RESUMO
BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful disease affecting flexures and other skin regions, producing nodules, abscesses and skin tunnels. Laser treatment targeting hair follicles and deroofing of skin tunnels are standard HS interventions in some countries but are rarely offered in the UK. OBJECTIVES: To describe current UK HS management pathways and influencing factors to inform the design of future randomized controlled trials (RCTs). METHODS: THESEUS was a nonrandomized 12-month prospective cohort study set in 10 UK hospitals offering five interventions: oral doxycycline 200â mg daily; oral clindamycin and rifampicin both 300â mg twice daily for 10 weeks, extended for longer in some cases; laser treatment targeting hair follicles; deroofing; and conventional surgery. The primary outcome was the combination of clinician-assessed eligibility and participant hypothetical willingness to receive each intervention. The secondary outcomes were the proportion of participants selecting each intervention as their final treatment option; the proportion who switch treatments; treatment fidelity; and attrition rates. THESEUS was prospectively registered on the ISRCTN registry: ISRCTN69985145. RESULTS: The recruitment target of 150 participants was met after 18â months, in July 2021, with two pauses due to the COVID-19 pandemic. Baseline demographics reflected the HS secondary care population: average age 36â years, 81% female, 20% non-White, 64% current or ex-smokers, 86% body mass index ≥ 25, 68% with moderate disease, 19% with severe disease and 13% with mild disease. Laser was the intervention with the highest proportion (69%) of participants eligible and willing to receive treatment, then deroofing (58%), conventional surgery (54%), clindamycin and rifampicin (44%), and doxycycline (37%). Laser was ranked first choice by the greatest proportion of participants (41%). Attrition rates were 11% and 17% after 3 and 6â months, respectively. Concordance with doxycycline was 52% after 3â months due to lack of efficacy, participant choice and adverse effects. Delays with procedural interventions were common, with only 43% and 26% of participants starting laser and deroofing, respectively, after 3â months. Uptake of conventional surgery was too small to characterize the intervention. Switching treatment was uncommon and there were no serious adverse events. CONCLUSIONS: THESEUS has established laser treatment and deroofing for HS in the UK and demonstrated their popularity with patients and clinicians for future RCTs.
Assuntos
Clindamicina , Hidradenite Supurativa , Feminino , Humanos , Adulto , Masculino , Clindamicina/uso terapêutico , Rifampina , Hidradenite Supurativa/cirurgia , Doxiciclina/uso terapêutico , Estudos de CoortesRESUMO
BACKGROUND: Chromobacterium is a genus of fourteen species with validly published names, most often found in soil and waters in tropical and subtropical regions around the world. The most well-known species of the genus, C. violaceum, occasionally causes clinically relevant infections; cases of soft tissue infections with septicemia and fatal outcomes have been described. CASE PRESENTATION: Here, we present a clinical case report of a 79-year-old man from Sweden with a soft-tissue infection and septicemia. The pathogen was identified as a strain of Chromobacterium species, but not C. violaceum. The patient was treated with clindamycin and ciprofloxacin and recovered well. CONCLUSIONS: This case report demonstrates the potential of Chromobacterium species as infectious agents in immunocompetent patients. It also indicates the existence of a novel species.
Assuntos
Infecções por Bactérias Gram-Negativas , Sepse , Masculino , Humanos , Idoso , Chromobacterium , Suécia , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/microbiologia , Ciprofloxacina/uso terapêutico , Clindamicina/uso terapêutico , Infecções por Bactérias Gram-Negativas/microbiologiaRESUMO
BACKGROUND: This case involves a 28-year-old pregnant woman (39w+2) who was admitted to obstetrics due to abdominal tightness and bacteremia with Gardnerella vaginalis which developed after caesarean section and vaginal myomectomy. METHODS: A blood culture was performed, and the bacteria were identified through mass spectrometry. RESULTS: Mass spectrometry data indicated that the infection bacteria were Gardnerella vaginalis. The patient's temperature returned to normal after oral ampicillin in combination with clindamycin. CONCLUSIONS: Gardnerella vaginalis bacteremia is very rare in clinical practice, and the combination of ampicillin and clindamycin has a good therapeutic effect. This study may provide a reference for the diagnosis and treatment of Gardnerella vaginalis bacteremia.
