Multiple Site Decontamination in ICU patients: a real life pre/post study

doi:10.21203/rs.3.rs-1974251/v1

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Multiple Site Decontamination in ICU patients: a real life pre/post study

https://doi.org/10.21203/rs.3.rs-1974251/v1

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Background: Decontamination regimen decreases acquired infection (AI) incidence but remains controversial, mostly because it contained a course of intravenous antibiotic. Multiple site decontamination (MSD), that do not included systemic antibiotics, has been less studied but is associated with lower risk of ventilator associated pneumonia (VAP), bloodstream infection (BSI) and multidrug resistant micro-organisms (MDRO) acquisition. We aimed to confirm these favorable outcomes.

Methods: A prospective pre/post-observational study was conducted in 5 ICUs in western France. Among them, 4 implemented MSD whereas the last one applied standard care (SC) during all study period. Patients who required intubation were eligible for study and divided into two groups: MSD group if they were admitted in an ICU that already implemented MSD and SC group otherwise. Primary objective was AI incidence.

Results: 1346 patients were available for analysis (334 in the MSD and 1012 patients in the SC group). In a multivariable Poisson regression model, MSD was independently associated with a decreased incidence of AI (IRR = 0.33; 95%CI [0.18-0.60] p<0.001). A non-parsimonious propensity-score matching resulted in 334 patient-pairs with well-balanced baseline characteristics. There were a lower incidence of AI (6.3% vs 20.7% p<0.001), VAP (3.6% vs 16.2% p <0.001) and BSI (3.0% vs 7.2% p = 0.029) in the MSD group as compared with the SC group. Five patients (1.5%) and 11 (3.3%) acquired a MDRO respectively (p=0.206).

Conclusion: MSD is associated with a decrease risk of AI, VAP and BSI with no increase in MDRO acquisition.

Critical care

Pneumonia

Bacteremia

mortality

Acquired infection

Ventilated patients receiving multiple site decontamination (MSD) have a decreased risk of acquired infection, without increase in MDRO acquisition. There was a lower consumption of high resistance promoting betalactam in ICU that implemented MSD.

Intensive-care unit (ICU) acquired infections (AI) are life threating complications of critical illness (1-5). AI prevention methods target both routes of AI that are consequences of exogenous but mainly endogenous colonization (6, 7). Among them, selective decontamination is the only one that decreases AI incidence but also mortality in area with low anti-microbial resistance rate (8-10). However, this therapy remains controversial, mostly because studies that reported favorable results were in the vast majority conducted in the Netherlands and contained a short course of intravenous systemic antibiotic, rising concern about spreading antibiotic resistance (11). Nevertheless, other decontamination regimens have been studied, of whom multiple site decontamination (MSD) that do not included systemic antibiotics, which has been associated with favorable outcomes on AI, including ventilator associated pneumonia (VAP), bloodstream infection (BSI), multidrug resistant micro-organisms (MDRO) acquisition and potentially ICU mortality (12-15). We aimed to confirm this favorable outcomes following MSD implementation.

Patients and setting

Anticipating a change in daily practice with MSD implementation in some ICUs, a prospective pre/post observational study was conducted in 5 ICUs in Bretagne, western France. Among them, 4 implemented MSD whereas the last one applied standard care (SC) during all study period and served for statistical adjustment on temporal trend in AI incidence. From 7^th September 2020 until 31^th December 2021 all adults who required mechanical ventilation for 24 hours or more were eligible at the exception of those with liberty deprivation, pregnant women and patients younger than 18 years old who were excluded from the study. In addition to standard care, 4 ICUs implemented MSD during study period for the prevention of acquired infections in patients with expected intubation duration > 24 hours throughout the duration of intubation. Date of implementation was not set by the study but depends on local parameters. MSD is a variant of selective digestive decontamination, which consists of the administration of topical antibiotics including gentamicin, polymyxin and amphotericin B, four times daily in the oropharynx and the gastric tube, chlorhexidine body-wash once daily and a 5-day nasal mupirocin course. Of note, one ICU (ICU 3 - Quimper) did not perform the two last components that are chlorhexidine body-wash and mupirocine nasal course because for practical reasons. Details about the MSD regimen are reported in supplementary data. Patients in ICU 5 (Lorient) received standard care alone. Eligible patients were divided into two groups: MSD group if they were admitted in an ICU that already implemented a decontamination regimen and SC group if they were admitted in an ICU that have not yet, or will not, implements MSD. The study protocol received approval from the Rennes Hospital ethics committee (comité d’éthique du CHU de Rennes avis 19-52). Patients or closest relative were informed of the anonymous prospective collection of the data and had the possibility not to participate in the study. In case of refusal, the data were not collected accordingly. This manuscript follows the STROBE statement for reporting cohort studies.

