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1.
Clin Infect Dis ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38801783

RESUMEN

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.

2.
Pharm Res ; 41(5): 967-982, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38637438

RESUMEN

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.


Asunto(s)
Antibacterianos , Clindamicina , Pie Diabético , Piel , Staphylococcus aureus , Clindamicina/administración & dosificación , Pie Diabético/tratamiento farmacológico , Pie Diabético/microbiología , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Staphylococcus aureus/efectos de los fármacos , Animales , Piel/microbiología , Piel/metabolismo , Poliésteres/química , Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos , Administración Cutánea , Parche Transdérmico , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Portadores de Fármacos/química
3.
J Am Acad Dermatol ; 90(5): 1006.e1-1006.e30, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38300170

RESUMEN

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

4.
J Infect Chemother ; 30(8): 785-788, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38185364

RESUMEN

Oxazolidinones, such as tedizolid and linezolid, are bacteriostatic antibiotics that inhibit protein synthesis. Based on the findings from animal studies and their mechanism of action, these antibiotics are considered for managing toxic shock caused by clindamycin-resistant Group A Streptococcus (GAS; Streptococcus pyogenes). However, clinical reports on their usage in such cases are limited. Herein, we report a case of a 67-year-old woman with chronic myeloid leukemia who presented with fever, facial swelling, and myalgia. She was diagnosed with cellulitis and empirically treated with meropenem. Blood culture later revealed GAS, and she was diagnosed with streptococcal toxic shock syndrome. The antibiotic regimen was adjusted based on sensitivity results, with clindamycin initially replaced by linezolid and later switched to tedizolid owing to concerns about potential bone marrow suppression. Her condition improved, and she was discharged 15 days after admission. Therefore, tedizolid may be a safer option for managing toxic shock syndrome in patients with comorbidities that include thrombocytopenia.


Asunto(s)
Antibacterianos , Clindamicina , Choque Séptico , Infecciones Estreptocócicas , Streptococcus pyogenes , Humanos , Femenino , Anciano , Choque Séptico/tratamiento farmacológico , Choque Séptico/microbiología , Antibacterianos/uso terapéutico , Streptococcus pyogenes/efectos de los fármacos , Streptococcus pyogenes/aislamiento & purificación , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/complicaciones , Clindamicina/uso terapéutico , Farmacorresistencia Bacteriana , Resultado del Tratamiento , Oxazolidinonas/uso terapéutico , Oxazolidinonas/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Celulitis (Flemón)/tratamiento farmacológico , Celulitis (Flemón)/microbiología , Pruebas de Sensibilidad Microbiana , Tetrazoles
5.
Acta Paediatr ; 113(7): 1694-1700, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38578153

RESUMEN

AIM: To compare the prophylactic efficacy of ampicillin and clindamycin against vertical transmission of group B Streptococcus from mothers to their infants by evaluating the rates of group B Streptococcus colonisation. METHODS: We retrospectively extracted data for mothers who delivered at Showa University Northern Yokohama Hospital between 1 October 2017 and 31 March 2021 and tested positive for antepartum group B Streptococcus, and their infants. The chi-square test was used to compare the rates of group B Streptococcus colonisation, sepsis, and meningitis. We conducted a multivariate logistic regression analysis, including the time interval between membrane rupture and delivery, chorioamnionitis, and maternal intrapartum fever (≥38.0°C). RESULTS: Two hundred fifty-nine mothers and their infants were eligible. Ampicillin and clindamycin were administered to 150 and 109 mothers, respectively. In the ampicillin and clindamycin groups, 12.0% (18/150) and 37.6% (41/109) infants were group B Streptococcus positive, respectively. The rate of group B Streptococcus colonisation among infants was significantly lower in the ampicillin group (p < 0.001). Multivariate regression analysis showed similar results (p < 0.001). No sepsis or meningitis cases were observed in either group. CONCLUSION: Prophylactic efficacy of clindamycin against the vertical transmission of group B Streptococcus is lower than that of ampicillin.


