Single-dose intra-procedural ceftriaxone during endoscopic ultrasound fine-needle aspiration of pancreatic cysts is safe and effective: results from a single tertiary center

Amir Klein, Rose Qi, Shyam Nagubandi, Eric Lee, Vu Kwan

Westmead Hospital, Sydney, Australia

Department of Gastroenterology and Hepatology, Westmead Hospital, Sydney, Australia

Correspondence to: Dr Amir Klein, Department of Gastroenterology and Hepatology, Westmead Hospital, Crn Hawkesbury & Darcy Roads, Sydney, Westmead New South Wales 2145, Australia, e-mail: aaklein4@gmail.com
Received 17 October 2015; accepted 28 November 2016; published online 22 December 2016
DOI: https://doi.org/10.20524/aog.2016.0118
© 2017 Hellenic Society of Gastroenterology

Abstract

Background Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is universally used for the investigation and diagnosis of pancreatic cystic lesions (PCL). Infectious complications following EUS-FNA of PCL are rare. Antibiotic prophylaxis to reduce the risk of infection is recommended; however, there is no consensus on the optimal regimen or route of administration. Potential advantages of a single-dose intravenous (IV) antibiotic over a prolonged oral regimen include simplicity, guaranteed delivery and fewer antibiotic related adverse events, but there are only limited data to support this. We aimed to investigate the safety and efficacy of a single 1 g dose of IV ceftriaxone in preventing infectious complications following EUS-FNA of PCL.

Methods A retrospective analysis was conducted of EUS-FNA of PCL procedures performed at our center. We reviewed patient medical records for any presentation to a hospital in our district within 30 days of the procedure. An infectious complication was defined as fever/rigors, or bacteremia, or abdominal pain accompanied by imaging or laboratory results suggestive of infection, within 30 days of the procedure. Data collection included patient demographics, procedural data and outcome.

Results EUS-FNA of 204 PCL (mean size 18.0 mm) was performed. Successful fluid aspiration was achieved in 94% of cases. Single-dose IV ceftriaxone was given in 146/204 (72%) cases. Four patients had a complication (pancreatitis n=1, post-procedural pain n=3). No infectious complications and no IV antibiotic-related adverse events were identified.

Conclusion A single dose of IV ceftriaxone appears to be a safe, effective and convenient intervention for preventing infectious complications after FNA.

Keywords: Endoscopic ultrasound, fine-needle aspiration, antibiotics, infectious complications

Ann Gastroenterol 2017; 30 (2): 237-241


Introduction

Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is universally used for the investigation and diagnosis of pancreatic cystic lesions (PCL). Infectious complications (i.e. fever, infected cyst or bacteremia) following EUS-FNA are uncommon, with a reported incidence of 0-6% in various studies [1-6]. Furthermore, prospective data from studies that used antibiotic prophylaxis suggest a very low risk (0-1.4%) of infectious complications [7-9]. However, whilst the incidence is low, post-FNA infection can result in readmission to hospital and adverse patient experience.

Although antibiotic prophylaxis to reduce the risk of infection is recommended by both the American Society of Gastrointestinal Endoscopy and the European Society of Gastrointestinal Endoscopy, there is no consensus on the optimal regimen or route of administration [1,10]. Previous studies reported on the use of single-dose intravenous (IV) regimens, such as ciprofloxacin, or piperacillin/tazobactam, while commonly used 3-5 day oral regimens include ciprofloxacin or amoxicillin/clavulanic acid [7,11]. Potential advantages of a single-dose IV antibiotic over a prolonged oral regimen include simplicity, guaranteed delivery and potentially fewer antibiotic related adverse events; however, there are only limited data to support this.

Ceftriaxone is a third-generation semisynthetic cephalosporin with a long half-life. It is administered IV or intramuscularly, with an overall excellent safety profile, and has a broad spectrum of activity against Gram-positive, Gram-negative aerobic, and some anaerobic bacteria [12,13]. Ceftriaxone is well-established as the drug of choice for surgical prophylaxis [14,15].

We herein aimed to establish the safety and efficacy of a single-dose intraprocedural antibiotic (1 g IV ceftriaxone) in preventing infectious complications following EUS-FNA of PCL.

Patients and methods

Design

We conducted a single-center retrospective analysis of the safety and efficacy of single-dose IV antibiotics during EUS-FNA of PCLs. The study was approved by the local human research and ethics committee (HREC LNRSSA/15/WMEAD/121).

