- Email: [email protected]
Antibiotic prophylaxis
INFECTION
Antibiotic prophylaxis
SSI is a common postoperative complication, affecting nearly 5% of patients overall and accounting for 14% of healthcareassociated infections.3 The true incidence of SSI may in fact be higher given the increasing proportion of surgery done on a daycase basis; many cases are now identified and treated in the community. Table 1 shows the variation in incidence of SSI with the type of surgery. SSI can lead to increased length of stay and additional costs in the order of hundreds to thousands of pounds depending on the severity and site of infection.5 Consequences for patients include the need for further surgery, additional antibiotic therapy and adverse effects associated with this, scarring, long-term discomfort, and impact on emotional wellbeing. SSI affecting anastomotic or graft sites can be life or limb threatening; SSI contributes to at least a third of all postoperative deaths.6 Risk of SSI occurs when there is bacterial contamination of the wound; the development of infection is then mediated by the virulence of the contaminating organism and the host’s natural immunological defences. The organisms that cause SSI are usually endogenous to the patient and come from their skin or any viscus that is opened. Exogenous infection develops when the wound is contaminated preoperatively (e.g. a traumatic wound), perioperatively from instruments or the theatre environment, or postoperatively before the wound has healed. Surgery can also involve transient bacteraemia, which is an important mechanism
Charlotte Hall Joanna Allen Gavin Barlow
Abstract Surgical site infection (SSI) is a common postoperative complication which leads to significant morbidity and mortality. The aim of antibiotic prophylaxis is to reduce the incidence of SSI by preventing the development of infection due to colonizing or contaminating organisms at the operative site. It is used as an adjunct to, rather than a replacement for, other evidence-based interventions to prevent wound infection, such as the use of skin antiseptics. The choice of antimicrobial agent(s) used is dependent on how clean the operation is, the operative site (which determines the likely organisms), and a variety of patient factors including the presence of allergies and colonization with resistant organisms such as meticillin-resistant Staphylococcus aureus (MRSA). The practicalities of antibiotic prophylaxis administration are discussed. Not all operations require antibiotic prophylaxis; use of antibiotics in any context, including as prophylaxis, can be associated with adverse effects, specifically an increased risk of Clostridium difficile infection (CDI) and resistance development. Prophylaxis should therefore be used responsibly. This article will address some of the common misconceptions about its use and special patient circumstances requiring deviation from the usual guidance.
Surgical site infection incidence in England by type of surgery (adapted from national surveillance data4). These data take into account SSI diagnosed as an inpatient and on readmission to hospital
Keywords Antibiotics; infection control; prophylaxis; surgical prophylaxis; surgical site infection
Surgical site infection
Type of surgery
Surgical site infection (SSI) is infection arising in a wound created by a surgical procedure or postoperative infection of any cavity, bone, joint or tissue that was involved in the surgery. It includes infection of prostheses inserted during an operation.1 SSI is diagnosed if infection occurs within 30 days of surgery (or within one year when an implant is affected), and is classified according to the tissues involved2: Superficial incisional e infection involving only skin or subcutaneous tissue at the incision site. Deep incisional e infection involving deep soft tissues (e.g. fascial and muscle layers) of the incision. Organ space e infection involving any part of the anatomy other than the incision that was opened or manipulated during the operation.
Orthopaedic Hip prosthesis Knee prosthesis Repair neck of femur Repair long bone fracture Vascular Limb amputation General vascular Neurosurgery Cranial Spinal Gastrointestinal Large bowel Small bowel Cholecystectomy Gastric Bile duct/liver/pancreatic Others Abdominal hysterectomy Breast Cardiac (non CABG) Cardiac (CABG)
Charlotte Hall MBBS BSc MRCP DTM&H is a Specialty Registrar in Infectious Diseases at Castle Hill Hospital, Hull, UK. Conflicts of interest: none declared. Joanna Allen MBChB BSc MRCP DTM&H is a Specialty Registrar in Infectious Diseases at Castle Hill Hospital, Hull, UK. Conflicts of interest: none declared. Gavin Barlow MBChB MD FRCP DTM&H is a Consultant in Infectious Diseases at Castle Hill Hospital, Hull, UK. Conflicts of interest: none declared.
SURGERY --:-
Incidence of SSI (%)
Median time to infection (days)
0.7 0.6 1.4 1.2
15 16 14 16
3.2 2.8
12 11
1.5 1.1
17 14
10.2 6.7 4.7 2.0 6.0
8 8 7 8 8
1.4 0.9 1.2 4.5
9 12 12 12
Table 1
1
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
Who is at risk of SSI and who needs prophylaxis?
in the development of infection at implant sites distant to the infection. Antimicrobial prophylaxis targets the perioperative risk of infection.
Multiple factors determine the patient’s risk of developing SSI, but predominantly risk is determined by the following: Wound environment e low haemoglobin, presence of necrotic tissue or foreign bodies, dead space, and patient colonization by MRSA (meticillin-resistant Staphylococcus aureus), Lancefield gp A/C/G Streptococci or other resistant organisms. Patient characteristics including host defence e extremes of age, presence of shock/hypoxia/hypothermia, glycaemic control, chronic illness, immunosuppressive agents, nutritional state, obesity, coexisting infection, ASA score (see below), previous SSI. Pathogen exposure e virulence of organisms, size of inoculum. Operation factors e length of scrub, skin asepsis, preoperative shaving and skin preparation, length of operation, theatre ventilation, equipment sterilization, foreign material at surgical site, surgical drains, surgical technique (haemostasis, trauma, closure). The US Centre for Disease Control NNIS (National Nosocomial Infections Surveillance) risk index9 is an internationally used scoring system based on: American Society of Anesthesiologists (ASA) score; this is calculated preoperatively by the anaesthetist and a score of >2 (3 ¼ a patient with a severe systemic disease that limits activity but is not incapacitating) is associated with increased risk of SSI. Wound class, reflecting state of contamination of the wound. Duration of operation, reflecting technical aspects of the operation.
The rationale behind antibiotic prophylaxis The aim of antibiotic prophylaxis in surgery is to prevent SSI whilst minimizing the collateral damage that occurs with all antibiotic use. This entails: (1) Using antibiotics for which there is evidence of effectiveness (i.e. a biologically appropriate agent which has, ideally, been shown in a high-quality trial to reduce infection rates); (2) minimizing the effect of antibiotics on patients’ normal flora and host defences; and (3) minimizing other adverse effects. The predominant target for prophylactic antibiotics is the wound; antibiotics are given to reduce the contaminating bacterial load so that it does not overwhelm natural host defences leading to infection. The targets of antibiotics therefore are skin/ mucosal colonizing and contaminating organisms at the operative site. Generally, for operations above the waist this involves targeting Gram positive bacteria (staphylococci and streptococci), and for operations below the waist Gram positive and Gram negative bacteria (e.g. Escherichia coli). For trauma with open wounds and in oral or abdominal operations, anaerobic cover must also be considered. Antibiotic prophylaxis should not be used to prevent postoperative complications which are unrelated to the wound or surgical site, e.g. catheter-related urinary tract infections following non-urological procedures, healthcare-associated pneumonia, and intravenous access device infections. Antibiotic prophylaxis should cover the most likely infecting organisms, not all potential pathogens, and should not be used to treat developing wound infection; in this case, a treatment course of antibiotics, the choice of agent for which may be different to prophylaxis, should be prescribed. Use of prophylactic antibiotics is not a replacement for optimal patient preparation, good surgical technique and theatre environment. These factors will not be explored here, but are at least as or more important than antibiotic prophylaxis; the 2008 SSI NICE guidance7 and 2013 quality statements8 provide further information. The decision to administer prophylaxis should take into account national guidelines (e.g. SIGN/NICE), BNF advice, local patterns of drug resistance, local epidemiology of Clostridium difficile infection (CDI), and local consensus guidelines developed by anaesthetists, antibiotic pharmacists, infection specialists and surgeons. The decision must balance the individual’s risk of SSI, potential severity of consequences of SSI, effectiveness of prophylaxis in that operation, and the potential adverse consequences such as colitis. The need for prophylaxis is not always as black or white as sometimes appears in local or national guidance. In our own Trust a patient died of recrudescent C. difficile infection triggered by, as recommended in local guidance, a single dose of co-amoxiclav prior to percutaneous endoscopic gastrostomy insertion. The fact the patient had recently had CDI was not considered when an alternative lower risk agent or no prophylaxis would have been more appropriate. Decisions about challenging patients must therefore be multidisciplinary with discussions between surgeons and infection experts occurring preoperatively.
