American Journal of Infection Control 42 (2014) 122-8
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
journal homepage: www.ajicjournal.org
Major article
Sustained low incidence of central venous catheter-related infections over six years in a Swedish hospital with an active central venous catheter team Fredrik Hammarskjöld MD, PhD a, b, *, Sören Berg MD, PhD c, Håkan Hanberger MD, PhD b, Knut Taxbro MD a, Bo-Eric Malmvall MD, PhD b, d a
Department of Anesthesia and Intensive Care, Ryhov County Hospital, Jönköping, Sweden Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköping University, Linköping, Sweden Division of Cardiothoracic Anesthesia and Intensive Care, Department of Medical and Health Science, Faculty of Health Science, Linköping University, Linköping, Sweden d Futurum the Academy for Health Care, Jönköping County Council, Jönköping, Sweden b c
Key Words: Central venous catheter-related bloodstream infection Intravascular catheter Nosocomial infection Statistical process control
Background: There are limited data on the long-term effects of implementing a central venous catheter (CVC) program for prevention of CVC infections. The aims of this study were to evaluate the incidence of CVC colonization, catheter-related infections (CRI), catheter-related bloodstream infections (CRBSI), and their risk factors over a 6-year period in a hospital with an active CVC team. Methods: We conducted a continuous prospective study aiming to include all CVCs used at our hospital during the years 2004 to 2009, evaluating colonization, CRI, CRBSI, and possible risk factors. Results: A total of 2,772 CVCs was used during the study period. Data on culture results and catheterization time were available for 2,045 CVCs used in 1,674 patients. The incidences of colonization, CRI, and CRBSI were 7.0, 2.2, and 0.6 per 1,000 CVC-days, respectively. Analysis of quarterly incidences revealed 1 occasion with increasing infection rates. Catheterization time was a risk factor for CRI but not for CRBSI. Other risk factors for CRI were hemodialysis and CVC use in the internal jugular vein compared with the subclavian vein. Hemodialysis was the only risk factor for CRBSI. Conclusion: We found that a CRI prevention program led by an active CVC team and adhered to by the entire staff at a county hospital is successful in keeping CVC infections at a low rate over a long period of time. Copyright Ó 2014 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Central venous catheter (CVC)-related bloodstream infections (CRBSI) are common and can cause excessive morbidity and substantial economic costs and be potentially lethal. There are 80,000 CRBSI annually in the United States.1 Several studies have shown that the implementation of basic hygiene routines can significantly reduce the number of CRBSI.1-5 Most of these studies, however, have evaluated this effect over relatively short periods of time. There are limited data on the long-term effects after such intervention. Pronovost et al showed that the incidence of CRBSI continues to
* Address correspondence to Fredrik Hammarskjöld, MD, PhD, Department of Anesthesia and Intensive Care, Länssjukhuset Ryhov, 551 85 Jönköping, Sweden. E-mail address: [email protected] (F. Hammarskjöld). Supported by grants from Futurum the Academy for Health-care, Jönköping County Council, Jönköping, Sweden. Conflicts of interest: None to report.
decrease after the completion of a study on implementing a bundle for CVC insertion and care on intensive care units (ICUs).2 This finding was supported by another ICU study over a period of 4 years.4 A continuous decline in the incidence of CRBSI was also reported in a European ICU study of hospitals participating in a surveillance program, with intermittent registration over 5 years.6 In 1999, we introduced an educational and follow-up program based on previous recommendations from the Centers for Disease Control and Prevention for basic hygiene routines on insertion, care, and removal of CVCs.7 Since then, all wards and outpatient departments (OPDs) at our 500-bed hospital have participated in this program. We evaluated the effects of this program in a 16-month study in 2001 and 2002 and found a CRBSI incidence of 0.44/1,000 days.8 To analyze the long-term effect of this program, we conducted a continuous prospective 6-year study, from 2004 through 2009,
0196-6553/$36.00 - Copyright Ó 2014 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2013.09.023
F. Hammarskjöld et al. / American Journal of Infection Control 42 (2014) 122-8
studying CVC colonization, catheter-related infection (CRI), CRBSI, and possible risk factors. The study was approved by the Regional Ethics Review Board in Linköping (reference number M203-09). METHODS AND MATERIALS Setting The hospital is a 500-bed, public, county hospital supporting most medical and surgical specialties. The ICU is a 7-bed general ICU with a median patient Acute Physiology and Chronic Health Evaluation II (Apache II) score9 of 18. Inpatients outside the ICU were treated on various medical and surgical wards. The hospital has no cardiothoracic surgery or neurosurgery and no transplantation activity. Outpatients were treated in a wide range of OPD clinics, including chronic hemodialysis, parenteral nutrition at home, oncology, infectious diseases, and palliative care. Study design We performed a prospective, observational, cohort study from 2004 up to and including 2009. All units using CVCs were instructed to perform a tip culture on CVC removal. Our aim was to study all CVCs used at the hospital. However, for various reasons, tip culture was not performed in all patients (missed culture, transfer to other hospital, accidental removal). Hence, we analyzed all cultured CVCs where insertion and removal dates were given. Exclusion criteria were patients with subcutaneous venous ports, peripherally inserted CVCs, and CVCs used in the neonatal setting. The medical records of all patients included were examined by one of the investigators (F.H.) registering diagnosis, insertion date and hospital, vein, type of catheter, Systemic Inflammatory Response Syndrome (SIRS),10 Apache II score, reasons for removal, antibiotic treatment, microbial cultures, CRI, CRBSI, and mortality. Adherence to the CVC routines was not evaluated. CVC team, insertion, and care Since 1999, the hospital has had a CVC team, consisting of 2 anesthesiologists and 1 ICU nurse. This team is responsible for all written documents concerning CVC insertion, care, and removal. Written instructions are repeatedly distributed to every unit and are also available on the hospital intranet for all staff handling patients with CVCs. All CVCs are inserted by anesthesiologists, who regardless of previous experience are trained under supervision to perform CVC insertion according to instructions. ICU nurses are trained at the start of their appointment and thereafter every other year so as to ensure high adherence to the CVC care routines. Ward and OPD nurses manage the daily care of CVCs outside the ICU. These nurses are supervised by specially trained department nurses, who constitute a hospital network that relies on the CVC team. Furthermore, the CVC team, or the anesthesiologist on call, are available around the clock for handling CVC problems. Tip cultures of all removed CVCs are used as surveillance and follow-up of the infection prevention program. Since 2006, we have monthly assessments of adherence to basic hygiene rules throughout the hospital, as part of a general quality program. The catheters were inserted by an anesthesiologist with maximal sterile precautions (cap, mask, gown, gloves, and large drape) using the Seldinger technique. The multilumen CVCs inserted in our ICU were all chlorhexidine/silver sulfadiazine catheters. No other CVCs were antimicrobiologic. The insertion site was treated with a solution of 0.5% chlorhexidine (wt/vol) in 70% alcohol (SCHA) and allowed to dry for 1 to 2 minutes prior to insertion. No prophylactic antibiotics were given. All catheters were
