BRMO Module 5 Evidence-tabellen

Choi, 2021

Type of study: retrospective cohort

Setting and country: university hospital, South Korea, 2013 - 2017

Funding and conflicts of interest: from text: “The authors have no conflicts of interest to disclose.” No information on funding.

Inclusion criteria:

- Patients with ischemic or hemorrhagic stroke

- Patients in whom VRE was cultured through a rectal swab

- Patients who have confirmed VRE negative

Exclusion criteria:- Patients with a stroke onset more than 6 months

- Patients with insufficient medical records were excluded

N total at baseline: 52

Important prognostic factors²:age ± SD: 65.63 ± 13.45

Sex: 56% F

Describe intervention:

VRE

Rectal samples, weekly

Confirmed by culturing

Length of follow-up:

Until clearance

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures:

Clearance: 3 consecutive negative samples.

Mean duration of the VRE

Colonization: 39.08 ± 44.22 days

11.38 ± 6.40 days without antibiotics

51.39 ± 48.22 days with antibiotics (p<0.01)

Aim is to identify risk factors for prolonged carriage.

Davido, 2018

Type of study: retrospective multicenter study

Setting and country: tertiary care hospitals, France, Jan 2015 – Dec 2016

Funding and conflicts of interest: The authors declare that they have no competing interests.

Inclusion criteria:

All patients hospitalized with previously known or confirmed Extensively Drug-Resistant infection

Exclusion criteria:

None mentioned

N total at baseline: 125

Important prognostic factors²:

age ± SD: 63 ± 19

Sex: ratio M/F 2.6

72.8% of CRE (n = 91), 24.8% of VRE (n = 31) and 2.4% (n = 3) co-colonized with CRE and VRE

Describe intervention:

XDR: Extensively Drug-Resistant bacteria: CRE and VRE

Rectal samples, weekly

Confirmed by culturing

Length of follow-up:

median follow-up of 96 days (0–974)

Loss-to-follow-up:

Not reported

Incomplete outcome data:

N (%): 9 (7.2%)

Reasons (describe): n=9 were included in an ongoing study: FeDEX (NCT03029078) to eradicate the infection using FMT.

Outcome measures:

Clearance: 2 negative samples, one week interval

Median time for decolonization was 49 days (1–1091)

We observed a spontaneous decolonization in 48.2% (n = 56) of cases.

Prior antimicrobial therapy was reported in 38.4% (n=48) of cases. Conversely, 17.6% (n=22) received antibiotics during follow-up

Of note, 14.4% (n = 18) were followed after 1 year (of which 13 were decolonized and 5 colonized patients).

Gedik, 2014

Type of study: retrospective study

Setting and country: hematology department, Turkey, November 2010 and November 2012

Funding and conflicts of interest:

Inclusion criteria:

- All patients in the hematology department >14 yo, with febrile

neutropenia due to chemotherapy for hematological cancers

Exclusion criteria:

- patients treated for other hematological diseases

N total at baseline: 126

Important prognostic factors²:

age ± SD: 51.73 ± 14.4

Sex: 60 F (47.6%)

Describe intervention:

VRE

Rectal samples,

Wound (n = 1), urine (n = 1), and sputum (n = 1) cultures

Confirmed by culturing

Length of follow-up: not reported

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures:

Clearance: 2 negative tests, 2 weeks apart

Mean number of VRE colonization days per patient: 34.27 ± 13.12 days

Haverkate, 2014

Type of study: prospective cohort study

Setting and country: 13 ICUs in Europe: France, Greece, Latvia, Italy, Luxembourg, Spain, Portugal, Slovenia, May 2008 – Apr 2011

Funding and conflicts of interest: from text: “This study was supported by the European Commission under the Life Science Health Priority of the 6^th Framework Program (MOSAR network contract LSHP-CT-2007-037941). M.J.M.B. and M.R.H. were supported by the Netherlands Organization of Scientific Research (VICI NWO Grant 918.76.611 and Priority Medicines Antimicrobial Resistance Grant 205100013). M.C.J.B., M.J.M.B, and C.B-B. were supported by funding from the European Community [R-GNOSIS Integrated project (FP7/2007-2013) under grant agreement no. 282512].” No declared conflicts of interest.

