Clinical Radiology 70 (2015) 223e234

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Review

Antibiotics in interventional radiology J.A. Sutcliffe, J.H. Briggs, M.W. Little, E. McCarthy, A. Wigham, M. Bratby, C.R. Tapping, S. Anthony, R. Patel, J. Phillips-Hughes, P. Boardman, R. Uberoi* Department of Radiology, Oxford University Hospitals, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK

art icl e i nformat ion Article history: Received 23 March 2014 Received in revised form 28 September 2014 Accepted 30 September 2014

The range and number of interventional procedures is rapidly increasing each year. A major complication associated with many procedures is infection, which can result in serious adverse outcomes for the patient. Consequently, antibiotics are amongst the most common pharmaceuticals used by the interventionist, particularly for non-vascular procedures, yet almost no randomized controlled trial data exist to inform our decision when formulating appropriate antibiotic prophylaxis regimens. The purpose of this review is to provide an update on the utilization of antibiotics for common interventional radiology procedures, focusing on timing and duration of antibiotic prophylaxis. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Introduction Twenty-five years have passed since the first critical review of antibiotic prophylaxis in interventional radiology was published by Spies et al.1 but there still remains limited evidence for their use during interventional procedures. Spies et al.1 drew upon the surgical and medical literature in order to formulate a rational basis for the use of prophylactic antibiotics. They adapted the National Academy of Sciences/National Research Council (NAS/NRC) classification of surgical wounds2 for interventional procedures, which grouped procedures into four categories: clean, clean contaminated, contaminated, and dirty. Although not directly transferable this approach seemed reasonable. However, advances in clinical technology, such as minimally invasive techniques, and the emergence of antibiotic-resistant organisms have created new challenges * Guarantor and correspondent: R. Uberoi, Department of Radiology, Oxford University Hospitals, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK. Tel.: þ44 (0) 1865 741166; fax: þ44 (0) 1865 220801. E-mail address: [email protected] (R. Uberoi).

for the prevention of procedure-related infections, severely limiting the use of this classification as an approach to antibiotic prophylaxis in modern interventional radiology.3,4 Furthermore, broad-spectrum antibiotics can adversely affect the normal gastrointestinal flora, which may predispose patients to Clostridium difficile colitis or select for antibiotic-resistant bacterial strains such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.5 Antibiotic prophylaxis is only one aspect of reducing the risk of infection. Strict adherence to aseptic technique is as important as ever to reduce the risk of infection. This process begins when selecting the environment in which to operate and includes good skin preparation, maintenance of good sterile technique, and post-procedural wound care. Despite the limited evidence available there has been little appetite for undertaking randomized controlled trials (RCT) in the last 25 years to assess the need for antibiotic prophylaxis in interventional radiology, as they have now become the standard of care. The following recommendations are based on a comprehensive literature search including systematic

http://dx.doi.org/10.1016/j.crad.2014.09.021 0009-9260/Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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reviews, prospective and retrospective studies, and evidence obtained from expert committee reports. A judgement has also been made regarding the level of the evidence supporting these recommendations and graded according to the definitions set by the American College of Cardiology/American Heart association Task Force on Practice Guidelines.6 A fourth category has been added to the levels of evidence and describes insufficient evidence from the literature (see Appendix A).

Timing and duration of antibiotic prophylaxis In the late 1950s and early 1960s, it was demonstrated that antibiotic prophylaxis gave maximum suppression when given before the infectious challenge, i.e., 2 h19 but this will be dependent on the half-life of the antibiotic being given.

Antibiotic resistance The prevalence of multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus, vancomycinresistant enterococci, and extended-spectrum beta-lactamase producing Gram-negative bacilli, has increased in recent years and has had a dramatic effect on our ability to

fight hospital-acquired infection. The origin of this resistance is multifactorial and includes the increased use of invasive medical devices, increasing number of immunocompromised patients, lapses in infection-control practices, the non-selective use of broad-spectrum antibiotics, and the overuse and misuse of antibiotics in human healthcare and in animal feeds.20,21 Therefore, care needs to be taken when selecting an antibiotic for prophylactic use and should be specifically directed at organisms likely to be encountered during the procedure, ideally with a narrow spectrum of activity. Implementation of better hygiene measures, more effective preventative infection control, and restricted use of antibiotics in the human food chain also have a major role.22