123
secured with monofilament sutures, and the site was dressed with a semipermeable dressing (Tegaderm HP; 3M Healthcare, St. Paul, MN). CVC insertion was documented in the patient’s records after completion of the procedure and registered on a computer. Tunneled CVC sutures were removed, and no semipermeable dressing was used when the subcutaneous cuff had firmly healed. Every third day (every seventh day for OPD patients), dressing, stopcocks, and injection membranes were changed, and the insertion site was treated with SCHA. Heparin flushing and locks were not routinely used, except for patient on hemodialysis outside the ICU. The catheters were flushed after every infusion with 10 mL of saline, 4 times, to prevent occlusion. Resting CVCs (>24 hours) were not routinely flushed. Lipid solutions were administered via a separate lumen when a multilumen catheter was used. All CVCs were supposed to be cultured on removal. Microbiology The catheters were removed after site treatment with SCHA that was allowed to dry. The distal 5 cm of the CVC tip was cut off and deposited in a sterile container and cultured using a semiquantitative standardized roll plate method.11 The tip culture result was considered positive if 1 or more colony-forming units (CFU) were found. The CVC tips were cultured within 18 hours after removal. Blood cultures were performed when clinically indicated by sampling blood from another vessel. The bottles were incubated 6 days using an automated blood culture system (BAc/ALERT; bioMériuex, Inc, Durham, NC). Isolates were identified using standard methods at the local microbiology laboratory. Antibiotic susceptibility tests were performed according to Swedish standards (www.srga.org; January 1, 2007). Definitions CVC colonization was defined as a positive tip culture with 1 CFU regardless of clinical symptoms.8 The reason for this was to evaluate whether tip culture alone could be a surrogate marker for CRI or CRBSI. We also used a second, commonly employed, definition of colonization (15 CFU).11 CRI was defined as a positive tip culture from a patient having at least 2 SIRS symptoms at CVC removal, and no other known source of infection, independently of blood culture results.8,10,12 CRBSI was defined as isolation of microorganisms from the tip culture and a blood culture drawn from another vessel (within 48 hours prior or after CVC removal) that were indistinguishable.12 Isolates were regarded as indistinguishable if they shared the same phenotype and antibiogram. Duration of catheterization was defined as the number of days from insertion to removal of the CVC. All catheters that were used to some extent in the ICU were regarded as ICU catheters. Statistical analysis Associations and differences among groups were assessed using
c2 test, Student t test, or Mann-Whitney test as appropriate. The correlations between different incidences were evaluated with Spearman rank correlation test. Variations of variables over time were analyzed using linear regression analysis (LR). Univariate logistic regression analyses were performed to estimate the risk for colonization, CRI, and CRBSI. Multiple logistic regression models, controlling for catheterization time with following stepwise introduction of significant risk factors, were performed. All analyses were conducted using a statistical software package (version 19.0 for Windows; IBM SPSS, Armonk, NY). Variations in incidence over time were analyzed with statistical process control (SPC) methods.13 Seldom occurring events (CRI and
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F. Hammarskjöld et al. / American Journal of Infection Control 42 (2014) 122-8
CRBSI) were analyzed using geometrical charts, evaluating the number of CVCs removed between each infection episode. The central line (CL) and upper control line (UL) were defined as follows: CL ¼ mean 0.693 and UL ¼ mean þ 3 O(mean (mean þ 1)). Frequently occurring events (colonization) were analyzed using individual charts, evaluating quarterly incidences of colonization (CL ¼ mean, UL ¼ CL þ 2.66 moving range, and lower control limit (LL) ¼ CL e 2.66 moving range). Special causes of variation were defined as a run of 8 or more points on one side on the central line, 1 point outside the upper or lower control limit, or a run of 6 or more points all trending up or down. SPC analyses were conducted using a statistical software package (Microsoft Excel 2010; Microsoft Corp, Redmond, WA). RESULTS Patients and CVCs A total of 2,053 CVCs was cultured during the study period, representing 74% of all CVCs used at the hospital. Insertion date could not be found in 8 cases, and, hence, 2,045 catheters from 1,674 patients were included in the study. The median patient age was 65 years (range, 0.2-99), and 57% were male; 1,453 of the catheters were to some extent used on the ICU, and the median Apache II score of the ICU patients was 22 (range, 2-44). The median duration of catheterization was 8 days (range, 0-1,617) giving a total of 45,026 CVC-days. The proportion of patients with SIRS was 42% in all patients and 54% in the ICU group. Diagnosis, insertion hospital, catheter type, vein, and reasons for removal are presented in Table 1. Antibiotics were used in 1,521 (74.4%) cases on the day of CVC removal. Blood cultures were taken at the time of removal in 578 (28.3%) cases. Four hundred one CVCs (19.6%) were removed from patients who died with their catheter in place. There was a continuous increase in the number of CVCs used each year (Table 2) from 269 to 424 (LR; adjusted r2 ¼ 0.95, b ¼ 33.6, P ¼ .001). There was also an increase in the use of the internal jugular vein from 31% of all CVCs to 58% (LR; adjusted r2 ¼ 0.90, b ¼ 6.0, P ¼ .003) and a decrease in the use of the subclavian vein, from 49% to 22% (LR; adjusted r2 ¼ 0.91, b ¼ 5.9, P ¼ .002) over the study period. There were no other trends detected over time concerning patient and CVC characteristics. Colonization Three hundred fourteen (15.4%) of all CVCs showed microbial growth on tip cultures, which represents a colonization incidence of 7.0 per 1,000 CVC-days. Forty-nine CVCs were found to have more than 1 isolate. The incidences of colonization over time for all patients and different subgroups are presented in Table 2. There was a significant correlation between the quarterly colonization incidences defined as 1 CFU as compared with 15 CFU (r ¼ 0.89, P < .05) (Fig 1). The predominant species were coagulase-negative staphylococci (CoNS) (63.8%), Candida albicans (7.9%), Staphylococcus aureus (7.5%), Enterococcus faecalis (5.8%), and Enterococcus faecium (2.1%). All other species represented less than 2%. CRI and CRBSI Fifty-two (2.5%) of the 2,045 CVC episodes were classified as having CRI and 29 (1.5%) a CRBSI. The incidence of CRI and CRBSI were 1.2 and 0.6 per 1,000 CVC-days, respectively. The incidences of CRI and CRBSI over time for all patients and different subgroups are presented in Table 2. There was a significant correlation between the quarterly incidences of CRI and CRBSI (r ¼ 0.83, P < .05) (Fig 1).
