INTRODUCTION
Reliable venous access is critical for cancer patients. Totally implantable venous access devices (TIVADs) are commonly placed to facilitate delivery of intravenous chemotherapy. Compared to exteriorized catheters, TIVADs have the advantages of requiring little maintenance and having a low infection rate. [1]
Although TIVAD infections are uncommon compared to other types of catheters, the consequences of a TIVAD infection can be considerable for the patient in whom infection occurs. Central line associated blood stream infections (CLABSI) are costly, and usually requires removal of the device. In addition, subsequent treatment of the infection can delay administration of chemotherapy and require an increase in the level of care (e.g., hospital admission or home intravenous therapy).
The consequences of CLABSI to both patients and providers have been highlighted in the lay press and medical literature in recent years. Recent policies outlined by the Centers for Medicare and Medicaid Services [4], the Joint Commission [5] and the United States Department of Health [6] have made reduction of CLABSI a priority.
In order to reduce the risk of insertion-related CLABSI, prophylactic administration of an antibiotic prior to central line placement has been recommended by some practitioners [7–9]. For a single patient, the administration of a single dose of an antibiotic may seem inconsequential. As a general practice, however, unwarranted antibiotic use adds time, expense, and potential complications in the form of allergic reaction, C. difficile infection, and antibiotic resistance [10, 11]. Limiting cumulative exposure to antibiotic therapy for both the individual and the population as a whole is a critical step towards maintaining sensitivity to currently available antibiotics.
Because there is little evidence to justify the use of prophylactic antibiotics for patients undergoing TIVAD implantation in the interventional radiology suite, it has been our practice not to use them. The purpose of this paper is to report the 30 day infection rate for TIVADs placed in cancer patients by interventional radiologists without the use of prophylactic antibiotics.
MATERIALS AND METHODS
An Institutional Review Board waiver was granted for this retrospective review. The patient archiving communication system (PACS) at a single cancer center was queried to obtain a list of all patients who underwent TIVAD placement from January 1, 2009 through December 31, 2009. TIVADs removed within 30 days of placement were identified by cross referencing a PACS query of TIVAD placement with TIVAD removals from January 1, 2009 through January 30, 2010. Review of patient charts and available imaging studies was performed to confirm that TIVADs not removed remained in place at day 30 following placement.
Retrospective chart review was performed to collect patient demographic data including age, sex and cancer diagnosis. Variables in the placement including site, device type and size of the port were also recorded. Laboratory data including white blood cell count (WBC), platelet count, prothrombin time, international normalized ratio (INR), and partial thromboplastin time were recorded at the time of the procedure and for 30 days following implantation. Date, dose and type of any concomitant antibiotic and chemotherapy administered within 30 days of placement were also recorded.
The list of patients with TIVADs removed within 30 days of placement was cross-referenced with microbiology data to identify patients with positive blood cultures. The records of these patients were reviewed using CDC surveillance definitions for laboratory-confirmed central line-associated bloodstream infection (CLABSI) events. These criteria include a primary blood stream infection (1 positive culture for non-skin flora, 2 positive cultures for skin flora) in a patient who had a central venous catheter in place within 48 hours before the development of infection not related to an infection at another site.
Our technique for TIVAD placement has been described previously [12]. Pre-procedure laboratory evaluation includes WBC, platelet count and INR. Patients with absolute neutrophil count (ANC) < 1 at the time of placement were routinely given 1 gm cefazolin sodium pre-procedure. Patients with platelet counts of <20 K/mcl were transfused with 2 units of platelets peri-procedure, and patients with platelet counts of 20-49K/mcl were transfused 1 unit. Patients with INR > 2.0 were treated with Vitamin K until the INR is < 2.0 for placement. Since 2008, we have followed the recommendations of several governing agencies, including the Institute for Healthcare Improvement (IHI) and the Joint Commission, by adopting as standard procedure the components of the central venous care bundle prior to device insertion bundle [13, 14].
The access site was prepped with chlorhexidine and then draped with sterile towels. Ultrasound was used for venous access, which is achieved with a 21 gauge micropuncture system (Cook biomedical, Bloomington IN). A subcutaneous pocket was created on the anterior chest wall 4-8 cm from the venous access site. The catheter was tunneled from the pocket site to the venous puncture site. The micropuncture was exchanged over a wire for a peel away sheath and the catheter is advanced through the sheath to the high right atrium. The peel away sheath was removed and the catheter was cut to an appropriate length so that the tip was in the high right atrium or distal superior vena cava. The catheter was then attached to the port. The port was aspirated and flushed and placed in the pocket which was closed with interrupted resorbable subcutaneous stitches and either a running subcuticular stitch and/or Dermabond (Ethicon, Somerville, NJ) at the discretion of the operator.