Patients

Patients who underwent ambulatory EUS-FNA of PCLs at our hospital between March 2006 and December 2015 were identified through an endoscopy reporting database program (ProVation MD, version 5 - ProVation Medical Inc. USA; or Endoscribe - Health Communication Network, Australia).

Procedure

Westmead Hospital is a tertiary referral center for the Western Sydney local health district, with an annual EUS case volume of over 600. Two consultant gastroenterologists with extensive EUS experience, or their advanced endoscopy fellows under direct supervision, performed all EUS procedures. Procedures were performed under conscious sedation using midazolam, fentanyl, and propofol. Standard EUS-FNA technique was used in all cases. The choice of FNA needle size was at the discretion of the endoscopist: generally, a 19 G or 22 G needle was used for a trans-gastric approach and a 22 G or 25 G for a trans-duodenal approach. Whenever possible cysts were drained to dryness. The decision to administer periprocedural antibiotics (1 g IV ceftriaxone) for non-penicillin allergic patients, or to prescribe oral antibiotics (3-5 days of amoxicillin/clavulanic acid or ciprofloxacin) on discharge from the endoscopy unit was at the discretion of the consultant performing the procedure. Patients were monitored for 1-2 h following the procedure prior to discharge. Analysis of fluid amylase and carcinoembryonic antigen were performed in the hospital pathology lab. Cytology was reported by a specialist cytologist.

Data collection

Data collection included patient demographics, procedural data and outcome. We reviewed the patient’s endoscopy report, their computerized medical records and any presentation to a hospital in our district within 30 days of the procedure. In our health district, computerized medical record software (Powerchart), which includes procedure reports, admission and discharge letters, imaging studies and all laboratory data, has been available since 2006.

Complications

An infectious complication was defined as fever/rigors, or bacteremia, accompanied by clinical symptoms such as abdominal pain, nausea and vomiting, or by radiological or laboratory evidence of an abdominal infection, all within 30 days of the procedure. Pancreatitis was defined as a ≥3-fold elevation in amylase or lipase, or typical findings on computed tomography accompanied by an appropriate clinical scenario.

Statistical analysis

Continuous data are presented as mean + standard deviation or median + interquartile range (IQR). Categorical data are presented as frequencies. The association between categorical variables was assessed using the chi-square or the Monte Carlo exact test, as needed.

Results

Patients

One hundred eighty-four patients (mean age 63 years, 60% female), underwent EUS+FNA of 204 PCLs (median size 20 mm, IQR 16-30) between March 2006 and December 2015. Single-dose IV ceftriaxone was given in 146 procedures, oral antibiotics for 3-5 days were given in 23 procedures and in 35 procedures periprocedural antibiotics were inadvertently omitted (Fig. 1).

thumblarge

Figure 1 Study flowchart

PCLs

The main indications for the procedure included evaluation of newly diagnosed PCL (84%), or surveillance of known PCL (16%). Cyst types were serous (23%), mucinous (14%), intraductal papillary mucinous neoplasms (40%), cystic tumors (17%), or undetermined (6%). Cysts were located in the pancreatic head (31%), neck (12%), body (38%), or tail (12%). Morphologically, cysts were also classified as simple (61%), oligocystic (25%), polycystic (9%), or suspected cystic tumor (5%). Fluid type was recorded as clear/watery (62%), thick/viscous (30%), turbid (5%), or pus (3%).

Procedure

EUS+FNA was attempted in 204 PCLs. Fluid was successfully aspirated in 191/204 (94%) of the cases. Most commonly, a 22 G needle was used (72%) followed by 19 G (17%) and 25 G (11%). An average of 1.3 passes were made (range 1-5). A summary of the descriptive data is presented in Table 1.

Table 1 Patient lesions and procedural characteristics

thumblarge

A total of 6 (3%) procedure-related complications were recorded in patients receiving antibiotics. Three patients had post-procedure pancreatitis (2 patients that received an oral regimen and 1 patient who received IV ceftriaxone), and 3 patients had postoperative pain that was resolved in all cases with conservative management. No infectious adverse events were encountered and no antibiotic-related adverse events were recorded in patients receiving periprocedural antibiotics. In the group of patients who did not receive antibiotics (n=35), there was one case (3%) of an infectious complication. Table 2 summarizes the complications and outcomes.

