ABSTRACT
Although 12 g/day sulbactam/ampicillin (SBT/ABPC) is approved in Japan, differences in the frequency of adverse effects induced by conventional (≤6 g/day) and high (≥9 g/day) doses remain unclear. We performed a retrospective observational study on SBT/ABPC-treated hospitalized adult patients with pneumonia from October 2015 to January 2018 to compare the safety between high and low doses. Patients were divided into high-dose (≥9 g/day, n = 200) and low-dose (≤6 g/day, n = 246) groups. We used logistic regression to determine propensity scores for the high-dose and low-dose groups and compared the incidence of adverse effects after propensity score adjustment (n = 200 in each group). Following propensity score adjustment, the frequency of elevated alanine aminotransferase (ALT) level was still significantly higher in the high-dose group than in the low-dose group (21% versus 11%, p = 0.006). In contrast, the frequencies of elevated alkaline phosphatase, aspartate aminotransferase, and serum creatinine levels and decreased white blood cell and platelet counts, and incidence of anemia, were not. Changes in blood urea nitrogen levels, erythrocyte count, and hematocrit were not significantly different between the two dose groups. There were two cases of rash reported to the Pharmaceuticals and Medical Devices Agency as an adverse effect in the high-dose group. Thirty-day mortality rates were not significantly different after propensity score adjustment. Our analysis suggests that an increase in the ALT grade was more frequent in patients treated with a daily dose of SBT/ABPC of ≥9 g.
Subject(s)
Pneumonia , Sulbactam , Adult , Ampicillin , Aspartate Aminotransferases , Drug Therapy, Combination , Humans , Japan/epidemiology , Retrospective Studies , Sulbactam/adverse effectsABSTRACT
BACKGROUND: Vancomycin is commonly used to treat Enterococcus faecium (E. faecium) bacteremia. However, there are very few studies on the association between the trough concentration, area under the curve from 0 to 24 h /minimum inhibitory concentration (AUC24/MIC) ratio, and the therapeutic effect of vancomycin on E. faecium bacteremia. This study aimed to investigate the associations between vancomycin pharmacokinetic/pharmacodynamic parameters, patient characteristics, and mortality in patients with E. faecium bacteremia. METHODS: This retrospective study included patients with E. faecium bacteremia who received vancomycin between April 2012 and February 2018 at a single acute care hospital in Japan. Patients who received renal replacement therapy (hemodialysis or continuous hemodiafiltration), had an unmeasured serum vancomycin concentration, with unmeasured laboratory values, or received other antibiotics for treating E. faecium bacteremia were excluded from the study. The bivariate associations between 30-day all-cause mortality and patient characteristics were assessed. RESULTS: Among 87 patients diagnosed with E. faecium bacteremia, 45 were included in the final analysis. Of these, 12 (26.7%) died within 30 days of the diagnosis. The vancomycin trough concentration was higher in the 30-day all-cause mortality patients than in the survival patients (20.5 vs. 14.6 µg/mL; P = 0.022). There was no significant difference in the proportion of patients with a vancomycin AUC24/MIC ≤389 between the groups. The 30-day all-cause mortality patients showed a higher Charlson Comorbidity Index (CCI) and Sequential Organ Failure Assessment score at the first measurement of the vancomycin trough concentration than the survival patients. The same finding was observed among patients with a high CCI score (≥5 points). CONCLUSIONS: Whereas the vancomycin trough concentration and AUC24/MIC ratio were not associated with mortality in patients with E. faecium bacteremia, disease severity was associated with mortality in these patients.
ABSTRACT
Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are becoming increasingly common worldwide. Although CPE infections can be fatal, few reports in the literature have described effective and successful treatments for infectious diseases caused by several types of IMP CPE, and, to our knowledge, no reports have described the successful treatment of IMP-6 CPE infections. We describe two patients who developed bacteremia caused by IMP-6 CPE after surgery for cancer who were successfully treated with amikacin plus high-dose prolonged-infusion meropenem. Both patients were treated over a 2-week period using amikacin 15 mg/kg at various intervals based on therapeutic drug monitoring and meropenem 2000 mg infused over 3 hours every 12 hours. The dosages of amikacin and meropenem were determined based on the creatinine clearance of each patient. Both patients were cured of their bacteremia and did not experience any antibiotic-related adverse effects. Based on the outcomes of these patients, it appears that amikacin plus high-dose prolonged-infusion meropenem may be safe and effective for the treatment of bacteremia caused by IMP-6 CPE.
