Findings of the International Nosocomial Infection Control Consortium (INICC), Part III Effectiveness of a Multidimensional Infection Control Approach to Reduce Central Line—Associated Bloodstream Infections in the Neonatal Intensive Care Units of 4 Developing Countries

Abstract

Objective
To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection control approach to reduce central line-associated bloodstream infection (CLABSI) rates.

Setting
Four neonatal intensive care units (NICUs) of INICC member hospitals from El Salvador, Mexico, Philippines, and Tunisia.

Patients
A total of 2,241 patients hospitalized in 4 NICUs for 40,045 bed-days.

Methods
We conducted a before-after prospective surveillance study. During Phase 1 we performed active surveillance, and during phase 2 the INICC multidimensional infection control approach was implemented, including the following practices: (1) central line care bundle, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback of CLABSI rates, and (6) performance feedback of infection control practices. We compared CLABSI rates obtained during the 2 phases. We calculated crude stratified rates, and, using random-effects Poisson regression to allow for clustering by ICU, we calculated the incidence rate ratio (IRR) for each follow-up time period compared with the 3-month baseline.

Results
During phase 1 we recorded 2,105 CL-days, and during phase 2 we recorded 17,117 CL-days. After implementation of the multidimensional approach, the CLABSI rate decreased by 55%, from 21.4 per 1,000 CL-days during phase 1 to 9.7 per 1,000 CL-days during phase 2 (rate ratio, 0.45 [95% confidence interval, 0.33–0.63]). The IRR was 0.53 during the 4–12-month period and 0.07 during the final period of the study (more than 45 months).

Conclusions
Implementation of a multidimensional infection control approach was associated with a significant reduction in CLABSI rates in NICUs.

Full text

infection control and hospital epidem iology march 2013, vol. 34, no. 3
Tuesday Jan 08 2013 10:33 AM/ICHE32745/2013/34/3/sgardiner/pmilne/pmilne//ms review complete/1002/use-graphics/narrow/default/
original article
Findings of the International Nosocomial Infection Control
Consortium (INICC), Part III: Effectiveness of a Multidimensional
Infection Control Approach to Reduce Central Line–Associated
Bloodstream Infections in the Neonatal Intensive Care
Units of 4 Developing Countries
Victor Daniel Rosenthal, MD;
1
Lourdes Duen˜as, MD;
2
Martha Sobreyra-Oropeza, MD;
3
Khaldi Ammar, MD;
4
Josephine Anne Navoa-Ng, MD;
5
Ana Concepcio´n Bran de Casares, RN;
2
Lilian de Jesu´ s Machuca, RN;
2
Nejla Ben-Jaballah, MD;
4
Asma Hamdi, MD;
4
Victoria D. Villanueva, RN;
5
Marı´a Corazon V. Tolentino, RN
5
control approach to reduce central line–associated bloodstream infection (CLABSI) rates.
setting. Four neonatal intensive care units (NICUs) of INICC member hospitals from El Salvador, Mexico, Philippines, and Tunisia.
patients. A total of 2,241 patients hospitalized in 4 NICUs for 40,045 bed-days.
methods. We conducted a before-after prospective surveillance study. During Phase 1 we performed active surveillance, and during
phase 2 the INICC multidimensional infection control approach was implemented, including the following practices: (1) central line care
bundle, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback of CLABSI rates, and (6) performance feedback of
infection control practices. We compared CLABSI rates obtained during the 2 phases. We calculated crude stratified rates, and, using
random-effects Poisson regression to allow for clustering by ICU, we calculated the incidence rate ratio (IRR) for each follow-up time
period compared with the 3-month baseline.
results. During phase 1 we recorded 2,105 CL-days, and during phase 2 we recorded 17,117 CL-days. After implementation of the
multidimensional approach, the CLABSI rate decreased by 55%, from 21.4 per 1,000 CL-days during phase 1 to 9.7 per 1,000 CL-days
during phase 2 (rate ratio, 0.45 [95% confidence interval, 0.33–0.63]). The IRR was 0.53 during the 4–12-month period and 0.07 during
the final period of the study (more than 45 months).
conclusions. Implementation of a multidimensional infection control approach was associated with a significant reduction in CLABSI
rates in NICUs.
Infect Control Hosp Epidemiol 2013;34(3):000-000
Affiliations: 1. International Nosocomial Infection Control Consortium, Buenos Aires, Argentina; 2. Hospital Nacional de Nin˜os Benjamin Bloom, San
Salvador, El Salvador; 3. Hospital de la Mujer, Mexico City, Mexico; 4. Hoˆpital d’Enfants, Tunis, Tunisia; 5. St. Luke’s Medical Center, Quezon City,
Philippines.
Received November 17, 2011; accepted October 6, 2012; electronically published January XX, 2013.
䉷2013 by The Society for Healthcare Epidemiology of America. All rights reserved. 0899-823X/2013/3403-00XX$15.00. DOI: 10.1086/669511
Central line–associated bloodstream infections (CLABSIs) have
long been associated with excess lengths of stay, increased hos-
pital costs, and increased attributable mortality in studies from
developed countries
1-5
and, more recently, from the developing
world.
6-19
Several studies have highlighted the extreme vulner-
ability of neonates hospitalized in neonatal intensive care units
(NICUs) to attributable mortality due to device-associated
healthcare-associated infections (DA-HAI) in developed coun-
tries, with rates ranging from 24% in the presurfactant era to
11% in the postsurfactant era.
5,20-22
The burden of CLABSIs in
the NICU is not limited to mortality, and studies have found
associations between newborn sepsis and adverse consequences
in the central nervous system, longer duration of mechanical
ventilation, and higher incidence of hepatic fibrosis and chronic
lung disease.
22-26
This serious threat to the safety of newborns
hospitalized in NICUs has been addressed in a wide number
of studies, most from high-income settings, in which it was
shown that implementation of infection control programs and
practice bundles—including hand hygiene, maximal barriers,
skin antisepsis, and timely central line (CL) removal, among
objective. To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional infection

