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ALL YOU NEED TO KNOW ABOUT ANTIBIOTICS AND SEPSIS Harish Bava and Elena Boby Reviewed by Dr Claudia Bayne Here’s what we do: ■ Weekly tutorials open to all! ■ Focussed on core presentations and teaching diagnostic technique If you’re new here… ■ Bstudentsl students, for medical ■ Reviewed by doctors to ensure W elcome to accuracy T eaching ■ We’ll keep you updated about our Things! upcoming events via email and groupchats!Antibiotics Harish BavaWhat will we be covering? ■ Antibiotics – what they are, how they work and common classes ■ Types of bacteria ■ Common antibiotics used in common conditions and penicillin allergy ■ Important side-effects of commonly used antibiotics ■ High-yield drug-drug interactions ■ When to consider antibiotics in a GP settingPoll How confident are you currently about antibiotics, its uses in common conditions and common side-effects?What are antibiotics? ■ A drug used to treat infectionscaused by bacteria and other microorganisms ■ They are made of chemical substances produced by living organisms, made by soil bacteria and fungi. Some are also made syntheticallyHow do antibiotics work? What are the main mechanisms of antibiotics?How do antibiotics work? What are the main mechanisms of antibiotics? ■ Inhibition of cell wall synthesis – results in cell lysisHow do antibiotics work? What are the main mechanisms of antibiotics? ■ Inhibition of cell wall synthesis – results in cell lysis ■ Inhibition of protein synthesis – interferes with prokaryotic ribosomesHow do antibiotics work? What are the main mechanisms of antibiotics? ■ Inhibition of cell wall synthesis – results in cell lysis ■ Inhibition of protein synthesis – interferes with prokaryotic ribosomes ■ Injury to plasma membrane – changes in permeability – loss of metabolites and/or cell lysisHow do antibiotics work? What are the main mechanisms of antibiotics? ■ Inhibition of cell wall synthesis – results in cell lysis ■ Inhibition of protein synthesis – interferes with prokaryotic ribosomes ■ Injury to plasma membrane – changes in permeability – loss of metabolites and/or cell lysis ■ Inhibition of nucleic acid (DNA/RNA) synthesis– interfere with DNA replication and transcriptionHow do antibiotics work? What are the main mechanisms of antibiotics? ■ Inhibition of cell wall synthesis – results in cell lysis ■ Inhibition of protein synthesis – interferes with prokaryotic ribosomes ■ Injury to plasma membrane – changes in permeability – loss of metabolites and/or cell lysis ■ Inhibition of nucleic acid (DNA/RNA) synthesis– interfere with DNA replication and transcription ■ Inhibition of synthesis of essential metabolites– competitive inhibition of key enzymesExamples of each class of antibiotic Examples of each class of antibiotic ■ 𝛽-lactams – Penicillin(amoxicillin, benzylpen),Cephalosporins (ceftriaxon,cefuroxim), Carbapenems (meropenem ,ertapenem) ■ Glycopeptides – Vancomycin ■ Tetracyclines – Doxycycline, lymecycline ■ Aminoglycosides – Gentamicin, neomycin, streptomycin ■ Macrolides – clarithromycin, erythromycin, azithromycin ■ Lincosamides - clindamycin ■ Quinolones – ciprofloxacin, levofloxacin ■ Polymyxin B ■ Anti-fungal – fluconazole, ketoconazole ■ Sulphonamides ■ Trimethoprim Examples of each class of antibiotic ■ 𝛽-lactams – Penicilli(amoxicillin, benzylpen)Cephalosporins ■ You can use the following (ceftriaxo,cefuroxime, Carbapenems meropenem ertapenem ) pneumonic to help you: ■ Glycopeptides – Vancomycin ■ Tetracyclines – Doxycycline, lymecycline ■ Britain’s Got Talent ■ Aminoglycosides – Gentamicin, neomycin, streptomycin Always Made Live Quick ■ Macrolides – clarithromycin, erythromycin, azithromycin Performances Appear ■ Lincosamides - clindamycin Superbly Tremendous ■ Quinolones – ciprofloxacin, levofloxacin ■ Polymyxin B ■ Anti-fungal – fluconazole, ketoconazole ■ Sulphonamides ■ TrimethoprimCan you match the mechanism to the class of antibiotic? 