Assuntos
Bacteriemia , Miomectomia Uterina , Vaginose Bacteriana , Feminino , Gravidez , Humanos , Adulto , Gardnerella vaginalis , Gestantes , Clindamicina/uso terapêutico , Cesárea/efeitos adversos , Ampicilina/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Vaginose Bacteriana/tratamento farmacológico , VaginaRESUMO
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.
Assuntos
Antibacterianos , Clindamicina , Choque Séptico , Infecções Estreptocócicas , Streptococcus pyogenes , Humanos , Feminino , Idoso , Choque Séptico/tratamento farmacológico , Choque Séptico/microbiologia , Antibacterianos/uso terapêutico , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/isolamento & purificação , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/complicações , Clindamicina/uso terapêutico , Farmacorresistência Bacteriana , Resultado do Tratamento , Oxazolidinonas/uso terapêutico , Oxazolidinonas/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Celulite (Flegmão)/tratamento farmacológico , Celulite (Flegmão)/microbiologia , Testes de Sensibilidade Microbiana , TetrazóisRESUMO
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a global concern, primarily as a cause of skin and soft tissue infections, particularly in young people. Here, we describe a case of unilateral multiple lymphadenitis caused by the CA-MRSA sequence type (ST) 834 strain. A previously healthy 15-year-old girl was referred to our hospital with fever and swollen lymph nodes in the right axillary, cubital, and groin regions. Imaging examinations revealed enlargement of the lymph nodes in these areas but no swelling in any other lymph nodes. The patient had self-destructive lymph nodes in her groin. MRSA was detected in all swollen lymph node samples. Antimicrobial susceptibility tests showed that MRSA was susceptible to clindamycin and levofloxacin, leading to the suspicion of CA-MRSA. Genetic analysis revealed that all strains were ST834 and carried the staphylococcal cassette chromosome mec IV and the toxic shock syndrome toxin-1 gene but not the Panton-Valentine leukocidin gene. The patient was treated with linezolid followed by oral clindamycin. This was a rare case of unilateral multiple lymphadenitis caused by ST834 CA-MRSA. Although ST834 strains are rarely reported, lymphadenitis has been frequently reported and is considered more likely to cause lymphadenitis than other CA-MRSA strains.
Assuntos
Antibacterianos , Infecções Comunitárias Adquiridas , Linfadenite , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Feminino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Adolescente , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Linfadenite/microbiologia , Linfadenite/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Clindamicina/uso terapêutico , Testes de Sensibilidade Microbiana , Linezolida/uso terapêuticoRESUMO
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
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.
Assuntos
Ampicilina , Antibacterianos , Clindamicina , Transmissão Vertical de Doenças Infecciosas , Infecções Estreptocócicas , Streptococcus agalactiae , Humanos , Ampicilina/uso terapêutico , Clindamicina/uso terapêutico , Feminino , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Estudos Retrospectivos , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/transmissão , Gravidez , Antibacterianos/uso terapêutico , Recém-Nascido , Adulto , Antibioticoprofilaxia/métodos , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológicoRESUMO
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
OBJECTIVES: The study aims to overview German dentists' development of antibiotic and analgesic prescriptions from 2012 to 2021. MATERIALS AND METHODS: A longitudinal database analysis was performed based on the annual reports of the "Research Institute for Local Health Care Systems" (WIdO, Berlin). RESULTS: From 2012 until 2021, dental antibiotic prescriptions fell by 17.9%. In contrast, the dental proportion of antibiotic prescriptions compared to all antibiotic prescriptions in Germany increased from 9.1 to 13.6%. Aminopenicillins enhanced their share from 35.6 to 49.4%, while clindamycin prescriptions declined from 37.8 to 23.4%. The proportion of ibuprofen prescriptions significantly increased from 60.4% in 2012 to 79.0% in 2021. CONCLUSIONS: Since 2013, the most frequently prescribed antibiotic by German dentists has been amoxicillin reaching nearly half of all dental antibiotic prescriptions in 2021. Simultaneously, the proportion of clindamycin has steadily decreased, but the level is still high compared to international data. During the past decade, ibuprofen as a first-line analgesic in German dentistry was continuously gaining in importance. CLINICAL RELEVANCE: Aminopenicillins have the best risk-benefit balance in dentistry, but the use of antibiotics generally must be limited only to cases of severe infections or compromised patients. Pre-existing diseases or permanent medications should always be considered when choosing an analgesic.