2 infection control and hospital epidemiolo gy march 2013, vol. 34, no. 3
Tuesday Jan 08 2013 10:33 AM/ICHE32745/2013/34/3/sgardiner/pmilne/pmilne//ms review complete/1002/use-graphics/narrow/default/
table 1. Characteristics of Participating Hospitals
NICUs NICU patients Period
Country
Mexico 1 563 Oct 2003–June 2005
Philippines 1 217 Jan 2006–Dec 2009
Salvador 1 1,270 Jan 2007–Aug 2009
Tunisia 1 191 Oct 2008–May 2009
Type of hospital
Academic teaching 3 (75) 1,678 ...
Public hospital 1 (25) 563 ...
note. Data are no. or no. (%). NICU, neonatal intensive care unit.
others—were associated with a reduction in the incidence den-
sity of CLABSIs.
2,27-28
The rates determined with implementation of the INICC
Surveillance Program showed that the CLABSI incidence den-
sity is high in NICUs of developing countries. To progress
beyond these findings, we implemented a multidimensional
infection control approach that included practice bundles for
CLABSI prevention, education, outcome surveillance, process
surveillance, and feedback of CLABSI rates as well as per-
formance feedback of infection control practices. In this third
part of our study, we report an analysis of the specific impact
of this preventive strategy on CLABSI rates in NICUs of
developing countries.
methods
Setting and Study Design
The study was conducted in 4 NICUs in 4 INICC member
hospitals in 4 countries (El Salvador, Mexico, Philippines,
and Tunisia) on 3 continents (South America, Africa, and
Asia). The INICC surveillance methodology, including the
statistical methods used, has been fully described in Rosenthal
et al.
29
The study period was from October 2003 to December
2009 and was divided into 2 phases: phase 1 (baseline period;
first 3 months of participation of each NICU) and phase 2
(which included all the following months of participation of
each NICU). At each hospital there is a microbiology labo-
ratory to provide in vitro susceptibility testing of clinical iso-
lates by standardized methods, as described in US Centers
for Disease Control and Prevention (CDC)/National Health-
care Safety Network (NHSN) definitions. However, labora-
tory testing is uncommon and is frequently avoided in prac-
tice in these NICUs in developing countries.
30
Intervention Period (Phase 2)
The intervention period was initiated after 3 months of par-
ticipation in the INICC Surveillance Program. The average
length of the intervention period was 23.5 months (standard
deviation, 16.7; range, 5–48). The INICC multidimensional
infection control approach included the following items: (1)
bundle of infection control interventions, (2) education, (3)
outcome surveillance, (4) process surveillance, (5) feedback
of CLABSI rates, and (6) performance feedback of infection
control practices.
Components of CL Care Bundle for CLABSI
The bundle consisted of the following elements: (1) perfor-
mance of hand hygiene before CL insertion or manipula-
tion;
31
(2) use of an all-inclusive CL cart or kit;
32
(3) use of
maximal sterile barrier precautions during CL insertion;
33
(4)
presence of sterile dressing at insertion site;
34,35
(5) good con-
dition of sterile dressing at insertion site;
34,35
(6) disinfection
of catheter hubs, needleless connectors, and infection ports
before accessing the line;
36,37
and (7) removal of nonessential
CLs.
38,39
Education
Regarding education of healthcare personnel involved in the
insertion, care, and maintenance of CLs about CLABSI pre-
vention,
27
infection control practitioners received education
on the following practices: (a) performance of direct obser-
vation of hand hygiene compliance; (b) placement and con-
dition of sterile gauze or sterile polyurethane dressing on the
insertion site;
31,40
(c) gauze dressing replacement every 48 hours
and replacement of transparent semipermeable membrane
dressings at least every 7 days, with the recording of the date
and time of the dressing replacement; and (d) use of structured
observation tools at regularly scheduled intervals.
31,41
INICC Methodology
The INICC Surveillance Program included 2 components:
outcome surveillance (DA-HAI rates and their adverse effects,
including mortality rates) and process surveillance (adherence
to hand hygiene and other basic preventive infection control
practices).
42
Investigators were required to complete outcome
and process surveillance forms at their hospitals, which were
then sent for monthly analysis to the office of the INICC
headquarters in Buenos Aires.
Outcome Surveillance
Outcome surveillance was performed applying the definitions
for HAIs developed by the CDC for the NHSN program.
30
Additionally, INICC methods were adapted to the limited-

