RESUMO
INTRODUCTION: Diabetic foot infection (DFI) is one of the complications of diabetes mellitus. Clindamycin (CLY) is one of the antibiotics recommended to treat DFI, but CLY given orally and intravenously still causes many side effects. METHODS: In this study, we encapsulated CLY in a bacteria sensitive microparticle system (MP-CLY) using polycaprolactone (PCL) polymer. MP-CLY was then delivered in a separable effervescent microarray patch (MP-CLY-SEMAP), which has the ability to separate between the needle layer and separable layer due to the formation of air bubbles when interacting with interstitial fluid in the skin. RESULT: The characterization results of MP-CLY proved that CLY was encapsulated in large amounts as the amount of PCL polymer used increased, and there was no change in the chemical structure of CLY. In vitro release test results showed increased CLY release in media cultured with Staphylococcus aureus bacteria and showed controlled release. The characterization results of MPCLY-SEMAP showed that the developed formula has optimal mechanical and penetration capabilities and can separate in 56 ± 5.099 s. An ex vivo dermatokinetic test on a bacterially infected skin model showed an improvement of CLY dermatokinetic profile from MP-CLY SEMAP and a decrease in bacterial viability by 99.99%. CONCLUSION: This research offers proof of concept demonstrating the improved dermatokinetic profile of CLY encapsulated in a bacteria sensitive MP form and delivered via MP-CLY-SEMAP. The results of this research can be developed for future research by testing MP-CLY-SEMAP in vivo in appropriate animal models.
Assuntos
Antibacterianos , Clindamicina , Pé Diabético , Pele , Staphylococcus aureus , Clindamicina/administração & dosagem , Pé Diabético/tratamento farmacológico , Pé Diabético/microbiologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Pele/microbiologia , Pele/metabolismo , Poliésteres/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Administração Cutânea , Adesivo Transdérmico , Humanos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Portadores de Fármacos/químicaRESUMO
BACKGROUND: Adalimumab monotherapy for hidradenitis suppurativa (HS) is often insufficient with a maximum clinical efficacy of 60% in Hidradenitis Suppurativa Clinical Response (HiSCR) and limited effect on draining tunnels. Data suggest that adalimumab therapy could be improved by concomitant antibiotics. OBJECTIVE: To compare the clinical effectiveness of adalimumab with clindamycin and rifampicin versus adalimumab monotherapy after 12 weeks. METHODS: This retrospective study included patients who started adalimumab with additional clindamycin and rifampicin and patients treated with adalimumab monotherapy, matched on sex and refined Hurley score. The primary outcome measure was the difference in change in the International Hidradenitis Suppurativa Severity Score System (IHS4) at 12 weeks. RESULTS: In total, 62 patients were included in the combination therapy group (n = 31) and adalimumab monotherapy group (n = 31), showing comparable IHS4 scores; 32.5 versus 29, p = 0.87 at baseline respectively. The combination therapy demonstrated greater clinical effectiveness expressed in median IHS4 improvement (-20 vs. -9, p < 0.001), IHS4-55 (74% vs. 36%, p = 0.002), median draining tunnel reduction (-4 vs. -2, p < 0.001) and pain response (47% vs. 27%, p = 0.02). CONCLUSION: Adalimumab initiated with clindamycin and rifampicin shows greater clinical effectiveness than adalimumab monotherapy. An important difference in effect was observed in the decrease of draining tunnels, addressing a serious limitation of adalimumab monotherapy.