Assuntos
Antibacterianos , Clindamicina , Humanos , Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Ibuprofeno/uso terapêutico , Analgésicos/uso terapêutico , Alemanha , Penicilinas , PrescriçõesRESUMO
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
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.
Assuntos
Anti-Infecciosos , Fasciite Necrosante , Choque Séptico , Infecções dos Tecidos Moles , Infecções Estreptocócicas , Animais , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Linezolida/farmacologia , Linezolida/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Choque Séptico/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenesRESUMO
BACKGROUND: Antimicrobial susceptibility testing (AST) is not routinely performed for Clostridioides difficile and data evaluating minimum inhibitory concentrations (MICs) are limited. We performed AST and whole genome sequencing (WGS) for 593 C. difficile isolates collected between 2012 and 2017 through the Centers for Disease Control and Prevention's Emerging Infections Program. METHODS: MICs to 6 antimicrobial agents (ceftriaxone, clindamycin, meropenem, metronidazole, moxifloxacin, and vancomycin) were determined using the reference agar dilution method according to Clinical and Laboratory Standards Institute guidelines. Whole genome sequencing was performed on all isolates to detect the presence of genes or mutations previously associated with resistance. RESULTS: Among all isolates, 98.5% displayed a vancomycin MIC ≤2 µg/mL and 97.3% displayed a metronidazole MIC ≤2 µg/mL. Ribotype 027 (RT027) isolates displayed higher vancomycin MICs (MIC50: 2 µg/mL; MIC90: 2 µg/mL) than non-RT027 isolates (MIC50: 0.5 µg/mL; MIC90: 1 µg/mL) (P < .01). No vanA/B genes were detected. RT027 isolates also showed higher MICs to clindamycin and moxifloxacin and were more likely to harbor associated resistance genes or mutations. CONCLUSIONS: Elevated MICs to antibiotics used for treatment of C. difficile infection were rare, and there was no increase in MICs over time. The lack of vanA/B genes or mutations consistently associated with elevated vancomycin MICs suggests there are multifactorial mechanisms of resistance. Ongoing surveillance of C. difficile using reference AST and WGS to monitor MIC trends and the presence of antibiotic resistance mechanisms is essential.
Assuntos
Clostridioides difficile , Infecções por Clostridium , Humanos , Estados Unidos/epidemiologia , Vancomicina/farmacologia , Vancomicina/uso terapêutico , Metronidazol/uso terapêutico , Clindamicina/uso terapêutico , Moxifloxacina/uso terapêutico , Clostridioides/genética , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Genômica , Testes de Sensibilidade Microbiana , RibotipagemRESUMO
BACKGROUND: The use of oral antimicrobial agents in patients with short bowel syndrome (SBS) is challenging due to the changes in gastrointestinal anatomy that may result in diminished absorption and altered drug bioavailability. Prospective studies evaluating bioavailability of antimicrobial agents after oral administration in SBS patients are lacking. OBJECTIVES: To determine the bioavailability of orally administered antimicrobial agents commonly used for treatment in SBS patients to guide clinical decision making when faced with infections. METHODS: We performed an explorative, clinical study investigating the pharmacokinetics (PK) of clindamycin, ciprofloxacin, flucloxacillin and fluconazole in SBS patients with intestinal failure. Participants received a combination of two antimicrobial agents simultaneously. To determine the oral bioavailability, participants received a single oral and IV dose of both agents on two occasions, after which they underwent intensive PK sampling on six predefined time points up to 12 hours after administration. Primary outcome was the oral bioavailability of these antimicrobial agents. Secondary outcomes were intravenous PK characteristics following non-compartmental analysis. RESULTS: Eighteen SBS patients were included: the mean (SD) age was 59 (17) years and 61% of participants were female. The median observed (IQR) bioavailability of ciprofloxacin, clindamycin, flucloxacillin and fluconazole were 36% (24-50), 93% (56-106), 50% (32-76) and 98% (61-107), respectively. CONCLUSION: The bioavailability of selected antimicrobial agents in certain patients with SBS appeared to be better than expected, providing a feasible treatment option. Due to the large observed differences between patients, therapeutic drug monitoring should be part of the treatment to safeguard adequate exposure in all patients. TRIAL REGISTRATION: Registered in the Dutch Trial Register (NL7796) and EudraCT number 2019-002587-28.
