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1.
Skinmed ; 22(5): 375-378, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39433524

RESUMO

CabtreoTM (1.2% clindamycin phosphate, 0.15% adapalene, and 3.1% benzoyl peroxide) or IDP-126 topical gel was approved by the US Food and Drug Administration (FDA) in October 2023 for the treatment of moderate to severe acne vulgaris in patients aged ≥12 years. Its effectiveness and safety were evaluated in two phase 3 trials (Trial 1 and Trial 2). In both trials, subjects were randomized into two groups, one received IDP-126 gel and the other received vehicle gel. The primary efficacy end point was treatment success at week 12, defined as subjects achieving at least a 2-grade reduction from baseline in Evaluator's Global Severity Score (EGGS) and a final score ranging from 0 (clear) to 1 (almost clear) as well as reduced counts of inflammatory and non-inflammatory lesions. In Trial 1 (N = 183), treatment success was achieved in 49.6% (61/122) of subjects in the IDP-126 group versus 24.9% (15/61) of subjects in the vehicle group (P < 0.01). In Trial 2 (N = 180), treatment success was achieved in 50.5% (61/120) of subjects in the IDP-126 group versus 20.5% (12/60) of subjects in the vehicle group (P < 0.01). IDP-126 is therefore recommended to be applied as a thin layer to the affected area once daily.


Assuntos
Acne Vulgar , Clindamicina , Fármacos Dermatológicos , Combinação de Medicamentos , Géis , Humanos , Acne Vulgar/tratamento farmacológico , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Administração Cutânea , Peróxido de Benzoíla/administração & dosagem , Peróxido de Benzoíla/uso terapêutico , Feminino , Masculino , Adapaleno/administração & dosagem , Adapaleno/uso terapêutico , Adolescente , Adulto
2.
Front Cell Infect Microbiol ; 14: 1402346, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39463760

RESUMO

Objective: Bacterial vaginosis is a disease caused by vaginal microecology disorder, which seriously affects female health. At present, there are many drugs to treat BV, and this study aims to compare the efficacy and safety of multiple drugs for BV through a network meta-analysis (NMA). Methods: All studies were sourced from PubMed and Embase databases from the establishment date to April 13, 2023. We evaluated the clinical cure success rate and adverse effects (abnormal increase in vaginal discharge, external genital irritation, and vulvar itching) and performed subgroup analyses of the clinical cure success rate for different modes of administration. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis. Results: We included 42 studies that met the criteria, involving a total of 8382 patients. Network meta-analysis results showed that metronidazole and secnidazole had a higher rate of adverse reactions than placebo (RR 7.06; 95%-CI 2.61-19.10, RR 4.03; 95%-CI 1.63-9.98), the adverse reaction rate of probiotics group was lower than that of metronidazole group (RR 0.44; 95%-CI 0.21-0.93). The clinical cure rate of oral ornidazole was better than clindamycin (RR 16.08; 95%-CI 1.72-150.47), Secnidazole (RR 8.17; 95%-CI 1.66-40.25) and probiotics. Direct meta-analysis results showed that ornidazole had a better clinical cure rate than Secnidazole (RR 1.22; 95%-CI 1.10-1.34), oral ornidazole had a better clinical cure rate than Secnidazole (RR 1.23; 95%-CI 1.11-1.36). The clinical cure rate of vaginal application of sucrose was better than metronidazole (RR 1.12; 95%-CI 1.03-1.21) and metronidazole had a lower clinical cure rate than probiotics (RR 0.68; 95%-CI 0.52-0.88). Conclusions: The results of this systematic review and network meta-analysis suggest that ornidazole may be an effective alternative for the treatment of BV, and that sucrose and probiotics are potential BV treatments that need to be validated by more high-quality clinical studies in the future.


