Preventing and managing infection

• Demonstrate knowledge in the importance of vaccines in reducing antimicrobial resistance • Understand why self-limiting bacterial or viral infections are unlikely to benefit from antimicrobials • Demonstrate knowledge of when not to prescribe antimicrobials, and use of alternatives, such as the removal of invasive devices (e.g. intravenous or urinary catheters and incision and drainage of abscesses [source control]). • Demonstrate an understanding of the rationale and use of perioperative prophylactic antimicrobials to prevent surgical site infection • Describe narrow spectrum antimicrobials

• Antimicrobial resistance an inevitable consequence of antimicrobial usage • If we can vaccine prevent a disease we should • Vaccine preventable bacterial infections •Vaccine preventable viral infections that pre-dispose to bacterial infections • Vaccine preventable viral infections that are inappropriately treated with antibiotics • Bacteria are excellent at adapting to, and colonising new and hostile environments•Antibiotics are a hostile environment for bacteria, therefore resistance is inevitable•Resistance encouraged by ‘sub-lethal’ doses of antibiotics•Microbiome organisms exposed to antibiotics are encouraged to express resistance genes

Many of the organisms in the UK vaccine schedule are bacteria -Many cause severe infection, with the 3 main causes of bacterial meningitis included Neisseria Meningitidis, Haemophilus Influenzae (B), Streptococcus pneumoniae Some other bacteria on the schedule cause toxin mediated disease: Corynebacterium diphtheriae, Clostridium tetani, Toxoid vaccines illicit immune response against the Toxin, rather than the bacterial cell

Vaccine preventable viral infections that pre-dispose to bacterial infections- influenza virus has primary infection, viral upper respiratory tract infection • Influenza is associated with secondary bacterial infections Pneumonia Otitis media • ‘Flu vaccines not perfect, but do reduce numbers of severe infections and deaths • Antigenic drift in Influenza viruses mean annual vaccination needed•Inactivated (dead) and attenuated (live) ‘flu vaccines used in UK

• Symptoms and signs of viral and bacterial infections can be similar • Upper respiratory tract infections are good examples • Otitis media • Pharyngitis/ tonsillitis • Microbiological tests are often not available in time to guide prescribers • Some vaccine preventable viral diseases could present like bacterial infections Rotavirus, mumps, influenza are three viral infections that can be vaccine prevented. Each of them they cause a clinical condition which in some cases would lead to antibiotics being prescribed. Prevention of these infections can therefore reduce the pressure to prescribe antibitoics.Rotavirus: acute gastroenteritis;Mumps: orchitis and parotitis (inflammation of the gonads and parotid salivary 8 glands;Influenza: upper respiratory tract infection

Bordetella pertussis (whooping cough)-given as part of ‘6 in 1’. Haemophilus influenzae (incapsulated type B) A gram negative coccus that causes respiratory infection and meningitis. Aactuallywe sometimes call it a gram negative cocco-bacillus. ‘Bacillus’ is an older word for ‘rod’ and H. Influenzae looks sometime like a really short rod. I prefer the word rod over bacillus when describing gram stain appearances. This is because there are a genus gram of positive aerobic spore forming bacteria called Bacillus (e.g. Bacillus anthracis, the cause of Anthrax), and that can cause confusion. Streptococcus pneumoniae. Cause of pneumonia, other respiratory infections and meningitis. Gram positive coccus in pairs and short chains. Neisseria meningitidis. Cause of meningitis. Gram negative coccus.Corynebacterium diphtheriae: gram positive rod, causes Diphtheria via action of an exotoxin6 Clostridium tetani: anaerobic spore forming gram positive rod. Causes Tetanus via action of a neurotoxin: tetanospasmin.Toxoids are inactivated toxins. So toxoid vaccines are seeking to illicit an immune reaction to the toxin, rather than the bacteria that makes the

