A Matched Case-Case-Control Study of the Impact of Clinical Outcomes and Risk Factors of Patients with IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan

Abstract

IMP-type carbapenemase, found in various Gram-negative bacteria, has been increasingly detected worldwide. We aimed to study the outcomes and risk factors for acquisition of IMP-type carbapenemase-producing carbapenem-resistant Enterobacteriaceae (IMP-CRE), as this has not been evaluated in detail. We conducted a matched case-case-control study of patients from whom IMP-CRE isolates were obtained. All patients who tested positive for IMP-CRE were included and matched with those having carbapenem-susceptible Enterobacteriaceae (CSE) and with controls at a ratio of 1:1:2. The risk factors for acquisition between CRE and CSE groups, and mortality which were calculated using multivariate logistic regression model with weighting according to the inverse probability of propensity scores were compared. In total, 192 patients (96 CRE and CSE each; 130 Enterobacter cloacae and 62 Klebsiella spp.) were included. IMP-11 type was present in 43 patients, IMP-1 in 33, and IMP-60 and IMP-66 in 1; 31 (32.3%) patients with CRE and 34 (35.4%) with CSE developed infections. Multivariate analysis identified the following independent risk factors: gastrostomy, history of intravenous therapy or hemodialysis, and previous exposure to broad spectrum β-lactam antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, and carbapenems. On propensity score-adjusted analysis, mortality in the CRE and CSE groups (15.0% versus 19.5%, respectively) were similar. We found that IMP-CRE may not contribute to worsened clinical outcomes compared to CSE, and gastrostomy, previous intravenous therapy, hemodialysis, and broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Fluoroquinolone and aminoglycosides are potentially useful antibiotics for IMP-CRE infections.

A case–control study of the clinical and economic impact of infections caused by Carbapenemase-producing Enterobacterales (CPE)

“…Baseline comorbidities and septic shock at the infection were found to be predictors of 30-and 90-day mortality, as previously reported [12][13][14][15]25]. Although inappropriate antibiotic therapy was not independently associated with higher mortality, it was independently associated with increased clinical failure.…”

“…Conflicting results have been published on the impact of CPE infections on clinical outcomes [12][13][14][15]. Apart from carbapenem resistance itself, other factors, such as patient comorbidities, host response, source and severity of the infection, therapeutic management, type of microorganism, mechanism of carbapenem resistance and virulence factors, are likely to play a role in these discrepancies.…”

“…Despite the development of these novel antibiotics, treatment options for metallo beta-lactamase (MBL) mediated resistance patterns are limited. Although previous studies [10,[12][13][14][15][16][17] have analysed the clinical and economic burden related to CPE infections, in the present work we assessed clinical response, mortality, resource consumption and economic impact as a whole to give a more comprehensive view of a global problem. In the present study, we hypothesised that patients admitted with active infections caused by CPE have worse clinical outcomes, consume more resources and incur higher economic costs compared to patients admitted with infections caused by susceptible or non-MDR bacteria.…”

Cefiderocol, a Siderophore Cephalosporin, as a Treatment Option for Infections Caused by Carbapenem-Resistant Enterobacterales

“…Risk factors for CRE colonisation and/or infection are similar to those identified for all CR Gram-negative infections [10], being associated with the host (e.g., older age), hospitalisation (e.g., number of previous hospitalisations, emergency department stay[2 days prior to intensive care unit admission), treatment (e.g., previous exposure to antibiotics) and procedures (e.g., invasive procedures/indwelling devices), recent surgery, immunocompromised status and organ transplantation [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25], chronic skin ulcers [13], along with mechanical ventilation and patient movement between hospital departments [26].…”

Genetic Factors of Klebsiella Pneumoniae Antibiotic Resistance

“…Данные гены представляют собой генные кассеты, объединенные с интегронами, которые обеспечивают встраивание генных кассет в геном микроорганизма. Частота выявления изолятов, продуцирующих IMP, намного меньше, чем изолятов, продуцирующих другие β-лактамазы (KPC, VIM, NDM или OXA-48) [31,[40][41][42].…”