The Effect of Double Carbapenem Regimen in the Management of Carbapenem-Resistant Klebsiella pneumoniae Infections: A Report of Five Cases.

The treatment of infections caused by carbapenem-resistant organisms is challenging. Carbapenems in combination with vaborbactam and relebactam are recommended to treat infections caused by extensively drug-resistant organisms including carbapenemase-producing isolates, while ceftazidime-avibactam plus aztreonam, or cefiderocol is recommended for infections caused by New Delhi metallo beta-lactamase (NDM)-producing Enterobacteriaceae. As, in India, except for ceftazidime-avibactam and aztreonam, the other drugs are not approved for marketing, in this case report, the role of a double carbapenem regimen (ertapenem plus meropenem) in the treatment of carbapenem-resistant Klebsiella pneumoniae infections has been presented. In one case, the in vitro effect of the double carbapenem regimen on pan drug-resistant (PDR) K. pneumoniae isolates from a blood culture specimen of a critically ill patient using a time-kill study is presented. In this case, only a double carbapenem regimen with 2 MIC (minimum inhibitory concentration) meropenem + 2 MIC ertapenem demonstrated bactericidal activity by inhibition of bacterial growth of PDR K. pneumoniae isolate, at four and eight hours, which was sustained till 24 hours. However, while 2 MIC meropenem + 2 MIC colistin inhibited bacterial growth at four hours and eight hours, bacterial regrowth occurred by 24 hours. In addition, four cases of critically ill patients with infections caused by carbapenem-resistant Enterobacteriaceae are presented in whom a double carbapenem regimen was recommended for treatment. Of these four cases, a complete clinical cure was observed in three cases, and a microbiological cure in the fourth case. As the double carbapenem regimen demonstrated effect in an in vitro time-kill study in the first case and on clinical outcomes in three out of the latter four cases, it appears to be a life-saving, salvage therapy in infections caused by carbapenem-resistant K. pneumoniae in India.