1. Inhibition of cell wall synthesis a) Quinolones 2. Inhibition of protein wall synthesis b) Polymyxin B (antibacterial, fluconazole) 3. Injury to plasma membrane c) Tetracyclines, macrolides, 4. Inhibition of nucleic acid (DNA/RNA) aminoglycosides, lincosamides synthesis d) 𝛽-lactams and glycopeptides 5. Inhibition of synthesis of essential metabolites e) Sulphonamides, trimethoprim Can you match the mechanism to the class of antibiotic? 1. Inhibition of cell wall a) Quinolones synthesis b) anti-fungal)(antibacterial, 2. Inhibition of protein wall synthesis c) Tetracyclines, macrolides, aminoglycosides, 3. Injury to plasma membrane lincosamides d) 𝛽-lactams and 4. Inhibition of nucleic acid glycopeptides (DNA/RNA) synthesis 5. Inhibition of synthesis of e) trimethoprims, essential metabolites Can you match the mechanism to the class of antibiotic? 1. Inhibition of cell wall a) Quinolones synthesis b) anti-fungal)(antibacterial, 2. synthesisn of protein wall c) Tetracyclines, macrolides, 3. Injury to plasma membrane aminoglycosides, lincosamides 4. Inhibition of nucleic acid d) 𝛽-lactams and (DNA/RNA) synthesis glycopeptides 5. Inhibition of synthesis of essential metabolites e) trimethoprims, Can you match the mechanism to the class of antibiotic? 1. Inhibition of cell wall a) Quinolones synthesis b) anti-fungal)(antibacterial, 2. synthesisn of protein wall c) Tetracyclines, macrolides, 3. Injury to plasma membrane aminoglycosides, lincosamides 4. Inhibition of nucleic acid d) 𝛽-lactams and (DNA/RNA) synthesis glycopeptides 5. Inhibition of synthesis of essential metabolites e) trimethoprims, Can you match the mechanism to the class of antibiotic? 1. Inhibition of cell wall a) Quinolones synthesis b) anti-fungal)(antibacterial, 2. synthesisn of protein wall c) Tetracyclines, macrolides, 3. Injury to plasma membrane aminoglycosides, lincosamides 4. Inhibition of nucleic acid d) 𝛽-lactams and (DNA/RNA) synthesis glycopeptides 5. Inhibition of synthesis of essential metabolites e) trimethoprims, Can you match the mechanism to the class of antibiotic? 1. Inhibition of cell wall a) Quinolones synthesis b) anti-fungal)(antibacterial, 2. synthesisn of protein wall c) Tetracyclines, macrolides, 3. Injury to plasma membrane aminoglycosides, lincosamides 4. Inhibition of nucleic acid d) 𝛽-lactams and (DNA/RNA) synthesis glycopeptides 5. Inhibition of synthesis of essential metabolites e) trimethoprims,Gram positive and negative What does this actually mean? ■ Regarding the cell wall structure – the peptidoglycan cell wall ■ Gram +ve has a thick peptidoglycan cell wall whereas gram –ve is thinnerGram positive and negative What does this actually mean? ■ Regarding the cell wall structure – the peptidoglycan cell wall ■ Gram +ve has a thick peptidoglycan cell wall whereas gram –ve is thinner – Dye is retained less in gram -ve bacteria and appears pink or red – Dye is retained more in gram +ve bacteria and appears purple – What investigation is performed to determine this information?Gram positive and negative What does this actually mean? ■ Regarding the cell wall structure – the peptidoglycan cell wall ■ Gram +ve has a thick peptidoglycan cell wall whereas gram –ve is thinner – Dye is retained less in gram -ve bacteria and appears pink or red – Dye is retained more in gram +ve bacteria and appears purple – This is detected in blood cultures ■ Gram +ve/Gram -ve is identified first (e.g. gram -ve rods) ■ Specific bacteria is identified second (e.g. Escherichia coli) ■ Sensitivities and resistances are identified third (e.g. sensitive to ciprofloxacin, resistant