Assuntos
Antibacterianos , Metronidazol , Metanálise em Rede , Probióticos , Vaginose Bacteriana , Humanos , Vaginose Bacteriana/tratamento farmacológico , Feminino , Metronidazol/uso terapêutico , Metronidazol/efeitos adversos , Metronidazol/análogos & derivados , Probióticos/uso terapêutico , Probióticos/efeitos adversos , Resultado do Tratamento , Antibacterianos/uso terapêutico , Antibacterianos/efeitos adversos , Clindamicina/uso terapêutico , Clindamicina/efeitos adversos , Nitroimidazóis/uso terapêutico , Nitroimidazóis/efeitos adversos
3.
J Drugs Dermatol ; 23(10): 857-861, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39361698

RESUMO

BACKGROUND: Although triple-combination therapies for acne are generally more efficacious than dual-combinations or topical monotherapy, this benefit may be offset by reduced adherence to a complicated treatment regimen. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB; Cabtreo®, Ortho Dermatologics) gel is the first triple-combination topical approved for the treatment of acne. By delivering multiple active ingredients as a fixed-dose combination, CAB gel may improve ease of use, which can benefit both treatment adherence and efficacy. The objective of this study was to compare the application characteristics of CAB gel with the layered application of its 3 individual active ingredients. METHODS: In this split-face study, adults with acne-prone skin (N=25), self-applied CAB gel (0.3 cc) to 1 side of the face and layered benzoyl peroxide cream, adapalene gel, and clindamycin gel (0.1 cc each) on the opposite side. CAB and clindamycin gels were compounded with pyranine, which fluoresces under blue light. Photos taken under blue light were used to assess the uniformity of product application, and participants rated the evenness, speed, and ease of the 2 application regimens, as well as overall preference. RESULTS: Investigator-assessed evenness of application favored CAB gel over layered application in 100% of participants. All participants rated the application of CAB gel as more uniform, easier, and faster. Most (96%) preferred CAB gel for use at home. CONCLUSION: Fixed-dose CAB gel was applied more evenly than separate application of its 3 active ingredients. By addressing 3 of the main acne pathogenic pathways in a single, easy-to-apply formulation, CAB gel may improve the efficacy of and adherence to acne treatment. J Drugs Dermatol. 2024;23(10):857-861. doi:10.36849/JDD.8430.


Assuntos
Acne Vulgar , Administração Cutânea , Peróxido de Benzoíla , Clindamicina , Fármacos Dermatológicos , Combinação de Medicamentos , Géis , Preferência do Paciente , Humanos , Acne Vulgar/tratamento farmacológico , Clindamicina/administração & dosagem , Adulto , Feminino , Peróxido de Benzoíla/administração & dosagem , Masculino , Adulto Jovem , Fármacos Dermatológicos/administração & dosagem , Resultado do Tratamento , Adolescente , Adapaleno/administração & dosagem
4.
J Drugs Dermatol ; 23(10): 873-881, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39361705

RESUMO

BACKGROUND: Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) is the only fixed-dose triple-combination treatment approved for acne. This post hoc analysis assessed the impact of sex on efficacy and safety/tolerability of CAB. METHODS: In two multicenter, double-blind, phase 3 studies (NCT04214639 and NCT04214652), participants aged ≥9 years 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 by sex. Assessments included treatment success (≥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 were significantly greater with CAB versus vehicle irrespective of sex (females: 53.7% vs 23.0%; males: 43.1% vs 24.6%; P<0.05, both). CAB-treated female and male participants both experienced greater reductions from baseline versus vehicle in inflammatory (females: 77.7% vs 57.9%; males: 77.5% vs 57.1%; P<0.001, both) and noninflammatory lesions (females: 72.5% vs 45.6%; males: 72.3% vs 49.6%; P<0.001, both). Acne-QoL improvements from baseline to week 12 were significantly greater with CAB than vehicle. No significant differences in any efficacy measures between CAB-treated males and females were observed. Most TEAEs were of mild-to-moderate severity; no sex-based trends for safety/tolerability were observed. CONCLUSIONS: CAB demonstrated comparable efficacy, quality-of-life improvements, and safety in female and male participants with moderate-to-severe acne. As the first fixed-dose, triple-combination topical formulation, CAB represents an important new treatment for acne. J Drugs Dermatol. 2024;23(10):873-881. doi:10.36849/JDD.8484.