Assuntos
Anti-Infecciosos , Síndrome do Intestino Curto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Floxacilina , Clindamicina/uso terapêutico , Estudos Prospectivos , Fluconazol , Administração Oral , CiprofloxacinaRESUMO
BACKGROUND: Despite recent advances for treating cerebral toxoplasmosis (CT), monitoring the parasite burden and treatment response is still challenging. miRNAs are small non-coding RNAs with regulatory functions that can be used in diagnosis and treatment monitoring. We investigated the changes in miR-146a, BAG-1 gene, IL-6, and IL-10 tissue levels in the brain of BALB/c mice with chronic CT caused by the PRU strain of T. gondii following anti-parasitic and antibiotic treatment. METHOD: Fifty-three 6-to 8-week-old BALB/c mice were infected using intraperitoneal inoculation of cerebral cysts of T. gondii PRU strain and then divided into five groups as follows: group 1 included mice treated with 100 mg/kg/d Atovaquone (AT), group 2 included mice treated with 400 mg/kg/d clindamycin (CL), group 3 included mice treated with combination therapy (AT + CL), group 4 included infected untreated mice as a positive control (PC), and; group 5 included uninfected untreated mice as negative control (NC). After the completion of the treatment course, tissue level of mir-146a, miR-155, BAG-1 gene, IL-6, and IL-10 was investigated with real-time polymerase chain reaction. The IL-6/IL-10 ratio was calculated as an indicator of immune response. Moreover, brain cyst numbers were counted on autopsy samples. RESULTS: miR-146a, IL-6, IL-10, and BAG-1 genes were expressed in PC, but not in the NC group; miR-146a, IL-6, IL-10, and BAG-1 gene expression were significantly lower in AT, CL, and AT + CL compared with PC. MiR-146a and BAG-1 levels in AT and CL were not different statistically, however, they both had lower levels compared to AT + CL (P < 0.01). There was no difference in the expression of IL-6 and IL-10 between treatment groups. BAG-1 expression was significantly lower in AT, than in CL and AT + CL (P < 0.0089 and < 0.002, respectively). The PC group showed a higher ratio of IL-6/IL-10, although this increase was not statistically significant. It is noteworthy that the treatment with AT reduced this ratio; in the inter-group comparison, this ratio showed a decrease in the AT and AT + CL compared to the PC. The number of brain tissue cysts was significantly lower in AT, CL, and AT + CL, than in PC (p < 0.0001). AT had significantly lower brain cysts than CL and AT + CL (P < 0.0001). CONCLUSION: It seems that the factors studied in the current research (microRNA and cytokines) are a suitable index for evaluating the response to antiparasitic and antibiotic treatment. However, more studies should be conducted in the future to confirm our findings.
Assuntos
Cistos , MicroRNAs , Toxoplasma , Toxoplasmose Cerebral , Animais , Camundongos , Toxoplasmose Cerebral/tratamento farmacológico , Atovaquona/farmacologia , Atovaquona/uso terapêutico , Citocinas/metabolismo , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Interleucina-10/genética , Interleucina-6 , Toxoplasma/metabolismo , MicroRNAs/genética , AntibacterianosRESUMO
BACKGROUND: We sought to define the frequency of antibiotic resistance over time in a collection of invasive GBS isolates derived from infant early-onset disease (EOD), late-onset disease (LOD), and late-late onset disease (LLOD). METHODS: A multicenter retrospective review of infants born from 1970 to 2021 with GBS isolated from blood, cerebrospinal fluid, synovial fluid, cellulitis, or bone. All isolates were serotyped and antimicrobial susceptibility testing performed using disk diffusion. RESULTS: The most common serotypes in our 2017 isolates were III (n = 1112, 55.1%), Ia (n = 445, 22%), Ib (n = 182, 9%) and II (n = 146, 7.2%). A total of 945 (46.8%) isolates were from infants with EOD, 976 (48.3%) from LOD, and 96 (4.75%) from LLOD. All isolates were penicillin-susceptible. Compared to strains isolated <2000, strains isolated ≥2000 showed significantly greater frequency of erythromycin (4.0% to 32.3%, P < 0.0001) and clindamycin (1.5% to 17.5%, P < 0.0001) resistance. Year of isolation (≥2000) and serotype V were significantly associated with erythromycin and/or clindamycin resistance. CONCLUSIONS: We document a rapid and significant increase in clindamycin and erythromycin resistance. As clindamycin may be considered in severely penicillin-allergic women needing GBS intrapartum prophylaxis, obstetricians, pediatricians, and neonatologist should be aware of this disturbing trend. IMPACT: Group B streptococcal strains isolated from infants with invasive infection have become more resistant to second-line antibiotics over time. In this epidemiologic study of 2017 group B streptococci isolated from 1970 to 2021, penicillin susceptibility remained uniform; however, resistance to erythromycin and clindamycin increased significantly over time across all capsular serotypes. Clindamycin resistance exceeded 20% by 2010 in most serotypes. While penicillin remains the treatment of choice for group B streptococcal infant disease, pediatricians and neonatologists should be aware of the high prevalence of resistance to clindamycin, a recommended alternative drug used for intrapartum-antibiotic prophylaxis in penicillin-allergic women.
