RESUMEN
The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro models may predict the efficacy of antibiotic regimens against CR-GNB. A systematic review and meta-analysis was performed including pharmacokinetic/pharmacodynamic (PK/PD) and time-kill (TK) studies examining the in vitro efficacy of antibiotic combinations against CR-GNB [PROSPERO registration no. CRD42019128104]. The primary outcome was in vitro synergy based on the effect size (ES): high, ES ≥ 0.75, moderate, 0.35 < ES < 0.75; low, ES ≤ 0.35; and absent, ES = 0). A network meta-analysis assessed the bactericidal effect and re-growth rate (secondary outcomes). An adapted version of the ToxRTool was used for risk-of-bias assessment. Over 180 combination regimens from 136 studies were included. The most frequently analysed classes were polymyxins and carbapenems. Limited data were available for ceftazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam. High or moderate synergism was shown for polymyxin/rifampicin against Acinetobacter baumannii [ES = 0.91, 95% confidence interval (CI) 0.44-1.00], polymyxin/fosfomycin against Klebsiella pneumoniae (ES = 1.00, 95% CI 0.66-1.00) and imipenem/amikacin against Pseudomonas aeruginosa (ES = 1.00, 95% CI 0.21-1.00). Compared with monotherapy, increased bactericidal activity and lower re-growth rates were reported for colistin/fosfomycin and polymyxin/rifampicin in K. pneumoniae and for imipenem/amikacin or imipenem/tobramycin against P. aeruginosa. High quality was documented for 65% and 53% of PK/PD and TK studies, respectively. Well-designed in vitro studies should be encouraged to guide the selection of combination therapies in clinical trials and to improve the armamentarium against carbapenem-resistant bacteria.
Asunto(s)
Antibacterianos/farmacología , Sinergismo Farmacológico , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Amicacina/farmacología , Compuestos de Azabiciclo/farmacología , Carbapenémicos/farmacología , Ceftazidima/farmacología , Cefalosporinas/farmacología , Colistina/farmacología , Combinación de Medicamentos , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Fosfomicina/farmacología , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Imipenem/farmacología , Técnicas In Vitro , Pruebas de Sensibilidad Microbiana , Polimixinas/farmacología , Rifampin/farmacología , Tazobactam/farmacología , Tobramicina/farmacologíaRESUMEN
The present study aimed to analyze the effect of LED phototherapy on the presence of hyalinization and root resorption during orthodontic tooth movement (OTM) in rats and to measure the amount of tooth movement. Eighty rats were allocated into two groups: LED and control (CON), where the LED rats were irradiated with infrared LED (850 nm, 30 mW) for 5 min during the first five days of OTM and where controls were not irradiated. Both groups were subdivided into four subgroups (n=10) according to the date of euthanasia (4, 7, 14 and 21 days). Five out of ten LED21 and five of ten CON21 rats were submitted to micro-computed tomography (µCT); µCT scans were taken on days 0, 7, 14 and 21. For histological study, maxillae were processed to light microscopy using Hematoxylin-Eosin (HE) and Tartrate-Resistant Acid Phosphatase (TRAP) histochemistry. The amount of tooth movement did not differ between LED and CON. Hyalinization was observed at the pressure areas in both groups, and it did not show a statistically significant difference between the groups. Root resorption was also observed in both groups after 7 days and it did not represent any differences between the two groups. LED phototherapy was not able to increase the amount of OTM. Similar characteristics of hyalinization and root resorption were observed in both groups.
Asunto(s)
Resorción Radicular , Técnicas de Movimiento Dental , Animales , Ratas , Ratas Wistar , Fosfatasa Ácida Tartratorresistente , Microtomografía por Rayos XRESUMEN
Abstract The present study aimed to analyze the effect of LED phototherapy on the presence of hyalinization and root resorption during orthodontic tooth movement (OTM) in rats and to measure the amount of tooth movement. Eighty rats were allocated into two groups: LED and control (CON), where the LED rats were irradiated with infrared LED (850 nm, 30 mW) for 5 min during the first five days of OTM and where controls were not irradiated. Both groups were subdivided into four subgroups (n=10) according to the date of euthanasia (4, 7, 14 and 21 days). Five out of ten LED21 and five of ten CON21 rats were submitted to micro-computed tomography (μCT); μCT scans were taken on days 0, 7, 14 and 21. For histological study, maxillae were processed to light microscopy using Hematoxylin-Eosin (HE) and Tartrate-Resistant Acid Phosphatase (TRAP) histochemistry. The amount of tooth movement did not differ between LED and CON. Hyalinization was observed at the pressure areas in both groups, and it did not show a statistically significant difference between the groups. Root resorption was also observed in both groups after 7 days and it did not represent any differences between the two groups. LED phototherapy was not able to increase the amount of OTM. Similar characteristics of hyalinization and root resorption were observed in both groups.
Resumo O presente estudo tem como objetivo analisar o efeito da fototerapia LED na presença da hialinização e reabsorção radicular durante o movimento dentário ortodôntico (MDO) em ratos, e a mensuração da quantidade de movimento dentário. Oitenta ratos foram alocados em dois grupos: LED e Controle (CON), os ratos foram irradiados com um LED infravermelho (850nm, 30mW) por 5 minutos durante os cinco primeiros dias da MDO; e o grupo controle não foi irradiado. Ambos os grupos foram subdivididos em 4 subgrupos (n=10) de acordo com a data da eutanásia (4, 7, 14 e 21 dias). Cinco dos dez ratos LED21 e cinco dos dez ratos CON21foram submetidos a microtomografia computadorizada (μCT); As μCT foram realizadas nos dias 0, 7, 14 e 21. Para o estudo histológico, as maxilas foram processadas para microscopia de luz, usando hematoxilina-eosina (HE) e Fosfatase ácido Tartrate-Resistente (TRAP) para histoquímica. A quantidade de movimento dentário não diferiu entre o LED e o CON. A hialinização foi observada nas áreas de pressão em ambos os grupos e não mostrou diferença estatisticamente significante. Reabsorção radicular também foi observada em ambos os grupos depois de 7 dias e não houve diferença entre os grupos. A fototerapia LED não aumentou a quantidade de MDO. Características similares de hialinização e reabsorção radicular foram observadas em ambos os grupos