Assuntos
Acne Vulgar , Peróxido de Benzoíla , Clindamicina , Fármacos Dermatológicos , Combinação de Medicamentos , Géis , Humanos , Acne Vulgar/tratamento farmacológico , Clindamicina/administração & dosagem , Clindamicina/efeitos adversos , Clindamicina/análogos & derivados , Feminino , Masculino , Método Duplo-Cego , Adulto , Peróxido de Benzoíla/administração & dosagem , Peróxido de Benzoíla/efeitos adversos , Adolescente , Adulto Jovem , Resultado do Tratamento , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Administração Cutânea , Fatores Sexuais , Criança , Adapaleno/administração & dosagem
6.
Antimicrob Agents Chemother ; 68(10): e0069124, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39287404

RESUMO

The therapeutic challenges of orthopedic device-related infections and emerging antimicrobial resistance have attracted attention to drug delivery technologies. This study evaluates the preclinical efficacy of local single- and dual-antibiotic therapy against implant-associated osteomyelitis (IAO) using a drug-eluting depot technology, CarboCell, that provides sustained release of high-dose antibiotics and allows for strategic in situ placement in relation to infectious lesions. Clindamycin and gentamicin were formulated in CarboCell compositions. One-stage-revision of tibial Staphylococcus aureus IAO was conducted in 19 pigs. Pigs were treated locally with CarboCell containing either gentamicin alone for 1 week or a co-formulation of gentamicin and clindamycin for 1 or 3 weeks. Bone, soft tissue, and antibiotic depots were collected for microbiology, histology, and HPLC analyses. Supporting in vivo release studies of CarboCell formulations were performed on mice. Both single- and dual-antibiotic CarboCell formulations were developed and capable of eradicating the infectious bacteria in bone and preventing colonization of implants inserted at revision. Eradication in soft tissue was observed in all pigs after 3 weeks and in 6/9 pigs after 1 week of treatment. Neutrophil counts in bone tissue were below the infection cut-off in all pigs receiving the dual-antibiotic therapies, but above in all pigs receiving the single-antibiotic therapy. Histological signs of active bone reorganization and healing were observed at 3 weeks. In conclusion, all CarboCell formulations demonstrated strong therapeutic activity against IAO, eradicating S. aureus in bone tissue and preventing colonization of implants even without the addition of systemic antibiotic therapy.


Assuntos
Antibacterianos , Clindamicina , Gentamicinas , Osteomielite , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Gentamicinas/uso terapêutico , Gentamicinas/farmacologia , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Clindamicina/uso terapêutico , Clindamicina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Staphylococcus aureus/efeitos dos fármacos , Suínos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Modelos Animais de Doenças , Camundongos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Feminino , Preparações de Ação Retardada
7.
BMC Res Notes ; 17(1): 252, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39252055

RESUMO

OBJECTIVE: The purpose of this study is a new update on the resistance profile, Macrolide-Lincosamide-Streptogramin B resistance mechanisms and biofilm formation in the Staphylococcus aureus isolated from health care workers (HCWs) nasal carriage at a children's teaching hospital in Babol (Northern Iran). RESULTS: A total of 143 non-repetitive nasal swab samples were collected from volunteers, where 53.8% (n; 77/143) were HCWs, 33.6% (n; 48/143) medical students, and 12.6% (n; 18/143) resident students. The prevalence of nasal carriers of S. aureus was 22.4% (n; 32/143), among them, 40.6% (n; 13/32) were identified as methicillin-resistant Staphylococcus aureus (MRSA( carriers. Antimicrobial susceptibility testing showed that erythromycin (68.8%, n; 22/32) and ciprofloxacin (15.6%, n; 5/32) had the highest and lowest resistance rate, respectively. The frequency of resistance genes in the strains was as follows; ermC (n; 17/32, 53.1%), ermA (n; 11/32, 34.4%), ermB (n; 6/32, 18.7%), ereA (n; 3/32, 9.4%). Moreover, 50.0% (n; 16/32), 28.1% (n; 9/32) and 21.8% (n; 7/32) of isolates were strongly, weakly and moderately biofilm producer, respectively. Macrolides-lincosamides-streptogramins B (MLSB) antibiotic resistance among S. aureus isolates from HCWs nasal carriage have found significant prevalence rates throughout the globe. It is crucial to remember that the development of biofilms and MLS B antibiotic resistance are both dynamic processes.


