RESEARCH PAPER

PICC Line Associated Blood Stream Infections:
an Analysis of Host and Device Factors

Turki Alkully a Sandra Hensley b Sadik Khuder c Naveena Luke d Mohammed Ruzieh e and Joan Duggan1 , f

Coresponding author(s): 1 joan.duggan@utoledo.edu

aDepartment of Gastroenterology, University of Toledo Medical Center, Toledo, OH 43614, USA,,bDivision of Infectious Diseases, University of Toledo Medical Center,
Toledo OH 43614, USA,,cDepartments of Medicine and Public Health, University of Toledo Medical Center, Toledo OH 43614, USA,,dDepartment of Physiology and
Pharmacology , University of Toledo Medical Center, Toledo OH 43614, USA,,eDepartment of Internal Medicine, University of Toledo Medical Center, Toledo OH
43614, USA,, and f Department of Medicine, University of Toledo Medical Center, Toledo OH 43614, USA.

Background: Risk factors for PICC CLABSI (peripherally inserted
central venous catheter/ central line associated bloodstream in-
fections) have been evaluated in a limited number of prospective
and retrospective studies with conflicting results. Methods: A
six year retrospective review of PICC CLABSI within a single
institution was performed. PICC CLABSI cases were matched
to uninfected controls and host and device data were extracted
from comprehensive medical record reviews. A statistical anal-
ysis of PICC CLABSI risk factors compared to matched con-
trols was performed. Results: 6756 patients had a PICC line
placed during the study period (January 1, 2008 - December 31,
2013). Fifty-six (0.83%) CLABSI were identified and matched to
245 uninfected controls. Factors associated with PICC CLABSI
included: sepsis (P<0.0001), history of smoking (P=0.002), hy-
perlipidemia (P=0.048), duration of PICC (P<0.0001), area of in-
sertion (P=0.019), use of de-clotting agents ( P=0.0009), compli-
cation after PICC line insertion (P=0.0008), and use of anti-MRSA
antibiotics after PICC insertion ( P=0.006). In multivariant anal-
ysis, there was a significant association between PICC CLABSI
and sepsis (OR=4.9, CI 2.2-11.1), history of smoking (OR=2.9, CI
1.3 { 6.2) and gastrostomy (OR=6.5, CI 2.2 { 19.4). Conclusions:
Risk factors for PICC CLABSI in an institution with low rates of in-
fection include both host factors (sepsis, smoking, gastrostomy
tube) and device factors (area of insertion, complications, use of
de-clotting agents, anti-MRSA antibiotics after PICC placement,
and PICC duration). Preventative measures targeting modifiable
risk factors may decrease rates of PICC CLABSI in the future.

peripherally inserted central venous catheter | blood streem infections

In recent years, peripherally inserted central venous catheters(PICC) have increasingly replaced subclavian or internal jugu-
lar central venous catheters (CVC) in both the outpatient and inpa-
tient setting. This significant increase in the use of PICCs can be
explained by many factors, including ease of insertion, improved

patient comfort, and favorable cost profile (1, 2). PICC are often
considered to have a superior safety profile than CVC (3). Some
studies have also indicated that PICC have a decreased incidence
of central line associated bloodstream infections (CLABSI) when
compared with CVC (4-6), but a more recent meta-analysis showed
that PICC used in the inpatient setting may have a risk of infection
similar to CVC (7).

