Top Ten Epidemiology and Infection Control Papers of

the Year

Basic Research, Chlorhexidine, GNR, VRE, UTI,
environmental cleaning
Andreas F. Widmer, MD,MS,FIDSA,FSHEA
Deputy Head of Dept. Infectious Diseases & Hospital
Epidemiology, Basel, Switzerland
Core Member Patient Safety Program WHO, Geneva
President of Swiss National Surveillance System
Disclosures: nothing to disclose
Bench Research & Infection
Control
Life Expectancy
Skin Commensuals and Immunity
Rapid development of antimicrobial
Resistance by Morbidistat
Globally, no matter how old a person is, life expectancy is increasing.
Life expectancy at birth increased
- 10.7 years for males and
- 12.6 years for females from 1970 to 2010.
- mortality is decreasing in every age bracket, although it is decreasing more slowly among
young adults.
Percent Decline in Mortality rate, 1970 - 2010

Wang H.Lancet 2012; 380: 207194
female
male
Commensal microbiota control the balance of effector
and regulatory T cells in the skin tissue.
Distinct Commensal Niches Control T cell Cytokine Production in the Gut and Skin in
Germ-free Mice
The skin microbiota have an autonomous role in controlling the local inflammatory milieu and
tuning resident T lymphocyte function.
Protective immunity to a cutaneous pathogen was found to be critically
dependent on the skin microbiota
Germ-
free mice
Germ-free
mice, artificially
colonized with
S.epidermidis
Naik S et al. Science 2012:337:1115
Flow cytometric analysis of IL-17A production
in live CD45 + TCRb + cells

Impact on handhygiene to endogenous
flora and protective immunity?
specific pathogen-free (SPF) conditions
S.epidermidis
Shower
The morbidostat is a continuous-culture device that automatically
tunes drug concentration to maintain constant growth inhibition
The assay runs in cycles
of growth periods (t =
11 min) and adds
dilutions with either
fresh medium (green) or
drug solution (magenta).
The population is diluted
with antibiotic solution
when the OD exceeds
ODTHR (0.15) and the
net growth over the
complete cycle is
positive (OD > 0)
Toprak E et al. Nature Genetics 2012;44:101-6
Morbidostat
A culture-independent sequence-based metagenomics
approach to the investigation of an outbreak of Shiga-
toxigenic Escherichia coli O104:H4.
Loman NJ. et al JAMA 2013;309:1502-10
Recovery of Sequences From the Outbreak Strain From
the Outbreak Metagenome Through Iterative Filtering

Loman NJ. et al JAMA 2013;309:1502-10
Environmental gene tags: Short sequences of DNA that
contain genes in whole or in part that can be used to identify
and characterize the organisms from which they originate.
Pre-emptive Antimicrobial
Treatment to prevent Emergence
of Antimicrobial Resistance

Urinary Tract Infections
Open bone Fractures

Selection of studies for meta-analysis of trials investigating antibiotic
prophylaxis for urinary tract infections after removal of urinary
catheter
Marshall J. BMJ 2013;346:f3147 (Published June 11)
Lower Incidence of UTI after Removal of Urinary
Catheter by antimicrobial prophylaxis: A meta-analysis


Marshall J. BMJ 2013;346:f3147 (Published June 11)

Short duration of antibiotic prophylaxis in open fractures does
not enhance risk of subsequent infection: Case-control study

Multivariable analysis
Variable Odds ratio (95% CI) p-value
Gustilo and Anderson grade
Grade IIIa Reference
Grade IIIb 1.7 (0.3 to 10.6) 0.59
Grade IIIc 12.5 (2.7 to 57.8) 0.001
Delay first to second surgery 0.9 (0.8 to 1.0) 0.824
Wound closure during first surgery 0.4 (0.1 to 1.1) 0.624
Intramedullar reaming 1.1 (0.3 to 3.9) 0.94
Plate osteosynthesis 0.6 (0.2 to 2.1) 0.742
Median duration of antibiotic
therapy (days)
1.0 (0.96 to 1.09) 0.91
Antibiotic therapy
1 day Reference
2 to 3 days 0.3 (0.1 to 3.3) 0.949
4 to 5 days 0.6 (0.2 to 2.1) 0.243
> 5 days 1.6 (0.5 to 6.1) 0.432
Dunkel N& Uckay. I. Bone Joint J 2013;95-B:8317
Vancomycin-resistant Enterococci
Commensal anaerobic
bacteria suppress VRE
colonization in antibiotic-
treated mice.
Ubeda C et al. Infect. Immun. 2013;81:965-973
Mice infected 10
8
VRE CFU after
1 week of ampicillin treatment
Mice were orally gavaged for 3
consecutive days, starting 1 day after
antibiotic cessation, with PBS, a
suspension of fecal pellets from untreated
mice (feces), or an aerobic (aero) or
anaerobic (anaero) culture of fecal
microbiota from untreated mice.

