Successful ceftazidime-avibactam treatment of MDR-KPC-positive Klebsiella pneumoniae infection in a patient with traumatic brain injury

Abstract

Rationale:Carbapenem-resistant Enterobacteriaceae infections are a serious health care problem, because of the high mortality. Carbapenem resistance is mainly caused by carbapenemases production, including Klebsiella pneumoniae carbapenemase (KPC). Ceftazidime-avibactam is a new cephalosporin/β-lactamase inhibitor combination for the treatment of complicated urinary, intra-abdominal infections, and nosocomial pneumonia caused by gram negative, or other serious gram-negative infections.Patient concerns:We showed the case of a 27-year-old patient, hospitalized for traumatic brain injury and chest trauma, with KPC-producing Klebsiella pneumoniae infection.Diagnoses:Blood and bronchial aspirate culture analysis detected an infection caused by MDR Klebsiella pneumoniae, resistant to meropenem, ertapenem, piperacillin/tazobactam, amoxicillin/clavulanic acid, aztreonam, ceftazidime, cefotaxime, cefepime, amikacin, ciprofloxacin, trimethoprim/sulfamethoxazole, colistin while it showed an intermediate sensitivity to gentamicin and was sensitive to ceftazidime-avibactam. Molecular analyses revealed that the isolate belonged to the epidemic clone sequence type 258 (ST258) carrying blaKPC-3, blaTEM-1, and blaSHV-11genes.Interventions:After various combined antibiotic therapies without improvements, he was treated with ceftazidime-avibactam, on a compassionate-use basis.Outcomes:With ceftazidime-avibactam monotherapy clinical and microbiological clearance was obtained. A week after the end of the therapy microbiological analysis was repeated and a positive rectal swab for KPC-Klebsiella pneumoniae was found, becoming negative after 1 month. Moreover, the patient did not show any relapses for up to 18 weeks.Lessons:This case indicates that ceftazidime-avibactam monotherapy could be efficacious against KPC positive Klebsiella pneumoniae infections.

In vitro and in vivo bactericidal activity of ceftazidime-avibactam against Carbapenemase–producing Klebsiella pneumoniae

“…Laurent adopted a combined pharmacotherapy regimen of dual carbapenems to provide a new approach in the treatment of CRE-induced infections [ 31 ]. As a novel β-lactam/β-lactamase inhibitor, studies have shown that ceftazidime-avibactam can successfully cure the infections due to Enterobacteriaceae with bla KPC [ 32 – 35 ]. Nevertheless, it is worth to be noticed that with the increasing application of ceftazidime-avibactam, the resistant strains and failed cases have been reported [ 6 , 7 , 36 ].…”

Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 Escherichia coli High-Risk Clone

“…Although the in vivo clinical efficacy of ceftazidime-avibactam has been widely demonstrated [ 12 , 13 ], several studies have recently reported in K. pneumoniae epidemic clones the emergence of new ceftazidime-avibactam resistant KPC enzymes derived from point mutations in bla KPC-2 and bla KPC-3 genes, frequently after the antibiotic exposure [ 16 , 17 , 18 ]. In all cases, in vitro meropenem susceptibility was fully or partially restored due to these bla KPC mutations resulting in KPC-producing K. pneumoniae isolates with a phenotype resembling that of ESBL producers [ 16 , 17 , 18 ].…”

“…In February 2015, the U.S. Food and Drug Administration (FDA) approved the ceftazidime-avibactam combination as an alternative to carbapenems in patients with complicated intra-abdominal and urinary tract infections caused by MDR Gram-negative bacteria isolates [ 11 ]. Since then, several studies have demonstrated the in vivo efficacy of ceftazidime-avibactam in the treatment of infections caused by KPC-producers [ 12 , 13 , 14 ]. Moreover, a recent study has supported the presumptive use of ceftazidime-avibactam against carbapenem resistance E. coli isolates, including members of the ST131 lineage [ 15 ].…”

The Epidemiology, Evolution, and Treatment of KPC-Producing Organisms

“…Prospective studies support the in vivo efficacy of ceftazidime-avibactam against ceftazidime-resistant isolates, with one study showing it to be superior to best available therapy (BAT), mostly carbapenems, in UTIs caused by these organisms [73•]. There are limited but growing clinical data illustrating ceftazidime-avibactam efficacy in treating infections in humans caused by KPC-producing pathogens [74][75][76].…”