Table 1 Insertion and removal data of the 2,045 central venous catheter episodes
Total number of CVCs Inserting hospital Study hospital Other Primary diagnosis Cardiovascular Gastrointestinal Oncology Infection Trauma Others Vein Subclavian vein Internal jugular vein Femoral vein External jugular vein Unknown Type of CVC Single lumen Multilumen Dialysis Tunneled, dialysis Tunneled, 1 or 2 lumen PA introducer PA catheter Unknown Reasons for removal No need for CVC Malfunction Suspicion of CVC infection Accidental Pneumothorax Thrombosis Unknown
No.
%
2,045
100
1,796 249
87.8 12.2
372 302 273 688 144 266
18.2 14.8 13.3 33.6 7.0 13.0
627 1,017 332 13 56
30.7 49.7 16.2 0.6 2.7
483 911 308 42 59 123 84 35
23.6 44.5 15.1 2.1 2.9 6.0 4.1 1.7
1,543 90 338 7 1 1 65
75.5 4.4 16.5 0.3 0.05 0.05 3.2
CVC, central venous catheter; PA, pulmonary artery.
However, there were no significant correlations between the quarterly incidences of colonization, using either of the definitions, and CRI or CRBSI (Fig 1). Fifty-four (2.6%) patients had a CRI and/or a CRBSI, which gave an incidence of 1.2 per 1,000 days. Two cases of CRBSI were not classified as CRI because documentation of SIRS symptoms was missing. Blood cultures were negative in 8 of the 52 cases of CRI. In 7 of these 8 cases, the patients were treated with antimicrobial drugs, and, in 3 patients, the microorganisms, found on tip culture, were sensitive to the drug used. In 17 cases of CRI, blood culture was not performed. In 21 of the 29 cases of CRBSI, the patient was receiving antimicrobial drugs on removal of the CVC, and, in 12 of these, the microorganisms were sensitive to the antimicrobial drug. The microorganism most frequently isolated on tip culture in cases of CRI and CRBSI were CoNS (31%), C albicans (24%), S aureus (19%), E faecalis (9%), and Candida glabrata (3%). The median catheterization time to CRI/CRBSI was 14 days (range, 1-645). There was no significant difference in time to CRI/CRBSI for infections caused by bacteria or Candida, with median of 14 days (range, 3-645) and 13 days (range, 1-30), respectively. SPC using an individual chart did not reveal any occasion where the variation in incidence of colonization was higher or lower than expected by natural (common cause) variation (Fig 2). Analysis with geometrical charts for CRI and CRBSI revealed 2 occasions where the number of CVCs removed between 2 consecutive CRIs and CRBSIs were higher than expected, which indicated a period with infection rates lower than expected. One period of 6 consecutive measurements of CRBSI revealed a continuous downward run indicating a period of insufficient performance (Fig 2).
F. Hammarskjöld et al. / American Journal of Infection Control 42 (2014) 122-8
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Table 2 Annual number of CVCs and incidences per 1,000 CVC-days for colonization and infections
CVCs, n All ICU Non-ICU Hemodialysis* Vein Subclavian vein, n (%)y Internal jugular vein, n (%)y Femoral vein, n (%)y Colonizationz All ICU Non-ICU Hemodialysis* CRIz All ICU Non-ICU Hemodialysis* CRBSIz All ICU Non-ICU Hemodialysis*
2004
2005
2006
2007
2008
2009
267 203 64 14
267 200 67 13
332 233 99 21
369 270 99 10
387 268 119 26
423 279 144 23
130 (49) 83 (31) 39 (15)
114 (43) 103 (39) 44 (17)
116 (35) 151 (46) 56 (17)
93 (25) 200 (54) 61 (17)
80 (21) 236 (61) 61 (16)
94 (22) 244 (58) 71 (17)
Total 2,045 1,453 592 107 627 (31) 1,017 (50) 332 (16)
7.2 16.7 3.5 2.3
5.9 14.1 1.8 3.0
5.6 15.7 2.6 2.4
7.7 12.6 4.7 10.4
8.8 19.2 4.4 5.0
6.7 15.0 4.2 1.6
7.0 15.5 3.6 3.0
1.8 4.7 0.8 0.5
0.9 2.8 0 0
1.2 4.7 0 0
1.1 1.7 0.8 2.6
1.3 3.2 0.5 1.0
0.8 1.7 0.5 0
1.2 3.0 0.4 0.4
0.6 0.7 0.5 0.5
0.9 2.8 0 0
0.8 2.6 0.2 0
0.5 0.4 0.5 2
0.7 1.2 1.2 0.5
0.5 0.9 0.4 0.3
0.6 1.4 0.3 0.4
CRBSI, catheter-related bloodstream infection; CRI, CVC-related infection; CVC, central venous catheter; ICU, intensive care unit. *Hemodialysis outside the ICU. y Percentage of all CVCs. z Incidence per 1,000 catheter-days.
