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Supplementary Appendix

Table 1. Systematic literature review search strategy

MEDLINE, EMBASE, CINHAL, Global Index Medicus, Cochrane Library and the Outbreak Database were searched from their date of inception to January 2017.

Abstracts were also searched from Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); American Society of Microbiology (ASM) Microbe;

European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); Infectious Diseases Society of America (IDSA) Annual Scientific Meeting ID-Week; and International Conference on Prevention and Infection Control (ICPIC) from 2012 to 2016. Search terms included a combination of 3 concepts: 1.

Carbapenemase/Carbapenem resistance, 2. Core infection control measures, and 3. Primary infection outcomes. Search strategy for Medline is shown here. Slightly adapted versions were used for other aforementioned databases according to their input formats.

We included studies (in English, French, Spanish, Italian, Portuguese or German) that assessed the impact of any IPC measure on CRE-CRAB-CRPsA transmission in inpatient facilities (i.e. acute care and long-term care facilities) including both endemic and epidemic settings. Outcomes included incidence or prevalence of CRE- CRAB-CRPsA infection or colonization. IPC measures part of centrally-designed national/regional programs for healthcare facility implementation and locally-led facility interventions were included. We excluded studies solely dealing with: bacterial isolate collection/identification, sequencing, susceptibility testing; basic science/animal models; treatment; selective decontamination; perioperative prophylaxis; antibiotic stewardship; and contaminated duodenoscopes or other endoscopes (this is a specialized IPC area where search criteria may have not fully captured all relevant papers). Studies whose full-text could not be retrieved or reviews that did not report original data were also excluded.

Concept 1

Carbapenemase/Carbapenem resistance

Concept 2

Core infection control measures

Concept 3

Primary infection outcomes Carbapenem resistan* [tiab] OR

“Carbapenem non susceptible”

[tiab] OR

"carbapenemase" [Supplementary Concept] OR

Carbapenemase [tiab] OR Carbapenemases [tiab] OR

"beta-lactamase KPC-2, Klebsiella pneumoniae"[Supplementary Concept] OR

(((("beta-lactamase KPC-3, Enterobacter cloacae"

[Supplementary Concept]) OR

"beta-lactamase KPC-3, Klebsiella pneumoniae" [Supplementary Concept]) OR

"beta-lactamase KPC-2"

[Supplementary Concept]) OR

"beta-lactamase KPC-1"

[Supplementary Concept]) OR

Hand hygiene [Mesh] OR “Hand hygiene” [tiab] OR

Hand disinfection [Mesh] OR “Hand disinfection” [tiab] OR

“Hand washing” [tiab] OR “Handwashing” [tiab] OR Infection control [Mesh] OR

“Prevention and control”[Subheading] OR

“Infection control” [tiab] OR

“Infection prevention” [tiab] OR Universal precautions [Mesh] OR

Transmission based precautions [tiab] OR Droplet precaution* [tiab] OR

Contact precaution* [tiab] OR Airborne precaution* [tiab] OR Isolation precaution* [tiab] OR Standard precaution* [tiab] OR Universal precaution* [tiab] OR Precaution* [tiab] OR

Population surveillance [Mesh] OR Surveillance [tiab] OR

(“population surveillance” [Majr:NoExp]) OR “sentinel surveillance” [Majr] OR Disposable equipment [Mesh] OR

Infectious Disease Transmission, Professional-to-Patient [Mesh] OR

"Disease Transmission, Infectious"

[Majr] OR

Cross infection [Mesh] OR Rate [tiab] OR

Rates [tiab] OR Incidence [tiab] OR Prevalence [tiab] OR Cases [tiab] OR Proportion [tiab] OR Transmission [tiab] OR

Hospital acquired infection* [tiab] OR Healthcare associated infection* [tiab]

OR

Health care associated infection* [tiab]

OR

Healthcare related infection* [tiab] OR

Health care related infection* [tiab] OR

HAI [tiab] OR

(2)

"beta-lactamase KPC-3, E coli"

[Supplementary Concept] OR KPC [tiab] OR

VIM [tiab] OR

Verona integron [tiab] OR NDM [tiab] OR

New Delhi metallo [tiab] OR OXA [tiab] OR

IMP [tiab] OR

Imipenemase [tiab] OR MBL [tiab] OR

Metallo-β [tiab]

Equipment [tiab] OR Decontamination [tiab] OR Cleaning [tiab] OR

Disinfection [tiab] OR Sterilization [tiab] OR

"Patient Isolation"[Mesh] OR Isolation [tiab] OR

Screening [tiab] OR Cohorting [tiab] OR

"Education"[Mesh] OR Education [tiab] OR Training [tiab] OR

Learning [tiab] OR Knowledge [tiab] OR Competence [tiab] OR

“Care bundle” [tiab] OR Bundle [tiab] OR

Checklist [tiab] OR Checklists [tiab] OR Intervention* [tiab] OR

High impact intervention* [tiab] OR Audit* [tiab] OR

"Clinical Audit"[Mesh] OR Management [tiab] OR Guideline* [tiab] OR Attitude* [tiab] OR Motivation [tiab] OR Competence [tiab] OR Innovation [tiab] OR

"Quality Improvement"[Mesh] OR “Quality improvement” [tiab] OR “Quality improvements” [tiab] OR

Practic* [tiab] OR Routine [tiab] OR Procedure* [tiab] OR

“Requirement” [tiab] OR “Requirements” [tiab] OR

“Policy” [tiab] OR “Policies” [tiab] OR

“Strategy” [tiab] OR “Strategies” [tiab] OR Care pathway* [tiab] OR

Modification of care [tiab]

HCAI [tiab] OR

Nosocomial infection* [tiab] OR

“Cross infection” [tiab] OR

“Cross transmission” [tiab]

(3)

Table 2. GRADE evidence profile for Effective Practice and Organization of Care (EPOC) studies

# of Studies (Design)

Quality assessment ¥ Results Quality

Limitations Inconsistency Indirectness Imprecision Publication bias Outcome: Incidence of CRE infection

8 ITS studies

Serious Not Serious Serious Not Serious Uncertain 7/8 studies reported a significant negative change in slope from pre- to post-intervention

6/7 studies reported a significant negative change in level from pre- to post-intervention

(level could not be calculated for one study)

Low

Outcome: Incidence of CRE infection or colonization 1 ITS

study

Serious Not Serious Serious Serious Uncertain 0/1 study reported a significant change in slope or level from pre- to post-intervention

Very low Outcome: Incidence of CRE blood stream infection

2 ITS studies

Serious Not Serious Serious Not Serious Uncertain 2/2 studies reported a significant negative change in slope from pre- to post-intervention

1/2 studies reported a significant negative change in level from pre- to post-intervention

Low

Outcome: Prevalence of CRE colonization 1 ITS

study

Serious Not Serious Serious Serious Uncertain 0/1 study reported significant change in slope from pre- to post-intervention

1/1 study reported a significant negative change in level from pre- to post- intervention

Very low

Outcome: Incidence of CRAB 2 ITS

studies

Serious Not Serious Serious Serious Uncertain 1/2 studies reported a significant negative change in slope from pre- to post-intervention

1/1 study reported a significant negative change in level from pre- to post- intervention

(level could not be calculated for one study)

Very low

Outcome: Incidence of CRAB infections and/or colonization 2 ITS

studies

Serious Not Serious Serious Not Serious Uncertain 2/2 studies reported a significant negative change in slope from pre- to post-intervention

1/2 studies reported a significant negative change in level from pre- to post- intervention

Low

Outcome: Incidence of CRPsA 2 ITS

studies

Serious Not Serious Serious Not Serious Uncertain 1/2 studies reported a significant negative change in slope from pre- to post-intervention

1/2 studies reported a significant negative change in level from pre- to post- intervention

Low

(4)

Outcome: Incidence of CRAB and CRPsA colonization 1 ITS

study

Serious Not Serious Serious Serious Uncertain 0/1 study reported a significant change in slope or level from pre- to post-intervention

