29 Jun -2 Jul 2011

Geneva , Switzerland

Dr WONG Tin YauHead, ICB, CHP

What (are new G-ve)? GREATEST risk to public health!

Where/ When (are they found)?

How (serious is the problem)?

What (measures are used to deal with them)?

What (lessons have we learnt so far)?

T.R. Walsh / International Journal of Antimicrobial Agents 36S3 (2010) S8–S14

Greatest clinical threat

Walsh T. Int J Antimicrob Agents 2010 ;36 ( supp 3) S8-S14

On 2011年7月27日,

明報即時新聞

染超級細菌 荷蘭27人死

荷蘭鹿特丹的馬斯城醫院26日宣布，一種不明疫情近兩個月已在荷蘭造成27人

死亡，所有死者例均感染一種超級細菌。

馬斯城醫院的一名醫生向記者說，目前已確認這種超級細菌屬於克雷伯氏菌

，該院與荷蘭多家醫療科研機構正試圖確認該病菌是否和所有死亡病例有直接

關係。

馬斯城醫院於6月1日首次發布消息稱，有兩名患者在感染這種病菌後死亡。26

日，該院公布的最新統計數據說，目前仍有78人確診感染了這種病菌，1967人

疑似感染。該院說，預計確診病例將繼續增加，但「疫情依然在控制中，因為

在最近一星期內沒有新發現的確診患者。」

此前，這種超級細菌曾在法國、以色列和印度等國引發疫情。

% of Carbapenem Resistant

Klebsiella pneumoniae blood isolates EARS-NET, 2009

EARS-NET 2009 annual report, ECDC

Data from the Greek System for the Surveillance of Antimicrobial (http://www.mednet.gr/whonet)

Vatopoulos Eurosurveillance 2008

Kitchel B. AAC 2009 , 53: 3365-3369

Kumarasamy TLID August 11, 2010

11 August 2010: article in Lancet Infect Dis & global media coverage

17 August 2010: ECDC “Epidemiological update”

27 August 2010: ECDC threat assessment posted on EWRS

20 September 2010: ECDC questionnaire survey I to EU Member States, Iceland and Norway

By 4 October 2010: a total of 77 cases reported from 13 countries since 2008

April 2011: ECDC questionnaire survey II

By 31 March 2011: total of 107 cases reported in 13 countries

Magiorakos and Kleinkaupf. ECDC 2011. Struelens, et al. Eurosurveillance 2010, 15(46).pii:19716

107 cases in 13 countries.

Among 55 travel history available.

31 cases received healthcare or travelled to India or Pakistan

5 cases had received healthcare in the Balkans

13 cases of presumed secondary transmission in Europe

Source: ECDC, 2011. Struelens M, et al. Eurosurveillance 2010; 15(46). pii:19716.

Asymptomatic colonisation

Wound infection / Diabetic foot

Lower urinary tract infection

Upper urinary tract infection

Nosocomial pneumonia / VAP

Intra-abdominal / pelvic infection

Bacteraemia / septicaemia

Neurosurgical meningitis

SEVERITY

Klebsiella pneumoniae

Escherichia coli

Enterobacter spp.

Citrobacter freundii

Morganella morganii

Proteus mirabilis

Source: ECDC, 2010. Struelens M, et al. Eurosurveillance 2010; 15(46). Pii: 19716.

0 5 10 15

Colonisation

UTI

SSTI

Abdominal

BSI

Source: ECDC, 2010. Struelens M, et al. Eurosurveillance 2010; 15(46). pii: 19716.

Indian Journal of Medical Microbiology, July 17, 2010

“New Delhi metallo-beta-lactamases (NDM) is a nomenclature that Indians cannot be proud of … The virtual nonexistence of antibiotic policies and guidelines in India … is a major driver of the emergence and spread of multidrug resistance in India. This is augmented by the unethical and irresponsible marketing practices of the pharmaceutical industry, and encouraged by the silence and apathy of the regulating authorities. Poor microbiology services in most parts of the country add to the problem.”

Environmental Study

171 swabs

- 156 grew meropenem resistant

Gram-negatives)

- 51/171(29.8%) were positive for NDM-1

UNDERESTIMATION!!!

50 water samples

- 14 grew meropenem resistant

Gram-negatives)

- 2 out of 50 (4%) were positive for NDM-1

Carriage rates: Pakistan: prevalence of 27.1% in in-patients and 13.8% in out-patients.

Perry et al., Jul 2011 JAC

Only been known for 5 years and has already spread to 28 countries.

Nobody in Southern Asia knows how big the problem is.

The potential for the inter-bacteria transfer is unprecedented.

NDM-1 will inevitably spread to all Gram-negative bacteria.

Pipeline drugs will struggle to cover NDM-1 positive bacteria.

1 – Risk factors for patient infection or colonisation

Prior use of antimicrobials◦ Any antimicrobial◦ Carbapenems (associated with a high risk estimate)◦ Other antimicrobials (fluoroquinolones, cephalosporins, anti-

pseudomonal penicillins, metronidzole)

Cross-border transfer of patientsStrong evidence that it is associated with risk for transmission when:◦ Patients are transferred from countries with high rates of CPE

to healthcare facilities in other countries◦ Patients had received medical care abroad in areas with high

rates of CPE

Transfer of patients within units of same hospital◦ Immunosuppression◦ Severity of illness◦ Invasive procedures Source, ECDC, 2011

2 – Infection control measures for prevention of spread

Effective measures during an outbreak:

◦ Active surveillance by rectal screening for CPE

◦ Cohort nursing for patients who are positive for CPE

◦ Additional contact precautions for patients who are positive for CPE

Source: ECDC, 2011

Carbapenemase-producing Enterobacteriaceae are spreading worldwide including in Europe.