Fig 1. Quarterly incidences of central venous catheter colonization, catheter-related infection, and catheter-related bloodstream infection. CVC, central venous catheter; CFU, colony-forming units; CRI, CVC-related infection; CRBSI, CVC-related bloodstream infection.
All patients with a CRI or a CRBSI were successfully treated with antimicrobial drugs. Seventeen of these patients died during their hospital stay but for other reasons than CRI or CRBSI; we thus recorded no case of CVC infection mortality. Risk factor analysis Univariate logistic regression analyses revealed that catheterization time did not increase the risk for colonization or CRBSI but
increased the risk for CRI (odds ratio [OR], 1.002 per day; 95% confidence interval [CI]: 1.000-1.004, P ¼ .042). Multivariate analysis controlling for catheterization time showed the following risk factors for colonization: non-ICU use (OR, 1.3; 95% CI: 1.0-1.7, P ¼ .029), no antibiotics on removal (OR, 1.6; 95% CI: 1.3-2.1, P < .0001), internal jugular vein as opposed to subclavian vein (OR, 2.4; 95% CI: 1.7-3.3, P < .0001), and femoral vein as opposed to subclavian and jugular vein (OR, 1.4; 95% CI: 1.0-1.9, P ¼ .035). However, the risk for non-ICU use was not significant when
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F. Hammarskjöld et al. / American Journal of Infection Control 42 (2014) 122-8
Fig 2. Statistical process control: Individual chart representing the quarterly incidences of colonization showing variations exclusively explained by natural variation. Geometrical chart representing the number of removed central venous catheters between each episode of catheter-related bloodstream infection. Lined circles represents 2 periods of low infection rates not explained by natural variations. Dotted oval represents a period with increasing infection rate not explained by natural variation. CVC, central venous catheter; CRBSI, CVC-related bloodstream infection.
F. Hammarskjöld et al. / American Journal of Infection Control 42 (2014) 122-8
antibiotic treatment or hemodialysis was controlled for. The risk factors for CRI were hemodialysis (OR, 2.8; 95% CI: 1.0-7.7, P ¼ .048) and internal jugular vein as opposed to the subclavian vein (OR, 2.6; 95% CI: 1.2-5.7, P ¼ .016). Risk factor for CRBSI was hemodialysis (OR, 4.5; 95% CI: 1.3-14.9). DISCUSSION The main finding of this study was a sustained low incidence of CVC colonization (7.0 per 1,000 catheter-days), CRI (1.2 per 1,000 CVC-days), and CRBSI (0.6 per 1,000 CVC-days) over a period of 6 years in an entire hospital patient population, with an active CVC team, where structured hygiene routines for CVC insertion, care, and removal had been implemented. Our routines for insertion and care are based on previous recommendations from the Centers for Disease Control and Prevention7 and also follow the new recommendations from 2011.14 The recommendations have been evaluated in previous studies by us and others1,8 and have been constant throughout the study. The only exception to these guidelines in this study was the use of the femoral vein as a vascular access in selected ICU patients. The hospital’s CVC team, available for education and support in the care of patients with a CVC, was formed in 1999 and has since been well established. The team or a trained anesthesiologist is available for support around the clock. All anesthesiologists are well educated in the insertion and care of CVCs, and anesthesiologists without special training are not allowed to perform the insertion procedure. Furthermore, there is a high awareness throughout the hospital of the risks for CVC infections, and results indicate good adherence to CVC hygiene routines. This awareness is promoted by a continuously ongoing education and surveillance program with tip cultures offered by the CVC team. The results from the surveillance are annually reported to all units using CVCs. We did not observe any mortality related to CVC infections. This may be due to the low incidence of CRI and CRBSI and high awareness of the importance of preventing CVC infections. Mortality can increase as a result of CVC infections, but the direct mortality rate has been difficult to define.14,15 We have not been able to evaluate the adherence to our routines, but levels of CRBSI may act as a surrogate and indirect marker of staff performance.4 We believe that high adherence and an active CVC team supporting the entire hospital are the cornerstones in low incidences of CRI and CRBSI. We have used the incidences of 3 different indicators of infectious complications related to the use of CVCs: colonization, CRI, and CRBSI. The reason for studying colonization is that it provides a picture of possible microorganisms, including their resistance patterns, thus providing guidance when treating CVC infections. The presence of microorganisms on cultured catheter tips is itself a reminder, serving to increase clinical awareness of the risk for CVC infection.6 This justifies, in our opinion, the routine of CVC tip culture for all CVCs removed.16 However, we could not verify previous findings that colonization may be used as a surrogate indicator of CRI or CRBSI.17 Most studies use CRBSI as an end point for severe infections where the point of entry of the causative microorganism is the CVC. However CRBSI, in our opinion, is a too narrow definition because it requires positive blood cultures and thus has several limitations: not always performed, antimicrobial treatment preventing growth of microorganisms, intermittent release of microorganism to the blood, and inappropriate transportation or delay in coming to the laboratory. We believe CRI to be the most valuable clinical measurement because it captures all patients with SIRS symptoms who have microorganisms on their CVC. A recent European study used a CRI definition similar to ours.16 One difficulty with the CRI definition is that the CVC must be removed for culture. Another difficulty is that
127
most patients with a CVC and SIRS symptoms do not have a CVC infection.17 However, in clinical practice these patients must be evaluated by the physician responsible, who decides which action should be taken. This includes decisions on removing the CVC and performing blood cultures. Thus, in the clinical setting we prefer the quarterly incidence of CRI as an indicator of the quality of CVC care. CRBSI incidences reported by others, from both ICU and non-ICU settings, vary from around zero to 10 per 1,000 CVC-days.5 Several studies, mainly from ICUs, have shown that implementing simple CVC routines are successful in decreasing CRBSI incidence to a very low level (
Contents lists available at ScienceDirect
American Journal of Infection Control
American Journal of Infection Control
journal homepage: www.ajicjournal.org
Major article
Sustained low incidence of central venous catheter-related infections over six years in a Swedish hospital with an active central venous catheter team Fredrik Hammarskjöld MD, PhD a, b, *, Sören Berg MD, PhD c, Håkan Hanberger MD, PhD b, Knut Taxbro MD a, Bo-Eric Malmvall MD, PhD b, d a