Very low

CRE: Carbapenem-resistant Enterobacteriaceae; CRAB: Carbapenem-resistant Acinetobacter baumannii; CRPsA: Carbapenem-resistant Pseudomonas aeruginosa;

EPOC: Effective Practice and Organization of Care

* Studies with at least ten pre-intervention and ten post-intervention data points were considered to have better power to detect a change in slope and level

¥Limitations in design and implementation of studies suggesting high likelihood of bias; inconsistency of results across studies; indirectness of evidence such as indirect population, intervention, control or outcomes; Unexplained heterogeneity or inconsistency of results; imprecision of results (i.e. wide conference intervals);

high probability of publication bias

(5)

Table 3. Summary of non-Effective Practice and Organization of Care (EPOC) studies according to CRE, CRAB, and CRPsA*

Study author, journal, year

Study design;

setting

Main interventions Timing Patient outcomes Results pre- intervention

Results post- intervention CRE (n=35)

Abboud et al, JHI, 2016

Uncontrolled before- after study; ICU in Brazil

Pre-intervention:

1) Active surveillance (Weekly rectal and inguinal swabs)

2) Contact precautions

3) Cohorting in a dedicated ICU room 4) Hand hygiene training

5) Guidelines for cleaning services Post-intervention:

1) Bedside provision of alcohol-based handrub 2) Daily chlorhexidine baths

3) Enhanced environmental cleaning (Performed by monitored nursing staff in the patients’ environment) 4) Careful use of colistin by infectious disease doctors

Pre- intervention:

April-September 2013

Post- intervention:

October 2013- December 2014

1) CRE prevalence of colonization 2) CRE CLABSIs incidence 3) CRE rate of SSI (Assessed within 30 days of surgery)

1) 26.8%

2) 2.07/1,000 central-line days 3) 2.4%

1) 9.3% (p<0.001) 2) 0.23/1,000 central-line days (p<0.002) 3) 0.8% (p<0.003)

Adler et al, JCM, 2013

Before-after case counts; Neonatal ICU in Israel

Pre-intervention:

1) Infection control practices that included hand hygiene and isolation procedures were implemented in the neonatal ICU and throughout the hospital but with suboptimal compliance

2) Surveillance for CRE was performed on admission in all high-risk patients and as part of contact

investigation Post-intervention:

1) Cohorting in a separate location with dedicated staff 2) Closing the ICU to new admissions

3) Reinforcing IPC practices (Hand hygiene, contact precautions, cleaning)

4) Weekly rectal cultures + contacts surveillance (Prior to the outbreak, surveillance was performed in high-risk pts but with low compliance)

5) Close monitoring of exposed infants (Contacts of positive cases) on admission to other hospitals

Pre- intervention:

March-May 2012 (Retrospective data) Post- intervention:

July-December 2012

1) Incidence of OXA-48 CRE cases (i.e.

colonization and infection)

1) 27 new cases were identified before the intervention (incidence reached 9 cases/week)

1) 5 cases from June- September 2012; No new case from October-December 2012

Agodi et al, JCM, 2011

Before-after case counts; ICU in Israel

1) Active surveillance on admission 2) Isolation

3) Dedicated nurses

4) Implementation of contact precautions (Use of disposable gloves and gowns)

5) Hand hygiene, contact precautions and environmental cleaning monitoring

6) Weekly meetings between ICU and IPC staff

Pre- intervention:

October 2008- February 2009 Post- intervention:

March-June 2009

1) Incidence of KPC-3 cases (i.e. colonization and infection)

1) 10 cases/week (Peak)

1) 1 case/week

Ben-David et al, Infect Control Hosp Epidemiol,

Uncontrolled before- after study; National programme involving

1) Periodic on-site assessments of infection control policies and resources using a score composed of 16 elements (e.g. presence of an infection control

Pre- intervention:

2008

1) CRE prevalence of colonization (Newly discovered

1) 12%

(2008 prevalence survey)

1) 9.5% (2010 prevalence survey);

7.9% (p= .008) (2011

(6)

2014 13 post-acute care hospitals in Israel

consultant, hand hygiene compliance monitoring, availability of alcohol-based hand-rub etc.) 2) Weekly reports in all wards to the national centre for infection control (carriage prevalence, compliance) Some measures varied by ward type:

1) Active surveillance on admission and of contacts of positive cases and cohorting in skilled nursing, long- term mechanical ventilation, and sub-acute wards 2) Contact precautions only in rehabilitation wards

Post- intervention:

2010-2013

colonization) prevalence survey);

3.5% (p< 0.001) (2013 prevalence survey)

Borgia et al, CID, 2012

Before-after case counts; Tertiary care hospital in Canada

Pre-intervention:

Routine screening for CPE rectal colonization among close contacts of known CPE-colonized patients Post- intervention:

1) Active surveillance

(Weekly screening in the affected units) 2) Contact precautions

3) Isolation

4) Restricted visitor policy

5) Pre-emptive isolation of pts transferred from affected units to other units

6) Point prevalence surveillance in the ICU for pts whose stay had overlapped with cases

7) Discharge screening

Post- intervention:

September- November 2011

1) Incidence of NDM-1 CRE cases (i.e.

colonization and infection)

1) No pre- intervention data

1) No further transmission was detected in any affected unit and the outbreak was declared over on 24 November 2011

Chitnis et al, Infect Control Hosp Epidemiol, 2012

Longitudinal study of CRE prevalence; Long- term care facility (LTCF) in USA

Multiphase-intervention:

Phase 1 (January 2010):

1) Active surveillance (Sputum and urine cultures) and pre-emptive isolation of all pts on admission

Phase 2 (July 2010):

1) Active surveillance

(Rectal swab) on admission to all pts 2) Staff education

3) Compliance monitoring (Hand hygiene and gloves and gowns use)

4) Weekly reminders of appropriate cleaning practices Phase 3 (September 2010):

1) Biweekly point prevalence Phase 4 (December 2010):

1) Staff and patients cohorting, 2) Daily staff meetings to increase communication within the facility and discuss CRE prevention measures

Phase 5 (March 2011):

1) Daily compliance monitoring (Hand hygiene and gloves and gowns use) and observations of staff using invasive devices and conducting daily patient assessments

Phase 6 (April 2011)

1) Biweekly conference calls with local and state health departments and the Centers for Disease Control and Prevention

Additional measures:

Pre- intervention:

March 2009- July 2010 (Retrospective data) Post- intervention:

July 2010-2011

1) CRE “transmission”

(Number of initially negative pts that became positive in hospital)

2) % of newly detected CRE/all screened pts 3) CRE prevalence (% of positive pts/all hospitalized pts) 4) CRE bacteraemia incidence

1) 16 cases (July 2010) 4) 1/month

1) 6 cases (February 2011) 2) Newly detected CRE: 44%-->0%

(July 2010-July 2011) 3) CRE prevalence:

49%-->8%

(July 2010- July 2011) 4) 3.6 episodes/

1,000 patient-days (October 2010); 0 episodes/

1,000 patient-days (June 2011)

*Multiphase intervention difficult to assess

(7)

1) Dedicated equipment and staff in the ICU, unnecessary urinary catheter’s use reduction Cohen et al,

Infect Control Hosp Epidemiol, 2011

Uncontrolled before- after study; 775-bed tertiary care hospital in Italy

Multiphase-intervention:

Phase 1 (March 2006):

Contact precautions and isolation in single-rooms of CR-Kp patients

Phase 2 (March 2007: a national intervention was implemented):

1) Cohorting with dedicated staff

2) Hand hygiene and environmental cleaning enforcement

3) Compliance monitoring 4) Active surveillance of contact patients

5) Flagging of positive patients in the medical record Phase 3 (August 2008):

1) Weekly active surveillance of all ICU patients Phase 4 (March 2009):

1) Selective surveillance of patients admitted to the emergency department

Phases through March 2006- 2010

1) Incidence of CR-Kp infection

2) Prevalence of CR-Kp colonization and infection

1) No pre- intervention data 2) No pre- intervention data

1) Phase 1: Mean 8.4/1,000 hospital- beds; Phase 2: Mean 13.4/1,000 hospital- beds (p <001); Phase 3: Mean 8.3/1,000 hospital-beds (p =0.76); Phase 4:

