go to japanese page

Susceptibility, Safety and Clinical Outcome of a Fixed-dose (24 g/day) of a Combination of Ampicillin and Cloxacillin for Infective Endocarditis as Empiric Therapy: Retrospective Study
1)Department of Pharmacy, Juntendo University Hospital, 2)Department of General Medicine, Juntendo University Faculty of Medicine
Takuya AZECHI1), Yuji HIRAI2), Yuki UEHARA2), Hiroshi SASANO1), Toshihiro YOSIZAWA1), Hiroshi MATSUMOTO1), Mizuki AOSHIMA1) & Toshio NAITO2)
(Received October 3, 2018)
(Accepted May 23, 2019)
Key words: ampicillin, cloxacillin, infective endocarditis, empiric therapy

Methicillin-susceptible Staphylococcus aureus (MSSA) remains a major cause of morbidity and mortality in the healthcare setting. However, no single agent of anti-staphylococcal penicillin is available in Japan. The European Society of Cardiology (ESC) guidelines 2015 recommend antimicrobial combination empiric therapy using ampicillin (ABPC), cloxacillin (MCIPC) and gentamycin for native valve infective endocarditis (NVE). A fixed-dose combination drug of ABPC and MCIPC (ABPC/MCIPC) is the only product which contains anti-staphylococcal penicillin. There are few reports for empiric therapy using ABPC/MCIPC, similar to the empiric therapy for NVE patients according to the ESC guidelines, in Japan. To evaluate the susceptibility, safety and clinical outcome of empiric therapy for NVE using ABPC/MCIPC, a retrospective investigation was performed. NVE was defined according to the modified Duke criteria. Patients aged over 18 years with NVE, and who were given intravenous ABPC/MCIPC (24 g/day), were included in the study between January 2015 and August 2017 at Juntendo University Hospital (1023-bed university hospital).

Eight patients were included. Five out of 8 patients were male. The median age was 68.5 (34 to 76) years. Blood cultures were positive for MSSA (n=2), viridians group streptococci (n=3), and others (n=3). Except for one case, all organisms were susceptible to ABPC and/or MCIPC. Six out of 8 patients were treated with ABPC/MCIPC as empiric therapy for 2-6 days (median; 3.5 days). Two out of eight developed phlebitis due to ABPC/MCIPC. On the other hand, two with MSSA continued to be given ABPC/MCIPC as definitive therapy. In one, however, administration was discontinued due to acute renal failure and exanthema on day 12. The antimicrobial regimen was then changed to vancomycin with ceftriaxone.

These results suggested the high safety of ABPC/MCIPC treatment for NVE patients as empiric therapy, although the results are in a small number of cases from a single hospital. On the other hand, we could not confirm the safety of high-dose ABPC treatment as definitive therapy over the longer term. Further studies are required to evaluate the safety of long-term ABPC/MCIPC treatment on NVE patients in Japan.

[ Kansenshogaku Zasshi 93: 649-654, 2019 ]

To read the PDF file you will need Adobe Reader installed on your computer.