Radiological interventions Non-vascular interventions Radiologically inserted gastrostomy (RIG) The technique of RIG was first described in 1981 and was an alternative to endoscopic gastrostomy.23 The technique involves fixing the stomach to the anterior abdominal wall via one or more gastropexies before inserting a 12e14 F gastrostomy tube through the anterior abdominal wall and into the stomach. The incidence of peristomal infections for transoral procedures ranges between 5.4e30%.24 One of the advantages of RIG is that it does not traverse the oropharynx, and therefore, does not expose the gastrostomy tube or track to the oral flora. Thus infective complications of RIG placement are rare, with a reported incidence of 2%.25 Most infectious complications are minor skin infections related to skin or mucosal flora and respond well to treatment, ie Staphylococcus epidermidis, Staphylococcus aureus, and Corynebacterium species.26 Although the use of prophylactic antibiotics has been shown to reduce the infection rate in transorally placed gastrostomies, their value in RIG has not been demonstrated. There is some evidence, however, that they may be useful in certain populations. In a retrospective study, Cantwell et al.27 assessed the use of prophylactic antibiotics for percutaneous radiological gastrostomy and gastrojejunostomy in 57 outpatients with head and neck cancer. In patients who had not received prophylactic antibiotics there was a 15% peristomal infection rate (n ¼ 3) compared with none in those who had received prophylactic antibiotics, demonstrating significantly fewer infections in the latter group (p ¼ 0.039). Currently, there is no consensus in the literature on whether antibiotic prophylaxis is required, and while some endorse their use in selected patients, others do not routinely use them.27,28 Cantwell et al.27 suggested two regimens in patients with head and neck cancer: 1 g cephazolin intravenously (IV) at the time of the procedure followed by 500 mg cephalexin twice-daily for 5 days orally or via gastrostomy or 600 mg clindamycin IV at the time of the procedure followed by 600 mg clindamycin twice-daily for 5 days orally or via gastrostomy.

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Percutaneous nephrostomy (PCN) PCN and antegrade ureteric stenting are frequently used to decompress obstructed collecting systems. The UK nephrostomy audit29 examined over 3200 nephrostomies over a 29 month period from 285 hospitals, demonstrating a post-procedural sepsis rate of only 0.01%. However, sepsis was a factor in the four recorded deaths and in the majority of major complications. As is the case with instrumentation of an obstructed biliary system, post-procedural bacteraemia is probably related to mechanical agitation of an infected system and the passage of a needle through the kidney providing transient communication between the collecting system and the surrounding vasculature The use of ultrasound can reduce the number of passages through the kidney and potentially reduce the rate of infectious complications.30 PCN is frequently used in patients who have clinical evidence of infection. In patients who have evidence of sepsis, they should be treated empirically until the organism is known. However, those without evidence of infection can be separated into those with and without risk factors. These include advanced age, diabetes, bladder dysfunction, indwelling catheter, calculi, ureterointestinal anastomosis, previous manipulation, and bacteriuria.19,28,31,32 Cochran et al.31 demonstrated that in patients with risk factors, the risk of sepsis was 50% without prophylaxis compared to 9% when prophylaxis was given. They found no statistically significant difference in patients without risk factors, although this may have been due to the small sample size (n ¼ 24). In a study involving 353 patients undergoing upper urinary tract tests or treatments, Matsumoto et al.33 showed that pyuria and hydronephrosis prior to the procedure were risk factors for febrile infectious complications. Organisms that commonly infect the urinary tract are Escherichia coli, Klebsiella species, Proteus species, and Enterococcus faecalis and other Enterobacteriaceae. Consequently, common prophylactic regimens include 1 g ceftriaxone IV,19,26,28 1.5e3 g ampicillin/sulbactam IV19,26 and 1g ampicillin with 120 mg gentamicin IV.19 In a double-blind RCT involving 100 patients a single oral dose of 500 mg ciprofloxacin was equally as effective as IV cefazolin in preventing post-procedural urinary tract infection and was associated with markedly overall lower costs.34 Oral ciprofloxacin should be given 60 min before the procedure.35

Transjugular intrahepatic portosystemic shunt (TIPS) Infection is documented in up to 20% of patients following TIPS procedures.36 Infection of the stent lumen, named endotipsitis, occurs with an incidence of 1.3%.37,38 Bacteraemia is said to be due to mesenteric bacteria seeding the systemic system and that pyrexia may be secondary to an inflammatory response in the liver following stent insertion.39 The most commonly encountered organisms post TIPS include Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella species, Lactobacillus acidophilus, Gemella morbillorum, Acinetobacter species, Streptococcus sanguis, Streptococcus bovis, and Candida albicans.37,40,41 The majority are enteric organisms. Studies