Mean 4.3/1,000 hospital-beds (p=0.27) 2) Phase 1: Mean 10.4/1,000 hospital- beds; Phase 2: Mean 20.2/1,000 hospital- beds (p<001); Phase 3: Mean 17.4/1,000 hospital-beds (p= . 77); Phase 4: Mean 13.5/1,000 hospital- beds (p= .6)

*Multiphase intervention difficult to assess

Dautzenberg et al,

Euro Surveillance, 2014

Before-after case counts; Hospital in the Netherlands

1) Immediate assistance (specialized staff) from the National Institute of Health

2) Educational meetings to enforce basic IPC measures 3) Staff screening

(Throat and rectal swabs) and environmental screening in the ICU

4) Attribution of patients to risk categories for CRE acquisition. Patients were flagged according to their risk-category in their medical record

5) Retrospective (since January 2009) and prospective screening (Weekly screening - rectum, throat and infection sites - for all patients from June 2011 to January 2012)

Pre- intervention:

January 2009- May 2011 Post- intervention:

June-July 2011 (After 2 OXA-48 Kp pts were detected)

1) Incidence of OXA-48 Kp colonization

1) 43 OXA-48 pts (Retrospective screening)

1) 73 patients (Prospective screening)

*Findings couldn’t be epidemiologically linked to the outbreak

Forcina et al, Bone Marrow Transplantation, 2016

Longitudinal study of CRE prevalence;

Haematology patients, after hematopoietic stem cell

transplantation in Italy

1) Weekly active surveillance 2) Contact precautions

3) Stopping antimicrobial prophylaxis (that is, levofloxacin) during neutropenic fever in carriers and starting a combined empirical broad-spectrum antimicrobial therapy

Pre- intervention:

January 2011- June 2012 (Retrospective data) Post- intervention:

1) Nosocomial transmission (i.e. ≥2 related KPC-Kp infection/colonization cases of the same clone and an epidemiological link)

2) KPC-Kp-BSI

1) 55.6%

2) 4% (±2%)

1) 45.1%

2) 1% (±1%) (p = 0.01)

(8)

July 2012- October 2015

(In pts at 1-year post transplant) Fournier et al,

Euro Surveillance, 2014

Uncontrolled before- after study; 38 hospitals in France

Phase 1 (2004):

1) Contact precautions

2) Dedicated nursing staff (If possible)

3) All new cases had to be communicated to the hospital management

4) Stop transfer of positive patients to other units or hospitals. Patients could be transferred only with >3 negative swabs

5) Contact screening

6) Enhanced hand hygiene and environmental cleaning 7) Triple cohorting, weekly surveillance and antibiotic restriction whenever a secondary case was detected 8) Flagging of patients in their medical record to allow prompt identification in case of readmission

Phase 2 (2009) additional measures:

1) Screening and

pre-emptive isolation of all patients hospitalized abroad in the preceding year

2) Regular visits by the “central IPC team” to verify compliance with the intervention measures in case of outbreaks

Phase 1:

2004-2009 Phase 2:

2009-2012

1) Proportion of CPE events resulting in an outbreak

2) % of secondary cases

1) 50%

(2004-2008) 2) 69%

1) 10% (p=0.02) (2011)

2) 23% (p<0.001)

Giuffre et al, JHI, 2013

Before-after case counts; Neonatal ICU in Italy

Pre- intervention (Since June 2009):

Active surveillance

(Weekly nasal and rectal swabs) Post-intervention:

1) Isolation in the incubator

(Index cases) and cohorting in a separate location 2) Contact precautions

3) Temporary restriction of admissions 4) Standard infection control procedures (Hand hygiene, cleaning and sanitization of the environment)

5) Weekly educational meetings for staff 6) Environmental cultures

Pre-intervention September- November 2012 Post-

intervention:

December 2012- June 2013 (7- month follow- up)

1) Prevalence of KPC-Kp colonization

1) 10 cases in 3 months (Sept-Nov)

1) No further cases of colonization or infection in the following 7 months

Haverkate et al, Infect Control Hosp Epidemiol, 2015

Modelling study; 4 different long-term acute care hospitals (LTACHs) participating in a bundled KPC control

intervention in USA

1) Screening all patients on admission and doing point prevalence surveys every 2 weeks

2) Daily chlorhexidine baths to all patients 3) Staff education

4) Hand hygiene compliance monitoring

5) Different cohorting strategies in each facility (One had a cohort ward with dedicated staff, one single rooms with no dedicated staff, the other two had mixed-cohort wards with KPC positive and negative patients cared by the same staff)

June 2012- June 2013

1) Incidence of KPC colonization compared across LTACHs

1) N/A 1) The number of

acquisitions per 1,000 patient-days was lower in LTACHs with a pure cohort ward or single rooms for colonized patients compared with mixed-cohort wards but 95% confidence intervals overlapped Kassis-Chikhani

et al,

Before-after case counts; Transplant unit

Phase 1:

1) Single room isolation

Phase 1:

December 2003-

1) Rates of VIM-1-Kp secondary cases (i.e.

1) 5 secondary cases (5 infections)

1) 2 secondary cases (2 colonization

(9)

Euro Surveillance, 2010

in France 2) Contact precautions 3) Hand hygiene promotion

4) Staff training to ensure compliance with IPC measures

Phase 2:

1) Triple cohorting

(Cases, contacts and newly admitted pts) with dedicated nursing staff

2) Restriction of admissions (Only emergencies and transplants)

3) Daily meetings to verify compliance with IPC measures

4) Antibiotic use restrictions (Especially Imipenem)

5) Pts were informed of their status and advised to inform doctors in case of any hospital readmission 6) Screening of contacts on readmission was maintained until December 2005

June 2004 Phase 2:

June-October 2004

colonization or infection)

detections)

Kochar et al, Infect Control Hosp Epidemiol.

2009

Uncontrolled before- after study; 10-bed ICU in USA

Phase 1 (January 2004-December 2005):

1) Contact precautions (Gloves and gowns at the bed- side)

2) Enhanced environmental cleaning

3) IPC staff encouraged compliance with contact precautions

4) Active surveillance with rectal swabs on admission and once a week

(For CR-Acinetobacter) Phase 2 (January-April 2006):

1) Active surveillance also for CR Pseudomonas and Kp 2) Flagging of patients in the medical record

3) Two-days ICU closure to undergo extensive cleaning (March 2006)

4) Patients and staff cohorting at one end of the ICU 5) More dispensers for alcohol-based handrub were added in the ICU

6) Strict compliance with infection control measures was enforced

Pre- intervention:

January 2004- April 2006 Post- intervention:

April 2006- December 2007

1) Incidence of CR-Kp infection

1) 9.7± 2.2/

1,000 patient-days

1) 3.7 ± 1.6/

1,000 patient-days

Lee et al, AJE, 2016

Modelling study; USA Authors used Regional Healthcare Ecosystem Analyst (RHEA) simulation model and Orange County (California) patient-level data to simulate the spread of CRE throughout Orange County healthcare facilities under 3 scenarios: no specific control measures, facility-level infection control efforts (Uncoordinated control measures), and a coordinated regional effort

Data available:

2011–2012

1) Prevalence of CRE 1) No pre- intervention data

1) In the absence of specific CRE control measures, national prevalence reached 11.1%, 10 years after introduction;

uncoordinated and coordinated approaches resulted in 72.2% and 77%

averted cases, respectively, by year 5; At year 5,

(10)

coordinated regional control programme resulted in 21.3%

averted cases Lowe et al,

Infect Control Hosp Epidemiol, 2013

Before-after case counts; Hospital in Canada

Pre-intervention:

1) Contact precautions but no active surveillance on admission

(Only contact screening)

Weekly screening was performed if a case was admitted to the ward

Post-intervention:

1) Active surveillance

(On admission for previously hospitalized patients) 2) A flag in the electronic patient record allowed identification of contacts if readmitted to the hospital 3) Reinforcement of routine practices (Hand hygiene and environmental cleaning compliance monitoring) 4) The practice of using sinks to dispose of bath water and other liquids was stopped (After cultures from sinks were found positive) and sinks and sink traps were replaced