Self limiting infections • Benefit and risk balance • Antimicrobials Self- limiting infecitons- Innate immune system acts fast against invaders Barriers Mucosal antibody (IgA) Clearance mechanisms such as muco-ciliary escalator Phagocytes such as macrophages and neutrophils Fever Benefit and risk balance- Antibiotics are good drugs, but overuse limits their usefulness Antibiotic benefit is for the individual but risk of resistance is to the population - RESISTANCE Increasingly aware of risks to individual taking antibiotics also C. diff in elderly Microbiome dysfunction in young- IBS, childhood astmha, obesity, cancer Longer and higher doses of antibiotics are more toxic

Benefit and risk balance- Antibiotics are good drugs, but overuse limits their usefulness Antibiotic benefit is for theindividual but risk of resistance is to the population - RESISTANCE Increasingly aware of risks to individual taking antibiotics also C. diff in elderly Microbiome dysfunction in young- IBS, childhood astmha, obesity, cancer Longer and higher doses of antibiotics are more toxic

Many classes of antibiotics, divided according to their site of action in the bacterial cell We want antibiotics that have Selective Toxicity The majority of agents act on the Cell wall The mechanisms of bacterial protein synthesis is another major target

Beta lactam drugs and the peptidoglycan cell wall Beta lactams are the commonest prescribed antibiotics Penicillin-type agents are the commonest beta-lactams Eukaryotes have no cell wall-so a good antibiotic target Cell wall madeof Peptidoglycan Beta-lactams inhibit cross linking of Peptidoglycan chains • Monomers of n-acetyl muramic acid (NAMA) and n-acetyl glucosamine (NAG) form a complex polymer called Peptidoglycan • These monomers are formed into chains • The chains are ‘cross-linked’ by the action of the transpeptidase enzyme. This enzyme catalyses binding between amino acids on NAMA monomers on adjacent chains. The effect is a net structure. These nets stack on top of one another to form a multi-layered cell wall. • The transpeptidase enzyme is also known as the penicillin binding protein: This enzyme is inhibited by allbeta lactam drugs • The penicillin structure has the 4-membered beta-lactam ring at its centre. All beta-lactam antibiotics have this ring at their core. • Beta-lactam drugs therefore stop bacterial cells from making cell walls

• Don’t treat Self limiting and viral infections • Consider the Source of the infection • Drain Abscess and collections • Remove Implantable or temporary medical devices

Abscess: a localised collection of pus surrounded by inflamed tissue Some bacteria particularly associated with abscess -Streptococcus pyogenes -Staphylococcus aureus A containment measure, leading tor elease of pus outside the body Antibiotics NOT good for collections-drainage is primary treatment Control the SOURCE

Many devices used in medicine E.gs Some temporary such as catheters Some permanent like pacemakers and joint prostheses Temporary devices tend to be colonised with bacteria in Biofilm Antibiotics NOT good against biofilm Control the SOURCE

• Many surgeries will inevitably result in infection •Prophylactic antimicrobials are reasonable because of the high chance of postoperative infection • Antibiotics immediately prior to surgery are shown to reduce post operative infection. The measures taken to prevent infection are essential to surgery Ventilated operating theatres Gloves and gowns Sterile instruments Skin preparation Antibiotic prophylaxis Surgical infection remains a critical and frequent adverse effect of surgery

• What do we mean by spectrum of activity of antimicrobials • Intention is to give the most narrow spectrum we can • Good clinical practice, knowledge of microbiology and good diagnostics allow us to give narrow spectrum antimicrobials • Start Smart then Focus approach

Spectrum of activity The range of the bacteria an antibiotic can inhibit the growth of Broad spectrum antibiotics for sepsis when we don’t know the source Narrow spectrum cause less ecological damage We prefer narrow spectrum treatment where possible Don’t give antibiotics without some evidence of infection- take samples and culture bacteria Record everything- stop, switch, change antibiotics treatment and attempt to get to narrow spec asap

Good clinical practice, knowledge of microbiology and good diagnostic practice First review the patient symptoms and signs Second consider where in the body is the inflammation/ infection 2 things to do in infection medicine- give antibiotics early, and before we have microbiological results (which can take 48 hours); and limit antibiotic use generally and always give narrow spectrum antibiotics whenever possible.