SURGERY --:-
With an increasing score the risk of SSI increases In the UK, the principal determinant in guidelines of whether to give antibiotic prophylaxis or not is how ‘clean’ the operation is. Four classes of operation exist, with an increasing rate of bacterial contamination and subsequent risk of SSI2,9: Clean e an operation in which no inflammation is encountered. The respiratory, alimentary and genitourinary tracts are not entered. There is no break in aseptic operating theatre technique. Primary wound closure is undertaken e.g. sebaceous cyst excision. Clean-contaminated e an operation in which the respiratory, alimentary or genitourinary tract is entered but there is no significant spillage (e.g. appendicectomy). Contaminated e an operation in which acute inflammation (without pus) is encountered or where there is visible contamination of the wound. For example, gross spillage from a hollow viscus during the operation or open/compound injuries operated on within 4hours. Operations in which there is a major break in aseptic technique also fall into this category; e.g. colorectal surgery. Dirty e operations in the presence of pus or devitalized tissue, a previously perforated hollow viscus, or open/compound injuries more than 4 hours old. Antibiotic prophylaxis should be administered to patients who are undergoing the following types of operation7,8:
2
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
Guide to likely organisms and potential antibiotic choices Surgical site
Common organisms
Potential antibiotics (IV unless stated)
Staphylococcus aureus, ß-haemolytic streptococci
1 Flucloxacillin or 2 Glycopeptide
Skin organisms, Gram negative bacilli, anaerobes
1 Co-amoxiclav or 2 Flucloxacillin or Glycopeptide plus Gentamicin or 3 Cefuroxime plus Metronidazole (with all of above)
Gram negative bacilli
1 2 3 4
Gram negative bacilli, group B streptococci, anaerobes
1 Co-amoxiclav* or 2 Cefuroxime plus Metronidazole or 3 Clindamycin plus Gentamicin (the latter should only be given after the cord is clamped in C-section)
Vascular Arterial reconstruction
Skin organisms
Amputation
Skin organisms, anaerobes
1 Co-amoxiclav or 2 Flucloxacillin or Glycopeptide plus Gentamicin or 3 Cefuroxime As above plus Metronidazole (with all of above)
Orthopaedic Major closed fractures and implant surgery
Skin organisms
All surgery Skin organisms Gastrointestinal Oesophagectomy Pancreatic surgery Colectomy
Genitourinary Transrectal biopsy
Co-amoxiclav or Gentamicin or Cefuroxime or Ciprofloxacin (can be given orally)
Transurethral resection prostate *If antibiotic prophylaxis is given for transurethral procedures, recent (within 6 months) MSU results should be reviewed Obstetric/gynaecological Caesarean section Vaginal/abdominal hysterectomy
*Not in C-section when antibiotics given before skin incision (NICE)
Gram negative bacilli (if surgery below waist)
Open fracture
Skin organisms, Gram negative bacilli, anaerobes
Head and neck
Oropharyngeal streptococci and anaerobes
1 Flucloxacillin or 2 Glycopeptide plus Gentamicin (if below the waist) or monotherapy with: 1 Co-amoxiclav or 2 Cefuroxime 1 Co-amoxiclav or 2 Glycopeptide plus Gentamicin or Cefuroxime plus Metronidazole (with all of the above suggestions for open fracture) 1 Co-amoxiclav or 2 Glycopeptide plus metronidazole* or 3 Clindamycin* * Consider addition of Gentamicin to the second and third regimens above if Gram negatives are of concern (continued on next page)
SURGERY --:-
3
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
Table 2 (continued ) Surgical site
Common organisms
Potential antibiotics (IV unless stated)
Thoracic Coronary artery bypass grafts Pneumonectomy
Skin organisms, Strep pneumoniae, Gram negative bacilli
1 Co-amoxiclav or 2 Flucloxacillin or Glycopeptide plus Gentamicin or 3 Cefuroxime
Neurosurgery Craniotomy
Skin organisms
1 Flucloxacillin or 2 Glycopeptide
Note: Glycopeptide ¼ Vancomycin or teicoplanin; the latter can be given as a bolus whereas Vancomycin must be given as a prolonged infusion.
Table 2
clean surgery involving prosthesis or implant placement (e.g. joint replacement) clean-contaminated surgery contaminated surgery. It should not be used routinely for clean, uncontaminated surgery that does not involve prosthesis or implant placement unless high-quality evidence suggests considerable benefit over no prophylaxis. Prophylaxis should not be used for dirty surgery as in this circumstance a treatment course of antibiotics should be prescribed. Specific guidance by individual operation is not covered in this article, but is available within the SIGN guideline.1 Guidelines generally cover elective operations, and emergency operations in the clean (e.g. open reduction internal fixation (ORIF) of closed fracture) or clean-contaminated (e.g. C-section) setting. If a surgeon believes prophylaxis is required for a procedure for which it is not routinely recommended, for example if a patient is at particularly high risk of SSI, then the case should be discussed with an infection expert with the decision clearly documented in the case-notes.
antibiotic administration. For patients who state they are allergic to penicillin (or another antibiotic), the history should include symptoms and signs, severity of the reaction, time course, temporal proximity to other drugs, and whether they have since had a penicillin (or beta-lactam) without adverse effect. The patient’s GP may need to be contacted if clarification is required. Patients who report anaphylaxis, laryngeal oedema, bronchospasm, hypotension, urticaria, local swelling or pruritic rash whilst taking penicillin should not receive beta-lactam antibiotic prophylaxis.1 Beta-lactam antibiotics include penicillins, betalactam/beta-lactamase inhibitor combinations, cephalosporins and carbapenems. Although a history of a simple rash occurring more than 24 hours after starting penicillin (or other beta-lactam) is not an absolute contraindication to beta-lactam therapy in patients with severe or life-threatening infection, the risk of an adverse reaction, which might be difficult to diagnose in the perioperative period, is generally considered to outweigh the benefit for patients with such a history. Local policies should recommend at least one alternative regimen to be used in such circumstances.
Factors determining what antibiotics to use
MRSA (meticillin-resistant S. aureus) carriage MRSA carriage is a predictor for MRSA-associated SSI, and may be a risk factor for SSI incidence.1 All NHS organizations should have MRSA screening policies for patients undergoing surgery. Almost all elective (including day case) and emergency admissions are screened for MRSA using swabs from the nose, axilla and groin (as well as other open wounds the patient has). The few exceptions to this, e.g. day case ophthalmology/endoscopy, were previously detailed in Department of Health guidance.10 In 2014, a modified admission MRSA screening guideline was published by the Department of Health which suggests that a more focused, cost-effective approach to screening should be utilised.11 Under this guidance, the mandatory screening of all admissions will be streamlined to (1) all patients being admitted to high risk specialties (defined as vascular, renal/dialysis, neuro- and cardio-thoracic surgery, haematology/oncology/bone marrow transplant, orthopaedics/trauma, and all intensive care units) and/or (2) All patients previously identified as colonized with or infected by MRSA.11 Ideally, screening for elective patients should take place during preoperative assessment to allow time for decolonization if the screen is positive.
Spectrum of cover The antibiotic chosen for prophylaxis must cover the spectrum of pathogens that are likely to cause SSI at that site; see Table 2. The local antibiotic protocol (where one exists) should be used as this will have been developed taking into account factors such as the local epidemiology of antibiotic resistance and CDI and cost. Penicillin allergy True penicillin allergy is relatively rare, but important to detect. This is because patients allergic to penicillin are more likely to be allergic to other beta-lactam agents (e.g. cephalosporins), which are commonly used for surgical prophylaxis. Many patients consider themselves to be allergic to penicillin when in fact they have suffered non-immunological adverse reactions, in particular diarrhoea or vomiting. This can be clarified by accurate history taking at the preoperative assessment and is important as the alternative non-beta-lactam agents recommended for patients with true penicillin allergy are likely to be less effective. Allergy means the development of a rash or anaphylactic or anaphylactoid reaction that is temporally associated with
SURGERY --:-
4
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
caesarean section; advice has previously tended to favour administration at the time of cord clamping rather than at skin incision to reduce fetal exposure. Recent SIGN review did not identify a rise in neonatal morbidity with administration at skin incision and there is concern about whether delay increases the risk of maternal SSI. Current guidance is that antibiotics may be administered either pre-incision or after cord clamping,1 although the former may be more optimal.
If an elective patient is found to be MRSA colonized they should receive decolonization treatment preoperatively according to local guidance (usually mupirocin nasal cream topically every 8 hours plus triclosan (Aquasept)/octenidine (Octenisan)) washes daily for 5 days. There is some debate about the need to demonstrate clearance preoperatively. On the one hand, this provides reassurance to the patient and surgeon, although a notable proportion of patients will not be cleared due to, for example, resistance or poor application, but on the other hand any delay between decolonization and surgery increases the risk of a higher skin bacterial load at the time of surgery or recolonization from the environment. Decolonization therapy (and re-screening) should occur as close to the time of operation as possible. If the patient cannot be screened preoperatively (e.g. emergency surgery) and they are at high risk of being or known to be colonized with MRSA (nursing or residential home resident, previous colonization, recent hospitalization, extensive recent antibiotic exposure), the prophylactic regimen should include MRSA cover (usually a glycopeptide) and decolonization should be commenced as early as possible in the perioperative period.