Department of Anesthesia and Intensive Care, Ryhov County Hospital, Jönköping, Sweden Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköping University, Linköping, Sweden Division of Cardiothoracic Anesthesia and Intensive Care, Department of Medical and Health Science, Faculty of Health Science, Linköping University, Linköping, Sweden d Futurum the Academy for Health Care, Jönköping County Council, Jönköping, Sweden b c
Key Words: Central venous catheter-related bloodstream infection Intravascular catheter Nosocomial infection Statistical process control
Background: There are limited data on the long-term effects of implementing a central venous catheter (CVC) program for prevention of CVC infections. The aims of this study were to evaluate the incidence of CVC colonization, catheter-related infections (CRI), catheter-related bloodstream infections (CRBSI), and their risk factors over a 6-year period in a hospital with an active CVC team. Methods: We conducted a continuous prospective study aiming to include all CVCs used at our hospital during the years 2004 to 2009, evaluating colonization, CRI, CRBSI, and possible risk factors. Results: A total of 2,772 CVCs was used during the study period. Data on culture results and catheterization time were available for 2,045 CVCs used in 1,674 patients. The incidences of colonization, CRI, and CRBSI were 7.0, 2.2, and 0.6 per 1,000 CVC-days, respectively. Analysis of quarterly incidences revealed 1 occasion with increasing infection rates. Catheterization time was a risk factor for CRI but not for CRBSI. Other risk factors for CRI were hemodialysis and CVC use in the internal jugular vein compared with the subclavian vein. Hemodialysis was the only risk factor for CRBSI. Conclusion: We found that a CRI prevention program led by an active CVC team and adhered to by the entire staff at a county hospital is successful in keeping CVC infections at a low rate over a long period of time. Copyright Ó 2014 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Central venous catheter (CVC)-related bloodstream infections (CRBSI) are common and can cause excessive morbidity and substantial economic costs and be potentially lethal. There are 80,000 CRBSI annually in the United States.1 Several studies have shown that the implementation of basic hygiene routines can significantly reduce the number of CRBSI.1-5 Most of these studies, however, have evaluated this effect over relatively short periods of time. There are limited data on the long-term effects after such intervention. Pronovost et al showed that the incidence of CRBSI continues to
* Address correspondence to Fredrik Hammarskjöld, MD, PhD, Department of Anesthesia and Intensive Care, Länssjukhuset Ryhov, 551 85 Jönköping, Sweden. E-mail address: [email protected] (F. Hammarskjöld). Supported by grants from Futurum the Academy for Health-care, Jönköping County Council, Jönköping, Sweden. Conflicts of interest: None to report.
decrease after the completion of a study on implementing a bundle for CVC insertion and care on intensive care units (ICUs).2 This finding was supported by another ICU study over a period of 4 years.4 A continuous decline in the incidence of CRBSI was also reported in a European ICU study of hospitals participating in a surveillance program, with intermittent registration over 5 years.6 In 1999, we introduced an educational and follow-up program based on previous recommendations from the Centers for Disease Control and Prevention for basic hygiene routines on insertion, care, and removal of CVCs.7 Since then, all wards and outpatient departments (OPDs) at our 500-bed hospital have participated in this program. We evaluated the effects of this program in a 16-month study in 2001 and 2002 and found a CRBSI incidence of 0.44/1,000 days.8 To analyze the long-term effect of this program, we conducted a continuous prospective 6-year study, from 2004 through 2009,
0196-6553/$36.00 - Copyright Ó 2014 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajic.2013.09.023
F. Hammarskjöld et al. / American Journal of Infection Control 42 (2014) 122-8
studying CVC colonization, catheter-related infection (CRI), CRBSI, and possible risk factors. The study was approved by the Regional Ethics Review Board in Linköping (reference number M203-09). METHODS AND MATERIALS Setting The hospital is a 500-bed, public, county hospital supporting most medical and surgical specialties. The ICU is a 7-bed general ICU with a median patient Acute Physiology and Chronic Health Evaluation II (Apache II) score9 of 18. Inpatients outside the ICU were treated on various medical and surgical wards. The hospital has no cardiothoracic surgery or neurosurgery and no transplantation activity. Outpatients were treated in a wide range of OPD clinics, including chronic hemodialysis, parenteral nutrition at home, oncology, infectious diseases, and palliative care. Study design We performed a prospective, observational, cohort study from 2004 up to and including 2009. All units using CVCs were instructed to perform a tip culture on CVC removal. Our aim was to study all CVCs used at the hospital. However, for various reasons, tip culture was not performed in all patients (missed culture, transfer to other hospital, accidental removal). Hence, we analyzed all cultured CVCs where insertion and removal dates were given. Exclusion criteria were patients with subcutaneous venous ports, peripherally inserted CVCs, and CVCs used in the neonatal setting. The medical records of all patients included were examined by one of the investigators (F.H.) registering diagnosis, insertion date and hospital, vein, type of catheter, Systemic Inflammatory Response Syndrome (SIRS),10 Apache II score, reasons for removal, antibiotic treatment, microbial cultures, CRI, CRBSI, and mortality. Adherence to the CVC routines was not evaluated. CVC team, insertion, and care Since 1999, the hospital has had a CVC team, consisting of 2 anesthesiologists and 1 ICU nurse. This team is responsible for all written documents concerning CVC insertion, care, and removal. Written instructions are repeatedly distributed to every unit and are also available on the hospital intranet for all staff handling patients with CVCs. All CVCs are inserted by anesthesiologists, who regardless of previous experience are trained under supervision to perform CVC insertion according to instructions. ICU nurses are trained at the start of their appointment and thereafter every other year so as to ensure high adherence to the CVC care routines. Ward and OPD nurses manage the daily care of CVCs outside the ICU. These nurses are supervised by specially trained department nurses, who constitute a hospital network that relies on the CVC team. Furthermore, the CVC team, or the anesthesiologist on call, are available around the clock for handling CVC problems. Tip cultures of all removed CVCs are used as surveillance and follow-up of the infection prevention program. Since 2006, we have monthly assessments of adherence to basic hygiene rules throughout the hospital, as part of a general quality program. The catheters were inserted by an anesthesiologist with maximal sterile precautions (cap, mask, gown, gloves, and large drape) using the Seldinger technique. The multilumen CVCs inserted in our ICU were all chlorhexidine/silver sulfadiazine catheters. No other CVCs were antimicrobiologic. The insertion site was treated with a solution of 0.5% chlorhexidine (wt/vol) in 70% alcohol (SCHA) and allowed to dry for 1 to 2 minutes prior to insertion. No prophylactic antibiotics were given. All catheters were
