Background: Mycobacterium abscessus frequently causes severe infections, yet its pathophysiological features and treatment regimens have not been established. Case Report: We present five cases of severe pneumonia due to Mycobacterium abscessus infection in Japan. All cases were diabetic patients, with possible acceleration to pneumonia due to co-infection with other microorganisms. However, following a short period of hospitalization and combination therapy with intravenous imipenem/cilastatin and amikacin, all the cases were successfully treated as outpatients with oral clarithromycin and sitafloxacin. Conclusion: M. abscessus infections can become severe in the presence of diabetes mellitus and co-infection with other chronic infectious organisms. Sitafloxacin might be a key drug in the treatment of M. abscessus infection in future.

Indoxyl sulfate (IS) is a protein-bound uremic toxin that progressively accumulates in plasma during chronic kidney disease (CKD), and its accumulation is associated with the progression of CKD. This study examined the intestinal secretion of IS using in situ single-pass intestinal perfusion in a rat model of renal insufficiency, MRP2- and BCRP-overexpressing Sf9 membrane vesicles, and Caco-2 cell monolayers. An in situ single-pass perfusion study in CKD model rats demonstrated that a small amount of IS is secreted into intestinal lumen after iv administration of IS, and the clearance increased AUC-dependently. An excess amount of IS (3 mm) partially inhibited the MRP2- and BCRP-mediated uptake of specific fluorescent substrates, CDCF and Lucifer yellow, respectively, into the membrane vesicles, although IS was not taken up at a physiological concentration, 10 μm. In the Caco-2 cell monolayers, the IS transport was higher in the absorptive direction than in the secretory direction (p < 0.05). p-Aminohippuric acid (PAH) strongly inhibited IS transport in both directions (absorptive, p = 0.142; secretory, p < 0.01). Given that the blood IS levels are much higher than those in the intestinal lumen, it is possible that this unknown PAH-sensitive system contributes to the intestinal IS secretion. Although in situ inhibition study is needed to confirm that this unknown transporter mediates the in vivo intestinal secretion of IS, we speculate that this unknown active efflux system works as a compensatory excretion pathway for excess organic anions such as IS especially in end-stage renal disease.

Background: Due to the relatively high renal toxicity of vancomycin injection (VCM), setting an initial dose that achieves a trough that ranges between 10 and 20 μg/mL on day 3 is important to ensure safety and minimize side-effects, especially for patients with low renal function. To address these issues, the revised 2016 Therapeutic Drug Monitoring (TDM) Guidelines for Antimicrobial Agents (GL2016) proposed the use of a renal function-based, estimate glomerular filtration rate (eGFR) nomogram for setting the dose of VCM in Japan. Methods: Our hospital introduced the use of the GL2016 in September 2016 for the patients administered VCM. After setting the initial VCM dose using 1) a conventional VCM analysis software and 2) the GL2016 eGFR nomogram, the measured trough values on day 3 were compared and evaluated in this study. Results: With the VCM analysis software, the mean measured trough value in the a-total group (n = 53) was 12.8 ± 4.7 μg/mL. With the eGFR nomogram, the mean measured trough value in the b-total group (n = 13) was 9.6 ± 4.6 μg/mL. However, when the different severities of renal function were compared, the mean measured trough value was more significantly lower in the b-1 group than in the a-1 group among subjects with G2 and above (eGFR ≥ 60 mL/min/1.73 m 2), but it was similar between the a-2 group and the b-2 group among subjects with G3 and below

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We report two cases of pazopanib (PAZ)-induced liver injury in patients with metastatic renal cell carcinoma. The first patient was a 70-year-old female who was diagnosed with right renal cell carcinoma and showed tumor embolism in the inferior vena cava. PAZ was started but discontinued after about one month due to a grade four liver injury. The second patient was a 60-year-old male who was diagnosed with left renal cell carcinoma and suspected multiple lung metastases. PAZ was started following a laparoscopic left radical nephrectomy but was stopped after about a month due to a grade three liver injury. We analyzed the plasma PAZ concentrations for treatment evaluation. High plasma PAZ concentrations were observed in both patients after PAZ treatment began. Severe liver injury after PAZ administration may be associated with high plasma PAZ concentrations; hence, we should reduce PAZ dosage early. We also recommend monitoring plasma PAZ concentrations, if possible, so that physicians can either reduce the dosage or discontinue treatment to avoid further liver damage.