effectiveness of program to reduce clabsisin nicus3
Tuesday Jan 08 2013 10:33 AM/ICHE32745/2013/34/3/sgardiner/pmilne/pmilne//ms review complete/1002/use-graphics/narrow/default/
table 2. Characteristics of Patients Hospitalized in Neonatal Intensive Care
Units during Phase 1 (Baseline Period) and Phase 2 (Intervention Period)
Baseline Intervention P
No. of months 3 23.5
a
No. of patients 374 1,867
No. of bed-days 5,654 34,391
No. of CL-days 2,105 17,117
CL use ratio, mean (95% CI) 0.37 (0.19–0.21) 0.50 (0.49–0.50) .0001
CL duration, mean ⳲSD, days 5.63 Ⳳ12.0 9.18 Ⳳ20.2 .0001
Sex, no. (%)
Male 241 (64) 1,117 (60) .2587
Female 133 (36) 748 (40) .3983
Weight, mean ⳲSD, kg 2.37 Ⳳ0.87 2.31 Ⳳ0.84 .0001
note. CI, confidence interval; CL, central line; SD, standard deviation.
a
Range, 5–45; SD, 16.7.
resource setting of developing countries because of their dif-
ferent socioeconomic status.
42
Outcome surveillance included
rates of CLABSIs (cases per 1,000 CL-days), microorganism
profile, bacterial resistance, length of stay, and mortality in
NICUs.
42
CLABSI Rate Calculation
Outcomes measured during the surveillance period included
the incidence density rate of CLABSIs (cases per 1,000 CL-
days), which was calculated by dividing the total number of
CLABSIs by the total number of CL-days and multiplying
the result by 1,000.
42
INICC and CDC methodologies differ
in how CL-days are calculated. According to INICC meth-
odology, CL-days are calculated for each CL in situ, which
are counted separately when calculating the time at risk. By
contrast, according to CDC methodology CL-days are cal-
culated for each day a patient has 1 or more CLs in place.
That is, if CDC methodology is applied, a patient with 2 CLs
in situ for 1 day will contribute 1 day at risk, whereas if
INICC methodology is applied, the patient will contribute 2
CL-days. Occasionally, this can lead to a CL DU ratio of more
than 1 in ICUs where patients routinely have more than 1
CL in place.
Process Surveillance
Process surveillance was designed to assess compliance with
easily measurable key infection control practices, such as sur-
veillance of compliance rates for hand hygiene practices and
specific measures for the prevention of CLABSIs.
42
The hand
hygiene compliance rate was based on the frequency with
which hand hygiene was performed as indicated in healthcare
worker (HCW) infection control training. Observing infec-
tion control practitioners were trained to record hand hygiene
opportunities and compliance on a form during randomly
selected observation periods of 30 minutes to 1 hour 3 times
a week. In particular, the INICC direct observation comprised
the My 5 Moments for Hand Hygiene, as recommended by
the World Health Organization, which included monitoring
of the following moments: (1) before patient contact, (2)
before an aseptic task, (3) after body fluid exposure risk, (4)
after patient contact, and (5) after contact with patient sur-
roundings.
43
Although HCWs knew that hand hygiene prac-
tices were regularly monitored, they were not informed of
the schedule for hand hygiene observations.
CL care compliance was also monitored, and data on com-
pliance with CL care measures were recorded 5 days a week
on a form that evaluated whether infection control procedures
were correctly carried out by the HCW. The infection control
practitioner observing the activity in the NICU completed a
standardized form that contained the following data: total
number of inserted CLs for each patient for the whole ICU;
total number of dressings placed to protect the puncture site;
total number of dressings, specifying the type of dressing
(sterile gauze or transparent dressing) used to protect the
puncture site; total number of dressings in correct condition,
evaluating whether the dressing was clean, dry, and adhered
correctly to the puncture site; and total number of cases in
which the dates of insertion were written in the administra-
tion set of the patient or the dressing.
42
Feedback of DA-HAI Rates
Every month, the INICC research team at the INICC head-
quarters in Buenos Aires prepared and sent to each infection
control team (ICT) a final report on the results of outcome
surveillance data sent by investigators at each hospital—that
is, monthly DA-HAI rates, length of stay, bacterial profile and
resistance, and mortality.
42
Feedback of DA-HAI rates is pro-
vided to HCWs working in the NICU by communicating the
outcomes of patients. The resulting rates were reviewed by
the ICT at monthly meetings, where charts were analyzed.
Statistical graphs and visuals were displayed in prominent
locations inside the ICU to provide an overview of rates of
DA-HAIs. This infection control tool is important to increase
awareness about outcomes of patients at their ICU, to enable
the ICT and ICU staff to focus on the necessary issues, and

4 infection control and hospital epidemiolo gy march 2013, vol. 34, no. 3
Tuesday Jan 08 2013 10:33 AM/ICHE32745/2013/34/3/sgardiner/pmilne/pmilne//ms review complete/1002/use-graphics/narrow/default/
table 3. Hand Hygiene (HH) and Central Line (CL) Care Improvement during Phase 1 (Baseline
Period) and Phase 2 (Intervention Period)
Phase 1 Phase 2 RR (95% CI) P
No. of HH opportunities
All 669 2,262 ...
NICU A 121 318 ...
NICU B 505 1,090 ...
NICU C 43 854 ...
HH compliance, % (no.)
All 51.4 (344) 71.5 (1,618) 1.39 (1.24–1.56) .0001
NICU A 60.3 (73) 60.7 (193) 1.01 (0.77–1.32) .9653
NICU B 45.9 (232) 57.8 (630) 1.26 (1.08–1.46) .0027
NICU C 90.7 (39) 93.1 (795) 1.03 (0.74–1.42) .8738
No. of observed CL
All 2,009 20,031 ...
NICU A 1,632 18,652 ...
NICU B 325 787 ...
NICU C 52 592 ...
CL with sterile gauze, % (no.)
All 70.1 (1,409) 83.7 (16,771) 1.19 (1.13–1.26) .0001
NICU A 68.6 (1,120) 83.3 (15,545) 1.39 (1.31–1.48) .0001
NICU B 72.9 (237) 98.1 (772) 1.35 (1.16–1.56) .0001
NICU C 100.0 (52) 76.7 (454) 0.77 (0.58–1.02) .0690
CL with sterile gauze in good
condition, % (no.)
All 91.8 (1,845) 95.7 (19,176) 1.04 (0.99–1.09) .0883
NICU A 95.6 (1,561) 96.0 (17,902) 1.15 (1.09–1.21) .0001
NICU B 71.4 (232) 86.9 (684) 1.22 (1.05–1.41) .0094
NICU C 100.0 (52) 99.7 (590) 1.00 (0.75–1.32) .9813
note. CI, confidence interval; NICU, neonatal intensive care unit; RR, relative risk.
to apply specific strategies for improvement of high DA-HAI
rates.
Performance Feedback
Upon processing the hospitals’ process surveillance data on
a monthly basis, the INICC research team at the INICC head-
quarters in Buenos Aires prepares and sends to each ICT a
final report on the results of process surveillance rates, in-
cluding compliance with hand hygiene and care of CLs.
42
Performance feedback is provided to HCWs working in the
NICU by communicating the assessment of practices rou-
tinely performed by them. The resulting rates are reviewed
by the ICT at monthly meetings where charts are analyzed,
and statistical graphs and visuals are posted inside the ICU
to provide an overview of rates measuring compliance with
infection control practices. This infection control tool is key
to enable the ICT and ICU staff to focus on the necessary
strategies for improvement of low compliance rates.
Definitions
CLABSI is included in the following definitions.
Laboratory-confirmed CLABSI. When CLABSI is sus-
pected, the CL is removed aseptically and the distal 5 cm of
the catheter is amputated and cultured, using the standardized
semiquantitative method.
44
Concomitant blood cultures are
drawn percutaneously in most cases. In each hospital, stan-
dard laboratory methods are used to identify microorganisms,
and standardized susceptibility testing is performed.
A patient with a CL in place is considered to have a CLABSI
when a recognized pathogen is isolated from 1 or more per-
cutaneous blood cultures after 48 hours of catheterization,
the pathogen cultured from the blood is not related to an
infection at another site, and the patient has 1 or more of
the following signs or symptoms: fever (temperature of 38⬚C
or higher), chills, or hypotension. With skin commensals
(diphtheroids, Bacillus species, Propionibacterium species,
coagulase-negative staphylococci, or micrococci), the organism
must be recovered from 2 or more separate blood cultures.
30
Clinically suspected CLABSI. When either blood cultures
are not obtained or no organisms are recovered from blood
cultures, there is no apparent infection at another site, and
the physician institutes antimicrobial therapy, a patient with
a CL in place who has at least 1 of the following clinical signs
with no other recognized cause was considered to have clin-
ically suspected CL-associated bloodstream infection: fever
(temperature of 38⬚C or higher), hypotension (systolic blood
pressure of 90 mm Hg or lower), or oliguria (20 mL/hour
or lower).
45