Route of administration Generally, the IV route should be used, although some antibiotics do reach equivalent tissue concentration when given orally (e.g. fluoroquinolones). Very little data exists on the efficacy or timing of oral prophylaxis, although it is often adopted for common daycase urological procedures, such as trans-rectal prostate biopsy. In some types of surgery alternative routes are used either alone or combined with IV prophylaxis:1 topical administration for grommet insertion impregnated cement for cemented joint replacements in addition to IV prophylaxis intracameral in cataract surgery and intracameral or intravitreal prophylaxis in penetrating eye injury intraventricular antibiotics during VP shunt neurosurgery in addition to IV antibiotics use of gentamicin-impregnated collagen fleeces or implants in AP resection for colonic carcinoma and between the sternum in cardiac surgery12,13
Practicalities: dose, timing, route of administration and duration To prevent SSI, the tissue concentration of any prophylactic agent used must be at an effective concentration (above the minimum inhibitory concentration (MIC) of any contaminating bacteria) at the time of initial skin incision. Antibiotics must therefore be administered at the correct dose and right time, and by the correct route, taking into account the pharmacokinetic profile of the antibiotics used.
Duration For many types of surgery, a single dose of antibiotic is adequate providing the half-life of the antibiotic covers the operation period. Additional doses are generally only needed for longer operations or when using agents with a short half-life. An additional dose of prophylactic antibiotic may be needed if: The operation lasts more than 4 hours and the antibiotic used has a pharmacokinetic profile similar to cefazolin1; in the UK, this includes flucloxacillin, co-amoxiclav and cefuroxime. There is intraoperative blood loss >1500 ml (25 ml/kg in children).1 This is because serum antibiotic concentrations are reduced by blood loss and fluid replacement, especially early in the operation when the serum levels are high, leading to levels falling below the minimum inhibitory concentration (MIC) of target bacteria. Any extra doses of antibiotic should be given after fluid resuscitation. The operation is prolonged beyond the half-life of the antibiotic used. One notable exception to the rule that a single dose of antibiotic is usually adequate is arthroplasty, where 24 hours of prophylaxis continues to be used in many centres as there is some evidence that this lowers rates of reoperation compared to a single dose.1 There is considerable debate about the need for this, however, as some centres have low SSI with single-dose regimens. Documentation of the administration of prophylactic antibiotics is often poor, but should be as for therapeutic prescriptions; minimal documentation such as ‘prophylactic antibiotics given’ in the anaesthetic or surgical record alone is unacceptable as it
Dose In general, the dose used for prophylaxis should be the same as that used for treatment1 (e.g. flucloxacillin 1 g is the usual dose for the in-patient treatment of skin/soft tissue infection and for surgical prophylaxis). For many of the commonly used prophylactic agents, the first dose does not require adjustment in renal impairment, but the timing and/or dose of subsequent doses (when recommended) may need adjustment. When adjusting dosing in patients with renal impairment, the estimated creatinine clearance using the Cockroft-Gault formula, rather than the estimated glomerular filtration rate (eGFR), should be used; advice can be sought from microbiology, infectious diseases or pharmacy. If the patient is on renal-replacement therapy, discussion with a renal physician/pharmacist is prudent. Timing Prophylaxis should be started in almost all circumstances at or less than 60 minutes prior to the first skin incision, and as close to incision time as practically possible.1 To ensure sufficient tissue concentrations are reached at the time of skin incision, however, it may need to be administered earlier for operations in which a tourniquet is used,6 if the antibiotic regimen includes an agent with a prolonged infusion time (e.g. vancomycin infusions should be started 90 minutes prior to skin incision1) or if oral prophylaxis is used. Historically there has been some debate about the timing of administration of prophylactic antibiotics in the setting of
SURGERY --:-
5
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
professionals to their asplenic status. Communication with primary care providers to ensure plans for completion of vaccination schedules, boosters, and ongoing antibiotic supply is vital.
promotes clinical errors and does not facilitate audit. Prophylactic antibiotics should be prescribed either on a dedicated proforma that is then filed in the case-notes or on the once only (STAT) section of the drug chart.
Other immunocompromized patients This includes those with HIV infection, undergoing chemotherapy, on immunosuppressive drugs, or with functional immunosuppression (e.g. due to leukaemia). These patients should receive the same prophylaxis as immunocompetent patients, but extra vigilance for the development of SSI is needed.
Special groups A variety of patient factors influence prophylaxis options. Some antibiotics, e.g. aminoglycosides, should be avoided during pregnancy. Co-morbidities that may impact on antibiotic choice include: long QT syndrome (macrolides and quinolones can cause further QT prolongation); epilepsy (quinolones lower the seizure threshold); G6PD deficiency (nitrofurantoin, quinolones and sulphonamides can precipitate haemolytic crises); myasthenia gravis (many antibiotics can worsen symptoms); and acute intermittent porphyria (multiple antibiotics can precipitate crises). Likewise, the British National Formulary and/or pharmacy, microbiology or infectious diseases should be consulted regarding potential drug interactions.
Patients at risk of infective endocarditis Infective endocarditis (IE) can occur following bacteraemia in patients with predisposing cardiac lesions.a Historically, this led to all such patients receiving prophylactic antibiotics for dental and surgical procedures. However, 2008 NICE guidance17 recommended a change in this practice, and antibiotic prophylaxis to prevent IE is no longer routinely recommended for these patients. The basis for this is that there is no consistent data showing a relationship between having such procedures and development of IE, the clinical effectiveness of antibiotic prophylaxis to prevent IE is unproven and prophylaxis may have severe negative consequences (e.g. anaphylaxis). All at-risk patients should receive information on IE prevention, including the risks and benefits of antibiotic prophylaxis and an explanation of why it is no longer routinely recommended, the importance of maintaining good oral health, and the symptoms that may indicate IE. However, prophylactic antibiotics for the sole purpose of preventing IE should not be administered except in the circumstance of GI or GU surgery at a site where there is suspected infection, when antibiotics that cover IE causing organisms (mainly Gram positive bacteria) should be given.17
MSSA (meticillin-sensitive S. aureus) colonized patients. MSSA is not systematically screened for in the majority of NHS Trusts in the same way as for MRSA. There is some evidence that decolonizing patients who are nasal carriers of MSSA reduces the risk of developing infection,14 although a Cochrane review found the protective effect disappeared if only SSI was included in the subgroup analysis (possibly due to a lack of statistical power).15 Patients known to be nasal or skin carriers of MSSA who are undergoing surgery with a high risk of major morbidity should receive preoperative or perioperative decolonization therapy as for MRSA.1 Patients undergoing splenectomy Individuals with an absent or dysfunctional spleen are at lifelong risk of overwhelming infection, particularly from encapsulated organisms (most commonly Streptococcus pneumoniae). Patients should receive pneumococcal, meningococcal, Haemophilus influenzae type b (Hib) and influenza vaccinations. In elective surgery this should occur at least 2 weeks prior to surgery. In emergency cases, immunizations should ideally be given two weeks after surgery when physiological recovery has occurred (they should be given prior to discharge or a clear plan made with the patient’s general practitioner for immunization at two weeks). For patients undergoing chemotherapy, immunizations should, ideally, be given at least two weeks before chemotherapy commences. All high-risk patients (<16 or >50 years old or those with an inadequate serological response to pneumococcal vaccination, history of invasive pneumococcal disease, underlying haematological malignancy) should be offered lifelong prophylactic antibiotics (e.g. penicillin V 500 mg/12 hours oral or erythromycin 500 mg/12 hours oral). Lower risk patients are still at increased risk in the immediate postoperative period and should be given antibiotics, but counselled as to the risks and benefits of continuing lifelong some may choose to stop.16 Written advice about infection and the risks of overseas travel (in particular the risk of malaria) should be given to patients prior to discharge with a supply of appropriate antibiotics for emergency use. Patients should carry a card to alert health
SURGERY --:-
Paediatrics The principles of prophylaxis are the same with paediatric practice generally being extrapolated from adult prophylaxis guidance with appropriate choice and dose adjustment depending on the age and weight of the child; see SIGN guidance and local antibiotic policy for more information. The Paediatric BNF provides antibiotic dosing information. Obese patients Physiological changes in obesity affect the distribution, protein binding, metabolism and clearance of antimicrobials. Tissue distribution, in particular, is affected for hydrophilic antibiotics (b-lactams, aminoglycosides, glycopeptides) because approximately one-third of adipose tissue is water, leading to a greater volume of distribution (Vd) and lowered tissue concentrations. For lipophilic drugs (fluoroquinolones, macrolides, lincosamides, tetracyclines, tigecycline), the Vd also generally increases (to what extent is unpredictable). Antibiotic clearance is also altered by obesity.18
a
‘At-risk patients are those with acquired regurgitant or stenotic valvular disease, valve replacement, structural congenital heart disease (excluding isolated atrial septal defect and repaired patent ductus arteriosus), previous infective endocarditis, and hypertrophic cardiomyopathy.
6
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
histamine-2 antagonists, and the presence of a CDI outbreak on the ward.