Strategies for AI prevention and diagnosis

Strategies for VAP and BSI prevention were let at each ICU discretion but they were no modification of practices during study period at the exception of MSD implementation in concerned ICUs. Standard-care consists of semi recumbent position for all patients unless contra-indicated, 4 time daily cuff pressure monitoring and there were no specific protocol for ulcer prophylaxis.

VAP diagnosis was systematically associated with a pulmonary sample which can be an endotracheal aspiration, a broncho-alveolar lavage or a distally protected sample. During study period, physicians were asked to complete a check list for each VAP suspicion in order to collect crucial data for VAP classification by the dedicated team in each center (supplementary data). AI diagnosis was suspected by treating physician but was final diagnosis was confirmed by a dedicated member of the nosocomial infection committee (CLIN) in each hospital.

Definition

Each center had a CLIN for the prevention and prospective census of AI and applied the recommendations of the French Society for Hospital Hygiene for the prevention and treatment of infection (available at https://sf2h.net/publications/actualisation-precautions-standard-2017). Infection was considered acquired in the ICU when it was diagnosed 48 hours after admission and was not incubating on admission. AI were diagnosed by the treating physician. BSI was defined as a positive blood culture occurring 48 hours or more after admission. Regarding common skin contaminants, 2 positives blood cultures drawn on separate occasions were required (2). The diagnosis of VAP was considered in patients ventilated for 48 hours or more and until 48 hours after extubation and was based on clinical signs (fever, purulent sputum, hypoxia), radiological findings (new infiltrate on chest-X-ray or CT scan), and leukocytosis (16). Microorganisms responsible for infection were considered as MDRO according to the European Society of Clinical Microbiology and Infectious Disease definition (17).

Classification of antibiotic according with their intrinsic risk of selection of antimicrobial resistance is not consensual. Experts considered that in addition to their spectrum, the global impact of antibiotics on the microbiota and their impact on ‘colonization resistance’ have to be considered (18). They provide a 6 ranks consensual scale. For the purpose of the study, we classified beta-lactams of the 3 first ranks as low resistance promoting antibiotics (Penicillin, Amoxicillin-clavulanic acid, 3^rd generation cephalosporins, and the 3 last as high resistance promoting antibiotics (Piperacillin + Tazobactam, Cefepim, Ceftazidim and Penems).

Primary and secondary endpoints

The primary endpoint was AI incidence, and secondary endpoints were specific VAP and BSI incidences as well as in ICU mortality and high resistance promoting antibiotics consumption in both groups.

Statistical analysis

Statistical analysis was performed with the statistical software R 4.1.1. Categorical variables were expressed as percentages and continuous variables as median and interquartile range (IQR). The chi-square test and Fisher exact test were used to compare categorical variables and the Man-Whitney U test or the Wilcoxon for continuous variables. Antibiotic consumptions were expressed as the number of defined daily doses (DDD) for 1000 patients-days as defined by the world health organization (https://www.who.int/tools/atc-ddd-toolkit/about-ddd) and were compared using chi-square test. In order to draw unbiased marginal estimates of exposure effect, a propensity-score matched analysis was performed. Propensity score was calculated using a non parsimonious model (including all available baseline characteristics including center of admission but at the exception of period of admission) and correspond for each patient to his probability to be admitted in an ICU where MSD has already been implemented. Using the “MatchIt” package, a k-nearest neighbor algorithm was used for propensity-score matching with a 1:1 ratio. The balance between matched groups was evaluated by the analysis of the standardized mean differences after weighting. A post-matching difference < 0.1 was considered as an optimal bias reduction.

Risk factors for acquired infections and hospital death were estimated using logistic regression and Kaplan-Meier survival curves with log-rank test were used for survival analysis. Incidence rate were compared using a Poisson regression model. Multivariable analysis were performed in complete cases. All tests were two-sided, and p<0.05 was considered statistically significant.