effectiveness of program to reduce clabsisin nicus5
Tuesday Jan 08 2013 10:33 AM/ICHE32745/2013/34/3/sgardiner/pmilne/pmilne//ms review complete/1002/use-graphics/narrow/default/
table 4. Central Line (CL)–Associated Bloodstream Infection (CLABSI) Rates among
Patients Hospitalized in Neonatal Intensive Care Units (NICUs) during Phase 1 (Baseline
Period) and Phase 2 (Intervention Period)
Phase 1 Phase 2 RR (95% CI) P
No. of CLABSIs
All 45 166 ...
NICU A 21 136 ...
NICU B 19 23 ...
NICU C 1 4 ...
NICU D 4 3 ...
No. of CL-days
All 2,105 17,117 ...
NICU A 1,473 14,346 ...
NICU B 399 1,663 ...
NICU C 37 585 ...
NICU D 196 523 ...
CLABSI rate, cases per 1,000 CL-days
All 21.4 9.7 0.45 (0.33–0.63) .0001
NICU A 14.3 9.5 0.66 (0.42–1.05) .0797
NICU B 47.6 13.8 0.29 (0.16–0.53) .0001
NICU C 27.0 6.8 0.25 (0.03–2.26) .1840
NICU D 20.4 5.7 0.28 (0.06–1.26) .0758
note. CI, confidence interval; RR, rate ratio.
Statistical Methods
Patient characteristics during the baseline and intervention
periods in each NICU were compared using the Fisher exact
test for dichotomous variables and the unmatched Student t
test for continuous variables. VCStat (Castiglia) was used to
calculate 95% confidence intervals (CIs). Relative risk (RR)
ratios with 95% CIs were calculated for comparisons of rates
of CLABSIs using Epi Info, version 6 (CDC). Differences with
Pvalues less than .05 by 2-sided tests were considered sig-
nificant. Furthermore, we explored the change in CLABSI
rates following an ICU joining the INICC by looking at the
follow-up period stratified by 3-month periods over the first
year, 6-month periods over the second and third years, and
then yearly afterward (to somewhat allow for fewer subjects
in ICUs with longer periods of follow-up). We calculated
crude stratified rates, and, using random-effects Poisson re-
gression to allow for clustering by ICU, we calculated the
incidence rate ratio (IRR) for each follow-up time period
compared with the baseline 3 months. Device-days were in-
cluded in the model as an offset with the coefficient con-
strained to be 0 (patients with no device use during admission
were excluded from these analyses). We performed an ad-
ditional regression considering “time since ICU joined
INICC” as a continuous variable in months and calculated
the IRR for reduction in HAIs for each month of follow-up.
Ethics
Every hospital’s institutional review board agreed to the study
protocol, and patient confidentiality was protected by codi-
fying the recorded information, making it identifiable only
to the ICT.
results
Over the whole study period, 2,241 patients hospitalized for
40,045 bed-days in 4 NICUs were enrolled, for a total of
19,222 CL-days. The first NICUs to participate in the study
began collecting data in October 2003, and the latest data
included in this analysis are from December 2009.
The participating hospitals were summarized and classified
according to number of NICUs, number of NICU patients
per hospital, type of hospital, and country. Most of the pa-
tients enrolled were from academic teaching hospitals (75%).
All participating hospitals were from developing countries
(Table 1).
Sex of patients was similar during the baseline and inter-
vention phases. However, we observed a decrease in the pa-
tients’ weight mean during phase 2 (from 2.37 to 2.31 kg;
). We documented 2,105 CL-days, for a CL use meanPp.001
of 0.37, during the baseline period and 17,117 CL-days, for
a CL use mean of 0.50, during the intervention period (Table
2).
Regarding compliance rates, during this study we were not
able to measure hand hygiene compliance and CL compliance
of 1 of the participating NICUs. At the remaining 3 NICUs,
hand hygiene compliance improved significantly, from 51.4%
to 71.5%. Likewise, the presence of catheters with sterile gauze
or sterile transparent dressing rose from 70.1% to 83.7% (RR,
1.19 [95% CI, 1.13–1.26]; ; Table 3).Pp.0001
Regarding CLABSI rates, during phase 1 (baseline period)
there were 45 CLABSIs, for an overall baseline rate of 21.4
per 1,000 CL-days. During phase 2, after implementation of
the multidimensional infection control approach, there were
166 CLABSIs, for an incidence density of 9.7 per 1,000 CL-