Antimicrobial agents with a narrow therapeutic window (e.g. aminoglycosides) are often dosed according to weight, but it has not yet been established what index of weight is optimal (e.g. total, ideal, lean mass), given the complex pharmacokinetics and pharmacodynamics in obese patients. Other antibiotics are set at a standard dose, which may lead to sub-optimal tissue concentrations in obese patients, leading to an increased risk of SSI and resistance evolving. Some data support giving a higher induction dose of b-lactams and vancomycin in obese patients to optimize tissue concentrations, e.g. flucloxacillin 1.5 g instead of 1 g, but more research is needed.19 Local antibiotic guidance and/or infection experts should be consulted about the high-risk obese patient.
Other important issues Patient information: Information about the risk of healthcare-associated infection and SSI should be provided to patients preoperatively with additional specific information to MRSA carriers (see links to information sheets below).1,8 The risks and benefits of antibiotic prophylaxis should be discussed and patients informed if they will receive it. As around 70% of SSIs present in the community post discharge, information about postoperative wound care and recognizing the signs of SSI must also be provided. All institutions should have access to written materials for patients.1 Audit: This must be undertaken on a regular basis to assess compliance with local antibiotic prophylaxis guidelines and act as a driver for change when practice is sub-optimal. The SIGN guidelines provide criteria for standards and minimum record keeping for audit purposes. Sources of advice: Whilst local guidelines will help you with most cases, they will not cover all eventualities. Choice of antibiotic and dosing can be difficult in some cases, particularly when multiple allergies, polypharmacy and co-morbidities are present. It is also important to consider any history of previous surgical site infection. Complex cases should be discussed with your local antibiotic/infection pharmacist or microbiologist or infectious diseases physician. Some additional sources of information are suggested below. A
Patients with intercurrent infection Those with pre-existing infection that is being treated should still receive antibiotic prophylaxis and then return to the preoperative regimen. One special circumstance is those undergoing urological surgery with a proven urinary tract infection (UTI), where the prophylaxis should be tailored to cover the sensitivities of the organism identified. If a patient is deemed at operation to need therapeutic antibiotics, the prophylactic regimen may not necessarily be appropriate; relevant operative samples for microbiological testing should be ascertained and local antibiotic guidance consulted regarding the optimal postoperative regimen.
Potential negative implications of prophylaxis All antibiotic use, whether for prophylaxis or therapy or appropriate or not, carries a risk of harm through adverse reactions (e.g. rash, anaphylaxis), risk of colonization and subsequent infection with C. difficile, and the emergence of antibiotic resistance. It is these risks that drive the antibiotic stewardship agenda and advice to use the narrowest spectrum antibiotic possible for the shortest time and only when anticipated clinical benefit outweighs potential risks. Although some studies have shown that yeast-containing ‘bioyoghurts’ and natural yoghurt may reduce the incidence of antibiotic-associated diarrhoea, their use alongside antibiotic prophylaxis for SSI prevention is not currently routinely recommended.1 All antibiotics will suppress to some extent the normal, protective mucosal bacterial flora and facilitate the development of colonization with C. difficile and antibiotic resistant pathogens (e.g. MRSA). In general, these issues are greater with broader spectrum agents (e.g. third generation cephalosporins, fluoroquinolones, clindamycin, carbapenems and beta-lactam/ beta-lactamase inhibitors such as co-amoxiclav). Even a single dose of a cephalosporin (and very likely other antibiotics too) appears to increase the carriage of C. difficile20 and the incidence of C. difficile infection;21 the latter is not a benign condition and contributes notably to morbidity, length of hospital stay and mortality. Patients who have other risk factors for C. difficile colonization are particularly vulnerable, the exact prophylaxis to be used requiring careful preoperative assessment. Risk factors include age >65, previous CDI, nursing or residential home residents, recent or prolonged hospital stay, extensive co-morbidities, GI surgery, severe intercurrent illness, poor nutritional state, use of proton pump inhibitors or
SURGERY --:-
REFERENCES 1 Scottish Intercollegiate Guidelines Network (SIGN). Antibiotic prophylaxis in surgery: a national clinical guideline (Guideline number 104). Edinburgh. July 2008 (updated April 2014). Online at, www. sign.ac.uk. 2 Mangram AJ, Horan TC, Pearson ML, et al. The hospital infection control practices advisory committee (HICPAC): guideline for the prevention of surgical site infection. Infect Control Hosp Epidemiol 1999; 20: 247e78. 3 Smyth ET, McIlvenny G, Enstone JE, et al. Four country healthcare associated infection prevalence survey 2006: overview of the results. J Hosp Infect 2008; 69: 230e48. 4 Public Health England. Surveillance of surgical site infections in NHS hospitals in England. 2013/14. London: Public Health England. December 2014. Available from: www.gov.uk/phe. 5 Coello R, Charlett A, Wilson J, et al. Adverse impact of surgical site infections in English hospitals. J Hosp Infect 2005; 60: 93e103. 6 Astagneau P, Rioux C, Golliot F, et al. Morbidity and mortality associated with surgical site infections: results from the 1997e1999 INCISO surveillance. J Hosp Infect 2001; 48: 267e74. 7 National Institute for Health and Clinical Excellence (NICE). NICE guideline 74: surgical site infection. October 2008. Online at: www. nice.org.uk. 8 National Institute for Health and Clinical Excellence (NICE). NICE quality standard QS49: prevention and control of healthcareassociated infections. October 2013. Online at: www.nice.org.uk.
7
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
9 Culver DH, Horan TC, Gaynes RP, et al. Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infections Surveillance System. Am J Med 1991; 91(3B): 152Se7. 10 Department of Health (DoH). MRSA screening operational guidance 2. December 2008. Online at: http://webarchive.nationalarchives.gov. uk. 11 Department of Health. Implementation of modified admission MRSA screening for NHS. 2014. Online at: http://www.gov.uk/. 12 Eklund AM, Valtonen M, Werkkala KA. Prophylaxis of sternal wound infections with gentamicin-collagen implant: randomized controlled study in cardiac surgery. J Hosp Infect 2005; 59: 108e12. 13 Friberg O, Dahlin LG, Levin LA, et al. Cost effectiveness of local collagen-gentamicin as prophylaxis from sternal wound infections in different risk groups. Scand Cardiovasc J 2006; 40: 117e25. 14 Kallen AJ, Wilson CT, Larson RJ. Perioperative intranasal mupirocin for the prevention of surgical site infections; systematic review of the literature and meta-analysis. Infect Control Hosp Epidemiol 2005; 26: 916e22. 15 van Rijen M, Bonten M, Wenzel R, et al. Mupirocin ointment for preventing Staphylococcus aureus infections in nasal carriers. Cochrane Database Syst Rev 2008; 4: CD006216. 16 Davies JM, Lewis MPN, Wimperis J, et al. Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen: prepared on behalf of the British Committee for Standards in Haematology by a Working Party of the HaematoOncology Task Force. Br J Haematol 2011; 155: 308e17. 17 National Institute for Health and Clinical Excellence (NICE). NICE guideline 64: prophylaxis against infective endocarditis. March 2008. Online at: www.nice.org.uk. 18 Falagas ME, Karageorgopoulos DE. Adjustment of dosing of antimicrobial agents for bodyweight in adults. Lancet 2010; 375: 248e51. 19 Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy 2007; 27: 1081e91.
SURGERY --:-
20 Privitera G, Scarpellini P, Ortisi G, et al. Prospective study of Clostridium difficile intestinal colonization and disease following singledose antibiotic prophylaxis in surgery. Antimicrob Agents Chemother 1991; 35: 208e10. 21 Carignan A, Allard C, Pepin J, et al. Risk of Clostridium difficile infection after perioperative antibiotic prophylaxis before and during an outbreak of infection due to a hypervirulent strain. Clin Infect Dis 2008; 46: 1338e43. FURTHER READING AND RESOURCES Information leaflets for patients: B SSI: http://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/365839/Monitoring_surgical_wounds_for_ infection_information_for_patients.pdf B MRSA: http://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/330925/MRSA_information_for_patients.pdf B C. difficile: http://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/339322/Clostridium_difficile_fact_sheet.pdf SIGN guideline and quick reference guides: www.sign.ac.uk Cochrane reviews database: www.cochrane.org/cochrane-reviews British National Formulary: www.bnf.org (adult), http://bnfc.org/bnfc/ index.htm (paediatric) National Institute for Health and Clinical Excellence (NICE) guidelines: www.nice.org.uk Public Health England surgical site infection surveillance service: http://www.gov.uk/surgical-site-infection-surveillance-service-ssiss Other articles related to SSI in Surgery: B Phillips J, O’Grady H and Baker E. Prevention of surgical site infections. Surgery 2014;32(9):468e471. B Kelly K and Monson JRT. Hospital acquired infections. Surgery 2012; 30(12):640e644. B Thompson S and Ridgway EJ. Rational antibiotic use in surgery. Surgery 2009;27(10):435e40.