Population

Among the 2293 eligible patients admitted during study period, 947 were not intubated or less than 24 hours leaving 1346 patients available for analysis. Among them 334 where admitted in an ICU that already has implemented MSD and constituted the MSD group whereas 814 where admitted in those ICUs before MSD implementation and 198 others where admitted in an ICU that did not implemented MSD during study period (this 1012 patients constituted the standard-care group) (Figure 1). Baseline characteristics are reported in Table 1, age was 65 years [55-72], SAPS II was 54 [40-68], patients were mostly admitted from home (63%) and 121 patients (8.9%) were colonized with an extended-spectrum betalactamase producing Enterobacteriaceae (ESBL-PE) at admission.

Acquired Infections incidence in full population

They were 349 AI (258 VAP and 91 BSI) in the standard-care group among 14 464 patients days as compared with 37 AI (25 VAP and 12 BSI) among 3 528 patients-days in the MSD group (p<0.05 for all infection site). There were 37 MDRO acquisition in the standard-care group as compared with 5 in the MSD group (p = 0.074) (Supplementary Table 1). In a multivariable Poisson regression model, MSD was independently associated with a decreased incidence of AI (incidence rate ratio [IRR] = 0.33; 95%CI [0.18-0.60] p<0.001) as was admission for unplanned surgery (IRR = 0.56; 95%CI [0.32-0.98] p=0.044), conversely, coronavirus infectious disease 2019 (IRR = 1.48; 95%CI [1.13-1.94] p=0.004) and presence of a vascular catheter during period at risk for AI (IRR = 2.49; 95%CI [1.16-5.32] p=0.019) were associated with an increased risk (Table 2). Trends in AI incidence in each ICU are reported in Figure 2 and Supplementary Figure 1.

Propensity score matched analysis

In order to obtain two groups of patients that only differ with the use of MSD, a non parsimonious propensity-score matching was performed. Matching process resulted in 334 patient-pairs with well balanced baseline characteristics (Table 1). Outcomes of these patients are reported in Table 3. There were 25 AI in the MSD group among 3528 patients-days (including 2626 ventilator-days) and 102 AI in the standard-care group among 4275 patient-days (including 3401 ventilator-days) (IRR = 0.29; 95%CI [0.19-0.45] p <0.001) as a consequence of 13 (5 VAP per 1000 ventilator-days) and 72 VAP (21 per 1000 ventilator-days) in each group respectively (IRR = 0.22; 95%CI [0.11-0.39] p <0.001) and 12 and 30 BSI in each group respectively (IRR = 0.48; 95%CI [0.25-0.94] p = 0.029). The favorable result on AI incidence was consistent among various subgroups of patients (Supplementary Figure 2) including patients who did not received antibiotic at admission. Results were similar when the 41 patients from ICU 3 (MSD without chlorhexidine daily body wash) were removed from the analysis. Of note there were no interaction between MSD administration and systemic antibiotic administration at admission (p = 0.77) suggesting that effects of both treatments are not synergic. There were no statistical differences in other outcomes despite a lower number of patients who acquired ESBL-PE colonization in the MSD group (3 vs 10 p = 0.089).

Microorganisms responsible for infection

There were no differences in distribution of microorganisms responsible for AI in between groups (Table 4). There were 2 AIs due to MDRO in the MSD group (1 Methicillin resistant Staphylococcus aureus in a patient without previous colonization screening and 1 Vancomycin resistant Enterococcus faecium in a prior ICU colonized patient) as compared with 8 AIs due to MDRO in the standard-care group (p = 1.0).

Antibiotic consumption

Curative antibiotic consumptions during pre- and post-implementation periods of the ICUs that implemented MSD are reported in Table 5. They were an increased of low resistance promoting antibiotic consumption in the post-implementation period particularly penicillin and amoxicillin-acid clavulanic, whereas there were a decrease of 3^rd generation cephalosporin (with and without anti-pseudomonas activity), cefepim, carbapenems and finally a decrease of high resistance promoting antibiotic consumption overall (as defined as cefepim, ceftazidime, piperacillin with tazobactam or carbapenems).

In this pragmatic pre/post observational study we confirmed that MSD implementation is associated with a lower incidence of AI, VAP and BSI with no increase in the incidence of MDRO acquisition.

Favorable outcomes have been reported with various decontamination regimens including selective digestive and oropharyngeal decontaminations but also chlorhexidine bodywash and mupirocine (8-10, 12, 19). Noteworthy, all the studies that reported favorable outcomes were conducted in area with low prevalence of antibiotic resistance. In contrast, the largest study of decontamination regimens in higher resistance incidence rate did not support its application (20). In the present study either, they were a low resistance rate with less than 10 % of ESBL-PE prevalence rate and results should be therefore confirm in other resistance settings (14).