Post- intervention:

January 2011- March 2012

1) Rates of NDM-1-Kp secondary cases (i.e.

colonization and infection)

1) No pre- intervention data

1) 7 secondary cases

*No further transmission of NDM1-Kp identified after February 2012

Meletis et al, New

Microbiologica, 2015

Uncontrolled before- after study; National program to control CRE spread in a tertiary care hospital in Greece

1) Surveillance of infections 2) Isolation or cohorting

3) Contact precautions and hand hygiene compliance enforcement

Pre- intervention:

November 2007- October 2010 Post- intervention:

November 2010- October 2013 (Retrospective data)

1) CR-Kp prevalence of infections

1) 60% (ICU pts); 32%

(Non-ICU pts)

1) 58.59% (p= 0.879) (ICU-pts);31.7%

(p= 0.968) (Non-ICU pts)

Munoz-Price et al, Infect Control Hosp Epidemiol, 2010

Uncontrolled before- after study; 70-bed LTACH in USA

1) Chlorhexidine baths

2) Enhanced environmental cleaning 3) Surveillance cultures on admission 4) Isolation, contact precautions and dedicated equipment

5) Staff education 6) Environmental cultures

Pre- intervention:

January- June 2008 Post- intervention:

July-December 2008

1) KPC prevalence of colonization 2) Rates of secondary cases (i.e. Colonization and infection)

1) 21%

(Baseline PPS in 6/2008)

2) 8 secondary cases

1) 12%, 5%, 3%,0%, and 0%

(5-point prevalence surveys were performed during a 5-month period) (p< 0.001) 2) 2 secondary cases Pinheiro Freire

et al, JAC, 2016

Before-after case counts;

26 kidney transplant recipients in Brazil

Pre-intervention (Since January 2009):

1) Active surveillance

(On admission for all transferred patients. Weekly in the ICU and after September 2012 weekly in the kidney transplant unit)

Post-intervention (Started in April 2014):

2) Hand hygiene training

3) Feedback and audits of IPC practices

Pre- intervention:

January 2009- April 2014 (Retrospective data) Post-

1) Incidence of CR- Enterobacter gergoviae (CREG) cases of colonization and infection

1) In the period 2009- 2014, the CREG incidence per quarter ranged from zero to 2.68/1,000 kidney transplant recipients- days in the kidney transplant unit.

1) 5 new acquisitions (May-August 2014); 3 new acquisitions (September- December 2014); No more cases were identified after August 2014

(11)

4) Isolation or cohorting 5) Contact precautions

6) Revision of the cleaning/sterilization protocols for devices used in urological procedures

7) Environmental cultures

8) Staff hands cultures (including surgeons)

intervention:

May-December 2014

Poulou et al, JCM, 2012

Uncontrolled before- after study; KPC-Kp endemic hospital in Greece

Phase 1 (2009):

1) IPC enforcement 2) Contact precautions, 3) Cohorting whenever feasible Phase 2 (2010):

1) Immediate notification of positive cases to staff 2) Isolation or cohorting

3) Contact precautions and hand hygiene enforcement 4) Hand hygiene compliance monitoring

5) Enhanced environmental cleaning

6) Information concerning KPC was provided to families

7) Limitation of patients transfers Phase 3 (2011):

1) Additional single rooms built in the ICU 2) Additional dedicated staff

Pre- intervention:

2009 Post- intervention:

2010-2011

1) Incidence of CR-Kp 2) Incidence of hospital- acquired

CR-Kp cases (i.e. a person whose clinical sample yielded CRE and using hospital-acquired infection definitions from Centers for Disease Control and Prevention)

1) 0.52/1,000 patient days

2) 0.36/1,000 patient days (2009)

1) 0.32/1,000 patient days in 2010 (p=0.075); 0.21/1,000 patient days in 2011 (p=0.0028)

2) 0.19/1,000 patient days in 2010 (p=

0.058); 0.1/1,000 patient days in 2011 (p 0.0012)

Rossi Gonçalves et al, JHI, 2016

Before-after case counts; ICU in Brazil

1) Active surveillance of all patients on admission to the ICU and then weekly thereafter (September 2013 to August 2015)

2) Single room isolation and contact precautions 3) ICU closed to new admissions

Post- intervention:

May-June 2015

1) Incidence of KPC cases (i.e. Colonization and infection)

1) No

pre-intervention data

1) 0.93/1,000 patient- days

(May 2015);

0.39/1,000 patient- days (June 2015) Semin-Pelletier

et al, JHI, 2015

Before-after case counts; Hospital in France

Phase 1 (From June 2013):

1) Active surveillance

(On admission for all high-risk patients+ weekly contact screening in the units were positive patients were present)

2) Reinforcement of both contact precautions and room surface disinfection

3) Dedicated staff

4) Weekly meetings to evaluate IPC measures in place Phase 2 (June-July 2013 and then again in September 2013)

5) Triple cohorting with dedicated staff

(CPE cases, contacts and newly admitted patients)

First epidemic period:

June-October 2013 Second epidemic period:

November 2013- August 2014

1) Rates of OXA-48 Kp secondary cases (i.e.

Colonization and infection)

1) No pre- intervention data

1) First epidemic period: 34 cases;

Second epidemic period: 39 secondary cases

Sypsa et al, PLoS ONE, 2012

Modelling study;

Surgical unit of a tertiary-care hospital in Greece

Modelling of effects of different levels of hand hygiene compliance and reduction in colonized patients through active surveillance, based on epidemiological and infection control data recorded during a prospective observational study conducted in the surgical unit

Prospective data collection period:

May 2009- June 2010

1) CR-Kp transmission (New acquisitions)

1) No pre- intervention data

1) Reproduction number R0 reached 2 under the observed hand hygiene compliance (21%) Vergara-Lopez

et al, CMI, 2013

Uncontrolled before- after study; ICU in Spain

Pre-intervention:

>1 month stay in the ICU underwent active screening by rectal and pharyngeal swabbing

Post-intervention:

Pre- intervention:

2008

1) Incidence of MP-8 Klebsiella oxytoca cases (i.e. Colonization and infection)

1) 2.08/100 patient- days (Bimonthly average number in 2008)

1) 1.91 cases/100 patient-days (Phase 1); 1.24 cases/100 patient-days (Phase

(12)

Phase 1:

1) Active surveillance

(All patients admitted to the ICU were screened once a week and at discharge)

2) Contact precautions and isolation in individual cubicles

3) Reinforcement of standard IPC measures 4) Reinforcement of environmental cleaning (Performed twice a day)

5) Regular educational sessions

6) Environmental and staff screening cultures Phase 2:

1) Nurse cohorting

2) Establishment of a minimum patients to nurse ratio 3) Review of the clean/dirty circuit

4) Review of the use of broad spectrum antibiotics 5) Enhanced cleaning (and repainting) of every ICU room

Phase 3 and 4 (At this point an occult reservoir was suspected):

1) Collection of samples from the drainpipes and traps of sinks

2) Sink’s removal

(But new cases were clustered in a cubicle whose horizontal drainage system was connected with the eliminated sink)

3) Elimination of the horizontal drainage system

Post- intervention:

Phase 1:

March-July 2009 Phase 2:

August 2009- June 2010 Phase 3:

August 2010- June 2011 Phase 4:

September 2011-Follow up until April 2013

2); 0.82 cases/100 patient-days (Phase 3)

Burton et al, IdWeek, 2012

Uncontrolled before- after study; ICUs in 3 hospitals in USA

1) Active surveillance of all patients on admission and once a week thereafter

2) Rapid contact isolation after detection of new cases Pre- intervention:

Baseline KPC colonization was measured every week during a 22-week period Post-

intervention:

6 weeks (But no clear time points)

1) KPC prevalence of colonization

1) 7.4% 1) 3.5%

(p=0.0009; 52.7%

reduction)