Inclusion criteria:

- All patients colonized with HRE, MRSA meticilline-resistente Staphylococcus aureus (meticilline-resistente Staphylococcus aureus ), or VRE in at least one of the two last cultures during the first admission and at least one readmission to the same ICU

Exclusion criteria:

None mentioned

N total at baseline: 125

Important prognostic factors²:

age (at admission) (IQR): 63.0 (51.0–75.0)

Sex: 47 (37.6%) F

Describe intervention:

VRE

Swabs were obtained from the perineal area (for detection of HRE and VRE), and wounds (if present, for detection of HRE, MRSA, and VRE).

Swabs taken at hospital stay and at readmission.

Length of follow-up:

Not reported

Loss-to-follow-up:

Not reported

Incomplete outcome data:

N (%): 5 (4%)

Reasons (describe): not reported

Outcome measures:

Clearance: 2 negative samples

Median time to clearance in months (95%CI): 1.5 (0.06-10.3) (19 episodes)

“Naturally, it was impossible to determine exact times until clearance for patients noncolonized upon readmission, resulting in interval-censored data”

Jimenez, 2021

Type of study: retrospective cohort

Setting and country: 2 community hospitals and 2 major referral tertiary-care teaching centres, Miami, Jan 2012 – Dec 2016

Funding and conflicts of interest: from text: “AJ, MJT, BI, VP, OM, GR, KS, and KF report no potential

conflict of interest. LSMP reports receiving grants from Cepheid and served as advisor to Paratek and Entasis. YD reports grants and personal fees from MSD and Shionogi, grants from Pfizer, Astellas, Kanto Chemical, personal fees from bioMerieux, Gilead, AstraZeneca, outside the submitted work. LA reports personal fees from Achaogen, Nabriva therapeutics, Paratek, Roche diagnostics, WebMD, Pfizer Latin America, and from MSD, outside the submitted work. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.”

Inclusion criteria:

- patients admitted to any unit of the acute care facilities that had their first CPE detected in either surveillance or clinical cultures and who also had two or more subsequent surveillance cultures collected during admission to any of the ICU.

Exclusion criteria:

- Patients with their first CPE isolated prior to the study period.

N total at baseline: 75

Important prognostic factors²: cleared:

age ± SD: 54.1 ± 18.8

Sex: 17 (68%) F

Describe intervention (treatment/procedure/test):

CPE

Rectal and tracheal aspirate samples

Upon admission, then weekly

Length of follow-up:

Until discharge or transfer out of the ICU

Median: 83 days (IQR: 36-241 days)

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures:

Clearance: 2 or more negative samples from initial source, and no CPE from other sources.

 The overall median time for clearance was 80 days (Range, 16-457).

25 (33%) patients met the criteria for CPE clearance while 50 (67%) did not clear.

Lim, 2018

Type of study: prospective cohort

Setting and country: tertiary care hospital, South Korea, Nov 2010 – Oct 2016

Funding and conflicts of interest: The authors declare no conflicts of interest. No external funding was received.

Inclusion criteria:

- age ≧ 16 years with confirmed CPE infection or colonization.

Exclusion criteria:

- outpatients and patients with CPE types other than NDM-1 or KPC.

N total at baseline: 147

Important prognostic factors²:

age (IQR): 63.0 (53.0-72.0)

Sex: 45 (36%) F

CPE:

106 with NDM-1 and

41 with KPC

Describe intervention (treatment/procedure/test):

CPE

rectal swab or stool culture, urine culture and/or draining fluid culture, weekly follow-up cultures

Follow-up culture specimens included rectal swabs or stool samples plus urine cultures for all CPE-positive individuals

Length of follow-up:

Until discharge

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures:

Clearance: 3 consecutive negative samples sampled in 1 week

N=12 clearance

The time from CPE identification to clearance was a median of 27.5 days (IQR 23.8-37.8 days).

Lister, 2016

Type of study: prospective cohort study

Setting and country: 44 neonatal inpatient service, Australia

Funding and conflicts of interest: The authors declare no conflicts of interest. No statement on funding.

Inclusion criteria:

- neonates with VRE infection after an outbreak.