Assuntos
Antibacterianos , Biofilmes , Portador Sadio , Clindamicina , Pessoal de Saúde , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Clindamicina/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/fisiologia , Staphylococcus aureus/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/fisiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/epidemiologia , Portador Sadio/microbiologia , Irã (Geográfico) , Masculino , Adulto , Feminino , Eritromicina/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Farmacorresistência Bacteriana/genética
8.
J Chromatogr A ; 1736: 465388, 2024 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-39326379

RESUMO

Clindamycin phosphate (CP) exhibits good enantioselectivity for many basic drugs, but its separation effect for most amino alcohol drugs is not satisfactory. In this work, a deep eutectic solvent (DES) chiral selector based on CP was prepared for the first time and utilized as a single chiral selector in nonaqueous capillary electrophoresis (NACE) to separate twelve amino alcohol drugs. Compared with unmodified CP, the separations of model drugs in the DES chiral selector system were significantly improved. Most amino alcohol drugs could be completely separated, and the peak shapes were good. In addition, we used infrared spectroscopy and nuclear magnetic resonance method to study the specific separation mechanism and explored the reasons why DES chiral selector has better enantioselectivity. This work is the first to directly modify antibiotic chiral selector into DES, indicating a direction for us to develop novel chiral recognition materials.


Assuntos
Amino Álcoois , Clindamicina , Eletroforese Capilar , Solventes , Estereoisomerismo , Eletroforese Capilar/métodos , Clindamicina/química , Clindamicina/análogos & derivados , Clindamicina/isolamento & purificação , Amino Álcoois/química , Amino Álcoois/isolamento & purificação , Solventes/química
9.
Clin Oral Investig ; 28(10): 538, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39304566

RESUMO

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


Assuntos
Antibacterianos , Humanos , Estudos Retrospectivos , Masculino , Feminino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Adulto , Testes de Sensibilidade Microbiana , Farmacorresistência Bacteriana , Idoso , Metronidazol/uso terapêutico , Metronidazol/farmacologia , Adolescente , Clindamicina/uso terapêutico , Clindamicina/farmacologia , Criança , Penicilinas , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Doenças da Boca/microbiologia , Hospitalização
10.
Curr Pharm Des ; 30(40): 3155-3163, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39219122

RESUMO

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 METHODS: 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.


Assuntos
Antibacterianos , Clindamicina , Clindamicina/análise , Clindamicina/química , Antibacterianos/análise , Antibacterianos/química , Química Verde , Cromatografia Líquida de Alta Pressão , Humanos
11.
Biomater Sci ; 12(20): 5253-5265, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39235306

RESUMO

A major risk associated with surgery, including bone tissue procedures, is surgical site infection. It is one of the most common as well as the most serious complications of modern surgery. A helpful countermeasure against infection is antibiotic therapy. In the present study, a methodology has been developed to obtain clindamycin-modified polymer-ceramic hybrid composite coatings for potential use in bone regenerative therapy. The coatings were prepared using a UV-light photocrosslinking method, and the drug was bound to a polymeric and/or ceramic phase. The sorption capacity of the materials in PBS was evaluated by determining the swelling ability and equilibrium swelling. The influence of the presence of ceramics on the amount of liquid bound was demonstrated. The results were correlated with the rate of drug release measured by high-performance liquid chromatography (HPLC). Coatings with higher sorption capacity released the drug more rapidly. Scanning electron microscopy (SEM) imaging was carried out comparing the surface area of the coatings before and after immersion in PBS, and the proportions of the various elements were also determined using the EDS technique. Changes in surface waviness were observed, and chlorine ions were also determined in the samples before incubation. This proves the presence of the drug in the material. The in vitro tests conducted indicated the release of the drug from the biomaterials. The antimicrobial efficacy of the coatings was tested against Staphylococcus aureus. The most promising material was tested for cytocompatibility (MTT reduction assay) against the mouse fibroblast cell line L929 as well as human osteoblast cells hFOB. It was demonstrated that the coating did not exhibit cytotoxicity. Overall, the results signaled the potential use of the developed polymer-ceramic hybrid coatings as drug carriers for the controlled delivery of clindamycin in bone applications. The studies conducted were the basis for directing samples for further in vivo experiments determining clinical efficacy.