Asunto(s)
Ampicilina , Antibacterianos , Clindamicina , Transmisión Vertical de Enfermedad Infecciosa , Infecciones Estreptocócicas , Streptococcus agalactiae , Humanos , Ampicilina/uso terapéutico , Clindamicina/uso terapéutico , Femenino , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Estudios Retrospectivos , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/transmisión , Embarazo , Antibacterianos/uso terapéutico , Recién Nacido , Adulto , Profilaxis Antibiótica/métodos , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico
6.
J Shoulder Elbow Surg ; 33(4): 940-947, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38104721

RESUMEN

BACKGROUND: Periprosthetic joint infection (PJI) is a common source of failure following elbow arthroplasty. Perioperative prophylactic antibiotics are considered standard of care. However, there are no data regarding the comparative efficacy of various antibiotics in the prevention of PJI for elbow arthroplasty. Previous studies in shoulder, hip, and knee arthroplasty have demonstrated higher rates of PJI with administration of non-cefazolin antibiotics. The elbow has higher rates of PJI than other joints. Therefore, this study evaluated whether perioperative antibiotic choice affects rates of PJI in elbow arthroplasty. MATERIALS AND METHODS: A single-institution, prospectively collected total joint registry database was queried to identify patients who underwent primary elbow arthroplasty between 2003 and 2021. Elbows with known infection prior to arthroplasty (25) and procedures with incomplete perioperative antibiotic data (7) were excluded, for a final sample size of 603 total elbow arthroplasties and 19 distal humerus hemiarthroplasties. Cefazolin was administered in 561 elbows (90%) and non-cefazolin antibiotics including vancomycin (32 elbows, 5%), clindamycin (27 elbows, 4%), and piperacillin/tazobactam (2 elbows, 0.3%) were administered in the remaining 61 elbows (10%). Univariate and multivariate analyses were conducted to determine the association between the antibiotic administered and the development of PJI. Infection-free survivorship was estimated using the Kaplan-Meier method. RESULTS: Deep infection occurred in 47 elbows (7.5%), and 16 elbows (2.5%) were diagnosed with superficial infections. Univariate analysis demonstrated that patients receiving non-cefazolin alternatives were at significantly higher risk for any infection (hazard ratio [HR] 2.6, 95% confidence interval [CI] 1.4-5.0; P < .01) and deep infection (HR 2.7, 95% CI 1.3-5.5; P < .01) compared with cefazolin administration. Multivariable analysis, controlling for several independent predictors of PJI (tobacco use, male sex, surgical indication other than osteoarthritis, and American Society of Anesthesiologists score), showed that non-cefazolin administration had a higher risk for any infection (HR 2.8, 95% CI 1.4-5.3; P < .01) and deep infection (HR 2.9, 95% CI 1.3-6.3; P < .01). Survivorship free of infection was significantly higher at all time points for the cefazolin cohort. DISCUSSION: In primary elbow arthroplasty, cefazolin administration was associated with significantly lower rates of PJI compared to non-cefazolin antibiotics, even in patients with a greater number of prior surgeries, which is known to increase the risk of PJI. For patients with penicillin or cephalosporin allergies, preoperative allergy testing or a cefazolin test dose should be considered before administering non-cefazolin alternatives.


Asunto(s)
Artritis Infecciosa , Artroplastia de Reemplazo de Cadera , Infecciones Relacionadas con Prótesis , Humanos , Masculino , Cefazolina/uso terapéutico , Profilaxis Antibiótica/métodos , Codo , Infecciones Relacionadas con Prótesis/prevención & control , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Antibacterianos/uso terapéutico , Artritis Infecciosa/prevención & control , Estudios Retrospectivos
7.
J Arthroplasty ; 39(1): 242-249.e2, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37380142

