Welcome to the NES course on Antimicrobials. Tonight we are going to provide an update on this currently high profile area.
These are the objectives for the course.
In 2008 ScotMARAP was published by Scottish Government making recommendations for use of antimicrobials by NHS Boards. This followed on from the Antimicrobial Prescribing Policy and Practice publication of 2005 which made recommendations for use of antimicrobials ain hospitals. The Scottish Antimicrobial Prescribing Group (SAPG) was set up to progress the recommendations of ScotMARAP. SAPG is a national multidisciplinary clinical forum hosted by Scottish Medicines Consortium. The HAI Taskforce within SGHD is responsible for ensuring standards are developed and implemented to reduce HAI throughout the NHS is Scotland. Antimicrobial management is one aspect of this HAI agenda.
Prudent prescribing is essential to ensure antibiotics are used appropriately. What do we mean by this? Prescribers should think – does this patient need an antibiotic not which one will I choose? If an antibiotic is necessary follow local policy and ensure correct regimen used.
Policies are essential to ensure patients get the right antibiotic – aim to give an effective treatment with minimal ecological effect on resistance. Policies must be evidence based and take into account local resistance patterns.
All pharmacists have a role to play in ensuring that antibiotics are used appropriately. Specialist role was developed in response to problems with emerging resistance and knowledge that new broad spectrum agents not being used wisely. In England funding allocated to each hospital for 2-year period to address problems. No specific framework or guidance to work to and after 2 years many posts disappeared. In Scotland framework was developed first. Initially Antimicrobial Pharmacists appointed on ad-hoc basis according to priorities of individual Boards. The influence of inappropriate antimicrobial use on Healthcare Associated Infections (HAIs) prompted the Scottish Government to allocate additional funding for Antimicrobial Pharmacists in all Boards.
Hospital Pharmacists working on the wards or in the Dispensary/Aseptic Service have a vital role to play in policing antimicrobial use. Approximately one third of patients in hospital are prescribed an antibiotic and up to half of these prescriptions may be inappropriate. Inappropriate use, wrong dosage regimens, penicillin use in allergic patients, prolonged courses, broad spectrum rather than narrow spectrum are common in hospital practice.
High level prescribing data can identify use of non-policy antibiotics and also high users of antibiotics. Some prescribers may prescribe antibiotics for self-limiting viral conditions. Some prescribers may use broad spectrum agents routinely – there are few indications for these in primary care. Often prescribers are unaware that their practice is inappropriate. Comparison with other prescriber can highlight problem areas and encourage improvement. Primary care data does not link antibiotic to clinical indication so difficult to get clinical data without carrying out an audit.
Community pharmacists should be familiar with antibiotics they expect to see on prescriptions. Although they will not know the indication if they are unsure about a prescription can ask the patient what it has been prescribed for. Non-policy antibiotics and unusual dosage regimens should be queried to ensure that patients get the most effective treatment for their infection and are not exposed to undue risk of resistance. Most upper respiratory tract infections in adults and children are viral and do not require antibiotics. Community pharmacists are in an ideal position to advise patients on symptomatic relief and the likely course of the infection. Elderly patients in Nursing Homes are at high risk of CDAD and infection with resistant organisms. The use of antibiotics in this patient group should be restricted to cases where there is clear evidence of infection. In particular antibiotic treatment of UTI should only be commenced based on clinical symptoms not dipstick tests or positive urine culture results.
To provide more in-depth background information on bacteria and which antibiotics are used in which infections we have supplied a second presentation on the DVD. We had suggested that you should view this before coming to this session. If you have not done so you may wish to do view it after the session. We will however cover the main points here.
There are four main groups of bacteria which are classified according to their sensitivity to antimicrobials. Further details about the four groups can be found in the Bugs and Drugs presentation.
Certain organisms tend to cause infections in certain parts of the body. This is important since we are often treating infections ‘blindly’ with empirical therapy. There are few occasions where a bacteriological result will be available at the time of prescribing. For many conditions it is not possible to get a sample for bacteriological investigation so it is essential that empirical therapy is right. Narrow spectrum agents are preferable but in some cases broader spectrum agents or a combination of narrow spectrum agents may be required if an infection could be due to a range of organisms.
Penicillin has good activity against Streptococci which are found mainly in the respiratory tract and on the skin. The other agents also cover Staphylococci of which the main pathogen is Staph. Aureus. All are active against methicillin sensitive Staph. Aureus (MSSA) but flucloxacillin and erythromycin are not active against methicillin resistant Staph. Aureus (MRSA). Clindamycin is associated with high risk of C. difficile. The glycopeptides, vancomycin and teicoplanin, and daptomycin can only be given intravenously. Linezolid has a similar spectrum of activity but is also available in tablet or liquid formulation. The use of these agents is restricted to reduce emergence of resistance and contain cost.