Numbers of VRE CFU in the fecal pellets
of infected mice were analyzed 5 weeks
after infection (n = 8 to 10). Limit of
detection, 10 CFU/10 mg. ***,
significantly different (P < 0.001) from
the PBS group; ns, not significant.
c
o
n
t
r
o
l

Ubeda C et al. Infect. Immun. 2013;81:965-973
Colonization with the Barnesiella genus
correlates with VRE elimination: BMT Patients
Bacterial density with Barnesiella genus of BMT patients
Low Risk for VRE colonization
High
Chlorhexidine
Disinfectants
Bass P et al. AJIC 2013;41:345-8
Preoperative bathing or
showering with skin antiseptics
to prevent surgical site infection
Webster J, Cochrane DSR 2012
JHI 2012;82:71-84
AJIC 2013;41:167-73
Effect of Daily Chlorhexidine Bathing on
Hospital-Acquired Infection
KaplanMeier Estimates of Time to Primary Bloodstream Infection.
Climo MW et al. N Engl J Med 2013;368:533-542.
Day 16
Multicenter, cluster-
randomized, nonblinded
crossover trial to
evaluate the effect of
daily bathing with
chlorhexidine-
impregnated washcloths
on the acquisition of
MDROs and the
incidence of hospital-
acquired bloodstream
infections
Effect of Daily Chlorhexidine Bathing on
Hospital-Acquired Infection
Microbiology of BSIs
Climo MW et al. N Engl J Med 2013;368:533-542.
intervention control
The benefit of chlorhexidine bathing reported by Climo and colleagues (Feb.
7 issue)1 appears to be a reduction in the rate of bloodstream infections
due to coagulase-negative staphylococci.
Anthony L. Esposito, M.D. N Engl J Med 2013; 368:2330-2332June 13, 2013
There may be an overestimation of the cumulative probability because data from
patients who were discharged (or who died) without having a bloodstream infection
were censored. A more suitable and valid approach would be to treat patient
outcomes as competing events.
Martin Wolkewitz, . N Engl J Med 2013; 368:2330-2332June 13, 2013

Moreover, rates of acquisition of methicillin-resistant S. aureus (MRSA) and
vancomycin-resistant enterococci (VRE) bacteremia were primary end points but from
the text and Table 2 of the article we cannot distinguish acquisition and infection.

Ben Cooper, Ph.D. N Engl J Med 2013; 368:2330-2332June 13, 2013


Letters to the Editor
Climo MW et al. N Engl J Med 2013;368:533-542.

Methods:

unmasked, cluster-randomised, two 6-month periods crossover
10 PICUs (>2 month old children) at 5 US hospitals
Feb 2008-Sept 2010, daily bathing with either standard bathing
practices or using a 2% CHG cloth

Results:
Reduction of bacteraemia incidence in the PP population
receiving CHG bathing (328/1000 days, 227458) compared
with standard practices (493/1000 days, 391615; IRR 064,
042098).
NS reduction in the ITT population
Slide: Courtesy of R Skov.