RESUMEN

BACKGROUND: The aim of the present study was to compare causative bacteria and their antibiotic resistance profiles in patients developing a periprosthetic joint infection (PJI) based on preoperative prophylactic antibiotic regimens in primary total hip (THA) and primary total and unicompartmental knee arthroplasty (TKA/UKA). METHODS: We reviewed all cases of PJI occurring after primary THA and primary TKA/UKA, between 2011 and 2020 in a tertiary referral hospital. The standard preoperative prophylactic antibiotic for primary joint arthroplasty was cefuroxime and recommended second-line agent was clindamycin. Patients were divided by the replaced joint and analyzed independently. RESULTS: In the THA group, culture-positive PJI was detected in 61 of 3,123 (2.0%) cefuroxime-administered cases and 6 of 206 (2.9%) noncefuroxime-administered cases. In the TKA/UKA group, culture positive PJI was identified in 21 of 2,455 (0.9%) cefuroxime-administered cases and in 3 of 211 (1.4%) noncefuroxime administered cases. The most commonly isolated bacteria in both groups were coagulase negative staphylococci (CNS). There were no statistically significant differences of pathogen spectrum depending on the preoperative antibiotic regimen detected. Antibiotic resistance of isolated bacteria was significantly different in 4 of 27 (14.8%) analyzed antibiotics in THA and in 3 of 22 (13.6%) analyzed antibiotics in TKA/UKA. In all cohorts, a high occurrence of oxacillin-resistant CNS (50.0 to 100.0%) and clindamycin-resistant CNS (56.3 to 100.0%) has been observed. CONCLUSION: The use of the second-line antibiotic did not influence the pathogen spectrum or antibiotic resistance. However, an alarmingly high proportion of CNS strains was resistant to clindamycin.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Hipersensibilidad a las Drogas , Hipersensibilidad , Infecciones Relacionadas con Prótesis , Humanos , Antibacterianos/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Cefuroxima , Clindamicina , Farmacorresistencia Microbiana , Hipersensibilidad/complicaciones , Hipersensibilidad/tratamiento farmacológico , Medición de Resultados Informados por el Paciente , Penicilinas , Infecciones Relacionadas con Prótesis/etiología , Estudios Retrospectivos , Staphylococcus
8.
Drug Dev Res ; 85(3): e22182, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38704829

RESUMEN

Our research aims to reduce the bacterial resistance of clindamycin against Gram-positive bacteria and expand its range of bacterial susceptibility. First, we optimized the structure of clindamycin based on its structure-activity relationship. Second, we employed the fractional inhibitory concentration method to detect drugs suitable for combination with clindamycin derivatives. We then used a linker to connect the clindamycin derivatives with the identified combined therapy drugs. Finally, we tested antibacterial susceptibility testing and conducted in vitro bacterial inhibition activity assays to determine the compounds. with the highest efficacy. The results of our study show that we synthesized clindamycin propionate derivatives and clindamycin homo/heterodimer derivatives, which exhibited superior antibacterial activity compared to clindamycin and other antibiotics against both bacteria and fungi. In vitro bacteriostatic activity testing against four types of Gram-negative bacteria and one type of fungi revealed that all synthesized compounds had bacteriostatic effects at least 1000 times better than clindamycin and sulfonamides. The minimum inhibitory concentration (MIC) values for these compounds ranged from 0.25 to 0.0325 mM. Significantly, compound 5a demonstrated the most potent inhibitory activity against three distinct bacterial strains, displaying MIC values spanning from 0.0625 to 0.0325 mM. Furthermore, our calculations indicate that compound 5a is safe for cellular use. In conclusion, the synthesized compounds hold great promise in addressing bacterial antibiotic resistance.


Asunto(s)
Antibacterianos , Clindamicina , Diseño de Fármacos , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Clindamicina/farmacología , Clindamicina/síntesis química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Relación Estructura-Actividad , Humanos , Bacterias Grampositivas/efectos de los fármacos , Antifúngicos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química
9.
Int J Mol Sci ; 25(8)2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38673971

RESUMEN

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.


Asunto(s)
Antibacterianos , Infecciones Bacterianas , Materiales Biocompatibles , Clindamicina , Sistemas de Liberación de Medicamentos , Humanos , Clindamicina/uso terapéutico , Clindamicina/administración & dosificación , Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos/métodos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/prevención & control , Portadores de Fármacos/química , Animales
10.
BMC Oral Health ; 24(1): 551, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734599

RESUMEN

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.


Asunto(s)
Clindamicina , Fluconazol , Geles , Liposomas , Nanopartículas , Tamaño de la Partícula , Enfermedades Periodontales , Clindamicina/administración & dosificación , Clindamicina/uso terapéutico , Nanopartículas/química , Fluconazol/administración & dosificación , Fluconazol/farmacología , Enfermedades Periodontales/tratamiento farmacológico , Antifúngicos/administración & dosificación , Antifúngicos/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Microscopía Electrónica de Transmisión , Temperatura , Rastreo Diferencial de Calorimetría , Candida albicans/efectos de los fármacos , Viscosidad , Lípidos/química , Humanos
11.
J Contemp Dent Pract ; 25(3): 231-235, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38690695

RESUMEN

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.