8
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
Antibiotic prophylaxis
SSI is a common postoperative complication, affecting nearly 5% of patients overall and accounting for 14% of healthcareassociated infections.3 The true incidence of SSI may in fact be higher given the increasing proportion of surgery done on a daycase basis; many cases are now identified and treated in the community. Table 1 shows the variation in incidence of SSI with the type of surgery. SSI can lead to increased length of stay and additional costs in the order of hundreds to thousands of pounds depending on the severity and site of infection.5 Consequences for patients include the need for further surgery, additional antibiotic therapy and adverse effects associated with this, scarring, long-term discomfort, and impact on emotional wellbeing. SSI affecting anastomotic or graft sites can be life or limb threatening; SSI contributes to at least a third of all postoperative deaths.6 Risk of SSI occurs when there is bacterial contamination of the wound; the development of infection is then mediated by the virulence of the contaminating organism and the host’s natural immunological defences. The organisms that cause SSI are usually endogenous to the patient and come from their skin or any viscus that is opened. Exogenous infection develops when the wound is contaminated preoperatively (e.g. a traumatic wound), perioperatively from instruments or the theatre environment, or postoperatively before the wound has healed. Surgery can also involve transient bacteraemia, which is an important mechanism
Charlotte Hall Joanna Allen Gavin Barlow
Abstract Surgical site infection (SSI) is a common postoperative complication which leads to significant morbidity and mortality. The aim of antibiotic prophylaxis is to reduce the incidence of SSI by preventing the development of infection due to colonizing or contaminating organisms at the operative site. It is used as an adjunct to, rather than a replacement for, other evidence-based interventions to prevent wound infection, such as the use of skin antiseptics. The choice of antimicrobial agent(s) used is dependent on how clean the operation is, the operative site (which determines the likely organisms), and a variety of patient factors including the presence of allergies and colonization with resistant organisms such as meticillin-resistant Staphylococcus aureus (MRSA). The practicalities of antibiotic prophylaxis administration are discussed. Not all operations require antibiotic prophylaxis; use of antibiotics in any context, including as prophylaxis, can be associated with adverse effects, specifically an increased risk of Clostridium difficile infection (CDI) and resistance development. Prophylaxis should therefore be used responsibly. This article will address some of the common misconceptions about its use and special patient circumstances requiring deviation from the usual guidance.
Surgical site infection incidence in England by type of surgery (adapted from national surveillance data4). These data take into account SSI diagnosed as an inpatient and on readmission to hospital
Keywords Antibiotics; infection control; prophylaxis; surgical prophylaxis; surgical site infection
Surgical site infection
Type of surgery
Surgical site infection (SSI) is infection arising in a wound created by a surgical procedure or postoperative infection of any cavity, bone, joint or tissue that was involved in the surgery. It includes infection of prostheses inserted during an operation.1 SSI is diagnosed if infection occurs within 30 days of surgery (or within one year when an implant is affected), and is classified according to the tissues involved2: Superficial incisional e infection involving only skin or subcutaneous tissue at the incision site. Deep incisional e infection involving deep soft tissues (e.g. fascial and muscle layers) of the incision. Organ space e infection involving any part of the anatomy other than the incision that was opened or manipulated during the operation.
Orthopaedic Hip prosthesis Knee prosthesis Repair neck of femur Repair long bone fracture Vascular Limb amputation General vascular Neurosurgery Cranial Spinal Gastrointestinal Large bowel Small bowel Cholecystectomy Gastric Bile duct/liver/pancreatic Others Abdominal hysterectomy Breast Cardiac (non CABG) Cardiac (CABG)
Charlotte Hall MBBS BSc MRCP DTM&H is a Specialty Registrar in Infectious Diseases at Castle Hill Hospital, Hull, UK. Conflicts of interest: none declared. Joanna Allen MBChB BSc MRCP DTM&H is a Specialty Registrar in Infectious Diseases at Castle Hill Hospital, Hull, UK. Conflicts of interest: none declared. Gavin Barlow MBChB MD FRCP DTM&H is a Consultant in Infectious Diseases at Castle Hill Hospital, Hull, UK. Conflicts of interest: none declared.
SURGERY --:-
Incidence of SSI (%)
Median time to infection (days)
0.7 0.6 1.4 1.2
15 16 14 16
3.2 2.8
12 11
1.5 1.1
17 14
10.2 6.7 4.7 2.0 6.0
8 8 7 8 8
1.4 0.9 1.2 4.5
9 12 12 12
Table 1
1
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
Who is at risk of SSI and who needs prophylaxis?
in the development of infection at implant sites distant to the infection. Antimicrobial prophylaxis targets the perioperative risk of infection.
Multiple factors determine the patient’s risk of developing SSI, but predominantly risk is determined by the following: Wound environment e low haemoglobin, presence of necrotic tissue or foreign bodies, dead space, and patient colonization by MRSA (meticillin-resistant Staphylococcus aureus), Lancefield gp A/C/G Streptococci or other resistant organisms. Patient characteristics including host defence e extremes of age, presence of shock/hypoxia/hypothermia, glycaemic control, chronic illness, immunosuppressive agents, nutritional state, obesity, coexisting infection, ASA score (see below), previous SSI. Pathogen exposure e virulence of organisms, size of inoculum. Operation factors e length of scrub, skin asepsis, preoperative shaving and skin preparation, length of operation, theatre ventilation, equipment sterilization, foreign material at surgical site, surgical drains, surgical technique (haemostasis, trauma, closure). The US Centre for Disease Control NNIS (National Nosocomial Infections Surveillance) risk index9 is an internationally used scoring system based on: American Society of Anesthesiologists (ASA) score; this is calculated preoperatively by the anaesthetist and a score of >2 (3 ¼ a patient with a severe systemic disease that limits activity but is not incapacitating) is associated with increased risk of SSI. Wound class, reflecting state of contamination of the wound. Duration of operation, reflecting technical aspects of the operation.
The rationale behind antibiotic prophylaxis The aim of antibiotic prophylaxis in surgery is to prevent SSI whilst minimizing the collateral damage that occurs with all antibiotic use. This entails: (1) Using antibiotics for which there is evidence of effectiveness (i.e. a biologically appropriate agent which has, ideally, been shown in a high-quality trial to reduce infection rates); (2) minimizing the effect of antibiotics on patients’ normal flora and host defences; and (3) minimizing other adverse effects. The predominant target for prophylactic antibiotics is the wound; antibiotics are given to reduce the contaminating bacterial load so that it does not overwhelm natural host defences leading to infection. The targets of antibiotics therefore are skin/ mucosal colonizing and contaminating organisms at the operative site. Generally, for operations above the waist this involves targeting Gram positive bacteria (staphylococci and streptococci), and for operations below the waist Gram positive and Gram negative bacteria (e.g. Escherichia coli). For trauma with open wounds and in oral or abdominal operations, anaerobic cover must also be considered. Antibiotic prophylaxis should not be used to prevent postoperative complications which are unrelated to the wound or surgical site, e.g. catheter-related urinary tract infections following non-urological procedures, healthcare-associated pneumonia, and intravenous access device infections. Antibiotic prophylaxis should cover the most likely infecting organisms, not all potential pathogens, and should not be used to treat developing wound infection; in this case, a treatment course of antibiotics, the choice of agent for which may be different to prophylaxis, should be prescribed. Use of prophylactic antibiotics is not a replacement for optimal patient preparation, good surgical technique and theatre environment. These factors will not be explored here, but are at least as or more important than antibiotic prophylaxis; the 2008 SSI NICE guidance7 and 2013 quality statements8 provide further information. The decision to administer prophylaxis should take into account national guidelines (e.g. SIGN/NICE), BNF advice, local patterns of drug resistance, local epidemiology of Clostridium difficile infection (CDI), and local consensus guidelines developed by anaesthetists, antibiotic pharmacists, infection specialists and surgeons. The decision must balance the individual’s risk of SSI, potential severity of consequences of SSI, effectiveness of prophylaxis in that operation, and the potential adverse consequences such as colitis. The need for prophylaxis is not always as black or white as sometimes appears in local or national guidance. In our own Trust a patient died of recrudescent C. difficile infection triggered by, as recommended in local guidance, a single dose of co-amoxiclav prior to percutaneous endoscopic gastrostomy insertion. The fact the patient had recently had CDI was not considered when an alternative lower risk agent or no prophylaxis would have been more appropriate. Decisions about challenging patients must therefore be multidisciplinary with discussions between surgeons and infection experts occurring preoperatively.