Galani et al, ECCMID, 2014

Uncontrolled before- after study; Hospital in Greece

1) Single room isolation 2) Contact precautions

3) Contact precautions and hand hygiene compliance monitoring

4) Colistin and carbapenem restriction ICU specific measures:

1) Cohorting and contact screening 2) Active surveillance of all pts twice/week

Pre- intervention:

January-August 2012

(Retrospective data) Post- intervention:

January-August

1) CR prevalence of colonization 2) Incidence of CR infections

1) 35.2%

(ICU) 2) 4.8/ 1,000 patient-days

1) 11.15%, (p<0.0001) (ICU) 2) 1.4/1,000 patient- days

(13)

2013 Galani et al,

ICAAC, 2015

Uncontrolled before- after study; Hospital in Greece

1) Single room isolation 2) Contact precautions

3) Contact precautions and hand hygiene compliance monitoring

4) Colistin and carbapenem restriction ICU specific measures:

1) Cohorting and contact screening 2) Active surveillance of all pts twice/week

Pre- intervention:

January- December 2012 (Retrospective data) Post- intervention:

January- December 2014

1) Prevalence of CR-Kp infections (Out of all Kp infections)

2) CR prevalence of colonization

1) 14.29% of all Kp infections 2) 20.2%

(ICU)

1) 8.27% of all Kp infections (p=0.048) 2) 11.8%

(p <0.0001) (ICU)

Huang et al, ICAAC, 2014

Uncontrolled before- after study; Hospital in USA

1) Implementation of antimicrobial stewardship 2) Hand hygiene campaigns

3) Enhanced cleaning of frequently touched surfaces and mobile medical equipment

4) Contact precautions (Only if a “portal of exit”

existed)

Revision of clinical cultures from 2009-2012

1) CR-Kp incidence of infections per 100 admissions (Overall) 2) CR-Kp incidence of hospital-acquired infections per 100 admissions

1) No pre- intervention data 2) No pre- intervention data

1) 0.29 (2009); 0.34 (2010); 0.19 (2011);

0.18 (2012) (p=0.0002) 2) 0.19 (2009); 0.19 (2010); 0.11 (2011);

0.08 (2012);

(p=0.0001) Kaiser et al,

IDWeek, 2012

Before-after case counts; 651-bed medical centre with 3 critical care units in USA

1) Standard infection control practices reinforcement 2) Hand hygiene, contact precautions

3) Enhanced disinfection of equipment and high-touch surfaces

4) Environmental cultures 5) Active surveillance (Bimonthly)

6) Room decontamination with vaporized hydrogen peroxide

7) Daily disinfection of room’s sinks (50% of cultures were positive for CRE)

8) Chlorhexidine baths (February 2011)

Then frequency of disinfection of room’s sinks was reduced to 2-3 times/week

(October 2011-January 2012)

Pre- intervention:

2006 Post- intervention:

2007-2012

1) CRE incidence of cases (colonization and infection)/1,000 patient days

1) 0.34/1,000 patient-days (2006)

1) 1.12 (2007); 1.81 (2008); 2.31 (2009);

2.14 (2010);0.14 (June 2010-February 2011); 0.19 (October 2011- January 2012 when the frequency of sink’s disinfection was reduced); 0.30 (> February 2012 when daily sink disinfection was reinstituted)

Karampatakis et al, ECCMID, 2014

Before-after case counts; Solid-organ transplant unit in Greece

Phase 1 (March-August 2012):

No active surveillance

Phase 2 (September 2012-February 2013):

Active surveillance

Phase 3 (March-September 2013):

Active surveillance and enhanced infection control measures (Isolation or cohorting and contact precautions)

Post- intervention:

February 2012- September 2013

1) CR-Kp incidence of infections

2) Incidence CR-Kp colonization (i.e. newly discovered colonization)

1) No pre- intervention data 2) No pre- intervention data

1) Phase 1:

1.29/1,000 bed-days;

Phase 2: 3.27/1,000 bed-days; Phase 3:

3.95/1,000 bed-days 2) Phase 2: 17.1%;

Phase 3: 18.2%

Malato et al, Haematologica, 2014

Before-after case counts; Haematology unit in Italy

Phase 1:

1) Active surveillance of all patients (Weekly screening)

2) Education

3) Hand hygiene promotion 4) Isolation of carriers

Phase 1:

January 2012- July 2013 Phase 2:

July 2013-June

1) Incidence and prevalence of KPC colonization (Newly discovered colonization) and

1) No pre- intervention data

1) 30% (July- September 2013);

4.17% (October- December 2013); 4%

(Until June 2014)

(14)

Phase 2 (> July 2013):

1) Drastic reduction in the number of beds 2) Chlorhexidine baths for all colonized pts 3) Access and adequate equipment of hand hygiene stations (e.g., clean sinks and/or alcohol) was ensured 4) Contact precautions

2014 Incidence of BSI

Mularoni et al, ECCMID, 2015

Uncontrolled before- after study; Organ transplant center in Italy

1) Contact precautions 2) Nurse cohorting

3) Chlorhexidine baths for all CRE positive pts 4) Contact screening

5) Enhanced environmental cleaning

6) Hand hygiene and contact precautions compliance monitoring

7) Antibiotic stewardship promotion 8) Staff education

(Only after July 2013)

Pre- intervention:

2012 Post- intervention:

2013-2014

1) CRE incidence of hospital-acquired infections

1)1.6/100,000 patient-days (2012)

1) 1.3/100,000 patient-days (2013);

0.7/100,000 patient- days

(the decrease was significant between January and August 2014)

Peng et al, JMII, 2015

Before-after case counts; ICU in Taiwan

1) Active surveillance of asymptomatic carriers on admission to the ICU

Pre- intervention:

January-April 2012 Post intervention:

2013

1) Incidence of hospital- acquired infections

1) 10.33% 1) 4.02%

Quiros et al, IdWeek, 2014

Uncontrolled before- after study; ICU in Argentina

Phase 1 (July 2010):

1) Active surveillance of asymptomatic carriers on admission to the ICU and weekly thereafter Phase 2 (End of 2011):

1) Chlorhexidine 2% daily baths to all ICU patients

Phase 1:

July 2010- December 2011 Phase 2: January 2012-December 2013

1) Incidence of hospital- acquired cases (Colonization or infection)

1) 7.21/1,000 admissions

1) 3.86/1,000 admissions (p < 0.01) (But there was a 135% increase in incoming colonization pressure)

Themeli- Digalaki et al, CMI, 2012

Uncontrolled before- after study; Impact of a national CRE control program in one tertiary care hospital in Greece

1) Hand hygiene promotion 2) Contact precautions 3) Isolation or cohorting 4) Dedicated staff

Pre- intervention:

October 2010 Post- intervention:

November 2010- October 2011

1) KPC-Kp incidence of infections

1) 4.8/10,000 patient-days

1) 3/10,000 patient- days (p=0.16)

CRAB (n=21)

Barbolla et al, Am J Infect Control, 2008

Before-after study with case counts; ICU in Argentina

1) Surveillance cultures – patients (rectal, oropharyngeal, axilla); Staff hands

2) Contact precautions for colonised/infected patients 3) Environmental screening, including air samples 4) Enhanced hand hygiene

5) After week 7 – enhanced environmental cleaning with hypochlorite and other products

10-week study (July-September 2003):

Pre- intervention:

Initial 7 weeks

1) Patient screening swabs positive for CRAB 2) Positive

environmental samples 3) ICU staff screening swabs positive for CRAB

1) 13% (76.6% one CRAB clone) 2) 70/157 (44.6%) 3) 14/50 (28%) 4) 32% in 2003

1) 15/186 (8.1%) (p=0.17) 2) 2/49 (4%) (p=0.000001) 3) 3/32 (9.4%) (p=0.21)

(15)

Post- intervention:

Last 3 weeks

(i.e. hands)

4) Total % of patients with CRAB infection

4) 16% in 2004 (p=0.0033)

*but later returned to baseline

Chaulagain et al, Jpn. J. Infect.

