Antibiotic prophylaxis in the era of multidrug-resistant bacteria

Figures & data

Table 1. Components of SOD and SDD.

	SDD	SOD	Medication used
Systemic	X		3rd Generation cephalosporin, (i.e. cefotaxim 1000 mg 4 times daily) during the first 4 days of admission
Mouthpaste	X	X	Tobramycin 2%, amphotericin 2%, colistin 2%; 4 times daily
Intestinal	X		Aminoglycoside (i.e. tobramycin 80 mg 4 times daily) Polymyxin (i.e. colsitin or polymyxin E 100 mg 4 times daily) Antifungal antibiotic (i.e. amphotericin B 500 mg 4 times daily)

SDD: Selective digestive tract decontamination; SOD: Selective oropharyngeal decontamination.

Table 2. Results from Dutch decolonization studies in ICU patients.

	SDD compared to standard care			SOD compared to standard care^‡
	ARR	NNT	RRR	ARR	NNT	RRR
Mortality
Day 28 mortality	3.5%^‡*	29	13.0%^‡*	2.9%*	34	11.0%*
ICU mortality	3.4%^‡*	29	15.2%^‡*	2.3%*	43	10.4%*
In hospital mortality	2.7%^‡*	37	8.5%^‡*	3.4%*	29	10.8%*
ICU acquired bacteremia
≥ 1 episode	6.4%^§	16	49.0%^§	4.0%	25	30.8%
HRMO	0.6%^§	170	6.0%^§	OR 1.10 [0.59-2.07]^§	ND	ND
Candida species and other yeast	0.7%^§	152	7.0%^§	OR 1.16 [0.61-2.21]^§	ND	ND
Glucose-non-fermenting Gram-negative rods (GNF-GNR)	1.0%^‡	98	55.6%^‡	0.9%	110	50.0%
Enterobacteriaceae	3.6%^‡	28	82%^‡	1.3%	78	30.0%

*Calculated from OR adjusted for APACHE II score, age, intubation status, reason for admission, and gender.

^‡De Smet et al. [9].

^§De Smet et al. [22]: analysis of patients with ICU length of stay > 3 days from [9].

ARR: Absolute risk reduction; HRMO: Highly resistant microorganism; ND: Not determined; NNT: Number needed to treat; OR: Odds ratio [95% confidence interval]; RRR: Relative risk reduction; SC: Standard care; SDD: Selective digestive tract decontamination; SOD: Selective oropharyngeal decontamination.

Table 3. Requirements for prophylactic use of antibiotics in decolonization strategies.

	Antibiotic resistance level*
Requirement	Low	Moderate-high	Remark
1. Effectiveness demonstrated for relevant outcomes in individual studies	Yes	No	Convincing evidence from three studies in settings with low levels of resistance [9-11]. Aggregated data from other settings do suggest an effect on mortality, without evidence from individual trials [26]
2. Short-term ecological safety demonstrated	Yes	No	No evidence of increased resistance in the short term in settings with low levels of resistance [9-11]. Increased prevalence of colonization with gram positives and MRSA and resistance to cephalosporins during SDD in settings with moderate-high levels of antibiotic resistance [5,13-16]
3. Long-term ecological safety demonstrated	No	No	No increase in resistance rates during SDD in two studies with follow-up for up to 5 years [13,23]. Increased point-prevalence of resistance to cephalosporins after discontinuation of SDD in one multi-center study [17], which was not observed in another study [6]
4. Ecological safety after ICU discharge demonstrated	No	No	No data available (study ongoing^‡)
5. Ecological safety in non-culturable flora demonstrated	No	No	No data available (study ongoing^‡)
6. Cost-effectiveness demonstrated	No	No	No data available (study ongoing^‡)

*Low is defined as < 5% of bacteremia episodes caused by MRSA for S. aureus, VRE for enterococci and extended spectrum beta lactamase or carbapenamase producing strains for Enterobacteriaceae [9-11]). Moderate-high: settings not meeting the criteria for low levels of resistance.

^‡M. Bonten, personal communication.

MRSA: Methicillin-resistant Staphylococcus aureus; SDD: Selective digestive tract decontamination.

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