to clarithromycin)Gram positive and negative What does this actually mean? ■ Regarding the cell wall structure – the peptidoglycan cell wall ■ Gram +ve has a thick peptidoglycan cell wall whereas gram –ve is thinner – Dye is retained less in gram -ve bacteria and appears pink or red – Dye is retained more in gram +ve bacteria and appears purple – This is detected in blood cultures ■ Gram +ve/Gram -ve is identified first (e.g. gram -ve rods) ■ Sensitivities and resistances are identified third (e.g. sensitive to ciprofloxacin, resistant to clarithromycin) ■ Gram –ve bacteria have a protective capsule that prevents ingestion from WBC ■ They can be found in cocci, bacilli or branching filaments ■ Why is this important? – Important as different classes of Abx will target different bacteriaGram stains ■ Can you identify which one is gram +ve and which is gram –ve?Gram stains ■ Can you identify which one is gram +ve and which is gram –ve? Gram +ve bacteria Gram -ve bacteriaExamples and main ones to remember Cocci Bacilli (rod) (Everything else) Neisseria Salmonella, Shigella, Legionella, Gram -ve Klebsiella, Brucella Haemophilus, Escherichia Coli Actinomyces Staphylococcus Bacillus Gram +ve Streptococcus Clostridium Enterococcus Corynebacterium ListeriaAntibiotic coverage for common bacteriaClasses of Abx and gram coverage ■ This picture shows the different coverages of antibiotics, which is very useful to know and remember when choosing which antibiotic to prescribeSBA ■ A patient has come in with a gastrointestinal infection, and blood cultures have been sent to identify the source of the infection. Results show a gram –ve bacteria. Which of the following antibiotic classes would you not choose to prescribe for this infection? 1. Aminoglycosides 2. Macrolides 3. Tetracyclines 4. Sulphonamides 5. QuinolonesSBA ■ A patient has come in with a gastrointestinal infection, and blood cultures have been sent to identify the source of the infection. Results show a gram –vebacteria. Which of the following antibiotic classes would you not consider to prescribe for this infection? 1. Aminoglycosides – this has gram –ve coverage only and would be considered 2. Macrolides – this has gram +ve coverage only 3. Tetracyclines – this has both gram +ve and –ve coverage and would be considered 4. Sulphonamides - this has both gram +ve and –ve coverage and would be considered 5. Quinolones - this has both gram +ve and –ve coverage and would be consideredCommon conditions There are quite a few common conditions in which you will need to knowthe best antibiotic to give: ■ Pneumonia ■ UTI ■ Cellulitis ■ Tonsillitis ■ Sinusitis ■ Otitis media ■ Salmonella ■ Campylobacter enteritis ■ Meningitisdes dificile (This is not an exhaustive list, and does not include all the infections from the UKMLA content map)SBA What classes of antibiotics can you not give if a patient is allergic to penicillin? 1. Quinolones 2. Aminoglycosides 3. Macrolides 4. Beta-lactams 5. SulphonamidesSBA What classes of antibiotics can you not give if a patient is allergic to penicillin? 1. Quinolones – penicillin is not a quinolone 2. Aminoglycosides - penicillin is not an aminoglycoside 3. Macrolides – penicillin is not a macrolide 4. Beta-lactams – penicillin is a beta-lactam. Cephalosporins and Carbapenems should also not be used to prevent cross-reactivity 5. Sulphonamides – penicillin is not a sulphonamideCommon conditions Condition First-line Abx If allergic to penicillin (general rule of thumb, use a macrolide) Community-acquired Amoxicillin or Co-amoxiclav Clarithromycin pneumonia Atypical pneumonia Clarithromycin Hospital-acquired or Co-amoxiclav Clarithromycin aspiration pneumonia UTI Nitrofurantoin or trimethoprim Cellulitis Flucloxacillin Clarithromycin Tonsilitis