The risk factors for inpatient CVC and PICC have been evalu-
ated in a number of prospective and retrospective studies (8-10) and
multiple strategies to decrease infection rates have been evaluated
and successfully implemented. Several studies have examined se-
lected risk factors for CLABSI in PICC (11-13), including patient
and device associated risk factors and post-placement line manage-
ment, with some conflicting results. A deeper understanding of the
risk factors for CLABSI in PICC may help in the development of
additional appropriate prophylactic strategies to decrease the inci-
dence of infection. Given the increasing number of PICC used in the
inpatient and outpatient settings and the devastating consequences
of CLASBI, this may result in significant improvements in patient
care and safety. In our institution, a dedicated PICC line team used a
multi-faceted approach to PICC line insertion and maintenance and
achieved one of the lowest rates of CLABSI in the nation sustained
for over a 5-year period of time (14). In this current study, a ret-
rospective analysis of PICC-associated bloodstream infections was
undertaken using data collected from a six year period of time in an
institution which had achieved very low infection rates of CLABSI
to evaluate patient and device factors that may be associated with

Submitted: 02/20/2020, published: 02/27/2021.

translation@utoledo.edu UTJMS 2020 Vol. 8 25–32

mailto:joan.duggan@utoledo.edu


inpatient PICC CLABSI in this setting.

Materials and Methods

Study Design and Subjects

The study was approved by the Institutional Review Board at
the University of Toledo Medical Center (UTMC) and consisted
of a retrospective analysis within the institution of all patients age
>18 years who had a PICC line inserted by a dedicated PICC line
team using maximal barrier precautions. The study period was be-
tween January 1st, 2008 and December 31st, 2013. PICC CLABSI
cases were identified using the National Healthcare Safety Network
(NHSN) definition for blood stream infections. All PICC CLABSI
cases underwent chart review using the NHSN definition. Patients
meeting the NHSN CLASBSI definition who had a PICC line in-
serted outside of UTMC or a PICC CLABSI documented at less
than two calendar days from insertion date were excluded from anal-
ysis.

Data Collection

PICC CLABSI cases occurring during the study period were
obtained from the infection prevention department and also through
review of billing codes. Patient information and information re-
garding the PICC insertion and maintenance were obtained by a
comprehensive medical record review and review of billing codes.
The International Classification of Diseases - 9th revision (ICD- 9)
was used during the period of study. PICC CLABSI cases were
matched to uninfected controls with similar age, gender, race and
time of admission within a six-month period (January 1 to June 30
and July 1 to December 31).

PICCs insertion and maintenance protocol

All PICC lines were inserted by a dedicated PICC team using
portable ultrasonography guidance. Placements were done under
maximal sterile barrier precautions, which included sterile gown,
sterile gloves, cap and use of a full body drape. Chlorhexidine
gluconate 2% was used to sterilize the skin prior to insertion and
chlorhexidine gluconate dressings were placed after insertion. The
position of the PICC tip was verified by chest radiography prior to
usage of the line. The PICC team performed line checks and dress-
ing changes weekly. The PICC line team used the de-clotting agent
alteplase in cases of catheter occlusion on an as needed basis as per
manufacture instructions.

Definition of variables

The variables collected through chart documentation and billing
code review were defined prior to data extraction. Patient demo-
graphics of age, race, gender, and time period of insertion (January
1 through June 30 and July 1 through December 31). were collected.
Past medical and surgical history, home medications, hospital med-
ications, and the course of the hospitalization including microbiol-
ogy data were extracted through review of both the electronic med-
ical record and the paper chart as applicable. The duration of the
PICC line was calculated in days from insertion until PICC removal
or documented CLABSI. Steroid use was defined as any systemic
steroid intake within 30 days before or after the PICC placement
but not including use of intranasal, inhaled, or topical preparations.
Statin and non-steroidal anti-inflammatory drug (NSAID) use was
defined as use of any medication in these classes except for top-
ical NSAIDS within 30 days before or after PICC line insertion.
Antibiotic therapy was divided into usage of any non-topical an-
tibiotic 30 before or after PICC insertion and was further divided

into MRSA coverage if the patients received at least two doses
of Vancomycin, Daptomycin, Linezolid, Bactrim or Doxycycline.
Active chemotherapy was defined as receipt of oral or intravenous
chemotherapy treatment within 30 days before or after PICC line
placement. Transfusion of blood products was defined as receipt
of any blood products such as packed red blood cells, platelets, or
fresh frozen plasma during the hospital observation period.