Assuntos
Adalimumab , Clindamicina , Quimioterapia Combinada , Hidradenite Supurativa , Rifampina , Humanos , Hidradenite Supurativa/tratamento farmacológico , Adalimumab/uso terapêutico , Adalimumab/administração & dosagem , Rifampina/uso terapêutico , Rifampina/administração & dosagem , Clindamicina/uso terapêutico , Clindamicina/administração & dosagem , Estudos Retrospectivos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: A once-daily, three-pronged approach using an antibiotic, antibacterial, and retinoid may provide faster acne improvement versus monotherapy or dual-combination products. This post hoc analysis compared threshold acne lesion reductions with clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel—the first FDA-approved triple-combination topical acne product—to its dyads and vehicle. METHODS: Phase 2 (N=741; NCT03170388) and phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, 12-week studies randomized participants aged ≥9 years with moderate-to-severe acne to once-daily CAB or vehicle gel; the phase 2 study included three additional dyad gel arms. The pooled percentage of participants achieving ≥33%, ≥50%, and ≥75% reduction in inflammatory and noninflammatory acne lesions was evaluated. RESULTS: As early as week 4 in the phase 2 study, ≥33% reduction in inflammatory lesions occurred in a significantly greater percentage of CAB gel-treated participants (82.7%) than with the 3 dyads and vehicle (61.1-69.8%; P<0.05, all). These early reductions were sustained throughout the study, with significantly (P<0.05) more CAB-treated participants achieving ≥50% reduction in inflammatory lesions versus dyads and vehicle from weeks 4-12. By week 12, CAB led to substantial reductions of ≥75% in significantly more participants than dyads and vehicle (65.8% vs 49.9-51.2% and 21.6%; P<0.05, all). Similar trends were observed for noninflammatory lesions in the phase 2 study and for inflammatory and noninflammatory lesions in the phase 3 studies. CONCLUSIONS: Lesion count reductions were significantly greater with CAB versus its dyads and vehicle gel as early as week 4, with substantial reductions observed after 12 weeks of treatment. This faster-acting and sustained efficacy of CAB gel—coupled with its optimized formulation, once-daily dosing, and tolerability—may positively impact treatment adherence. J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7907.
Assuntos
Acne Vulgar , Combinação Adapaleno e Peróxido de Benzoil , Clindamicina , Humanos , Acne Vulgar/diagnóstico , Acne Vulgar/tratamento farmacológico , Antibacterianos/administração & dosagem , Clindamicina/administração & dosagem , CriançaRESUMO
Clindamycin is a lincosamide-derivate antibiotic that has been widely used both systemically and topically for approximately 5 decades. The antimicrobial profile of clindamycin primarily covers several gram-positive bacteria and anaerobic bacteria, with multiple clinical applications supported in the literature and with widespread real-world use. Topical clindamycin has been used primarily for the treatment of acne vulgaris, with both monotherapy and combination therapy formulations available commercially. This article reviews the use of clindamycin as a topical agent with emphasis on therapy for acne vulgaris, and addresses modes of action, reported anti-inflammatory properties that may relate to therapeutic outcomes, recommendations to avoid the emergence of antibiotic-resistant bacteria, tolerability and safety considerations, and published data from clinical studies completed over a span of several years. A discussion of a newly FDA-approved triple-combination formulation is also included. J Drugs Dermatol. 2024;23(6):438-445. doi:10.36849/JDD.8318.
Assuntos
Acne Vulgar , Administração Cutânea , Antibacterianos , Clindamicina , Humanos , Acne Vulgar/tratamento farmacológico , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Resultado do Tratamento , Farmacorresistência BacterianaRESUMO
BACKGROUND: Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined. METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values. Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle). CONCLUSIONS: Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.8148.
Assuntos
Acne Vulgar , Fármacos Dermatológicos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Acne Vulgar/tratamento farmacológico , Acne Vulgar/diagnóstico , Humanos , Resultado do Tratamento , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Administração Cutânea , Combinação de Medicamentos , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Administração OralRESUMO
BACKGROUND: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) is the first fixed-dose triple-combination approved for the treatment of acne. This post hoc analysis investigated the efficacy and safety of CAB in pediatric (<18 years) and adult (greater than or equal to 18 years) participants. METHODS: In two multicenter, double-blind, phase 3 studies (NCT04214639 and NCT04214652), participants greater than or equal to 9 years of age with moderate-to-severe acne were randomized (2:1) to 12 weeks of once-daily treatment with CAB or vehicle gel. Pooled data were analyzed for pediatric and adult subpopulations. Assessments included treatment success (greater than or equal to 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 0 [clear] or 1 [almost clear], inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At week 12, treatment success rates for both pediatric and adult participants were significantly greater with CAB (52.7%; 45.9%) than with vehicle (24.0%; 23.5%; P<0.01, both). CAB-treated participants in both subgroups experienced greater reductions from baseline versus vehicle in inflammatory (pediatric: 78.6% vs 50.4%; adult: 76.6% vs 62.8%; P<0.001, both) and noninflammatory lesions (pediatric: 73.8% vs 41.1%; adult: 70.7% vs 52.2%; P<0.001, both). Acne-QoL improvements from baseline to week 12 were significantly greater with CAB than with a vehicle. Most TEAEs were of mild-to-moderate severity; no age-related trends for safety/tolerability were observed. Conclusions: CAB gel demonstrated comparable efficacy, quality of life improvements, and safety in pediatric and adult participants with moderate-to-severe acne. As the first fixed-dose, triple-combination topical formulation, CAB represents an important new treatment option for patients with acne. J Drugs Dermatol. 2024;23(6):394-402. doi:10.36849/JDD.8357.