Dis, 2012

Non-controlled before- after study

(retrospective); 707- bed tertiary care center in 2 intensive care units (ICU) including surgical and medical intensive care units in South Korea

1) Strict environmental cleaning of the ICU with dedicated cleaning equipment

2) Effective sterilization of reusable medical equipment 3) Attention to proper hand hygiene practices 4) Use of contact precautions

5) Continued ICU personnel educational programs 6) Appropriate administrative guidance and support 7) Adequate compliance with the control program

Pre- intervention:

January 2004- March 2004 Post- intervention:

April 2004- December 2004

Number of CRAB (OXA- 51) cases –

infections/colonization

30 cases in 3 months 35 cases in 9 months

Chen et al, Médecine et maladies infectieuse, 2015

Non-controlled before- after study;

tertiary referral hospital in northern Changhua, Taiwan

1) Contact isolation 2) Cohorting

3) Environmental cleaning and meeting 4) Daily chlorhexidine bathing

5) Monitoring adherence to IPC measures (hand hygiene, bathing, cleaning and gowning/gloving) 6) In-service education

7) Antimicrobial stewardship and champions

Pre- intervention:

January 2002- December 2009 Post-

intervention:

January 2010- December 2013

1) Incidence density of HAI

2) Incidence density of CRAB infection

1) 5.23/1000 patient- days

2) 177.79 person- years/ 100,000 admissions

1) 0.6/ 1,000 patient days (p< 0.001) 2) 137.76 person- years/ 100,000 admissions (p < 0.001)

Chmielarczyk et al, J Hosp Infect, 2012

Non-controlled before- after study; 526-bed teaching hospital including two cardiac surgery ICUs in Poland

1) Temporary close the affected ICUs 2) Series of staff educational training sessions 3) Change environmental cleaning and

decontaminating procedures to include daily cleaning of all equipment with a hypochlorite

4) Decontaminate both ICUs using the Steris vaporised hydrogen peroxide (vH2O2)

5) Apply Centers for Disease Control and p IPC interventions

6) Do a mandatory screening of patients and staff for MDR-AB colonization

Outbreak 1:

Pre- intervention:

January- December 2009 Post-

intervention:

December 2009- August 2010 Outbreak 2: Pre- intervention:

September- October 2010 Post-

intervention: 18 October 2010- 2011

1) MDR-AB infections in outbreak 1

2) MDR-AB infections in outbreak 2

1) 20 cases 2) 8 cases

1) 0 cases 2) 0 cases

Choi et al, Korean Med Sci, 2010

Before-after study with case counts; ICU in South Korea

1) Surveillance – patients and environment 2) Strict contact precautions

3) Enhanced cleaning with sodium dichlorocyanurate 4) Cessation of open respiratory suctioning – change to closed-suctioning system to reduce airborne spread 5) Enhanced education on hand hygiene and environmental contamination

Pre- intervention:

September 2007-April 2008 Post-

intervention:

1) CRAB cases (i.e.

Colonisation or infection)

1) 49 cases 1) 8 cases

*No new cases after Aug 2008

(16)

6) Single rooms and cohorting 7) Disposable gowns/gloves

8) Reduced number of staff in contact with colonised/infected patients

9) Enhanced antimicrobial stewardship with computerised prescribing limitations

May-August 2008

Corbella et al, J Clin Micro, 2000

Before-and-after study;

ICU in Spain

1) Sequential ICU closures for decontamination 2) Enhanced cleaning

3) Strict adherence to multimodal cross-transmission IPC protocols with monitoring

4) Enhanced staff education 5) Restricted carbapenem use

6) Computer-assisted prescribing/ consumption 7) Surveillance (rectal swabs) on ICU admission and weekly and environment

8) Data feedback to staff

Pre- intervention:

January-June 1997 Post- intervention:

July 1997-June 1998

*Period for step- wise

intervention is unclear

1) CRAB cases (i.e.

Colonisation or infection) per ICU admissions

2) CRAB environmental contamination

1) 18 CRAB patients/

100 ICU admissions 2) No pre- intervention data

1) 6.3 cases/ 100 ICU admissions 2) Marked reduction in environmental CRAB

Doidge et al, Infect Control Hosp Epidemiol, 2010

Before-after study with case counts; ICU in Australia

1) Surveillance – twice-weekly patient endotracheal aspirate cultures, plus rectal/nasal/wound cultures on days 3-5 of ICU and on discharge

2) Environmental surveillance

3) Single rooms and contact precautions 4) Partial temporary ICU closure

5) 1Enhanced cleaning (with oxidising disinfectant –

“Virkon” – “potassium peroxomonosulphate 50%, sodium alkyl benzene sulphonate 15%, and sulpharnic acid 5%”)

Pre- intervention:

January 2004- August 2006 Post- intervention:

August-October 2006

1) CRAB cases (i.e.

Colonisation or infection)

1) 41 CRAB patients 1) 6 CRAB patients Aug-Oct 2006

* single case in 2007 and no cases in 2008

Enoch et al, J Hosp Infection, 2008

Before-after study with case counts; ICU in UK

1) Surveillance screening thrice-weekly 2) Single rooms and cohorting

3) Barrier precautions (gowns, gloves, masks) 4) Minimise contact

5) Ward closure 6) Management meetings 7) Hand hygiene

8) Enhanced environmental cleaning with hypochlorite 9) Temporary ICU closure

Pre- intervention:

Timing unclear Post- intervention 3 weeks

1) Patient CRAB colonisation and infection

1) 6 cases 1) 2 cases when ICU temporarily closed, then 11 cases followed by no new cases

Ke et al, BMC Proc, 2011

Assessment of data mining surveillance system; Taiwan

1) Simple descriptive study of system efficacy Unclear 1) CRAB isolates 1) No pre- intervention data

2) Anomaly analysis able to detect CRAB- infected patients Kochar et al,

Infect Control Hosp Epidemiol.

2009

Retrospective observational study;

ICUs in USA

1) Contact isolation, including use of disposable gowns and gloves.

2) Cohorting

3) Hand hygiene was “encouraged”

4) Decontamination environment with aerosolised foam quaternary ammonium wipes. Patient-related

Pre- intervention:

2004-2006 Post- intervention:

1) CRAB cases (i.e.

Colonisation/

infection)

1) 8.1 + 4.2 1) 5.2 + 3.7

(17)

and other surfaces wiped at least once/day.

5) Surveillance – rectal swabs for CRAB on admission to ICU and weekly

6) IPC team meetings with staff

Additional measures in January-April 2006:

1) Rectal swabs also assessed for KPC and CRPsA 2) Notation in medical records

3) ICU closed for 2 days in March 2006 for intensive cleaning

4) ABHR added to ICU

5) Additional staff meetings held to enforce IPC interventions, plus use of antibacterial wipes for environmental cleaning twice-daily

2006-2008

Kohlenberg et al, J Med Microbiol, 2009

Non-controlled before- after study; University medical centre in Germany

Phase 1:

1) Contact precautions including in single rooms 2) Hand hygiene before and after patient care 3) Surfaces disinfected daily with an aldehyde- containing disinfectant

4) Education with special emphasis on hand hygiene and disinfection

Phase 2:

1) Patients harbouring the outbreak strain were cohorted in one part of the unit with a separate entrance and separate teams of personnel

2) Active surveillance of all ICU patients on admission, once weekly thereafter and on discharge

Outbreak occurred in two phases:

Phase 1:

February 27- April 2006 Phase 2: June- November 2006

1) CRAB cases (i.e.