Phenoxymethylpenicillin Erythromycin Otitis media Amoxicillin Erythromycin Salmonella Ciprofloxacin Campylobacter enteritis Clarithromycin Clostridiodes dificile Oral vancomycin Meningitis CeftriaxoneCommon conditions Condition First-line Abx If allergic to penicillin (general rule of thumb, use a macrolide) Community-acquired Amoxicillin or Co-amoxiclav Clarithromycin pneumonia Atypical pneumonia Clarithromycin Hospital-acquired or Co-amoxiclav Clarithromycin aspiration pneumonia UTI Nitrofurantoin or trimethoprim Cellulitis Flucloxacillin Clarithromycin Tonsilitis Phenoxymethylpenicillin Erythromycin Otitis media Amoxicillin Erythromycin Salmonella Ciprofloxacin Campylobacter enteritis Clarithromycin Clostridiodes dificile Oral vancomycin Meningitis Ceftriaxone IMPORTANT NOTE: Though these are commonly prescribed, you should always refer to Eolas/Microguide for your local trust-specific guidelinesImportant side-effects of antibiotics to remember Drug Side-effect Amoxicillin Rash with infectious mononucleosis Co-amoxiclav Cholestasis Flucloxacillin Cholestasis several weeks after use Erythromycin Gastrointestinal upset Prolongs QT interval Ciprofloxacin Lowers seizure threshold Tendonitis Metronidazole Reaction following alcohol ingestion Doxycycline Photosensitivity Trimethoprim Rashes, including photosensitivity Pruritus Suppression of haematopoiesisSBA A 59-year-old patient was started on an antibiotic for an episode of bacterial tonsilitis last week. The patient has now come in having had palpitations and four episodes of syncope in the last three days and one episode of a seizure this morning. The patient’s ECG shows a HR of 120 and a QTc interval of 480ms. What antibiotic was this patient likely started on? 1. Co-amoxiclav 2. Nitrofurantoin 3. Ciprofloxacin 4. Erythromycin 5. MetronidazoleSBA A 59-year-old patient was started on an antibiotic for an episode of bacterial tonsilitis last week. The patient has now come in having had palpitations and four episodes of syncope in the last three days and one episode of a seizure this morning. The patient’s ECG shows a HR of 120 and a QTc interval of 480ms. What antibiotic was this patient likely started on? 1. Co-amoxiclav – causes cholestasis, not prolonged QT 2. Doxycycline – causes photosensitivity, not prolonged QT 3. Ciprofloxacin – can be a cause of seizures, but does not explain the prolonged QT 4. Erythromycin – a common side-effect is prolonged QT interval 5. Metronidazole – can be a cause of palpitations but not seizures and prolonged QTImportant drug-drug interactions There are some important interactions of antibiotics with other medicationsthat you must be aware of as some can be life-threatening and need immediate attention Can anyone give me any important examples they can think of?Important drug-drug interactions ■ Macrolides (e.g. clarithromycin) and statins ■ Macrolides (e.g. clarithromycin) and warfarin ■ Trimethoprim and methotrexateImportant drug-drug interactions ■ Macrolides (e.g. clarithromycin) and statins – causes increased risk of rhabdomyolysis – Should always stop statins when starting a patient on clarithromycin or erythromycin ■ Macrolides (e.g. clarithromycin) and warfarin– macrolides are a p450 inhibitor – Increases INR and bleeding risk of patients ■ Trimethoprim and methotrexate – causes myelosuppression – Causes bone marrow aplasiaHow do you decide when to give Abx? ■ In the GP setting, we have to consider when antibiotics are indicated for certain conditions, dependent on the presentation ■ To aid in this, we have scores that can be used such as: – FeverPAIN – to identify bacterial streptococcal pharyngitis – Centor criteria – to identify whether tonsillitis is bacterial or not ■ The primary aim is to determine whether the infection is a bacterial