Assuntos
Acne Vulgar , Peróxido de Benzoíla , Clindamicina , Fármacos Dermatológicos , Combinação de Medicamentos , Géis , Qualidade de Vida , Humanos , Acne Vulgar/tratamento farmacológico , Clindamicina/administração & dosagem , Clindamicina/efeitos adversos , Clindamicina/análogos & derivados , Criança , Método Duplo-Cego , Adolescente , Feminino , Masculino , Adulto , Peróxido de Benzoíla/administração & dosagem , Peróxido de Benzoíla/efeitos adversos , Resultado do Tratamento , Adulto Jovem , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Administração Cutânea , Índice de Gravidade de DoençaRESUMO
Bone infections are still a major problem in surgery. To avoid severe side effects of systemically administered antibiotics, local antibiotic therapy is increasingly being considered. Using a pressure-based method developed in our group, microporous ß-TCP ceramics, which had previously been characterized, were loaded with 2% w/v alginate containing 50 mg/mL clindamycin and 10 µg/mL rhBMP-2. Release experiments were then carried out over 28 days with changes of liquid at defined times (1, 2, 3, 6, 9, 14, 21 and 28d). The released concentrations of clindamycin were determined by HPLC and those of rhBMP-2 by ELISA. Continuous release (anomalous transport) of clindamycin and uniform release (Fick's diffusion) of BMP-2 were determined. The composites were biocompatible (live/dead, WST-I and LDH) and the released concentrations were all antimicrobially active against Staph. aureus. The results were very promising and clindamycin was detected in concentrations above the MIC as well as a constant rhBMP-2 release over the entire study period. Biocompatibility was also not impaired by either the antibiotic or the BMP-2. This promising approach can therefore be seen as an alternative to the common treatment with PMMA chains containing gentamycin, as the new composite is completely biodegradable and no second operation is necessary for removal or replacement.
Assuntos
Antibacterianos , Materiais Biocompatíveis , Proteína Morfogenética Óssea 2 , Clindamicina , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/farmacocinética , Clindamicina/administração & dosagem , Clindamicina/química , Clindamicina/farmacocinética , Humanos , Materiais Biocompatíveis/química , Staphylococcus aureus/efeitos dos fármacos , Cinética , Fosfatos de Cálcio/química , Animais , Teste de Materiais , Proteínas Recombinantes/química , Cerâmica/química , Fator de Crescimento Transformador beta , Alginatos/química , Implantes Absorvíveis , Testes de Sensibilidade MicrobianaRESUMO
Targeted therapy represents a real opportunity to improve the health and lives of patients. Developments in this field are confirmed by the fact that the global market for drug carriers was worth nearly $40 million in 2022. For this reason, materials engineering and the development of new drug carrier compositions for targeted therapy has become a key area of research in pharmaceutical drug delivery in recent years. Ceramics, polymers, and metals, as well as composites, are of great interest, as when they are appropriately processed or combined with each other, it is possible to obtain biomaterials for hard tissues, soft tissues, and skin applications. After appropriate modification, these materials can release the drug directly at the site requiring a therapeutic effect. This brief literature review characterizes routes of drug delivery into the body and discusses biomaterials from different groups, options for their modification with clindamycin, an antibiotic used for infections caused by aerobic and anaerobic Gram-positive bacteria, and different methods for the final processing of carriers. Examples of coating materials for skin wound healing, acne therapy, and bone tissue fillers are given. Furthermore, the reasons why the use of antibiotic therapy is crucial for a smooth and successful recovery and the risks of bacterial infections are explained. It was demonstrated that there is no single proven delivery scheme, and that the drug can be successfully released from different carriers depending on the destination.
Assuntos
Antibacterianos , Infecções Bacterianas , Materiais Biocompatíveis , Clindamicina , Sistemas de Liberação de Medicamentos , Humanos , Clindamicina/uso terapêutico , Clindamicina/administração & dosagem , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos/métodos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Portadores de Fármacos/química , AnimaisRESUMO
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.
