Emergence of colistin resistance in Enterobacteriaceae after the introduction of selective digestive tract decontamination in an intensive care unit

Abstract

Selective decontamination of the digestive tract (SDD) selectively eradicates aerobic Gram-negative bacteria (AGNB) by the enteral administration of oral nonabsorbable antimicrobial agents, i.e., colistin and tobramycin. We retrospectively investigated the impact of SDD, applied for 5 years as part of an infection control program for the control of an outbreak with extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae in an intensive care unit (ICU), on resistance among AGNB. Colistin MICs were determined on stored ESBL-producing K. pneumoniae isolates using the Etest. The occurrence of both tobramycin resistance among pathogens intrinsically resistant to colistin (CIR) and bacteremia caused by ESBL-producing K. pneumoniae and CIR were investigated. Of the 134 retested ESBL-producing K. pneumoniae isolates, 28 were isolated before SDD was started, and all had MICs of <1.5 mg/liter. For the remaining 106 isolated after starting SDD, MICs ranged between 0.5 and 24 mg/liter. Tobramycin-resistant CIR isolates were found sporadically before the introduction of SDD, but their prevalence increased immediately afterward. Segmented regression analysis showed a highly significant relationship between SDD and resistance to tobramycin. Five patients were identified with bacteremia caused by ESBL-producing K. pneumoniae before SDD and 9 patients thereafter. No bacteremia caused by CIR was found before SDD, but its occurrence increased to 26 after the introduction of SDD. In conclusion, colistin resistance among ESBL-producing K. pneumoniae isolates emerged rapidly after SDD. In addition, both the occurrence and the proportion of tobramycin resistance among CIR increased under the use of SDD. SDD should not be applied in outbreak settings when resistant bacteria are prevalent.

Fig 1

Monthly observed numbers of patients harboring extended-spectrum beta-lactamase-producing K. pneumoniae between 2001 and 2008 (n = 197). The ICU was closed from January through April 2003.

Fig 2

Susceptibility to colistin among 134 extended-spectrum beta-lactamase-producing K. pneumoniae isolates, as retrospectively determined by the Etest method. MICs (mg/liter) are shown.

Fig 3

Monthly occurrence of CIR isolates (n = 2,572) between 2001 and 2008.

Fig 4

Segmented regression analysis showing the relationship between the introduction of SDD and tobramycin resistance among CIR isolates (black dots). The logistic regression model fit (solid lines) is shown, together with its 95% confidence interval (dashed lines).

Fig 5

Proportions of tobramycin-resistant isolates from surveillance cultures (black dots) and clinically indicated cultures (gray triangles) between 2001 and 2009. The logistic regression model fit (solid lines) is shown, together with its 95% confidence interval (dashed lines).

Fig 6

Monthly occurrence of bacteremia caused by CIR (Proteus, Morganella, and Serratia spp.) and extended-spectrum beta-lactamase-producing K. pneumoniae between 2001 and 2008.