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assessing antibiotic prophylaxis at TIPS have conflicting results, and at present, there are no clinical trials demonstrating any benefit. However, these patients generally have a poor medical status and are unlikely to withstand infection; consequently, most authors give some form of antibiotic prophylaxis.19,26,28,42e45 Third-generation cephalosporins are the most commonly used, particularly ceftriaxone, which can reduce infection in patients with cirrhosis when a one-off dose of 1 or 2 g is given.46 Treatment with cefotiam, meanwhile, had no statistically significant effect on post-TIPS infection.47 Ryan et al.19 advocate ampicillin/ sulbactam because it gives superior cover against Enterococcus faecalis. In addition, patients who undergo multiple TIPS procedures and those with central venous catheters (CVCs) in situ are at increased risk of infection, and it is suggested that the CVCs should be removed following the TIPS procedure.47

Percutaneous transhepatic cholangiogram and biliary drainage Bile duct drainages are classified as “dirty” in up to 30% of malignant obstruction and up to 60% of benign obstruction,48 meaning there is purulent inflammation or perforation. The post-procedure infection rate is lower in the benign group, but can be as high as 40%.48,49 In 2012, the UK Biliary Drainage and Stenting Registry recorded a total of 833 procedures performed by 62 operators from 44 institutions. They reported post-procedure minor sepsis in 7.7% of cases and major sepsis in 3.5%.50 This compares well with the analysis of the Society of Interventional Radiology Standards of Practice Committee, which reported an incidence of 2.5% for major sepsis for both percutaneous transhepatic biliary drainage and percutaneous cholecystostomy.51 Post-procedural bacteraemia is thought to be secondary to mechanical agitation of an infected biliary system and the passage of a needle through the liver providing transient communication between the biliary system and the surrounding vasculature. The use of ultrasound can reduce the number of passages through the liver and potentially reduce the rate of infectious complications.30 Risk factors for bacterial colonization include age, diabetes mellitus, fever, acute cholecystitis, and previous biliary surgery, while the risk factors for sepsis are previous biliary instrumentation and bilio-enteric anastomosis.19,47,52,53 The most commonly cultured organism post-biliary intervention are Enterococcus species, while Escherichia coli and Clostridium species are associated with 75% of fatal biliary sepsis.19,53 Other commonly cultured organisms include Klebsiella species, Streptococcus viridans, Enterobacter cloacae, Bacteroides species, and several yeasts.19 As a result, most authors agree on the use of antibiotic prophylaxis,19,26,54 but not on the most appropriate agent. Some advocate the use of third-generation cephalosporins due to their high rate of biliary excretion,19 whereas others advocate the addition of a broad-spectrum beta-lactam antibiotic, such as mezlocillin,52 or the use of ampicillin/sulbactam due to their activity against Enterococcus species.19 Typical regimens include 1 g ceftriaxone IV,19,26,28 1 g cefotetan IV with 4 g mezlocillin IV,55 1.5e3 g

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ampicillin/sulbactam IV and 2 g ampicillin IV with 1.5 mg/ kg gentamicin IV. Venkatesan et al.56 recommend vancomycin or clindamycin and an aminoglycoside in patients with penicillin allergy.

Paracentesis and thoracentesis Percutaneous drainage of ascitic and pleural fluid may be performed in order to determine the aetiology or to provide symptomatic relief. In most cases, the fluid is sterile. Cervini et al.57 studied 2489 thoracenteses and 2536 paracenteses performed over a 2 year period. No infections occurred following thoracentesis and only four infections occurred following paracentesis (0.16%). Infections were primarily skin flora and included Staphylococcus aureus and Streptococcus viridans. Most patients improved following antibiotics. However, one died 5 days following paracentesis, although death was thought to be due to multi-organ failure.57 The British Thoracic Society have issued guidelines for pleural procedures and thoracic ultrasound58 stating that antibiotic prophylaxis is not recommended for non-trauma patients requiring a chest drain. Similarly, guidelines on paracentesis for ascites in malignancy59 and ascites in cirrhosis60 do not recommend antibiotic prophylaxis. Several studies have examined the use of tunnelled percutaneous catheters, predominantly for the treatment of malignant ascites and pleural effusions. These reported relatively minor infectious complications, which responded well to prompt wound care and oral antibiotics.61e64 No studies have investigated the use of prophylactic antibiotics with these devices, but given their low infection rate, are unlikely to be beneficial.