SURGERY --:-
With an increasing score the risk of SSI increases In the UK, the principal determinant in guidelines of whether to give antibiotic prophylaxis or not is how ‘clean’ the operation is. Four classes of operation exist, with an increasing rate of bacterial contamination and subsequent risk of SSI2,9: Clean e an operation in which no inflammation is encountered. The respiratory, alimentary and genitourinary tracts are not entered. There is no break in aseptic operating theatre technique. Primary wound closure is undertaken e.g. sebaceous cyst excision. Clean-contaminated e an operation in which the respiratory, alimentary or genitourinary tract is entered but there is no significant spillage (e.g. appendicectomy). Contaminated e an operation in which acute inflammation (without pus) is encountered or where there is visible contamination of the wound. For example, gross spillage from a hollow viscus during the operation or open/compound injuries operated on within 4hours. Operations in which there is a major break in aseptic technique also fall into this category; e.g. colorectal surgery. Dirty e operations in the presence of pus or devitalized tissue, a previously perforated hollow viscus, or open/compound injuries more than 4 hours old. Antibiotic prophylaxis should be administered to patients who are undergoing the following types of operation7,8:
2
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
Guide to likely organisms and potential antibiotic choices Surgical site
Common organisms
Potential antibiotics (IV unless stated)
Staphylococcus aureus, ß-haemolytic streptococci
1 Flucloxacillin or 2 Glycopeptide
Skin organisms, Gram negative bacilli, anaerobes
1 Co-amoxiclav or 2 Flucloxacillin or Glycopeptide plus Gentamicin or 3 Cefuroxime plus Metronidazole (with all of above)
Gram negative bacilli
1 2 3 4
Gram negative bacilli, group B streptococci, anaerobes
1 Co-amoxiclav* or 2 Cefuroxime plus Metronidazole or 3 Clindamycin plus Gentamicin (the latter should only be given after the cord is clamped in C-section)
Vascular Arterial reconstruction
Skin organisms
Amputation
Skin organisms, anaerobes
1 Co-amoxiclav or 2 Flucloxacillin or Glycopeptide plus Gentamicin or 3 Cefuroxime As above plus Metronidazole (with all of above)
Orthopaedic Major closed fractures and implant surgery
Skin organisms
All surgery Skin organisms Gastrointestinal Oesophagectomy Pancreatic surgery Colectomy
Genitourinary Transrectal biopsy
Co-amoxiclav or Gentamicin or Cefuroxime or Ciprofloxacin (can be given orally)
Transurethral resection prostate *If antibiotic prophylaxis is given for transurethral procedures, recent (within 6 months) MSU results should be reviewed Obstetric/gynaecological Caesarean section Vaginal/abdominal hysterectomy
*Not in C-section when antibiotics given before skin incision (NICE)
Gram negative bacilli (if surgery below waist)
Open fracture
Skin organisms, Gram negative bacilli, anaerobes
Head and neck
Oropharyngeal streptococci and anaerobes
1 Flucloxacillin or 2 Glycopeptide plus Gentamicin (if below the waist) or monotherapy with: 1 Co-amoxiclav or 2 Cefuroxime 1 Co-amoxiclav or 2 Glycopeptide plus Gentamicin or Cefuroxime plus Metronidazole (with all of the above suggestions for open fracture) 1 Co-amoxiclav or 2 Glycopeptide plus metronidazole* or 3 Clindamycin* * Consider addition of Gentamicin to the second and third regimens above if Gram negatives are of concern (continued on next page)
SURGERY --:-
3
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
Table 2 (continued ) Surgical site
Common organisms
Potential antibiotics (IV unless stated)
Thoracic Coronary artery bypass grafts Pneumonectomy
Skin organisms, Strep pneumoniae, Gram negative bacilli
1 Co-amoxiclav or 2 Flucloxacillin or Glycopeptide plus Gentamicin or 3 Cefuroxime
Neurosurgery Craniotomy
Skin organisms
1 Flucloxacillin or 2 Glycopeptide
Note: Glycopeptide ¼ Vancomycin or teicoplanin; the latter can be given as a bolus whereas Vancomycin must be given as a prolonged infusion.
Table 2
clean surgery involving prosthesis or implant placement (e.g. joint replacement) clean-contaminated surgery contaminated surgery. It should not be used routinely for clean, uncontaminated surgery that does not involve prosthesis or implant placement unless high-quality evidence suggests considerable benefit over no prophylaxis. Prophylaxis should not be used for dirty surgery as in this circumstance a treatment course of antibiotics should be prescribed. Specific guidance by individual operation is not covered in this article, but is available within the SIGN guideline.1 Guidelines generally cover elective operations, and emergency operations in the clean (e.g. open reduction internal fixation (ORIF) of closed fracture) or clean-contaminated (e.g. C-section) setting. If a surgeon believes prophylaxis is required for a procedure for which it is not routinely recommended, for example if a patient is at particularly high risk of SSI, then the case should be discussed with an infection expert with the decision clearly documented in the case-notes.
antibiotic administration. For patients who state they are allergic to penicillin (or another antibiotic), the history should include symptoms and signs, severity of the reaction, time course, temporal proximity to other drugs, and whether they have since had a penicillin (or beta-lactam) without adverse effect. The patient’s GP may need to be contacted if clarification is required. Patients who report anaphylaxis, laryngeal oedema, bronchospasm, hypotension, urticaria, local swelling or pruritic rash whilst taking penicillin should not receive beta-lactam antibiotic prophylaxis.1 Beta-lactam antibiotics include penicillins, betalactam/beta-lactamase inhibitor combinations, cephalosporins and carbapenems. Although a history of a simple rash occurring more than 24 hours after starting penicillin (or other beta-lactam) is not an absolute contraindication to beta-lactam therapy in patients with severe or life-threatening infection, the risk of an adverse reaction, which might be difficult to diagnose in the perioperative period, is generally considered to outweigh the benefit for patients with such a history. Local policies should recommend at least one alternative regimen to be used in such circumstances.
Factors determining what antibiotics to use
MRSA (meticillin-resistant S. aureus) carriage MRSA carriage is a predictor for MRSA-associated SSI, and may be a risk factor for SSI incidence.1 All NHS organizations should have MRSA screening policies for patients undergoing surgery. Almost all elective (including day case) and emergency admissions are screened for MRSA using swabs from the nose, axilla and groin (as well as other open wounds the patient has). The few exceptions to this, e.g. day case ophthalmology/endoscopy, were previously detailed in Department of Health guidance.10 In 2014, a modified admission MRSA screening guideline was published by the Department of Health which suggests that a more focused, cost-effective approach to screening should be utilised.11 Under this guidance, the mandatory screening of all admissions will be streamlined to (1) all patients being admitted to high risk specialties (defined as vascular, renal/dialysis, neuro- and cardio-thoracic surgery, haematology/oncology/bone marrow transplant, orthopaedics/trauma, and all intensive care units) and/or (2) All patients previously identified as colonized with or infected by MRSA.11 Ideally, screening for elective patients should take place during preoperative assessment to allow time for decolonization if the screen is positive.
Spectrum of cover The antibiotic chosen for prophylaxis must cover the spectrum of pathogens that are likely to cause SSI at that site; see Table 2. The local antibiotic protocol (where one exists) should be used as this will have been developed taking into account factors such as the local epidemiology of antibiotic resistance and CDI and cost. Penicillin allergy True penicillin allergy is relatively rare, but important to detect. This is because patients allergic to penicillin are more likely to be allergic to other beta-lactam agents (e.g. cephalosporins), which are commonly used for surgical prophylaxis. Many patients consider themselves to be allergic to penicillin when in fact they have suffered non-immunological adverse reactions, in particular diarrhoea or vomiting. This can be clarified by accurate history taking at the preoperative assessment and is important as the alternative non-beta-lactam agents recommended for patients with true penicillin allergy are likely to be less effective. Allergy means the development of a rash or anaphylactic or anaphylactoid reaction that is temporally associated with
SURGERY --:-
4
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
caesarean section; advice has previously tended to favour administration at the time of cord clamping rather than at skin incision to reduce fetal exposure. Recent SIGN review did not identify a rise in neonatal morbidity with administration at skin incision and there is concern about whether delay increases the risk of maternal SSI. Current guidance is that antibiotics may be administered either pre-incision or after cord clamping,1 although the former may be more optimal.
If an elective patient is found to be MRSA colonized they should receive decolonization treatment preoperatively according to local guidance (usually mupirocin nasal cream topically every 8 hours plus triclosan (Aquasept)/octenidine (Octenisan)) washes daily for 5 days. There is some debate about the need to demonstrate clearance preoperatively. On the one hand, this provides reassurance to the patient and surgeon, although a notable proportion of patients will not be cleared due to, for example, resistance or poor application, but on the other hand any delay between decolonization and surgery increases the risk of a higher skin bacterial load at the time of surgery or recolonization from the environment. Decolonization therapy (and re-screening) should occur as close to the time of operation as possible. If the patient cannot be screened preoperatively (e.g. emergency surgery) and they are at high risk of being or known to be colonized with MRSA (nursing or residential home resident, previous colonization, recent hospitalization, extensive recent antibiotic exposure), the prophylactic regimen should include MRSA cover (usually a glycopeptide) and decolonization should be commenced as early as possible in the perioperative period.