Exclusion criteria:

None reported

N total at baseline: 21

Important prognostic factors²:

age ± SD: not reported

Sex: not reported

Describe intervention (treatment/procedure/test):

VRE

Stool samples, at least 3 over a 9-month period

Length of follow-up: not reported

Loss-to-follow-up:

N=0

Incomplete outcome data:

N=5, 2 or less samples submitted.

Outcome measures:

Clearance: 3 consecutive negative stool samples collected at least 1 week apart

N=19 (100%) returned at least 1 sample,

N=18 returned at least 2 samples,

N=16 returned 3 or more samples

N=19 (100%) returned a terminal negative sample.

N=14 achieved outcome of 3 consecutive negative samples,

with the remaining 5 returning 1 (n = 1) or 2 (n = 4) terminal negative stool samples.

N=7 on antibiotics

Miu, 2016

Type of study: retrospective cohort

Setting and country: postacute care hospital in Hong Kong, Jan 2010 – Dec 2014

Funding and conflicts of interest: The authors declare no conflicts of interest. No statement on funding.

Inclusion criteria:

- patients admitted to the unit with VRE colonization or

- the date of positive culture for those patients acquiring the organism in the postacute care hospital through target screening using either rectal swab or stool culture.

Exclusion criteria:

None reported

N total at baseline: 121

Important prognostic factors²:

age ± SD: 81.45 ± 10

Sex: 27 (22.35%) F

Describe intervention (treatment/procedure/test):

VRE

Rectal swabs or stool culture

Frequency unclear

Length of follow-up:

Until discharge

Loss-to-follow-up:

N=0

Incomplete outcome data:

N=0

Outcome measures:

Clearance: at least 3 consecutive negative samples, taken at least 1 week apart. Date of clearance: last negative sample.

The median time to VRE clearance during hospitalization was 43 days.

43 patients (35.5%) were considered cleared during hospital stay, and 78 (64.5%) had clearance within the observation period

Nordberg, 2018

Type of study: prospective cohort

Setting and country: 2 NICUs, Sweden, Nov 2008 – Mar 2009

Funding and conflicts of interest: from text: “The study was supported by grants from Strama (Swedish strategic programme against antibiotic resistance), Karolinska Institutet funds, the Samaritan Foundation, Society Milk Droplet Stockholm and the HKH Crown Princess Lovisa's Association for Child Care. All authors report no conflicts of interest relevant to this article.”

Inclusion criteria:

all neonates colonized with intestinal ESBL-KP/EC at discharge from the NICU

Exclusion criteria:

None reported

N total at baseline: 17

Important prognostic factors²:

Gestational age: n (%)

>37 weeks: 3 (21)

32-37 weeks: 3 (21)

28-32 weeks: 2 (14)

<28 weeks: 6 (42)

Sex: 42% F, 57% M

Describe intervention (treatment/procedure/test):

ESBL-KP/EC (EPE)

Faecal samples every second month for 2 years after discharge; the children were cultured again three times during 6 successive weeks at age 5 years.

Length of follow-up: 2 years after discharge, or at age of 5.

Incomplete outcome data:

N (%): 3 (17%)

Reasons (describe): n=3 death

Outcome measures:

The median length of EPE colonization was 12.5 months (range 5-68 months)

Overdevest, 2016

Type of study: prospective cohort

Setting and country: LTCF, Netherlands, Mar 2013 – Apr 2014

Funding and conflicts of interest: The authors declare no conflicts of interest. From text: “This material is based in part upon work supported by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, grant # 1 I01 CX000920-01A1 (J.R.J.)”

Inclusion criteria:

- residents of an LTCF

Exclusion criteria:

None reported

N total at baseline: 296

Important prognostic factors²:

age: 78 (range: 46–98, SD: 11)

Sex: 170 (57.4%) F

Describe intervention (treatment/procedure/test):

ESBL-E

Culturing faeces or rectal swabs 2-3 months

Length of follow-up:

Until discharge

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

Outcome measures:

Clearance: 1 negative sample

Conversion to ESBL-negative was observed for 13 of 39 ESBL-ST131 carriers, vs 18 of 29

carriers of other ESBL-E (p = 0.03).

Survival analysis showed that the half-life of carriage for ESBL-ST131 was 13 months, compared with 2-3 months for

other strains (p < 0.001).

Sohn, 2013

Type of study: single-center retrospective cohort study

Setting and country: tertiary care hospital in Seoul, Korea, Jan 2008 – Sep 2009

Funding and conflicts of interest: The authors declare no conflicts of interest. No statement on funding.

