Trends in the annual incidence of carbapenem-resistant Klebsiella pneumoniae bloodstream infections: a 8-year retrospective study in a large teaching hospital in northern Italy

Bloodstream infections (BSI) due to carbapenem-resistant (C-R) Klebsiella pneumoniae (Kp) are of global concern from both clinical and public health standpoints. Indeed, these severe infections are caused by rapidly spreading clones that are frequently resistant to almost all the antibiotics used in the everyday clinical practice [1–6].

Occurring especially across Southern Europe, the rapid diffusion of C-R Kp has worryingly impressed the medical community, and several guidelines have been recently developed to reduce the spread of these difficult-to-treat gram-negative rods [7–9]. In Italy, carbapenem resistance among blood Kp isolates has dramatically increased from 1.3 % in 2009 to 29.1 % in 2012, and even higher rates of 34.3 % have been reported in 2013 [10, 11]. With the aim of more clearly investigate this alarming C-R Kp diffusion, we retrospectively assessed the epidemiology of C-R Kp BSI in a large teaching hospital in northern Italy over a 8-year period.

Between January 2007 and December 2014, we identified 511 episodes of Kp BSI, 349 of which were caused by C-R Kp (68.3 %). These episodes occurred in 327 patients, of whom 19 had recurrent infections (5.8 %). The median age of patients was 68 years (interquartile range [IQR] 57–76). As many as 231/349 C-R Kp BSI occurred in males (66.2 %), thus defining a 2:1 male to female ratio. The median time to C-R Kp BSI diagnosis from hospital admission was 24 days (IQR 12–45), and the median length of hospital stay was 52 days (IQR 30–90).

Overall, the incidence of Kp BSI (C-R plus C-S) increased from 0.50/10,000 patient-days in 2007 to 2.42/10,000 patient-days in 2014 (Chi square for trend p < 0.001). The singular trends of C-R Kp BSI and C-S Kp BSI over the study period are depicted in Fig. 1. As shown in the figure, the overall increase in the incidence of Kp BSI was mostly due to C-R Kp BSI, although a less marked but significant increase of C-S Kp BSI was also observed (Chi square for trend p = 0.004).

Finally, crude 30-day mortality was higher in patients with C-R Kp BSI than in those with C-S Kp BSI (36.1 vs. 23.5 %, respectively). However, this comparison was not further considered in our analyses, since it could not be adjusted for some important clinical confounders (e.g., severity of illness, type of antibiotic therapy) that were not explored in this epidemiologic study.

From 2007 to 2014 we noticed an impressive increase of more than 300 % in the incidence of Kp BSI in our hospital, that was mostly driven by C-R strains. This finding is of particular concern, since C-R Kp BSI carry a heavy burden in terms of morbidity and mortality [3–6].

A worrisome and persistent increase of carbapenem-resistance among Kp isolates has been reported in Italy since 2005, with current national rates being as high as 34 % [11, 12]. Our experience confirms this picture, since we observed a rapid increase in the incidence of C-R Kp BSI starting from 2007, that peaked at 1.75/10,000 patient-days in 2012. A temporary decrease was then observed in 2013, possibly because of the intensification of our hospital-based infection control measures (i.e., rapid identification of colonized and/or infected patients trough a centralized and computerized laboratory-based alert system, patient dedicated use of gowns and gloves) that occurred at that time. Starting from the same period, an active surveillance of colonized patients and their contacts was also implemented, by means of rectal swab and according to European guidelines [9].

All these measures have been already proven to reduce the incidence of infections due to multidrug resistant gram negatives, including C-R Kp [15–19]. However, after the temporary decrease mentioned above, the incidence of C-R Kp BSI in our hospital rose again to 1.77/10,000 patient-days in 2014. Although a lack of adherence to contention measures might have occurred in some cases, another factor possibly underlie this increase that mostly occurred outside the ICU. Indeed, we recently observed that some C-R Kp intestinal carriers in low risk wards (i.e., wards other than ICU or cancer wards) might not be considered at risk (and thus not screened) even if all recommended infection-control protocols are adopted [20]. This finding suggests that a considerable number of unknown carriers might be circulating in our hospital that are not subjected to contact precautions because of the unawareness of their status. This possibility is rather worrisome, since it could lead to an uncontrolled C-R Kp diffusion, thus fueling the reservoir of patients who possibly develop C-R Kp BSI [20, 21]. In such an uncontrolled endemic setting, further infection-control efforts (e.g., a dynamic redefinition of wards to adopt universal screening through regular point-prevalence surveys) might be necessary to successfully counteract the alarming spread of C-R Kp.

The present study has some important limitations. First, we could not depict the true pattern of C-R Kp diffusion, since only blood C-R Kp isolates were considered. However, C-R Kp BSI can provide a reliable picture of this diffusion, since blood cultures are collected from nearly all patients with C-R Kp BSI because of the symptomatic nature of the infection. Conversely, any possible estimation based on colonized patients would have been affected by an important selection bias due to the differences in the number of screened patients across the study years. Second, the retrospective nature of the study prevented us from investigating the degree of compliance to infection-control measures during the study period, as well as the molecular characteristics of C-R Kp isolates. In this regard, a major limitation is the lack of information about both the clonal type of Kp isolates and their mechanisms of resistance to carbapenems. Finally, this was a single center study, and incidences of C-R Kp BSI may differ significantly across centers. Therefore, any extrapolation of our findings to other settings should be made with due caution.

In our hospital a dramatic increase in the incidence of C-R Kp BSI occurred from 2007 to 2014 that appeared to be only temporarily arrested by the intensification of hospital-based infection-control measures. More concerted efforts are necessary to tackle this alarming C-R Kp diffusion. Because of the dramatic shortage in antibiotics active against C-R Kp, further improvements in our infection-control protocols are also of paramount importance to curtail the high number of deaths due to C-R Kp BSI.