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.

Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula

“…The variety and wide array of genes coding for resistance to numerous antibiotic classes within clusters were also notable findings supporting the previous notion. It also explains how members of the clone develop to being extremely drug resistant, or even pan-drug resistant, which was already observed in the region [8,30].…”

“…Numerous high-risk K. pneumoniae clones, among them ST14, have now been identified [2]. ST14 strains have been reported to produce a wide range of carbapenemases: apart from being the sequence type from which the bla NDM-1 gene was first identified [18], various bla KPC [9,19,20], bla NDM [21,22], and bla OXA-48-like [6,[23][24][25][26] alleles or double carbapenemase producers have been reported from different parts of the world, including the Middle East [7,8,[27][28][29][30][31]. Furthermore, ST14 strains appear to be one of the most wide-spread, highly resistant CRE clones in Dubai [8].…”

The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases

“…Of the remaining 90 studies, 37 were excluded due to the reasons listed in Figure 2 , wherein the entire process of article selection is illustrated. Overall, 35 in vitro studies [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] and 18 in vivo studies [ 4 , 47 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , …”

“…The relative majority (7 out of 18) were conducted in the US [ 50 , 51 , 52 , 56 , 57 , 62 , 65 ]. The remaining were performed in the following countries: France (3), Italy (3), Australia (1), Greece (1), Mexico (1), Netherlands (1), Saudi Arabia (1), Spain (1) [ 4 , 47 , 53 , 54 , 55 , 58 , 59 , 60 , 61 , 63 , 64 ]. All of them were case reports/case series, barring two different cohorts (one retrospective, another prospective) of patients from Italy and Greece affected by NDM-producing isolates [ 4 , 47 ].…”

Whole Genome Characterization of the High-Risk Clone ST383 Klebsiella pneumoniae with a Simultaneous Carriage of blaCTX-M-14 on IncL/M Plasmid and blaCTX-M-15 on Convergent IncHI1B/IncFIB Plasmid from Egypt

“…Both mentioned plasmids exhibited a very high similarity to our plasmid (99.9% nucleotide identity and 99% sequence length) as detected by BLASTn tool and visualized by BRIG. In addition, pEGY22_CTX-M-14 revealed a high similarity (99.9% nucleotide identity and 91% sequence length) to pSA-KpST14-OXA48-2 (GenBank accession NZ_CP071281.1) recovered from K. pneumoniae ST14 isolated from the Middle East region, specifically, from Saudi Arabia [47], implicating a geographical spread of this plasmid replicon (Figure 1B).…”