Statistical Analyses

All data underwent statistical analyses using SPSS 21.0 soft-
ware. The correlation between PICC CLABSI and risk factors was
determined using chi-square test. Multivariate analysis was done
using logistic regression. Two tailed P value < 0.05 was considered
to be statistically significant.

Results

A total of 6756 patients underwent a PICC line placement dur-
ing the study period (January 1, 2008 thru December 31, 2013).
Fifty-six (0.83%) infected cases were identified and matched to 245
uninfected controls. The final analysis included 301 patients total.

The demographic characteristics, comorbid diseases and medi-
cations (statins, NSAIDs, steroids) for both groups are shown in Ta-
ble 1. There was a significant association between an infected PICC
and a diagnosis of sepsis (P<0.0001) hyperlipidemia (P=0.048) or a
history of smoking documented on the initial assessment (P=0.002).
There was no significant correlation between PICC CLABSI and
the use of statins (OR: 0.95, 95% CI [0.52-1.72], P=0.87), NSAIDs
(OR: 0.82, 95% CI [0.34-1.97], P=0.67) and/or steroids (OR: 1.01,
95% CI [0.54-1.88], P=0.96) either 30 days before or after insertion
(P>0.05).

Device related factors among infected PICC lines and the
matched control group are listed in Table 2. There was a correla-
tion between PICC infection and the duration of PICC use (mean:
14 days vs 7 days, P<0.0001). There was significant correlation
with PICC line infection and the following use of de-clotting agents
(OR:0.22, 95% [CI:0.08-0.57], P=0.0009), complication after PICC
line insertion (OR:4.22, 95%CI [1.72-10.34], P=0.0008) and the use
of MRSA coverage antibiotics after PICCs insertion but not in the
30 days prior to insertion (OR:2.26, 95%CI [1.24-4.10], P=0.006).

The most common PICC insertion vein was the basilic vein
(n=196, 65.11%) and insertion in the median cubital vein was asso-
ciated with an increased risk of infection (OR:0.32, 95% CI [0.12-
0.86], P=0.019). Most of PICC lines were inserted in non-intensive
care units including the rehabilitation unit and the general medi-
cal/surgical units (n=225, 74.75%). There was no significant corre-
lation between PICC CLABSI and number of lumens in the PICC
(P>0.05).

There was a significant association with presence of a gastros-
tomy tube (OR:0.20, 95%CI [0.09-0.44], P:<0.0001) and mechan-
ical ventilation (OR:1.99,95%CI [1.04-3.80], P=0.03) with PICC
CLABSI compared to matched controls (Table 3). There was
no correlation between a PICC CLABSI and presence of a Fo-
ley catheter or tracheostomy tube, transfusion of blood products
after PICC placement or performance of an esophagogastroduo-
denoscopy (EGD) or colonoscopy during the admission. In the
multivariate logistic regression analysis (Table 4), there was a sig-
nificant association between PICC CLABSI and sepsis (OR:4.92,
95%CI [2.18-11.13], P:<0.0001), history of smoking (OR:2.87,
95%CI [1.33-6.19], P:0.007) and presence of a gastrostomy tube
(OR:6.51, 95%CI [2.19-19.39], P>0.0008).

26 translation@utoledo.edu Alkully et al.



Table 5 demonstrates the microbiological data. The majority
of the PICC CLABSI during the study period were caused by co-
agulase negative staphylococci (n=15, 26.79%), enteric gram neg-

ative rods (n= 14, 25.00%), polymicrobic bacterial infections (n=
9, 16.07%), candida species (n=7, 12.50%), or coagulase positive
staphylococci (n= 3, 5.36%).

Table 1.Demographics, comorbidities and medications for patients with PICC CLABSI compared to case matched controls.