cause or viral causeF everP AIN criteria ■ 1 point for each of the following: – Fever over 38ºC – Purulence (pharyngeal/tonsillar exudate) – Attend rapidly (onset of 3 days or less) – Severely inflamed tonsils – No cough or coryzal symptoms ■ 0-1 – 13-18% likelihood of isolating streptococci ■ 2-3 – 34-40% likelihood of isolating streptococci ■ 4-5 – 62-65% likelihood of isolating streptococci ■ A higher score would suggest that antibiotics are likely indicated ■ This score is comparing the main symptoms that distinguish between viral and bacterial causes of infections of the throatCentor criteria ■ 1 point for each of the following: – Presence of tonsillar exudate – Tender anterior cervical lymphadenopathy or lymphadenitis – History of fever – Absence of cough ■ 0-2 – 3-17% likelihood of isolating Streptococci ■ 3-4 – 32-56% likelihood of isolating Streptococci ■ A high Centor score suggests a strong likelihood of bacterial tonsillitisSBA A 19-year-old patient has come in complaining of a 3-day history of sore throat and fevers. The patient does not complain of any cough. You examine the patient and find that there is cervical lymphadenopathy, and when examining the throat, you find tonsillar exudate. The patient has no known allergies. Are antibiotics indicated, and if so, what antibiotic would you prescribe? 1. No, Centor score of 1 2. Yes, Centor score of 3, give amoxicillin 3. Yes, Centor score of 4, give clarithromycin 4. Yes, Centor score of 4, give phenoxymethylpenicillin 5. No, Centor score of 2SBA A 19-year-old patient has come in complaining of a 3-day history of sore throat and fevers. The patient does not complain of any cough. You examine the patient and find that there is cervical lymphadenopathy, and when examining the throat, you find tonsillar exudate. The patient has no known allergies. Are antibiotics indicated, and if so, what antibiotic would you prescribe? 1. No, Centor score of 1 – wrong score 2. Yes, Centor score of 3, give amoxicillin – wrong score, wrong antibiotic 3. Yes, Centor score of 4, give clarithromycin – correct score, wrong antibiotic as the patient is not known to be allergic to penicillin 4. Yes, Centor score of 4, give phenoxymethylpenicillin – correct. The patient is not allergic to penicillin, and this is the first-line antibiotic 5. No, Centor score of 2 - wrong scoreWhat is the biggest complication of infections? ■ SEPSISSepsis Elena BobyDefinitions Sepsis: life-threatening organ dysfunction caused by a dysregulated host response to an infection Septic shock: circulatory, cellular, and metabolic abnormalities associated with a greater risk of mortality than with sepsis alone' Clinical Signs Patient X (22 M) is admitted to the resp ward for pneumonia, overthe last 3 days he has been recovering steadily but observations this morning show a RR 23, O2 sats of 94% (on air), BP 95/80, PR 100, Temp 38.2, the patient is alert. What is this patient’s NEW2 score? A - 5 B- 6 C - 7 D- 8Patient X (22 M) is admitted to the resp ward for pneumonia, over the last 3 days he has been recovering steadily but observations this morning show a RR 23, O2 sats of 94% (on air), BP 95/80, PR 100, Temp 38.2, the patient is alert. What is this patient’s NEW2 score? 