Percutaneous abscess drainage Antibiotic use in abscess drainage crosses the line between prophylaxis and treatment. Most patients are already likely to be on treatment, at least empirically. The Standards of Practice Committee for the Society of Interventional Radiology26 propose that antibiotic prophylaxis be reserved for patients with clinical symptoms and signs of infection, such as fever and leucocytosis to avoid the unnecessary use of wide-spectrum antibiotics. In patients with abscesses, sepsis is a risk, particularly if antibiotic coverage is inadequate. There is a risk of abscess rupture, either due to aggressive manipulation of the guide wire or an immature abscess wall, leading to contamination of the surrounding cavity/space.65 Where empirical antibiotic therapy has already commenced, knowledge of the timing of the administration is important, as it may be necessary to administer an additional dose prior to performing the procedure. Timing will be dependant infusion times of the antibiotic agent. If empirical antibiotics have not been started and infection suspected, then knowledge of the most likely causative organisms is essential. The most common organisms in pleural infection, whether community acquired or hospital acquired, are anaerobes, particularly Streptococci species, Staphylococci species, Enterococci species and Gram-negative microbes

such as Escherichia coli, other Coliforms, Proteus species, Enterobacter species, and Pseudomonas aeruginosa.66 The British Thoracic Society recommends penicillins (e.g. amoxicillin), penicillins combined with b-lactamase inhibitors (e.g., co-amoxiclav and piperacillinetazobactam) and cephalosporins due their ability to penetrate the pleural space. Aminoglycosides should be avoided due to their poor penetration of the pleural space and possibility of inactivation in the presence of pleural fluid acidosis.67 In liver abscesses, the most common organisms are Enterobacter species, Streptococcus species, Escherichia species, Staphylococcus species, Klebsiella species, anaerobes including Bacteroides species and Pseudomonas species.68e71 There are many recommended antibiotic regimens, but the most common are third-generation cephalosporins (e.g., ceftriaxone)70 to which Webb et al.68 and Pang et al.71 recommend adding metronidazole. Liu et al.70 also recommend a carbapenem (e.g., imipenem or meropenem), an anti-pseudomonal penicillin with a b-lactamase inhibitor (e.g., piperacillinetazobactam) and a fluoroquinolone (e.g., ciprofloxacin) with or without an aminoglycoside. To each of these, Webb et al.68 recommend the addition of metronidazole to ensure coverage of anaerobic organisms. Other regimens include ampicillin, gentamicin, and metronidazole68,71 and vancomycin, gentamicin, and metronidazole.68 In the abdomen, the most common organisms involved in community-acquired infection are Enterobacteriaceae, Streptococcus species and anaerobes, in particular Bacteroides fragilis. These are also found in hospital-acquired infections in addition to Enterococcus species and Candida species.72 The World Society of Emergency Surgery Consensus Conference guidelines in 2010 recommended critically ill patients with community-acquired intraabdominal infections should be treated with co-amoxiclav or ciprofloxacin and metronidazole, whereas critically ill patients with hospital-acquired infections should be treated with piperacillin, tigecycline, and echinocandin.72 In more stable patients, or in those with risk factors for extendedspectrum beta-lactamase-producing Gram-negative bacilli, alternatives should be considered.72 These regimens are not recommendations for antibiotic prophylaxis, but empirical treatment prior to obtaining culture data, and it is important that the regimens employed should follow local guidelines.

Percutaneous biopsy The use of antibiotic prophylaxis for percutaneous biopsy has not proven beneficial except where it is necessary to traverse the rectum.32 The most common indication for transrectal biopsy is transrectal ultrasound (TRUS) prostate biopsy. The majority of infections occur within the first week following the procedure, and the most common organism isolated on urine and blood cultures is Escherichia coli.73,74 A large RCT of 537 patients receiving oral ciprofloxacin or placebo before prostate biopsy revealed the incidence of bacteriuria to be significantly lower in the antimicrobial group.75 Subsequently, guidance was published by the Canadian Urological

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Association in 201076 and the American Urological Association in 201274 recommending that broad-spectrum Gram-negative antibiotics, such as fluoroquinolones, should be administered prior to biopsy. The American Urological Society also recommend first/second/thirdgeneration cephalosporins.74 In a RCT involving 231 patients undergoing TRUS and randomized into three arms, Aron et al.77 demonstrated that a single dose of oral ciprofloxacin plus tinidazole was equally as effective as the same combination give for 3 days. Concern has also been raised about the increasing association between TRUS biopsy and subsequent infection with fluoroquinolone-resistant Escherichia coli76,78 with some centres adding an IV aminoglycoside to minimize the incidence of urinary tract infections post-TRUS biopsy.79,80