Inclusion criteria:

- inpatients thought to be at risk for VRE because of prolonged hospitalization, antibiotic use, referral from another health care facility, intensive care unit (ICU) stay, receiving a transplant, or proximity to other patients with VRE

Exclusion criteria:None reported

N total at baseline: 127

Important prognostic factors²:

Age (mean ± SD): 58.9 ± 14.4

Sex: n=49 (38.5%) F

Describe intervention (treatment/procedure/test):

VRE

Rectal or stool cultures, weekly

Length of follow-up:

until clearance

Incomplete outcome data:

N=36 readmitted or loss to follow up

Outcome measures:

Clearance: VRE-negative rectal (or stool) cultures on at least 3 consecutive occasions 1 week or longer apart in outpatient setting. Date of clearance (event in survival analysis): last positive culture

N=68 cleared

The median duration of culture

positivity was estimated at 5.57 weeks (range 0–50.14 weeks)

Weterings, 2022

Type of study: open, dynamic cohort study

Setting and country: nursing homes, Netherlands, March 2013 - June 2019

Funding and conflicts of interest: no conflicts of interest, no funding.

Inclusion criteria:

Residents with at least one ESBL-E positive rectal or faecal swab obtained in a prevalence survey during the study period

Exclusion criteria:

None reported

N total at baseline: 112

Important prognostic factors²:

Age (mean ± SD): 82 years (IQR: 75–88)

Sex: 63/112 (56.3%) female

ESBL type:

ESBL-ST131: n=66 (58.9%)

ESBL-non-ST131: n=46 (41.1%)

Describe intervention (treatment/procedure/test):

ESBL-E. coli

Culture of rectal or faecal samples, every quarter

Length of follow-up:

17.9 months (IQR: 6.0–40.6) for ESBL-ST131

10.1 months (IQR: 2.8–30.2) for ESBL-non-ST131

Incomplete outcome data:

N=

Outcome measures:

Clearance: after a previous ESBL-E positive culture, at least one rectal or faecal swab did not reveal ESBL-E or when strain typing showed a different MLST or cluster type than found in the previous ESBL-E positive culture of the resident

🡪 additional analysis when clearance is 2 negative swabs instead of 1

median time to clearance of 13.0 months (95% CI 0.0–27.9) for ESBL-ST131 compared to 11.2 months (95% CI 4.8–17.6) for ESBL-non-ST131 (p =0.044).

Cleared:

31/66 ESBL-ST131 carriers (47.0%) and in 26/46 ESBL-non-ST131 carriers (56.5%)

Wangchinda, 2022

Type of study: two prospective cohort studies

Setting and country: tertiary care university hospital, Thailand. Nov 2018 – Nov 2020

Funding and conflicts of interest: no conflicts of interest. Funding by grants from the Thailand Center of Excellence for Life Sciences (TCELS), the National Research Council of Thailand (NRCT) and the Faculty of Medicine Siriraj Hospital, Mahidol University.

Inclusion criteria:

- hospitalized patients aged ≥18 years who had CRE isolated from clinical specimens submitted to the microbiology laboratory on randomly selected surveillance days (cohort II: discharged).

Exclusion criteria:

None reported

N total at baseline: 353 (of which 225 colonized)

Important prognostic factors2:

Age (mean ± SD): 68.5 ± 17.5

Sex: 114 (50.7%) male

Describe intervention:

CRE

Stool or rectal swab samples

Length of follow-up:

6 months, 1 year, 2 years

Incomplete outcome data:

Not reported

Outcome measures:

Clearance: one negative sample

Duration of CRE colonization in stool was <1 year in 50.0%

of cohort I patients, and <2 years in 91.4% of patients in cohort II.