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secured with monofilament sutures, and the site was dressed with a semipermeable dressing (Tegaderm HP; 3M Healthcare, St. Paul, MN). CVC insertion was documented in the patient’s records after completion of the procedure and registered on a computer. Tunneled CVC sutures were removed, and no semipermeable dressing was used when the subcutaneous cuff had firmly healed. Every third day (every seventh day for OPD patients), dressing, stopcocks, and injection membranes were changed, and the insertion site was treated with SCHA. Heparin flushing and locks were not routinely used, except for patient on hemodialysis outside the ICU. The catheters were flushed after every infusion with 10 mL of saline, 4 times, to prevent occlusion. Resting CVCs (>24 hours) were not routinely flushed. Lipid solutions were administered via a separate lumen when a multilumen catheter was used. All CVCs were supposed to be cultured on removal. Microbiology The catheters were removed after site treatment with SCHA that was allowed to dry. The distal 5 cm of the CVC tip was cut off and deposited in a sterile container and cultured using a semiquantitative standardized roll plate method.11 The tip culture result was considered positive if 1 or more colony-forming units (CFU) were found. The CVC tips were cultured within 18 hours after removal. Blood cultures were performed when clinically indicated by sampling blood from another vessel. The bottles were incubated 6 days using an automated blood culture system (BAc/ALERT; bioMériuex, Inc, Durham, NC). Isolates were identified using standard methods at the local microbiology laboratory. Antibiotic susceptibility tests were performed according to Swedish standards (www.srga.org; January 1, 2007). Definitions CVC colonization was defined as a positive tip culture with 1 CFU regardless of clinical symptoms.8 The reason for this was to evaluate whether tip culture alone could be a surrogate marker for CRI or CRBSI. We also used a second, commonly employed, definition of colonization (15 CFU).11 CRI was defined as a positive tip culture from a patient having at least 2 SIRS symptoms at CVC removal, and no other known source of infection, independently of blood culture results.8,10,12 CRBSI was defined as isolation of microorganisms from the tip culture and a blood culture drawn from another vessel (within 48 hours prior or after CVC removal) that were indistinguishable.12 Isolates were regarded as indistinguishable if they shared the same phenotype and antibiogram. Duration of catheterization was defined as the number of days from insertion to removal of the CVC. All catheters that were used to some extent in the ICU were regarded as ICU catheters. Statistical analysis Associations and differences among groups were assessed using
c2 test, Student t test, or Mann-Whitney test as appropriate. The correlations between different incidences were evaluated with Spearman rank correlation test. Variations of variables over time were analyzed using linear regression analysis (LR). Univariate logistic regression analyses were performed to estimate the risk for colonization, CRI, and CRBSI. Multiple logistic regression models, controlling for catheterization time with following stepwise introduction of significant risk factors, were performed. All analyses were conducted using a statistical software package (version 19.0 for Windows; IBM SPSS, Armonk, NY). Variations in incidence over time were analyzed with statistical process control (SPC) methods.13 Seldom occurring events (CRI and
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CRBSI) were analyzed using geometrical charts, evaluating the number of CVCs removed between each infection episode. The central line (CL) and upper control line (UL) were defined as follows: CL ¼ mean 0.693 and UL ¼ mean þ 3 O(mean (mean þ 1)). Frequently occurring events (colonization) were analyzed using individual charts, evaluating quarterly incidences of colonization (CL ¼ mean, UL ¼ CL þ 2.66 moving range, and lower control limit (LL) ¼ CL e 2.66 moving range). Special causes of variation were defined as a run of 8 or more points on one side on the central line, 1 point outside the upper or lower control limit, or a run of 6 or more points all trending up or down. SPC analyses were conducted using a statistical software package (Microsoft Excel 2010; Microsoft Corp, Redmond, WA). RESULTS Patients and CVCs A total of 2,053 CVCs was cultured during the study period, representing 74% of all CVCs used at the hospital. Insertion date could not be found in 8 cases, and, hence, 2,045 catheters from 1,674 patients were included in the study. The median patient age was 65 years (range, 0.2-99), and 57% were male; 1,453 of the catheters were to some extent used on the ICU, and the median Apache II score of the ICU patients was 22 (range, 2-44). The median duration of catheterization was 8 days (range, 0-1,617) giving a total of 45,026 CVC-days. The proportion of patients with SIRS was 42% in all patients and 54% in the ICU group. Diagnosis, insertion hospital, catheter type, vein, and reasons for removal are presented in Table 1. Antibiotics were used in 1,521 (74.4%) cases on the day of CVC removal. Blood cultures were taken at the time of removal in 578 (28.3%) cases. Four hundred one CVCs (19.6%) were removed from patients who died with their catheter in place. There was a continuous increase in the number of CVCs used each year (Table 2) from 269 to 424 (LR; adjusted r2 ¼ 0.95, b ¼ 33.6, P ¼ .001). There was also an increase in the use of the internal jugular vein from 31% of all CVCs to 58% (LR; adjusted r2 ¼ 0.90, b ¼ 6.0, P ¼ .003) and a decrease in the use of the subclavian vein, from 49% to 22% (LR; adjusted r2 ¼ 0.91, b ¼ 5.9, P ¼ .002) over the study period. There were no other trends detected over time concerning patient and CVC characteristics. Colonization Three hundred fourteen (15.4%) of all CVCs showed microbial growth on tip cultures, which represents a colonization incidence of 7.0 per 1,000 CVC-days. Forty-nine CVCs were found to have more than 1 isolate. The incidences of colonization over time for all patients and different subgroups are presented in Table 2. There was a significant correlation between the quarterly colonization incidences defined as 1 CFU as compared with 15 CFU (r ¼ 0.89, P < .05) (Fig 1). The predominant species were coagulase-negative staphylococci (CoNS) (63.8%), Candida albicans (7.9%), Staphylococcus aureus (7.5%), Enterococcus faecalis (5.8%), and Enterococcus faecium (2.1%). All other species represented less than 2%. CRI and CRBSI Fifty-two (2.5%) of the 2,045 CVC episodes were classified as having CRI and 29 (1.5%) a CRBSI. The incidence of CRI and CRBSI were 1.2 and 0.6 per 1,000 CVC-days, respectively. The incidences of CRI and CRBSI over time for all patients and different subgroups are presented in Table 2. There was a significant correlation between the quarterly incidences of CRI and CRBSI (r ¼ 0.83, P < .05) (Fig 1).
