Comparison of simulated candidemia detection during prophylactic antifungal therapy.

BACKGROUND: We investigated the neutralization performance of various automated blood culture systems for antifungal agents with regard to the most commonly isolated Candida species. METHODS: In this study, we evaluated the time to detection (TTD) of simulated candidemia for 6 Candida spp. (C. albicans, C. auris, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis) in 3 automated blood culture systems (BACTEC™ FX, BACT/ALERT® 3D, and BACT/ALERT® VIRTUO®), with or without trough and peak levels of eight antifungal agents (amphotericin B, anidulafungin, caspofungin, fluconazole, itraconazole, micafungin, posaconazole, and voriconazole). RESULTS: Caspofungin and micafungin significantly prolonged the TTDs for most of the tested strains in the 3 blood culture instruments, especially at peak concentrations. CONCLUSION: Peak concentrations of caspofungin and micafungin influence the performance of blood culture detection systems. Therefore, one should be careful about the possibility of prolonged TTDs for candidemia when using the abovementioned antifungal agents.

Bacterial culture and antibiotic susceptibility in patients with acute appendicitis.

PURPOSE: Essential treatment of acute appendicitis is surgical resection with the use of appropriate antibiotics. In order to effectively treat acute appendicitis, it is important to identify the microorganism of acute appendicitis and evaluate the effective antibiotics. METHODS: A total of 694 patients who underwent appendectomy for acute appendicitis and had positive microbial result between 2006 and 2015 were recruited. For microbial assessment, luminal contents of the appendix were swabbed after appendectomy. In patients with periappendiceal abscess, the specimens were obtained from abscess fluid. The patient characteristics, operative data, use of antibiotics, the results of microbiology, and postoperative morbidities including surgical site infection (SSI) were retrospectively reviewed. RESULTS: The mean age was 38.2 (± 19.8) years, and 422 patients (60.8%) were male. Most of the operations were performed by conventional laparoscopy (83.1%), followed by single-port laparoscopy (11.8%). The most common microorganism was Escherichia coli (64.6%), which was susceptible to amoxicillin/clavulanate, ciprofloxacin, most cephalosporins, piperacillin/tazobactam, and imipenem. The second most common microorganism was Pseudomonas aeruginosa (16.4%), which was resistant to amoxicillin/clavulanate and cefotaxime. The rate of postoperative morbidity was 8.6%, and the most common type was superficial SSI (6.2%), followed by ileus (1.2%), gastroenteritis (0.7%), and organ/space SSI (0.3%). P. aeruginosa (odds ratio = 2.128, 95% confidence interval 1.077-4.206, P = 0.030) was the only significant microorganism associated with SSI according to multivariate analysis adjusting for other clinical factors. CONCLUSIONS: In perforated appendicitis, the use of empirical antibiotics seems to be safe. In some cases of Pseudomonas infection, adequate antibiotics should be considered.

Combined treatment with silibinin and epidermal growth factor receptor tyrosine kinase inhibitors overcomes drug resistance caused by T790M mutation.

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) produce an initially dramatic response in lung cancer patients harboring a mutation in the EGFR gene, development of acquired resistance is almost inevitable. A secondary mutation of threonine 790 (T790M) is associated with approximately half of the cases of acquired resistance. This study investigated whether the addition of silibinin to therapy with gefitinib or erlotinib could overcome T790M-mediated drug resistance considering that silibinin has various antitumor effects, including EGFR modulation. Silibinin selectively reduced the activity of the EGFR family (EGFR, ErbB2, and ErbB3) through the inhibition of receptor dimerization in lung cancer cells with EGFR mutations, but not in those harboring the wild type. In primary and acquired resistant cells with T790M, addition of silibinin enhanced the ability of EGFR-TKIs to downregulate EGFR signals and to inhibit cell growth. Similarly, the combination of silibinin and erlotinib effectively suppressed tumor growth in erlotinib resistance-bearing PC-9 xenografts. The results indicate that the addition of silibinin to EGFR-TKIs is a promising strategy to overcome T790M-mediated drug resistance.

Impact of extensive drug resistance on treatment outcomes in non-HIV-infected patients with multidrug-resistant tuberculosis.

BACKGROUND: Recently, serious concerns about extensively drug-resistant tuberculosis (XDR-TB), which shows resistance to second-line anti-TB drugs in addition to isoniazid and rifampicin, have been raised. The aim of this study was to elucidate the impact of extensive drug resistance on treatment outcomes in non-human immunodeficiency virus (HIV)-infected patients with multidrug-resistant tuberculosis (MDR-TB). METHODS: Patients who received the diagnosis of and treatment as having MDR-TB at Seoul National University Hospital (Seoul, Republic of Korea) between January 1996 and December 2005 were included. The definition of XDR-TB was TB caused by bacilli showing resistance to both isoniazid and rifampicin and also showing resistance to any fluoroquinolone and to at least 1 of the following 3 injectable anti-TB drugs: capreomycin, kanamycin, and amikacin. To identify the impact of extensive drug resistance on treatment outcomes, univariate comparison and multiple logistic regression were performed. RESULTS: A total of 211 non-HIV-infected patients with MDR-TB were included in the final analysis. Among them, 43 patients (20.4%) had XDR-TB. Treatment failure was observed in 19 patients (44.2%) with XDR-TB, whereas treatment of 46 patients (27.4%) with non-XDR-TB failed (P=.057). The presence of extensive drug resistance (adjusted odds ratio [OR], 4.46; 95% confidence interval [CI], 1.35-14.74) and underlying comorbidity (adjusted OR, 2.62; 95% CI, 1.00-6.87) were independent risk factors for treatment failure. However, a higher level of albumin was inversely associated with treatment failure (adjusted OR, 0.87; 95% CI, 0.77-0.97). CONCLUSION: The presence of extensive drug resistance, the presence of comorbidity, and hypoalbuminemia were independent poor prognostic factors in non-HIV-infected patients with MDR-TB.