Asunto(s)
Amoxicilina , Antibacterianos , Recubrimiento Dental Adhesivo , Resinas Epoxi , Materiales de Obturación del Conducto Radicular , Humanos , Materiales de Obturación del Conducto Radicular/química , Técnicas In Vitro , Clindamicina , Ensayo de Materiales , Análisis del Estrés Dental , Obturación del Conducto Radicular/métodos
12.
Clin Infect Dis ; 77(8): 1120-1125, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37310038

RESUMEN

Antimicrobials are commonly prescribed and often misunderstood. With more than 50% of hospitalized patients receiving an antimicrobial agent at any point in time, judicious and optimal use of these drugs is paramount to advancing patient care. This narrative will focus on myths relevant to nuanced consultation from infectious diseases specialists, particularly surrounding specific considerations for a variety of antibiotics.


Asunto(s)
Antiinfecciosos , Enfermedades Transmisibles , Humanos , Antibacterianos/uso terapéutico , Clindamicina , Enfermedades Transmisibles/tratamiento farmacológico
13.
Clin Infect Dis ; 76(2): 346-350, 2023 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-36056891

RESUMEN

Group A Streptococcus (GAS) necrotizing soft tissue infections and toxic shock syndrome remain high-mortality conditions. In vitro and animal model data, as well as multiple observational studies, suggest adjunctive clindamycin (ie, given with a beta-lactam) reduces invasive GAS infection mortality by inhibiting exotoxin production. Unfortunately, clindamycin resistance in GAS has been rapidly increasing in the United States since the mid-2010s, although the clinical significance of this remains unclear. Linezolid is a promising alternative adjunctive agent to which US GAS isolates remain near-universally susceptible, with a similar mechanism of action and similar in vitro evidence of GAS virulence factor attenuation. However, the clinical data supporting linezolid's value in severe GAS infections are far more limited. Here the authors review the data and reasoning behind a general preference for clindamycin or linezolid in a focused, pro-con debate format.


Asunto(s)
Antiinfecciosos , Fascitis Necrotizante , Choque Séptico , Infecciones de los Tejidos Blandos , Infecciones Estreptocócicas , Animales , Clindamicina/farmacología , Clindamicina/uso terapéutico , Linezolid/farmacología , Linezolid/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Choque Séptico/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes
14.
Emerg Infect Dis ; 29(5)2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37080963

RESUMEN

Clindamycin and ß-lactam antibiotics have been mainstays for treating invasive group A Streptococcus (iGAS) infection, yet such regimens might be limited for strains displaying MLSB phenotypes. We investigated 76 iGAS isolates from 66 patients in West Virginia, USA, during 2020-2021. We performed emm typing using Centers for Disease Control and Prevention guidelines and assessed resistance both genotypically and phenotypically. Median patient age was 42 (range 23-86) years. We found 76% of isolates were simultaneously resistant to erythromycin and clindamycin, including all emm92 and emm11 isolates. Macrolide resistance was conferred by the plasmid-borne ermT gene in all emm92 isolates and by chromosomally encoded ermA, ermB, and a single mefA in other emm types. Macrolide-resistant iGAS isolates were typically resistant to tetracycline and aminoglycosides. Vulnerability to infection was associated with socioeconomic status. Our results show a predominance of macrolide-resistant isolates and a shift in emm type distribution compared with historical reports.


Asunto(s)
Eritromicina , Infecciones Estreptocócicas , Humanos , Eritromicina/farmacología , Antibacterianos/farmacología , Clindamicina , Macrólidos , West Virginia/epidemiología , Farmacorresistencia Bacteriana/genética , Pruebas de Sensibilidad Microbiana , Infecciones Estreptocócicas/epidemiología , Streptococcus pyogenes/genética , Fenotipo
15.
Bioorg Med Chem Lett ; 91: 129364, 2023 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-37295615

RESUMEN

Hydrogen-tritium exchange is widely employed for radioisotopic labeling of molecules of biological interest but typically involves the metal-promoted exchange of sp2-hybridized carbon-hydrogen bonds, a strategy that is not directly applicable to the antibiotic iboxamycin, which possesses no such bonds. We show that ruthenium-induced 2'-epimerization of 2'-epi-iboxamycin in HTO (200 mCi) of low specific activity (10 Ci/g, 180 mCi/mmol) at 80 °C for 18 h affords after purification tritium-labeled iboxamycin (3.55 µCi) with a specific activity of 53 mCi/mmol. Iboxamycin displayed an apparent inhibition constant (Ki, app) of 41 ± 30 nM towards Escherichia coli ribosomes, binding approximately 70-fold more tightly than the antibiotic clindamycin (Ki, app = 2.7 ± 1.1 µM).