Table 1 Insertion and removal data of the 2,045 central venous catheter episodes
Total number of CVCs Inserting hospital Study hospital Other Primary diagnosis Cardiovascular Gastrointestinal Oncology Infection Trauma Others Vein Subclavian vein Internal jugular vein Femoral vein External jugular vein Unknown Type of CVC Single lumen Multilumen Dialysis Tunneled, dialysis Tunneled, 1 or 2 lumen PA introducer PA catheter Unknown Reasons for removal No need for CVC Malfunction Suspicion of CVC infection Accidental Pneumothorax Thrombosis Unknown
No.
%
2,045
100
1,796 249
87.8 12.2
372 302 273 688 144 266
18.2 14.8 13.3 33.6 7.0 13.0
627 1,017 332 13 56
30.7 49.7 16.2 0.6 2.7
483 911 308 42 59 123 84 35
23.6 44.5 15.1 2.1 2.9 6.0 4.1 1.7
1,543 90 338 7 1 1 65
75.5 4.4 16.5 0.3 0.05 0.05 3.2
CVC, central venous catheter; PA, pulmonary artery.
However, there were no significant correlations between the quarterly incidences of colonization, using either of the definitions, and CRI or CRBSI (Fig 1). Fifty-four (2.6%) patients had a CRI and/or a CRBSI, which gave an incidence of 1.2 per 1,000 days. Two cases of CRBSI were not classified as CRI because documentation of SIRS symptoms was missing. Blood cultures were negative in 8 of the 52 cases of CRI. In 7 of these 8 cases, the patients were treated with antimicrobial drugs, and, in 3 patients, the microorganisms, found on tip culture, were sensitive to the drug used. In 17 cases of CRI, blood culture was not performed. In 21 of the 29 cases of CRBSI, the patient was receiving antimicrobial drugs on removal of the CVC, and, in 12 of these, the microorganisms were sensitive to the antimicrobial drug. The microorganism most frequently isolated on tip culture in cases of CRI and CRBSI were CoNS (31%), C albicans (24%), S aureus (19%), E faecalis (9%), and Candida glabrata (3%). The median catheterization time to CRI/CRBSI was 14 days (range, 1-645). There was no significant difference in time to CRI/CRBSI for infections caused by bacteria or Candida, with median of 14 days (range, 3-645) and 13 days (range, 1-30), respectively. SPC using an individual chart did not reveal any occasion where the variation in incidence of colonization was higher or lower than expected by natural (common cause) variation (Fig 2). Analysis with geometrical charts for CRI and CRBSI revealed 2 occasions where the number of CVCs removed between 2 consecutive CRIs and CRBSIs were higher than expected, which indicated a period with infection rates lower than expected. One period of 6 consecutive measurements of CRBSI revealed a continuous downward run indicating a period of insufficient performance (Fig 2).
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Table 2 Annual number of CVCs and incidences per 1,000 CVC-days for colonization and infections
CVCs, n All ICU Non-ICU Hemodialysis* Vein Subclavian vein, n (%)y Internal jugular vein, n (%)y Femoral vein, n (%)y Colonizationz All ICU Non-ICU Hemodialysis* CRIz All ICU Non-ICU Hemodialysis* CRBSIz All ICU Non-ICU Hemodialysis*
2004
2005
2006
2007
2008
2009
267 203 64 14
267 200 67 13
332 233 99 21
369 270 99 10
387 268 119 26
423 279 144 23
130 (49) 83 (31) 39 (15)
114 (43) 103 (39) 44 (17)
116 (35) 151 (46) 56 (17)
93 (25) 200 (54) 61 (17)
80 (21) 236 (61) 61 (16)
94 (22) 244 (58) 71 (17)
Total 2,045 1,453 592 107 627 (31) 1,017 (50) 332 (16)
7.2 16.7 3.5 2.3
5.9 14.1 1.8 3.0
5.6 15.7 2.6 2.4
7.7 12.6 4.7 10.4
8.8 19.2 4.4 5.0
6.7 15.0 4.2 1.6
7.0 15.5 3.6 3.0
1.8 4.7 0.8 0.5
0.9 2.8 0 0
1.2 4.7 0 0
1.1 1.7 0.8 2.6
1.3 3.2 0.5 1.0
0.8 1.7 0.5 0
1.2 3.0 0.4 0.4
0.6 0.7 0.5 0.5
0.9 2.8 0 0
0.8 2.6 0.2 0
0.5 0.4 0.5 2
0.7 1.2 1.2 0.5
0.5 0.9 0.4 0.3
0.6 1.4 0.3 0.4
CRBSI, catheter-related bloodstream infection; CRI, CVC-related infection; CVC, central venous catheter; ICU, intensive care unit. *Hemodialysis outside the ICU. y Percentage of all CVCs. z Incidence per 1,000 catheter-days.