Percutaneous tumour ablation Percutaneous ablation [radiofrequency ablation (RFA), cryoablation, and microwave ablation] was first developed for use in liver lesions, but later extended to include lung, adrenal, and renal tumours. Infective complications following RFA of liver tumours can be severe and include liver abscesses, cholangitis, and peritonitis. Fortunately complications are rare and have been reported in 6 h), stenting of surgically difficult to reach areas due to the large morbidity and mortality of surgical-resection procedures and known colonization of the patient. Venkatesan et al.26 recommend 1 g cefazolin IV in high-risk patients or vancomycin or clindamycin in patients with penicillin allergy.

Stent grafts Prophylactic antibiotics in stent graft procedures is routine at most centres and infection of stent grafts is rare, below 1%,101 with a mortality between 18e29%.101e104 Infection may occur as a result of intra-operative contamination of the graft, as a secondary infection after seeding from a remote source or following the formation of an aorto-enteric fistula.105 Fistulas may result from vascular inflammatory processes, such aortitis, stent graft migration, vascular or bowel erosion by the metallic components used

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in grafts, and coils or fabric failure.105 Ducasse et al.102 have also demonstrated a possible link to the operating environment with 62.5% of all infections procedures performed in the interventional suite as opposed to the operating theatre. In a study investigating 1432 endovascular aneurysm repair (EVAR) and thoracic EVAR (TEVAR) procedures covered by prophylactic antibiotics over a 13 year period 12 stent graft infections were identified.101 Of these one-third were due to Staphylococcus species, one-third due to Streptococcus species, and the remaining third due to Escherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, and Listeria monocytogenes. The incidence was significantly higher in the emergency setting (0.56% versus 2.79%; p ¼ 0.002), probably due to improper planning and preparation in the emergency setting, whereas there was no significant difference between EVAR and TEVAR procedures. During the study period, three of the 12 patients with infection died. Therefore, despite the rarity of stent graft infection, most authors believe the high mortality justifies the use of prophylactic antibiotics.19,28,101 Suggested regimens include 1 g cephazolin IV19,26,28,93 or vancomycin or clindamycin in patients with penicillin allergy.26

Closure devices A meta-analysis of RCTs,106 which included 7528 patients, examining the efficacy of vascular closure devices following angiography and angioplasty demonstrated an infection rate of 0.6% and is similar to other large studies.107 The most common organism was Staphylococcus aureus108 and the sequelae can be severe and include groin cellulitis and femoral arteritis.107,109 Certain factors are known to increase the risk of infection and include obesity, diabetes mellitus, re-intervention within 1 week, and re-intervention in a groin in which a percutaneous closure device has been placed in the last 6 months.107,110 In 2013, Jaffan et al.111 performed a large systematic literature review and metaanalysis, which included 3606 arterial accesses in which a vascular closure device was used during percutaneous endovascular aortic repair. They found a groin infection rate of 0.003% (2/592) in patients who received antibiotic prophylaxis and 0.002% (5/3014) in patients who did not receive antibiotic prophylaxis. There was no statistical significance between the two groups (p ¼ 0.3232), although this may be due to the small number of infections in the two groups. At present, given the low infection rate and risks associated with antibiotic prophylaxis, their use is not recommended.

Uterine artery embolization Uterine artery embolization is now a well-accepted treatment option for symptomatic fibroids and is included in the National Institute for Health and Care Excellence (NICE) pathway for heavy menstrual bleeding. After embolization, infarcted submucosal fibroids are at risk of infection.112 This may occur either by direct invasion of bacteria or secondary to failure of the mechanical and immunological function of the endocervix.113,114 The risk of infection lies between 0.2e2%.114e116 In the Ontario Uterine Fibroid Embolization Trial, which included 555 women, prophylactic antibiotics were only routinely given at four

centres, whereas the remaining four reserved prophylaxis for high-risk patients. They reported two hysterectomies related to infection following 570 procedures, one in each group.115,117 There have been four reported deaths in the literature, two related to sepsis118,119 and two following pulmonary embolism.120,121 The most common organisms encountered are skin commensals, i.e., Staphylococcus species and Streptococcus species, and these have been cultured in sepsis following embolization.118 Despite the low complication rate and lack of evidence, antibiotic prophylaxis is widely used.19,26,28,93,122e124 The joint working party of the Royal College of Radiologists and the Royal College of Obstetricians and Gynaecologists in the UK state that although data on the use of perioperative antibiotics are limited, ultimately the use of antibiotics is at the discretion of local hospital policy. They conclude that evidence for the use of prophylactic antibiotic therapy in vaginal hysterectomy, caesarean section, and colorectal surgery would suggest that single-dose antibiotic prophylaxis is reasonable and that a drug combination such as metronidazole with a cephalosporin, a quinolone such as ciprofloxacin, gentamicin, or amoxicillin may be used, but ultimately the use of antibiotics is at the discretion of local hospital policy.125