Asunto(s)
Antibacterianos , Clindamicina , Antibacterianos/química , Clindamicina/química , Clindamicina/metabolismo , Hidrógeno , Tritio/química , Rutenio/química
16.
Paediatr Perinat Epidemiol ; 37(3): 239-251, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36651636

RESUMEN

BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). STUDY SELECTION AND DATA EXTRACTION: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2  = 62%, and 0.59 (95% CI 0.42, 0.82), I2  = 0 before; and 0.95 (95% CI 0.81, 1.11), I2  = 59%, and 0.90 (95% CI: 0.72, 1.12), I2  = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.


Asunto(s)
Nacimiento Prematuro , Vaginosis Bacteriana , Femenino , Humanos , Recién Nacido , Embarazo , Antibacterianos/uso terapéutico , Clindamicina/uso terapéutico , Metronidazol/uso terapéutico , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/prevención & control , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/prevención & control
17.
J Am Acad Dermatol ; 89(5): 927-935, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37656094

RESUMEN

BACKGROUND: A three-pronged acne treatment approach-combining an antibiotic, antibacterial agent, and retinoid-may provide greater efficacy than single/double treatments. Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (IDP-126) is the first fixed-dose triple-combination in development for acne. OBJECTIVE: To confirm efficacy, safety, and tolerability of IDP-126 gel in acne treatment. METHODS: Two phase 3, double-blind, 12-week studies randomized participants aged ≥9 years with moderate-to-severe acne (N = 183; N = 180) 2:1 to once-daily IDP-126 or vehicle gel. Co-primary endpoints comprised participants achieving ≥2-grade reduction from baseline in Evaluator's Global Severity Score (EGSS) and clear/almost clear skin (treatment success) and change from baseline in inflammatory/noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: At week 12, 49.6% and 50.5% of participants achieved treatment success with IDP-126 versus 24.9% and 20.5% with vehicle (P < .01, both). IDP-126 also provided significantly greater reductions in inflammatory/noninflammatory lesions versus vehicle (least-squares mean percent range: 72.7% to 80.1% vs 47.6% to 59.6%; P < .001, all). Most TEAEs were of mild-moderate severity. LIMITATIONS: Inter-observer bias/variation in acne severity ratings, limited treatment duration, and population differences that may not generalize to real-world populations. CONCLUSION: The innovative fixed-dose, triple-combination IDP-126 gel was efficacious and well tolerated in 2 clinical studies of participants with moderate-to-severe acne.

18.
J Cutan Pathol ; 50(10): 864-868, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37430411

RESUMEN

A 61-year-old African-American female with moderately controlled Hailey-Hailey disease (HHD) presents to the emergency department with a rash and fever. One day prior to her presentation, she was started on oral clindamycin for a tooth extraction procedure. Her physical examination shows diffuse erythema on the trunk and extremities with multiple nonfollicular pustules. A punch biopsy of her upper extremity revealed intraepidermal acantholysis, neutrophilic spongiosis, and subcorneal pustules. The perivascular and interstitial superficial dermal infiltrate is mixed and composed of predominantly neutrophils, with lymphocytes and rare eosinophils. These findings suggest a superimposed acute generalized exanthematous pustulosis (AGEP) in the background of HHD. AGEP is a potentially severe cutaneous condition characterized by the abrupt onset of numerous nonfollicular pustules in a background of pruritic edematous erythroderma. To date, only two case reports have described AGEP in patients with HHD. Early diagnosis of AGEP is essential to initiate prompt and aggressive systemic therapy, prompt medication cessation, close monitoring for end-organ damage, and improve overall morbidity and mortality.