Table 2 Complications in patients receiving intravenous ceftriaxone (n=146)

thumblarge

Since our study spanned nearly a decade of clinical practice, we also analyzed the results according to years. We compared the results from procedures performed up to and including 2010 to those performed between 2011 and 2015. We found no differences in the indications, percentage of procedures where antibiotics were administered, the type of antibiotics given and the rate of complications (Table 3). We also found no differences in the study endpoints when comparing different cyst types, although the numbers for each group in this comparison were very small and hence it is difficult to draw conclusions.

Table 3 Comparison between procedures performed up to and including 2010 and those performed between 2011 and 2015

thumblarge

Discussion

EUS+FNA of PCLs has an overall favorable safety profile. However, compared to EUS+FNA of solid lesions, it appears to have a higher risk of infectious complications [1,10]. Current data demonstrate a low risk of infectious complications; however, most studies are retrospective and differ in design, patient characteristics and the use of antibiotics.

In a large retrospective study by Lee et al [16], 603 FNA were performed and only 1 patient developed an infectious complication. Antibiotics (fluoroquinolones, ampicillin, vancomycin, or gentamicin) were given at the discretion of the endoscopists and usually in cases of large cysts or incomplete drainage. However, this was not associated with a reduction in infectious complications. In a more recent study, Guarenir et al [17] reported on 1 case of cyst infection and 3 cases of antibiotic-related adverse events in a cohort of 88 patients who were given periprocedural antibiotics. In this study, multiple antibiotic regimens were used (levofloxacin in 78 cases, ciprofloxacin plus metronidazole in 3 cases, vancomycin plus gentamicin in 2 cases, piperacillin-tazobactam in 2 cases, and single-dose amoxicillin-clavulanate plus metronidazole, ampicillin, or doxycycline in 3 cases).

There are few prospective studies reporting on infectious complications in patients following EUS-FNA of PCLs. Barawi et al [2] reported no infectious complications in EUS-FNA of 108 lesions. In a study by Tarantino et al [7], 298 patients received a single dose of piperacillin/tazobactam followed by 3-5 days of oral antibiotics). Four patients (1.3%) developed fever following the procedure. Finally, Marinos et al [11] reported no infectious complications in a cohort of 85 EUS-FNA cases that were given a single IV dose of piperacillin/tazobactam or ciprofloxacin. While the results of these studies are encouraging, complex regimens involving parenteral antibiotics hours in advance of the procedure or oral courses after the procedure increase the complexity of the procedure and may result in non-adherence.

IV ceftriaxone is well-established and frequently used as the drug of choice for surgical prophylaxis [14,15]. It has an excellent safety profile and can be administered as a single IV dose during the procedure, making it an attractive alternative to more complex parenteral and oral regimens previously described. It is also less likely to contribute to the possible future development of complex antibiotic resistance. Although our study was not powered to perform a comparison of complications between the IV ceftriaxone regimen and the oral regimen, or the cases, which did not receive any antibiotics, encouragingly we had no infectious complications and no antibiotic-associated adverse events.

This study has a number of limitations. A retrospective analysis is prone to biases. The patients referred to our endoscopy unit for EUS are generally from our local health district. On discharge following EUS-FNA, all patients are routinely advised to contact us and seek medical treatment if they feel unwell in the days following the procedure. They are provided with a copy of the procedure report, which contains instructions and a telephone number for contacting our center in the event of any complications or re-presentation to medical services. We recognize that theoretically this may occur outside our local health district or in private rooms; however, we believe it is not very likely. We relied on medical records to detect complications following EUS-FNA. We elected not to contact the patients directly, since we believed there would be significant recall bias. Our sample size was not large enough to perform any comparative analysis. However, since the therapeutic intervention reported here has not been previously reported to our knowledge and the body of evidence in this area is lacking, we believe our results are important and will present physicians performing EUS-FNA with an additional, non-inferior alternative for the prevention of infectious complications.

In conclusion, EUS-FNA of pancreatic cystic lesions is safe. A single dose of intraprocedural IV ceftriaxone is a convenient, safe and effective intervention to prevent infectious complications following FNA. These results can serve as a platform to design a multicenter randomized control trial that can further investigate the role of antibiotic prophylaxis during EUS-FNA of PCLs.