Immediately after placement, the port was accessed with a Huber needle and flushed with heparinized saline. If the patient was scheduled for chemotherapy on the same day, the Huber needle was left in place for use; otherwise, it was removed. A sterile dressing was applied.
Statistical analysis
To determine if pre-procedure WBC, pre-procedure platelet count, post-procedure WBC, or post-procedure platelet count differed between patients who developed CLABSI and to those that did not, two-sample, t-tests were performed. To determine if pre-procedure ANC < 1, administration of antibiotics pre-procedure, or administration of chemotherapy on the day of the procedure differed between patients who developed CLABSI and to those that did not, Fisher’s exact tests were performed. All tests were two-sided and P-values <0.05 were considered statistically significant. Analyses were performed in SAS (version 9.2, SAS Institute Inc., Cary, NC).
RESULTS
1183 implantable ports were placed in 1167 patients in the one-year study period. Eighteen patients had 2 implantable ports placed. Patient demographics are shown in Table 1. Mean age was 59.2 years (range 16-92); there were 717 females and 467 males. Breast, colorectal cancer, lymphoma and pancreatic carcinoma were the most common diagnoses. Thirty-seven patients (3.2%) died within 30 days of port placement.
Table 1.
Demographic data of the patients who underwent IVAD removal within 30 days of placement for documented or presumed infection.
| Tumor type | WBC pre | WBC nadir | Plt pre | Plt nadir | Abx same day | Chemo same day | Port type | |
|---|---|---|---|---|---|---|---|---|
| CLABSI | ||||||||
| 47M | CNS lymphoma | 11.4 | 0.1 | 138 | 23 | RIJ PowerPort | ||
| 63 F | Ovarian cancer | 9.6 | 6.4 | 413 | 290 | Gemcitibine | RIJ MRI port | |
| 36 F | Unknown primary | 7.2 | 4.1 | 216 | 168 | RIJ PowerPort | ||
| 61F | Ovarian cancer | 2.5 | 1.7 | 230 | 25 | RIJ PowerPort | ||
| 70F | Unknown primary | 3.8 | 3.2 | 257 | 247 | RIJ PowerPort | ||
| 52F | Breast cancer | 10.6 | 0.5 | 363 | 20 | RIJ PowerPort | ||
| 58 F | Uterine cancer | 3.6 | 1.0 | 329 | 136 | RIJ PowerPort | ||
| CELLULITIS/NON-CLABSI INFECTION | ||||||||
| 57F | Hepatocellular carcinoma | 6.9 | 0.6 | 267 | 44 | RIJ MRI port | ||
| 70M | Gastric cancer | 6.4 | 3.3 | 210 | 100 | Ceftriaxone | RIJ MRI port | |
| 63F | Lymphoma | 5.3 | 2.9 | 270 | 142 | Cephalexin | RIJ PowerPort | |
| 62 F | Lung cancer | 7.6 | 2.2 | 139 | 78 | Cefazolin | RIJ PowerPort | |
| 23 F | Lymphoma | 11.4 | 0.1 | 46 | 2 | RIJ MRI port |
Thirty-seven (3.2%) were double-lumen TIVADs and 1144 (96.7%) were single lumen TIVADs. With the exception of 2 translumbar and one placed from right brachiocephalic access, TIVADs were placed in the right internal (1139, 96.2%) or left internal (42, 3.5%) jugular veins.
The pre placement and 30 day post placement nadir WBC and platelet counts are shown in Table 2.
Table 2.