Assuntos
Clindamicina , Fluconazol , Géis , Lipossomos , Nanopartículas , Tamanho da Partícula , Doenças Periodontais , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Nanopartículas/química , Fluconazol/administração & dosagem , Fluconazol/farmacologia , Doenças Periodontais/tratamento farmacológico , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Microscopia Eletrônica de Transmissão , Temperatura , Varredura Diferencial de Calorimetria , Candida albicans/efeitos dos fármacos , Viscosidade , Lipídeos/química , HumanosRESUMO
PURPOSE: The aim of this study was to quantify the prophylactic effect of high-dose gentamicin and clindamycin antibiotic-loaded bone cement (ALBC) during revision total hip (rTHA) or knee (rTKA) arthroplasty for aseptic reasons. The hypothesis was that the raw surgical site infection (SSI) rate is lower when this particular cement is used in comparison with cement loaded with standard-dose gentamicin during rTHA or rTKA for aseptic reasons. METHODS: This retrospective study included 290 consecutive patients undergoing aseptic rTHA or rTKA. Two consecutive cohorts were defined: the first (control group) involved 145 patients where ALBC with gentamicin only was used; the second (study group) involved 145 patients where ALBC with high-dose gentamicin and clindamycin was used. The primary endpoint was the raw SSI rate after 24 months. RESULTS: The raw SSI rate was 8/145 (6%) in the control group and 13/145 (9%) in the study group (odds ratio 0.62, p = 0.26). There was a significant impact of the presence of any risk factor on the SSI rate (15/100 versus 6/169, odds ratio = 4.25, p = 0.002), but no significant impact of any individual risk factor. No complication or side effect related to ALBC was observed in either group. CONCLUSION: These results do not support the routine use of gentamicin and clindamycin ALBC for fixation of revision implants after rTHA and rTKA for aseptic reasons.
Assuntos
Antibacterianos , Artroplastia de Quadril , Artroplastia do Joelho , Cimentos Ósseos , Clindamicina , Gentamicinas , Infecções Relacionadas à Prótese , Reoperação , Infecção da Ferida Cirúrgica , Humanos , Gentamicinas/administração & dosagem , Clindamicina/administração & dosagem , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Estudos Retrospectivos , Masculino , Feminino , Artroplastia do Joelho/efeitos adversos , Idoso , Antibacterianos/administração & dosagem , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/prevenção & controle , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/etiologia , Fatores de RiscoRESUMO
PURPOSE OF REVIEW: The aim of this study was to present recent microbiological, experimental, clinical and tolerance data for cotrimoxazole and clindamycin in the specific field of skin and soft tissue infections (SSTIs). RECENT FINDINGS: Staphylococcus aureus and streptococci remain the leading cause of SSTIs. Cotrimoxazole is a good anti-Gram-positive agent with preserved activity against methicillin-susceptible and methicillin-resistant S. aureus (MRSA) and streptococci. Although clindamycin has good methicillin-susceptible S. aureus activity, a growing number of resistant MRSA and streptococci have been reported. Strong experimental data support the antitoxin activity of clindamycin, but clinical observations remain scarce. Several recent randomized trials involving cotrimoxazole and/or clindamycin demonstrate the efficacy and tolerance of both drugs. The oral formulation of both drugs may facilitate the implementation of early switch and early discharge protocols in clinical practice. SUMMARY: Recent publications demonstrate that cotrimoxazole and clindamycin remain reliable and realistic therapeutic approaches for SSTIs.