A major modification with usual decontamination regimens was the absence of systemic intravenous antibiotic administration at admission. In a randomized control trial, Camus et al. observed no differences in AI incidence among patients receiving topical antibiotic alone or not but demonstrated that combination of such topical regimen with chlorhexidine bodywash and mupirocine (constituting MSD) had synergic effect and efficiently decreases AI (12). A trend toward a lower mortality rate in patients receiving MSD was noticed but deserves to be confirmed (15). In the present study, results support MSD application whether patients received systematic antibiotic at admission or not. It is unknown whether decontamination regimens that include systemic antibiotic are more efficient than MSD in decreasing AI.

Regarding mortality, Plantinga et al. reported in an individual patient data meta-analysis that selective digestive decontamination is more efficient than selective oropharyngeal decontamination in improving patient survival (21). The differences between both regimens are administration of a gastroduodenal suspension of topical antibiotics and a 4-day course of intravenous cephalosporin, therefore they could not precise which of theses interventions is responsible for the improved outcome. Conversely, Liberati et al. reported in a systematic review that despite topical antibiotic alone are associated with a lower incidence of VAP there is no effect on mortality (22). The physio pathological reason for improved survival in patients receiving decontamination regimens is not elucidated. Herein, attributable mortality of VAP is questionable, especially in medical patients (11) and BSI attributable mortality is low, representing about 2 % of the ICU deaths (5). Other mechanism that AI prevention may be involved such as microbiota modification and deserve to be further studied (22).

Decreased risk of MDRO acquisition with decontamination regimens has been previously described (13, 21). In our study either, there were no increase in MDRO acquired colonization nor AI but the small amount of event preclude further conclusions.

Strengths of this study are the pragmatic pre/post multi-centric prospective design, with large sample size. However, some limitations should be acknowledged. First, it was conducted in a favorable area with low MDRO incidence rate and results should not be generalized in all settings. Second, study protocol was unmasks and AI management may have been influenced. However, they were no modification in institutional protocol in any ICU during study period regarding AI diagnosis, census and treatment. Moreover, even tough VAP diagnosis could be consider as subjective (23), BSI diagnosis is less questionable. Lastly, some residual confounders could have influenced the outcomes.

To conclude, MSD implementation is associated with a lower incidence of AI, VAP and BSI among ICUs patients with no increase in MDRO acquisition. Larger cluster randomized trial are warranted to further confirm this favorable results.

AI: acquired infection

MSD : Multiple Site Decontamination

VAP : ventilator associated pneumonia

BSI : bloodstream infection

MDRO : multidrug resistant micro-organisms

SC : standard care

ICU : Intensive Care Unit

CLIN : comité de lute contre les infections nosocomiales

STROBE : STrengthening the Reporting of OBservational studies in Epidemiology

CT : Chest tomography

SAPS II : simplified acute physiology score II

ESBL-PE : extended-spectrum betalactamase producing Enterobacteriaceae

Ethics approval and consent to participate

This study respects the French reference method MR004. Patients or closest relatives were informed of the retrospective collection of the data and only those who did not provide opposition to their participation in the study were enrolled. The Rennes Hospital ethics committee approved the study (comité d’éthique du CHU de Rennes) approved the study protocol (avis 19-52).

Consent for publication

Not applicable

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests

Funding

No funding was received

Authors' contributions

All authors participated to acquisition of data, NM, FLG, NB, GR and PF participated to the conception and design of the study, NM, PF and CD performed the analysis and interpretation of data, NM drafted the article, all authors finally approved the submitted version .

Acknowledgements

NM would like to thanks Christophe CAMUS for is wise advices and the time spend on the transmission of his knowledge in the field of decontamination.

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Table 1. Baseline characteristics of study patients.