Summary Box

What is already known:


  • Infectious complications following endoscopic ultrasound fine-needle aspiration (EUS-FNA) are uncommon, with a reported incidence of 0-6%

  • Both the American and the European Societies of Gastrointestinal Endoscopy recommend antibiotic prophylaxis following EUS-FNA of pancreatic cystic lesions to reduce the risk of infection

  • There is no consensus on the optimal antibiotic regimen or route of administration

  • Previous reports used complex antibiotic regimens

What the new findings are:


  • In this retrospective analysis, single-dose IV ceftriaxone was effective for the prevention of infectious complications following EUS-FNA of pancreatic cysts

  • There were no antibiotic-associated adverse events with this regimen

  • This offers clinicians a simple and safe alternative to more complex and prolonged antibiotic regimens

References

1. Early DS, Acosta RD, Chandrasekhara V, ASGE Standards of Practice Committee. Adverse events associated with EUS and EUS with FNAGastrointest Endosc 2013; 77: 839-843.

2. Barawi M, Gottlieb K, Cunha B, Portis M, Gress F, A prospective evaluation of the incidence of bacteremia associated with EUS-guided fine-needle aspirationGastrointest Endosc 2001; 53: 189-192.

3. Levy MJ, Norton ID, Wiersema MJ, Prospective risk assessment of bacteremia and other infectious complications in patients undergoing EUS-guided FNAGastrointest Endosc 2003; 57: 672-678.

4. Janssen J, König K, Knop-Hammad V, Johanns W, Greiner L, Frequency of bacteremia after linear EUS of the upper GI tract with and without FNAGastrointest Endosc 2004; 59: 339-344.

5. O’Toole D, Palazzo L, Arotçarena R, Assessment of complications of EUS-guided fine-needle aspirationGastrointest Endosc 2001; 53: 470-474.

6. Wiersema MJ, Vilmann P, Giovannini M, Chang KJ, Wiersema LM, Endosonography-guided fine-needle aspiration biopsy: diagnostic accuracy and complication assessmentGastroenterology 1997; 112: 1087-1095.

7. Tarantino I, Fabbri C, Di Mitri R, Complications of endoscopic ultrasound fine needle aspiration on pancreatic cystic lesions: final results from a large prospective multicenter studyDig Liver Dis 2014; 46: 41-44.

8. Williams DB, Sahai AV, Aabakken L, Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experienceGut 1999; 44: 720-726.

9. Bournet B, Migueres I, Delacroix M, Early morbidity of endoscopic ultrasound: 13 years’ experience at a referral centerEndoscopy 2006; 38: 349-354.

10. Polkowski M, Larghi A, Weynand B, Learning, techniques, and complications of endoscopic ultrasound (EUS) -guided sampling in gastroenterology: European Society of Gastro-intestinal Endoscopy (ESGE) Technical Guideline2012; 190-205.

11. Marinos E, Lee S, Jones B, Corte C, Kwok A, Leong RW, Outcomes of single-dose peri-procedural antibiotic prophylaxis for endoscopic ultrasound-guided fine-needle aspiration of pancreatic cystic lesionsUnited European Gastroenterol J 2014; 2: 391-396.

12. Brogden RN, Ward A, Ceftriaxone. A reappraisal of its antibacterial activity and pharmacokinetic properties, and an update on its therapeutic use with particular reference to once-daily administrationDrugs 1988; 35: 604-645.

13. Richards DM, Heel RC, Brogden RN, Speight TM, Avery GS, Ceftriaxone. A review of its antibacterial activity, pharmacological properties and therapeutic useDrugs 1984; 27: 469-527.

14. Geroulanos S, Marathias K, Kriaras J, Kadas B, Cephalosporins in surgical prophylaxisJ Chemother 2001; 13: Spec No 123-26.

15. Gorbach SL, The role of cephalosporins in surgical prophylaxisJ Antimicrob Chemother 1989; 23: Suppl D61-70.

16. Lee LS, Saltzman JR, Bounds BC, Poneros JM, Brugge WR, Thompson CC, EUS-guided fine needle aspiration of pancreatic cysts: a retrospective analysis of complications and their predictorsClin Gastroenterol Hepatol 2005; 3: 231-236.

17. Guarner-Argente C, Shah P, Buchner A, Ahmad NA, Kochman ML, Ginsberg GG, Use of antimicrobials for EUS-guided FNA of pancreatic cysts: a retrospective, comparative analysisGastrointest Endosc 2011; 74: 81-86.

Conflict of Interest: None