Cohort I:

N=23 no positive follow up (54.8%)

Cleared:

33% 6 months

50% 1 year

Median clearance (days): 119 (range 37 – 486) (n=19)

Cohort II:

N=93

Cleared:

47.3% 1 year

91.4% 2 years

Shenoy, 2014

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs and observational studies

Literature search from January 1990 until July 2012

A: Montecalvo, 1995

B: Brennen, 1998

C: Goetz, 1998

D: Bhorade, 1999

E: Weinstein, 1999

F: D’Agata, 2011

G: Wong, 2001

H: Byers, 2002

I: Hachem en Raad, 2002

J: Mascini, 2003

K: Huang, 2007 (2 articles)

L: Park, 2011 (2 articles)

M: Yoon, 2011

Study design:

RCT: G

Prospective cohort: A, B, C, D, E, F, I, J

Retrospective cohort: H, K, L, M

Setting and Country:

A: USA

B: USA

C: USA

D: USA

E: Canada

F: USA

G: USA

H: USA

I: USA

J: Netherlands

K: USA

L: South Korea

M: South Korea

Source of funding and conflicts of interest:

From text: “Support for this work provided by: The Institute for Health Technology Studies; NIH T32 A107061; 2010 MGH Clinical Innovation Award; Departmental Funds; CFAR (NIH P30 AI060354) and the Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Awards 8UL1TR000170-05 and 1 UL1 RR02578). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Inclusion criteria SR:

- report on screening from at least one anatomical site

- clearance: at least one microbiological result

- absence of treatment or decolonization therapy

Exclusion criteria SR:

- none mentioned

13 studies included

Important patient characteristics at baseline:

N, mean age

A: n=86,

B: n=36

C: n=210,

D: n=10,

E: n=24,

F: n=13,

G: n=24,

H: n=116,

I: n=28,

J: n=11

K: n=394,

n=126

L: n=89

n=723

M: n=58,

Describe intervention:

Site and screening for VRE:

CX = culture,

T = strain typing performed,

PCR = polymerase chain reaction

A: Perianal, CX; T

B: Rectal, CX

C: Rectal or stool, CX

D: Rectal or stool, CX

E: Rectal, CX

F: Rectal, CX

G: Rectal, CX

H: Rectal, CX; T

I: Stool, CX

J: Rectal, CX; T; PCR

K: Rectal, CX; PCR

L: Rectal, CX

M: Rectal, CX

End-point of follow-up:

A: 18 weeks

B: 25 weeks

C: not reported

D: 2 weeks

E: 25 weeks

F: 3 weeks

G: 3 weeks

H: 86 weeks

I: 13 weeks

J: 26 weeks

K: 52 weeks

L: 39 weeks

M: 19 weeks

For how many participants were no complete outcome data available?

(intervention/control)

A: 50

B: not reported

C: 61

D: 6

E: 0

F: 6

G: 4

H: 0

I: 0

J: not reported

K: not reported

L: 359

M: not reported

Outcome measure-1

Defined as

A: 1 negative CX on admission

and weekly negative culture

during admission

B: 2 negative CX on 2 separate samplings

C: 1 negative CX on 2 separate samplings

D: 1 negative CX on 5 separate samplings

E: 1 negative CX on at least 3 separate samplings

F: 1 negative culture on at least 2 separate samplings

G: 1 negative CX on 3 separate samplings

H: 1 negative CX on 3 separate samplings

I: 1 negative CX on at least 2 separate samplings

J: 3 negative CX on at least 3 separate samplings

K: 1 negative CX

L: 1 negative CX on 3 separate samplings

M: 1 negative CX on 3 separate samplings

Outcome measure 1

weeks to clearance, % cleared

A: 18 weeks, 2%

B: 10 weeks, 50%

C: 14 weeks, 40%

D: n/a, 0%

E: 25 weeks, 38%

F: 1 week, 8%

G: 3 weeks, 21%

H: 22 weeks, 64%

I: 13 weeks, 4%

J: 6 weeks, 50%

K: 9 weeks, 24%

43 weeks, 84%

L: 16 weeks, 10%

9 weeks, 12%

M: 19 weeks, 28%

Facultative:

Brief description of author’s conclusion

Personal remarks on study quality, conclusions, and other issues (potentially) relevant to the research question

Level of evidence: GRADE Grading Recommendations Assessment, Development and Evaluation (Grading Recommendations Assessment, Development and Evaluation ) (per comparison and outcome measure) including reasons for down/upgrading

Sensitivity analyses (excluding small studies; excluding studies with short follow-up; excluding low quality studies; relevant subgroup-analyses); mention only analyses which are of potential importance to the research question

Heterogeneity: clinical and statistical heterogeneity; explained versus unexplained (subgroup analysis)