Asunto(s)
Pustulosis Exantematosa Generalizada Aguda , Exantema , Pénfigo Familiar Benigno , Humanos , Femenino , Persona de Mediana Edad , Pustulosis Exantematosa Generalizada Aguda/tratamiento farmacológico , Pustulosis Exantematosa Generalizada Aguda/etiología , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Clindamicina/efectos adversos , Pénfigo Familiar Benigno/tratamiento farmacológico , Exantema/patología , Piel/patología
19.
Ann Clin Microbiol Antimicrob ; 22(1): 30, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37098571

RESUMEN

BACKGROUND: Finegoldia magna (formerly known as Peptococcus magnus or Peptostreptococcus magnus) belonging to phylum Firmicutes, class Clostridia and genus Finegoldia, is the only species known to cause infections in human beings. Amongst Gram positive anaerobic cocci, F. magna is known to be the most virulent with a high pathogenic potential. Significant upsurge in antimicrobial resistance among anaerobes has been documented by various studies. F. magna is known to be susceptible to most of the anti-anaerobic antimicrobials, however, multidrug resistant strains are being reported in literature. The present study was undertaken to highlight the role of F. magna in clinical infections and to analyze their antimicrobial susceptibility patterns. METHODS: The present study was conducted in a tertiary care teaching hospital in Southern India. 42 clinical isolates of F. magna recovered from diverse clinical infections between January 2011 to December 2015 were studied. These isolates were subjected to antimicrobial susceptibility testing against metronidazole, clindamycin, cefoxitin, penicillin, chloramphenicol and linezolid. RESULTS: Among the 42 isolates studied, majority of them were revived from diabetic foot infections (31%) followed by necrotizing fasciitis (19%) and deep-seated abscesses (19%). All the F. magna isolates showed good in-vitro activity against metronidazole, cefoxitin, linezolid and chloramphenicol. Clindamycin and penicillin resistance were observed against 9.5% and 2.4% of the isolates respectively. However, ß-lactamase activity was not detected. CONCLUSION: The antimicrobial resistance among anaerobes varies from pathogen to pathogen and region to region. Hence, a deep understanding of resistance pattern is necessary for better management of clinical infections.


Asunto(s)
Antiinfecciosos , Clindamicina , Humanos , Antibacterianos/farmacología , Cefoxitina , Metronidazol , Linezolid , Pruebas de Sensibilidad Microbiana , Bacterias Anaerobias , Cloranfenicol
20.
Dermatology ; 239(4): 670-674, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37080176

RESUMEN

BACKGROUND: Antibiotic resistance is a major concern, especially in hidradenitis suppurativa (HS). However, antibiotics form a cornerstone in its treatment. Topical clindamycin is known to cause bacterial resistance but is still advised as monotherapy for the treatment of mild to moderate HS. METHODS: This is a randomized, controlled, assessor-blinded, intra-patient pilot trial to compare the clinical efficacy of clindamycin-benzoyl peroxide gel with clindamycin lotion in patients with mild to moderate HS. Two contralateral body sites were randomized for treatment in each patient. The primary outcome was the difference in the International Hidradenitis Suppurativa Severity Score (IHS4) between the two groups after 12 weeks. Secondary objectives were feasibility of the intra-patient design, efficacy within treatment groups, effect on HS pain, HS itch, patient satisfaction, antibiotic resistance, and the prolonged efficacy after 16 weeks. RESULTS: Ten patients were included, resulting in two groups of 10 treated body sites. No significant differences were found between the two groups for all measurements after 12 or 16 weeks, while both therapies led to an improvement in the IHS4, pain, and itch scores. A significant decrease was observed in the IHS4 for both the clindamycin lotion (-1.5; p < 0.05) and the clindamycin-benzoyl peroxide gel (-2; p < 0.01) after 16 weeks, and the pain scores were reduced from 7 to 2.5, p < 0.01 and 6.5 to 3, p = 0.03, respectively. Using the IHS4-55, we identified 50% of patients as responders in both groups after 12 weeks. The intra-patient design, however, unexpectedly appeared to hinder the inclusion of patients. CONCLUSION: Clindamycin-benzoyl peroxide gel showed favorable clinical efficacy results, similar to clindamycin lotion, suggesting that it could replace clindamycin lotion in the treatment of mild to moderate HS and to prevent antibiotic resistance. A larger controlled trial is needed to validate these results.


Asunto(s)
Acné Vulgar , Hidradenitis Supurativa , Humanos , Clindamicina/uso terapéutico , Proyectos Piloto , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/complicaciones , Acné Vulgar/tratamiento farmacológico , Antibacterianos/uso terapéutico , Peróxido de Benzoílo/uso terapéutico , Resultado del Tratamiento , Dolor/etiología , Índice de Severidad de la Enfermedad
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