Route of administration Generally, the IV route should be used, although some antibiotics do reach equivalent tissue concentration when given orally (e.g. fluoroquinolones). Very little data exists on the efficacy or timing of oral prophylaxis, although it is often adopted for common daycase urological procedures, such as trans-rectal prostate biopsy. In some types of surgery alternative routes are used either alone or combined with IV prophylaxis:1 topical administration for grommet insertion impregnated cement for cemented joint replacements in addition to IV prophylaxis intracameral in cataract surgery and intracameral or intravitreal prophylaxis in penetrating eye injury intraventricular antibiotics during VP shunt neurosurgery in addition to IV antibiotics use of gentamicin-impregnated collagen fleeces or implants in AP resection for colonic carcinoma and between the sternum in cardiac surgery12,13
Practicalities: dose, timing, route of administration and duration To prevent SSI, the tissue concentration of any prophylactic agent used must be at an effective concentration (above the minimum inhibitory concentration (MIC) of any contaminating bacteria) at the time of initial skin incision. Antibiotics must therefore be administered at the correct dose and right time, and by the correct route, taking into account the pharmacokinetic profile of the antibiotics used.
Duration For many types of surgery, a single dose of antibiotic is adequate providing the half-life of the antibiotic covers the operation period. Additional doses are generally only needed for longer operations or when using agents with a short half-life. An additional dose of prophylactic antibiotic may be needed if: The operation lasts more than 4 hours and the antibiotic used has a pharmacokinetic profile similar to cefazolin1; in the UK, this includes flucloxacillin, co-amoxiclav and cefuroxime. There is intraoperative blood loss >1500 ml (25 ml/kg in children).1 This is because serum antibiotic concentrations are reduced by blood loss and fluid replacement, especially early in the operation when the serum levels are high, leading to levels falling below the minimum inhibitory concentration (MIC) of target bacteria. Any extra doses of antibiotic should be given after fluid resuscitation. The operation is prolonged beyond the half-life of the antibiotic used. One notable exception to the rule that a single dose of antibiotic is usually adequate is arthroplasty, where 24 hours of prophylaxis continues to be used in many centres as there is some evidence that this lowers rates of reoperation compared to a single dose.1 There is considerable debate about the need for this, however, as some centres have low SSI with single-dose regimens. Documentation of the administration of prophylactic antibiotics is often poor, but should be as for therapeutic prescriptions; minimal documentation such as ‘prophylactic antibiotics given’ in the anaesthetic or surgical record alone is unacceptable as it
Dose In general, the dose used for prophylaxis should be the same as that used for treatment1 (e.g. flucloxacillin 1 g is the usual dose for the in-patient treatment of skin/soft tissue infection and for surgical prophylaxis). For many of the commonly used prophylactic agents, the first dose does not require adjustment in renal impairment, but the timing and/or dose of subsequent doses (when recommended) may need adjustment. When adjusting dosing in patients with renal impairment, the estimated creatinine clearance using the Cockroft-Gault formula, rather than the estimated glomerular filtration rate (eGFR), should be used; advice can be sought from microbiology, infectious diseases or pharmacy. If the patient is on renal-replacement therapy, discussion with a renal physician/pharmacist is prudent. Timing Prophylaxis should be started in almost all circumstances at or less than 60 minutes prior to the first skin incision, and as close to incision time as practically possible.1 To ensure sufficient tissue concentrations are reached at the time of skin incision, however, it may need to be administered earlier for operations in which a tourniquet is used,6 if the antibiotic regimen includes an agent with a prolonged infusion time (e.g. vancomycin infusions should be started 90 minutes prior to skin incision1) or if oral prophylaxis is used. Historically there has been some debate about the timing of administration of prophylactic antibiotics in the setting of
SURGERY --:-
5
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
professionals to their asplenic status. Communication with primary care providers to ensure plans for completion of vaccination schedules, boosters, and ongoing antibiotic supply is vital.
promotes clinical errors and does not facilitate audit. Prophylactic antibiotics should be prescribed either on a dedicated proforma that is then filed in the case-notes or on the once only (STAT) section of the drug chart.
Other immunocompromized patients This includes those with HIV infection, undergoing chemotherapy, on immunosuppressive drugs, or with functional immunosuppression (e.g. due to leukaemia). These patients should receive the same prophylaxis as immunocompetent patients, but extra vigilance for the development of SSI is needed.
Special groups A variety of patient factors influence prophylaxis options. Some antibiotics, e.g. aminoglycosides, should be avoided during pregnancy. Co-morbidities that may impact on antibiotic choice include: long QT syndrome (macrolides and quinolones can cause further QT prolongation); epilepsy (quinolones lower the seizure threshold); G6PD deficiency (nitrofurantoin, quinolones and sulphonamides can precipitate haemolytic crises); myasthenia gravis (many antibiotics can worsen symptoms); and acute intermittent porphyria (multiple antibiotics can precipitate crises). Likewise, the British National Formulary and/or pharmacy, microbiology or infectious diseases should be consulted regarding potential drug interactions.
Patients at risk of infective endocarditis Infective endocarditis (IE) can occur following bacteraemia in patients with predisposing cardiac lesions.a Historically, this led to all such patients receiving prophylactic antibiotics for dental and surgical procedures. However, 2008 NICE guidance17 recommended a change in this practice, and antibiotic prophylaxis to prevent IE is no longer routinely recommended for these patients. The basis for this is that there is no consistent data showing a relationship between having such procedures and development of IE, the clinical effectiveness of antibiotic prophylaxis to prevent IE is unproven and prophylaxis may have severe negative consequences (e.g. anaphylaxis). All at-risk patients should receive information on IE prevention, including the risks and benefits of antibiotic prophylaxis and an explanation of why it is no longer routinely recommended, the importance of maintaining good oral health, and the symptoms that may indicate IE. However, prophylactic antibiotics for the sole purpose of preventing IE should not be administered except in the circumstance of GI or GU surgery at a site where there is suspected infection, when antibiotics that cover IE causing organisms (mainly Gram positive bacteria) should be given.17
MSSA (meticillin-sensitive S. aureus) colonized patients. MSSA is not systematically screened for in the majority of NHS Trusts in the same way as for MRSA. There is some evidence that decolonizing patients who are nasal carriers of MSSA reduces the risk of developing infection,14 although a Cochrane review found the protective effect disappeared if only SSI was included in the subgroup analysis (possibly due to a lack of statistical power).15 Patients known to be nasal or skin carriers of MSSA who are undergoing surgery with a high risk of major morbidity should receive preoperative or perioperative decolonization therapy as for MRSA.1 Patients undergoing splenectomy Individuals with an absent or dysfunctional spleen are at lifelong risk of overwhelming infection, particularly from encapsulated organisms (most commonly Streptococcus pneumoniae). Patients should receive pneumococcal, meningococcal, Haemophilus influenzae type b (Hib) and influenza vaccinations. In elective surgery this should occur at least 2 weeks prior to surgery. In emergency cases, immunizations should ideally be given two weeks after surgery when physiological recovery has occurred (they should be given prior to discharge or a clear plan made with the patient’s general practitioner for immunization at two weeks). For patients undergoing chemotherapy, immunizations should, ideally, be given at least two weeks before chemotherapy commences. All high-risk patients (<16 or >50 years old or those with an inadequate serological response to pneumococcal vaccination, history of invasive pneumococcal disease, underlying haematological malignancy) should be offered lifelong prophylactic antibiotics (e.g. penicillin V 500 mg/12 hours oral or erythromycin 500 mg/12 hours oral). Lower risk patients are still at increased risk in the immediate postoperative period and should be given antibiotics, but counselled as to the risks and benefits of continuing lifelong some may choose to stop.16 Written advice about infection and the risks of overseas travel (in particular the risk of malaria) should be given to patients prior to discharge with a supply of appropriate antibiotics for emergency use. Patients should carry a card to alert health
SURGERY --:-
Paediatrics The principles of prophylaxis are the same with paediatric practice generally being extrapolated from adult prophylaxis guidance with appropriate choice and dose adjustment depending on the age and weight of the child; see SIGN guidance and local antibiotic policy for more information. The Paediatric BNF provides antibiotic dosing information. Obese patients Physiological changes in obesity affect the distribution, protein binding, metabolism and clearance of antimicrobials. Tissue distribution, in particular, is affected for hydrophilic antibiotics (b-lactams, aminoglycosides, glycopeptides) because approximately one-third of adipose tissue is water, leading to a greater volume of distribution (Vd) and lowered tissue concentrations. For lipophilic drugs (fluoroquinolones, macrolides, lincosamides, tetracyclines, tigecycline), the Vd also generally increases (to what extent is unpredictable). Antibiotic clearance is also altered by obesity.18
a
‘At-risk patients are those with acquired regurgitant or stenotic valvular disease, valve replacement, structural congenital heart disease (excluding isolated atrial septal defect and repaired patent ductus arteriosus), previous infective endocarditis, and hypertrophic cardiomyopathy.
6
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
histamine-2 antagonists, and the presence of a CDI outbreak on the ward.