Assuntos
Antibacterianos/administração & dosagem , Clindamicina/administração & dosagem , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Animais , Quimioterapia Combinada , Humanos , Infecções dos Tecidos Moles/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
BACKGROUND: Exotoxins secreted from Staphylococcus aureus or Streptococcus pyogenes act as superantigens that induce systemic release of inflammatory cytokines and are a common cause of toxic shock syndrome (TSS). However, little is known about TSS caused by coagulase-negative staphylococci (CoNS) and the underlying mechanisms. Here, we present a rare case of TSS caused by Staphylococcus simulans (S. simulans). CASE PRESENTATION: We report the case of a 75-year-old woman who developed pneumococcal pneumonia and bacteremia from S. simulans following an influenza infection. The patient met the clinical criteria for probable TSS, and her symptoms included fever of 39.5 °C, diffuse macular erythroderma, conjunctival congestion, vomiting, diarrhea, liver dysfunction, and disorientation. Therefore, the following treatment was initiated for bacterial pneumonia complicating influenza A with suspected TSS: meropenem (1 g every 8 h), vancomycin (1 g every 12 h), and clindamycin (600 mg every 8 h). Blood cultures taken on the day after admission were positive for CoNS, whereas sputum and pharyngeal cultures grew Streptococcus pneumoniae (Geckler group 4) and methicillin-sensitive S. aureus, respectively. However, exotoxins thought to cause TSS, such as TSS toxin-1 and various enterotoxins, were not detected. The patient's therapy was switched to cefazolin (2 g every 8 h) and clindamycin (600 mg every 8 h) for 14 days based on microbiologic test results. She developed desquamation of the fingers on hospital day 8 and was diagnosed with TSS. Conventional exotoxins, such as TSST-1, and S. aureus enterotoxins were not detected in culture samples. The serum levels of inflammatory cytokines, such as neopterin and IL-6, were high. CD8+ T cells were activated in peripheral blood. Vß2+ population activation, which is characteristic for TSST-1, was not observed in the Vß usage of CD8+ T cells in T cell receptor Vß repertoire distribution analysis. CONCLUSIONS: We present a case of S. simulans-induced TSS. Taken together, we speculate that no specific exotoxins are involved in the induction of TSS in this patient. A likely mechanism is uncontrolled cytokine release (i.e., cytokine storm) induced by non-specific immune reactions against CoNS proliferation.
Assuntos
Síndrome da Liberação de Citocina/complicações , Choque Séptico/complicações , Infecções Estafilocócicas/complicações , Staphylococcus aureus/isolamento & purificação , Staphylococcus/isolamento & purificação , Streptococcus pneumoniae/isolamento & purificação , Idoso , Antibacterianos/administração & dosagem , Hemocultura , Cefazolina/administração & dosagem , Clindamicina/administração & dosagem , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas/sangue , Feminino , Humanos , Testes de Sensibilidade Microbiana , Choque Séptico/tratamento farmacológico , Escarro/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Resultado do TratamentoRESUMO
BACKGROUND: Tetracyclines and clindamycin plus rifampicin combination therapy are both considered first-line therapy in current hidradenitis suppurativa guidelines. However, evidence for their efficacy is drawn from small studies, often without validated outcomes. OBJECTIVE: To assess the 12-week efficacy of oral tetracyclines and a combination of clindamycin and rifampicin. METHODS: A prospective, international cohort study performed between October 2018 and August 2019. RESULTS: In total, 63.6% of the included 283 patients received oral tetracyclines, and 36.4% were treated with clindamycin and rifampicin. Both groups showed a significant decrease in International Hidradenitis Suppurativa Severity Score System from baseline (both P < .001). The Hidradenitis Suppurativa Clinical Response (HiSCR) was achieved in 40.1% and 48.2% of patients, respectively (P = .26). Patient characteristics or disease severity were not associated with the attainment of HiSCR or the minimal clinically important differences for the Dermatology Life Quality Index and pain. LIMITATIONS: Cohort study. Respectively, 23.9% and 19.4% of patients had to be excluded from the HiSCR analysis for the tetracycline and combination therapy group because of a low abscess and nodule count at baseline. CONCLUSION: This study shows significant efficacy of both tetracycline treatment and clindamycin and rifampicin combination therapy after 12 weeks in patients with hidradenitis suppurativa. No significant differences in efficacy were observed between the 2 treatments, regardless of disease severity.
Assuntos
Clindamicina/administração & dosagem , Hidradenite Supurativa/tratamento farmacológico , Rifampina/administração & dosagem , Tetraciclinas/administração & dosagem , Adulto , Clindamicina/efeitos adversos , Estudos de Coortes , Combinação de Medicamentos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rifampina/efeitos adversos , Tetraciclinas/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Infection is a major complication following cerebral spinal fluid (CSF) diversion procedures for hydrocephalus. However, pediatric risk factors for surgical site infection (SSI) are currently not well defined. Because a SSI prevention bundle is increasingly introduced, the purpose of this study was to evaluate risk factors associated with SSIs following CSF diversion surgeries following a SSI bundle at a single quaternary care pediatric hospital. METHODS: We performed a retrospective cohort study of patients undergoing CSF diversion procedures from 2017 to 2019. SSIs were identified prospectively through continuous surveillance. We performed unadjusted logistic regression analyses and univariate analyses to determine an association between SSIs and patient demographics, comorbidities and perioperative factors to identify independent risk factors for SSI. RESULTS: We identified a total of 558 CSF diversion procedures with an overall SSI rate of 3.4%. The SSI rates for shunt, external ventricular drain (EVD) placement, and endoscopic third ventriculostomy (ETV) were 4.3, 6.9 and 0%, respectively. Among 323 shunt operations, receipt of clindamycin as perioperative prophylaxis and presence of cardiac disease were significantly associated with SSI (O.R. 4.99, 95% C.I. 1.27-19.70, p = 0.02 for the former, and O.R. 7.19, 95% C.I. 1.35-38.35, p = 0.02 for the latter). No risk factors for SSI were identified among 72 EVD procedures. CONCLUSION: We identified receipt of clindamycin as perioperative prophylaxis and the presence of cardiac disease as risk factors for SSI in shunt procedures. Cefazolin is recommended as a standard antibiotic for perioperative prophylaxis. Knowing that unsubstantiated beta-lactam allergy label is a significant medical problem, efforts should be made to clarify beta-lactam allergy status to maximize the number of patients who can receive cefazolin for prophylaxis before shunt placement. Further research is needed to elucidate the mechanism by which cardiac disease may increase SSI risk after shunt procedures.
