Antibiotic Prophylaxis

The approach to this subject has been revolutionised by the NICE Guidance Prophylaxis against infective endocarditis issued in March 2008.¹ It points out that antibiotics have been prescribed to at-risk patients before dental and certain non-dental procedures for the last fifty years without any proper evidence-base. NICE cites the following:

• Recent guidance from the British Association for Antimicrobial Chemotherapy and the American Heart Association highlight that in most cases there may be as much if not more risk of exposure to transient bacteraemia from daily activities such as tooth-brushing, flossing and chewing gum than there is from any dental procedure.
• The hitherto accepted link between infective endocarditis (IE) and interventional procedures does not stand up well to the cold light of research.
• The efficacy of antibiotic prophylactic regimes is questionable.
• Antibiotic prophylaxis against IE for dental procedures may lead to a greater number of deaths through fatal anaphylaxis than a strategy of no antibiotic prophylaxis, and is not cost effective.

NICE therefore advises that antibiotic prophylaxis should not routinely be offered to patients at risk of developing IE.

The guidance advises that patients at risk of IE should be given clear and consistent information about prevention, including:

• The benefits and risks of antibiotic prophylaxis, and an explanation of why antibiotic prophylaxis is no longer routinely recommended
• The importance of maintaining good oral health
• Symptoms that may indicate infective endocarditis and when to seek expert advice
• The risks of undergoing invasive procedures, including non-medical procedures such as body piercing or tattooing

• For people undergoing dental procedures
• For people undergoing non-dental procedures at the following sites:
  • upper and lower gastrointestinal tract
  • genitourinary tract; this includes urological, gynaecological and obstetric procedures, and childbirth
  • upper and lower respiratory tract; this includes ear, nose and throat procedures and bronchoscopy

Antibacterial prophylaxis against endocarditis is not required.² However, this applies to surgery on clean skin. Prophylaxis should be considered if procedures on infected areas are carried out (e.g. treatment of wound infections) if the surgery cannot be postponed until the infection is treated.³ The NICE guidance makes no mention of dermatological procedures per se but based on comments about skin wound infections, it would make sense to consider antibiotic prophylaxis if the area to be operated on was infected.

Antibiotic prophylaxis is not required for patients having dental treatment who are immunosuppressed (including transplant patients and patients with indwelling intraperitoneal catheters), providing there is no other indication for prophylaxis. There is little evidence that such patients acquire infection after dental procedures.^1,2

• The evidence to support the use of prophylactic antibiotics is extremely sparse.^4,5
• Intercurrent infection should be treated as appropriate.
• The frequency of joint infection after dental treatment is extremely small, the risk of streptococcal infection even smaller.
• The recent NICE guidance, commenting on the insignificant degree of bacteraemia caused by dental procedures, is likely to add further weight to this argument.¹

• The World Health Organisation (WHO) guidance was issued in 2004. It was revisited in 2008 in the light of several subsequent trials but has not been substantially altered.
• WHO do not consider primary prophylaxis, which would involve the systematic investigation of all patients presenting with sore throat, to be cost-effective. They therefore recommend only secondary prevention - i.e. the treatment with antibiotics of patients suffering from proven rheumatic fever. Treatment needs to be lengthy and continuous (see details below). Rheumatic fever is rare in this country, and is mainly seen in children aged 5-14 in developing countries.
• WHO recommend secondary prophylaxis with oral phenoxymethylpenicillin 250 mg twice daily. For patients allergic to penicillin sulfadiazine 1G daily (500 mg daily for patients under 30 kg) or erythromycin 250 mg twice daily may be given.
• Parenteral treatment is an option and there is some evidence that it is more effective than oral treatment. Compliance with an oral regime also requires considerable motivation, and the route of administration should be tailored to the needs of the individual patient. The dosage regime is benzylpenicillin by single intramuscular injection every 3- 4 weeks, ≥30kg: 1.2 million units <30kg: 600,000 units
• The duration of treatment is controversial. Many of the UK trials were done in the 1950s when rheumatic fever was more virulent and frequent than it is today, and many of the modern trials are done in countries where this situation still prevails. The current WHO guideline is:
  • Patients without proven carditis - five years after the last attack or until 18 years of age (whichever longer)
  • Patient with carditis - ten years after the last attack or until 26 years of age (whichever longer)
  • Patients with more severe valvular disease or who have had valve surgery - lifelong

• Rifampicin is recommended first line treatment:
  • 600 mg every 12 hours for 2 days for an adult
  • 10 mg/kg every 12 hours for 2 days for a child over 1 year
  • 5 mg/kg for a child under one year
• Alternatives are:
  • Ciprofloxacin (unlicensed use) 500 mg as a single dose (child 5-12 years 250 mg)
  • I/m ceftriaxone (unlicensed use) 250 mg as a single dose (child under 12 years 125 mg)

Systematic evidence is limited due to the ethics of not giving prophylaxis to a control sample, and there is therefore limited information as to which contacts to treat. Contact tracing is normally undertaken by local public health clinicians, and further guidance has been issued by the Health Protection Agency,as follows:

Prophylaxis indicated

Irrespective of vaccination status, chemoprophylaxis should be offered to the following individuals:

• Those who have had prolonged close contact with the case in a household type setting during the seven days before onset of illness, e.g.
• Those living and/or sleeping in the same accommodation
• Pupils in the same dormitory
• Boy/girlfriends
• University students sharing a kitchen in a hall of residence
• Those who have had transient close contact with a case only if they have been directly exposed to large particle droplets/secretions from the respiratory tract of a case around the time of admission to hospital (e.g. healthcare workers).

