Successful treatment of a Carbapenem-resistant Klebsiella pneumoniae carrying bla OXA-48 , bla VIM-2 , bla CMY-2 and bla SHV- with high dose combination of imipenem and amikacin

Abstract

We describe a case of 58-year-old man with septic shock due to Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) bloodstream infections (BSI) who was successfully treated with a high dose association of amikacin and imipenem combined with continuous venovenous hemodiafiltration (CVVHDF).A Klebsiella pneumoniae (Kp) was isolated from the catheter culture and from two blood samples, drawn from the catheter before removal and from a peripheral vein. The Kp was intermediate to Amikacin (MIC = 16 μg/ml) and was resistant to all other antibiotics including Imipenem (MIC = 4 μg/ml), Colistin (MIC = 16 μg/ml) and Tigecycline (MIC = 4 μg/ml) according to the Clinical and Laboratory Standards Institute (CLSI) published in 2011. PCR amplification and sequencing verified the presence of blaOXA-48, blaVIM-2, blaCMY-2 and blaSHV-1 genes.Amikacin was given at a dose of 30 mg/kg (2.5 g) in a 30 min infusion and the dose of imipenem was increased to 1 g every 6 h despite patient's altered renal function (Creatinine Clearance = 25 ml/min). To avoid amikacin nephrotoxicity and to allow the use of high doses of imipenem, continuous venovenous hemodiafiltration (CVVHDF) (blood flow, 200 ml/h; dialysate, 1000 ml/h; ultrafiltrate, 2000 ml/h) was initiated 1 h after the start of the amikacin infusion and continued thereafter.The patient improved hemodynamically and norepinephrine was stopped five days after antibiotherapy adaptation.

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

“…Therefore, a serious challenge of anti-infection therapy for CRE has been raised in clinical practice. Studies have revealed that compared to use carbapenems antibiotics alone, in the combination of carbapenems with other antibacterial agents such as tigecycline or polymyxin [ 25 – 28 ], amikacin [ 29 ] or fosfomycin [ 30 ] can considerably improve the outcomes of patient with CR-KP infection. Laurent adopted a combined pharmacotherapy regimen of dual carbapenems to provide a new approach in the treatment of CRE-induced infections [ 31 ].…”

Treatment of Infections by OXA-48-Producing Enterobacteriaceae

“…Only 3/7 (42.8%) patients treated with this regimen achieved a clinical cure and survived. However, the addition of amikacin to a carbapenem, when there is susceptibility to amikacin, achieved better outcomes, with 3/4 (75%) patients with OXA-48 bloodstream infections treated with this regimen surviving (27,66). Colistin has been used in combination with both tigecycline and fosfomycin in six and four patients, respectively, in a large retrospective case series by Navarro-San Francisco et al which documented survival rates of 5/6 (83%) and 3/4 (75%) (27).…”

Bioinformatic analyses of plasmid resistome changes in pOXA-48

“…Aminoglycoside antibiotics including amikacin, gentamicin, kanamycin, streptomycin, and tobramycin alongside carbapenems such as meropenem/imipenem represent valid combination treatment therapies yielding synergistic effects for infections caused by carbapenem resistant Enterobacteriaceae (CRE) (Hajjej et al ., 2016; Terbtothakun et al ., 2021). The presence of multiple aminoglycoside genes encoding aminoglycoside-modifying enzymes (AMEs) among all three pOXA-48 AMR variants may prevent synergistic therapies involving both carbapenems and aminoglycosides.…”