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Determination of the mutant prevention concentration (MPC) and the mutant selection window (MSW) of antimicrobial agents used to treat pathogenic bacteria is important in order to apply effective antimicrobial therapies. Here, we determined the MPCs of the major topical antimicrobial agents against Propionibacterium acnes and Staphylococcus aureus which cause skin infections and compared their MSWs. Among the MPCs of nadifloxacin and clindamycin, the clindamycin MPC was determined to be the lowest against P. acnes. In contrast, the nadifloxacin MPC was the lowest against S. aureus. Calculations based on the minimum inhibitory concentrations and MPCs showed that clindamycin has the lowest MSW against both P. acnes and S. aureus. Nadifloxacin MSWs were 4-fold higher against P. acnes than against S. aureus. It is more likely for P. acnes to acquire resistance to fluoroquinolones than S. aureus. Therefore, topical application of clindamycin contributes very little to the emergence of resistant P. acnes and S. aureus strains.

An intensive survey of naturally-occurring regulators of polar auxin transport (PAT) was conducted in two oriental medicinal species from the Asteraceae, Saussurea costus and Atractylodes japonica, using the radish hypocotyl bioassay system and physicochemical analyses. Costunolide and santamarine were identified as well as dehydrocostus lactone from S. costus roots, and atractylenolide II and (+)-eudesma-4(14),7(11)-dien-8-one from Atractylodes japonica rhizomes as physiologically novel compounds possessing inhibitory activities of PAT. Costunolide and santamarine showed ca. 40% inhibition of PAT in the radish hypocotyl segments at a dose of 2.5 μg/plant and 1 μg/plant, respectively. Inhibitory effects of atractylenolide II and (+)-eudesma-4(14),7(11)-dien-8-one were ca. 10 times lower than those of costunolide and santamarine. Structure-activity relationships and possible mechanisms to inhibit PAT are also discussed.

IMP-type carbapenemase, found in various Gram-negative bacteria, has been increasingly detected worldwide. We aimed to study the outcomes and risk factors for acquisition of IMP-type carbapenemase-producing carbapenem-resistant Enterobacteriaceae (IMP-CRE), as this has not been evaluated in detail. We conducted a matched case-case-control study of patients from whom IMP-CRE isolates were obtained. All patients who tested positive for IMP-CRE were included and matched with those having carbapenem-susceptible Enterobacteriaceae (CSE) and with controls at a ratio of 1:1:2. The risk factors for acquisition between CRE and CSE groups, and mortality which were calculated using multivariate logistic regression model with weighting according to the inverse probability of propensity scores were compared. In total, 192 patients (96 CRE and CSE each; 130 Enterobacter cloacae and 62 Klebsiella spp.) were included. IMP-11 type was present in 43 patients, IMP-1 in 33, and IMP-60 and IMP-66 in 1; 31 (32.3%) patients with CRE and 34 (35.4%) with CSE developed infections. Multivariate analysis identified the following independent risk factors: gastrostomy, history of intravenous therapy or hemodialysis, and previous exposure to broad spectrum β-lactam antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, and carbapenems. On propensity score-adjusted analysis, mortality in the CRE and CSE groups (15.0% versus 19.5%, respectively) were similar. We found that IMP-CRE may not contribute to worsened clinical outcomes compared to CSE, and gastrostomy, previous intravenous therapy, hemodialysis, and broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Fluoroquinolone and aminoglycosides are potentially useful antibiotics for IMP-CRE infections.