Endpoints
The primary outcome of the Pediatric SCRUB trial was
bacteraemia, which we defined as any single positive
blood culture, including those that grew commensal skin
organisms (eg, coagulase-negative staphylococci).
Lancet 2013; 381: 1099106
Lancet 2013; 381: 1099106
Comparision Incidence Catheter-related Infections with
CHX Gel Dressing vs Control
Cumulative risk of major-CRI with chlorhexidine-
gel dressings and non-antiseptic dressings,
Colonization with highly adhesive non-
chlorhexidine dressings vs standard dressing

Timsit F. Am J Respir Crit Care Med. 2012 Oct 4.
Major Catheter-related infection:
Catheter colonization and clinical sepsis or CR-BSI
Routine (3d) versus clinically indicated replacement of peripheral
intravenous catheters: a randomised controlled equivalence trial
(per-patient analysis)
Rickard CM et al. Lancet 2012;380:1066-74
Ethanol locks to prevent catheter-related bloodstream
infections in parenteral nutrition:
a meta-analysis.
Ethanol 70% with and w/l flushing vs
heparin lock
Oliveira C. Pediatrics 2012;129:318
Distribution of Enterobacteriaceae and associated ESBL
and AmpC -lactamases in Neonates ( 1500 to <2500 g)

Kothari C et al. BMC Microbiology 2013;13:136
Safdarjung Hospital, New Delhi
Distribution of Enterobacteriaceae and associated ESBL and
AmpC -lactamases in low-birth Neonates in New Delhi, India
0%
10%
20%
30%
40%
50%
60%
70%
80%
Day 0 Day 21 Day 60
% ESBL positive
% ESBL pos2
Kothari C et al. BMC Microbiology 2013;13:136
Safdarjung Hospital, New Delhi
Antimicrob Resist Infect Control. 2013 Jun 12;2(1):20. [Epub ahead of print]
Pasricha J, Koessler T, Harbarth S, Schrenzel J, Camus V, Cohen G, Perrier A, Pittet D, Iten A

Study design: observational study using rectal swabs on admission and
discharge
1072 patients screened,
51 (4.8%) were carriers of an ESBL-E at admission.
Of 473 patients who underwent admission and discharge screening,
21 (4.4%) acquired an ESBL-E.

Risk factors colonized on admission
diabetes mellitus without end-organ complications (OR 2.8 [1.1-7.1])
connective tissue disease (OR 7.2 [1.2-44.6],
and liver failure (OR 8.4 [1.5-45.4])

Risk factors for Acquisition
Receipt of a first- or second-generation cephalosporin (OR 9.25 [2.2-37.8]),
intra-hospital transfer (OR 6.7 [1.7-26.1]),
and a hospital stay >21 days (OR 25.1 [4.2-151.7])
Carriage of extended-spectrum beta-lactamase-producing
enterobacteriacae among internal medicine patients in Switzerland.


Rate of Transmission (R
0
)
of
Extended-spectrum beta-lactamases (ESBL)-producing
Enterobacteriaceae
without contact isolation


S. Tschudin-Sutter, M.D., R. Frei, M.D. M. Dangel, MPH, A. Stranden

, PhD,
A.F. Widmer

M.D, MSc,FIDSA,FSHEA

Sarah Tschudin-Sutter
1
, M.D., Reno Frei
2
, M.D. Marc Dangel
1
, MPH, Anne Stranden
1
, PhD,
Andreas F. Widmer
1
M.D MSc
Clin Infect Dis. 2012 Sep 24. [Epub ahead of print]

University Hospital Basel, Switzerland

133/220 (60%)
screened for ESBL-carriage by rectal swab
Screening not performed in 87
contact patients:

Discharged at time result obtained
Under antibiotics with activity against
ESBL

324 patients
infected/colonized with
ESBL-producing Enterobacteriaceae
93/324 (28.7%)
Index cases
220
Contact patients
From June 1999 to April
2011, 324 patients
infected or colonized
with an ESBL-producing
Enterobacteriaceae
accounted for 551
admissions.

Clin Infect Dis. 2012 Sep 24.
Confirmed transmissions:
2/133 (1.5%)
After mean 7.5d of exposure
Incidence of Nosocomial Transmission of E.coli ESBL
Clin Infect Dis. 2012 Sep 24.

