BackgroundAs a new generation antihistamine, fexofenadine has been widely used in allergic diseases. However, there is still a lack of collective evidence regarding the antihistamine effects and safety profiles of fexofenadine relative to other antihistamine drugs and placebo. Therefore, we aimed to systematically evaluate the antihistamine effects and safety of fexofenadine.MethodsAn electronic literature search of randomized controlled trials (RCTs) was performed using Embase, Cochrane and PubMed from establishment to January 1st, 2018. RCTs comparing the antihistamine effects or safety (adverse events, sedative effects, and cognitive/psychomotor function) of fexofenadine with either other antihistamines or placebo for healthy subjects and patients with allergy were selected.ResultsFifty-one studies of 14,551 participants met the inclusion criteria. When compared with the first-generation antihistamines, fexofenadine produced significantly lower adverse events frequency (OR = 0.446; 95% CI: 0.214 to 0.929, P = 0.031), significantly lower sedative effects frequency (OR = 0.265; 95% CI: 0.072 to 0.976, P = 0.046) and significantly less change of all cognitive/psychomotor function. When compared with the second-generation antihistamines, fexofenadine produced significantly marginal sedative effects (OR = 0.59; 95% CI, 0.38 to 0.93; P = 0.02) and significantly less change of most of the cognitive/psychomotor function. When compared with placebo, fexofenadine produced more significant antihistamine effects.ConclusionsFexofenadine has a positive antihistamine effect, which is probably no worse than the second-generation antihistamines. Fexofenadine probably has a favorable safety profile, which is more likely better than that of the first-generation antihistamines. There is lack of data to support that fexofenadine has a better overall safety profile compared to the second-generation antihistamines, however, some presently available evidence on sedative effects and certain aspects of cognitive/psychomotor function favors fexofenadine. Therefore, fexofenadine may be worthy of recommendation for safety related workers.

PurposeThe main objective of our meta-analysis was to examine the in vitro synergistic effect of meropenem-based combination therapies against Acinetobacter baumannii through a systematic review of the existing literature.MethodsAn extensive search was performed with no restrictions on date of publication, language, and publication type. Our study evaluated the main conclusions drawn from various studies describing the synergistic activity of combination therapies in vitro.ResultsIn this review, 56 published studies were included. Our report included data on 20 types of antibiotics combined with meropenem in 1,228 Acinetobacter baumannii isolates. In time-kill studies, meropenem combined with polymyxin B and rifampicin showed synergy rates of 98.3% (95% CI, 83.7%–100.0%) and 89.4% (95% CI, 57.2%–100.0%), respectively, for Acinetobacter baumannii, modest synergy rates were found for meropenem combined with several antibiotics such as colistin and sulbactam, and no synergy effect was displayed in the combination of meropenem and ciprofloxacin, whereas in checkerboard method, the synergy rates of polymyxin B and rifampicin were 37.0% (95% CI, 0.00%–100.0%) and 56.3% (95% CI, 8.7%–97.8%), respectively.ConclusionWe found that time-kill studies generally identified the greatest synergy, while checkerboard and Etest methods yielded relatively poor synergy rates. Further well-designed in vivo studies should be carried out to confirm these findings.

We have conducted systematic structural modification, deconstruction, and reconstruction of the berberine core with the aim of lowering its cytotoxicity, investigating its pharmacophore, and ultimately, seeking novel synergistic agents to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. A structure-activity relationship study of 95 analogues led us to identify the novel scaffold of N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(substituted phenyl)acetamides 7 a-l, which exhibited remarkable levels of in vitro synergistic antifungal activity. Compound 7 d (N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-2-(2-fluorophenyl)acetamide) significantly decreased the MIC₈₀ values of fluconazole from 128.0 μg mL⁻¹ to 0.5 μg mL⁻¹ against fluconazole-resistant C. albicans and exhibited much lower levels of cytotoxicity than berberine toward human umbilical vein endothelial cells.

Given that tigecycline-based combination therapy is recognized as a valuable option for the treatment of tigecycline-resistant Acinetobacter baumannii, we conducted this systematic review and meta-analysis to assess the overall evidence of its effectiveness. The synergy rate was defined as the primary outcome that was calculated separately for time-kill, Etest, and checkerboard microdilution methods. The secondary outcomes were bactericidal activity and the efficacy of combination treatment on the development of resistance. In total, 37 published papers and 16 conference proceedings were included. Nine classes consisting of 22 antibiotic types in combination with tigecycline against 1,159 A. baumannii strains were reported in the analysis. For the time-kill studies, combination therapy showed a synergy rate of 37.9% (95% confidence interval [CI], 30.7-46.5); the highest synergy rate was 67.4% (95% CI, 27.3-91.9) for tigecycline in combination with colistin. Moreover, combination with amikacin or colistin could efficiently inhibit the development of tigecycline resistance. Compared with checkerboard microdilution and Etest methods, time-kill studies always showed higher synergy rates. Altogether, these results suggest that the in vitro tigecycline-based combinations resulted in moderate synergy rates and that several combinations could suppress the resistance of A. baumannii to tigecycline, which should be further confirmed in animal models and clinical trials.