Assuntos
Clindamicina , Infecções Estreptocócicas , Humanos , Lactente , Feminino , Clindamicina/uso terapêutico , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Farmacorresistência Bacteriana , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Eritromicina/uso terapêutico , Streptococcus agalactiae , Penicilinas/uso terapêutico , Testes de Sensibilidade MicrobianaRESUMO
PURPOSE OF REVIEW: The incidence of necrotizing soft-tissue infections (NSTI) has increased during recent decades. These infections are still associated with high morbidity and mortality, underlining a need for continued education of the medical community. This review will focus on practical approaches to management of NSTI focusing on antibiotic therapies and optimizing the management of group A streptococcus (GAS)-associated NSTIs. RECENT FINDINGS: Antibiotic therapy for NSTI patients faces several challenges as the rapid progression of NSTIs mandates broad-spectrum agents with bactericidal action. Current recommendations support using clindamycin in combination with penicillin in case of GAS-documented NSTIs. Linezolide could be an alternative in case of clindamycin resistance. SUMMARY: Reducing the time to diagnosis and first surgical debridement, initiating early broad-spectrum antibiotics and early referral to specialized centres are the key modifiable factors that may impact the prognosis of NSTIs. Causative organisms vary widely according to the topography of the infection, underlying conditions, and geographic location. Approximately one third of NSTIs are monomicrobial, involving mainly GAS or Staphylococcus aureus . Data for antibiotic treatment specifically for necrotizing soft-tissue infections are scarce, with guidelines mainly based on expert consensus.
Assuntos
Clindamicina , Pele , Humanos , Clindamicina/uso terapêutico , Antibacterianos/uso terapêutico , Linezolida , ConsensoRESUMO
Invasive Group B Streptococcus (GBS) can infect pregnant women, neonates, and older adults. Invasive GBS serotype VIII is infrequent in Alberta; however, cases have increased in recent years. Here, genomic analysis was used to characterize fourteen adult invasive serotype VIII isolates from 2009 to 2021. Trends in descriptive clinical data and antimicrobial susceptibility results were evaluated for invasive serotype VIII isolates from Alberta. Isolate genomes were sequenced and subjected to molecular sequence typing, virulence and antimicrobial resistance gene identification, phylogenetic analysis, and pangenome determination. Multilocus sequencing typing identified eight ST42 (Clonal Complex; CC19), four ST1 (CC1), and two ST2 (CC1) profiles. Isolates were susceptible to penicillin, erythromycin, chloramphenicol, and clindamycin, apart from one isolate that displayed erythromycin and inducible clindamycin resistance. All isolates carried genes for peptide antibiotic resistance, three isolates for tetracycline resistance, and one for macrolide, lincosamide, and streptogramin resistance. All genomes carried targets currently being considered for protein-based vaccines (e.g., pili and/or Alpha family proteins). Overall, invasive GBS serotype VIII is emerging in Alberta, primarily due to ST42. Characterization and continued surveillance of serotype VIII will be important for outbreak prevention, informing vaccine development, and contributing to our understanding of the global epidemiology of this rare serotype.
Assuntos
Clindamicina , Infecções Estreptocócicas , Recém-Nascido , Humanos , Feminino , Gravidez , Idoso , Sorogrupo , Clindamicina/uso terapêutico , Streptococcus agalactiae , Infecções Estreptocócicas/microbiologia , Alberta/epidemiologia , Filogenia , Tipagem de Sequências Multilocus , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Eritromicina/uso terapêutico , Genômica , Testes de Sensibilidade MicrobianaRESUMO
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.