Pre and post TIVAD placement laboratory values and clinical factors in patients who did and did not develop CLABSI within 30 days of implantation.
| Non-CLABSI | CLABSI | p value | |
|---|---|---|---|
| WBC (K/mcl) pre (mean) | 8.1 | 6.5 | 0.26 |
| WBC (K/mcl) nadir (mean) | 6.1 | 2.3 | 0.002 |
| Platelets (K/mcl) pre (mean) | 303 | 339 | 0.67 |
| Platelet nadir (K/mcl) (mean) | 217 | 135 | 0.049 |
| Chemotherapy same day | 147/1171 | 1/12 | 0.39 |
| Antibiotics same day | 7/1102 | 0/81 | 0.59 |
| ANC <= 1.0 at placement | 18/1176 | 0/7 | 0.90 |
WBC: white blood cell count
ANC: absolute neutrophil count
CLABSI: Central line associated blood stream infection
One hundred forty-eight (12.5%) ports were used on the day of placement for administration of chemotherapy. Eighty-one (6.8%) patients received antibiotics on the day of implantation. Of these, seventy patients (5.9%) received antibiotics at the time of port placement for reasons unrelated to prophylaxis for TIVAD placement. An additional 18 (1.5%) patients were neutropenic at the time of TIVAD placement (ANC < 1) and these patients were administered a prophylactic IV dose of cephalexin 1 hour prior to the procedure.
Thirteen ports (1.1%) were removed within 30 days of placement, 12 of these were removed for suspected or known infection. One port was removed and replaced because the catheter tip had migrated from the superior vena cava into the internal jugular vein. The charts of the 12 patients who had ports removed for suspected or known infection were retrospectively reviewed by an Infection Prevention Practitioner.Using CDC criteria, 7 (0.6% of ports placed, 54% of those removed for suspected infection) were removed for CLABSI. One patient who received an antibiotic (1632 mg gemcitabine IV) the day of implantation developed CLABSI. The remaining 6 patients with CLABSI were not treated with antibiotics prior to TIVAD placement. Bacterial isolates are shown in Table 3. There was no significant difference between the rate of TIVAD removal for CLABSI in patients that received pre-procedure antibiotics vs patient that did not received pre-procedure antibiotics. (p<0.59)
Table 3.
Clinical indication for IVAD removal within 30 days of placement, and bacterial isolates associated with CLABSI.
| Days in place | Indication for removal | Organism 1 | Organism 2 | |
|---|---|---|---|---|
| CLABSI | ||||
| Patient 1 M ** | 15 | bacteremia | Coag negative staph | Pseudomonas aeruginosa |
| Patient 3 F ** | 9 | bacteremia | Enterobacter cloacae | Enterococcus faecium |
| Patient 4 F ** | 21 | bacteremia | Beta hemolytic strep G | |
| Patient 8 F ** | 19 | bacteremia | Coag negative staph | |
| Patient 9 F ** | 6 | bacteremia | Klebsiella pneumonia | |
| Patient 10 F ** | 25 | bacteremia | Coag negative staph | |
| Patient 11 F ** | 6 | bacteremia | Pseudomonas aeruginosa | |
| CELLULITIS/NON-CLABSI INFECTION | ||||
| Patient 2 F | 1 | Cellulitis (tunnel) | None | |
| Patient 5 M | 21 | bacteremia | Strep viridans | |
| Patient 6 F | 15 | Fever, leukocytosis | Enterococcus | |
| Patient 7 F | 12 | Cellulitis (port pocket) | None | |
| Patient 12 F | 27 | bacteremia | Escherichia coli |
Ten of twelve ports removed within 30 days and 6 of 7 with documented CLABSI were in females. None of the 12 patients who had an ANC < 1 at the time of placement (and received prophylaxis) developed CLABSI.
The majority (1164/1167) of patients received chemotherapy within 30 days of port placement. In 148 (12.5%), the port was left accessed with a Huber needle and patients received chemotherapy on the same day of port placement. One of the documented CLABSI was in a patient who received gemcitabine the same day as port placement.
DISCUSSION
Oncology patients often require long-term intermittent access for chemotherapy, frequent blood draws and IV contrast administration for imaging studies. TIVADs are commonly the ideal device to meet these needs while minimizing adverse affects on lifestyle.
Since the 1999 publication by the Institute of Medicine [15] regarding the prevalence of hospital acquired infections, strategies to reduce CLABSI have become a focus of attention and resources. Prophylactic antibiotics prior to TIVAD placement is one of the practices that have been employed to minimize CLABSI related to central line placement [7–9].
There are, however, significant risks of injudicious use of antibiotics. Frequent use of antibiotics and cumulative antibiotic dose are known to promote antibiotic resistance and development of Clostridium difficile colitis [10]. Even a single dose of IV cephalosporin has been shown to change the intestinal flora of healthy volunteers [11].