Assuntos
Antibacterianos , Cerâmica , Clindamicina , Preparações de Ação Retardada , Staphylococcus aureus , Clindamicina/química , Clindamicina/administração & dosagem , Clindamicina/farmacologia , Cerâmica/química , Cerâmica/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Preparações de Ação Retardada/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Liberação Controlada de Fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Humanos , Animais , Camundongos , Polímeros/química , Linhagem Celular
12.
Int J Pharm Compd ; 28(4): 271-277, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39094040

RESUMO

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that may have profound effects on the patient's quality of life. A personalized HS combination therapy treatment was prescribed to a 54-year-old female suffering from multiple painful sores, as follows: naltrexone capsules titrated from 0.5 mg up to 4.5 mg; pentoxifylline 5%, rifampin 2%, clindamycin 1%, and glycolic acid topical cream. Clinical improvements were observed using two disease-specific outcome measures: Hurley Staging System and HS Score. The patient's HS improved from Stage II (moderate) to Stage I (mild), and the HS score decreased from 103 points with five anatomical regions reported, to 19 points with only three regions affected. Furthermore, the before and after treatment photographs showed a visible reduction in the number of boils/skin abscesses and an overall recovery. Improvements were also observed across all domains of the patient's self-reported quality of life (Hidradenitis Suppurativa Quality of Life Assessment). The patient did not experience any undesirable effects. Compounded medications may be customized to meet the patient's special needs and may be adjusted throughout the course of treatment to match the patient's individual progress. Although further studies are necessary, this personalized, combination therapy may be a key treatment option in HS.


Assuntos
Clindamicina , Quimioterapia Combinada , Hidradenite Supurativa , Pentoxifilina , Rifampina , Humanos , Feminino , Hidradenite Supurativa/tratamento farmacológico , Pessoa de Meia-Idade , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Pentoxifilina/administração & dosagem , Pentoxifilina/uso terapêutico , Rifampina/administração & dosagem , Administração Oral , Qualidade de Vida , Administração Tópica , Antibacterianos/administração & dosagem , Resultado do Tratamento , Combinação de Medicamentos
13.
Int J Pharm Compd ; 28(4): 316-320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39094043

RESUMO

The individual physicochemical stabilities of Allopurinol, Clindamycin Hydrochloride, Naltrexone Hydrochloride, Spironolactone and Ursodiol in the proprietary suspending vehicle PCCA SuspendIt® have been previously studied and published by the author. Accordingly, Beyond-Use-Dates (BUDs) of 180 days were assigned to the five drugs based on the results of the respective studies. The data were donated to the United States Pharmacopeia (USP) for possible adoption as Official Compounded Drug Monographs. Following an extensive review process, all five studies were approved and published by the USP. However, due to a lack of microbiological stability information, the BUDs were limited to 90 days. The current study was undertaken as a follow-up project to determine the microbiological stability of these five drugs in PCCA SuspendIt® utilizing the same compounding procedures from the original studies. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The goal was to provide a viable, compounded alternative for Allopurinol, Clindamycin Hydrochloride, Naltrexone Hydrochloride, Spironolactone and Ursodiol in a thixotropic liquid dosage form, with an extended BUD of 6 months to meet patient needs. Given that the physical and chemical stabilities of all five drugs have been previously established and adopted by the USP as official compounded monographs, additional microbiological stability data would allow the official BUDs in the USP to be extended to 180 days to conform to the physicochemical stabilities. The current study showed that the preservative system in PCCA SuspendIt® successfully protected all the suspensions from growth of challenge microorganisms per the USP Chapter <51> AME Test. The results of the current study combined with the previous physicochemical studies demonstrate the following: Allopurinol is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature over a bracketed allopurinol concentration range of 10 - 20 mg/mL. Clindamycin Hydrochloride is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature at a concentration of 10-mg/mL of clindamycin. Naltrexone Hydrochloride is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, over a bracketed naltrexone hydrochloride concentration range of 0.5 - 5.0 mg/mL. Spironolactone is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature at a concentration of 5 mg/mL of spironolactone. Ursodiol is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, over a bracketed ursodiol concentration range of 50 - 100 mg/mL. Taken collectively, the current study in conjunction with the earlier studies provide viable, compounded alternatives for Allopurinol, Clindamycin Hydrochloride, Naltrexone Hydrochloride, Spironolactone and Ursodiol in the suspending vehicle PCCA SuspendIt in liquid dosage forms, with an extended beyond-use-date to meet patient needs.


