Comparative Effectiveness of Aminoglycosides, Polymyxin B, and Tigecycline for Clearance of Carbapenem-Resistant Klebsiella pneumoniae from Urine

Abstract

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an increasingly common cause of health careassociated urinary tract infections. Antimicrobials with in vitro activity against CRKP are typically limited to polymyxins, tigecycline, and often, aminoglycosides. We conducted a retrospective cohort study of cases of CRKP bacteriuria at New York-Presbyterian Hospital from January 2005 through June 2010 to compare microbiologic clearance rates based on the use of polymyxin B, tigecycline, or an aminoglycoside. We constructed three active antimicrobial cohorts based on the active agent used and an untreated cohort of cases that did not receive antimicrobial therapy with Gram-negative activity. Microbiologic clearance was defined as having a follow-up urine culture that did not yield CRKP. Cases without an appropriate follow-up culture or that received multiple active agents or less than 3 days of the active agent were excluded. Eighty-seven cases were included in the active antimicrobial cohorts, and 69 were included in the untreated cohort. The microbiologic clearance rate was 88% in the aminoglycoside cohort (n ‫؍‬ 41), compared to 64% in the polymyxin B (P ‫؍‬ 0.02; n ‫؍‬ 25), 43% in the tigecycline (P < 0.001; n ‫؍‬ 21), and 36% in the untreated (P < 0.001; n ‫؍‬ 69) cohorts. Using multivariate analysis, the odds of clearance were lower for the polymyxin B (odds ratio [OR], 0.10; P ‫؍‬ 0.003), tigecycline (OR, 0.08; P ‫؍‬ 0.001), and untreated (OR, 0.14; P ‫؍‬ 0.003) cohorts than for the aminoglycoside cohort. Treatment with an aminoglycoside, when active in vitro, was associated with a significantly higher rate of microbiologic clearance of CRKP bacteriuria than treatment with either polymyxin B or tigecycline.

Carbapenem-resistant Enterobacteriaceae in special populations: Solid organ transplant recipients, stem cell transplant recipients, and patients with hematologic malignancies

“…On the other hand, aminoglycoside monotherapy may be efficacious in the treatment of CRE UTIs; however, rates of associated nephrotoxicity and clinical success have varied. 27,33,76,78 While available as a parenteral agent in Europe, fosfomycin is only available in an oral powder formulation in the United States, and this formulation has only been evaluated for the treatment of UTIs. CRE are often susceptible to fosfomycin, 79 and thus fosfomycin is an attractive option as an oral therapy for CRE UTIs, particularly in kidney transplant recipients where it would be preferable to avoid aminoglycosides.…”

“…4 Two cohort studies demonstrated high mortality rates in patients with CRE bloodstream infections who were treated with tigecycline monotherapy, and one showed similar rates of microbiologic clearance of CRKP bacteriuria between patients treated with tigecycline and untreated patients. [74][75][76] Gentamicin is the most active aminoglycoside against CRE, with reported susceptibility rates of 13% to over 90%, depending upon the geographic region. 8,66 CRE susceptibility rates are typically lower to amikacin, and almost all CRE are resistant to tobramycin.…”

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“…Observational data suggest that these drugs may be superior to polymyxin B or tigecycline when strictly targeting carbapenem-resistant Klebsiella sp. in the urine and have been successfully used in a limited number of patients with UTIs [15].…”

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“…Aminoglycosides concentrate in the kidneys and urine and appear to be effective, as monotherapy, in the treatment of urinary tract infections due to CRE. 102 In a retrospective cohort of patients with CRE bacteriuria, microbiologic clearance rates were significantly higher for aminoglycosides (88%) compared to the polymyxin B cohort (64%), tigecycline cohort (43%), and untreated controls (36%). 102 The multivariate analysis confirmed treatment with an aminoglycoside with in vitro activity was independently associated with microbiological clearance.…”

“…102 In a retrospective cohort of patients with CRE bacteriuria, microbiologic clearance rates were significantly higher for aminoglycosides (88%) compared to the polymyxin B cohort (64%), tigecycline cohort (43%), and untreated controls (36%). 102 The multivariate analysis confirmed treatment with an aminoglycoside with in vitro activity was independently associated with microbiological clearance. 102 To optimize concentrations at the site of infection, aminoglycosides can be aerosolized.…”