Assuntos
Hidrocefalia/cirurgia , Infecção da Ferida Cirúrgica/epidemiologia , Adolescente , Antibacterianos/administração & dosagem , Antibioticoprofilaxia/efeitos adversos , Doenças Cardiovasculares/complicações , Criança , Pré-Escolar , Clindamicina/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Procedimentos Neurocirúrgicos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Acne vulgaris is the most common dermatological disorder worldwide, causing significant physical and psychological morbidity. Topical combination therapy has shown superior efficacy compared to monotherapy, especially when combined with retinoids. Few studies have directly compared combined formulations. This evaluator-blinded pilot study compared the efficacy and tolerability of two marketed topical combination acne gels, clindamycin 1%-tretinoin 0.025% (CT) and benzoyl peroxide 2.5%-adapalene 0.1% (BA) in 20 patients with mild to moderate acne vulgaris. Gels were applied daily on opposite sides of the face for 21 days. The primary outcome was difference in transepidermal water loss (TEWL) at the end of treatment. Secondary endpoints were skin moisture content measurement, Investigators' Global Assessment, subject self-assessments (SSA) of burning/stinging, itching, erythema, and dryness/scaling, and Comparative Participant Satisfaction Questionnaire (CPSQ). Efficacy was assessed by inflammatory and non- inflammatory acne efflorescences counts. TEWL increased significantly for both CT and BA (+57.74%, P=0.002; +58.77%, P<0.001); skin moisture content significantly decreased only for BA (-16.47%, P=0.02). Only BA showed a significant increase in erythema and dryness/scaling (P=0.027 and P=0.014) and in SSA burning/stinging (P=0.04). Patient satisfaction evaluation also reflected the strong BA irritation. Although CT and BA both reduced acne lesions (P<0.001) and more patients preferred to continue with CT, subject perception of acne improvement was higher for BA. These findings suggest that CT and BA have similar efficacy in the treatment of mild to moderate papulopustular acne. However, CT was better tolerated than BA by both medical and subject evaluation. CT is an effective and tolerated treatment option.J Drugs Dermatol. 2021;20(3):295-301. doi:10.36849/JDD.2021.5641.
Assuntos
Acne Vulgar/tratamento farmacológico , Combinação Adapaleno e Peróxido de Benzoil/administração & dosagem , Clindamicina/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Tretinoína/administração & dosagem , Acne Vulgar/diagnóstico , Combinação Adapaleno e Peróxido de Benzoil/efeitos adversos , Administração Cutânea , Adolescente , Adulto , Clindamicina/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Combinação de Medicamentos , Eritema/induzido quimicamente , Eritema/epidemiologia , Feminino , Géis , Humanos , Masculino , Satisfação do Paciente/estatística & dados numéricos , Projetos Piloto , Prurido/induzido quimicamente , Prurido/epidemiologia , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Resultado do Tratamento , Tretinoína/efeitos adversos , Perda Insensível de Água/efeitos dos fármacos , Adulto JovemRESUMO
Glyphosate is the most commonly used broad-spectrum, non-selective herbicide in the world. The toxicity is supposed to be due to uncoupling of oxidative phosphorylation and the surfactant polyoxyethylene amine (POEA)- mediated cardiotoxicity. Clinical features of this herbicide poisoning are varied, ranging from asymptomatic to even death. There is no antidote and aggressive supportive therapy is the mainstay of treatment for glyphosate poisoning. We present a 69-year-old female patient with suicidal consumption of around 500 ml of Glycel®. Initially, gastric lavage was done and intravenous fluids were given. Within two hours of presentation, the patient developed respiratory distress needing intubation, hypotension needing vasopressor support, and severe lactic acidosis. She also developed acute respiratory distress syndrome, hypokalemia, hypernatremia, and aspiration pneumonia. Our patient was critically ill with multiple poor prognostic factors, but with timely aggressive supportive management, the patient gradually recovered.