Transcatheter arterial chemoembolization Transcatheter arterial chemoembolization (TACE) is a common treatment option for patients with inoperable hepatocellular carcinoma or metastases. The most common infectious complication is abscess formation with a reported risk of 1e2% with a functional sphincter of Oddi and 0e15% in the presence of a bilioenteric anastomosis, biliary stent or sphincterotomy.126e130 Therefore, the most commonly encountered organisms are usually skin flora or enteric organisms.48,131 Abscesses are likely to form due to the presence of necrotic tissue post-embolization. It acts a nidus for infection and is further contaminated by biliary pathogens when reduction in flow of the larger hepatic vessels diverts chemoembolic agents in to the smaller biliary vasculature causing damage to the bile ducts.48 This is supported by the phenomenon seen in neuroendocrine tumours in which spasm or occlusion, probably mediated by hormone release, causes damage to the bile ducts.48 In a study of 210 patients undergoing 561 local treatments of liver tumours four of four patients who developed liver abscesses had neuroendocrine tumours, three had been treated by transhepatic arterial chemoembolization and one by percutaneous intra-tumour injection.132 An increased rate of infection has also been seen following chemoembolization of sarcoma metastases, but the mechanism is not understood.129 The consensus in the literature is in favour of antibiotic prophylaxis, although there is no consensus as to the agent.26,28,48,127 Many authors advocate agents to cover enteric organisms, particularly those in the high-risk groups.26,28,48 Suggested regimens for TACE include 1 g ceftriaxone IV,19,26,133 1.5e3 g ampicillin sulbactam IV19,26,133 and 1 g cefazolin IV with 500 mg metronidazole IV pre-procedure and until discharge, followed by co-amoxiclav for 5 days post-discharge.19,26,48,133

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Central venous access CVCs are the commonest type of vascular access associated with bacteraemia. The incidence lies between 0.6 and 6.5 episodes per 1000 catheter days and increases linearly with duration of catheter use.134 Infection constitutes the most challenging and life-threatening complication of vascular access, causing significant morbidity, mortality, and loss of access.135 Risk factors include the site at which the catheter is placed, the skill of the operator, the type of barrier precautions used, haematological diseases, neutropaenia, young age, high-dose chemotherapy, and parenteral nutrition.136,137 The most common organisms are those that colonize the skin and the catheter hub. Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, are most commonly implicated, but Staphylococcus aureus, Candida species and enterococci are also common. There are no studies demonstrating a reduction in the incidence of catheter-related infection following the use of oral and parenteral antibacterial or antifungal agents.138e140 However, two studies that evaluated the use of vancomycin in total parenteral nutrition in a neonatal population demonstrated a reduction in catheter-related bacteraemia.141,142 Spafford et al.141 also demonstrated a reduction in catheter-related bacteraemia. However, neither study recommended the widespread use of this practice due to the uncertainty surrounding the emergence of vancomycinresistant organisms. In a systematic review of antibiotic prophylaxis to prevent Gram-positive CVC infections in paediatric and adult oncology patients five studies were identified, which assessed flushing of the tunnelled-CVCs with a vancomycin/ heparin solution.143 The method reduced the incidence of tunnelled-CVC infections significantly (OR ¼ 0.43, 95% CI: 0.21e0.87). They also reviewed four studies evaluating the use of vancomycin/teicoplanin prior to tunnelled-CVC insertion and found no reduction in the incidence of Gram-positive infections (OR ¼ 0.42, 95% CI: 0.13e1.31). The consensus in the literature, therefore, is to recommend no prophylactic antibiotics prior to CVC insertion.26,138,139,143e146 However, exceptions are made in certain immunocompromised populations where prophylaxis may be considered on a case-by-case basis (i.e., oncology patients receiving chemotherapy, patients who are neutropaenic at the time of the CVC insertion, patients undergoing a bone marrow transplant, and neonates).26,143,144 A number of studies have shown a reduction in catheterrelated infections when maximum sterile barrier (MSB) precautions were used.138,144,145,147e150 These are defined as the use of a sterile gown, gloves, a hat, and full body drape. These were compared to sterile gloves and a small drape in an RCT involving 343 patients. Catheter-related septicaemia was 6.3 times higher in the sterile gloves and small drape only group (p ¼ 0.06). In addition, infection occurred much later in the MSB group.150 Given the relatively low cost of these measures, lack of adverse patient reactions, and the

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high cost associated with catheter-related infections, MSB precautions are recommended.