TIVAD placement in the IR suite is a “clean procedure,” as defined as by The National Academy of Sciences/National Research Council [16] (ie outside of the genitourinary, gastrointestinal and respiratory tracts, no local inflammation or intra-procedural contamination.) For clean procedures, there is no evidence to support use of antibiotic prophylaxis [17].
Guidelines for adult antibiotic prophylaxis published by the Society of Interventional Radiology in 2004 [8] supported empiric use of antibiotic prophylaxis. The updated 2010 guidelines, on the other hand, indicate that the benefit of antibiotic prophylaxis for central venous access is unproven, and acknowledges a lack of consensus on the use of routine prophylaxis [18]. Many of the references cited in arriving at this inconclusive recommendation are the same studies referenced by the Cochrane Review of 2007 [19] that concluded that antibiotic prophylaxis for placement of tunneled central venous catheters was not justified. Most studies, however, do not distinguish between TIVAD and tunneled catheter placement.
Despite how commonly these devices are placed, there is a paucity of data regarding the role of antibiotic prophylaxis prior to TIVAD placement in the literature. One recent study published in the American Journal of Surgery [7] looked at the infection rate for TIVAD placement by two surgeons. During the 3 year retrospective study, 103 patients were treated by one surgeon who used antibiotic prophylaxis and 356 by a second surgeon who did not. Nine patients (1.9%), all of whom had TIVADs placed by the surgeon who did not use antibiotic prophylaxis, developed blood stream infection within 30 days. The authors concluded that antibiotic prophylaxis may decrease early blood stream infection following TIVAD placement. However, the retrospective, non-randomized, poorly controlled nature of the trial make interpretation of the results difficult to extrapolate to TIVAD placed by interventional radiologists.
Two recent prospective trials from Europe have addressed the issue of surgical site infection in patients undergoing TIVAD placement by surgeons.. In a series from Italy [20], patients with solid tumors and no evidence of active infection were randomized to receive either a single dose of ceftazidime or placebo. TIVADs were placed by surgical cut down using either the cephalic or external jugular vein for access. Surgical sites were evaluated for 30 days after placement and TIVADs were accessed for chemotherapy no sooner than 10 days following implantation. None of the 108 patients developed surgical site or systemic infection. The authors conclude that with strict pre and post operative care, antibiotic prophylaxis is not necessary.
In a similar trial of 404 patients from Turkey [21], patients were randomized to receive either cefazolin or placebo. TIVADS were placed from the subclavian vein using Seldinger technique in the operating room. Superficial infections were seen in 2.7% and 1 TIVAD needed to be removed. There was no significant difference in the rate of infection between the patients who received antibiotic prophylaxis and those who did not. While an excellent study, the sample size was chosen to provide statistical power based on a 6% difference in surgical site infections between the two groups.
In our series, the rate of CLABSI following TIVAD placement without the use of prophylactic antibiotics in our experience is very low, 0.7%. This compares quite favorably with other series in which prophylactic antibiotics were administered [7–9]. Notably, we did not see any increase in the risk of infection in patients who had ports accessed and used the day of implantation. Patients who developed early CLABSI were noted to have lower WBC and platelet counts within 30 days following placement, but it is difficult to arrive at any risk modification based on this observation. None of the 12 patients who were neutropenic at the time of placement (and received prophylaxis) developed CLABSI.
The strengths of this study are that the same technique and guidelines were observed by all interventional radiologists placing the TIVADs. Because we are a quaternary cancer center and patients are actively followed, we were able to document 30 day follow-up on all patients in this series.
The major limitation of this study is that it is retrospective, and as such is without a comparison group of patients randomized to receive antibiotic prophylaxis. In order to conclusively determine whether antibiotic prophylaxis is warranted for TIVAD placement, a prospective randomized study with a sample size large enough to detect a difference between groups allowing for infection rates of <1-3% is required. Additionally, such a study might afford important information regarding the safety of placing TIVADs in patients who are, or are imminently likely to become, thrombocytopenic or neutropenic, and whose TIVADS are left accessed immediately after placement.