6 infection control and hospital epidemiolo gy march 2013, vol. 34, no. 3
Tuesday Jan 08 2013 10:33 AM/ICHE32745/2013/34/3/sgardiner/pmilne/pmilne//ms review complete/1002/use-graphics/narrow/default/
table 5. Central Line (CL)–Associated Bloodstream Infection (CLABSI) Stratified by the Length of Time That Each
Unit Has Participated in the International Nosocomial Infection Control Consortium (INICC)
ICUs CL-days CLABSIs
Crude CLABSI rate,
cases per 1,000 CL-days
IRR (95% CI) accounting
for clustering by ICU
Months since joining INICC
0–3 (baseline) 4 2,105 46 21.8 ...
4–12 4 6,514 72 11.1 0.53 (0.36–0.78)
13–23 2 7,445 73 9.8 0.46 (0.31–0.68)
24–35 2 2,692 19 7.1 0.43 (0.23–0.81)
36–48 1 466 1 2.1 0.07 (0.01–1.26)
a
Time since joining INICC in
months, per month 0.96 (0.95–0.98)
b
note. Shown are crude stratified rates determined using random-effects Poisson regression. IRR, incidence rate ratio.
a
.Pp.07
b
.Pp.001
figure 1. Evolution of central line–associated bloodstream infec-
tion rates in each neonatal intensive care unit (NICU).
days. These results showed a CLABSI rate reduction from
baseline of 54% (from 21.4 to 9.7 CLABSIs per 1,000 CL-
days; RR, 0.45 [95% CI, 0.33–0.63]; Table 4).
The stratified rates and rate ratios demonstrate a steadily
reducing trend in CLABSI rates as the time the ICU has
participated in the INICC increases (although data in the
final time period is quite sparse; Table 5 and Figure 1).
Regarding the microorganism profile, during phase 1 co-
agulase-negative staphylococci was the most frequently isolated
microorganism (28.6%). During phase 2 we observed wide
variation in the leading pathogens, which were coagulase-neg-
ative staphylococci (25%) and Enterobacter species (25%). The
percentage of coagulase-negative staphylococci did not change
significantly during phase 2 ( ; Table 6).Pp.8936
discussion
The analysis of our surveillance data during baseline showed
a high incidence density of CLABSIs in our NICUs, which
was reduced by 55% after implementation of the multi-
dimensional interventions. All the NICUs enrolled in this
study are from countries with lower-middle-income and
upper-middle-income economies,
46
whose DA-HAI rates
have been reported to be negatively influenced by their lim-
ited financial and personnel resources compared with those
of hospitals in developed economies.
19
Patient characteristics, such as sex, remained similar during
the whole study period; however, during phase 2 we observed
that the mean weight of patients had decreased. This differ-
ence in patients’ mean weight reinforces the fact that the
interventions were effective, because lower weight in neonatal
patients has been identified as a risk factor for CLABSI.
5,47
We found statistically significant improvements in hand
hygiene compliance and CL care, particularly in relation to
the presence and condition of catheters with sterile gauze or
sterile transparent dressing. Similarly, it was shown in a study
conducted in NICUs in Senegal that a multidimensional hos-
pital infection control program—which included clustering
of nursing care, minimal invasive care, and promotion of
early discharge of neonates, among other interventions—was
an effective tool in reducing CLABSIs in NICUs of developing
countries.
48
Additionally, we observed an increase in mean CL use,
which also strengthens our association between improved in-
fection control practices and reduction in CLABSI rate, be-
cause increased use of lines increases the risk that there will
be more infections.
49
In a prospective cohort study by Mahieu
et al,
49
it was demonstrated that catheter manipulations—
particularly disconnection of the central venous catheter,
which requires disinfection of the catheter hub—increased
the risk of CLABSIs in neonates.
Our multidimensional infection control approach was fo-
cused on CLABSI outcome and process surveillance, perfor-
mance feedback, education, adherence to infection control
guidelines, and implementation of a bundle of CL care tech-
niques, which were adopted as a comprehensive but simple
and feasible bundle for limited-resource settings. Over recent