Assuntos
Alopurinol , Clindamicina , Composição de Medicamentos , Estabilidade de Medicamentos , Naltrexona , Clindamicina/química , Clindamicina/administração & dosagem , Alopurinol/química , Naltrexona/química , Naltrexona/administração & dosagem , Espironolactona/química , Administração Oral
14.
Arch Dermatol Res ; 316(8): 573, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180541

RESUMO

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.


Assuntos
Pustulose Exantematosa Aguda Generalizada , Antibacterianos , Clindamicina , Humanos , Clindamicina/efeitos adversos , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Pustulose Exantematosa Aguda Generalizada/diagnóstico , Pustulose Exantematosa Aguda Generalizada/etiologia , Pustulose Exantematosa Aguda Generalizada/patologia , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Idoso , Adolescente , Idoso de 80 Anos ou mais , Adulto Jovem , Criança , Antibacterianos/efeitos adversos , Pré-Escolar , Lactente , Resultado do Tratamento , Pele/patologia , Pele/efeitos dos fármacos , Neutrófilos
15.
Am J Case Rep ; 25: e944508, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39182163

RESUMO

BACKGROUND Common causes of severely elevated transaminases, especially alanine transaminase, due to liver diseases include drug-induced liver injury and acute viral hepatitis, especially hepatitis E, which can present similarly in clinical practice. Broad differential diagnostic workup in patients with elevated transaminases is required to not overlook the possibility of hepatitis E infection. CASE REPORT We report on a 65-year-old asymptomatic man who was referred to the Emergency Department from the rehabilitation center due to markedly elevated liver transaminases. Physical examination revealed no jaundice or abdominal pain. Laboratory findings included severely elevated aspartate transaminase, alanine transaminase, and bilirubin levels. He was previously treated with imipenem/cilastatin and clindamycin for a surgical site infection of his jaw after the removal of a squamous cell carcinoma 2 weeks earlier. An ultrasound of the liver was unremarkable. Drug-induced liver injury was suspected, and all potentially hepatotoxic drugs, including antibiotics, were stopped. Due to the rapid and marked increase in liver transaminases, further tests were performed, including testing for hepatitis E. Serum anti-hepatitis E virus immunoglobulin M, immunoglobulin G antibodies, and hepatitis E virus-ribonucleic acid-polymerase chain reaction turned positive, and the diagnosis of hepatitis E was confirmed. Supportive care was applied. Liver transaminases decreased spontaneously. CONCLUSIONS The diagnostic workup in patients with markedly elevated liver transaminases and suspected drug-induced liver injury should include the screening for hepatitis E. Making the correct diagnosis is crucial given the differing treatment approaches, the implications on further therapy, and the risk of contagion of hepatitis E.


