Clinical Outcomes of Septic Patients with Carbapenemase Producing Klebsiella pneumoniae at a New York City Hospital

Background:  Carbapenemase producing Klebsiella pneumoniae (KPC) have emerged as a significant healthcare challenge due to limited treatment options and potential delays in initiating appropriate treatment.

Objective:  To evaluate whether septic patients with KPC bacteremia (cases) were more likely to have adverse outcomes compared to septic patients with Klebsiella pneumoniae bacteremia that were not KPC (controls).

Methods: A retrospective matched case control study was conducted at Montefiore Medical Center. All patients with sepsis and K pneumoniae bacteremia from 1/1/2008 to 6/30/2010 were identified and those with septic shock within 24 h of + blood culture (BC) collection or with + BC for other organisms within 10 d prior and 30 d after K pneumoniae + BC were excluded. Demographics, comorbidities, bacteremia source, time to administration of appropriate antibiotics, and time from onset of symptoms to BC collection were obtained. End points included: sepsis progression at 3 d, length of stay (LOS) and in-hospital all cause mortality at 7 and 30 d. Controls were matched to cases for age (±5 y), BC collection data (±6 m) and number of comorbidities. Empiric therapy was considered appropriate if the isolate had in vitro susceptibility to at least 1 drug given within 1 d from + BC.

Results:  32 cases were matched to 64 controls. Univariate analysis found no differences in age, gender, time from symptoms to BC collection and proportion of patients with severe sepsis within 24 h of BC. Types of comorbidities and bacteremia source were similar, except cases were more likely to have CHF and line sources and abdominal source was more common in controls. Cases were more likely to be hospital acquired (P<0.001), and to receive palliative care or to have DNR status (P=0.01) compared to controls. Cases were less likely to have received appropriate empiric antibiotics compared to controls (18% vs. 68%, P<0.001). Time to appropriate antibiotics was longer in cases (3 vs. 1 d, P<0.001). LOS, sepsis progression and 30 d mortality were significantly more frequent among cases by univariate analysis, but were no longer significant by multivariate analysis (Table1).

Conclusions:  KPC infected septic patients were not at increased risk of mortality, sepsis progression or longer LOS relative to KPC negative septic controls. The results suggest that once patients become septic (either KPC + or KPC-) that delays in initiating either appropriate or timely therapy may not influence outcome. This underscores the need for timely and appropriate antibiotic therapy early in the course of K pneumoniae infection to prevent progression to sepsis.

Table 1. Clinical Outcomes: Cases vs. Controls 

Outcomes	Case (n=32)	Control (n=64)	Univariate analysis P value	Multivariate analysis P value
Length of stay	14 (9.5, 28.5)	8 (4, 15)	0.005	0.07
Sepsis Progression	10 (31)	7 (11)	0.01	0.07
7 d mortality	6 (19)	3 (5)	0.06
30 d mortality	8 (25)	5 (8)	0.03	0.08