effectiveness of program to reduce clabsisin nicus7
Tuesday Jan 08 2013 10:33 AM/ICHE32745/2013/34/3/sgardiner/pmilne/pmilne//ms review complete/1002/use-graphics/narrow/default/
table 6. Microorganisms Related to Central Line–Associated Bloodstream Infec-
tions in Neonatal Intensive Care Units during Phase 1 (Baseline Period) and Phase
2 (Intervention Period)
Isolated microorganism Phase 1 Phase 2 RR (95% CI) P
Acinetobacter species 14.3 (1) 12.5 (1) 0.88 (0.05–13.9) .9247
Candida species 0.0 (0) 12.5 (1) ... .3495
Escherichia coli 14.3 (1) 12.5 (1) 0.88 (0.05–13.9) .9247
Enterobacter species 14.3 (1) 25.0 (2) 1.75 (0.16–19.30) .6434
Klebsiella species 14.3 (1) 0.0 (0) ... .2850
Staphylococcus aureus 14.3 (1) 0.0 (0) ... .2850
Coagulase-negative staphylococci 28.6 (2) 25.0 (2) 0.88 (0.12–6.21) .8936
Serratia species 0.0 (0) 12.5 (1) ... .3495
note. Data are % (no.). CI, confidence interval; RR, rate ratio.
decades, different successful strategies to reduce CLABSIs
have been described in the literature,
2,41,50
and in studies per-
formed in the United States it has been shown that a 40%
reduction in CLABSI incidence is feasible.
51-53
In a study con-
ducted by the INICC in 15 developing countries, it was shown
that after the inception of a strategy that included education,
performance feedback, and outcome and process surveillance,
there was a cumulative reduction of 54% in the CLABSI rate
and of 58% in the mortality rate.
54
Study Limitations
Although this study’s weakness stems from the fact that its
results cannot be generalized to all NICU patients in devel-
oping countries, the strength of the study is that it proved
that a multidimensional approach, including process and out-
come surveillance with a bundle of interventions, is a fun-
damental tool to understand and fight against the adverse
effects of CLABSIs in the NICUs of limited-resource settings.
During this study, we were not able to measure hand hygiene
compliance and CL compliance of 1 of the participating
NICUs. Additionally, we did not measure compliance with
all bundle components, and as of January 2012 the INICC
multidimensional approach includes the measurement of ev-
ery element of the bundle.
Conclusions
Implementation of the multidimensional infection control
program for CLABSI prevention showed that the CLABSI rate
reduction in our NICUs was related to the effectiveness of
our multidimensional strategy. Recognition of CLABSI as a
preventable DA-HAI is fundamental to motivating HCWs
and effecting cultural changes. However, we consider our
rates to also reveal opportunities for improvement, as they
are still higher than those in the developed world.
55,56
We expect that the multidimensional infection control and
prevention approach fostered by the INICC will increasingly
be carried out in the developing world and will successfully
achieve reductions in DA-HAI rates. The INICC provides
investigators with free training and methodological tools to
perform outcome and process surveillance, and the publi-
cation of the data confidentially collected in the INICC pro-
gram allows for boosting relevant scientific literature for
developing countries. For these reasons, every hospital world-
wide is invited to join the INICC network, which was estab-
lished to respond to the burden of DA-HAIs in limited-
resource countries.
acknowledgments
We thank the many healthcare professionals at each member hospital who
assisted with the conduct of surveillance in their hospital, including the
surveillance nurses, the clinical microbiology laboratory personnel, and the
physicians and nurses providing care for the patients during the study; with-
out their cooperation and generous assistance, the International Nosocomial
Infection Control Consortium (INICC) would not be possible. We also thank
Mariano Vilar, De´bora Lo´ pez Burgardt, Santiago Sua´rez, Denise Brito, Julieta
Sayar, Eugenia Manfredi, Luciana Soken, Dario Pizzuto, Ding Yuan, and
Isaac Kelmeszes, who work at the INICC headquarters in Buenos Aires, for
their hard work and commitment to achieving INICC goals; the INICC
country coordinators (Altaf Ahmed, Carlos A. A
´lvarez-Moreno, Anucha
Apisarnthanarak, Luis E. Cue´llar, Bijie Hu, Namita Jaggi, Hakan Leblebi-
cioglu, Eduardo A. Medeiros, Yatin Mehta, Toshihiro Mitsuda, and Lul Raka);
the INICC Advisory Board (Carla J. Alvarado, Nicholas Graves, William R.
Jarvis, Patricia Lynch, Dennis Maki, Cat Murphy, Russell N. Olmsted, Didier
Pittet, Wing Hong Seto, Syed Sattar, and William Rutala), who have so
generously supported this unique international infection control network;
and especially Patricia Lynch, who inspired us to follow our dreams despite
obstacles.
Financial support. Funding for the activities carried out at the INICC
headquarters were provided by the corresponding author (V.D.R.) and the
Foundation to Fight against Nosocomial Infections.
Potential conflicts of interest. All authors report no conflicts of interest
relevant to this article. All authors submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest, and the conflicts that the editors consider
relevant to this article are disclosed here.
Address correspondence to Victor Daniel Rosenthal, MD, Corrientes Av-
enue No. 4580, Floor 12, Apt. D, Buenos Aires 1195, Argentina (victor
_rosenthal@inicc.org).
references
1. Marschall J, Mermel LA, Classen D, et al. Strategies to prevent
central line–associated bloodstream infections in acute care hos-
pitals. Infect Control Hosp Epidemiol 2008;29(suppl 1):S22–S30.