Assuntos
Antibacterianos , Doença Hepática Induzida por Substâncias e Drogas , Hepatite E , Humanos , Masculino , Idoso , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatite E/diagnóstico , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Erros de Diagnóstico , Clindamicina/efeitos adversos , Clindamicina/uso terapêutico , Combinação Imipenem e Cilastatina , Alanina Transaminase/sangue
16.
J Microbiol Methods ; 224: 107009, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39098402

RESUMO

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.


Assuntos
Babesia , Babesiose , Clindamicina , Doenças do Cão , Carga Parasitária , Parasitemia , Reação em Cadeia da Polimerase em Tempo Real , Animais , Cães , Doenças do Cão/parasitologia , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Babesia/genética , Babesia/isolamento & purificação , Parasitemia/parasitologia , Parasitemia/veterinária , Babesiose/parasitologia , Babesiose/diagnóstico , Clindamicina/uso terapêutico , Carga Parasitária/métodos , Doxiciclina/uso terapêutico , Azitromicina/uso terapêutico , Metronidazol/uso terapêutico , Antiprotozoários/uso terapêutico , Naftoquinonas
17.
J ISAKOS ; 9(5): 100310, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39159823

RESUMO

BACKGROUND: Spontaneous infections involving muscles in the shoulder girdle are uncommon conditions rarely reported in the literature. The large musculature of shoulder girdle, complex communicating spaces into the periscapular region, and late glenohumeral joint involvement can cause delay in diagnosis of infections involving muscular portion of rotator cuff. The method of surgical drainage with involvement of scapulothoracic and subscapular spaces and prognosis can be challenging. METHODOLOGY: In this descriptive study, we included patients with shoulder girdle muscle abscess and analyzed the spread in the shoulder girdle and arm through various pathways radiologically. Debridement of the abscess in the subscapular muscle and adnexa was done through the dual approach, one with deltopectoral approach for the shoulder girdle and another incision anterior to the latissimus dorsi muscle for inferior subscapular spaces and gravity-dependent drainage of collection. RESULTS: The causative organism Staphylococcus aureus was isolated only in two patients out of four cases. In repeated collections, axillary and suprascapular nerve palsies were commonly encountered. Adequate debridement, antibiotic cover with vancomycin and clindamycin for six weeks, and rehabilitation restored normal functions of the shoulder in three patients. CONCLUSION: Unsuspecting nature of the subscapular abscess and similarities with common shoulder conditions at initial presentation often led to extensive shoulder girdle involvement via subscapular space, subcoracoid recess, and scapulothoracic space to adjacent areas. The dual approach provides adequate access to drain the collections in subscapularis muscle, subscapular spaces, and shoulder girdle. LEVEL OF STUDY: V.


Assuntos
Abscesso , Antibacterianos , Desbridamento , Drenagem , Infecções Estafilocócicas , Staphylococcus aureus , Humanos , Abscesso/cirurgia , Masculino , Staphylococcus aureus/isolamento & purificação , Drenagem/métodos , Desbridamento/métodos , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/cirurgia , Feminino , Adulto , Pessoa de Meia-Idade , Articulação do Ombro/cirurgia , Músculo Esquelético/cirurgia , Vancomicina/uso terapêutico , Vancomicina/administração & dosagem , Resultado do Tratamento , Ombro/cirurgia , Clindamicina/uso terapêutico , Clindamicina/administração & dosagem
18.
J Invest Dermatol ; 144(11): 2553-2561.e3, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39122144

RESUMO

Inflammation and the Gram-positive anaerobic bacterium Cutibacterium acnes, which is implicated in acne pathogenesis and pilosebaceous-unit inflammation, are the main targets of antibiotic-based therapy against acne vulgaris (acne). The most widely used antibiotics in acne therapy are tetracyclines, macrolides, and lincosamides. Unfortunately, C. acnes bacteria over the past several decades have demonstrated increased resistance to these antibiotics, particularly to clindamycin. The precise knowledge of how antibiotics interact with their clinical target is needed to overcome this problem. Toward this goal, we determined the structure of clindamycin in complex with the ribosome of C. acnes at 2.53 Å resolution using cryogenic electron microscopy. The galactose sugar moiety of clindamycin interacts with nucleotides of the 23S ribosomal RNA directly or through a conserved network of water-mediated interactions. Its propyl pyrrolidinyl group interacts with the 23S ribosomal RNA through van der Waals forces. Clindamycin binding to the C. acnes ribosome interferes with both: proper orientation of the aminoacyl group of the A-site bound transfer RNA that is needed for peptide bond formation and with the extension of the nascent peptide. Our data are important for advancing the understanding of antibiotic resistance and development of narrow-spectrum antibacterial drugs, which is an urgent need for contemporary antibiotic stewardship.


