Prospective Observational Study of the Impact of VIM-1 Metallo-β-Lactamase on the Outcome of Patients with Klebsiella pneumoniae Bloodstream Infections

Abstract

VIM-1-producing Klebsiella pneumoniae (VPKP) is an emerging pathogen. A prospective observational study was conducted to evaluate the importance of VIM production on outcome of patients with K. pneumoniae bloodstream infections (BSIs). Consecutive patients with K. pneumoniae BSIs were identified and followed up until patient discharge or death. A total of 162 patients were included in the analysis; 67 (41.4%) were infected with VPKP, and 95 were infected with non-VPKP. Fourteen of the patients infected with VPKP were carbapenem resistant (Carb r ) (MIC > 4 g/ml), whereas none of the non-VPKP exhibited carbapenem resistance. The patients infected with a Carb r organism were more likely (odds ratio, 4.08; 95% confidence interval [CI], 1.29 to 12.85; P ‫؍‬ 0.02) to receive inappropriate empirical therapy. The all-cause 14-day mortality rates were 15.8% (15 of 95) for patients infected with VIM-negative organisms, 18.9% (10 of 53) for those infected with VIM-positive carbapenem-susceptible organisms, and 42.9% (6 of 14) for those infected with VIM-positive Carb r organisms (P ‫؍‬ 0.044). In Cox regression analysis, age (hazard ratio [HR], 1.03; 95% CI, 1.01 to 1.06; P ‫؍‬ 0.021), rapidly fatal underlying disease (HR, 2.84; 95% CI, 1.26 to 6.39; P ‫؍‬ 0.012), and carbapenem resistance (HR, 2.83; 95% CI, 1.08 to 7.41; P ‫؍‬ 0.035) were independent predictors of death. After adjustment for inappropriate empirical or definitive therapy, the effect of carbapenem resistance on outcome was reduced to a level of nonsignificance. In patients with K. pneumoniae BSIs, carbapenem resistance, advanced, age, and severity of underlying disease were independent predictors of outcome, whereas VIM production had no effect on mortality. The higher mortality associated with carbapenem resistance was probably mediated by the failure to provide effective therapy.Over the last few years, the reliance on carbapenems has been challenged owing to the wide spread of acquired metallo-␤-lactamases [MBLs] (2,11,20,25,31). Two dominant groups of acquired MBLs have been recognized: the IMP and VIM types. This class of enzymes is characterized by the ability to hydrolyze carbapenems and all available ␤-lactams with the exception of aztreonam. Moreover, since the MBL genes are linked to other resistance determinants within the same integron or plasmid, MBL-producing organisms are commonly multidrug resistant, further compromising our therapeutic options (8,26,28).MBLs have spread throughout the world with an overall trend moving from Pseudomonas aeruginosa into Enterobacteriaceae (9,10,14,16,18,22,23,28). Recently, there have been several reports on the emergence of VIM-producing Klebsiella pneumoniae (VPKP), mainly in Southern Europe (16,20). In Greece, VPKP isolates are endemic in various hospitals and cause life-threatening infections (5,8,29). Based on previous reports (30) and on the National Surveillance System for Antibiotic Resistance Database (www.mednet.gr/whonet/top .htm), the dissemination of such isolates appears to have occurred in a r...

Factors Associated with Nosocomial Bloodstream Infection Caused by Carbapenem-Resistant Klebsiella pneumoniae and With Mortality, from a Single Center

“…Ben-David et al demonstrated ineffective antimicrobial therapy in all patients with CRKP and CSKP BSI (88% vs. 21%) associated with increased mortality [11]. Daikos et al also suggested that the effect of carbapenem resistance on mortality was probably mediated by the failure to provide effective antimicrobial therapy in patients with CRKP or CSKP infection (68% vs. 32%; OR 2.27, 95% CI 0.91-5.64) [12]. Although one study showed that tigecycline treatment appeared to be suitable for BSI caused by carbapenem-resistant Gramnegative bacteria [13], our study suggested that tigecycline could be associated with 100-fold risk of acquiring CRKP.…”

Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011)

“…18 In general, however, clinical data on the treatment of carbapenem-resistant Enterobacteriaceae infections are very limited and consist mainly of small case-series and brief reports. [18][19][20][21][22][23][24][25] Treatment options against infections due to MDR Gram-negative rods in leukemic and HSCT patients are summarized in Table 2.…”

“…Carbapenems may be a reasonable treatment option against carbapenemaseproducing K. pneumoniae provided that: (i) the carbapenem MIC for the infecting organism is ≤4 mg/L; (ii) a high-dose prolonged-infusion regimen is administered to drive the pharmacokinetic/ pharmacodynamic profile to acceptable exposures; and (iii) this class of agent is administered in combination with another active compound. 21 The caveat is that many carbapenemase producers are more substantially resistant, precluding such strategies.…”

“…Carbapenems may be a reasonable treatment option against carbapenemaseproducing K. pneumoniae provided that: (i) the carbapenem MIC for the infecting organism is ≤4 mg/L; (ii) a high-dose prolonged-infusion regimen is administered to drive the pharmacokinetic/ pharmacodynamic profile to acceptable exposures; and (iii) this class of agent is administered in combination with another active compound. 21 The caveat is that many carbapenemase producers are more substantially resistant, precluding such strategies.An ertapenem-doripenem combination may be of potential usefulness against KPC-producing K. pneumoniae based on a study in an immunocompetent murine thigh infection model based on the notion that the high affinity of KPC for ertapenem would "trap" the enzyme thus enhancing the activity of doripenem. …”

An optimized work-flow to reduce time-to-detection of carbapenemase-producing Enterobacteriaceae (CPE) using direct testing from rectal swabs

“…10 For clinicians and antimicrobial pharmacists, CPE pose a major challenge at the bedside as they significantly limit antimicrobial prescribing. 11 Morbidity and mortality are both increased in CPE infections, particularly bloodstream and respiratory infections, 12 with mortality rates ranging from 38-57%, 9 and poor outcomes in survivors, [13][14][15] emphasizing the need for commencement of timely targeted antimicrobial therapy to increase patient survival.…”