These agents all have activity against mainly gram-negative organisms. With the exception of UTIs, infections due to gram-negative organisms are generally seen in hospital practice. Ciprofloxacin use has declined recently due to its association with C. difficile and problems with resistance. It is still the drug of choice in UTI in men, upper urinary tract infections and certain respiratory infections. The aminoglycosides provide cover against a range of gram-negatives including pseudomonas. Gentamicin is the most widely used and is included in some surgical prophylaxis regimens as well as regimens to treat a variety of infections. Tobramicin use is restricted to cystic fibrosis. Amikacin is rarely used out with specialist areas. Aminoglycosides require therapeutic drug monitoring to ensure safe and effective treatment. Colistin, ceftazidime and aztreonam are used specifically for pseudomonal infections particularly in cystic fibrosis.
Metronidazole is the only agent with purely anaerobic cover. It is widely used in combination with other agents. The other anti-anaerobe agents have broader spectra of activity. They may be used in infections where more than one organism may be involved or where empirical treatment needs to cover a range of organisms.
A large number of broad spectrum agents are available but many are restricted to some degree in local antibiotic policies. Macrolides - Clarithromycin is used in respiratory infections and azithromycin in Chlamydia. Trimethoprim and nitrofurantoin are first line agents in lower UTI. Amoxicillin is first line agent in COPD and community acquired pneumonia. Cephalosporins are currently ‘out of favour’ due to their association with risk of C. difficile so their use is restricted to treatment of meningitis. The tetracyclines are widely used in primary care for oral treatment of acne. Doxycycline has also seen a resurgence in use for respiratory infections due to the demise of the cephalosporins. Levofloxacin and moxifloxacin are second line agents for respiratory infections. Their use is restricted due to risk of C. difficile and moxifloxacin has also be associated with hepatotoxicity. The remaining agents are all intravenous preparations used in hospital and usually only on advice of a microbiologist.
Respiratory infections are most common followed by UTI and SSTI. Up to half of infections in hospital are respiratory.
A variety of URTIs are seen in primary care – colds, coughs, sore throat, sinusitis, otitis media. Most are viral and few patients benefit from antibiotics. However patients often expect antibiotics if symptoms last more than a few days. The reality is that some of these conditions may take up to 3 weeks to resolve. Patient education by healthcare professionals verbally and/or using leaflets can reduce this expectation. Regular use of paracetamol or ibuprofen can help relieve symptoms and should be encouraged particularly in children with ear pain due to otitis media. Delayed prescriptions appear to reduce the rate of prescribing – patients may be given a post-dated prescription or may be asked to return in 3 days for review. However the fate of these prescriptions is unknown – do patients get the medicine dispensed and take it whether they are improving or not, keep the prescription or the medicine for future use?
Antibiotics only shorten duration of symptoms by 8 hours. You need to treat 30 children or 145 adults to prevent one case of otitis media.
Need to treat 20 children >2years and seven 6-24month olds to get pain relief in one at 2-7 days. Children with otorrhoea, or <2years with bilateral acute otitis media, have greater benefit but should still consider delayed prescribing. Macrolides are a less effective treatment because they concentrate intracellularly and Haemophilus, the most common causative organism, is an extracellular pathogen.
Benefits of antibiotics are small - 69% resolve in 7-10 days without antibiotics; and 84% resolve with antibiotics. Cochrane review concludes that amoxicillin and phenoxymethylpenicillin have similar efficacy to the other recommended antibiotics (macrolides and doxycycline).
Exacerbations of COPD are common particularly during winter months. Many cases are viral and may be difficult to isolate organisms from sputum so decision to treat with antibiotics based on assessment of sputum production.
Community acquired pneumonia (CAP) is common reason for admission to hospital and has high mortality rate – 20%. Organisms different from those causing hospital acquired pneumonia (HAP). These two conditions will be discussed in more detail in the Hospital Respiratory Workshop. CRB/CURB-65 scoring will be discussed in both respiratory workshops. Scores patients symptoms to identify those most at risk of death. Antibiotic treatment should be started promptly in all cases. In primary care single agent used. If no response in 48 hours consider admission or add clarithromycin first line or doxycycline to cover Mycoplasma infection (rare in over 65s).
