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Context: Fungal infections are very common, and several medications are used to treat them. Azoles are prescribed widely to treat fungal infections. In addition to therapeutic effects, any drug can be accompanied by side effects in patients. One of the most important complications in this regard is liver injury. Therefore, hepatotoxicity induced by azole antifungal drugs were reviewed in this study. Evidence Acquisition: English scientific papers were evaluated to review the effects of hepatotoxicity by azole antifungal agents, and the related studies' results were summarized using a table. The systematic search was implemented on electronic databases, including PubMed, Google Scholar, and Science Direct. Original articles and review articles that were published before April 1, 2022, were included in the study. Those articles without available full text or non-English articles were excluded. Also, articles that reported pediatric data were excluded. Results: Most studies have reported the effects of hepatotoxicity by azole antifungal agents, and their mechanisms have been described. Conclusions: Clinical evaluations regarding the hepatotoxicity of antifungal agents provided in the literature were reviewed. Therefore, it is recommended to prescribe these drugs with caution in high-risk patients suffering from liver diseases, and patients should be monitored for hepatotoxicity. However, more research is needed to evaluate the hepatotoxicity of azole antifungal agents and select appropriate drugs according to cost-effectiveness and the side effects' profiles, relying on lower incidence of this liver complication.
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Background: Pseudomonas aeruginosa is the most common microorganism found in the sputum culture of Cystic fibrosis (CF) patients causing the pulmonary destruction. Aminoglycosides have a low diffuse rate from lipid membranes, and respiratory system secretions. Regarding the burden of pulmonary exacerbation caused by the pseudomonas aeruginosa in cystic fibrosis patients in the long term and the limited number of clinical trials focused on appropriate treatment strategies, the present study evaluated the concurrent inhaled and intravenous aminoglycoside antibiotics for pulmonary exacerbation caused by the pseudomonas aeruginosa as a safe and effective treatment in children. Method: This study was a blinded, randomized clinical trial phase conducted in a tertiary referral pediatric teaching hospital from May 2021 to May 2022. The patients were randomly allocated to receive intravenously administered ceftazidime and Amikacin alone or with inhaled Amikacin. Forced expiratory volume (FEV1), Amikacin via the level, kidney function tests, audiometry, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), hospital stay, and bacterial eradication rate were compared in two therapy groups. Results: the average FEV1 has increased by 47% in Neb + group compared to Neb- group following treatment. Hospital stay was lower in Neb + group. No renal toxicity or ototoxicity was observed in both therapy groups. Pseudomonas aeruginosa eradication rate Neb- and Neb + groups were 44% and 69%, respectively (p-value = 0.15). Conclusion: Concurrent inhaled and intravenous Amikacin is safe and effective to treat Pseudomonas aeruginosa exacerbation in CF patients. Moreover, co-delivery antibiotics' route treatment increased the eradication rate. Although not statistically significant, never the less, it is clinically relevant. The intervention reduced the length of hospitalization in this group. Clinical Trial Registration: clinicaltrials.gov, identifier [IRCT20120415009475N10].
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We aimed to maximize the clinical response and effectiveness of colistin antibiotics in patients with multi-drug (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, there is an increasing interest in colistin combination therapy with other antibiotics and extended interval dosing regimens. This systematic review and meta-analysis aim is to evaluate if the combination therapy is superior to monotherapy with colistin regarding increased survival and also which dose interval is the most effective to utilize. English language, peer-reviewed journal publications from the first date available to 25 January 2022 were identified by searching the PubMed and Web of Science databases. Forest plots for overall and subgroups and funnel plots were graphed. 42 studies were included in the study. Among them, 38 studies were on combination therapy, and four on dose interval. The overall pooled odds ratio is 0.77 (CI: 0.62; 0.95) (p value < 0.017). The I^2 value was 43% (p value < 0.01). The Begg correlation test of funnel plot asymmetry showed no significant publication bias (0.064). The overall pooled odds ratio for Carbapenem is 0.74 (CI: 0.48; 1.13). A prospective randomized controlled trials (RCT) on 40 adults intensive care unit (ICU) patients with ventilator-associated pneumonia (VAP), comparing the mortality and ICU length of stay of 8- or 24- hour intervals regimens, showed that the ICU length of stay and ICU mortality were; 31.31, 35.3 days, and 32.06, 22.2% in groups 24-h interval and 8- hour interval (p value: 0.39, 0.87), respectively. It seems that combination therapy is associated with drug synergism and increased survival. The extended interval colistin administration may result in higher peak concentration and bacterial eradication. In both cases, we face a dearth of literature.