Characteristic PICCs CLABSI Matched Controls P-Value
n=56 n=245

Male Gender N, 27(48.21%) 105 (42.86%) 0.46
CHF N, 19(33.93%) 61(24.90%) 0.16

COPD N, ) 5 (8.93%) 22 (8.98%) 0.99
DM N, 17(30.36%) 87(35.51%) 0.46
CKD N, 9 (16.07%) 50(20.41%) 0.46

Active Cancer N, ) 12(21.43%) 39(15.92%) 0.32
Sepsis N, 26(46.43%) 28 (11.43%) <0.0001

Hypertension N, 22(39.2%) 110(44.90%) 0.44
Hyperlipidemia N, 18(32.14%) 49(20.00%) 0.048
C. Diff Infection N, 3 (5.36%) 12 (4.90%) 0.88

Acute Pancreatitis N, 5(8.93%) 10(4.08%) 0.13
BMI (kg/m2), Mean + SD 28.32 + 10.01 30.49 + 11.05 0.18

Smoking N, 25(44.64%) 58(24.0%) 0.002
Wound type III or IV, N/ 15/35 (42.85%) 47/132 (35.60%) 0.43

Total N (%)
Statin 22 (39.29%) 99 (40.41%) 0.87

NSAID 7 (12.50%) 36 (14.69%) 0.67
Steroid 18 (32.14%) 78 (31.84%) 0.96

CLABSI= Central line associated blood stream infection, OR= odd ratio, CI: confidence interval, CHF= congestive heart failure COPD=
chronic obstructive pulmonary disease, CKD= chronic kidney disease, C.diff infection= Clostridium Difficile infection, BMI= body mass

index.

Alkully et al. UTJMS 2020 Vol. 8 27



Table 2.Device Factors for Patients with PICC CLABSI compared to Case matched Controls.

Characteristic PICCs CLABSI Matched Controls P-Value
n=56 n=245

Duration (Days), Median 14 (7-32.5) 7(4-11) <0.0001

Unit of Placement
Non-ICU, N 42 (75.00%) 183 (74.69%) Ref

MICU/SICU, N (%) 14 (25.00%) 62 (25.51) 0.93

PICCs Insertion Site
Basilic,N 44(89.80%) 152 (82.61%) Ref

Cephalic, N 5 (10.20%) 32 (17.39%) 0.22
Median Cubital/Brachial, N 5 (10.20%) 53 (25.85%) 0.019

Indication
TPN, N 10 (55.56%) 26 (47.27%) Ref

Antibiotics, N 8 (44.44%) 29 (52.73%) 0.54
Chemotherapy, N 3 (23.08%) 1 (3.70%) 0.055

Use of Declotting Agent
Yes, N 9 (16.07%) 10 (4.08%) Ref
No, N 47 (83.93%) 235 (95.42%) 0.0009

Number of Lumens
Single, N 7 (12.50%) 36 (14.69%) Ref
Double, N 35 (62.50%) 168 (68.57%) 0.87
Triple, N 14 (25.00%) 39 (15.92%) 0.23

Complication During PICCs Insertion, N 25 (44.64%) 91 (37.14%) 0.29
Complications After PICCs Insertion, N 10 (17.86%) 12 (4.90%) 0.0008

MRSA Coverage Before Placement of PICCs, N 19 (33.93%) 78 (31.97%) 0.77
MRSA Coverage After Placement of PICCs, N 34 (60.71%) 99 (40.57%) 0.006

CLABSI= central line associated blood stream infection, MRSA= Methicillin-resistant Staphylococcus aureus, OR= odd ratio, CI=
Confidence interval.

28 translation@utoledo.edu Alkully et al.



Table 3. Medical Devices and Procedures Comparison of Study Groups.

