Natural History of Colonization With Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE)

A Systematic Review

Erica S Shenoy; Molly L Paras; Farzad Noubary; Rochelle P Walensky; David C Hooper

BMC Infect Dis. 2014;14(177)

Abstract

Background. No published systematic reviews have assessed the natural history of colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). Time to clearance of colonization has important implications for patient care and infection control policy.

Methods. We performed parallel searches in OVID Medline for studies that reported the time to documented clearance of MRSA and VRE colonization in the absence of treatment, published between January 1990 and July 2012.

Results. For MRSA, we screened 982 articles, identified 16 eligible studies (13 observational studies and 3 randomized controlled trials), for a total of 1,804 non-duplicated subjects. For VRE, we screened 284 articles, identified 13 eligible studies (12 observational studies and 1 randomized controlled trial), for a total of 1,936 non-duplicated subjects. Studies reported varying definitions of clearance of colonization; no study reported time of initial colonization. Studies varied in the frequency of sampling, assays used for sampling, and follow-up period. The median duration of total follow-up was 38 weeks for MRSA and 25 weeks for VRE. Based on pooled analyses, the model-estimated median time to clearance was 88 weeks after documented colonization for MRSA-colonized patients and 26 weeks for VRE-colonized patients. In a secondary analysis, clearance rates for MRSA and VRE were compared by restricting the duration of follow-up for the MRSA studies to the maximum observed time point for VRE studies (43 weeks). With this restriction, the model-fitted median time to documented clearance for MRSA would occur at 41 weeks after documented colonization, demonstrating the sensitivity of the pooled estimate to length of study follow-up.

Conclusions. Few available studies report the natural history of MRSA and VRE colonization. Lack of a consistent definition of clearance, uncertainty regarding the time of initial colonization, variation in frequency of sampling for persistent colonization, assays employed and variation in duration of follow-up are limitations of the existing published literature. The heterogeneity of study characteristics limits interpretation of pooled estimates of time to clearance, however, studies included in this review suggest an increase in documented clearance over time, a result which is sensitive to duration of follow-up.

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Table 1. Studies documenting duration of MRSA colonization meeting inclusion criteria.
Author year [ref]	Study ID	Design	Country	Year of study	Subject description	Screening site	Screening method	Latest documented follow up (weeks)	N	Lost to follow up (N)	Clearance defined	Weeks to documented clearance	% cleared
Sanford 1994 [11]	A	Retrospective cohort	USA	1989–1991	Hospitalized patients	Nares, axillae, perineum/groin, wound, sputum, tracheal aspirate	CX; T	240	36	*	2 negative CX	172	50%†
Mulhausen 1996 [12]	B	Prospective cohort	USA	1991–2	Residents at LTCFs	Nares	CX	52	47	34	1 negative CX on two separate samplings	52	13%
O'Sullivan 2000 [13]	C	Prospective cohort	Ireland	1994–5	Residents at LTCFs	Nares, throat, hairline, axillae, groin, perineum, skin lesions	CX; T	39	65	14	1 negative CX	26	49%
Scanvic 2001 [14]	D	Prospective cohort	France	1998	Hospitalized patients	Nares, skin, axillae, groin	CX; T	36 (a)	78	*	4 negative CX obtained from 2 sites	37	50%†
Ellis 2004 [15]	E	Prospective cohort	USA	2003	US Army personnel	Nares	CX; T	13	24	*	1 negative CX	9	67%
Cretnik 2005 [16]	F	Prospective cohort	Slovenia	2001–2	Residents and HCW at LTCFs	Nares, skin lesions, axillae, groin	CX; T	13	12	2	2 negative CX from 2 sites on 3 separate samplings	13	33%
Vriens 2005 [17]	G	Prospective cohort	Netherlands	1991–2001	Hospitalized patients	Nares, throat, perineum, wounds, skin lesions, urine and sputum	CX; PCR	104	57	21	All negative CX from up to 7 sites on 3 separate samplings	104	46%
Marschall 2006 [18]	H	Retrospective cohort	Switzerland	2000–3	Hospitalized patients	Nares, groin, skin lesions, tracheal secretions, urine	CX; T	231	80	*	All negative CX from up to 6 sites on 2 separate samplings	85	50%†
Ellis 2007 [19]	I	RCT	USA	2005	US Army personnel	Nares	CX; T	16	66	1	1 negative CX	16	64%
Simor 2007 [20]	J	RCT	Canada	2000–3	Hospitalized patients	Nares, perineum, skin lesions, catheter sites	CX; T	34	35	26	1 negative CX on 2 separate samplings	13	23%
Wendt 2007 [21]	K	RCT	Germany	2001–4	Hospitalized patients and residents at LTCFs	Nares, throat, groin, perineum, skin defects, any previously colonized site	CX; T	13	58	3	All negative CX at up to 7 sites on 5 separate samplings	4	12%
Lucet 2009 [22]	L	Prospective cohort	France	2003–4	Hospitalized patients discharged to home care	Nares, chronic skin lesions	CX	52	148	44	1 negative CX on 2 separate samplings	52	51%
Robicsek 2009 [23]	M	Retrospective cohort	USA	2006–7	Hospitalized patients	Nares	PCR	208	824	*	1 negative PCR	208	79%
Lautenbach 2010 [24]	N	Prospective cohort	USA	2008	Ambulatory patients and household contacts	Nares, axilla, throat; groin and perineum	CX; PCR; T	14	11	0	All negative cultures from up to 5 sites on 6 separate collections	14	73%
Manzur 2010 [25]	O	Prospective cohort	Spain	2005–7	Residents at LTCFs	Nares, decubitus ulcers	CX; T	77	231	104	1 negative CX on 2 separate collections	77	27%
Van Velzen 2011 [26]	P	Retrospective cohort	Scotland	2010	Hospitalized patients	Nares, perineum, axillae, throat, wounds and devices	CX; PCR; T	4	32	0	All negative cultures from up to 6 sites on 2 separate occasions	1	25%