	All patients			Matched patients
	SC	MSD	p-value	SC	MSD	p-value	SMD
Variables	n = 1012	n = 334		n = 334	n = 334
Age, year	65.34 [55.26 - 72.17]	64.69 [54.82 - 71.81]	0.403	65.01 [56.10 - 72.25]	64.69 [54.82 - 71.81]	0.564	0.06
Simplified acute physiology score II	53.00 [40.00 - 67.00]	58.00 [42.00 - 72.00]	0.003	57.00 [46.00 - 71.00]	58.00 [42.00 - 72.00]	0.637	0.05
Male – no. (%)	683 (67.5)	229 (68.6)	0.767	232 (69.5)	229 (68.6)	0.867	0.02
Immunodepression– no. (%)	132 (13.0)	25 (7.5)	0.008	24 (7.2)	25 (7.5)	1.000	0.01
Period of admission			<0.001			0.001	-
Fall 2020– no. (%)	310 (30.6)	0		128 (38.3)	0
Winter 2020– no. (%)	289 (28.6)	0		112 (33.5)	0
Spring 2021– no. (%)	279 (27.6)	20 (6.0)		80 (24.0)	20 (6.0)
Summer 2021– no. (%)	94 (9.3)	120 (35.9)		14 (4.2)	120 (35.9)
Fall 2021– no. (%)	40 (4.0)	194 (58.1)		0	194 (58.1)
Reason for admission			0.965			1.000
Trauma– no. (%)	45 (4.4)	14 (4.2)		15 (4.5)	14 (4.2)		0.01
Scheduled surgery– no. (%)	33 (3.3)	10 (3.0)		8 (2.4)	10 (3.0)		0.03
Urgent surgery– no. (%)	108 (10.7)	49 (14.7)		52 (15.6)	49 (14.7)		0.03
Medicine– no. (%)	871 (86.1)	275 (82.3)		274 (82.0)	275 (82.3)		0.01
Localization before admission			<0.001			0.739
Home– no. (%)	604 (59.7)	239 (71.6)		231 (69.2)	239 (71.6)		0.05
Acute care ward– no. (%)	309 (30.5)	80 (24.0)		91 (27.2)	80 (24.0)		0.08
Long care facility– no. (%)	10 (1.0)	3 (0.9)		2 (0.6)	3 (0.9)		0.03
Other ICU– no. (%)	89 (8.8)	12 (3.6)		10 (3.0)	12 (3.6)		0.03
COVID-19– no. (%)	282 (27.9)	39 (11.7)	<0.001	38 (11.4)	39 (11.7)	1.000	0.01
At admission ESBL-PE colonization– no. (%)	115 (11.4)	6 (1.8)	<0.001	6 (1.8)	6 (1.8)	1.000	0.00
Early management
Systemic antibiotic at admission – no. (%)	617 (61.0)	196 (58.7)	0.499	194 (58.1)	196 (58.7)	0.937	0.01
Vascular catheter – no. (%)	862 (85.2)	262 (78.4)	0.005	266 (79.6)	262 (78.4)	0.776	0.03

Note. SC : standard care. MSD : Multiple site decontamination. SMD : Standard mean difference. ICU : Intensive-care unit. COVID-19 : SARS-COV 2 associated infection disease. ESBL-PE : extended spectrum beta lactamase producing Enterobacteriaceae. SMD : standardized mean difference.

Table 2. Risk factors for acquired infection (Poisson regression test).

	Univariate			Multivariable
	IRR	95% CI	p-value	IRR	95% CI	p-value
MSD	0.34	0.22-0.53	<0.001	0.33	0.18-0.60	<0.001
Age, per supplementary year	1.00	0.99-1.01	0.75
Simplified acute physiology score II per supplementary point	1.00	0.99-1.01	0.83
Male	1.28	0.96-1.69	0.089	1.21	0.90-1.60	0.19
Immunodepression	1.17	0.84-1.62	0.34
Trauma	1.24	0.74-2.09	0.41
Reason for admission
Medicine	Ref	Ref	Ref	Ref	Ref	Ref
Scheduled surgery	1.05	0.52-2.13	0.89	1.11	0.55-2.26	0.77
Urgent surgery	0.46	0.26-0.81	0.007	0.56	0.32-0.98	0.044
Localization before admission
Home	Ref	Ref	Ref	Ref	Ref	Ref
Acute care ward	1.04	0.80-1.36	0.73	0.94	0.72-1.23	0.67
Long care facility	1.49	0.55-4.03	0.43	1.22	0.45-3.31	0.70
Other ICU	1.28	0.89-1.83	0.18	0.94	0.64-1.37	0.74
Period of admission
Fall 2020	Ref	Ref	Ref	Ref	Ref	Ref
Winter 2020	0.80	0.57-1.13	0.20	0.83	0.59-1.17	0.29
Spring 2021	0.93	0.69-1.26	0.63	0.84	0.61-1.15	0.27
Summer 2021	0.51	0.34-0.78	0.002	0.82	0.52-1.27	0.37
Fall 2021	0.51	0.32-0.81	0.004	1.28	0.69-2.35	0.43
COVID-19	1.82	1.43-2.30	<0.001	1.48	1.13-1.94	0.004
At admission ESBL-PE colonization	1.13	0.78-1.64	0.51
Vascular catheter	3.15	1.49-6.67	0.003	2.49	1.16-5.32	0.019
Systemic antibiotic at admission	0.91	0.71-1.16	0.44

Note. SC : standard care. MSD : Multiple site decontamination. ICU : Intensive-care unit. COVID-19 : SARS-COV 2 associated infection disease. ESBL-PE : extended spectrum beta lactamase producing Enterobacteriaceae.