Characteristic PICCs CLABSI Case Control OR (95%CI) P-Value
n=56 n=245

Foley Catheter, N 40 (72.73%) 149 (61.07%) 0.58 (0.30-1.12) 0.10
Gastrostomy, N 15 (26.79%) 17 (6.94%) 0.20 (0.09-0.44) <0.0001

Tracheostomy, N 1 (1.79%) 11 (4.49%) 0.38 (0.04-3.05) 0.35
EGD, N 3 (5.36%) 7 (2.86%) 1.92 (0.48-7.68) 0.34

Colonoscopy, N 1 (1.79%) 10 (4.08%) 0.42 (0.053-3.40) 0.40
Mechanical Ventilation, N 18 (32.14%) 47 (19.18%) 1.99 (1.04-3.80) 0.03

Blood Product Transfusion, 24 (42.86%) 94 (38.37%) 1.20 (0.66-2.17) 0.53

TPN: total parental nutrition, EGD: Esophagogastroduodenoscopy

Table 4. Multivariate logistic regression an of risk factors associated with PICC CLABSI

Characteristic Odds Ratio (95% Confidence Interval) P-Value
n=56 n=245

BMI (Kg/M2) 0.98 (0.95-1.02) 0.49
Sepsis 4.92 (2.18-11.13) <0.0001

Hyperlipidemia 1.98 (0.85-4.63) 0.11
Smoking 2.87 (1.33-6.19) 0.007

Use of Declotting Agent 0.29 (0.08-1.04) 0.059
Antibiotics use Before PICCs Insertion 1.21 (0.79-1.84) 0.36
Antibiotics use After PICCs Insertion 0.83(0.55-1.26) 0.39

TPN 3.88(0.88-17.00) 0.07
Mechanical Ventilation 1.17(0.47-2.93) 0.72

Gastrostomy 6.51(2.19-19.39) 0.0008
Foley catheter 0.98(0.39-2.44) 0.96
Tracheostomy 2.01(0.38-10.52) 0.40

BMI=body mass index; TPN=total parental nutrition.

Alkully et al. UTJMS 2020 Vol. 8 29



Table 5. Classes of antimicrobial infections in the PICC CLASBSI cases

Pathogen PICC CLABSI )
n=56

Polymicrobial, N 9 (16.07%)
Candida Species, N 7 (12.50%)

Gram Positive Bacteria

Coagulase Negative Staphylococcus N 15 (26.79%)
Enterococcus Species, N 5 (8.93%)

MRSA, N 2 (3.57%)
MSSA, N 1 (1.79%)

Gram Negative Bacteria

Klebsiella Pneumonia, N 7 (25.36%)
Escherichia Coli, N 4 (7.14%)

Serratia, N 3 (5.36%)
Pseudomonas Aeruginosa, N 1 (1.79)

Providencia, N 1 (1.79)
Sphingomonas, N 1 (1.79)

Discussion

CLABSI are potentially catastrophic for patient outcomes and
are associated with a significantly increased risk of mortality (15).
There have been a number of retrospective and prospective studies
that have evaluated risk factors for CLABSI in a variety of settings
and with a variety of intravascular devices. Based on the insights
generated from these studies, significant strides in the reduction of
CLABSI have occurred and successful programs to reduce the rates
of CLABSI to near zero have been piloted, primarily in ICU settings
(16, 17). In practice, PICC are increasingly being used for longer
durations in multiple hospital settings and the rates of CLABSI are
often similar to that seen with non-PICC CVC. In this study, a retro-
spective evaluation for risk factors associated with PICC CLABSI
in ICU and non-ICU hospital patients against a background of sus-
tained low rates of CLABSI was undertaken to evaluate potentially
novel host and/or device factors in this setting. The 5-year sustained
rate of PICC CLABSI was <1% in this study, which is lower than
the rate of infection for PICC CLABSI of 1.1% referenced in the
prevention guidelines (14, 18).