Inferior vena cava filter placement

Although inferior vena cava filters have been in use for nearly four decades and a variety of permanent and retrievable filters are now commercially available, infections involving these devices are extremely rare.151,152 When infection is present, it is frequently due to Staphylococcal species,151,152 reinforcing the need for good aseptic technique. Thus, the consensus within the literature is that antibiotic prophylaxis is not required in patients undergoing filter placement.

Conclusion To formulate appropriate antibiotic prophylactic antibiotic regimens it is necessary to have knowledge of the likely procedure-specific pathogens and infection issues and evidence in the form of RCTs. However, 25 years after the first review looking at antibiotic prophylaxis in interventional radiology there remains insufficient data to determine the utility of prophylactic antibiotics in interventional procedures, which has led to wide variations in practice with the potential to negatively impact outcomes. In addition, these wide variations can have a dramatic outcome on the overall costs of healthcare.34,137,153 Therefore, we have an opportunity to eliminate wasteful spending, reduce our impact on the emergence of antibiotic-resistant organisms, and improve healthcare outcomes, but further evidence is unquestionably needed. Most of the evidence presented in this paper comes from observational studies, case series, and the surgical literature, and although it aims to guide and inform readers, it should not be regarded as a rigorous set of rules. There are many varied practices in use in interventional radiology, many of which are valid, and until well-designed studies are performed to determine in which situations prophylactic antibiotics are necessary, which agents are best, and their preferred method of administration, there will remain many varied practices. Nevertheless, a number of things are clear: (1) prophylaxis when necessary should be given immediately prior to the procedure for optimum effect; (2) where possible single agents with a narrow spectrum of activity should be used to avoid the emergence of antibiotic resistance; (3) account should be taken of the clinical circumstances of the patient, including any surgical history; (4) the choice of agent is likely to differ between hospitals depending on local factors and resistant organisms and will require continuous review, preferably with input from the local microbiology department; (5) the importance of maximum sterile precautions cannot be overstated: given their relatively low cost, lack of adverse reactions, and effectiveness in reducing catheter-related infections, their use is strongly recommended. A summary of the findings can be found in Appendix B.

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Appendix A

Class

Definition

Level of evidence

Definition

I

Benefit >>> Risk Procedure/treatment SHOULD be performed/administered

A

IIa

Benefit >> Risk IT IS REASONABLE to perform procedure/administer treatment Benefit  Risk Procedure/treatment MAY BE CONSIDERED No benefit or may cause harm

B

Multiple populations evaluated Data derived from multiple randomized controlled trials or meta-analyses Dated derived from a single randomized controlled trial or randomized studies Only consensus opinion of experts, case studies, or standard of care Insufficient evidence to draw a conclusion

IIb III

C D

Appendix B APPENDIX B Procedure

Commonly encountered organisms

Summary of evidence

Regimens suggested in the literature

Reference

Level

of

recommendati

Level

on Percutaneous

Staphylococcus epidermidis

No consensus

-

gastrostomy

Staphylococcus aureus

Yes (patients with head and neck

1.

Corynebacterium species

cancer)

1 g cefazolin IV prior to procedure + 500 mg cephalexin bd po for 5

27,28

III

D

27

IIb

C

27

IIb

C

IIa

C

days 2.

600 mg clindamycin IV prior to procedure + 600 mg clindamycin bd po for 5 days

Only in high-risk patents (see text)

Percutaneous

Escherichia coli

1.

1 g ceftriaxone IV

19,26,28

nephrostomy

Klebsiella species

2.

1.5–3 g ampicillin/sulbactam IV

19,26

C

Proteus species

3.

1 g ampicillin + 120 mg gentamicin IV

19

C

Enterococcus faecalis

4.

500 mg ciprofloxacin po

34

B

1.

1.5–3 g ampicillin/sulbactam IV

19

2.

1–2 g ceftriaxone IV

46

Other Enterobacteriaceae TIPS

Staphylococcus aureus

Yes

Enterococcus faecalis

IIb

C B

Escherichia coli Klebsiella species Lactobacillus acidophilus Gemella morbillorum Acinetobacter species Streptococcus sanguis Streptococcus bovis Candida albicans Percutaneous

Enterococcus species

1.