Colonized or infected)

1) No pre- intervention data

1) 18 CRAB cases in Phase 1; 14 CRAB cases in Phase 2

Landman et al, J Antimicrob Chemother, 2012

Uncontrolled before- after study; 14 hospitals in New York, USA

1) GNB education 2) Cohorting – 3 sites 3) Cohorting of Staff – no sites

4) Increased IPC staff – 4/9; decreased 2/9; unchanged 3/9

5) No environmental interventions

Pre- intervention:

2006 Post-

intervention: 3- month study period in 2009

1) Clinical isolates of OXA-AB resistant to carbapenems

1) 18% 1) 29%

McGrath et al, Infect Control Hosp Epidemiol, 2011

Non-controlled before- after study; 36-bed Neonatal ICU in a university-affiliated teaching hospital in USA

1) Cohorting in separate nursery along with cohorting staff (primary interventions)

2. Contact isolation

3) The use of dedicated patient equipment

4) Routine daily cleaning of the patient’s environment 5) Enhanced environmental cleaning and dedicated equipment/supplies

6) Hand hygiene practices, including the use of hands- free faucets with clocks above the scrub sinks 7) Multidisciplinary outbreak meetings

8) Monitoring of lapses in infection control practices 9) Educational modules to alert staff and emphasis on IPC lapses

10) One-time active surveillance cultures

Outbreak period:

November 2009- January 2009

1) MDR-AB infections 1) No pre- intervention data

1) 6 infants with MDR-AB infections and then outbreak contained within 52 days

Meletis et al, Non-controlled before- Nationwide action plan with two objectives: Pre- 1) Non-duplicate CR 1) AB : 90/100 (90%) 1) AB : 132/156

(18)

New

Microbiologica, 2015

after study (retrospective);

250-bed tertiary-care hospital in Greece

1) Surveillance of infections attributed to MDR K.

pneumoniae, A. baumannii and P. aeruginosa via compulsory notification for estimation and follow-up of the incidence of these infections;

2) Implementation of IPC measures, emphasizing the isolation or cohorting of patients with infection or colonization and compliance with hand hygiene and contact precautions.

intervention:

November 2007- October 2010 Post- intervention: 1 November 2010- October 2013

isolates of A. baumannii in ICU patients 2) Non-duplicate CR isolates of A. baumannii in non-ICU patients.

2) AB : 50/66 (75.8%)

(84.6%, p>0.05) 2) AB: 75/114 (65.8%, p>0.05)

Messler et al, BMC Proc, 2011

Descriptive study; ICU and isolation ward in Germany

1) Implementation of contact isolation and cohorting 2) Disinfection of equipment and frequently touched surfaces

3) Closure of a common bathroom

4) Education of staff on contact and standard precautions

5) Surveillance cultures of tracheal secretions;

rectal/anal/groin swabs; wounds

6) Temporary ward closure to new admissions

Pre- intervention:

January to February 2011 Post- intervention:

February-March 2011

1) Positive screening swabs for CRAB

1) 5 1) 4, but no further

cases between 23/2/2011 to 15/3/2011

Molter et al, J Hosp Infection, 2016

Non-controlled before- after study; Medical (MICU) and a surgical (SICU) ICUs, 18-beds each in Germany

1) Extended contact precautions for all CRAB patients 2) A designated area for CRAB colonized/infected with a separate nursing team (cohorting)

3) Individual supplies for medication and healthcare equipment and separate rooms for dressing, recreation and storage

4) All equipment was disinfected immediately after use with an alcohol-based disinfectant

5) Stepwise reopening after disinfection of patient room with glucoprotamine

6) Active surveillance on admission and twice weekly 7) Weekly educational sessions for all staff

8) Additional ABHR dispensers at point of care

Pre- intervention:

December 2011 Post-

intervention:

December 2011- January 2012

1) CRAB cases (i.e.

Colonisation/ infection)

1) 10 cases 1) 0 CRAB cases

Orsi et al, J Chemotherapy, 2008

Before-after study with case counts; ICU in Italy

1) Centers for Disease Control and Prevention IPC measures reinforced (strict hand hygiene,

gowns/gloves, single rooms, restricted access to ICU) 2) Cohorting

3) Partial ward closure with allocation of specific CRAB ICU ward

4) Dedicated staff for CRAB patients 5) Surveillance – environment and staff hands 6) Enhanced cleaning with hypochlorite

Pre- intervention:

April-July 2004 Post- intervention:

July-December 2004

1) CRAB cases (i.e.

Colonisation/ infection)

1) 15/36 (41.7%) 1) 1/106 (0.9%)

Ray et al, Infect Control Hosp Epidemiol. 2010

Before-after study with case counts; Hospital in USA

1) IPC coordination meetings and education 2) Improved hand hygiene, environmental cleaning, adherence to PPE (gowns, gloves)

3) Ward closure

4) Environmental surveillance

5) Use of vH2O2 for ward/room disinfection (after terminal clean) at 24hs and weeks 1, 2 and 3.

Pre- intervention:

Prior to Feb 2008 Post- intervention:

After Feb 2008

*Exact time

1) MDR-AB cases (i.e.

Colonisation/ infection) 2) MDR-AB

environmental contamination

1) 3 cases 2) No pre- intervention data

1) 3 cases in Feb - early Mar 2008 followed by 7 cases 2) Marked reduction in environmental contamination with vH2O2 use2

(19)

periods unclear Themeli-

Digalaki et al, CMI, 2012

Uncontrolled before- after study with case counts: Hospital in Greece

1) IC team notification of positive cultures (infections and colonisations)

2) IPC bundle intervention including enhanced hand hygiene, contact precautions, isolation/cohorting of cases, and appointment of dedicated staff

Pre- intervention:

2010 Post- intervention:

2011

1)Incidence of CR-GNB infections

2) Incidence of CR-GNB infections in ICU

1) 9.5 infections/

10,000 patient-days 2) 18.6/1,000 patient-days

1) 5.0 infections/

10,000 patient-days (p=0.01)

2) 8.3/1,000 patient- days (p=0.007) Tsiatsiou et al,

Eur J Pediatr, 2015

Non-controlled before- after study;

3 Neonatal Intensive Care Units (NICUs) with 44 beds, including 15 intensive care beds in Greece

1) Active surveillance cultures for CRAB colonization in hospitalized neonates

2) Optimization of antimicrobial therapy 3) Ward closure to new admissions for 12 days 4) Cohorting of neonates

colonized or infected 5) Staff cohorting

6) Monitoring adherence to contact precautions 7) Evaluation and improvement of environmental cleaning and sterilization

8) Availability of replacement ABHR dispensers 9) Monitoring adherence to IPC practices 10) Education of all NICU staff and families

Pre- intervention:

Unclear Post- intervention:

September 2011-February 2012

1) Prevalence of CRAB infections

1) No pre- intervention data

1) “sustained reduction occurred in the prevalence of infected neonates (p<0.0001)”

Ushizawa et al, Jpn J Infect Dis, 2016

Non-controlled before- after study

(Retrospective data);

500-bed critical care center in a tertiary care hospital in Japan

1) Temporary closure of the Emergency department and termination of admission for 26 days

2) Single room accommodations for patients with MDR-AB colonization or infection

3) Adherence to proper hand hygiene before-after patient care

4) Staff cohorting

5) Education through training and video programs for staff

6) 3 times daily cleaning

7) Active surveillance cultures every 3 days on all patients

Pre- intervention:

September- March 2011 Post- intervention:

March-April 2012

1) Prevalence of MDR- AB cases (i.e.

Colonisation/ infection)

1)12 cases 1) 2 cases

CRPsA (n=10)

Crespo et al, J Clin Micro, 2004

Uncontrolled before- after study with case counts; Hospital in Colombia

1) Reinforcement of isolation procedures 2) Reinforcement of hand hygiene

3) Patient and environmental surveillance (nebulizers, ventilators, tubing, stethoscopes and patient sinks) as well as staff hands

Pre- intervention:

before May 2003 Post- intervention:

after May-June 2003

1) CRPsA cases (i.e.

Colonisation or infection)2 2) Environmental contamination (Sinks, stethoscopes)

1) 1-4 patient cases/month 2) No pre- intervention data

1) 1-2 cases/month 2) 2/9 sinks positive in Sept 2003; all environmental cultures negative in Nov 2003

Knoester et al, Clin Microbiol Infect, 2014

Uncontrolled before- after study; ICU in the Netherlands

1) Re-education of staff on basic hygiene 2) Auditing hygiene procedures

3) Patient rectal and throat swabs (post-Dec 2011) and 4 rounds of environmental screening (water, sink drains, furniture, devices)

4) Cohort screening of positive cases 5) Regulation of hand hygiene

Pre- intervention:

October 2010 Post- intervention:

December 2011-

1) CRPsA cases (i.e.

