Inappropriate empirical antibiotic use increases 90-day and ICU mortality in Klebsiella pneumoniae bacteraemia

A Hong Kong study of patients with Klebsiella pneumoniae bacteraemia has shown significantly increased 90-day and intensive care unit (ICU) mortality rates in patients who have received inappropriate empirical antibiotic treatment.

“Greater efforts are required to facilitate early and appropriate use of empirical antibiotics, including the use of current antibiogram, implementation of multidisciplinary sepsis management guidelines and establishment of relevant protocols among pharmacists, microbiologists, clinicians and nurses,” said the authors. [Hong Kong Med J 2021;27:247-257]

The retrospective cohort study included 984 patients (median age, 75 years; male, 59.0 percent) with K. pneumoniae bacteraemia who were prescribed appropriate (69.7 percent) or inappropriate (30.3 percent) empirical antibiotic treatment at Pamela Youde Nethersole Eastern Hospital between 1 January 2009 and 30 June 2017. The most common types of K. pneumoniae infection in the cohort were hepatobiliary tract infection (33.1 percent), urosepsis (24.4 percent) and respiratory tract infection (18.4 percent).

K pneumoniae infection led to an overall 90-day mortality rate of 32.7 percent, hospital mortality rate of 22.5 percent, and a median hospital stay of 10.68 days.

Extended-spectrum beta-lactamase (ESBL)–producing strains were detected in 11.5 percent of the patients. The risks of developing ESBL- (18.3 percent vs 10.5 percent; p=0.011) and carbapenem-resistant (CR) (0.056 percent vs 0.015 percent; p=0.003) infections were significantly higher in patients with vs without chronic renal failure.

Compared with patients treated with appropriate empirical antibiotics, those treated with inappropriate empirical antibiotics had significantly higher 90-day mortality rate (46.6 percent vs 26.7 percent; p<0.001) and hospital mortality rate (35.2 percent vs 16.9 percent; p<0.001).

Independent predictors of inappropriate empirical antibiotic use were ESBL or CR resistance (odds ratio [OR], 12.51; p<0.001), history of chronic kidney disease (OR, 1.81; p=0.007), mechanical ventilation (OR, 1.79; p=0.005), age >65 years (OR, 1.60; p=0.010), and respiratory tract infection (OR, 1.50; p=0.034).

Apart from those with respiratory tract infection (hazard ratio [HR], 2.94; p<0.01), those who received inappropriate or no empirical antibiotics (HR, 2.45; p<0.01) and those with ESBL-producing or CR isolates (HR, 1.64; p=0.004), patients with gastrointestinal infection (HR, 2.77; p<0.001), aged >65 years (HR, 1.79; p<0.001), with history of solid tumour (HR, 1.77; p<0.01), admitted through Department of Medicine (HR, 1.39; p<0.012), and those with a raised total Sequential Organ Failure Assessment (SOFA) score (HR, 1.09; p<0.001) were found to have significantly increased 90-day mortality rate.

Of 205 patients (20.8 percent of the cohort) who required ICU admission, 27.8 percent received inappropriate empirical antibiotics. 

In patients admitted to ICU, inappropriate vs appropriate empirical antibiotic treatment was associated with significantly higher rates of 90-day mortality (59.6 percent vs 25.0 percent; p<0.001), ICU mortality (35.1 percent vs 12.2 percent; p<0.001) and hospital mortality (56.1 percent vs 23.0 percent; p<0.001), as well as longer ventilator use (2 days vs 1 day; p=0.026).

Inappropriate use or no use of empirical antibiotics was the strongest independent predictor of 90-day mortality in patients admitted to ICU (HR, 3.00; p<0.001), followed by history of congestive heart failure (HR, 2.28; p<0.001), specific admitting department (HR, 1.94; p=0.016), and raised total SOFA score (HR, 1.17; p<0.001).

Of note, the risk of 90-day mortality was significantly reduced in patients with vs without history of diabetes mellitus in both the overall cohort (HR, 0.65; p=0.001) and among those admitted to the ICU (HR, 0.39; p=0.001).