1 g ceftriaxone IV

19,26,28

transhepatic

Escherichia coli

2.

1 g cefotetan IV + 4 g mezlocillin

19,26,55

C

Clostridium species

3.

1.5–3 g ampicillin/sulbactam IV

19,26

C

Klebsiella species

4.

2 g ampicillin IV + 1.5mg/kg gentamicin IV

26

C

Streptococcus viridans

5.

Vancomycin + clindamycin + aminoglycoside in penicillin allergy

26

C

cholangiogram

and

biliary drainage

Yes

IIa

C

Enterobacter cloacae Bacteroides species Several yeasts Paracentesis

and

Staphylococcus aureus

thoracocentesis

and

Streptococcus viridans

Not required

-

58–64

III

C

(As per local guidelines)

-

-

-

(As per local guidelines)

-

-

-

(As per local guidelines)

-

-

-

tunnelled percutaneous catheters Percutaneous abscess drainage: Pleura

Streptococcus species

Yes, if infection is suspected and

Staphylococcus species

empiric treatment has not started or if

Enterococcus species

empirical antibiotics have not been

Escherichia coli

administered recently

Other coliforms Proteus species Enterobacter species

Liver abscesses

Pseudomonas aeruginosa

Yes, if infection is suspected and

Enterobacter species

empiric treatment has not started or if

Streptococcus species

empirical antibiotics have not been

Escherichia species

administered recently

Staphylococcus species Klebsiella species Bacteroides species

Yes, if infection is suspected and

Pseudomonas species

empiric treatment has not started or if

Intra-abdominal

Enterobacteriaceae species

empirical antibiotics have not been

abscesses

Streptococcus species

administered recently

Bacteroides fragilis Enterococcus species Candida species

of

evidence

J.A. Sutcliffe et al. / Clinical Radiology 70 (2015) 223e234

231

Percutaneous biopsy

Skin flora

Not required

-

-

III

C

(TRUS)

Escherichia coli

Yes

1.

500 mg ciprofloxacin po

74–76

I

B

2.

1st/2nd/3rd generation cephalosporins

74

C

3.

500 mg ciprofloxacin po + 600 mg tinidazole po

77

B

1.

1 g cephazolin IV

19

2.

1.5–3g ampicillin/sulbactam IV

19,28

Percutaneous tumour ablation: Liver

No consensus but frequently used

Staphylococcus aureus Staphylococcus epidermidis

IIb

C

Enterococcus species

factors but frequently used

1.

1 g ceftriaxone IV

26

Proteus species

Yes in high-risk patients (see text)

2.

1.5–3 g ampicillin/sulbactam IV

28 19,26,28

III

C

1g cefazolin IV

19,26,100

IIb

C

Angiography/plasty

Skin flora

Bare-metal stents

Skin

flora,

particularly

Staphylococcus

Not required

-

Only in high-risk patents (see text)

1.

aureus

Stent grafts

C

No consensus in the absence of risk

Streptococcus species Renal

IIb

Streptococcus species

Yes

Staphylococcus species

2.

Vancomycin (if penicillin allergic)

19,26

3.

Clindamycin (if penicillin allergic)

19,26

1.

1 g cephazolin IV

19,26,28,93

2.

Vancomycin + clindamycin in penicillin allergy

26

C C IIb

C C

Escherichia coli Pseudomonas aeruginosa Enterobacter cloacae Listeria monocytogenes Closure devices Uterine

artery

Staphylococcus aureus

Not recommended

-

Staphylococcus species

No consensus but frequently used

1.

Cephalosporin with metronidazole

125

2.

A quinolone with metronidazole

125

3.

Gentamicin with metronidazole

125

4.

Amoxicillin with metronidazole

125

Streptococcus species

embolization

106,111

Transcatheter arterial

Skin flora

1.

1g ceftriaxone IV

19,26,133

embolization

Enteric organisms

2.

1.5–3 g ampicillin-sulbactam IV

19,26,133

3.

1 g cephazolin with 500 mg metronidazole pre-procedure + co-amoxiclav for 5/7

Central

venous

access

Coagulase-negative staphylococci

Not recommended (exceptions may

Staphylococcus aureus

be made on a case by case basis, see

Candida species

text)

-

III

A

IIb

C C

19,26,42,133 26,138,139,143,

C III

A

III

C

144,146,154

Enterococci Inferior

vena

cava

Staphylococcal species

Not required

Not required

151,152

filter placement

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