8 infection control and hospital epidemiol ogy march 2013, vol. 34, no. 3
Tuesday Jan 08 2013 10:33 AM/ICHE32745/2013/34/3/sgardiner/pmilne/pmilne//ms review complete/1002/use-graphics/narrow/default/
2. Pronovost P, Needham D, Berenholtz S, et al. An intervention
to decrease catheter-related bloodstream infections in the ICU.
N Engl J Med 2006;355(26):2725–2732.
3. Digiovine B, Chenoweth C, Watts C, Higgins M. The attributable
mortality and costs of primary nosocomial bloodstream infec-
tions in the intensive care unit. Am J Respir Crit Care Med 1999;
160(3):976–981.
4. Warren DK, Quadir WW, Hollenbeak CS, Elward AM, Cox MJ,
Fraser VJ. Attributable cost of catheter-associated bloodstream
infections among intensive care patients in a nonteaching hos-
pital. Crit Care Med 2006;34(8):2084–2089.
5. Powers RJ, Wirtschafter DW. Decreasing central line associated
bloodstream infection in neonatal intensive care. Clin Perinatol
2010;37(1):247–272.
6. Barnett AG, Beyersmann J, Allignol A, Rosenthal VD, Graves
N, Wolkewitz M. The time-dependent bias and its effect on extra
length of stay due to nosocomial infection. Value Health 2011;
14(2):381–386.
7. Higuera F, Rangel-Frausto MS, Rosenthal VD, et al. Attributable
cost and length of stay for patients with central venous catheter–
associated bloodstream infection in Mexico City intensive care
units: a prospective, matched analysis. Infect Control Hosp Ep-
idemiol 2007;28(1):31–35.
8. Rosenthal VD, Guzman S, Migone O, Crnich CJ. The attrib-
utable cost, length of hospital stay, and mortality of central line–
associated bloodstream infection in intensive care departments
in Argentina: a prospective, matched analysis. Am J Infect Control
2003;31(8):475–480.
9. Rosenthal VD, Guzman S, Migone O, Safdar N. The attributable
cost and length of hospital stay because of nosocomial pneu-
monia in intensive care units in 3 hospitals in Argentina: a
prospective, matched analysis. Am J Infect Control 2005;33(3):
157–161.
10. Rosenthal VD, Udwadia FE, Mun˜oz HJ, et al. Time-dependent
analysis of extra length of stay and mortality due to ventilator-
associated pneumonia in intensive-care units of ten limited-
resources countries: findings of the International Nosocomial
Infection Control Consortium (INICC). Epidemiol Infect 2011;
139(11):1757–1763.
11. Rosenthal VD, Dwivedy A, Calderon ME, et al. Time-dependent
analysis of length of stay and mortality due to urinary tract
infections in ten developing countries: INICC findings. J Infect
2011;62(2):136–141.
12. Barnett AG, Graves N, Rosenthal VD, Salomao R, Rangel-
Frausto MS. Excess length of stay due to central line–associated
bloodstream infection in intensive care units in Argentina, Bra-
zil, and Mexico. Infect Control Hosp Epidemiol 2010;31(11):
1106–1114.
13. Ramirez Barba EJ, Rosenthal VD, Higuera F, et al. Device-
associated nosocomial infection rates in intensive care units in
four Mexican public hospitals. Am J Infect Control 2006;34(4):
244–247.
14. Rosenthal VD. Device-associated nosocomial infections in lim-
ited-resources countries: findings of the International Nosoco-
mial Infection Control Consortium (INICC). Am J Infect Control
2008;36(10):S171.e7–S171.e12.
15. Rosenthal VD, Guzman S, Orellano PW. Nosocomial infections
in medical-surgical intensive care units in Argentina: attributable
mortality and length of stay. Am J Infect Control 2003;31(5):
291–295.
16. Tarricone R, Torbica A, Franzetti F, Rosenthal VD. Hospital costs
of central line–associated bloodstream infections and cost-
effectiveness of closed vs. open infusion containers: the case of
intensive care units in Italy. Cost Eff Resour Alloc 2010;8:8.
17. Moreno CA, Rosenthal VD, Olarte N, et al. Device-associated
infection rate and mortality in intensive care units of 9 Colom-
bian hospitals: findings of the International Nosocomial Infec-
tion Control Consortium. Infect Control Hosp Epidemiol 2006;
27(4):349–356.
18. Rosenthal VD, Guzman S, Crnich C. Device-associated noso-
comial infection rates in intensive care units of Argentina. Infect
Control Hosp Epidemiol 2004;25(3):251–255.
19. Rosenthal VD, Lynch P, Jarvis WR, et al. Socioeconomic impact
on device-associated infections in limited-resource neonatal in-
tensive care units: findings of the INICC. Infection 2011;39(5):
439–450.
20. Townsend TR, Wenzel RP. Nosocomial bloodstream infections
in a newborn intensive care unit: a case-matched control study
of morbidity, mortality and risk. Am J Epidemiol 1981;114(1):
73–80.
21. Pessoa-Silva CL, Miyasaki CH, de Almeida MF, Kopelman BI,
Raggio RL, Wey SB. Neonatal late-onset bloodstream infection:
attributable mortality, excess of length of stay and risk factors.
Eur J Epidemiol 2001;17(8):715–720.
22. Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very
low birth weight neonates: the experience of the NICHD Neo-
natal Research Network. Pediatrics 2002;110(2 pt 1):285–291.
23. Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neurodevelop-
mental and growth impairment among extremely low-birth-
weight infants with neonatal infection. JAMA 2004;292(19):
2357–2365.
24. Shah DK, Doyle LW, Anderson PJ, et al. Adverse neurodevel-
opment in preterm infants with postnatal sepsis or necrotizing
enterocolitis is mediated by white matter abnormalities on mag-
netic resonance imaging at term. J Pediatr 2008;153(2):170–175,
175.e1.
25. Lahra MM, Beeby PJ, Jeffery HE. Intrauterine inflammation,
neonatal sepsis, and chronic lung disease: a 13-year hospital
cohort study. Pediatrics 2009;123(5):1314–1319.
26. Hermans D, Talbotec C, Lacaille F, Goulet O, Ricour C, Colomb
V. Early central catheter infections may contribute to hepatic
fibrosis in children receiving long-term parenteral nutrition. J
Pediatr Gastroenterol Nutr 2007;44(4):459–463.
27. Eggimann P, Harbarth S, Constantin MN, Touveneau S, Chev-
rolet JC, Pittet D. Impact of a prevention strategy targeted at
vascular-access care on incidence of infections acquired in in-
tensive care. Lancet 2000;355(9218):1864–1868.
28. Apisarnthanarak A, Thongphubeth K, Yuekyen C, Warren DK,
Fraser VJ. Effectiveness of a catheter-associated bloodstream in-
fection bundle in a Thai tertiary care center: a 3-year study. Am
J Infect Control 2010;38(6):449–455.
29. Rosenthal VD, Ramachandran B, Duen˜as L. Findings of the
International Nosocomial Infection Control Consortium
(INICC), part I: effectiveness of a multidimensional infection
control approach on catheter-associated urinary tract infection
rates in pediatric intensive care units of 6 developing countries.
Infect Control Hosp Epidemiol 2012;33(7):696–703.
30. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance
definition of health care–associated infection and criteria for