UTIs are common in primary care, hospital and care facilities. Young women with symptoms usually do have a UTI (bacteria > 10 6 in urine) and should be treated empirically. Recurrent UTIs can be managed with nightly or post-coital antibiotic prophylaxis. During pregnancy urine samples are screened regularly to check for bacteriuria. Positive results treated regardless of whether symptoms present due to risk to foetus. In elderly women, many have bacteriuria but no symptoms of UTI – important to treat symptoms not lab results.
Cellulitis is most common skin/soft tissue infection. Occurs when bacteria breach skin barrier and spread into surrounding tissue. Symptoms are redness, pain and swelling. Often patient unaware of injury to skin and can occur in young fit individuals. Ensure adequate doses of antibiotics used to give good tissue penetration. Rapidly spreading requires urgent hospital admission to prevent potential complications – septicaemia, necrotising fasciitis. Leg ulcer swabs will always grow organisms as they are usually colonised but unless signs of infection do not use antibiotics. Leg ulcers should be viewed regularly to identify emerging infections which may require treatment.
Meningitis remains a killer disease but early identification of symptoms and prompt antibiotic treatment can save lives and prevent potential complications. Patient information leaflets and poster campaigns can heighten awareness amongst the public, particularly parents of young children and teenagers who are the ‘ at risk’ groups. Patients with a prosthetic heart valve or those with a history of endocarditis have for many years been given prophylactic antibiotics when undergoing surgical and dental procedures. Changes to national guidance in 2008 mean that few patients are now recommended to have prophylaxis due to lack of evidence for its benefits and potential adverse effects of overuse of antibiotics. Patients who previously received antibiotic prophylaxis may ask for reassurance about this.
MRSA is a worldwide problem. Methicillin resistance varies widely throughout Europe – lowest in Scandinavia and highest in Greece. UK at high end of spectrum. MRSA is generally a healthcare associated infection (HAI) and community MRSA is very rare in UK. Priority for NHS to reduce MRSA infections – Scottish Government have a HEAT target relating to all SABs (40% of these will be MRSA bacteraemias). A pilot study of screening all patients being admitted to hospital is underway to enable targeted screening in high risk areas.
MRSA is spread by contact. Infection control procedures are essential to prevent spread between patients by healthcare staff. Hand washing, aprons and gloves together with isolation is required. Patients in hospital or other healthcare facility who are colonised with MRSA require treatment with a nasal preparation to eradicate nasal carriage and skin decontamination with a product such as triclosan 1% or chlorhexidine 4%. Patients with MRSA infection, not just colonisation, require treatment with an intravenous glycopeptide or combination of two oral agents depending on severity of the infection.
Clostridium difficile currently high profile HAI. Most cases are associated with prior antibiotic use and elderly patients at highest risk. Many people have C. difficile, an anaerobe, within their gut living in harmony with range of other bacteria. Antibiotics alter the gut flora, reduce levels of other bacteria and allow C. difficile to overgrow resulting in C. difficile associated disease CDAD). Complications of CDAD include dehydration, hypotension and pseudomembranous colitis.
Patients with CDAD are themselves at risk but can also pose a risk to other patients as the organism is highly infectious. Isolation is essential and infection control procedures can prevent transfer to other patients by healthcare staff. Visitors also require to be vigilant with infection control measures. If possible antibiotics should be stopped but if essential for ongoing treatment of an infection, a low risk drug should be used. Treatment depends on severity. First line is usually metronidazole 400mg tid for 10-14 days. Oral vancomycin 125mg qid is an alternative – capsules or injection given orally (cheaper than capsules). Oral vancomycin is not absorbed so exerts a local effect on C. diff.
Unfortunately it is not as simple as it seems, all antibiotics have the potential to cause CDAD. In order to colonise the gut of a normal individual the resident gut flora which usually inhibit C. diff must be reduced. Typically diarrhoea starts within a few days of commencing antibiotics, although can occur up to 12 weeks after taking antibiotics. Very occasionally no antibiotics have been consumed.
We have covered the role of pharmacists in managing antibiotic use, common pathogens and infections and healthcare associated infections. Key point is that basic knowledge of ‘bugs and drugs’ can help pharmacists to promote rational and effective use of antimicrobials and make a real difference to current problems of antimicrobial resistance and healthcare associated infections. In the workshop sessions we will go on to look at some common infections in more detail using case studies to discuss pharmaceutical care issues.
Pharmaceutical Care of Patients with Infections Jacqueline Sneddon Project Lead for Scottish Antimicrobial Prescribing Group