Assuntos
Glicina/análogos & derivados , Herbicidas/intoxicação , Hipernatremia/etiologia , Hipopotassemia/etiologia , Pneumonia Aspirativa/etiologia , Síndrome do Desconforto Respiratório/etiologia , Idoso , Cefamandol/administração & dosagem , Cefamandol/análogos & derivados , Cefamandol/uso terapêutico , Cefoperazona/administração & dosagem , Cefoperazona/uso terapêutico , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Suplementos Nutricionais , Feminino , Glicina/intoxicação , Humanos , Hipernatremia/tratamento farmacológico , Hipopotassemia/tratamento farmacológico , Pneumonia Aspirativa/tratamento farmacológico , Potássio/administração & dosagem , Potássio/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Tentativa de Suicídio , Sulbactam/administração & dosagem , Sulbactam/uso terapêutico , Resultado do Tratamento , GlifosatoRESUMO
Osteomyelitis is one of the infections of the bone, and the treatment needs to the infection problems. Here, a local therapeutic approach for efficient drug delivery systems was designed to enhance the antibiotic drug's therapeutic activity. Calcium-Alginate nanoparticle (Ca-Alg) crosslinked phosphorylated polyallylamine (PPAA) was prepared through the salting-out technique, and it achieved 82.55% encapsulation of Clindamycin drug. The physicochemical characterizations of FTIR, SEM/EDX, TEM, and XRD were investigated to confirm the materials nature and formation. Clindamycin loaded Ca-Alg/PPAA system showed sustained Clindamycin release from the carrier. Cell viability was assessed in bone-related cells by Trypan blue assay and MTT assay analysis method. Both assay results exhibited better cell viability of synthesized materials against MG63 cells. MIC value of Ca-Alg/PPAA/Clindamycin in the Methicillin-resistant Staphylococcus aureus (MRSA) pathogen was 275 µg/mL, and it was 120 µg/mL for Enterobacter cloacae pathogen. The materials promising material for Osteomyelitis affected bone regeneration without any destructive effect and speedy recovery of infected parts from these investigations.
Assuntos
Clindamicina/química , Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Osteomielite , Poliaminas/química , Infecções Estafilocócicas , Staphylococcus aureus/química , Alginatos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Clindamicina/administração & dosagem , Preparações de Ação Retardada/uso terapêutico , Humanos , Osteomielite/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
This study aimed to evaluate the impact of the intervention targeting the redundant combination of antianaerobic antimicrobials on its incidence and associated antimicrobial consumption. To reveal the characteristics of the combination and the change in the related workload over time was an additional aim of the study. The combinations of metronidazole or clindamycin with antianaerobic antimicrobials were classified into redundant or acceptable, according to the target indications. A pharmacist-based prospective audit and feedback targeting the redundant antianaerobic combination was conducted. Segmented regression analysis was performed to evaluate the impact of the intervention. As a quantitative index of the interventional activity, the change in the number of signed consultation notes was evaluated. After the initiation of the intervention, the median monthly cumulative incidence of the redundant combination decreased from 5.29 (Interquartile range [IQR] 4.94-5.70) to 3.33 (IQR 2.87-3.71) (p < 0.001) per 1000 admissions per month. The consumption of concurrently administered metronidazole and clindamycin decreased from 3.34 (IQR 2.97-4.10) to 1.74 (IQR 1.19-1.93) (p < 0.001) per 1000 patient-days per month. Segmented regression analysis revealed that the monthly cumulative incidence decreased by 28.5% after the initiation of the intervention (change in level - 1.640, p = 0.019) and the monthly consumption decreased by 33.9% (change in level - 1.409, p = 0.009). The number of consultation notes per 1000 admissions per month decreased over time (regression coefficient - 0.004, p < 0.001). The pharmacist-based intervention significantly reduced the incidence and associated antimicrobial consumption of the redundant antianaerobic combination. The overall related workload reduced steadily over time.