Prophylaxis not indicated

(unless already identified as close contact):

• Staff and children attending same nursery or creche
• Students/pupils in same school/class/tutor group
• Work or school colleagues
• Friends
• Residents of nursing/residential homes
• Kissing on cheek or mouth (intimate kissing would normally bring the contact into the close prolonged contact category)
• Food or drink sharing or similar low level of salivary contact
• Attending the same social function
• Travelling in next seat on same plane, train, bus, or car

Rifampicin is recommended by the Department of Health:⁹

• 600 mg once daily for 4 days (regimen of choice for adults)
• Child 1-3 months 10 mg/kg once daily for 4 days
• Over 3 months 20 mg/kg once daily for 4 days (max. 600 mg daily)
• Should be given to all household contacts, irrespective of immunisation status, except for children under 4 who have been fully immunised
• Should also be offered to all room contacts - teachers and children - if two cases occur in a playgroup, nursery or creche within 120 days.⁹

• The Department of Health recommends erythromycin:⁹
  • For adults and children over 8 for 7 days 500 mg every 6 hours
  • For children 2-8 years 250 mg every 6 hours
  • Under 2 years 125 mg every 6 hours
  • The Green Book cites penicillin as another option
• Diphtheria is still prevalent in parts of Asia, South America, Africa and India, and may well re-emerge in the UK if immunisation rates are not maintained.⁹
• As well as antibiotic prophylaxis, partially or unimmunised individuals should complete immunisation according to the UK schedule.
• Completely immunised individuals should receive a single reinforcing dose of a diphtheria-containing vaccine according to their age.⁹

• UK guidelines recommend erythromycin:¹⁰
  • Adults and children over 8 years, 250-500 mg every 6 hours for 7 days
  • Children 2-8 years use 250 mg every 6 hours
  • Under 2 years 125 mg every 6 hours
• Evidence for antibiotic prophylaxis weak
• Because of well-known side effects of erythromycin (mainly gastrointestinal), clinicians should take a cautious approach to prescribing
• Prophylaxis should be offered to a household contact if :
  • A newborn baby or young infant
  • Any unimmunised member of their household
  • Contacts 5 years or over if they did not receive pre-school pertussis booster (not given to those born before 1996 in the UK).
  • No benefit in giving prophylaxis more than 21 days from the date of onset of the primary case. Unimmunised or partially immunised contacts should complete their course of vaccine.

• Evidence supports the use of phenoxymethylpenicillin:¹¹
  • 500 mg every 12 hours for adults.
  • Children under 5 years use 125 mg every 12 hours
  • 6-12 years use 250 mg every 12 hours
  • If cover also needed for H. influenzae in a child give amoxicillin instead:
  • Under 5 years 125 mg every 12 hours
  • Over 5 years 250 mg every 12 hours)
• A multi-centre randomised trial supported the use of antibiotic prophylaxis, irrespective of immunisation status, by the age of four months.¹²
• Erythromycin may be used for those allergic to penicillin, but effectiveness less well supported by evidence¹²
• One trial supported the cessation of prophylaxis at the age of five providing child had had at least two years of antibiotic, was fully immunised, and had had no episodes of pneumococcal infection or a splenectomy.¹³
• Parents should be counselled to report any febrile illness¹³
• Similar considerations apply to splenectomised patients or patients with hyposplenia, irrespective of immune status
• Evidence for stopping antibiotic prophylaxis less convincing, many experts advise continuing indefinitely

Benzylpenicillin 300-600 mg should be given by slow intravenous infusion or by intramuscular injection every 6 hours for 5 days. For penicillin-allergic patients, give metronidazole 400-500 mg every 8 hours.

• The Joint Tuberculosis Committee recommends chemoprophylaxis for the following:^16,17
  • Patients with documented recent tuberculin conversion
  • Tuberculin-positive children identified in BCG schools programme
  • Children under 2 years in close contact with smear-positive tuberculosis (including those previously vaccinated with BCG but now showing strongly positive tuberculin test)
  • Children under 16 years showing a positive tuberculin test at new immigrant or contact screening
  • Also consider for immigrant adults 16-34 years without a BCG scar but with strongly positive tuberculin test
• A regime of isoniazid 300 mg daily for 6 months to adults 5-10 mg/kg daily (max. 300 mg daily) to children.
• An alternative is isoniazid 300 mg daily rifampicin 600 mg daily (450 mg if less than 50 kg) for 3 months for adults and isoniazid 5-10 mg/kg daily (max. 300 mg daily) rifampicin 10 mg/kg daily (max. 600 mg daily) for children.
• There is a risk of hepatotoxicity with isoniazid, but this is far outweighed by the risk of developing TB if prophylaxis is not given.¹⁸