A number of risk factors identified in this study have also been
suggested in previous studies. While use of a declotting agent was
identified as a risk factor for infection, this may be a surrogate
marker for thrombosis, which has been identified previously as a
risk factor for infection in pediatric CLABSI (19, 20). Duration of
PICC line placement and complications after insertion, including
manipulation of the PICC line have been documented in other stud-
ies as risk factors for infection and were demonstrated in this study
as well (11). In a previous report of PICC CLABSI in a large ter-
tiary hospital with a higher rate of infection, use of TPN, duration of

PICC, mechanical ventilation, and gastrostomy were also reported
as risk factors for infection (13). In this study, the number of lu-
mens did not appear to be a risk factor for CLABSI but the majority
of lumens in both infected cases and matched controls were, how-
ever, single or double lumens with infrequent use of triple lumen
catheters (17.6%). In multivariant analysis, there were three risk
factors for PICC CLABSI that were significant but were not mod-
ifiable { sepsis on admission, presence of a gastrostomy tube, and
history of smoking. The presence of significant, non-modifiable risk
factors for PICC CLABSI raises the question of whether a target of
zero PICC CLABSI is obtainable and sustainable (16).

Nearly one-third of the organisms associated with CLABSI in
this study were gram-negative organisms, which is higher than that
reported in other reviews of PICC CLABSI (11, 13). In a previ-
ous study, gram-negative organisms caused the majority of PICC
CLABSI in children with PICU exposure while gram-positive or-
ganisms caused the majority of infections in those without PICU
exposure (21). Our retrospective study was undertaken in a single
institution which had a dedicated PICC team and did not include
pediatric patients. CLABSI generally occur from one or more of
the following sources { skin, device lumen, bloodstream seeding,
and/or rarely the infusate. Skin colonization with secondary catheter
colonization and subsequent CLABSI is the most common cause of
CVC infections (22, 23) resulting in the high incidence of gram pos-
itive skin commensals usually reported in CLABSI studies. In fact,
the successful strategies currently in place to reduce CLABSI rely in
large part on reduction of skin bacteria at the catheter insertion site.
Gastrostomy tubes as a significant risk factor for CLABSI have been
previously identified in a pediatric study (24) and may be a marker
for severity of illness or poor nutritional status. In the current study,
less than half of the PICC CLABSI were caused by gram positive

30 translation@utoledo.edu Alkully et al.



organisms but interestingly, use of an anti-MRSA antibiotic after,
but not before, line placement was associated with an increased risk
of infection. Gastrostomy tubes may also represent a route for the
transfer of enteric pathogens to the CVC. The route of bacterial
transfer is rarely through hematogenous dissemination regardless of
the method of placement [25, 26]. A recent study demonstrated,
however, that the presence of a gastrostomy tube was associated
with an increased risk of axillary colonization with gram negative
rods (27). It would be interesting to evaluate the changes in resident
axillary skin flora and colonization around the catheter site or other
alterations of the microbiome in the presence of gastrostomy tubes
especially with respect to the incidence and microbiology of PICC
CLABSI.

Previous studies have found an increased incidence of DVT in
patients using a PICC line compared to patients using other central
venous lines (28-30). Limiting the use of PICC lines in patients
predisposed to thrombus formation may be an important consider-
ation. As previously mentioned, PICC used in the inpatient setting
have a risk of infection similar to CVC (7, 31). The MPC (Michi-
gan PICC-CLABSI) score currently offers a promising way to deter-
mine whether PICC insertion would be the most appropriate method
of treatment for certain patient populations as it predicts the risk of
PICC-CLABSI development (32).

Conclusion

There were several limitations of this study. This was a review
of CLABSI in a single institution with a very limited number of
PICC CLABSI observed during the study period. Also, this was
a retrospective study and as with all non-prospective studies, not
all data points of interest were collected in all patients. This study
demonstrated risk factors for PICC CLABSI such as the presence of
gastrostomy tubes and history of smoking that may have increased
significance as the rates of PICC CLABSI decrease and additional
interventions are utilized to achieve the ultimate goal of elimination
of morbidity and mortality from central line bloodstream infections.

Conflict of interest

Authors declare no conflict of interest.

Authors’ contributions

JD and SH: conceived/designed the review, TA: performed the
data collection, TA, MR, SK: performed the data collection reviews
and formal analysis, and NL: reviewed and revised the manuscript.
All authors wrote the manuscript, read and approved the final docu-
ment.

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