Assuntos
Antibacterianos/administração & dosagem , Farmacêuticos , Prescrições/normas , Qualidade da Assistência à Saúde , Bactérias Anaeróbias/efeitos dos fármacos , Clindamicina/administração & dosagem , Humanos , Prescrição Inadequada , Metronidazol/administração & dosagem , Médicos , Estudos ProspectivosRESUMO
BACKGROUND: Bacterial vaginosis (BV) is estimated to affect 1 in 3 women globally and is associated with obstetric and gynaecological sequelae. Current recommended therapies have good short-term efficacy but 1 in 2 women experience BV recurrence within 6 months of treatment. Evidence of male carriage of BV-organisms suggests that male partners may be reinfecting women with BV-associated bacteria (henceforth referred to as BV-organisms) and impacting on the efficacy of treatment approaches solely directed to women. This trial aims to determine the effect of concurrent male partner treatment for preventing BV recurrence compared to current standard of care. METHODS: StepUp is an open-label, multicentre, parallel group randomised controlled trial for women diagnosed with BV and their male partner. Women with clinical-BV defined using current gold standard diagnosis methods (≥3 Amsel criteria and Nugent score (NS) = 4-10) and with a regular male partner will be assessed for eligibility, and couples will then be consented. All women will be prescribed oral metronidazole 400 mg twice daily (BID) for 7 days, or if contraindicated, a 7-day regimen of topical vaginal 2% clindamycin. Couples will be randomised 1:1 to either current standard of care (female treatment only), or female treatment and concurrent male partner treatment (7 days of combined antibiotics - oral metronidazole tablets 400 mg BID and 2% clindamycin cream applied topically to the glans penis and upper shaft [under the foreskin if uncircumcised] BID). Couples will be followed for up to 12 weeks to assess BV status in women, and assess the adherence, tolerability and acceptability of male partner treatment. The primary outcome is BV recurrence defined as ≥3 Amsel criteria and NS = 4-10 within 12 weeks of enrolment. The estimated sample size is 342 couples, to detect a 40% reduction in BV recurrence rates from 40% in the control group to 24% in the intervention group within 12 weeks. DISCUSSION: Current treatments directed solely to women result in unacceptably high rates of BV recurrence. If proven to be effective the findings from this trial will directly inform the development of new treatment strategies to impact on BV recurrence. TRIAL REGISTRATION: The trial was prospectively registered on 12 February 2019 on the Australian and New Zealand Clinical Trial Registry (ACTRN12619000196145, Universal Trial Number: U1111-1228-0106, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376883&isReview=true ).
Assuntos
Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Metronidazol/uso terapêutico , Parceiros Sexuais , Vaginose Bacteriana/tratamento farmacológico , Administração Intravaginal , Administração Oral , Antibacterianos/administração & dosagem , Austrália , Clindamicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Metronidazol/administração & dosagem , Nova Zelândia , Pênis/microbiologia , Estudos Prospectivos , Recidiva , Resultado do Tratamento , Vaginose Bacteriana/microbiologiaRESUMO
Currently employed methods for qualifying population physiologically-based pharmacokinetic (Pop-PBPK) model predictions of continuous outcomes (e.g., concentration-time data) fail to account for within-subject correlations and the presence of residual error. In this study, we propose a new method for evaluating Pop-PBPK model predictions that account for such features. The approach focuses on deriving Pop-PBPK-specific normalized prediction distribution errors (NPDE), a metric that is commonly used for population pharmacokinetic model validation. We describe specific methodological steps for computing NPDE for Pop-PBPK models and define three measures for evaluating model performance: mean of NPDE, goodness-of-fit plots, and the magnitude of residual error. Utility of the proposed evaluation approach was demonstrated using two simulation-based study designs (positive and negative control studies) as well as pharmacokinetic data from a real-world clinical trial. For the positive-control simulation study, where observations and model simulations were generated under the same Pop-PBPK model, the NPDE-based approach denoted a congruency between model predictions and observed data (mean of NPDE = - 0.01). In contrast, for the negative-control simulation study, where model simulations and observed data were generated under different Pop-PBPK models, the NPDE-based method asserted that model simulations and observed data were incongruent (mean of NPDE = - 0.29). When employed to evaluate a previously developed clindamycin PBPK model against prospectively collected plasma concentration data from 29 children, the NPDE-based method qualified the model predictions as successful (mean of NPDE = 0). However, when pediatric subpopulations (e.g., infants) were evaluated, the approach revealed potential biases that should be explored.