Bar-Yoseph, 2016

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCTs and observational studies

Literature search on 3 November 2015

CRE

A: Lübbert, 2014

B: Lübbert, 2013

C: Tascini, 2014

D: Feldman , 2013

E: Oren, 2013

F: Oren, 2013

G: Zimmerman, 2013

H: Saidel-Odes, 2012

I: Zuckerman , 2011

J: Ben-David, 2011

K: Schechner, 2011

ESBL

L: Rieg, 2015

M: Ruppe, 2015

N: Papst, 2015

O: Jallad, 2015

P: Lübbert, 2015

Q: Titelman, 2014

R: Gutiérrez-Urbón, 2014

S: Huttner, 2013

T: Birgand, 2013

U: Löhr, 2013

V: Strenger, 2013

W: Paltansing, 2013

X: Alsterlund, 2012

Y: Tham, 2012

Z: Li, 2012

AA: Rogers, 2012

AB: Oostdijk, 2012

AC: Abecasis, 2011

AD: Buehlmann, 2011

AE: Zahar, 2010

AF: Tängdén, 2010

AG: Weintrob, 2010

AH: Tandé, 2010

AI: Apisarnthanarak, 2008

AJ: Reddy, 2007

AK: Troche, 2005

AL: Paterson, 2001

Study design:

A: prospective cohort, surveillance for spontaneous eradication

B: retrospective cohort, single arm, active decolonization therapy

C: prospective cohort, active decolonization therapy

D: retrospective and prospective cohort, surveillance for spontaneous eradication

E: controlled clinical trial, active decolonization therapy arm

F: controlled clinical trial, surveillance for spontaneous eradication arm

G: retrospective and prospective cohort, surveillance for spontaneous eradication

H: RCT, double-blind, decolonization therapy versus placebo

I: prospective cohort, active decolonization therapy

J: retrospective cohort, surveillance for spontaneous eradication

K: retrospective cohort, surveillance for spontaneous eradication

L: prospective cohort, active decolonization therapy

M: prospective cohort, surveillance for spontaneous eradication

N: prospective cohort, surveillance for spontaneous eradication

O: prospective cohort, surveillance for spontaneous eradication

P: prospective cohort, surveillance for spontaneous eradication

Q: prospective cohort, surveillance for spontaneous eradication

R: prospective cohort, active decolonization therapy

S: RCT, double-blind, active decolonization therapy versus placebo

T: prospective cohort, surveillance for spontaneous eradication

U: prospective cohort, surveillance for spontaneous eradication

V: prospective cohort, surveillance for spontaneous eradication

W: prospective cohort, surveillance for spontaneous eradication

X: prospective cohort, surveillance for spontaneous eradication

Y: prospective cohort, surveillance for spontaneous eradication

Z: prospective cohort, surveillance for spontaneous eradication

AA: prospective cohort, surveillance for spontaneous eradication

AB: prospective cohort, active decolonization therapy

AC: prospective cohort, active decolonization therapy

AD: prospective cohort, active decolonization therapy

AE: prospective cohort, surveillance for spontaneous eradication

AF: prospective cohort, surveillance for spontaneous eradication

AG: prospective cohort, surveillance for spontaneous eradication

AH: prospective, single arm, surveillance for spontaneous eradication

AI: prospective cohort, surveillance for spontaneous eradication

AJ: prospective cohort, surveillance for spontaneous eradication

AK: prospective cohort, active decolonization therapy

AL: prospective cohort, active decolonization therapy

Setting and Country:

A: tertiary hospital, Germany

B: tertiary hospital, Germany

C: three tertiary hospitals, Italy

D: tertiary hospital and LTCF, Israel

E: tertiary hospital, Israel

F: tertiary hospital, Israel

G: primary hospital, Israel

H: tertiary hospital, Israel

I: tertiary hospital, Israel

J: 12 LTCF and rehabilitation centres , Israel

K: tertiary hospital, Israel

L: tertiary hospital outpatient, Germany

M: community, France

N: tertiary hospital, Slovenia

O: LTCF, Lebanon

P: community, Germany

Q: tertiary hospital, Sweden

R: tertiary neonatal ICU, Spain

S: tertiary hospital, Switzerland

T: tertiary hospital, France

U: tertiary neonatal ICU, Norway

V: tertiary neonatal ICU, Austria

W: community, Netherlands

X: community, Sweden

Y: community, Sweden

Z: medical students, China

AA: community, Australia

AB: 13 tertiary hospitals, Netherlands

AC: tertiary paediatric ICU, UK

AD: tertiary hospital, Switzerland

AE: tertiary hospital, France

AF: community, Sweden

AG: tertiary hospital, USA

AH: community, France

AI: tertiary hospital/community, Thailand

AJ: tertiary medical ICU, USA

AK: tertiary surgical ICU, France

AL: tertiary surgical ICU, USA

Source of funding and conflicts of interest:

From text: “Part of this work was funded by the EU Europese unie (Europese unie) project AIDA (grant Health-F3-2011-278348) to M. P.”

Inclusion criteria SR:

- RCTs, prospective or retrospective cohort studies, case–control studies or case series of five patients or more examining the natural history of MDR-E colonization, examining rates of carriage following decolonization or comparing decolonization and no decolonization.

- diagnosed through rectal swabs, stool samples or clinical cultures, residing in the healthcare setting or in the community

Exclusion criteria SR:

- studies assessing SDD in patients not selected by carriage

37 studies included

Important patient characteristics at baseline:

N, mean age

A: n=86, 62 (21–85)

B: n=14, 63 (41–82)

C: n=50, 63.7±NS

D: n=125, 67.5±NS

E: n=41, 53.4 (21–79)

F: n=47, 65 (26–99)

G: n=97, 78 (32–102)

H: n=40, 69±NS

I: n=15, 55 (32–80)

J: n=123, 72.7+16

K: n=66, 72±19

L: n=45, 57 (19–86)

M: n=245, 36±13

N: n=114, 61±16

O: n=57, 84.3±5.2

P: n=72, 34 (32–80)

Q: n=61, 58.3±NS

R: n=6, preterm neonates

S: n=58, 54.5 (19–81)

T: n=448, 62.8 (49–75)

"U: n=62, neonates and

adults"

V: n=25, neonates

W: n=133, 33 (19–82)

X: n=23, 40 (NS)

Y: n=58, 38 (1–83)

Z: n=41, 21 (20–23)

AA: n=20, 45.7 (NS)

AB: n=77, NS

AC: n=39, paediatric

AD: n=100, 67 (18–99)

AE: n=62, 12.5 (NS)

AF: n=24, 47 (NS)

AG: n=13, 29.1±7.3

AH: n=31, neonates

AI: n=24, 55 (21–65)

AJ: n=40, NS

AK: n=37, NS

AL: n=5, NS

% Immunocompromised:

A: 25.6 %

B: 7.1 %

C: NS %

D: NS %

E: 52.3 %

F: 26.4 %

G: NS%

H: 30%

I: 100%

J: NS %

K: 15.5 %

L: 33.3%

M: NS%

N: 7%

O: NS %

P: 0%

Q: NS%

R: NS%

S: 10.3%

T: NS%

U: NS%

V: NS%

W: NS%

X: NS%

Y: NS%

Z: NS%

AA: NS%

AB: NS%

AC: 5.5%

AD: 18%

AE: 46.8%

AF: 0%

AG: NS%

AH: NS%

AI: NS%

AJ: NS%

AK: NS%

AL: 100%

Describe intervention:

Swabs taken:

A: 1, 3, 6, 24, 48 months

B: weekly

C: every 4 days during therapy and at 6 months

D: 0.5, 1, 2, 3 months

E: weekly

F: not routine

G: not routine

H: 3, 7, 9, 14, 28, 42 days

I: thrice weekly, once weekly post-discharge

J: once

K: re-admissions

L: 0, 0.5, 1 and 1.5 months

M: 1, 2, 3, 6 and 12 months

N: every 3 months

O: 1, 3 months

P: 6 months

Q: 1, 3, 6, 12 months

R: 2 days post-treatment

S: 1, 7, 28 days post-treatment

T: re-admissions

U: monthly in first year, quarterly thereafter

V: 1, 2, 4, 6, 9, 12 months

W: 6 months

X: monthly to quarterly

Y: 3 or 8 months and 3 years

Z: every 2 weeks

AA: monthly

AB: bi-weekly

AC: bi-weekly

AD: 2 days post-treatment and re-admissions

AE: re-admissions

AF: 6 months

AG: bi-weekly for 2 weeks then weekly

AH: monthly

AI: every 2 weeks

AJ: re-admissions

AK: weekly

AL: 2, 14, 28 days post-treatment

End-point of follow-up:

A: 2 years

B: 9–154 days

C: 6 months

D: NS

E: 1–76 days

F: 20–737 days

G: 1 year

H: 7 weeks

I: NS

J: NS

K: 1–658 days

L: 3 months

M: 1 year

N: 2 years

O: 3 months

P: 6 months

Q: 12 months

R: 7 days

S: 28 days

T: NS

U: 3 years

V: 1 year

W: 6 months

X: 4.5 years

Y: 3 years

Z: 4 months

AA: 6 months

AB: 3-77 days

AC: NS

AD: 2 years

AE: 97-152 days

AF: 6 months

AG: 8 weeks

AH: NS

AI: 6 months

AJ: 1 year

AK: NS

AL: 28 days

For how many participants were no complete outcome data available?

A: 2/86 (2.3)

B: 0/14 (0)

C: 0/50 (0)

D: 0/125 (0)

E: 10/52 (19.2)

F: 55/102 (53.9)

G: 0/97 (0)

H: 1/40 (2.5)

I: 0/15 (0)

J: 0/128 (0)

K: 0/66 (0)

L: 0/45 (0)

M: 47/292 (16)

N: 15/114 (13.1)

O: 0/57 (0)

P: 23/49 (46.9)

Q: 0/61 (0) 12 months

R: 1/6 (16.6)

S: 7/58 (12)

T: 0/448 (0)

U: 0/62 (0)

V: 7/25 (28)

W: 6/133 (4.5)

X: 0/23 (0)

Y: 0/54 (0)

Z: 7/95 (7.3)

AA: 0/20 (0)

AB: 0/77 (0)

AC: 5/39 (12.8)

AD: 4/39 (10.2)

AE: 0/62 (0)

AF: 3/24 (12.5)

AG: 6/13 (46.1)

AH: 0/31 (0)

AI: 0/24 (0)

AJ: 0/40 (0)

AK: 0/37 (0)

AL: 1/5 (20)

Outcome measure-1

Defined as: number of negative cultures needed:

A: 3+PCR separated by 48 h

B: 3+PCR separated by 48 h

C: 2

D: 2+PCR, not followed by any positive

E: 3+PCR in at least 1 week

F: 3+PCR in at least 1 week

G: 1, not followed by any positive

H: 1

I: 3+PCR in at least 1 week

J: 1

K: 1+PCR

L: 1

M: 1

N: NS

O: 1

P: 1

Q: 1, not followed by any positive

R: 1

S: 1

T: 1

U: 3

V: 1

W: 1

X: 1, not followed by any positive

Y: 1

Z: 1

AA: 2

AB: 2

AC: 1

AD: 1, not followed by any positive

AE: 1

AF: 1

AG: 3, not followed by any positive

AH: 3

AI: NS

AJ: 1

AK: 2

AL: 1, not followed by any positive

Outcome measure 1

weeks to clearance, % cleared

See table 3 of study.

In healthcare settings, pooled ESBL/CRE colonization rates:

Without intervention 76.7% (95% CI 69.3%–82.8%) at 1 month to 35.2% (95% CI 28.2%– 42.9%) at 12 months of follow-up.

With decolonization: 37.1% (95% CI 27.5%–47.7%) at end of therapy and 57.9% (95% CI 43.1%–71.4%) at 1 month.

Among community dwellers, ESBL colonization decreased from 52.3% (95% CI 29.5%–74.2%) at 1 month to 19.2% (95% CI 9.7%–34.4%) at 6 months.

Facultative:

Brief description of author’s conclusion

Personal remarks on study quality, conclusions, and other issues (potentially) relevant to the research question

Level of evidence: GRADE (per comparison and outcome measure) including reasons for down/upgrading

Sensitivity analyses (excluding small studies; excluding studies with short follow-up; excluding low quality studies; relevant subgroup-analyses); mention only analyses which are of potential importance to the research question

Heterogeneity: clinical and statistical heterogeneity; explained versus unexplained (subgroup analysis)