Antimicrobial agents with a narrow therapeutic window (e.g. aminoglycosides) are often dosed according to weight, but it has not yet been established what index of weight is optimal (e.g. total, ideal, lean mass), given the complex pharmacokinetics and pharmacodynamics in obese patients. Other antibiotics are set at a standard dose, which may lead to sub-optimal tissue concentrations in obese patients, leading to an increased risk of SSI and resistance evolving. Some data support giving a higher induction dose of b-lactams and vancomycin in obese patients to optimize tissue concentrations, e.g. flucloxacillin 1.5 g instead of 1 g, but more research is needed.19 Local antibiotic guidance and/or infection experts should be consulted about the high-risk obese patient.
Other important issues Patient information: Information about the risk of healthcare-associated infection and SSI should be provided to patients preoperatively with additional specific information to MRSA carriers (see links to information sheets below).1,8 The risks and benefits of antibiotic prophylaxis should be discussed and patients informed if they will receive it. As around 70% of SSIs present in the community post discharge, information about postoperative wound care and recognizing the signs of SSI must also be provided. All institutions should have access to written materials for patients.1 Audit: This must be undertaken on a regular basis to assess compliance with local antibiotic prophylaxis guidelines and act as a driver for change when practice is sub-optimal. The SIGN guidelines provide criteria for standards and minimum record keeping for audit purposes. Sources of advice: Whilst local guidelines will help you with most cases, they will not cover all eventualities. Choice of antibiotic and dosing can be difficult in some cases, particularly when multiple allergies, polypharmacy and co-morbidities are present. It is also important to consider any history of previous surgical site infection. Complex cases should be discussed with your local antibiotic/infection pharmacist or microbiologist or infectious diseases physician. Some additional sources of information are suggested below. A
Patients with intercurrent infection Those with pre-existing infection that is being treated should still receive antibiotic prophylaxis and then return to the preoperative regimen. One special circumstance is those undergoing urological surgery with a proven urinary tract infection (UTI), where the prophylaxis should be tailored to cover the sensitivities of the organism identified. If a patient is deemed at operation to need therapeutic antibiotics, the prophylactic regimen may not necessarily be appropriate; relevant operative samples for microbiological testing should be ascertained and local antibiotic guidance consulted regarding the optimal postoperative regimen.
Potential negative implications of prophylaxis All antibiotic use, whether for prophylaxis or therapy or appropriate or not, carries a risk of harm through adverse reactions (e.g. rash, anaphylaxis), risk of colonization and subsequent infection with C. difficile, and the emergence of antibiotic resistance. It is these risks that drive the antibiotic stewardship agenda and advice to use the narrowest spectrum antibiotic possible for the shortest time and only when anticipated clinical benefit outweighs potential risks. Although some studies have shown that yeast-containing ‘bioyoghurts’ and natural yoghurt may reduce the incidence of antibiotic-associated diarrhoea, their use alongside antibiotic prophylaxis for SSI prevention is not currently routinely recommended.1 All antibiotics will suppress to some extent the normal, protective mucosal bacterial flora and facilitate the development of colonization with C. difficile and antibiotic resistant pathogens (e.g. MRSA). In general, these issues are greater with broader spectrum agents (e.g. third generation cephalosporins, fluoroquinolones, clindamycin, carbapenems and beta-lactam/ beta-lactamase inhibitors such as co-amoxiclav). Even a single dose of a cephalosporin (and very likely other antibiotics too) appears to increase the carriage of C. difficile20 and the incidence of C. difficile infection;21 the latter is not a benign condition and contributes notably to morbidity, length of hospital stay and mortality. Patients who have other risk factors for C. difficile colonization are particularly vulnerable, the exact prophylaxis to be used requiring careful preoperative assessment. Risk factors include age >65, previous CDI, nursing or residential home residents, recent or prolonged hospital stay, extensive co-morbidities, GI surgery, severe intercurrent illness, poor nutritional state, use of proton pump inhibitors or
SURGERY --:-
REFERENCES 1 Scottish Intercollegiate Guidelines Network (SIGN). Antibiotic prophylaxis in surgery: a national clinical guideline (Guideline number 104). Edinburgh. July 2008 (updated April 2014). Online at, www. sign.ac.uk. 2 Mangram AJ, Horan TC, Pearson ML, et al. The hospital infection control practices advisory committee (HICPAC): guideline for the prevention of surgical site infection. Infect Control Hosp Epidemiol 1999; 20: 247e78. 3 Smyth ET, McIlvenny G, Enstone JE, et al. Four country healthcare associated infection prevalence survey 2006: overview of the results. J Hosp Infect 2008; 69: 230e48. 4 Public Health England. Surveillance of surgical site infections in NHS hospitals in England. 2013/14. London: Public Health England. December 2014. Available from: www.gov.uk/phe. 5 Coello R, Charlett A, Wilson J, et al. Adverse impact of surgical site infections in English hospitals. J Hosp Infect 2005; 60: 93e103. 6 Astagneau P, Rioux C, Golliot F, et al. Morbidity and mortality associated with surgical site infections: results from the 1997e1999 INCISO surveillance. J Hosp Infect 2001; 48: 267e74. 7 National Institute for Health and Clinical Excellence (NICE). NICE guideline 74: surgical site infection. October 2008. Online at: www. nice.org.uk. 8 National Institute for Health and Clinical Excellence (NICE). NICE quality standard QS49: prevention and control of healthcareassociated infections. October 2013. Online at: www.nice.org.uk.
7
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005
INFECTION
9 Culver DH, Horan TC, Gaynes RP, et al. Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infections Surveillance System. Am J Med 1991; 91(3B): 152Se7. 10 Department of Health (DoH). MRSA screening operational guidance 2. December 2008. Online at: http://webarchive.nationalarchives.gov. uk. 11 Department of Health. Implementation of modified admission MRSA screening for NHS. 2014. Online at: http://www.gov.uk/. 12 Eklund AM, Valtonen M, Werkkala KA. Prophylaxis of sternal wound infections with gentamicin-collagen implant: randomized controlled study in cardiac surgery. J Hosp Infect 2005; 59: 108e12. 13 Friberg O, Dahlin LG, Levin LA, et al. Cost effectiveness of local collagen-gentamicin as prophylaxis from sternal wound infections in different risk groups. Scand Cardiovasc J 2006; 40: 117e25. 14 Kallen AJ, Wilson CT, Larson RJ. Perioperative intranasal mupirocin for the prevention of surgical site infections; systematic review of the literature and meta-analysis. Infect Control Hosp Epidemiol 2005; 26: 916e22. 15 van Rijen M, Bonten M, Wenzel R, et al. Mupirocin ointment for preventing Staphylococcus aureus infections in nasal carriers. Cochrane Database Syst Rev 2008; 4: CD006216. 16 Davies JM, Lewis MPN, Wimperis J, et al. Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen: prepared on behalf of the British Committee for Standards in Haematology by a Working Party of the HaematoOncology Task Force. Br J Haematol 2011; 155: 308e17. 17 National Institute for Health and Clinical Excellence (NICE). NICE guideline 64: prophylaxis against infective endocarditis. March 2008. Online at: www.nice.org.uk. 18 Falagas ME, Karageorgopoulos DE. Adjustment of dosing of antimicrobial agents for bodyweight in adults. Lancet 2010; 375: 248e51. 19 Pai MP, Bearden DT. Antimicrobial dosing considerations in obese adult patients. Pharmacotherapy 2007; 27: 1081e91.
SURGERY --:-
20 Privitera G, Scarpellini P, Ortisi G, et al. Prospective study of Clostridium difficile intestinal colonization and disease following singledose antibiotic prophylaxis in surgery. Antimicrob Agents Chemother 1991; 35: 208e10. 21 Carignan A, Allard C, Pepin J, et al. Risk of Clostridium difficile infection after perioperative antibiotic prophylaxis before and during an outbreak of infection due to a hypervirulent strain. Clin Infect Dis 2008; 46: 1338e43. FURTHER READING AND RESOURCES Information leaflets for patients: B SSI: http://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/365839/Monitoring_surgical_wounds_for_ infection_information_for_patients.pdf B MRSA: http://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/330925/MRSA_information_for_patients.pdf B C. difficile: http://www.gov.uk/government/uploads/system/uploads/ attachment_data/file/339322/Clostridium_difficile_fact_sheet.pdf SIGN guideline and quick reference guides: www.sign.ac.uk Cochrane reviews database: www.cochrane.org/cochrane-reviews British National Formulary: www.bnf.org (adult), http://bnfc.org/bnfc/ index.htm (paediatric) National Institute for Health and Clinical Excellence (NICE) guidelines: www.nice.org.uk Public Health England surgical site infection surveillance service: http://www.gov.uk/surgical-site-infection-surveillance-service-ssiss Other articles related to SSI in Surgery: B Phillips J, O’Grady H and Baker E. Prevention of surgical site infections. Surgery 2014;32(9):468e471. B Kelly K and Monson JRT. Hospital acquired infections. Surgery 2012; 30(12):640e644. B Thompson S and Ridgway EJ. Rational antibiotic use in surgery. Surgery 2009;27(10):435e40.
8
Crown Copyright Ó 2015 Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Hall C, et al., Antibiotic prophylaxis, Surgery (2015), http://dx.doi.org/10.1016/j.mpsur.2015.08.005