effectiveness of program to reduce clabsisin nicus9
Tuesday Jan 08 2013 10:33 AM/ICHE32745/2013/34/3/sgardiner/pmilne/pmilne//ms review complete/1002/use-graphics/narrow/default/
specific types of infections in the acute care setting. Am J Infect
Control 2008;36(5):309–332.
31. Rosenthal VD, Guzman S, Safdar N. Reduction in nosocomial
infection with improved hand hygiene in intensive care units of
a tertiary care hospital in Argentina. Am J Infect Control 2005;
33(7):392–397.
32. Berenholtz SM, Pronovost PJ, Lipsett PA, et al. Eliminating cath-
eter-related bloodstream infections in the intensive care unit.
Crit Care Med 2004;32(10):2014–2020.
33. Raad II, Hohn DC, Gilbreath BJ, et al. Prevention of central
venous catheter–related infections by using maximal sterile bar-
rier precautions during insertion. Infect Control Hosp Epidemiol
1994;15(4 pt 1):231–238.
34. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the
prevention of intravascular catheter-related infections. Clin In-
fect Dis 2011;52(9):e162–e193.
35. Pratt RJ, Pellowe CM, Wilson JA, et al. epic2: national evidence-
based guidelines for preventing healthcare-associated infections
in NHS hospitals in England. J Hosp Infect 2007;65(suppl 1):
S1–S64.
36. Casey AL, Worthington T, Lambert PA, Quinn D, Faroqui MH,
Elliott TS. A randomized, prospective clinical trial to assess the
potential infection risk associated with the PosiFlow needleless
connector. J Hosp Infect 2003;54(4):288–293.
37. Luebke MA, Arduino MJ, Duda DL, et al. Comparison of the
microbial barrier properties of a needleless and a conventional
needle-based intravenous access system. Am J Infect Control
1998;26(4):437–441.
38. Parenti CM, Lederle FA, Impola CL, Peterson LR. Reduction of
unnecessary intravenous catheter use: internal medicine house
staff participate in a successful quality improvement project.
Arch Intern Med 1994;154(16):1829–1832.
39. Lederle FA, Parenti CM, Berskow LC, Ellingson KJ. The idle
intravenous catheter. Ann Intern Med 1992;116(9):737–738.
40. O’Grady NP, Alexander M, Burns LA, et al. Guidelines for the
prevention of intravascular catheter-related infections. Am J In-
fect Control 2011;39(4 suppl 1):S1–S34.
41. Royer T. Implementing a better bundle to achieve and sustain
a zero central line–associated bloodstream infection rate. J Infus
Nurs 2010;33(6):398–406.
42. Rosenthal VD, Maki DG, Graves N. The International Noso-
comial Infection Control Consortium (INICC): goals and ob-
jectives, description of surveillance methods, and operational
activities. Am J Infect Control 2008;36(9):e1–e12.
43. Sax H, Allegranzi B, Chraiti MN, Boyce J, Larson E, Pittet D.
The World Health Organization hand hygiene observation
method. Am J Infect Control 2009;37(10):827–834.
44. Maki DG, Weise CE, Sarafin HW. A semiquantitative culture
method for identifying intravenous-catheter-related infection.
N Engl J Med 1977;296(23):1305–1309.
45. Emori TG, Culver DH, Horan TC, et al. National nosocomial
infections surveillance system (NNIS): description of surveil-
lance methods. Am J Infect Control 1991;19(1):19–35.
46. World Bank classification of economies. World Bank web-
site. http://web.worldbank.org/WBSITE/EXTERNAL/DATA
STATISTICS/0 ,,contentMDK:20421402∼pagePK:64133150
∼piPK:64133175∼theSitePK:239419,00.html. Published 2007.
Accessed October 5, 2008.
47. Tseng YC, Chiu YC, Wang JH, Lin HC, Su BH, Chiu HH.
Nosocomial bloodstream infection in a neonatal intensive care
unit of a medical center: a three-year review. J Microbiol Im-
munol Infect 2002;35(3):168–172.
48. Landre-Peigne C, Ka AS, Peigne V, Bougere J, Seye MN, Imbert
P. Efficacy of an infection control programme in reducing nos-
ocomial bloodstream infections in a Senegalese neonatal unit.
J Hosp Infect 2011;79(2):161–165.
49. Mahieu LM, De Dooy JJ, Lenaerts AE, Ieven MM, De Muynck
AO. Catheter manipulations and the risk of catheter-associated
bloodstream infection in neonatal intensive care unit patients.
J Hosp Infect 2001;48(1):20–26.
50. Pronovost PJ, Marsteller JA, Goeschel CA. Preventing blood-
stream infections: a measurable national success story in quality
improvement. Health Aff (Millwood) 2011;30(4):628–634.
51. Schulman J, Stricof R, Stevens TP, et al. Statewide NICU central-
line-associated bloodstream infection rates decline after bundles
and checklists. Pediatrics 2011;127(3):436–444.
52. Haley RW, Quade D, Freeman HE, Bennett JV. The SENIC
Project: study on the efficacy of nosocomial infection control
(SENIC Project): summary of study design. Am J Epidemiol
1980;111(5):472–485.
53. Hughes JM. Study on the efficacy of nosocomial infection con-
trol (SENIC Project): results and implications for the future.
Chemotherapy 1988;34(6):553–561.
54. Rosenthal VD, Maki DG, Rodrigues C, et al. Impact of Inter-
national Nosocomial Infection Control Consortium (INICC)
strategy on central line–associated bloodstream infection rates
in the intensive care units of 15 developing countries. Infect
Control Hosp Epidemiol 2010;31(12):1264–1272.
55. Edwards JR, Peterson KD, Mu Y, et al. National Healthcare
Safety Network (NHSN) report: data summary for 2006 through
2008, issued December 2009. Am J Infect Control 2009;37(10):
783–805.
56. Rosenthal VD, Jarvis WR, Jamulitrat S, et al. Socioeconomic
impact on device-associated infections in pediatric intensive care
units of 16 limited-resource countries: InternationalNosocomial
Infection Control Consortium findings. Pediatr Crit Care Med
2012;13(4):399–406.