title: Risk factors for treatment failure of polymyxin B monotherapy for carbapenem-resistant Klebsiella pneumoniae infections.
abstract: Polymyxins are reserved for salvage therapy of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for the combination of polymyxins with carbapenems or tigecycline, in vitro synergy tests are nonstandardized, and the clinical effect of synergy remains unclear. This study describes outcomes for patients with CRKP infections who were treated with polymyxin B monotherapy. We retrospectively reviewed the medical records of patients with CRKP infections who received polymyxin B monotherapy from 2007 to 2011. Clinical, microbiology, and antimicrobial treatment data were collected. Risk factors for treatment failure were identified by logistic regression. Forty patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved clinical cure as defined by clinician-documented improvement in signs and symptoms of infections, and 17/32 (53%) patients with follow-up culture data achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day mortality was 28%. In a multivariate analysis, baseline renal insufficiency was associated with a 6.0-fold increase in clinical failure after adjusting for septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to 29.59). Breakthrough infections with organisms intrinsically resistant to polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%) patients developed a new CRKP infection a median of 23 days after initial polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The clinical cure rate achieved in this retrospective study was 73% of patients with CRKP infections treated with polymyxin B monotherapy. Baseline renal insufficiency was a risk factor for treatment failure after adjusting for septic shock. Breakthrough infections with organisms intrinsically resistant to polymyxin B and development of resistance to polymyxin B in subsequent CRKP isolates are of concern.
authors: Department of Pharmacy, New York University Langone Medical Center, New York, New York, USA.
authors: Yanina
authors: Y
authors: Dubrovskaya
authors: Ting-Yi
authors: TY
authors: Chen
authors: Marco R
authors: MR
authors: Scipione
authors: Diana
authors: D
authors: Esaian
authors: Michael S
authors: MS
authors: Phillips
authors: John
authors: J
authors: Papadopoulos
authors: Sapna A
authors: SA
authors: Mehta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015780:Carbapenems / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D007710:Klebsiella Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000254:growth & development; D016015:Logistic Models; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011112:Polymyxin B / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D017211:Treatment Failure; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D011112:Polymyxin B
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