Colonisation/ infection)

1) Multiple cases (n>13)

2) One case (Jan 2012) after replacement of contaminated faucets, but subsequently had recurrence of patient

(20)

6) Isolation procedures (single rooms) 7) patient labelling

8) Cessation of device sharing 9) Auditing

10) Chlorination of sinks (later ceased), and faucet replacement

May 2012

*Step-wise introduction so exact timing unclear

cases after cessation of extended isolation measures in May 2012

Kochar et al, Infect Control Hosp Epidemiol.

2009

Retrospective observational study;

ICUs in USA

1) Contact isolation, including use of disposable gowns and gloves.

2) Cohorting

3) Hand hygiene was “encouraged”

4) Decontamination environment with aerosolised foam quaternary ammonium wipes. Patient-related and other surfaces wiped at least once/day.

5) Surveillance – rectal swabs for CRAB on admission to ICU and weekly

6) IPC team meetings with staff

Additional measures in January-April 2006:

1) Rectal swabs also assessed for KPC and CRPsA 2) Notation in medical records

3) ICU closed for 2 days in March 2006 for intensive cleaning

4) ABHR added to ICU

5) Additional staff meetings held to enforce IPC interventions, plus use of antibacterial wipes for environmental cleaning twice-daily

Pre- intervention:

2004-2006 Post- intervention:

2006-2008

1) CRPsA cases (i.e.

Colonisation/ infection)

1) 3.3 + 2.5 1) 3.8 + 2.1

Landman et al, J Antimicrob Chemother, 2012

Uncontrolled before- after study; 14 hospitals in New York, USA

1) GNB education 2) Cohorting – 3 sites 3) Cohorting of Staff – no sites

4) Increased IPC staff – 4/9; decreased 2/9; unchanged 3/9

5) No environmental interventions

Pre- intervention:

2006 Post-

intervention: 3- month study period in 2009

1) Clinical isolates of PsA resistant to

carbapenems

1) 61% imipenem- resistant PsA and 74% meropenem- resistant PsA

1) 69% imipenem- resistant PsA and 77% meropenem- resistant PsA

Liese et al.

DGHM, 2015

Uncontrolled before- after study;

Hematology ward

1) Enhanced environmental surveillance including weekly microbiological screening of sinks, toilets, and shower drains of all patient rooms

2) Detection of MBL-PsA led to immediate cleaning &

disinfection of the bathroom and re-sampling.

3) Two rounds of thorough environmental cleaning and disinfection in Nov 2014 and Feb 2015. Standard toilets were replaced by rimless toilets basins in May 2015 4) Screening results from rectal swabs taken on admission and at least weekly thereafter were used to determine colonization in patients.

5) Patient isolation if + cultures, plus room disinfection Pre- intervention:

Pre-Aug 2014 Post- intervention period:

Nov 2014 – Feb 2015

1) MBL-PsA colonisation in patients

2) Environmental samples of PsA

Unstated 1) Decrease of MBL-

PsA colonisations in patients without any observed infections.

2) Decrease of environmental occurrence of PsA (29/60 samples +ve – of which 10/29 (34,5%) were MBL- PsA)

Meletis et al, New

Non-controlled before- after study

Nationwide action plan with two objectives:

1) Surveillance of infections attributed to MDR K.

Pre- intervention:

1) Non-duplicate CR isolates of P. aeruginosa

1) PsA : 18/47 (37.5%)

1) PsA : 88/156 (56.4%, p<0.05)

(21)

Microbiologica, 2015

(retrospective);

250-bed tertiary-care hospital in Greece

pneumoniae, A. baumannii and P. aeruginosa via compulsory notification for estimation and follow-up of the incidence of these infections;

2) Implementation of IPC measures, emphasizing the isolation or cohorting of patients with infection or colonization and compliance with hand hygiene and contact precautions.

November 2007- October 2010 Post- intervention: 1 November 2010- October 2013

in ICU patients 2) Non-duplicate CR isolates of P. aeruginosa in non-ICU patients.

2) PsA : 22/123 (17.88%)

2) PsA: 36/149 (24.2%, p>0.05)

Mentzelopoulos et al, Intensive Care Med, 2007

Uncontrolled before- after study with cases counts; ICU in Greece

1) Use of disposable gloves, gowns and masks 2) Hand hygiene before/after patient contact; weekly lessons on IC.

3) Decontamination of areas with cases for 48 hours post-discharge/death

4) Surveillance cultures of staff and environment 5) Hand hygiene compliance auditing

Pre- intervention:

September 2005 Post-

intervention:

September- October 2005

1) Cases of VAP due to VIM1-PsA

1) 2 cases 1) 3 cases soon after start of intervention then cessation of further cases

Themeli- Digalaki et al, CMI, 2012

Uncontrolled before- after study with case counts: Hospital in Greece

1) IC team notification of positive cultures (infections and colonisations)

2) IPC bundle intervention including enhanced hand hygiene, contact precautions, isolation/cohorting of cases, and appointment of dedicated staff

Pre- intervention:

2010 Post- intervention:

2011

1)Incidence of CR-GNB infections

2) Incidence of CR-GNB infections in ICU

1) 9.5 infections/

10,000 patient-days 2) 18.6/1,000 patient-days

1) 5.0 infections/

10,000 patient-days (p=0.01)

2) 8.3/1,000 patient- days (p=0.007) Wendel et al,

Am J Infect Control, 2015

Uncontrolled before- after study with cases counts; Hospital, particularly surgical ICU, in Germany

1) Surveillance cultures of environment, including tap water in 2011 and 2012

2) Centers of Disease Control and Prevention contact precautions (use of gowns, gloves, masks) and standard precautions for all colonised/infected patients, including single rooms

3) Enhanced staff re-education on hygiene measures 4) Auditing of hygiene practices

5) Restriction of washbasin use (after May 2012), inflatable reusable hair washbasins were forbidden and sink traps in all rooms were changed

Pre- intervention:

2002-2012 Post- intervention:

April 2012-2014

1) CRPsA cases (i.e.

Colonisation/ Infection) 2) CRPsA environmental contamination

1) 27 cases 2) No pre- intervention data

1) 2 cases immediately after restrictions on washbasins were introduced and then no further cases 2) Marked reduction in environmental isolates, especially after replacement of sink traps

Yogeesha Babu et al, J Pure and Applied Microbiology, 2011

Uncontrolled before- after study; Burns Unit in India

1) Introduction of strict adherence to Centers of Disease Control and Prevention IPC measures – not described further

2) Some screening of staff hands

Pre- intervention:

2004-2007 Post- intervention:

2007-2009

*Exact periods uncertain

1) Patient burns wound cultures positive for PsA and resistant to imipenem

1) No pre- intervention data

2) “Percentage reduction of 8.6%...was observed”

ABHR: Alcohol-based handrubs, BSI: Bloodstream infections, CI: Confidence interval, CLABSI: Central line-associated bloodstream infection, CPE: Carbapenemase-producing Enterobacteriaceae, CR: Carbapenem-resistant, CRAB: Carbapenem-resistant Acinetobacter Baumanii, CRE: Carbapenem-resistant Enterobacteriaceae, CREG: Carbapenem-resistant Enterobacter gergoviae, CRPsA: Carbapenem-resistant Pseudomonas Aeruginosa, EPOC: Effective Practice and Organization of Care, GNB: Gram-negative bacteria, HAI: Healthcare- associated infections, ICU: Intensive care unit, IMI-R: Imipenem-resistant, IPC: Infection prevention and control, ITS: Interrupted time series, Kp: Klebsiella pneumoniae, KPC: Klebsiella pneumoniae carbapenemase, LTACHs: Long-term acute care hospitals, LTCF: Long-term care facilities, MBL: metallo-beta-lactamase, MERO-R: meropenem-resistant, MDR: Multidrug- resistant, MDR-AB: Multi-resistant Acinetobacter Baumanii, NDM: New Dehli metallo-beta-lactamase, NICU: Neonatal intensive care unit, OXA: Oxacillin, Pan-R: Pan-resistant, PPE:

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