their long axis and 1 mm thick slices were obtained from the midroots. The specimens were subjected to a push-out bond strength test and failure modes were also evaluated. Data was analyzed using Kruskal-Wallis and Dunn's post hoc tests. RESULTS: Group IV had significantly higher bond strength compared to other groups (p ≤ 0.05). No significant differences were found between other groups. While the sealer-antibiotic groups predominantly showed cohesive failure modes, the control group displayed both cohesive and mixed failure modes. CONCLUSION: Within the limitations of this study, the addition of TAM increased the push-out bond strength of AH Plus. CLINICAL SIGNIFICANCE: Amoxicillin, clindamycin, or TAM can be added to AH Plus for increased antibacterial efficacy without concern about their effects on the bond strength of the sealer. How to cite this article: Adl A, Shojaei NS, Ranjbar N. The Effect of Adding Various Antibiotics on the Push-out Bond Strength of a Resin-based Sealer: An In Vitro Study. J Contemp Dent Pract 2024;25(3):231-235.

Biofilm of Cutibacterium acnes: a target of different active substances.

BACKGROUND: Acne vulgaris is a chronic inflammatory dermatosis. Cutibacterium acnes plays a crucial role in the acne pathophysiology. Recent works present evidence of C. acnes growing as a biofilm in cutaneous follicles. This development is currently considered one of the leading causes of C. acnes in vivo persistence and resistance to antimicrobials used to treat acne. OBJECTIVE: Our objective was to evaluate the effects of various active compounds (clindamycin, erythromycin, doxycycline, and myrtle extract) on eight distinct, well-characterized strains of C. acnes following their growth in biofilm mode. METHODS/RESULTS: Cutibacterium acnes isolates from phylotypes IA1 and IA2 produce more biofilm than other phylotypes. No antibiotic effect was observed either during the curative test or preventive test. Myrtle extract at 0.01% (w/v) showed significant efficacy on the biofilm for C. acnes strains (curative assays). Furthermore, it appear that myrtle extract and doxycycline together reduce the overall biomass of the biofilm. A significant dose-dependent effect was observed during the preventive test, greater than the one observed under curative conditions, with an important loss of activity of the myrtle extract observed from 0.001% (w/v) concentration onwards. Transmission electron microscopy showed that bacteria treated with myrtle extract grew biofilms much less frequently than untreated bacteria. Additionally, when the quantity of myrtle extract grew, the overall number of bacteria dropped, indicating an additional antibacterial action. CONCLUSION: These findings support the hypothesis that the different C. acnes phylotypes have various aptitudes in forming biofilms. They also suggest that myrtle extract is a promising alternative as an anti-biofilm and antibacterial agent in fighting diseases caused by planktonic and biofilm C. acnes.

A Diagnostic Dilemma: Clindamycin-Resistant Group A Streptococcal Toxic Shock Syndrome Leading to Acute Respiratory Distress Syndrome (ARDS) With Multiple Possible Sources.

Group A Streptococcal (GAS) infections can potentially progress into streptococcal toxic shock syndrome (STSS) with multiorgan failure. Even with a benign presentation, GAS can rapidly lead to fatal necrotizing infections. While myositis and cutaneous infections are the typical initial presentation of STSS, genitourinary infections are a less common source. This report presents a case of a previously healthy woman with the chief complaint of ankle pain who subsequently developed streptococcal toxic shock syndrome and multiorgan failure from a Group A streptococcus infection of the genitourinary tract. She was treated with antibiotics and medical management for her septic shock and required prone ventilation for her acute respiratory distress syndrome (ARDS) but eventually recovered without surgery. This case highlights the importance of recognizing unusual presentations of Group A Strep infections, which have the potential to lead to rapid deterioration in patients. Also described are antibiotic and ventilator strategies that can be used to treat these severe systemic infections.

Thermosensitive and mucoadhesive gels containing solid lipid nanoparticles loaded with fluconazole and niosomes loaded with clindamycin for the treatment of periodontal diseases: a laboratory experiment.

BACKGROUND: Periodontal diseases may benefit more from topical treatments with nanoparticles rather than systemic treatments due to advantages such as higher stability and controlled release profile. This study investigated the preparation and characterization of thermosensitive gel formulations containing clindamycin-loaded niosomes and solid lipid nanoparticles (SLNs) loaded with fluconazole (FLZ), as well as their in vitro antibacterial and antifungal effects in the treatment of common microorganisms that cause periodontal diseases. METHODS: This study loaded niosomes and SLNs with clindamycin and FLZ, respectively, and assessed their loading efficiency, particle size, and zeta potential. The particles were characterized using a variety of methods such as differential scanning calorimetry (DSC), dynamic light scattering (DLS), and Transmission Electron Microscopy (TEM). Thermosensitive gels were formulated by combining these particles and their viscosity, gelation temperature, in-vitro release profile, as well as antibacterial and antifungal effects were evaluated. RESULTS: Both types of these nanoparticles were found to be spherical (TEM) with a mean particle size of 243.03 nm in niosomes and 171.97 nm in SLNs (DLS), and respective zeta potentials of -23.3 and -15. The loading rate was 98% in niosomes and 51% in SLNs. The release profiles of niosomal formulations were slower than those of the SLNs. Both formulations allowed the release of the drug by first-order kinetic. Additionally, the gel formulation presented a slower release of both drugs compared to niosomes and SLNs suspensions. CONCLUSION: Thermosensitive gels containing clindamycin-loaded niosomes and/or FLZ-SLNs were found to effectively fight the periodontitis-causing bacteria and fungi.