• Operations on stomach or oesophagus for carcinoma - the Scottish Intercollegiate Network Guidelines Network (SIGN) recommend antibiotics unless local guidelines specify exceptions. SIGN advise that the selection of antibiotics should be guided by local policy.
• An additional dose of prophylactic agent is not indicated in adults, unless there is blood loss of up to 1500 ml during surgery or haemodilution of up to 15 ml/kg.
• Open biliary surgery - a single dose of i/v cefuroxime, i/v metronidazole or i/v gentamicin should be given.²⁰
• Metronidazole may be given by suppositories, two hours before surgery to allow absorption.
• One trial suggested no benefit in giving antibiotic prophylaxis prior to elective laparoscopic cholecystectomy.²¹ However, further larger randomised trials are required before definitive guidance can be given on this issue.²²
• Resections of colon and rectum for carcinoma, and resections in inflammatory bowel disease, and appendicectomy - give a single dose of i/v gentamicin i/v metronidazole.
• An alternative is i/v cefuroxime i/v metronidazole or i/v co-amoxiclav alone.
• There is considerable evidence to support the role of pre-operative antibiotics in the reduction of post-operative infections.^23,24
• Endoscopic retrograde cholangiopancreatography is not mentioned in the SIGN guidance and antibiotic prophylaxis for this procedure is a controversial issue. One study did not support the use of antibiotic prophylaxis.²⁵ and it has been shown that the risk or bacteraemia can be reduced if infection control measures are increased.²⁶
• Prophylaxis may however, be important if there is bile stasis, pancreatic pseudocyst, a history of cholangitis or neutropenia.²⁷

• Transrectal prostate biopsy - SIGN recommend prophylactic antibiotics.¹⁹ Ciprofloxacin 500 mg orally 1-2 hours before the procedure is recommended.²⁰ Levofloxacin is an alternative.²⁸
• Additional intra-operative or postoperative doses of antibacterial may be given for prolonged procedures or if there is major blood loss.
• There is a significant risk of infection without antibiotic cover.²⁹

SIGN advise the use of antibiotics as prophylaxis.¹⁹ There is a discussion in the literature about the benefit of various regimes³⁰ and methods of delivery³¹ but no meta-analyses from which definitive guidance can be drawn.

• Caesarean section - SIGN support the use of prophylactic antibiotics unless local policies identify exceptions.¹⁹ A single dose of i/v cefuroxime is commonly used, administered immediately after the umbilical cord is clamped. If there is a history of penicillin or cephalosporin allergy, i/v clindamycin is an alternative.¹² Again, there is a discussion in the literature about various regimes,³² and also about the timing of medication.³³ One recent study found that the addition of intravenous azithromycin significantly reduced the risk of post-operative endometritis.³⁴
• Hysterectomy - SIGN recommend prophylaxis for both abdominal and vaginal procedures, unless local policies identify exceptions.¹⁹ Common regimes include a single dose of i/v cefuroxime plus i/v metronidazole, i/v gentamicin plus i/v metronidazole, or i/v co-amoxiclav alone.^35,35,36 There is some evidence that a two-dose regime is better, due to increased blood flow, and hence rapid clearance, from the operation site, particularly where the procedure is extensive, e.g. cancer surgery.³⁷
• Termination of Pregnancy - the standard guidance used to be to give antibiotic prophylaxis in all cases to prevent complications from pre-existing sexually-transmitted infection.³⁸ However, recent work suggests that such precautions may not necessary providing patients are carefully screened.³⁹ Oral metronidazole is commonly prescribed to prevent bacterial vaginosis,⁴⁰ but the evidence is weak, and larger randomised trials are needed.⁴¹ Doxycycline should be given if genital chlamydial infection cannot be ruled out.⁴² One trial using blanket cover for all patients with oral oxytetracycline and metronidazole suppositories reduced the rate of post-operative infection, presumably by treating undiagnosed bacterial vaginosis and chlamydia, and found that the cost-benefit of this approach was significant.⁴³

• Reconstructive arterial surgery of abdomen, pelvis or legs - SIGN recommend antibiotic prophylaxis.¹⁹ I/v cefuroxime or i/v gentamicin are commonly used, but oral ciprofloxacin offers a useful alternative.^44,45
• Additional intra-operative or postoperative doses may be necessary for lengthy procedures or if there is major blood loss.
• For patients at risk of anaerobic infections (e.g. those with diabetes, gas gangrene, undergoing amputation), add i/v metronidazole.⁴⁵
• Substitute i/v vancomycin for cefuroxime or gentamicin if there is a high risk of methicillin-resistant Staphylococcus aureus.⁴⁵
• There is some evidence that multiple doses regimes give better outcomes generally.^46,47