Hilty M. Clin Infect Dis. 2012 Oct;55(7):967-75
Conclusions. Household outweighs nosocomial transmission of
ESBL producers. The effect of hospital infection control measures
may differ between different species and clones of ESBL producers.
Colonization Sites of ESBL positive Patients

Tschudin-Sutter S, & Widmer AF. Infect Control Hosp Epidemiol. 2012 Nov;33(11):1170-1.
Buehlmann M & Widmer AF. Infect Control Hosp Epidemiol. 2010 Apr;31(4):427-
Distribution of single ESBL types in Enterobacteriaceae isolates from
retail chicken meat samples purchased in Greifswald and Berlin.
The prevalence of the ESBL genes (%) was calculated for Greifswald
(n=111), Berlin (n=76) and for the total of both groups (n=187).

Kola A. J. Antimicrob. Chemother 2012; 67: 26312634


100 markers for virulence
Resistance and other markers
Kluytmans J. Clin Infect Dis. 2013 Feb;56(4):478-87.
Slide: courtesy of J. Kluytmans
BSI from strains
identifed from
chickens
chicken strains
Colonization of the
gut of humans
Chicken only strains
Epidemiologic curve of HUS- and EHEC-Outbreak in
Germany (809 HUS- und 2717 EHEC cases)
RKI, Abschlussbericht EHEC O104, Deutschland 2011
EHEC:- E. coli Serovar O104:H4.
ESBL CTX-M 15
Estimated exposure: 27-100000 Germans
Shigatoxin- E. coli and enteroaggregative E. coli:
- Shigatoxin 1: - (negative)
- Shigatoxin 2 (vtx2a) : + (positive)
- Intimin (eae) : - (negative)
Estimate: 60,000 thousands Individuals
exposed in Germany
Buchholz U et al. N Engl J Med 2011;365:1763-1770

Course of STEC Carriage After Onset of Clinical Symptoms in
Patients Receiving Azithromycin and Untreated Patients
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Nischke M, JAMA , 2012;307:1046-52
Laboratory preparedness for detection and monitoring
of Shiga toxin 2-producing Escherichia coli O104:H4 in
Europe and response to the 2011 outbreak
Rosin P. Eurosurveillance, June 2013;18, Issue 25, 20
April 2011
December 2011
Healthcare-associated Infection
and Environment

Disinfectant Product Substitutions
Donskey CJ. AJIC. May 2013
Six of the 7 interventions were quasi-experimental
studies in which rates were compared before and
after interventions with no concurrent control group
Confounding factors not reported (e.g., hand hygiene
or Contact Precaution compliance)
Decrease in the incidence in 6 of 7 studies
A Long-Term Low-Frequency Hospital Outbreak of KPC-Producing
K. pneumoniae Involving a Persisting Environmental Reservoir
Tofteland S,. PLoS ONE 8(3): e59015.
6
10

The rate of HAI and/or MRSA or VRE colonization in ICU rooms
with copper alloy surfaces was signicantly lower than that in
standard ICU rooms (0.071 vs 0.123; ).
For HAI only, the rate was reduced from 0.081 to 0.034 (p<0.013)
Copper Surfaces Reduce the Rate of
Healthcare-Acquired Infections in the
ICU
Salgado CD.. Copper Surfaces Reduce the Rate of Healthcare-Acquired
Infections in the Intensive Care Unit Infect Control Hosp Epidemiol 2013;34(5):479-486
Frequency distribution of the Microbial Burden resident on all objects
(classified by type) during the intervention.
Schmidt MG et al. J. Clin. Microbiol. 2012;50:2217-2223
0 CFU/100 cm
2

1 to 250 CFU/100 cm
2
>250 CFU/100 cm
2

six copper-surfaced
objects (mean)
465 CFU/100 cm
2

(n = 2,714 objects),

control items (mean)
2,674 CFU/100 cm
2

(n = 2,831 objects
Latest Price & Chart for High Grade Copper
as of June 25, 2013

Origin of the Novel Avian Influenza A H7N9 Virus.
Morens DM et al. N Engl J Med 2013;368:2345-2348.
Case-control study of risk factors for human infection with
influenza A(H7N9) virus in Jiangsu Province, China, 2013
Risk Factor for Human infection A(H7N9)
Eurosurveillance, Volume 18, Issue 26, 27 June 2013
Infection Control
beyond Earth
Infection Prevention and Control During Prolonged Human Space Travel
Countermeasures during spaceflight
Compliance
check in outer
space
Mermel .L.Clin Infect Dis. 2013 Jan;56(1):123-30

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