Assuntos
Acne Vulgar , Antibacterianos , Clindamicina , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Acne Vulgar/tratamento farmacológico , Acne Vulgar/microbiologia , Microscopia Crioeletrônica , Ribossomos/metabolismo , Ribossomos/efeitos dos fármacos , RNA Ribossômico 23S/metabolismo , RNA Ribossômico 23S/genética , Biossíntese de Proteínas/efeitos dos fármacos , Propionibacterium acnes/efeitos dos fármacos , Propionibacterium acnes/metabolismo , Propionibacteriaceae/efeitos dos fármacos , Propionibacteriaceae/metabolismo , Modelos Moleculares
19.
J Med Microbiol ; 73(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38985141

RESUMO

Introduction. Maternal screening tests and prophylactic antibiotics are important to prevent neonatal and infant group B streptococcal (GBS) infections.Hypothesis/Gap Statement. The performance of enrichment broth media for GBS screening that are available in Japan is unclear. Whole-genome data of GBS isolates from pregnant women in Japan is lacking.Aim. The aim of this study was to compare the protocol performance of six enrichment broths and two subculture agar plates, which were all available in Japan, for GBS detection. In addition, we showed whole-genome data of GBS isolates from pregnant women in Japan.Methodology. We collected 133 vaginal-rectal swabs from pregnant women visiting clinics and hospitals in Nagasaki Prefecture, Japan, and compared the protocol performance of 6 enrichment broths and 2 subculture agar plates. All GBS isolates collected in this study were subjected to whole-genome sequencing analysis.Results. We obtained 133 vaginal-rectal swabs from pregnant women at 35-37 weeks of gestation from 8 private clinics and 2 local municipal hospitals within Nagasaki Prefecture, Japan. The detection rate of the protocol involving the six enrichment broths and subsequent subcultures varied between 95.5 and 100 %, depending on the specific choice of enrichment broth. The GBS carriage rate among pregnant women in this region was 18.8 %. All 25 isolates derived from the swabs were susceptible to penicillin, whereas 48 and 36 % of the isolates demonstrated resistance to erythromycin and clindamycin, respectively. The distribution of serotypes was highly diverse, encompassing seven distinct serotypes among the isolates, with the predominant serotype being serotype V (n = 8). Serotype V isolates displayed a tendency towards increased resistance to erythromycin and clindamycin, with all resistant isolates containing the ermB gene.Conclusion. There was no difference in performance among the culture protocols evaluated in this study. GBS strains isolated from pregnant women appeared to have greater genomic diversity than GBS strains detected in neonates/infants with invasive GBS infections. To confirm this result, further studies with larger sample sizes are needed.


Assuntos
Antibacterianos , Infecções Estreptocócicas , Streptococcus agalactiae , Vagina , Humanos , Streptococcus agalactiae/genética , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/isolamento & purificação , Streptococcus agalactiae/classificação , Feminino , Gravidez , Japão/epidemiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/epidemiologia , Antibacterianos/farmacologia , Vagina/microbiologia , Meios de Cultura/química , Complicações Infecciosas na Gravidez/microbiologia , Complicações Infecciosas na Gravidez/epidemiologia , Reto/microbiologia , Testes de Sensibilidade Microbiana , Sequenciamento Completo do Genoma , Adulto , Clindamicina/farmacologia , Genoma Bacteriano
20.
J Orthop Traumatol ; 25(1): 37, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048851

RESUMO

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 Risco
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