2 1 0 - patient in on air 0 - patient in on air 2 1 0 1So what do we do when Sepsis is suspected? The patient has a NEWS score of 7 - in hospital this will trigger a critical care outreach teamSBA Mr X has a NEWS score of 7 and as the F1 you need to initiate the management algorithm – so what do you do first? A) Take his temperature to make sure B) Assess his airway C) Give him broad spectrum antibiotics D) Give him a blood transfusion E) Expose him fully and see if he has a rashSBA Mr X is septic and as the F1 you need to initiate the management algorithm – so what do you do first? A)monitored, it unlikely temperature is wrongtient is being B) Assess his airway - In an acutely unwell patient, the initial management is ALWAYS A-E ASSESSMENT! C) Give him broad spectrum antibiotics - not the initial management D) Give him a blood transfusion - there is no indication for this E) Expose him fully and see if he has a rash - again, will be done eventually but not the initial managementInvestigations and management For a septic patient we follow the 'give 3, take 3' approach We give 1. Broad spectrum antibiotics eg co-amoxiclav + clarithromycin 2. Fluids – usually 500ml 0.9% NaCl over 15 minutes 3. Oxygen – usually high flow oxygen at 15L/min via non re-breathe mask titrated to a target of 94-98% How would the oxygen requirement change for a patient with COPD? A) 94-98% via venturi mask B) 96 - 100% via non re-breathe mask C) 88-92% via non re-breathe mask D) No change required How would the oxygen requirement change for a patient with COPD? A) 94-98% via venturi mask - the target saturation should be lower than for a non CO2 retainer because high levels of CO2 means the brain starts to rely on lower levels of O2 to breathe aka the hypoxic drive B) 96 - 100% via non re-breathe mask - saturation is way too high and a venturi should be used, not a non-rebreathe (for more controlled oxygen delivery) C) 88-92% via venturi mask D) No change requiredExample prescription: Oxygen 15l/min Example prescription: Fluids patient is fluid overloaded or has HF give 250ml instead of 500Example prescription: AntibioticsInvestigations and management We take (measure) 1. Bloods (for culture + FBC, U+Es, clotting, glucose, LFTs, CRP) - usually done when cannula is inserted during A-E) 2. Urine output – should be >O.5ml/kg.hr 3. Lactate (should be <2) In the case of Mr X, a 22 YO, which bacteria is it important to assess the serology for during blood culture (AKA most common cause of atypical pneumonia)? A) Mycoplasma B) Legionella pneumophila: C) Streptococcus pneumoniae D) Haemophilus influenzae In the case of Mr X, a 22 YO, which bacteria is it important to assess the serology for during blood culture, what is the most common cause of atypical pneumonia? A) Mycoplasma - most common cause of atypical pneumonia, usually seen in younger people B) Legionella pneumophila - this would be tested in urine, not blood C) Streptococcus pneumoniae - most common cause of CAP across all groups. The question asks specifically for ATYPICAL D) Haemophilus influenzae- more common in older smokers with a history of COPD Common complications of Sepsis 1. Septic Shock - a higher mortality complication of sepsis 2. Acute respiratory distress syndrome (ARDS) : Build up of fluid in the alveoli usually needing mechanical ventilation 3. Acute Kidney Injury (AKI) May require temporary dialysis as the kidneys are inflamed and unable to filter the blood 4. Disseminated intravascular coagulation (DIC) the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleedingWhich of the following is a red flag criteria for a patient suspected of sepsis A) Respiratory rate 21-24 B) Not passed urine in last 12-18 hours C) Recent chemotherapy D) Systolic B.P 91-100 mmHgWhich of the following is a red flag criteria for a patient suspected of sepsis A) Rthis is amber flag criteria, RR>=25 is a red flag B) Not passed urine in last 12-18 hours: is red flagber flag criteria, not passing urine in last 18 h/ UO < 0.5 ml/kg/hr C) Recent chemotherapy - since people have very weak immune systems, abx)ropenic sepsis has its own pathway (for instance broader spectrum D) Systolic B.P 91-100 mmHg: also amber flag, Systolic B.P <= 90 mmHg = red THANKS FOR W ATCHING! By Harish Bava + Elena Boby Reviewed by Dr Claudia Bayne on Medall and see you next week!