Risk factors include previous exposure to antimicrobials, transfer of patients between and within hospitals and travel.

Measures to prevent spread include active surveillance by rectal screening, cohort nursing and contact precautions for positive patients.

A majority of EU Member States have issued national guidance for detection, referral to reference laboratory, notification to health authorities and infection control measures.

In 2011, ECDC will

◦ Publish a risk assessment and guidance document.

◦ Test the EPIS rapid information exchange platform for extensively-resistant pathogens.

Source: ECDC, 2011. Update from Struelens M, et al. Eurosurveillance 2010; 15(46). pii: 19716.

Country

National guidance on:

Detection and surveillance methods

(N=16)

Referral to reference laboratory (N=14)

Notification to health authorities (N=12)

Infection control measures (N=13)

Austria P P PBelgium P P P P

Czech Republic P P PEstonia PFinland P P P PFrance P P P P

Germany P P PGreece P P P PIreland P P P

Netherlands P P P PNorway P P PPoland P P P P

Portugal P P P PSlovenia P P PSweden P P P P

United Kingdom P P P P

Grundmann H, et al. Eurosurveillance 2010; 15(46). pii:19711.

Guidelines available but small impact

Awareness of physicians of hi resistance rate and use of antibiotics

Public health undersized in health system

Strains not routinely typed

Hospitals outbreaks not adequately investigated

ICC in hospital no admin authority

ID specialist no training in epidemiology

Vatopoulos A. Eurosurveillance 2008

Seen for the first time in TASMC in Jan 2004 isolated from the urine of a surgical patient

◦ Patient discharge before result were reported –went unnoticed

No other cases until Jun 2004

Jun 30, 2004 – Outbreak in the NICU, three cases of late neonatal sepsis

◦ 3 other carriers

Traced to a mother which was GI carrier of the strain

◦ No foreign travel to the US

2004 no further cases during 6 months

2005-2007:

◦ 30 new cases, only two small (3 patients) time and space clusters

◦ In hospital mortality 33%

Typical phenotype – quinolone and amikacin S

◦ 18 isolates typed

3 PFGE genotypes all produce KPC-2

11 clone A )

5 clone B ) Similar plasmid encoding also for qnr B2

2 clone C )

◦ Repeated investigations did not identify the source

Marchaim D, AAC 2008; Chmelintzky L, AAC 2009

Leavitt A, AAC 2007

2005 – 2006

66% of isolates clonal

2007

＞95% of isolates clonal

Crude Mortality

Resistant Klebsiella – 21 died (44%)

Susceptible Klebsiella – 7 died (13%)

No Klebsiella – 1 died (2%)

Adusted impact of CRKP on mortality:

Compared with hospital controls – OR 5.0 (1.7-14.8), p=0.004

Compared with susceptible Klebsiella – OR 3.9 (1.1-13.6), p=0.03

Mortality with bacteremia 70%

Schwaber, AAC, 2008Finkelstein, ECCMID 2007Borer, ICHE 2009

Cohen MJ et al , ICHE, Jul2011, 32: 673-678

Cohen MJ et al , ICHE, Jul2011, 32: 673-678

Cohen MJ et al , ICHE, Jul2011, 32: 673-678

The second stage began in March 2007. Following the failure of CRKP containment and incompliance with new Israeli national regulations, cohorting of patients affected by CRKPwas initiated. Cohorting was established separately for medical and surgical services.Affected patients were admitted to separate areas, were managed by dedicated nursingstaff, and were allocated separate medical equipment. Entry to these areas was permittedonly after removal of white coats and donning of disposable gowns and gloves. Handhygiene on entrance and exit was scrupulously enforced. Affected patients in the intensivecare unit (ICU) were also managed in single patient rooms (rather than open-plan areas)and were treated by dedicated nursing staff who cared only for patients affected by CRKP.Infection control precautions were similar to those enforced in the cohort areas (ie,removal of white coats and donning of gowns and gloves on room entry, and increasedvigilance for hand hygiene). Environmental cleaning of the cohort areas was performedusing a solution containing 1,000 ppm sodium dichloroisocyanurate (NaDCC) anddetergent (Chlor-Clean; Guest Medical). Environmental cleaning was performed dailyaccording to a checklist. The checklist detailed

all sites to be cleaned and was marked and signed by the CRKP cohort staff. Compliancewas monitored by the infection control team. Further, active surveillance was performed

for all patients with an epidemiologic link to each patient newly found to harbor CRKP(“snow ball” active surveillance sampling) by culture of stool or rectal swab specimens.

Cohen MJ et al , ICHE, Jul2011, 32: 673-678

Low–level:

Strict eradication policy (search & destroy) should be implemented

Medium-to-high level:

Very active containment policy with ZERO tolerance to newly hospital-acquired cases and strict implementation (including areas where IC people normally do not like to go: LTCF etc)

Carmeli Y. CMI 2010Grundman H. Euro surveillance 2010

Microbiology: Screen all enterobacteriaceae for carbapenemases

Have an action plan ready for:

◦ Microbiologic confirmation

◦ Screening of all contacts of an index case

◦ Epidemiological investigation

◦ Eradication

Coordination & supervision by public health authorities with expertise in hospital IC

First detection of microbiologically confirmed case: Active search and destroy strategy

Carmeli Y. CMI 2010

Screening policies

◦ Define high-risk patient groups or countries

◦ Screen all high-risk patients

◦ Screening sites:

rectal swab or stool

◦ Preemptive isolation recommended while

awaiting results of screening