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Table 2 Identified studies in the context of ESBL-E or CR-E decolonization

From: Intestinal decolonization of Enterobacteriaceae producing extended-spectrum β-lactamases (ESBL): a retrospective observational study in patients at risk for infection and a brief review of the literature

Author, year; study type

Patients included

Pathogen

Decolonization regimena [duration]

Decolonization efficacy [definition, methods to detect]

Follow-up period

Resistance development

Remarks

Prospective ‘decolonization’ studies

Huttner et al., 2013; randomized, double-blind, placebo-controlled study [8]

Hospitalized carriers (n = 54)

ESBL-E (E. coli ~80 %, K. pneumoniae ~20 %)

Colistin 1,26 MU, neomycin 250 mg [10d] (plus nitrofurantoin 3 × 100 mg/d [5d] in urinary tract colonization) (n = 27) vs. placebo (n = 27)

52 % vs. 37 %; no significant difference [≥1 neg. rectal swab culture]

28 ± 7 days

No significant change in colistin or neomycin MICs

Extraintestinal colonization 50 % at baseline; systemic antibiotic treatment in 4 % of patients (vs. 19 % in placebo group)

Oren et al., 2013; prospective, controlled study [10]

Hospitalized carriers (n = 152), ~40 % of which with clinical infection

CR-E (K. pneumoniae ~90 %)

Colistin 2,5 MU (n = 16) or gentamicin 80 mg (n = 26) or combination (n = 8) [until decolonization, max. 60 d] vs. spontaneous eradication (n = 102)

44 % (42 %, 50 %, 37.5 %) vs. 7 %; significant difference [3 neg. consecutive rectal swabs cultures, neg. PCR testing of third swab]

Median f/u 33 days vs. 140 days

Gentamicin resistance 23 %; colistin resistance 6 %, combination 0 %

Systemic antibiotic treatment in ~40 % of patients in both groups

Saidel-Odes et al., 2012; randomized, double-blind, placebo-controlled study [9]

Hospitalized carriers (n = 40)

CR-E (K. pneumoniae)

Colistin 1 MU, gentamicin 80 mg, plus SOD [7d] (n = 20) vs. placebo (n = 20)

59 % vs. 33 %; no significant difference [neg. rectal swab culture]

42 days

None, gentamicin MIC remained ≤2 mg/ml and colistin MIC ≤0.094 mg/ml

Efficacy 61 % vs. 16 % at week 2; no impact on extraintestinal colonization (groin cultures 60 % positive)

Buehlmann et al., 2011; prospective, controlled study [11]

Infected patients (n = 83) or hospitalized carriers (n = 17)

ESBL-E (E. coli 71 %, K. pneumoniae 25 %)

Paromomycin 1 g (intestinal colonisation) [4d], diverse oral antibiotics (urinary tract colonization) [5d], chlorhexidine mouth rinse [5d] (n = 39) vs. spontaneous eradication (n = 61)

63 % (ITT analysis)/83 % (on treatment analysis) vs. 55 % [≥1 neg. throat and rectal swab and neg. urine culture]

Median f/u 24 months

n.d.

55 % of patients eliminated ESBL-E without decolonization regimen by systemic antibiotic treatment or surgery

SDD studies with ESBL-E or CR-E decolonization efficacy subgroup analysis or retrospective observational studies

Lübbert et al., 2013; retrospective, observational SDD study [12]

Hospitalized carriers (n = 52) or infected patients (n = 38)

CR-E (K. pneumoniae)

Colistin 1 MU, gentamicin 80 mg plus SOD [7d] (n = 14) vs. non SDD-control (n = 76)

43 % vs. 30 %; no significant difference [≥3 consecutive negative rectal swab PCRs separated by ≥48 h from one another]

Median f/u 48 days vs. 53 days

2/6 previous sensitive isolates acquired colistin resistance; 5/11 acquired gentamicin resistance

Systemic antibiotic treatment in 43 % of SDD group vs. 29 % non-SDD group

Oostdijk et al., 2012; post hoc subgroup analysis of prospective, randomized SDD study [13]

Hospitalized (ICU) carriers (n = 507)

3CR-E or AGR-Eb

Colistin 2,5 MU, tobramycin 80 mg, amphotericin B 500 mg plus SOD [until discharge]; no control group

73 % in 3CR-E (vs. 80 % in cephalosporin-sensitive isolates), 62 % in AGR-E(vs. 81 % in aminoglycoside-sensitive isolates) [2 consecutive rectal swab cultures]

Until ICU discharge

No significant resistance development in patients with decolonization failure

Decolonization after median duration of 5 days in 3CR-E, 5.5 days in AGR-E (vs. 4 days in respective sensitive isolates)

Abecasis et al., 2011; post hoc subgroup analysis of prospective SDD study [14]

Hospitalized (pediatric ICU) carriers (n = 28) or infected patients (n = 11)

ESBL-E

Colistin, tobramycin, parenteral cefotaxime [until ICU discharge, dose and duration not specified]; no control group

Overall 54 % (21/39), with follow-up 21/27 (78 %) [negative rectal swab culture]

Until ICU discharge

No tobramycin resistence development

In 9/23 patients with tobramycin-resistent isolates decolonization failed (vs. 0/16 with tobramycin-sensitive isolates)

Troché et al., 2005; post hoc subgroup analysis of prospective SDD study [15]

Hospitalized (ICU) carriers (n = 27) or infected patients (n = 10)

ESBL-E

Colistin 1.5 MU plus neomycin 500 mg or plus erythromycin 500 mg [until two negative rectal swabs or ICU discharge]; no control group

46 % [2 consecutive negative rectal swab cultures]

Until ICU discharge

n.d.

Systemic antibiotic treatment in ten infected patients

Nitschke et al., 2012; retrospective observational cohort studyc [16]

Patients with intestinal carriage of STEC with or without HUS (n = 65)

STEC O104:H4

Azithromycin [cumulative 3 g in 14 days] (n = 22) vs. spontaneous eradication (n = 43)

95 % vs. 19 %; significant difference [≥2 neg. stool cultures over a period of at least 6 days]

Mean f/u 41 days vs. 45 days

n.d.

Subsequently, 15 long term STEC carriers were treated with 3 days azithromycin with 100 % decolonization efficacy

Paterson et al., 2001; retrospective observational cohort studyc [17]

Hospitalized carriers (n = 7) or infected patients (n = 2)

ESBL-E (E. coli 67 %, K. pneumoniae 33 %)

Norfloxacin 2 × 400 mg/d [5d]; no control group

44 % [≥1 neg. stool culture]

28 days

n.d.

Transient ESBL-E suppression at day 2–3 after completion of norfloxacin in 9/9 patients

  1. ESBL-E extended-spectrum β-lactamase-producing Enterobacteriaceae, CR-E carbapenem-resistent Enterobacteriaceae, 3CR-E 3rd generation cephalosporin-resistant Enterobacteriaceae, AGR-E aminoglycoside-resistant Enterobacteriaceae, STEC O104:H4 shiga toxin–producing enteroaggregative Escherichia coli, HUS hemolytic uremic syndrome, ICU intensive care unit, n numbers, n.d. not determined, neg. negative, SDD selective digestive tract decolonization, SOD selective oral decontamination, MU million units, f/u follow-up, MIC minimal inhibitory concentration
  2. aDecolonization regimens were applied four times daily via oral route or nasogastric tube unless otherwise stated as dose per day (/d). bResistance against ceftazidime, cefotaxime and ceftriaxone were considered as proxy for ESBL production. cNot considered a SDD study