Table 3. Outcomes in matched patients pairs

	SC	MSD	p-value
Variables	n = 334	n = 334
ICU acquired infection– no. (%)	69 (20.7)	21 (6.3)	<0.001
Ventilator-associated pneumonia– no. (%)	54 (16.2)	12 (3.6)	<0.001
Bloodstream infection– no. (%)	24 (7.2)	10 (3.0)	0.022
Time from admission to first AI, days	9 [4 - 13]	9 [6 - 17]	1.000
ESBL-PE colonization acquisition– no. (%)	10 (3.0)	3 (0.9)	0.089
MDRO colonization acquisition– no. (%)	11 (3.3)	5 (1.5)	0.206
Length of stay, days	8 [4 - 16]	7 [4 - 13]	0.097
Length of mechanical ventilation, days	5 [2 - 13]	5 [2 - 10]	0.184
In ICU death– no. (%)	86 (25.7)	90 (26.9)	0.792

Note. SC : standard care. MSD : Multiple site decontamination. ICU : Intensive-care unit. ESBL-PE : extended spectrum beta lactamase producing Enterobacteriaceae. MDRO : Multi Drug Resistant Micro Organisms.

Table 4. Microorganisms responsible for the 127 AI of the 334 matched patients-pairs.

	SC	MSD	p
Variables	n = 102	n = 25
Staphylococcus aureus– no. (%)	24 (23.5)	3 (12.0)	0.322
Streptococcus sp. – no. (%)	7 (6.9)	3 (12.0)	0.660
Coagulase negativ Staphylococcus– no. (%)	7 (6.9)	5 (20.0)	0.103
Other Gram positive cocci – no. (%)	6 (5.9)	3 (12.0)	0.526
Enterobacteriaceae– no. (%)	42 (41.2)	7 (28.0)	0.325
Non-fermenting Gram negative Bacilli – no. (%)	21 (20.6)	4 (16.0)	0.61
MDRO – no. (%)	8 (7.8)	2 (8.0)	1.000
Vancomycin resistant Enterococcus sp. – no. (%)	0	1 (4.0)	0.20
Ceftazidime resistant Non-fermenting Gram Negativ bacilli– no. (%)	4 (3.9)	0 (0.0)	0.585
ESBL-PE– no. (%)	4 (3.9)	0 (0.0)	0.585
Colimicin resistant – no. (%)	1 (1.0)	0 (0.0)	1.000
Carbapenem resistant – no. (%)	1 (1.0)	0 (0.0)	1.000
Methicillin Resistant Staphylococcus aureus– no. (%)	0 (0.0)	1 (4.0)	0.197
Candida sp. – no. (%)	4 (3.9)	0 (0.0)	0.585
Aspergillus sp. – no. (%)	0 (0.0)	1 (4.0)	0.197
Others – no. (%)	6 (5.9)	1 (4.0)	1.000

Note. SC : standard care. MSD : Multiple site decontamination. ESBL-PE : extended spectrum beta lactamase producing Enterobacteriaceae. MDRO : Multi Drug Resistant Micro Organisms.

Table 5. Pre and post implementation antibiotic consumption in ICUs that implemented MSD.

DDD/1000 patient-days	Pre-implementation	Post-implementation
Low resistance promoting beta lactam
Penicillin	267	285	0.017
Amoxicillin and Clavulanic acid	210	241	<0.001
3^rd-Generation Cephalosporin	341	323	<0.001
Total	818	849	<0.001
High resistance promoting beta lactam
Ceftazidime	24	10	<0.001
Cefepim	93	54	<0.001
Piperacillin and Tazobactam	126	122	0.58
Carbapanem	58	39	<0.001
Total	302	227	<0.001
Others
Aminoglycoside	77	88	<0.001
Quinolone	51	67	<0.001
Vancomycin	36	36	0.95

DDD: defined daily dose.

No competing interests reported.

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Multiple Site Decontamination in ICU patients: a real life pre/post study

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NM would like to thanks Christophe CAMUS for is wise advices and the time spend on the transmission of his knowledge in the field of decontamination.

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