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
REFERENCES
- 1.Groeger JS, Lucas AB, Thaler HT et al. Infectious morbidity associated with long-term use of venous access devices in patients with cancer. Ann Intern Med. 1993. December 15;119(12):1168–74. [DOI] [PubMed] [Google Scholar]
- 2.Center for Diseaes Control. Guidelines for the prevention of intravascular catheter-related infections. MMWR 2002;51 [Google Scholar]
- 3.Centers for Medicare & Medicaid Services. Hospital acquired conditions. Baltimore, MD: US Department of Health and Human Services, Centers for Medicare & Medicaid Services; 2010. (available at www.cms.gov/hospitalacqcond/06_hospital-acquired_conditions.asp) [Google Scholar]
- 4.Hospital-Acquired Conditions (HAC) in Acute Inpatient Prospective Payment System (IPPS) Hospitals. Oct, 2010.
- 5.Joint Commission Accreditation Program: Hosptial National Patient Safety Goals, Effective January 1, 2011. (available at www.jointcommission.org/assets/1/6/2011_NPSGs_HAP.pdf)
- 6.US Department of Health and Human Services. National action plan to reduce healthcare associated infections. Washington DC: US Department of Health and Human Services; 2010. (available at www.hhs.gov/ash/initiatives/hai/actionplan/index.html) [Google Scholar]
- 7.Scaife CL, Gross ME, Mone MC et al. Antibiotic prophylaxis in the placement of totally implanted central venous access ports. Am J Surg 2010. December Vol 200(6): 719–723. [DOI] [PubMed] [Google Scholar]
- 8.Ryan JM, Ryan BM, Smith T. Antibiotic prophylaxis in interventional radiology. J Vasc Interv Radiol 2004;15:547–556 [DOI] [PubMed] [Google Scholar]
- 9.El-Sheik M, Vogt M, Wagner HJ. Combined ultrasound and fluoroscopy guided port catheter implantation--high success and low complication rate. Eur J Radiol. 2009. March;69(3):517–22 [DOI] [PubMed] [Google Scholar]
- 10.Ambrose NS, Johnson M, Burdon DW, Keighley MRB. The influence of a single dose of intravenous antibiotics on faecal flora and emergence of Clostridium difficile. J Antimicrobial Chemotherapy 1985. 13:319–326 [DOI] [PubMed] [Google Scholar]
- 11.Dancer SJ. The problem with cephalosporins. J Antimicrobial Chemotherapy 2011. 48:463–478. [DOI] [PubMed] [Google Scholar]
- 12.Gandhi RT, Getrajdman GI, Brown KT et al. Placement of subcutaneous chest wall ports ipsilateral to axillary lymph node dissection. J Vasc Interv Radiol. 2003. August;14(8):1063–5. [DOI] [PubMed] [Google Scholar]
- 13.Mermel LA. Prevention of intravascular catheter related infections. Ann Intern Med 2000. 132:391–402 [DOI] [PubMed] [Google Scholar]
- 14.Pronovost P, Needham D, Berenholtz S et al. An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 355;26:2725–2732 [DOI] [PubMed] [Google Scholar]
- 15.Institute of Medicine. To Err is Human: Building a Safer Health System. Kohn LT, Corrigan JM, Donaldson MS, eds. Washington, DC: National Academy Press, 1999. [PubMed] [Google Scholar]
- 16.Altemeier WA, Burke JR, Pruitt BA, Sandusky WR editors. Manual on control of infection in surgical patients. Philadelphia: Lippincott; 1984 [Google Scholar]
- 17.Knight R, Charbonneau P, Ratzer E et al. Prophylactic antibiotics are not indicated in clean general surgery cases. December 2001. 182(6) p682–686 [DOI] [PubMed] [Google Scholar]
- 18.Venkatesan AM, Kundu S, Sacks D et al. Practice guideline for adult antibiotic prophylaxis during vascular and interventional radiology procedures. JVIR 2010. 21(11) p 1611–1630 [DOI] [PubMed] [Google Scholar]
- 19.Prophylactic antibiotics for preventing early central venous catheter Gram positive infections in oncology patients. The Cochrane Collaboration 2009. [Google Scholar]
- 20.Di Carlo I, Toro A, Pulvirenti E et al. Could antibiotic prophylaxis be not necessary to implant totally implantable venous access devices? Randomized prospective study. Surgical Oncology 2011. 20:20–25 [DOI] [PubMed] [Google Scholar]
- 21.Karanlik H, Kurul S, Saip P et al. The role of antibiotic prophylaxis in totally implantable venous access device placement: results of a single-center prospective randomized trial. Am J Surg 2011. 202:10–15 [DOI] [PubMed] [Google Scholar]