Fig 1. Quarterly incidences of central venous catheter colonization, catheter-related infection, and catheter-related bloodstream infection. CVC, central venous catheter; CFU, colony-forming units; CRI, CVC-related infection; CRBSI, CVC-related bloodstream infection.
All patients with a CRI or a CRBSI were successfully treated with antimicrobial drugs. Seventeen of these patients died during their hospital stay but for other reasons than CRI or CRBSI; we thus recorded no case of CVC infection mortality. Risk factor analysis Univariate logistic regression analyses revealed that catheterization time did not increase the risk for colonization or CRBSI but
increased the risk for CRI (odds ratio [OR], 1.002 per day; 95% confidence interval [CI]: 1.000-1.004, P ¼ .042). Multivariate analysis controlling for catheterization time showed the following risk factors for colonization: non-ICU use (OR, 1.3; 95% CI: 1.0-1.7, P ¼ .029), no antibiotics on removal (OR, 1.6; 95% CI: 1.3-2.1, P < .0001), internal jugular vein as opposed to subclavian vein (OR, 2.4; 95% CI: 1.7-3.3, P < .0001), and femoral vein as opposed to subclavian and jugular vein (OR, 1.4; 95% CI: 1.0-1.9, P ¼ .035). However, the risk for non-ICU use was not significant when
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Fig 2. Statistical process control: Individual chart representing the quarterly incidences of colonization showing variations exclusively explained by natural variation. Geometrical chart representing the number of removed central venous catheters between each episode of catheter-related bloodstream infection. Lined circles represents 2 periods of low infection rates not explained by natural variations. Dotted oval represents a period with increasing infection rate not explained by natural variation. CVC, central venous catheter; CRBSI, CVC-related bloodstream infection.
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antibiotic treatment or hemodialysis was controlled for. The risk factors for CRI were hemodialysis (OR, 2.8; 95% CI: 1.0-7.7, P ¼ .048) and internal jugular vein as opposed to the subclavian vein (OR, 2.6; 95% CI: 1.2-5.7, P ¼ .016). Risk factor for CRBSI was hemodialysis (OR, 4.5; 95% CI: 1.3-14.9). DISCUSSION The main finding of this study was a sustained low incidence of CVC colonization (7.0 per 1,000 catheter-days), CRI (1.2 per 1,000 CVC-days), and CRBSI (0.6 per 1,000 CVC-days) over a period of 6 years in an entire hospital patient population, with an active CVC team, where structured hygiene routines for CVC insertion, care, and removal had been implemented. Our routines for insertion and care are based on previous recommendations from the Centers for Disease Control and Prevention7 and also follow the new recommendations from 2011.14 The recommendations have been evaluated in previous studies by us and others1,8 and have been constant throughout the study. The only exception to these guidelines in this study was the use of the femoral vein as a vascular access in selected ICU patients. The hospital’s CVC team, available for education and support in the care of patients with a CVC, was formed in 1999 and has since been well established. The team or a trained anesthesiologist is available for support around the clock. All anesthesiologists are well educated in the insertion and care of CVCs, and anesthesiologists without special training are not allowed to perform the insertion procedure. Furthermore, there is a high awareness throughout the hospital of the risks for CVC infections, and results indicate good adherence to CVC hygiene routines. This awareness is promoted by a continuously ongoing education and surveillance program with tip cultures offered by the CVC team. The results from the surveillance are annually reported to all units using CVCs. We did not observe any mortality related to CVC infections. This may be due to the low incidence of CRI and CRBSI and high awareness of the importance of preventing CVC infections. Mortality can increase as a result of CVC infections, but the direct mortality rate has been difficult to define.14,15 We have not been able to evaluate the adherence to our routines, but levels of CRBSI may act as a surrogate and indirect marker of staff performance.4 We believe that high adherence and an active CVC team supporting the entire hospital are the cornerstones in low incidences of CRI and CRBSI. We have used the incidences of 3 different indicators of infectious complications related to the use of CVCs: colonization, CRI, and CRBSI. The reason for studying colonization is that it provides a picture of possible microorganisms, including their resistance patterns, thus providing guidance when treating CVC infections. The presence of microorganisms on cultured catheter tips is itself a reminder, serving to increase clinical awareness of the risk for CVC infection.6 This justifies, in our opinion, the routine of CVC tip culture for all CVCs removed.16 However, we could not verify previous findings that colonization may be used as a surrogate indicator of CRI or CRBSI.17 Most studies use CRBSI as an end point for severe infections where the point of entry of the causative microorganism is the CVC. However CRBSI, in our opinion, is a too narrow definition because it requires positive blood cultures and thus has several limitations: not always performed, antimicrobial treatment preventing growth of microorganisms, intermittent release of microorganism to the blood, and inappropriate transportation or delay in coming to the laboratory. We believe CRI to be the most valuable clinical measurement because it captures all patients with SIRS symptoms who have microorganisms on their CVC. A recent European study used a CRI definition similar to ours.16 One difficulty with the CRI definition is that the CVC must be removed for culture. Another difficulty is that
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most patients with a CVC and SIRS symptoms do not have a CVC infection.17 However, in clinical practice these patients must be evaluated by the physician responsible, who decides which action should be taken. This includes decisions on removing the CVC and performing blood cultures. Thus, in the clinical setting we prefer the quarterly incidence of CRI as an indicator of the quality of CVC care. CRBSI incidences reported by others, from both ICU and non-ICU settings, vary from around zero to 10 per 1,000 CVC-days.5 Several studies, mainly from ICUs, have shown that implementing simple CVC routines are successful in decreasing CRBSI incidence to a very low level (
