Successful treatment of infective endocarditis due to pandrug-resistant Klebsiella pneumoniae with ceftazidime-avibactam and aztreonam

Abstract

Pandrug-resistant (PDR) K. pneumoniae refractory to conventional treatment has been reported worldwide, causing a huge burden on the healthcare system, patient safety and the economy. K. pneumoniae is a prominent opportunistic pathogen causing hospital-acquired and community-acquired infections, but is rarely associated with infective endocarditis. Currently, there are sparse data guiding the optimal regimen when commonly used antibiotics fail, notably for the treatment of endocarditis infections. Here we report our experience in treating a 40-year-old female with PDR K. pneumoniae infection of cardiovascular implantable electronic device (CIED) and right-sided infective endocarditis. Initial susceptibility testing of the incriminated pathogen showed an apparent susceptibility to colistin but the prolonged course of colistin, gentamicin and meropenem did not resolve the infection. However, the synergistic combinations of aztreonam with ceftazidime-avibactam was able to overcome resistance and clear the infection rapidly. Genome sequencing showed that the PDR K. pneumoniae isolate belongs to the international high-risk clone ST14. The isolate harbored genes encoding NDM-1, OXA-48, CTX-M-14b, SHV-28 and OXA-1, explaining resistance to all β-lactams, including carbapenems. It carried the armA gene conferring resistance to all clinically important aminoglycosides and had alterations in GyrA, ParC and MgrB, explaining resistance to ciprofloxacin and colistin.

Figure 1

Patient timeline for antimicrobial exposure, fever pattern, duration of persistence of infection in blood cultures with trends of important laboratory investigations. Important dates marked from left to right at the bottom represented the start of symptoms (03/Jan), first hospital admission (03/Feb), transfer to the second hospital (07/Feb), transfer to our cardiac centre (13/Feb), the start of the therapy CAZ/AVI plus ATM combination (17/Feb), date of the first negative culture (18/Feb) and date of discharge from hospital (14/Apr). Aug augmentin, Van vancomycin, Col colistin, Rif rifampicin, Gen gentamicin, Mer meropenem, CAZ/AVI ceftazidime/avibactam, ATM aztreonam, CRKP carbapenem-resistant Klebsiella pneumoniae, OXA-48 oxacillinase, NDM New Delhi Metallo-β-lactamase, Susc susceptible; Res resistant; PCT procalcitonin; CRP C-reactive protein; WBC white blood cells.

Figure 2

Sequence representation of the two carbapenemase-encoding plasmids carried by the SA-KpST14 isolate. (A) Genetic structure of pSA-KpST14-NDM-1 plasmid, (B) Gene composition of the bla-_NDM-1-bearing Tn125 transposon, (C) Genetic structure of pSA-KpST14-OXA48-2 plasmid, (D) Gene composition of the bla_OXA-48 -bearing Tn1999.2 transposon. The circular map was generated with the Blast Ring Image Generator (BRIG) software and the schematic diagram of the genetic structure was generated with Easyfig.