(a) Follow up at least 13 weeks since hospitalization; median clearance at 37 weeks reported; mean time since hospital discharge 36 weeks.
*Not documented; † Kaplan Meier estimates which do not provide information on those lost to follow up.
HCW: health care worker; LTCF: long term care facility; MRSA: methicillin resistant Staphylococcus aureus; N: number; CX: culture; T: typing of strain performed; PCR: polymerase chain reaction; RCT: randomized controlled trial.

Table 2. Studies documenting duration of VRE colonization meeting inclusion criteria.
Author year [ref]	VRE	Study ID	Design	Country	Year of study	Subject description	Screening site	Screening method	Latest documented follow up (weeks)	N	Lost to follow up (N)	Clearance defined	Weeks to documented clearance	% cleared
Montecalvo 1995 [27]	VREF	A	Prospective cohort	USA	1993–4	Hospitalized patients	Perianal	CX; T	18	86	50	1 negative CX on admission and weekly negative culture during admission	18	2%
Brennen 1998 [28]	VREF	B	Prospective cohort	USA	1993–4	Residents in LTCFs	Rectal	CX	25	36	*	2 negative CX on 2 separate samplings	10	50%†
Goetz 1998 [29]	VREF	C	Prospective cohort	USA	1994–6	Hospitalized patients	Rectal or stool	CX	*	210	61	1 negative CX on 2 separate samplings	14	40%†
Bhorade 1999 [30]	ND	D	Prospective cohort	USA	1996–8	Hospitalized patients	Rectal or stool	CX	2	10	6	1 negative CX on 5 separate samplings	N/A	0%
Weinstein 1999 [31]	VREF	E	Prospective cohort	Canada	1995	Hospitalized patients	Rectal	CX	25	24	0	1 negative CX on at least 3 separate samplings	25	38%
D'Agata 2001 [32]	ND	F	Prospective cohort	USA	1998	Hospitalized patients	Rectal	CX	3	13	6	1 negative culture on at least 2 separate samplings	1	8%
Wong 2001 [33]	ND	G	RCT	USA	*	Hospitalized patients and residents of LTCFs	Rectal	CX	3	24	4	1 negative CX on 3 separate samplings	3	21%
Byers 2002 [34]	ND	H	Retrospective cohort	USA	1994–6	Hospitalized patients	Rectal	CX; T	86	116	0	1 negative CX on 3 separate samplings	22	64%
Hachem and Raad 2002 [35]	VREF	I	Prospective cohort	USA	1997	Hospitalized patients	Stool	CX	13	28	0	1 negative CX on at least 2 separate samplings	13	4%
Mascini 2003 [36]	VREF	J	Prospective cohort	Netherlands	2000	Hospitalized patients	Rectal	CX; PCR;T	26	11 (a)	*	3 negative CX on at least 3 separate samplings	6	50%†
Huang 2007 [37]	ND	K1	Retrospective cohort	USA	2002–4	Hospitalized patients	Rectal	CX; PCR (b)	52	394 (c)	*	1 negative CX	9	24%
Huang 2007 [37]	ND	K	Retrospective cohort	USA	2002–4	Hospitalized patients	Rectal	CX; PCR (b)	52	126 (d)	*	1 negative CX	43	84%
Park 2011 [38]	ND	L1	Retrospective cohort	South Korea	2003–10	Hospitalized patients on chronic HD	Rectal	CX	39	89	20	1 negative CX on 3 separate samplings	16	10%
Park 2011 [38]	ND	L	Retrospective cohort	South Korea	2003–10	Hospitalized patients on non-chronic HD	Rectal	CX	35	723	339	1 negative CX on 3 separate samplings	9	12%
Yoon 2011 [39]	VREF	M	Retrospective cohort	South Korea	2006–9	Hospitalized patients	Rectal	CX	19	58	*	1 negative CX on 3 separate samplings	19	28%

(a) Only patients with non-epidemic strain were included in analysis. (b) One of four participating sites used both culture and PCR; the others used culture only. (c) Subset of patients admitted ≤ 60 days from last known positive culture. (d) Subset of patients admitted > 300 days from last known positive culture.
*Not documented; † Kaplan Meier estimates which do not provide information on those lost to follow up.
HCW: health care worker; HD: Hemodialysis; LTCF: long term care facility; VRE: vancomycin resistant enterococcus; VREF: E. faecium; ND: no distinction made between E. faecalis and E faecium; N: number; CX: culture; T; strain typing performed; PCR: polymerase chain reaction; RCT: randomized controlled trial.